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J R Alexander

Publications and source records attributed to J R Alexander.

At least 19 recordsLinked to original sources
PubMed2001

Use of filter paper for the collection and analysis of human whole blood specimens.

The Centers for Disease Control and Prevention and its partners have been operating the Newborn Screening Quality Assurance Program for >20 y. The program helps participating laboratories to evaluate and improve the quality of their newborn-screening testing efforts by providing quality control dried blood spot materials and proficiency-testing materials for the external evaluation of screening programs. The Newborn Screening Quality Assurance Program provides an independent evaluation of filter papers approved by the Food and Drug Administration for the collection of blood for clinical tests. These activities have created a mechanism for the validation of the filter paper blood collection device and the standardization of materials and methods for the analysis of dried blood spots.

Antibodies↗
PubMed1999

Validation of accuracy-based amino acid reference materials in dried-blood spots by tandem mass spectrometry for newborn screening assays.

BACKGROUND: Advances in technology and the earlier release of newborns from hospitals have pressed the demand for accurate calibration and improved interlaboratory performance for newborn screening tests. As a first step toward standardization of newborn screening aminoacidopathy tests, we have produced six-pool sets of multianalyte dried-blood-spot amino acid reference materials (AARMs) containing predetermined quantities of five amino acids. We describe here the production of the AARMs, validation of their amino acid contents, and characterization of their homogeneity and their stability in storage. METHODS: To each of six portions of a pool of washed erythrocytes suspended in serum we added Phe (0-200 mg/L), Leu (0-200 mg/L), Met (0-125 mg/L), Tyr (0-125 mg/L), and Val (0-125 mg/L). Six-pool sets (1300) were prepared, dried, and packaged. We used isotope-dilution mass spectrometry to estimate the endogenous amino acid concentrations of the AARMs and validate their final amino acid concentrations. We used additional tandem mass spectrometry analyses to examine the homogeneity of amino acid distribution in each AARM, and HPLC analyses to evaluate the stability of the amino acid contents of the AARMs. RESULTS: The absolute mean biases across the analytic range for five amino acids were 2.8-9.4%. One-way ANOVAs of the homogeneity results predicted no statistically significant differences in amino acid concentrations within the blood spots or within the pools (P >0.05). Regression slopes (0 +/- 0.01) for amino acid concentrations vs storage times and their P values (>0.05) showed no evidence of amino acid degradation at ambient temperatures, 4 degrees C, or -20 degrees C during the intervals tested. CONCLUSION: The validation, homogeneity, and stability of these blood spots support their use as a candidate national reference material for calibration of assays that measure amino acids in dried-blood spots.

Amino Acids↗
PubMed1999

Possible precipitants of psychiatric hospitalization in patients with major depression: results from the Jerusalem Collaborative Depression Project.

In spite of substantial advances in the treatment of major depression by pharmacotherapy and other means, a significant number of depressed patients require hospitalization. In the context of the Jerusalem Collaborative Depression Project, possible precipitants of psychiatric hospitalization were sought in a cohort of patients (n = 107) who were admitted to hospitals in the Jerusalem area during a 14-month period because of a depressive episode. The patients fulfilled DSM III-R criteria for major depression, single or recurrent; bipolar 1 disorder, depressed or mixed; bipolar 2, depressed. The cohort encompassed more than two thirds of potential subjects admitted during this period with the ICD-9 equivalents of the specified diagnoses (as reported to the Israel Ministry of Health National Psychiatric Case Register) and were similar to the entire potential population in terms of their diagnostic breakdown. The patients underwent extensive socio-demographic and clinical evaluation that included detailed documentation of treatment received prior to hospitalization. Notwithstanding the absence of a comparison group of depressed patients who were not hospitalized, a number of potential precipitants were identified. These included older age (55.2% > 60 years, 20.6% > 70 years), immigration to Israel during the preceding 5 years (34.7%), concomitant physical illness (60%) which was associated with moderate to severe disability in 41% and poor quality of antidepressant pharmacotherapy prior to hospitalisation (only 24.3% received an adequate trial of antidepressant medication). Further evaluation of these and other potential factors could facilitate targeting of patient groups at particular risk for hospitalization and reduce the need for it.

Adult↗
PubMed1999

TennCare: Tennessee's answer to runaway Medicaid costs.

TennCare was implemented in Tennessee on January 1, 1994, as the state's replacement program for Medicaid. Created through a demonstration waiver under Section 1115(a) of the Social Security Act, TennCare is unlike any other state Medicaid program in the nation because it includes coverage of uninsured and uninsurable Tennesseans. By contracting with managed care organizations (MCOs) to administer the Medicaid benefit package to TennCare enrollees, the state virtually privatized the program and dramatically shifted the state's responsibility from one of total administration to an oversight function only. Amid provider lawsuits, MCO contract controversy, and general chaos surrounding the new program, the implementation of TennCare created one of the most significant health care events in the state's history. This article provides an overview of the TennCare program and its impact on enrollees, providers, and the state budget.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1998

No evidence for significant linkage between bipolar affective disorder and chromosome 18 pericentromeric markers in a large series of multiplex extended pedigrees.

Bipolar affective disorder (BP) is a major neuropsychiatric disorder with high heritability and complex inheritance. Previously reported linkage between BP and DNA markers in the pericentromeric region of chromosome 18, with a parent-of-origin effect (linkage was present in pedigrees with paternal transmission and absent in pedigrees with exclusive maternal inheritance), has been a focus of interest in human genetics. We reexamined the evidence in one of the largest samples reported to date (1,013 genotyped individuals in 53 unilineal multiplex pedigrees), using 10 highly polymorphic markers and a range of parametric and nonparametric analyses. There was no evidence for significant linkage between BP and chromosome 18 pericentromeric markers in the sample as a whole, nor was there evidence for significant parent-of-origin effect (pedigrees with paternal transmission were not differentially linked to the implicated chromosomal region). Two-point LOD scores and single-locus sib-pair results gave some support for suggestive linkage, but this was not substantiated by multilocus analysis, and the results were further tempered by multiple test effects. We conclude that there is no compelling evidence for linkage between BP and chromosome 18 pericentromeric markers in this sample.

Adolescent↗
PubMed1995

Frequency of positive family history in bipolar patients in a catchment-area population.

1. Major family studies of bipolar disorder report the frequency of affective disorder among probands' relatives, but do not usually report the frequency of a positive family history among probands. A single previous study was not population based. 2. The Division of Psychiatry of Ben Gurion University provides virtually all psychiatric services for a catchment area of 300,000 people. The authors reviewed the charts of all 236 treated bipolar I patients in 1991, and interviewed 177 of them with a modified FH-RDC. 3. 48% of probands had a family history of mental illness. 4. However, the present methods of ascertainment may have been insufficiently sensitive.

Bipolar Disorder↗
PubMed1994

A possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3.

In a preliminary genome scan of 47 bipolar disorder families, we detected in one family a lod score of 3.41 at the PFKL locus on chromosome 21q22.3. The lod score is robust to marker allele frequencies, phenocopy rates and age-dependent penetrance, and remains strongly positive with changes in affection status. Fourteen other markers in 21q22.3 were tested on this family, with largely positive lod scores. Five of the other 46 families also show positive, but modest lod scores with PFKL. When all 47 families are analysed together, there is little support for linkage to PFKL under homogeneity or heterogeneity using lod score analysis, but the model-free affected-pedigree-member method yields statistically significant results (p < 0.0003). Our results are consistent with the presence of a gene in 21q22.3 predisposing at least one family to bipolar disorder.

Adolescent↗
PubMed1994

A pedigree series for mapping disease genes in bipolar affective disorder: sampling, assessment, and analytic considerations.

A series of 57 extended pedigrees with high density of bipolar affective disorder is described. Ascertainment and diagnostic procedures are documented and simulation studies to assess statistical power are carried out. The pedigrees, obtained in the US and Israel, are comprised of 1508 adult individuals with best estimate consensus diagnoses (12-71 relatives per pedigree), 490 of whom (including 401 sib pairs) meet criteria for a conservative disease definition (bipolar disorder or recurrent major depression). Cell lines have been established on 1324 of these individuals. Statistical power to detect linkage with lod score analysis, assuming autosomal dominant transmission and highly polymorphic DNA markers, is nearly 100% for alpha (proportion of linked families) = 30%, and 75% for alpha = 20%. This is the largest bipolar pedigree series reported to date; its unique features make it amenable to various gene detection techniques.

Bipolar Disorder↗
PubMed1993

Arterial oxygen saturation in preterm neonates without respiratory failure.

To obtain normal data on arterial oxygen saturation as measured by pulse oximetry (SpO2; Nellcor N200), we obtained 12-hour tape recordings of SpO2, photoplethysmographic waveforms, instantaneous pulse rate, and observations of breathing movements on 55 preterm neonates (25 girls) who had been admitted to one of four special care baby units but had no signs of respiratory distress and were breathing room air at 24 hours of age. Their median gestational age at birth was 35 weeks (range, 30 to 36), and their median age at the time of study 1 day (range, 1 to 7). Median baseline SpO2, measured only during regular breathing, was 99.4% (range, 90.7 to 100; 5th percentile, 95.5). Ten recordings (18%) contained a total of 83 episodes of desaturation (defined as a fall in SpO2 to < or = 80% for > or = 4 seconds). The 95th percentile for desaturation frequency was eight per recording. One infant had 55 episodes of desaturation and thus accounted for two thirds of all episodes observed. Only one of the episodes of desaturation in this infant, and none of those in the other nine infants, had been noted clinically, nor had the abnormally low baseline SpO2 (90.7%) in one infant. Baseline SpO2 in these nondistressed preterm neonates was higher than might be expected, given the SpO2 levels currently recommended for preterm infants with respiratory failure. A minority of infants, however, had a low baseline SpO2 or a high frequency of episodes of desaturation, the potential effects of which remain to be determined.

Arteries↗
PubMed1993

Diminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees.

The hypothesis that chromosomal region Xq27-28 harbours a gene for manic-depression has been a focus of interest in human genetics. X-linked inheritance of manic depressive illness has been re-examined in 3 multigeneration Israeli kindreds. Extension and re-evaluation of pedigree data, including new individuals, diagnostic follow-up, and analysis with DNA markers, shows greatly diminished support for linkage to Xq28. The peak lod scores in two of the pedigrees have dropped several lod units to clearly negative values at the RCP-F8-G6PD gene cluster. On the other hand, positive lod scores (Zmax = 2.09) are sustained in another pedigree at the same map location. None of the pedigrees show linkage to more proximal markers, including the Xq27 locus DXS98. Our analysis underscores the uncertainties in studying complex disorders.

Adult↗
PubMed1992

Arterial oxygen saturation in preterm infants at discharge from the hospital and six weeks later.

To obtain normal data on arterial oxygen saturation (SaO2) in preterm infants and to study early developmental changes in SaO2, we obtained overnight tape recordings of SaO2 and breathing movements in 160 preterm infants at their discharge from three special care baby units (mean gestational age at birth 33 weeks; at time of study, 37 weeks). One hundred ten infants (69%) underwent a second recording 6 weeks later. Median baseline SaO2 during regular breathing was 99.5% (range 88.7% to 100%) at discharge, and 100% (range 95.3% to 100%) at follow-up (p less than 0.001). The number of episodes of desaturation, defined as a fall in SaO2 to less than or equal to 80% for at least 4 seconds, corrected to the mean duration of recording (12.2 hours), decreased from a median of 3 (0 to 355) to 0 (0 to 17) (p less than 0.001). The median duration of each episode of desaturation remained unchanged (5.2 (4.0 to 22.7) vs 5.5 (4.2 to 24.0) seconds). At discharge, a small minority of infants had a clinically unrecognized low baseline SaO2 (lowest, 88.7%; 5th percentile, 95.7%) or a high number of desaturation episodes (the highest was six times the 95th percentile value). At follow-up, all outlying values had normalized. Follow-up recordings made between 42 and 47 weeks of gestational age (n = 53) were compared with similar recordings from 67 term infants at the same gestational age. The preterm infants had a significantly higher baseline SaO2 and no more desaturation than the infants born at term. Knowledge of normal ranges of oxygenation and their changes with age may be of value in identifying clinically undetected hypoxemia in preterm infants at discharge from the hospital. The potential influence of such hypoxemia on clinical outcome remains to be determined.

Birth Weight↗
PubMed1991

Breathing patterns and heart rates at ages 6 weeks and 2 years.

Forty-two randomly selected, full-term, healthy infants underwent 24-hour electrocardiographic recordings and breathing movements at about ages 6 weeks (median age, 43 days; range, 34 to 61 days) and 2 years (median age, 26 months; range, 21 to 35 months). The number and duration of apneic pauses of 3.6 seconds or longer were analyzed. Periodic apnea was defined as a sequence of three or more apneic pauses, each separated by fewer than 20 breaths. All other apneic pauses were defined as isolated. Median heart rates and respiratory rates, which were measured during regular breathing, decreased from 137/min and 35/min to 98/min and 21/min, respectively. The total duration of periodic apnea remained unchanged (median, 0.06 min/h vs 0.05 min/h). Although the median frequency of all isolated apneic pauses decreased from 3.6/h to 2.5/h, the number of those that were longer than 6 seconds increased from 0.37/h to 0.80/h, leading to an increase in the proportion of these pauses, among all isolated apneic pauses, from 10% at age 6 weeks to 32% at age 2 years. Only one apneic pause in one infant at age 6 weeks, but eight pauses in six children at age 2 years, were longer than 15 seconds. A knowledge of such normal variability in the duration of apneic pauses in older infants and young children is essential for the interpretation of pneumograms and alarms while monitoring breathing movements.

Abdominal Muscles↗
PubMed1991

Effect of daily variation in weather and sleep on seasonal affective disorder.

Analysis of daily self-ratings of energy for 10 patients diagnosed with seasonal affective disorder (SAD) revealed statistically significant seasonal patterns in eight patients (with all patients showing the most energy in the summer and the least energy in the winter). When weather was controlled for, the seasonal patterns in energy persisted in seven of the eight patients. In a lesser number of subjects (four), there were significant effects of weather after controlling for season; however, when the effects of weather on energy were examined separately for each season, 8 of the 10 subjects were found to be influenced by weather in at least one season. Daily sleep data showed statistically significant seasonal patterns in all 10 patients (with 6 subjects showing maximum sleep in winter and 4 in summer). As for the relationship between energy and sleep, a loss of energy appeared to predict longer sleep on that night and the next night (7 of 10 patients), whereas there was no evidence that prolonged sleep influenced energy on the following and subsequent days.

Adult↗
PubMed1991

Oxygen saturation and breathing patterns in infancy. 1: Full term infants in the second month of life.

Overnight 12 hour tape recordings were made of arterial oxygen saturation (SaO2, pulse oximeter in the beat to beat mode) and abdominal wall breathing movement on 67 healthy, full term infants between the ages of 29 and 54 (median 39) days. The median baseline SaO2 during regular breathing was 99.8% (range 97.0-100%). Fifty four infants (81%) had shortlived episodes during which SaO2 fell to 80% or less (desaturation); the median rate was 0.9 desaturations/hour, and the median duration of each desaturation was 1.2 seconds. The 97th centile value for the duration of all episodes in which SaO2 fell to less than or equal to 80% was 4.0 seconds. The frequency of desaturations was significantly higher, and their duration significantly longer, when the breathing pattern was non-regular rather than regular. The percentage of apnoeic pauses (greater than or equal to 4 seconds in duration) followed by a desaturation was higher during non-regular than regular breathing; it was particularly high during periodic breathing. A knowledge of normal variability of baseline measurements of oxygenation and of the relationship between oxygenation and breathing patterns in infants is essential to the use of pulse oximetry in clinical practice.

Humans↗
PubMed1991

Oxygen saturation and breathing patterns in infancy. 2: Preterm infants at discharge from special care.

Overnight 12 hour tape recordings of arterial oxygen saturation (SaO2, pulse oximeter in the beat to beat mode), breathing movements, and airflow were made on 66 preterm infants (median gestational age 34 weeks, range 25-36) who had reached term (37 weeks) and were ready for discharge from the special care baby unit. No infant was given additional inspired oxygen during the study. The median baseline SaO2 was 99.4% (range 88.9-100%). Eight infants had baseline SaO2 values below 97%, the lowest value observed in a study on full term infants. All but one infant had short-lived falls in SaO2 to less than or equal to 80% (desaturations), which were more frequent (5.4 compared with 0.9/hour) and longer (mean duration 1.5 compared with 1.2 seconds) than in full term infants. There was no evidence that gestational age at birth influenced the frequency or duration of desaturations among the preterm infants. The frequency of relatively prolonged episodes of desaturation (SaO2 less than or equal to 80% for greater than or equal to 4 seconds), however, decreased significantly with increasing gestational age (0.5, 0.4, 0.2, and 0.1 episodes/hour in infants at less than or equal to 32, 33-34, 35, and 36 weeks' gestational age, respectively). Analysis of the respiratory patterns associated with such episodes showed that 5% occurred despite both continued breathing movements and continuous airflow. Five infants had outlying recordings: three had baseline SaO2 values of less than 95% (88.9, 92.7, and 93.8%), and two had many prolonged desaturations (14 and 92/hour; median for total group 0.2, 95th centile 2.3). None of these five infants had been considered clinically to have dis order of oxygenation. Although these data are insufficient to provide information about outcome, we conclude that reference data on arterial oxygenation in preterm infants are important to enable the identification of otherwise unrecognized hypoxaemia.

Apnea↗