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Biomedical subjects

D Judge

Publications and source records attributed to D Judge.

At least 19 recordsLinked to original sources
PubMed1997

Empirical genomewide significance levels established by whole genome simulations.

The advent of high-resolution genetic maps and semiautomated genotyping technology has opened the way for genome screening in genetically complex traits. Many such screens are now under way, or completed, most using multipoint nonparametric linkage analysis of affected sibling pairs. This type of linkage analysis uses all the available genotype information to calculate the maximum lod score (MLS) value at each point in the genome, and thereby generates MLS profiles along each chromosome. Any positive MLS values indicate potential linkage, but the peaks in these profiles, which may be referred to as "hits," identify the most likely locations of disease susceptibility genes. However, such analysis presents serious problems of multiple testing, and the assessment of the statistical significance of hits has become a contentious issue [Lander and Kruglyak (1995) Nat Genet 11:241-247; Curtis (1996) Nat Genet 12:356-357; Witte et al. (1996) Nat Genet 12:355-356]. Having recently completed a genome screen in multiple sclerosis, we decided to investigate the statistical properties of our study by simulation. We report here in detail the results of this simulation study. Our main conclusion is that, for the particular set of families and markers used in our screen, an MLS of 3.2 carries a genome-wide significance of 5% (that is, there is a 5% probability of observing at least one false hit, above this threshold in a complete genome screen). This value is closer to the familiar limit of 3.0, originally suggested by Morton [1955; Am J Hum Genet 7:277-318] than to the more stringent limit of 4.0 recently proposed by Lander and Kruglyak [1995; Nat Genet 11:241-247]. This is somewhat reassuring, in view of the very large sample sizes that would be necessary to achieve adequate power to detect linkage at the more stringent threshold.

Female↗
PubMed1994

Survival of split calvarial bone grafts in a dog model.

To gain a better understanding of the strength and long term viability of split calvarial bone graft, nine mongrel dogs each received four trephine craniotomies (1.5 mm diameter). The harvested bone plugs were split through the diploe and a partial-thickness plug was returned to each craniotomy site. The unused partial-thickness plugs underwent strength testing. After 90-150 days the dogs were sacrificed, bone scans and X-rays of the graft recipient sites performed, and the grafted plugs harvested for strength testing and histologic examination. Bone scanning showed increased osteoblastic activity within the grafts, strength testing showed a progressive loss in strength over the 150 days, and histologic examination demonstrated a creeping substitution. These results imply a similar evolution in strength and remodeling to that seen in long-bone grafts, whose remodeling typically spans 1 year.

Animals↗
PubMed1993

Mice expressing a bovine basic fibroblast growth factor transgene in the brain show increased resistance to hypoxemic-ischemic cerebral damage.

BACKGROUND AND PURPOSE: Cerebral intraventricular infusion of acidic or basic fibroblast growth factor has been shown to attenuate ischemic damage to hippocampal CA1 neurons in the gerbil. The purpose of the present study was to determine if the basic fibroblast growth factor transgenic mouse has an enhanced ability to resist the effects of severe cerebral hypoxemia-oligemia. METHODS: Mice that were transgenic for bovine basic fibroblast growth factor were exposed to right carotid artery ligation, hyperglycemia, and 20 minutes of 1% carbon monoxide. After 5 days' recovery, brains were examined for histological damage. RESULTS: Counts of CA1 neurons in the right hippocampus showed a significantly higher number of neurons per millimeter CA1 in hypoxic-ischemic transgenic mice compared with nontransgenic controls (transgenic, 260 +/- 33; nontransgenic, 151 +/- 37 neurons per millimeter CA1; P < .05). CONCLUSIONS: The results indicate that basic fibroblast growth factor transgenic mice, as judged by CA1 hippocampal neuronal survival, have an enhanced ability to resist the effects of a complex hypoxic-ischemic cerebral insult.

Animals↗
PubMed1990

Anterior stromal micropuncture electron microscopic changes in the rabbit cornea.

Anterior stromal micropuncture has become an effective treatment for recurrent erosion. The healing process in rabbit corneas was investigated. Following micropuncture of the corneal surface with a 27-gauge needle knife, electron microscopy was carried out at regular intervals from time 0 through 5 months. The corneal incisions began to fill with epithelium by day 1. Activated keratocytes were adjacent to the basement membrane defect by 7 days. The basement membrane appeared to be healed at 2 and 4 weeks. Epithelial projections into the stromal incisions with underlying mature basement membrane persisted at 5 months postsurgery. Basement membrane reproduction occurred much more rapidly following needle puncture than after microdiathermy. This was thought to occur because the corneal epithelial cell was immediately exposed to type I collagen, whereas following microdiathermy, new type I collagen must be secreted on the necrotic collagen before the corneal epithelium will secrete basement membrane.

Animals↗
PubMed1989

Microwave energy compared with heater probe and BICAP in canine models of peptic ulcer hemorrhage.

The safety and efficacy of a new endoscopic microwave hemostatic device (Microtaze) was compared with BICAP and heater probe using previously established canine models of endoscopic hemostasis. Parameters evaluated included (a) depth of injury, (b) efficacy of hemostasis (bleeding gastric ulcer model), and (c) strength of coaptive bonding (mesenteric artery model). Depth of injury was graded histologically 1 wk after coagulation as the percentage of lesions showing gastric full-thickness damage for each probe. In depth-of-injury studies probes were applied at maximum force (established endoscopically with a specially designed force gauge) and at maximum power settings (50 W Microtaze, 30 J heater probe, dial setting 10 BICAP) to determine safety. There was no significant difference in the percentage of external muscle layer damage: 85%, 74%, and 86% for Microtaze, heater probe, and BICAP, respectively. Hemostasis was achieved 100% of the time in endoscopically induced bleeding gastric ulcers in heparinized dogs. Canine mesenteric arteries measuring 1-2 mm in diameter were isolated at laparotomy and coaptively sealed, and the bond strength was measured by application of hydrostatic pressure. Bursting pressures were not significantly different for Microtaze, heater probe, or BICAP probes (1062 +/- 77 mmHg, 863 +/- 85 mmHg, and 1154 +/- 139 mmHg, respectively). In conclusion, microwave energy may be applied endoscopically to produce hemostasis with similar safety and efficacy to BICAP and heater probe.

Animals↗
PubMed1988

The resting cardiointegram: correlation with stress thallium perfusion studies.

The cardiointegram is a noninvasive technique for the analysis of the electrical signals of the heart obtained by a transformation of the voltage versus time format by a series of integrations. The stress thallium perfusion study is a widely used test for the detection of coronary artery disease. In order to evaluate the correlation between the resting cardiointegram and the stress thallium 201 perfusion study, 20 patients with normal resting electrocardiograms underwent stress thallium tests and resting cardiointegrams. The cardiointegram was determined on two resting complexes of leads I, II, V4, V5, and V6 and called abnormal if five of ten complexes deviated outside a normalized template. There was concordance of the cardiointegram and the thallium study in 16 of 20 patients (80%). The sensitivity for the detection of coronary artery disease was 71%, and the specificity was 80%. The overall accuracy was 74%. Thus in patients with normal electrocardiograms, the cardiointegram is a useful noninvasive test for the detection of coronary artery disease.

Coronary Disease↗
PubMed1988

Routine reduction of pulse generator voltage.

The porous-tip electrode has led to a significant advancement in pacing system technology. Experience with 38 patients with unipolar tined CPI porous endocardial electrodes, is reported. All patients had programmable pulse generators, CPI model number 531. The voltage in this pulse generator can be reduced from 5 to 2.5 volts. The pulse width threshold (PWT) at implantation was 0.06 ms at 5 volts in all 38 patients, and the PWT at implantation varied between 0.06 and 0.16 ms at 2.5 volts, with a mean PWT of 0.092 +/- 0.026 ms. The 38 patients were restudied six months later. The mean PWT measured at 5 volts was 0.076 +/- 0.018 ms. The PWT measured at 2.5 volts varied between 0.08 and 0.30 ms with a mean PWT of 0.178 +/- 0.067 ms. Twenty-three patients were restudied one year after lead implantation. The PWT measured at 2.5 volts varied between 0.08 and 0.30 ms with a mean PWT of 0.156 +/- 0.061 ms. All of the pulse generators were reprogrammed to 2.5 volts. This permitted a substantial prolongation of the pulse generator life (three to five years) with an improvement in the cost effectiveness of the pulse generator.

Electrodes↗
PubMed1987

Maintenance of normal circulating levels of delta 4-androstenedione and dehydroepiandrosterone in simple obesity despite increased metabolic clearance rates: evidence for a servo-control mechanism.

To study the effect of obesity on the metabolism of adrenal androgens not bound to testosterone-estradiol-binding globulin, the MCRs of delta 4-androstenedione (A) and dehydroepiandrosterone (DHEA) were determined using constant infusion of unlabeled steroids to steady state in 8 normal weight and 19 obese nonhirsute eumenorrheic women. The blood production rates (PR) were calculated as the product of the MCR and the 24-h integrated serum concentrations (IC). The mean MCR and PR of A and DHEA were significantly higher in the obese women than in the normal weight women. There was, however, no difference in the mean IC of each androgen in the 2 groups. The MCR and PR of A and DHEA were each correlated with the body mass index (BMI; kilograms per m2). The MCR and PR of A and the MCR of DHEA were also correlated with the ratio of waist circumference to hip circumference (WHR). However, the PR of DHEA was not correlated with WHR. There was no correlation between the IC of either androgen and BMI or WHR. However, partial correlation analysis revealed that correction of the BMI for WHR resulted in a significant negative correlation between BMI and IC of A. We conclude that the MCR and PR of A and DHEA were increased in obese nonhirsute eumenorrheic women; there was a strong correlation between BMI and the MCR and PR of A and DHEA; upper segment obesity, as measured by WHR, was correlated with the MCR and PR of A and the MCR of DHEA, but not with the PR of DHEA; and circulating DHEA and A were maintained at normal levels in the obese eumenorrheic women despite an increase in the MCR, which suggests that a servo-mechanism is operative which registers the body size and adjusts the PR according to the MCR.

Adult↗
PubMed1978

Twins: causes of perinatal death in 12 United States cities and one African city.

The perinatal mortality rate in a large U. S. study was 139 per 1,000 births for twins and 33 per 1,000 for singletons. Sixteen per cent of the twin deaths were due to amniotic fluid infections, 11 per cent to premature rupture of the membranes, 8 per cent to the monovular twin transfusion syndrome, 8 per cent to large placental infarcts, 7 per cent to congenital anomalies, and the rest to over 20 other disorders. The perinatal mortality rate for monozygotic twins was 2.7 times that for dizygotic twins, mainly due to more amniotic fluid infections, congenital anomalies, and the twin transfusion syndrome in the monozygotic pairs. To study the role of poor maternal nutrition on twins, a similar study of perinatal mortality rates was undertaken in Addis Ababa, Ethiopia. Addis Ababa twins had 2.5 times the mortality rate of U. S. twins, mainly due to a higher frequency of amniotic fluid infections, abruptio placentae, cord accidents, obstructed labors, congenital syphillis, and the twin transfusion syndrome in the Ethiopians.

Abruptio Placentae↗
PubMed1977

Amniotic fluid infections in an African city.

Amniotic fluid infections were the most common cause of perinatal death in Addis Ababa, Ethiopia (21.8/1,000 live births). Most such infections appear to originate in the fetal membranes near the cervical os. The high rate of spread of these local infections into the amniotic fluid in Addis Ababa appears related to a lack of antimicrobial activity in amniotic fluids. Factors that adversely affected nutrition in the gravid woman, lack of prenatal medical care, and low water usage were associated with the high rate of fatal infections.

Amniotic Fluid↗
PubMed1975

Ragged-red fibers. A biochemical and morphological study.

Histochemical, ultrastructural and biochemical studies were performed on muscle biopsy specimens from a 30-year-old man with proximal limb weakness. Modified Gomori trichome stains of anterior tibial muscle revealed accumulations of red-staining material in the subsarcolemmal and intermyofibrillar regions of virtually every fiber (ragged-red fibers); these accumulations were rich in oxidative enzymes. Electron microscopy of this muscle showed that the red-staining areas consisted of large collections of abnormal-appearing mitochondria. Mitochondria isolated from the quadriceps muscle showed lack of respiratory control with alpha-glycerophosphate as substrate. However, the lack of respiratory control with alpha-glycerophosphate must be interpreted with caution since the quadriceps muscle was severely degenerated, and biochemical alterations of mitochondria may occur secondary to muscle degeneration itself. Nevertheless, this is the second reported case of lack of respiratory control with alpha-glycerophosphate in a patient with ragged-red fibers. Further interpretation of this defect and its significance must await more studies to determine whether this muscle mitochondrial abnormality is a common finding in the disorders in which ragged-red fibers are encountered.

Adenosine Triphosphatases↗