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Biomedical subjects

H R Cohen

Publications and source records attributed to H R Cohen.

At least 19 recordsLinked to original sources
PubMed1999

Functional expression of human and Arabidopsis protein phosphatase 2A in Saccharomyces cerevisiae and isolation of dominant-defective mutants.

Protein phosphatase 2A (PP2A), a heterotrimeric serine/threonine-specific protein phosphatase, comprises a catalytic subunit and two distinct regulatory subunits, A and B. The primary sequence of the catalytic (C) subunit is highly conserved in evolution, and its function has been shown to be essential in yeast, Drosophila and mice. In many eukaryotes, the C subunit is encoded by at least two nearly identical genes, impeding conventional loss-of-function genetic analysis. We report here the development of a functional complementation assay in S. cerevisiae that has allowed us to isolate dominant-defective alleles of human and Arabidopsis C subunit genes. Wild-type human and Arabidopsis C subunit genes can complement the lethal phenotype of S. cerevisiae PP2A-C mutations. Site-directed mutagenesis was used to create two distinct, catalytically impaired C subunit mutants of the human and Arabidopsis genes. In both cases, expression of the mutant subunit in yeast prevented growth, even in the presence of functional C subunit proteins. This dominant growth defect is consistent with a dominant-interfering mode of action. Thus, we have shown that S. cerevisiae provides a rapid system for the functional analysis of heterologous PP2A genes, and that two mutations that abrogate phosphatase activity exhibit dominant-defective phenotypes in S. cerevisiae.

Alleles↗
PubMed1998

The Toronto Tri-Hospital Gestational Diabetes Project. A preliminary review.

In this study, we assessed maternal-fetal outcomes in untreated patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes mellitus (GDM), examined the relationship between birth weight and mode of delivery among women with untreated borderline GDM, treated overt GDM, and normoglycemia, and established more efficient screening strategies for detection of GDM. This was a prospective analytic cohort study in which nondiabetic women aged > or = 24 years were eligible for enrollment. A 50-g glucose challenge test (GCT) and a 100-g oral glucose tolerance test (OGTT) were administered at 26 and 28 weeks gestational age, respectively. Risk factors for unfavorable maternal-fetal outcomes were recorded. Time since the last meal prior to the screening test was recorded, as well. Caregivers and patients were blinded to glucose values except when test results met the National Diabetes Data Group criteria for GDM. Maternal and fetal outcomes, including the mode of the delivery, were recorded in the postpartum period. Of 4,274 patients screened, 3,836 (90%) continued to the diagnostic oral glucose tolerance test. GDM was seen in 145 women. Increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of cesarean section, preeclampsia, macrosomia, and need for phototherapy, as well as an increased length of maternal and neonatal hospital stay. Multivariate analysis showed that increasing carbohydrate intolerance remained an independent predictor for various unfavorable outcomes, but the strength of the associations was diminished. Compared with normoglycemic control subjects, the untreated borderline GDM group had increased rates of macrosomia (28.7 vs. 13.7%, P < 0.001) and cesarean delivery (29.6 vs. 20.2%, P = 0.03). Usual care of known GDM patients normalized birth weights, but the cesarean delivery rate was about 33%, whether macrosomia was present or absent. An increased risk of cesarean delivery among treated patients compared with normoglycemic control subjects persisted after adjustment for multiple maternal risk factors. As for the screening tests, time since the last meal had a marked effect on mean plasma glucose. Receiver operating characteristic curve analysis allowed the selection of the most efficient cut points for the GCT based on the time since the last meal. These cut points were 8.2, 7.9, and 8.3 mmol/l (1 mmol/l = 18.015 mg/dl) for elapsed postprandial time of < 2, 2-3, and > 3 h, respectively. With this change from the current threshold of 7.8 mmol/l, the number of patients with a positive screening test dropped from 18.5 to 13.7%. There was an increase in positive predictive value from 14.4 to 18.7%. The overall rate of patient misclassification fell from 18.0 to 13.1%. In conclusion, increasing maternal carbohydrate intolerance in pregnant women without GDM is associated with a graded increase in adverse maternal and fetal outcomes. Infant macrosomia is an important factor in high cesarean delivery rates for women with untreated borderline GDM. Although detection and treatment of GDM normalizes birth weights, rates of cesarean delivery remain inexplicably high. Recognition of GDM may lead to a lower threshold for surgical delivery. The efficiency of screening for GDM can be enhanced by adjusting the current GCT threshold of 7.8 mmol/l to new values related to time since the last meal before screening. Further analyses are underway to elucidate whether maternal risk factors can be used to achieve additional efficiency gains in screening.

Birth Weight↗
PubMed1997

Intervention to reduce telephone prescription requests.

OBJECTIVE: To evaluate a systematic effort to reduce telephone orders for prescription medications in a community family practice. DESIGN: Three-year intervention project. SETTING: Solo family practice in Ottawa. PARTICIPANTS: All patients requesting telephone orders for prescription medications. INTERVENTIONS: A retrospective analysis of phone requests and orders was conducted on 1 continuous year's records. A new office policy was instituted on October 9, 1992, discouraging telephone orders for prescription medication. Prescription telephone requests and orders were then monitored continuously for the next 3 years. MAIN OUTCOME MEASURES: Number of telephone prescription requests and orders per half-day 1 year before the intervention compared with the number for the 3 years after the intervention. RESULTS: One year before the intervention, there were 4.96 telephone prescription requests per half-day: 3 years after the intervention this number fell to 0.85. One year before the intervention, the number of telephone prescription orders per half-day was 4.80; this number fell continuously to 0.67 during the 3 years following the intervention. CONCLUSIONS: We observed a reduction in the number of telephone prescription requests and orders following the introduction of an office policy that encouraged prescribing and renewing medication in person.

Drug Prescriptions↗
PubMed1995

Impact of increasing carbohydrate intolerance on maternal-fetal outcomes in 3637 women without gestational diabetes. The Toronto Tri-Hospital Gestational Diabetes Project.

OBJECTIVE: Our purpose was to assess maternal-fetal outcomes in patients with increasing carbohydrate intolerance not meeting the current criteria for the diagnosis of gestational diabetes. STUDY DESIGN: We conducted a prospective analytic cohort study in which nondiabetic women aged > or = 24 years, receiving prenatal care in three Toronto teaching hospitals, were eligible for enrollment. A glucose challenge test and an oral glucose tolerance test were administered at 26 and 28 weeks' gestation, respectively; risk factors for unfavorable maternal-fetal outcomes were recorded. Caregivers and patients were blinded to glucose values except when test results met the current criteria for gestational diabetes. RESULTS: Of 4274 patients screened, 3836 (90%) continued to the diagnostic oral glucose tolerance test. The study cohort was formed by the 3637 (95%) patients without gestational diabetes, carrying singleton fetuses. Increasing carbohydrate intolerance in women without overt gestational diabetes was associated with a significantly increased incidence of cesarean sections, preeclampsia, macrosomia, and need for phototherapy, as well as an increased length of maternal and neonatal hospital stay. Multivariate analysis showed that increasing carbohydrate intolerance is an independent predictor for various unfavorable outcomes. CONCLUSION: Increasing maternal carbohydrate intolerance in pregnant women without gestational diabetes is associated with a graded increase in adverse maternal-fetal outcomes.

Adult↗
PubMed1994

Impact of time since last meal on the gestational glucose challenge test. The Toronto Tri-Hospital Gestational Diabetes Project.

OBJECTIVE: The purpose of the study was to evaluate the impact of time since the last meal on the glucose challenge test and to find cut points that are most likely to predict the outcome of the oral glucose tolerance test in patients screened for gestational diabetes. STUDY DESIGN: This prospective analytic cohort study was carried out at the University of Toronto Perinatal Complex. A 50 gm glucose load was given at 26 weeks' gestation and the time since previous meal ingestion was recorded. At 28 weeks' gestation a 100 gm oral glucose tolerance test was administered. A total of 4274 eligible patients were screened. RESULTS: Time since the last meal had a marked effect on mean plasma glucose. Receiver-operator characteristic curve analysis with National Diabetes Data Group criteria to interpret the oral glucose tolerance allowed the selection of the most efficient cut points for the glucose challenge test on the basis of time since the last meal. These cut points were 8.2, 7.9, and 8.3 mmol/L for elapsed postprandial times of < 2, 2 to 3, and > 3 hours, respectively. With this change from the current threshold of 7.8 mmol/L the number of patients with a positive screening test dropped from 18.5% to 13.7%. There was an increase in positive predictive value from 14.4% to 18.7%. The rate of patient misclassification fell from 18.0% to 13.1%. CONCLUSION: We suggest that screening strategies for detection of gestational diabetes be reconsidered, to account for the impact of variable postprandial status on the test results.

Adult↗
PubMed1991

Peripartum cocaine use: estimating risk of adverse pregnancy outcome.

Pregnancy outcome of 83 patients with a positive urine toxicology screen for cocaine in the third trimester were reviewed. The outcomes of pregnancies complicated by cocaine abuse were compared to those of matched controls selected from our general obstetric population. We observed a statistically significant increase in the incidence of premature separation of the placenta, low birthweight infants, preterm deliveries, and the incidence of fetal distress requiring cesarean section. On admission, 55% of patients denied recent cocaine use. These observations have implications for planning perinatal services.

Abruptio Placentae↗
PubMed1985

Overview of computed tomography of the temporomandibular joint.

Computed tomography of the temporomandibular joint has been shown to be an accurate method of assessing the position of the disk. To date, we have examined over 500 patients with this modality and have found it also to be effective in the evaluation of other osseous and soft tissue abnormalities. An overview of temporomandibular joint pathology is presented, including the range of osteoarthritic changes from spur formation to complete fusion. Anterior dislocation, with and without reduction, and closed lock are demonstrated. A heretofore unreported phenomenon--posterior dislocation of the meniscus with open lock--is presented. Also shown is the computed tomography evaluation of splint therapy, which has not been dealt with in other publications.

Adult↗
PubMed1984

A subtraction technique in conventional angiography.

A subtraction technique is described for conventional angiography by which a superimposed vessel can be removed, allowing exact visualization of the area in question. The method is easy, requires only standard subtraction apparatus, and obviates the need for additional contrast material injections.

Angiography↗