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Biomedical subjects

Katherine Williams

Publications and source records attributed to Katherine Williams.

5 recordsLinked to original sources

Sexual dysfunction in major depression.

Little is known about the prevalence, typology, and natural course of non-drug-induced sexual dysfunction in patients with depression. Loss of libido has been reported in various studies to affect from 25% to 75% of patients with unipolar depression, and its prevalence appears to be correlated with the severity of depression. Disorders of arousal also appear to be relatively common in both men and women with major depression, of whom approximately 25% may experience problems with erection or lubrication. The scant available data regarding orgasmic difficulties in patients with depression who have not yet taken antidepressant medication suggest that they are more common than in the general population. The potential causes of sexual dysfunction in patients with depression are complex and little investigated, and future research must distinguish and explore the various biological, psychological, and psychosocial factors that are likely to be involved.

Antidepressive Agents↗

Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study.

OBJECTIVE: To determine the independent risk factors for coronary artery disease (CAD) in type 1 diabetes by type of CAD at first presentation. RESEARCH DESIGN AND METHODS: This is a historical prospective cohort study of 603 patients with type 1 diabetes diagnosed before 18 years of age between 1950 and 1980. The mean age and duration of diabetes at baseline were 28 (range 8-47) and 19 years (7-37), respectively, and patients were followed for 10 years. Patients with prevalent CAD were excluded from the study. Electrocardiogram (ECG) ischemia was defined by Minnesota Code (MC) 1.3, 4.1-3, 5.1-3, or 7.1; angina was determined by Pittsburgh Epidemiology of Diabetes Complications (EDC) study physician diagnosis; and hard CAD was determined by angiographic stenosis > or =50%, revascularization procedure, Q waves (MC 1.1-1.2), nonfatal myocardial infarction (MI), or CAD death. RESULTS: A total of 108 incident CAD events occurred during the 10-year follow-up: 17 cases of ECG ischemia, 49 cases of angina, and 42 cases of hard CAD (5 CAD deaths, 25 nonfatal MI or major Q waves, and 12 revascularization or > or =50% stenosis). Blood pressure, lipid levels, inflammatory markers, renal disease, and peripheral vascular disease showed a positive gradient across the groups of no CAD, angina, and hard CAD (P < 0.01, trend analysis, all variables), although estimated glucose disposal rate (eGDR) and physical activity showed inverse associations (P < 0.01, trend analysis, both variables). In addition, depressive symptomatology predicted angina (P = 0.016), whereas HbA(1) showed no association with subsequent CAD. CONCLUSIONS: These data suggest that although the standard CAD risk factors are still operative in type 1 diabetes, greater glycemia does not seem to predict future CAD events. In addition, depressive symptomatology predicts angina and insulin resistance (eGDR) predicts hard CAD end points.

Adult↗

Glycemia (or, in women, estimated glucose disposal rate) predict lower extremity arterial disease events in type 1 diabetes.

The purpose of this study was to determine the predictors of lower extremity arterial disease (LEAD) events in a type 1 diabetes population. Data are from the Pittsburgh Epidemiology of Diabetes Complications Study of childhood onset type 1 diabetes. At baseline, the study population had a mean age 28 (range, 8 to 47) years and duration 19 (range, 7 to 37) years. LEAD events, assessed by questionnaire or clinical examination, were defined as claudication (Rose questionnaire), foot ulceration, or lower extremity amputation. Estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated from glycosylated hemoglobin (HbA(1)), waist-to-hip ratio (WHR), and hypertension using an equation previously validated with hyperinsulinemic euglycemic clamp studies. There were incident LEAD events in 70 of 586 subjects during 10 years follow-up, giving an incidence density of 1.3 events/100 person-years. Incidence did not differ by gender. Major predictors of LEAD events were diabetes duration, low-density lipoprotein-cholesterol (LDL-C), heart rate, eGDR, log albumin excretion rate (AER), systolic blood pressure (SBP), hypertension, proliferative retinopathy, distal symmetric polyneuropathy, and overt nephropathy (each P <.001). HbA(1), low ankle brachial index (ABI) (<0.9), and a high ankle brachial difference (ABD) (SBP > or = 75 mm Hg) also predicted LEAD events. Cox modeling suggested that duration (P <.001), HbA(1) (P <.001), hypertension (P =.006), log albumin excretion rate (P =.011), and heart rate (P =.028) predicted events independently. The overall model with HbA(1) and hypertension was significantly better than with eGDR, while the alternate models in men were similar. In women, the model with eGDR showed a significantly better fit. Glycemia, insulin resistance, hypertension and renal disease are powerful predictors of symptomatic lower extremity arterial disease in type 1 diabetes.

Adolescent↗

Proteome and transcriptome analysis of retinoic acid-induced differentiation of human acute promyelocytic leukemia cells, NB4.

Acute promyelocytic leukemia (APL) is characterized by a translocation t(15:17) that fuses the retinoic acid receptor gene with the promyelocytic gene, which blocks differentiation to normal granulocytes. NB4 cells, derived from human acute promyelocytic leukemia, display this genotype and phenotype. All trans-retinoic acid (ATRA) induces differentiation of NB4 cell cultures in vitro and APL in vivo, although resistance to differentiation therapy frequently develops. To identify genes involved in differentiation, we compared gene expression at the mRNA and protein levels using microarray analyses and two-dimensional (2D) difference gel electrophoresis (DIGE), plus MALDI-TOF-TOF mass spectrometry. Differentially expressed transcripts were identified using oligonucleotide-based microarrays with targets representing almost 14 000 genes. Real time PCR was performed on a subset of genes whose products were shown to be differentially expressed using proteomic and/or genomic approaches. Our analyses identified 46 genes that were differentially expressed in NB4 +/- ATRA; 22 were identified using 2D-DIGE and 24 using microarray analysis. All but four of these genes were expressed at higher levels in differentiated cells, and several controlled cell structure (internal and cytoskelatal) or signal transduction. We observed that proteome analysis with DIGE and silver-stained 2D gel electrophoresis analyses revealed significant differences between the two measurement approaches. Furthermore, our data showed significant discordance between gene expression at the protein and transcript levels.

Cell Differentiation↗