What is your diagnosis? Refractory 'wound infection' in a dog.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
S Rich
Publications and source records attributed to S Rich.
Fludarabine, melphalan, and alemtuzumab conditioning in adults with standard-risk advanced acute myeloid leukemia and myelodysplastic syndrome.
PURPOSE: This prospective phase II study evaluated toxicity, relapse rate, progression-free survival, and overall survival after allogeneic transplantation and conditioning with fludarabine, melphalan, and alemtuzumab in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). PATIENTS AND METHODS: Fifty-two consecutive adults with AML and MDS were enrolled onto the study. Median age was 52 years (range, 17 to 71 years) and the majority of patients had high-risk disease, comorbidities, and/or modest reduction in performance status. Fifty-six percent of patients had unrelated or mismatched related donors. RESULTS: After a median follow-up of 18 months (range, 2 to 34 months), 1-year survival was 48% (95% CI, 34% to 61%), progression-free survival was 38% (95% CI, 25% to 52%), relapse rate was 27% (95% CI, 15% to 40%), and treatment-related mortality was 33% (95% CI, 20% to 46%). The cumulative probability of extensive chronic graft-versus-host disease (GVHD) was only 18% (95% CI, 8% to 40%); extensive chronic GVHD was only observed in recipients of unrelated donor transplants. Performance score and disease status were the major predictors of outcome. High-risk disease (ie, active AML or MDS with > 5% blasts) or even modest decreases in performance status were associated with poor outcomes. Patients with standard-risk leukemia (first or second complete remission) or MDS (< 5% blasts) had excellent outcomes despite unfavorable disease characteristics. CONCLUSION: Fludarabine and melphalan combined with in vivo alemtuzumab is a promising transplantation regimen for patients with AML or MDS and low tumor burden. For patients with active disease, this regimen provides at best modest palliation. Despite a low incidence of GVHD, transplantation is still associated with considerable nonrelapse mortality in patients with decreased performance status.
Acute Disease↗
Clonal diversity and stability of subgingival Eikenella corrodens.
Eikenella corrodens is a commensal subgingival bacterium commonly found in both periodontally nondiseased and diseased subjects. The present study examined the clonal diversity and stability of subgingival E. corrodens over time. Ninety-five subjects were enrolled at the baseline examination, including 44 periodontally nondiseased subjects and 51 subjects with aggressive periodontitis. Twenty-two nondiseased subjects and 11 subjects with aggressive periodontitis were subsequently reexamined after an average interval of 14 months. Two subgingival plaque samples were obtained from each subject to determine the total cultivable bacteria. In addition, multiple E. corrodens isolates from each sample were recovered for clonal analysis by arbitrarily primed PCR. The mean numbers of distinct E. corrodens clones harbored by nondiseased subjects and subjects with aggressive periodontitis were 1.3 and 3.0, respectively. Thirty-nine percent of the nondiseased subjects and 63% of the subjects with aggressive periodontitis harbored multiple clones of E. corrodens. The numbers of distinct E. corrodens clones increased significantly (Mann-Whitney ranking test, P < 0.05) in sites from patients with aggressive periodontitis, in sites with pocket depths of 4 mm or greater, in sites with a clinical attachment loss of 2 mm or greater, and in sites coinfected with Porphyromonas gingivalis. Comparison of E. corrodens clones recovered at the baseline and those recovered at the follow-up examination showed that E. corrodens colonization was not stable. Thirty-eight of the 66 follow-up samples (58%) showed a complete change (including de novo colonization of the sites or complete elimination of the organism from the sites) of the subgingival E. corrodens clonal types between the baseline and the follow-up examinations. Our results suggest a complexity of subgingival microbiota not seen previously.
Adolescent↗
Age and gender distributions of coronary artery calcium detected by electron beam tomography in 35,246 adults.
Electron beam tomography (EBT) is a noninvasive method used to detect coronary artery calcium (CAC). Due to the age-associated increase in incidence and magnitude of CAC, interpretation of results can be difficult. The purpose of this study was to develop a set of age- and gender-stratified CAC distributions to serve as standards for the clinical interpretation of EBT scans. Between 1993 and 1999, 35,246 asymptomatic subjects, 30 to 90 years of age, were self-referred for CAC screening using an Imatron EBT scanner. CAC score was calculated based on the number, areas, and peak computed tomographic density for each detected calcific lesion. CAC score in each coronary artery was equal to the sum of all lesions for that artery and the total CAC score was equal to the sum of the score of each artery. Total CAC scores were assigned to a percentile according to age and gender. CAC scores were reported at the 10th, 25th, 50th, 75th, and 90th percentiles for 16 age and/or gender groups. The prevalence of CAC increased with age for men and women. The extent of CAC differed significantly between men and women in the same age group. In summary, this study reports the distribution of CAC score by age and gender. Knowledge of the distribution of CAC, the effect of age on the total CAC score as well as the differences in total CAC scores that exist between men and women of similar age will assist the clinician in interpreting EBT CAC results.
Adult↗
Severe pulmonary hypertension: critical care clinics.
Pulmonary hypertension has many causes and therapies. A meticulous evaluation is critical. Substantial advances in medical therapy have occurred over the past decade, and the future treatment of this syndrome is promising, with many new medications on the horizon.
Anticoagulants↗
Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort.
BACKGROUND: Established determinants of fasting total homocysteine (tHcy) concentration include folate and vitamin B-12 status, serum creatinine concentration, and renal function. OBJECTIVE: Our objective was to examine the relation between known and suspected determinants of fasting plasma tHcy in a population-based cohort. DESIGN: We examined the relations between fasting plasma tHcy concentrations and nutritional and other health factors in 1960 men and women, aged 28-82 y, from the fifth examination cycle of the Framingham Offspring Study between 1991 and 1994, before the implementation of folic acid fortification. RESULTS: Geometric mean tHcy was 11% higher in men than in women and 23% higher in persons aged > or = 65 y than in persons aged < 45 y (P < 0.001). tHcy was associated with plasma folate, vitamin B-12, and pyridoxal phosphate (P for trend < 0.001). Dietary folate, vitamin B-6, and riboflavin were associated with tHcy among non-supplement users (P for trend < 0.01). The tHcy concentrations of persons who used vitamin B supplements were 18% lower than those of persons who did not (P < 0.001). tHcy was positively associated with alcohol intake (P for trend = 0.004), caffeine intake (P for trend < 0.001), serum creatinine (P for trend < 0.001), number of cigarettes smoked (P for trend < 0.001), and antihypertensive medication use (P < 0.001). CONCLUSIONS: Our study confirmed, in a population-based setting, the importance of the known determinants of fasting tHcy and suggested that other dietary and lifestyle factors, including vitamin B-6, riboflavin, alcohol, and caffeine intakes as well as smoking and hypertension, influence circulating tHcy concentrations.
Adult↗
Stenting to reverse left ventricular ischemia due to left main coronary artery compression in primary pulmonary hypertension.
Angina is a common symptom of severe pulmonary hypertension. Although many theories for the source of this pain have been proposed, right ventricular ischemia is the one most commonly accepted as the cause. We report on two patients with primary pulmonary hypertension who had angina with normal activity or on provocation. One patient had severe left ventricular dysfunction. Both were found to have severe ostial stenosis of the left main coronary artery as a result of compression from a dilated pulmonary artery. Both patients underwent stenting of the left main coronary artery with excellent angiographic results, and complete resolution of the signs and symptoms of angina and left ventricular ischemia. Left ventricular ischemia due to compression of the left main coronary artery may be a much more common mechanism of angina and left ventricular dysfunction in patients with pulmonary hypertension than previously acknowledged. Stenting of the coronary artery can be done safely with the resolution of these symptoms.
Aged↗
Increased prevalence of significant coronary artery calcification in patients with diabetes.
OBJECTIVE: Coronary artery disease is the major cause of morbidity and mortality in patients with diabetes. Detection of coronary artery disease before the first myocardial infarction and before anginal symptoms will allow for strategies designed to reduce the cardiovascular event rate in this group of patients. Electron beam-computed tomography (EBCT) is a noninvasive technology for evaluating the extent of coronary artery atherosclerosis that relies on the detection of coronary artery calcium (CAC). We used EBCT to detect significant coronary artery atherosclerosis in diabetic patients without symptoms of heart disease. RESEARCH DESIGN AND METHODS: We used EBCT to evaluate calcium in the coronary arteries of 139 consecutive diabetic patients scanned over a 20-month period. The CAC scores in this group were compared with a randomly selected nondiabetic control group and a control group that was selected to match a number of established cardiovascular risk factors. RESULTS: Patients with diabetes had a significant increase in the prevalence of CAC scores > or =400 (25.9%) compared with the randomly selected (7.2%) and matched (14.4%) nondiabetic control groups. Scores in this range have been reported to be highly predictive for abnormal stress myocardial perfusion tomography and subsequent coronary events. CONCLUSIONS: Our results, therefore, indicate a substantial prevalence of significant coronary artery disease in an asymptomatic diabetic patient population compared with nondiabetic control subjects. They also suggest that EBCT may be a useful approach for selecting a group of diabetic subjects who would benefit most from additional evaluation for subclinical coronary artery disease.
Calcinosis↗
Primary pulmonary hypertension: a vascular biology and translational research "Work in progress".
Primary pulmonary hypertension (PPH) is a syndrome of dyspnea, chest pain, and syncope defined by increased pulmonary vascular resistance and the absence of a known cause. It also occurs in a familial form, which is linked to unidentified genes on chromosome 2. This syndrome is characterized by abnormalities of pulmonary vascular biology in each compartment of the blood vessel. The lumen has a prothrombotic diathesis, the endothelium displays an excessive production of vasoconstrictors relative to vasodilators, and the smooth muscle cells are depolarized and calcium-overloaded, which is due in part to reduced expression of voltage-gated potassium channels (Kv). This causes vasoconstriction and may promote cell proliferation. The adventitia displays excessive remodeling, which is associated with exaggerated metalloproteinase and elastase activity. Conceptually, PPH seems to require a permissive genotype, a susceptible phenotype (eg, endothelial dysfunction) and, in many cases, an exogenous trigger (eg, an anorexigen). Although there is not a generally accepted, unifying hypothesis regarding its cause, impaired function and the expression of vascular and platelet Kv channels suggest PPH may be a disease of the ion channels. Abnormal matrix metalloproteinase and elastase activity could also explain the abnormal vascular tone, platelet activation, and remodeling in PPH. Although calcium-channel blockers and prostacyclin, particularly when coadministered with warfarin, improve survival, PPH has a 5-year mortality rate of approximately 50%. Pharmacological and gene therapies aimed at enhancing the activity of prostacyclin, nitric oxide synthases, and Kv channels or at inhibiting endothelin and matrix metalloproteinases are promising areas for future development.
Anticoagulants↗
Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial.
BACKGROUND: Pulmonary hypertension is a progressive and often fatal complication of the scleroderma spectrum of disease for which no treatment has been proven effective in a randomized trial. OBJECTIVE: To determine the effect of epoprostenol on pulmonary hypertension secondary to the scleroderma spectrum of disease. DESIGN: Randomized, open-label, controlled trial. SETTING: 17 pulmonary hypertension referral centers. PATIENTS: 111 patients with moderate to severe pulmonary hypertension. INTERVENTION: Epoprostenol plus conventional therapy or conventional therapy alone. MEASUREMENTS: The primary outcome measure was exercise capacity. Other measures were cardiopulmonary hemodynamics, signs and symptoms of pulmonary hypertension and scleroderma, and survival. RESULTS: Exercise capacity improved with epoprostenol (median distance walked in 6 minutes, 316 m at 12 weeks compared with 270 m at baseline) but decreased with conventional therapy (192 m at 12 weeks compared with 240 m at baseline). The difference between treatment groups in the median distance walked at week 12 was 108 m (95% CI, 55.2 m to 180.0 m) (P < 0.001). Hemodynamics improved at 12 weeks with epoprostenol. The changes in mean pulmonary artery pressure for the epoprostenol and conventional therapy groups were -5.0 and 0.9 mm Hg, respectively (difference, -6.0 mm Hg [CI, -9.0 to -3.0 mm Hg), and the mean changes in pulmonary vascular resistance were -4.6 and 0.9 mm Hg/L per minute, respectively (difference, -5.5 mm Hg/L per minute [CI, -7.3 to -3.7 mm Hg/L per minute). Twenty-one patients treated with epoprostenol and no patients receiving conventional therapy showed improved New York Heart Association functional class. Borg Dyspnea Scores and Dyspnea-Fatigue Ratings improved in the epoprostenol group. Trends toward greater improvement in severity of the Raynaud phenomenon and fewer new digital ulcers were seen in the epoprostenol group. Four patients in the epoprostenol group and five in the conventional therapy group died (P value not significant). Side effects of epoprostenol therapy included jaw pain, nausea, and anorexia. Adverse events related to the epoprostenol delivery system included sepsis, cellulitis, hemorrhage, and pneumothorax (4% incidence for each condition). CONCLUSIONS: Continuous epoprostenol therapy improves exercise capacity and cardiopulmonary hemodynamics in patients with pulmonary hypertension due to the scleroderma spectrum of disease.
Adult↗
Primary Pulmonary Hypertension.
Primary pulmonary hypertension has become a very treatable disease given the recent advances in medical therapy. Any patient with unexplained right ventricular enlargement or pulmonary hypertension needs a thorough workup to determine the cause. Patients with primary pulmonary hypertension should be referred to a specialized "Center of Excellence" to evaluate potential therapies on a case-by-case basis. Warfarin anticoagulation is generally recommended in all patients. Some patients (approximately 20%) will have a dramatic response to high doses of calcium channel blockers; the remainder are generally helped by the use of continuous intravenous prostacyclin therapy. Lung transplantation remains the final treatment option for patients in whom medical therapy fails.
Journal Article↗
Plasma vitamin B-12 concentrations relate to intake source in the Framingham Offspring study.
BACKGROUND: Low vitamin B-12 status is prevalent among the elderly, but few studies have examined the association between vitamin B-12 status and intake. OBJECTIVE: We hypothesized that vitamin B-12 concentrations vary according to intake source. DESIGN: Plasma concentrations and dietary intakes were assessed cross-sectionally for 2999 subjects in the Framingham Offspring Study. The prevalence of vitamin B-12 concentrations <148, 185, and 258 pmol/L was examined by age group (26-49, 50-64, and 65-83 y), supplement use, and the following food intake sources: fortified breakfast cereal, dairy products, and meat. RESULTS: Thirty-nine percent of subjects had plasma vitamin B-12 concentrations <258 pmol/L, 17% had concentrations <185 pmol/L, and 9% had concentrations <148 pmol/L, with little difference between age groups. Supplement users were significantly less likely than non-supplement-users to have concentrations <185 pmol/L (8% compared with 20%, respectively). Among non-supplement-users, there were significant differences between those who consumed fortified cereal >4 times/wk (12%) and those who consumed no fortified cereal (23%) and between those in the highest and those in the lowest tertile of dairy intake (13% compared with 24%, respectively), but no significant differences by meat tertile. Regression of plasma vitamin B-12 on log of intake, by source, yielded significant slopes for each contributor adjusted for the others. For the total group, b = 40.6 for vitamin B-12 from vitamin supplements. Among non-supplement-users, b = 56.4 for dairy products, 35.2 for cereal, and 16.7 for meat. Only the meat slope differed significantly from the others. CONCLUSIONS: In contrast with previous reports, plasma vitamin B-12 concentrations were associated with vitamin B-12 intake. Use of supplements, fortified cereal, and milk appears to protect against lower concentrations. Further research is needed to investigate possible differences in bioavailability.
Adult↗
Handling adverse event reports.
Explore the source record for details and available documents.
Adverse Drug Reaction Reporting Systems↗
Anorexigens and pulmonary hypertension in the United States: results from the surveillance of North American pulmonary hypertension.
BACKGROUND: The use of appetite suppressants in Europe has been associated with the development of primary pulmonary hypertension (PPH). Recently, fenfluramine appetite suppressants became widely used in the United States but were withdrawn in September 1997 because of concerns over adverse effects. MATERIALS AND METHODS: We conducted a prospective surveillance study on patients diagnosed with pulmonary hypertension at 12 large referral centers in North America. Data collected on patients seen from September 1, 1996, to December 31, 1997, included the cause of the pulmonary hypertension and its severity. Patients with no identifiable cause of pulmonary hypertension were classed as PPH. A history of drug exposure also was taken with special attention on the use of antidepressants, anorexigens, and amphetamines. RESULTS: Five hundred seventy-nine patients were studied, 205 with PPH and 374 with pulmonary hypertension from other causes (secondary pulmonary hypertension [SPH]). The use of anorexigens was common in both groups. However, of the medications surveyed, only the fenfluramines had a significant preferential association with PPH as compared with SPH (adjusted odds ratio for use > 6 months, 7.5; 95% confidence interval, 1.7 to 32.4). The association was stronger with longer duration of use when compared to shorter duration of use and was more pronounced in recent users than in remote users. An unexpectedly high (11.4%) number of patients with SPH had used anorexigens. CONCLUSION: The magnitude of the association with PPH, the increase of association with increasing duration of use, and the specificity for fenfluramines are consistent with previous studies indicating that fenfluramines are causally related to PPH. The high prevalence of anorexigen use in patients with SPH also raises the possibility that these drugs precipitate pulmonary hypertension in patients with underlying conditions associated with SPH.
Adult↗
Genetic polymorphisms of the IL-1alpha and IL-1beta genes in African-American LJP patients and an African-American control population.
BACKGROUND: A functional polymorphism of the interleukin-1 beta (IL-1beta) gene has been proposed to be a risk factor for periodontitis. In adult forms of periodontitis, non-smokers of northern European heritage carrying the "2" allele of the IL-1alpha-889 and the IL-1beta +3953 RFLPs in either the heterozygous or the homozygous state at both loci were observed to have a greater risk for developing severe periodontitis. Studies of early-onset periodontitis (EOP) found that allele "1" of both IL-1alpha-889 and IL-1beta +3953 was transmitted more frequently with the EOP phenotype. The purpose of the present study was to determine the prevalence of the IL-1alpha and IL-1beta genotype polymorphisms in an African-American (AA) control population and in 37 African-Americans with localized juvenile periodontitis (LJP). METHODS: The IL-1alpha +4845 and IL-1beta +3953 loci were genotyped by PCR amplification, followed by restriction enzyme digestion and gel electrophoresis. The IL-1alpha +4845 locus, in linkage disequilibrium (>99%) with IL-1alpha-889, was genotyped because it is technically easier. Data were analyzed using r x c contingency tables. RESULTS: The IL-1beta +3953 allele "1" was carried by >99% of the AA control population and by 100% of the AA LJP group, with most individuals being homozygous 1,1. The prevalence of the composite genotype with at least one allele "2" at each of the IL-1beta +3953 and IL-1alpha +4845 loci was 14% (AA control group) and 8% (AA LJP group). CONCLUSIONS: Given the high frequency of the IL-1beta allele "1" in the African-American population, it would appear that knowledge of this +3953 polymorphism would provide little diagnostic or predictive information for LJP.
Adult↗
Severe pulmonary hypertension associated with COPD.
Pulmonary hypertension can be associated with chronic obstructive pulmonary disease (COPD). Mild to moderate elevations in pulmonary artery pressures are commonly reported. Previous studies included patients initially diagnosed with COPD and subsequently evaluated for pulmonary hypertension. The occurrence of COPD in patients being evaluated for pulmonary hypertension has not been reported. We performed a retrospective chart review of approximately 600 patients evaluated in a large tertiary care pulmonary hypertension clinic. Subjects were included if they were older than 40 years, had no other secondary causes of pulmonary hypertension and had evidence of COPD by pulmonary function studies or thoracic computed tomography. Criteria was met by five subjects (3 males and 2 females, mean age = 65 years) all of whom were past smokers. The average mean pulmonary artery pressure (MPAP) was 59 +/- 7 mm Hg. The mean pulmonary vascular resistance (PVR) was 15.2 +/- 5 mmHg/liter/min. Only one patient had a fall in MPAP of more than 10% and a greater than 30% decline in PVR following infusion of adenosine to test vasodilator responsiveness. COPD is rare in a population referred primarily for evaluation of pulmonary hypertension. Although infrequent, severe pulmonary hypertension may be associated with COPD.
Adenosine↗
Progesterone receptors in the thymus are required for thymic involution during pregnancy and for normal fertility.
Thymocyte development is reported to be inhibited by pregnancy, although the impact of this effect on fertility is unknown. We demonstrate, using progesterone receptor null mutant mice, that the inhibitory effects of pregnancy hormones on T cell development require the presence of functional progesterone receptor (PR). A combination of hysterectomy, thymic immunohistochemistry, and transplant studies reveals that local expression of PR in thymic stromal cells is specifically required for thymic involution to occur. These cells, under the influence of progesterone, block T cell development at the early pre-T cell (CD3(-)CD44(+) CD25(+)) stage of development via a paracrine mechanism. In addition, age-related thymic involution is shown to occur by a separate PR-independent mechanism. Finally, pregnancy studies with thymic transplants from progesterone receptor null mutant mice to wild-type female recipients demonstrate that thymic stromal PR is required for normal fertility. Together, these observations provide evidence for a PR-dependent paracrine mechanism that blocks very early T cell lymphopoiesis during pregnancy and is essential for normal fertility.
Age Factors↗
Utility of electron beam computed tomography to stratify patients presenting to the emergency room with chest pain.
One hundred thirty-four patients presenting to the emergency room with the chief complaint of chest pain were studied with electron beam computed tomography scan. Electron beam computed tomography scanning had a 98% negative predictive value in this setting.
Adult↗