Biomedical subjects
J Sullivan
Publications and source records attributed to J Sullivan.
The Canadian Study of Cardiac Transplantation. Atherosclerosis. Investigators of the CASCADE Study.
OBJECTIVES: To describe risk factors associated with the development of transplantation coronary artery disease (TCAD). DESIGN: A retrospective study of the Canadian experience. PATIENTS: Seven hundred and nineteen patients with follow-up of at least 12 months following transplantation and a minimum of one coronary angiogram were analyzed. RESULTS: Two hundred and fourteen patients (30%) developed angiographic evidence of TCAD during an average follow-up of 50+/-25 months. Actuarial freedom rate from TCAD averaged 60%, and survival averaged 85% five years following transplantation. Abnormal coronary angiograms increased from 11% to 40% between the first and the fifth year following transplantation. The Cox multivariate final model showed that recipients of donor hearts of 50 years and older (RR 4.35, 95% CI 2.32 to 8.15), patients with two or more episodes of acute rejection (RR 1.56, 95% CI 1.11 to 2.21) and patients with a diagnosis of ischemic cardiomyopathy before transplantation (RR 1.38, 95% CI 1.03 to 1.84) were at higher risk of TCAD. The same risk factors also had a significant effect on survival, although patients who were administered a hepatic hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor during follow-up had a higher survival rate (95% versus 85%, P=0.01) five years following heart transplantation. CONCLUSIONS: Recipients of hearts from older donors, patients with an ischemic heart disease before transplantation and those with several episodes of acute rejection are at increased risk for TCAD. Patients who are administered an HMG-CoA reductase inhibitor during follow-up have a higher survival rate five years following transplantation.
A two-year, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles.
OBJECTIVE: To compare the effects of two doses of conjugated equine estrogen (CEE) and two of esterified estrogen plus methyltestosterone (E + A) in surgically menopausal women. STUDY DESIGN: A two-year, parallel-group, double-blind study of 311 women who were randomly assigned to one of four regimens: (1) CEE, 0.625 mg/d; (2) CEE, 1.25 mg/d; (3) esterified estrogens, 0.625 mg, + methyltestosterone, 1.25 mg/d; or (4) esterified estrogens, 1.25, + methyltestosterone, 2.5 mg/d. Study parameters were symptoms, lipids, bone mineral density, side effects and safety. RESULTS: All treatments prevented loss of bone in the spine and hip. The higher E + A dose increased spine and hip BMD more than other treatments (P < .002). All treatments improved menopausal symptoms, with non-significantly greater improvements in well-being and sexual interest in the E + A groups. Similar and significant decreases in low-density lipoprotein were observed in all groups, but high-density lipoprotein and triglycerides were increased only in the unopposed estrogen groups (P < .05). Hirsutism was uncommon and similar in all groups at two years. Discontinuation rates and reasons for withdrawal from the study were similar in both groups. No clinically significant side effects or laboratory test abnormalities were seen. CONCLUSION: As compared to estrogen alone, E + A significantly improved BMD and was well tolerated in surgically menopausal women.
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
The ligand for osteoprotegerin has been identified, and it is a TNF-related cytokine that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the osteoclast lineage and stimulates the rapid induction of genes that typify osteoclast development. OPGL directly activates isolated mature osteoclasts in vitro, and short-term administration into normal adult mice results in osteoclast activation associated with systemic hypercalcemia. These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development.
Valsartan in heart failure patients previously untreated with an ACE inhibitor.
OBJECTIVE: To evaluate the effect on cardiac hemodynamic parameters of valsartan in patients with chronic stable congestive heart failure previously untreated with ACE inhibitors. METHODS: After a 2 to 4 week run-in period, 116 adult outpatients were randomized to receive valsartan 40, 80 or 160 mg twice daily, the ACE inhibitor lisinopril 5/10 mg once daily, or placebo. At baseline and after 28 days of treatment, cardiac hemodynamic parameters were measured. Tolerability was assessed by adverse events and by any changes in systolic or diastolic blood pressure, body weight, heart rate, and routine laboratory parameters. RESULTS: For the 12 hour time point (trough), all doses of valsartan reduced mean pulmonary capillary wedge pressure (statistically significant for valsartan 40 mg and 160 mg), decreased systemic vascular resistance (statistically significant for all three valsartan doses and for lisinopril at peak and trough), and increased cardiac output (statistically significant for all three valsartan doses at peak, and for 80 and 160 mg at trough). There were no clinically relevant effects on any safety parameters. CONCLUSIONS: Valsartan has beneficial effects on cardiac hemodynamics, and is generally well tolerated in patients with congestive heart failure not taking ACE inhibitors.
28S and 18S rDNA sequences support the monophyly of lampreys and hagfishes.
Resolving the interrelationships of three major extant lineages of vertebrates (hagfishes, lampreys, and gnathostomes) is a particularly important issue in evolution, because the basal resolution critically influences our understanding of primitive vertebrate characters. A consensus has emerged over the last 20 years that lampreys are the sister group to the gnathostomes and the hagfishes represent an ancient, basal lineage. This hypothesis has essentially displaced the classical hypothesis of monophyly of the cyclostomes (lampreys plus hagfishes). To test these hypotheses, we compared nearly complete ribosomal DNA sequences from each of these major lineages, as well as those from a cephalochordate and a urochordate, which represent a paraphyletic outgroup for assessing the basal vertebrate relationships. For this comparison, 92%-99% complete 28S rDNA sequences were obtained from the lancelet Branchiostoma floridae, the hagfish Eptatretus stouti, the lamprey Petromyzon marinus, and cartilaginous fishes Hydrolagus colliei and Squalus acanthias and were then analyzed with previously reported 28S and 18S rDNA sequences from other chordates. We conducted conventional (nonparametric) bootstrap analyses, under maximum-likelihood, parsimony, and minimum-evolution (using LogDet distances) criteria, of both 28S and 18S rDNA sequences considered separately and combined. All these analyses provide moderate to very strong support for the monophyly of the cyclostomes. Furthermore, the currently accepted hypothesis of a lamprey-gnathostome clade is moderately rejected by the Kishino-Hasegawa test (P = 0.099) and resoundingly rejected by parametric bootstrap tests (P < 0.01) in favor of monophyly of living cyclostomes. Another significant finding is that the hagfish E. stouti has the longest 28S rDNA gene known in any organism (> 5,200 nt).
Reducing costs and improving processes for the interventional cardiology patient.
The cardiology unit at the University of Chicago Hospitals developed a cost-saving mechanism in the care of postinterventional cardiology patients, reducing time spent in the coronary care unit. Increased nursing education and training and better identification of patient outcomes made this collaborative effort a cost-saving and effective pilot.
Get real: clinical testing of patients' reading abilities.
Education of cancer patients is complicated by a number of factors including timing, understanding of medical terms, and anxiety-induced inattention. The concern about patient education has led to the common practice of providing brochures about cancer, responses to cancer, treatment, and management of side effects. This material is often written at reading levels that do not match the reading ability of the patient. Research has indicated that the stated educational level is not equivalent to reading level. Realistic testing of a patient's reading ability thus becomes important in choosing the correct educational materials. This article reviews seven common available tests and discusses in detail the use of the Rapid Estimation of Adult Literacy in Medicine (REALM).
Prenatal identification of de novo marker chromosomes using micro-FISH approach.
Chromosome microdissection combined with polymerase chain reaction (PCR) and reverse chromosome painting ('micro-FISH') is a powerful technique for the unequivocal identification of complex or subtle chromosomal aberrations. We have applied this technique to the prenatal diagnosis of three fetuses with de novo marker chromosomes. One small supernumerary satellited marker chromosome was shown to have originated from the fusion of the centromeric heterochromatin of one or both of chromosomes 14 and 22. The second marker was identified as i(9)(p10) while the third marker chromosome was shown to have been derived from the 1p13.1-1q21.3 region. At birth, the clinical outcome correlated well with that expected from the prenatal cytogenetic findings. Our study highlights the importance of the application of 'micro-FISH' to prenatal diagnosis.
Cutaneous metastases from adenocarcinoma of unknown primary.
Cutaneous manifestations of malignancy are not uncommon, especially in advanced disease. They may also occur early in malignant disease or they may even signify recurrence particularly if they are paraneoplastic in nature. Clinical diagnosis can be difficult because of the wide spectrum of appearance of these lesions, and, in many cases, because of the lack of an identifiable underlying primary. Presented here is the case of a 65-year-old woman with multiple inflammatory cutaneous metastases, which were sclerodermoid in nature. These appeared 14 months after initial diagnosis of adenocarcinoma of unknown primary (ACUP) and signified the beginning of a rapid deterioration in her condition. The coexistence of limited systemic sclerosis (scleroderma) and ACUP initially raised several interesting diagnostic possibilities. Adenocarcinoma of unknown primary and the sclerodermoid reaction in malignancy are discussed.
Treatment of community-acquired acute uncomplicated urinary tract infection with sparfloxacin versus ofloxacin. The Sparfloxacin Multi Center UUTI Study Group.
The efficacy and safety of a 3-day regimen of sparfloxacin were compared with those of a 3-day regimen of ofloxacin for the treatment of community-acquired acute uncomplicated urinary tract infections. Four hundred nineteen women were enrolled in a randomized, open-label, observer-blinded, multicenter study; 204 received sparfloxacin as a 400-mg loading dose on the first day and 200 mg once daily thereafter, and 215 received ofloxacin as 200 mg twice daily. A total of 383 patients met the criteria for clinical evaluability, and 174 were also bacteriologically evaluable; all treated patients were included in the safety analysis. Escherichia coli (86%) and Staphylococcus saprophyticus (4.6%) were the organisms most commonly isolated. Positive clinical responses were obtained 5 to 9 days after therapy in more than 92% of the patients in each group; sustained clinical cure rates 4 to 6 weeks after therapy were 78.3 and 76.9% in the sparfloxacin and ofloxacin groups, respectively. A positive bacteriologic response was observed in 98% of the bacteriologically evaluable patients in each treatment group at 5 to 9 days posttherapy and in 88.2 and 92.6% of the patients in the sparfloxacin and ofloxacin groups, respectively, 4 to 6 weeks after therapy. Almost 90% of all adverse events were of mild or moderate severity; the most frequent events at least possibly related to drug treatment were those common to the fluoroquinolones, namely, nausea, diarrhea, headache, insomnia, and photosensitivity. Photosensitivity was more frequent in the sparfloxacin group (6.9% versus 0.5% in the ofloxacin group); insomnia was more frequent in the ofloxacin group (3.7% versus 1.0% in the sparfloxacin group). These data suggest that a once-daily, 3-day regimen of sparfloxacin is effective and generally well tolerated in the treatment of acute uncomplicated urinary tract infections.
Vietnamese and Australian birth outcomes.
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Cardiac tamponade during laparoscopic Nissen fundoplication.
Laparoscopic Nissen fundoplication is becoming a popular technique in the surgical management of reflux disease. The advantages of laparoscopic surgery include shorter hospital stays, greater patient acceptance and decreased overall morbidity. Laparoscopic surgery eliminates the necessity for an upper abdominal incision and the consequent post-operative impairment of pulmonary mechanics. Laparoscopic Nissen fundoplication has been associated with a low incidence of severe peri-operative complications although of a different nature to those following the open procedure. We are reporting a rare case of acute cardiovascular collapse secondary to cardiac tamponade during laparoscopic Nissen fundoplication.
The risk of cerebrovascular accident in patients with asymptomatic critical carotid artery stenosis who undergo open-heart surgery.
OBJECTIVE: To investigate whether the presence of asymptomatic critical carotid stenosis (ASCCS) increases the risk of perioperative stroke during open-heart surgery, which carries a well-established risk of cerebrovascular accidents. DESIGN: A case series. SETTING: A university-affiliated hospital that is a major referral centre for cardiovascular surgery. PATIENTS: Forty-six patients with ASCCS who underwent open-heart surgery between January 1992 and January 1996. Of this group, 27 had bilateral and 19 had unilateral critical carotid artery stenosis. INTERVENTIONS: Various cardiac procedures were performed on the 46 patients: 33 underwent coronary bypass grafting, 12 had valve replacement and 1 had heart transplantation. MAIN OUTCOME MEASURE: Neurologic deficit. RESULTS: None of the patients had any perioperative neurologic deficit up to the date of discharge. CONCLUSIONS: Cardiac procedures, without prior carotid artery surgery, can be done in patients with ASCCS with no significant added risk of stroke. To achieve this, blood pressure should be kept stable intraoperatively, at slightly higher than normal pressure.
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
A novel secreted glycoprotein that regulates bone resorption has been identified. The protein, termed Osteoprotegerin (OPG), is a novel member of the TNF receptor superfamily. In vivo, hepatic expression of OPG in transgenic mice results in a profound yet nonlethal osteopetrosis, coincident with a decrease in later stages of osteoclast differentiation. These same effects are observed upon administration of recombinant OPG into normal mice. In vitro, osteoclast differentiation from precursor cells is blocked in a dose-dependent manner by recombinant OPG. Furthermore, OPG blocks ovariectomy-associated bone loss in rats. These data show that OPG can act as a soluble factor in the regulation of bone mass and imply a utility for OPG in the treatment of osteoporosis associated with increased osteoclast activity.
Identification of the major positive regulators of c-myb expression in hematopoietic cells of different lineages.
The c-myb gene is primarily expressed in hematopoietic cells, and it is overexpressed in many leukemias. The regulation of its expression is of critical importance in hematopoietic cells. We identified the major positive regulatory sites in the 5'-flanking sequence of the human c-myb gene, and we found that the positive regulators differed in cells of different lineages. In the Molt-4 T-cell line, two Ets-like binding sites were required for the expression of c-myb. The 5' site played a minor role in the regulation of c-myb expression, and we demonstrated that a protein of 67 kDa bound to this site. Antibodies against Ets proteins showed no cross-reactivity with this protein. We showed that Ets-1 bound to the 3'-regulatory site in the c-myb promoter by electrophoretic mobility shift assay and antibody studies. Both of these Ets-like binding sites were nonfunctional in the DHL-9 B-cell line and the K562 myeloid cell line. We identified a novel transcription factor of 50.5 kDa that was required for expression of c-myb in these cell lines.
Evolution of the mitochondrial cytochrome oxidase II gene in collembola.
The sequence of the mitochondrial COII gene has been widely used to estimate phylogenetic relationships at different taxomonic levels across insects. We investigated the molecular evolution of the COII gene and its usefulness for reconstructing phylogenetic relationships within and among four collembolan families. The collembolan COII gene showed the lowest A + T content of all insects so far examined, confirming that the well-known A + T bias in insect mitochondrial genes tends to increase from the basal to apical orders. Fifty-seven percent of all nucleotide positions were variable and most of the third codon positions appeared free to vary. Values of genetic distance between congeneric species and between families were remarkably high; in some cases the latter were higher than divergence values between other orders of insects. The remarkably high divergence levels observed here provide evidence that collembolan taxa are quite old; divergence levels among collembolan families equaled or exceeded divergences among pterygote insect orders. Once the saturated third-codon positions (which violated stationarity of base frequencies) were removed, the COII sequences contained phylogenetic information, but the extent of that information was overestimated by parsimony methods relative to likelihood methods. In the phylogenetic analysis, consistent statistical support was obtained for the monophyly of all four genera examined, but relationships among genera/families were not well supported. Within the genus Orchesella, relationships were well resolved and agreed with allozyme data. Within the genus Isotomurus, although three pairs of populations were consistently identified, these appeared to have arisen in a burst of evolution from an earlier ancestor. Isotomurus italicus always appeared as basal and I. palustris appeared to harbor a cryptic species, corroborating allozyme data.