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Showing papers by "Jewish Hospital published in 1997"


Journal ArticleDOI
TL;DR: Metformin decreases Izero in hyperinsulinemic PCOS patients, reverses the hyperinsulinemia-driven endocrinopathy, decreases PAI-1, and decreases Lp(a), and should thus reduce the increased risk of atherothrombosis in PCOS.
Abstract: Sixteen nondiabetic women with polycystic ovary syndrome (PCOS) aged 18 to 33 years were studied before and after 8 weeks on metformin (1.5 g/d) therapy to assess whether reducing hyperinsulinemia would reduce the levels of the major inhibitor of fibrinolysis, antigenic plasminogen activator inhibitor type 1 (PAI-1). Compared with six normal control women, PCOS women had a higher body mass index (BMI), waist to hip ratio, fasting insulin (Izero), insulin area under the curve during oral glucose tolerance testing (IA), glucose area under the curve during oral glucose tolerance testing (GA), IA/GA ratio, PAI-1, luteinizing hormone (LH) and ratio of LH to follicle-stimulating hormone (FSH), and free testosterone, and lower high-density lipoprotein (HDL) cholesterol (all P < .025). On metformin, BMI decreased 1.3% (P = .04), Izero 43% (P = .002), IA 31% (P = .03), GA 11% (P = .02), PAI-1 16% (P = .01), lipoprotein(a) [Lp(a)] 42% (P = .004), free testosterone 46% (P = .0006), LH 44% (P = .004), and the LH/FSH ratio 41% (P = .0001). On metformin, absolute and percent reductions in Izero correlated with absolute and percent reductions in PAI-1 (r = .60, P = .015 and r = .64, P = .008). On metformin, by stepwise multiple regression, the absolute reduction in Izero was a significant determinant of the absolute reduction in PAI-1 (partial R2 = 35%, P = .02), and the percent reduction in Izero was a significant determinant of the percent reduction in PAI-1 (partial R2 = 52%, P = .003). Metformin decreases Izero in hyperinsulinemic PCOS patients, reverses the hyperinsulinemia-driven endocrinopathy, decreases PAI-1, and decreases Lp(a), and should thus reduce the increased risk of atherothrombosis in PCOS.

256 citations


Journal ArticleDOI
TL;DR: It is speculated that primary, heritable thrombophilia or hypofibrinolysis causesThrombotic venous occlusion in the head of the femur, leading to venous hypertension and hypoxic death of bone (osteonecrosis).
Abstract: In 31 patients with osteonecrosis (primarily of the hip), 74% had 1 or more primary coagulation disorders. In 18 patients, 15 (83%) who had coagulation disorders, the osteonecrosis was initially identified as idiopathic and was not associated with known underlying drugs (glucocorticoids) or diseases (alcoholism, sickle cell disease, Gaucher's disease). In 13 patients, 8 (62 %) who had coagulation disorders, the osteonecrosis was initially identified as secondary, and was associated with glucocorticoids in 12 patients, and with alcoholism in 1. The coagulation disorders included thrombhophilia (increased tendency to intravascular thrombosis) and hypofibrinolysis (reduced ability to lyse thrombi). Of the 18 patients initially thought to have idiopathic osteonecrosis, thrombophilia alone was found in 12% (resistance to activated protein C in 6%, low protein C in 6%), hypofibrinolysis alone was found in 50% (high lipoprotein(a) in 44%, low stimulated tissue plasminogen activator activity was found in 6%), and mixed thrombophilia hypofibrinolysis was found in 22%. Resistance to activated protein C was more common in these 18 patients than in healthy controls (11% versus 0%), as was high lipoprotein(a) (67% versus 20%). Of the 13 patients with secondary osteonecrosis, thrombophilia alone was found in 8% (low protein C), hypofibrinolysis alone was found in 30% (high Lp(a) in 15%, low tissue plasminogen activator activity in 15%), and mixed thrombophilia hypofibrinolysis was found in 23%. Low tissue plasminogen activator activity was more common in the 13 patients with secondary osteonecrosis than in controls (27% versus 7%), as was low protein C (23% versus 0%). In aggregate, these findings lead us to the speculation that primary, heritable thrombophilia or hypofibrinolysis causes thrombotic venous occlusion in the head of the femur, leading to venous hypertension and hypoxic death of bone (osteonecrosis).

185 citations


Journal Article
TL;DR: Maximal prednisone doses, changes in body habitus in response to corticosteroid therapy, IgG aCL levels, and clinical evidence of venous thrombosis and vasculitis were associated with osteonecrosis in patients with SLE.
Abstract: Objective. To study clinical and laboratory factors in patients with systemic lupus erythematosus (SLE) to identify subgroups at extraordinary risk for developing osteonecrosis. Methods. 31 of 103 (30%) patients with SLE had developed osteonecrosis. Patients were studied to identify clinical characteristics that differentiated patients with and without osteonecrosis. Subjects were studied to determine whether and to what degree factors leading to thrombophilia (anticardiolipin antibodies, aCL) or hypofibrinolysis [lipoprotein(a)] are associated with osteonecrosis. Results. Clinically, the patients with osteonecrosis had significant increases in Cushingoid body habitus, thrombophlebitis, vasculitis, cigarette smoking, and preeclampsia. Highest prednisone dose was positively associated with osteonecrosis. Although IgG aCL were also found to be associated with osteonecrosis, particularly in the white patients with SLE, lipoprotein(a) levels were not increased in either the white or black patients. Conclusion. Maximal prednisone doses, changes in body habitus in response to corticosteroid therapy, IgG aCL levels, and clinical evidence of venous thrombosis and vasculitis were associated with osteonecrosis in patients with SLE.

185 citations


Journal ArticleDOI
TL;DR: The results suggest that the inactivation of the p16/cdk-cyclin/Rb cascade does not occur during malignant transformation but occurs during the immortalization by HPV in HPV-harbouring premalignant lesions, the in situ equivalent of immortalized cells.
Abstract: The p16 (MTS1) tumour-suppressor gene is a cyclin-dependent kinase (cdk) inhibitor that decelerates the cell cycle by inactivating the cdks that phosphorylate the retinoblastoma tumour-suppressor gene (Rb) protein (pRb). In cervical cancers, pRb is inactivated by the HPV E7 oncoprotein or by mutations. The hypothesis of earlier reports was that the disruption of the p16/cdk-cyclin/Rb cascade is essential for malignant cervical transformation/carcinogenesis. We previously established in vitro model systems of cervical cancer representing four steps of oncogenic progression initiated by the two most common oncogenic HPVs in ectocervical and endocervical epithelial cells. This report used these systems to investigate the role of p16 in cervical cancers. A dramatic enhancement of the p16 RNA level was observed after immortalization by HPV 16 or 18. Furthermore, the p16 protein was newly observed following immortalization. However, no further changes were found for RNA or protein levels after serum selection or malignant transformation. For three cervical carcinoma cell lines, similar high levels of p16 expression were seen. Point mutations or homozygous deletions of p16 were not observed in the in vitro systems or in clinical specimens. These results suggest that the inactivation of the p16/cdk-cyclin/Rb cascade does not occur during malignant transformation but occurs during the immortalization by HPV in HPV-harbouring premalignant lesions, the in situ equivalent of immortalized cells. Also suggested is that p16 has no role in the specific malignant transformation step from immortal premalignant lesions during the carcinogenesis of HPV-initiated cervical cancers.

121 citations


Journal ArticleDOI
TL;DR: The results suggest that changes in Mg2+ metabolism play important roles in stroke syndromes and in the etiology of cerebrovasospasm associated with cerebral hemorrhage.

89 citations


Journal ArticleDOI
TL;DR: Thrombophilia may cause thrombotic venous occlusion in the femoral head, with venous hypertension and hypoxic bone death, leading to Legg-Perthes disease.
Abstract: Thrombophilia may cause thrombotic venous occlusion in the femoral head, with venous hypertension and hypoxic bone death, leading to Legg-Perthes disease. Resistance to activated protein C, the most common thrombophilic trait, was measured in 64 children with Legg-Perthes disease. Genomic deoxyribonucleic acid was studied to delineate the CGA-->CAA substitution at position 1691 of the Factor V Leiden gene responsible for resistance to activated protein C. The activated protein C ratio was calculated by dividing clotting time obtained with activated protein C-calcium chloride by clotting time obtained with calcium chloride alone. Resistance to activated protein C, with a low activated protein C ratio (less than 2.19, the 5th percentile for 160 normal pediatric controls) was the most common coagulation defect, found in 23 of 64 children with Legg-Perthes disease versus 7 of 160 pediatric controls. Eight of 64 children with Legg-Perthes disease had a low activated protein C ratio and the mutant Factor V gene (7 heterozygotes, 1 homozygote) versus 1 of 101 normal pediatric controls. Two or 3 generation vertical and horizontal transmission of heterozygosity for the mutant Factor V gene was found in 4 of the 8 kindreds. Of 64 children with Legg-Perthes disease, only 14 (22%) had entirely normal coagulation measures. Resistance to activated protein C appears to be a pathogenetic cause of Legg-Perthes disease.

78 citations


Journal ArticleDOI
TL;DR: Chemical cross-linking/immunoprecipitation analyses revealed that 125I-TFPI was directly associated with HSPGs on the cell surface and that fXa binding increased the amount of125I- TFPI bound, suggesting that heparan sulfate proteoglycans (HSPGs) are required for the uptake and degradation of 125I/fXa complexes.

62 citations


Journal ArticleDOI
TL;DR: The case of a patient in whom multifocal osteonecrosis was found to be associated with coagulation abnormalities and hypofibrinolysis is reported.
Abstract: Osteonecrosis that is associated with the use of drugs such as corticosteroids14,24,32,35,39 or with underlying disease processes36,45,48,49 such as alcohol abuse39 has been characterized as secondary. Despite extensive investigations of the demographic characteristics of patients who have osteonecrosis32,35,39, as many as 39.5 per cent of these patients (934 of 2364 in one study39) have had no known risk factors, and the osteonecrosis has been characterized as idiopathic. However, as one of us (C. J. G.) and colleagues16-19,21-24,27 as well as others5,28,37,46 have shown, many instances of osteonecrosis that previously would have been regarded as idiopathic actually were associated with heritable thrombophilia (an increased tendency for intravascular thrombosis) and hypofibrinolysis (a reduced ability to lyse thrombi). The association between coagulation abnormalities and osteonecrosis has been recognized for more than thirty-five years2,28,37,41, but it has not been studied extensively, to our knowledge. Recent studies by one of us (C. J. G.) and colleagues16-24,27 and by others5,28,37,46 have redirected attention to this area. This association has major implications not only for the diagnosis and treatment of osteonecrosis but also for the screening of the relatives of affected individuals and the possible prevention of this and other thrombotic and thromboembolic disorders in those who are found to be at increased risk because of inherited thrombophilia or hypofibrinolysis17,18,21,22,24. We report the case of a patient in whom multifocal osteonecrosis was found to be associated with …

51 citations


Journal ArticleDOI
TL;DR: Oral complications develop in almost all patients, and their early recognition may result in the institution of prompt treatment and prolonged survival, and the detection of commonly occurring oral changes may support its diagnosis.
Abstract: Bone marrow transplantation, once regarded as experimental, has evolved into a standard treatment for a variety of malignancies. Considerable advances have been made in histocompatibility typing, pretransplantation chemotherapy, and posttransplantation immunosuppressive therapy as well as prophylaxis and treatment of infections. Oral complications develop in almost all patients, and their early recognition may result in the institution of prompt treatment and prolonged survival. Mucositis, often severe and extremely painful, develops in more than three quarters of bone marrow transplant recipients, and its prevention, unfortunately, remains unsatisfactory. Herpes simplex virus and Candida albicans account for most oral infections, although their incidence has been dramatically reduced by the institution of prophylactic agents. Graft versus host disease continues to be a significant complication of marrow transplantation, and the detection of commonly occurring oral changes may support its diagnosis.

43 citations


Journal ArticleDOI
TL;DR: Hypocholesterolemia in white and black men in NHANES I could not be attributed to hypocaloric intake or to protein, fat, or carbohydrate undernutrition, and may be associated with a reduced likelihood of coronary heart disease and with increased longevity.
Abstract: Our specific aim in a 10-year prospective study of 772 Cincinnati firemen (predominantly aged 26 to 46 years) was to determine the prevalence, attributes, and etiology of persistent hypobetalipoproteinemia, defined by entry low-density lipoprotein cholesterol (LDLC) less than 75 mg/dL A second specific aim was to cross-sectionally assess hypocholesterolemia (defined by total serum cholesterol [TC] 1, 130 v 133 mg/dL and 58 v 63 mg/dL) Compared with 32 men with entry LDLC less than 75 mg/dL but with less than 87% of follow-up LDLC less than 75 mg/dL, the 12 men with persistently low LDLC had lower mean Quetelet indices and diastolic blood pressure at entry (236 v 258, P = 056; 73 v 80 mm Hg, P = 03) and on follow-up study (245 v 269, P = 04; 72 v 79 mm Hg, P = 05) Of 12 men with persistently low LDLC, two had truncated apolipoprotein (apo) B (familial hypobetalipoproteinemia, two had the apo E genotype 2/3, and two had acquired hypobetalipoproteinemia that antedated mortality from melanoma by 9 years and from alcoholism by 2 years Comparable to white and black firemen aged 26 to 46 years, 29% and 36% of whom had entry serum TC less than 130 mg/dL, of 1,314 white and 165 black men in the NHANES I study (aged 26 to 46), 18% and 36% had hypocholesterolemia (entry TC 05) in men with entry TC less than 130 mg/dL compared with those with TC 130 to 230 or greater than 230 mg/dL Hypocholesterolemia in white and black men in NHANES I could not be attributed to hypocaloric intake or to protein, fat, or carbohydrate undernutrition There appear to be racial differences in the prevalence of hypocholesterolemia Blacks comprised 18% of the firemen's cohort but 42% of those with persistent hypobetalipoproteinemia; among NHANES I subjects, 36% of blacks were hypocholesterolemic versus 18% of whites Unless persistent hypobetalipoproteinemia reflects an underlying disease, alcoholism, etc, it is often heritable, and may be associated with a reduced likelihood of coronary heart disease (CHD) and with increased longevity

40 citations


Journal ArticleDOI
TL;DR: CABG in PVD patients is associated with significant major morbidity, which may preclude or alter the timing of subsequent VR, and this procedure is questioned if elective CABG is patients with severe peripheral vascular disease is a relatively high-risk procedure.

Journal ArticleDOI
TL;DR: The findings indicate that although the pulmonary vascular bed offers advantages of easy accessibility and a relatively large capacity, significant early cell destruction is an important limitation.

Journal ArticleDOI
TL;DR: It is suggested that women be instructed how to find and use their support systems and be told that most women do well and return to normal activities of daily living after CABS.
Abstract: In this longitudinal study of women after CABS, the women were coping admirably with good psychosocial and functional outcomes up to 3 months postoperatively. It is suggested that women be instructed how to find and use their support systems and be told that most women do well and return to normal activities of daily living after CABS.

Journal ArticleDOI
TL;DR: Evaluation of the potential benefits of hope to this population's adaptation to varying health states and ongoing research of hope in this population will be further demonstrated.

Journal ArticleDOI
TL;DR: The case of a healthy 23-year-old man who was seen in the urgent care center, given the diagnosis of dental infection, prescribed penicillin, and sent home complaining of myalgias, purulent drainage from around his teeth, chest pain, and dyspnea is reported.

Journal ArticleDOI
TL;DR: It is suggested that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention.
Abstract: Our specific aim was to examine the interface between risk factors for atherosclerosis, thrombosis, and hypofibrinolysis in a previously healthy 35-year-old male who had sustained a recent myocardial infarction. By angiography, the right, left main, and left anterior descending coronary arteries were smooth-walled, widely patent, and free of significant obstruction; the circumflex exhibited total, probably thrombotic occlusion of the distal large second marginal branch. The patient was found to have prothrombotic high homocysteine (46.4 mumol/L), prothrombotic resistance to activated protein C (ratio, 1.47), and hypofibrinolytic high plasminogen activator inhibitor (PAI-Fx) activity (54 U/mL). He was homozygous for the 677C-->T; A-->V mutation in the methylenetetrahydrofolate reductase (MTHFR) gene causing homocysteinemia, heterozygous for the mutant factor V Leiden gene causing resistance to activated protein C, and heterozygous for the 4G/5G polymorphism in the PAI-1 promoter gene causing high PAI-Fx. Other major risk factors for coronary artery disease included previously undiagnosed adult-onset diabetes, high triglycerides (291 mg/dL), and low high-density lipoprotein (HDL) cholesterol (26 mg/dL). The patient's prothrombotic status (homocysteinemia and resistance to activated protein C) and hypofibrinolysis (high PAI-Fx) apparently facilitated occlusive coronary artery thrombus formation and retention. Prothrombotic factors and hypofibrinolysis appear to play important pathogenetic roles in premature myocardial infarction. In patients with severe premature coronary artery disease, we suggest that interactions between prothrombotic factors, hypofibrinolysis, and hyperlipidemia-atherosclerosis be regularly evaluated, since such interactions may have ramifications for the outcome of short- and long-term secondary prevention. Moreover, in patients with heritable prothrombotic factors or hypofibrinolysis, it should be important to optimize lipid and lipoprotein cholesterol levels with the goal of stabilizing coronary plaques to reduce the likelihood of plaque rupture and thrombosis.

Journal ArticleDOI
TL;DR: Strategies based on the message-learning approach to persuasive communication that are applicable to nursing are explored.

Journal ArticleDOI
TL;DR: The Master's-prepared clinical nurse specialist can engage in research in a variety of settings, including serving as a research coordinator for clinical trials required for new drug development, according to a review of the literature.
Abstract: WITH ADVANCED CLINICAL EXPERTISE and knowledge of the research process, the Master's-prepared clinical nurse specialist can engage in research in a variety of settings, including serving as a research coordinator for clinical trials required for new drug development. Based on a review of the lit

Journal Article
Nunan Pj1, Giesy Bd
TL;DR: The goal of the physician treating the athlete with Morton's neuroma should be the same as that of the athlete, to relieve the pain while allowing the athlete to continue with his or her activity as much as possible.

Journal ArticleDOI
Jesse E. Adams1
TL;DR: It appears that measurement of troponin proteins will facilitate patient care in these difficult situations of cardiac injury after blunt chest wall trauma or cardiac surgery.




Journal ArticleDOI
W R Reinus1
TL;DR: In this article, the authors present a rule-based artificial neural network (RNN) language for the interpretation of medical images, which can be used to obtain expert advice on various topics from car mechanics to strategic business planning.
Abstract: T hroughout history, humans have used tools to automate labor-intensive tasks. Employing machines to replace manual labor is commonplace, but automation of cognitive jobs is now also becoming possible. Generally, some form of artificial intelligence is required for a machine to assume cognitive functions. To this end, many artificial intelligence computer languages have been developed that allow users to obtain expert advice on various topics from car mechanics to strategic business planning. These are primarily rule-based languages that evaluate data in a predictable and orderly fashion. These languages have served well for problems in which the parameters and their interrelationships are completely known. Unfortunately, rule-based languages do not lend themselves to tasks, such as interpretation of medical images, that require the integration of visual data with medical knowledge in the absence of explicitly defmed rules. As a result, attempts to apply rule-based artificial intelligence techniques to radiologic image interpretation has generally met with clinically ineffective results [1]. Another type of artificial intelligence, known as artificial neural networks, shows promise toward handling cognitive functions such as pattern recognition and can be applied to medicine and to radiology in particular [2]. Artificial neural networks are so named because they are inspired by, but not necessarily modeled after, biologic neural systems, with which they show some uncanny similarities in behavior. Standard linear computers, present on many desktops, are based on the Turing model. Turing was an early 20th century British mathematician who theorized that all cognitive behavior could be simulated with a ticker-tape with holes punched in sequence to show ones and zeroes. Assuming that the holes are in known positions on the tape in a predefined code, a machine with a counter (or central processing unit) could store and analyze all types of informarion. Turing’s idea appealed to cognitive behaviorists of the day who believed that this machine for information storage and processing represented the way the mind functions. Although Turing’s machine, with a central processing unit and address-relocatable memory, has served as an admirable paradigm for modem computers, no evidence exists that human brains actually function in this manncr. Indeed, a large body of evidence exists to the contrary. For example, human brains do not appear to have any single central processing unit. Tracing cognitive function has been exceedingly difficult, and no investigator to my knowledge has ever been able to locate a single set of neurons that correspond to a discrete memory or set of memories from a particular period of life. In fact, brain ablation studies suggest that human brains store information diffusely through networks that may even contain other, unrelated information. The difference in design between linear computers and artificial neural networks is manifested in the type of problems each is best suited to handle. Linear computers are fabubus for routine numerical manipulations such as addition, subtraction, multiplication, and division and for logic problems (Fig. 1). Networks, on the other hand, are not. Their entire construction is designed for pattern recognition via integration of information. This is much like a human brain. Although most of us are not proficient at manipulating even moderate numbers in our heads, we are capable of recognizing patterns quickly (Fig. 2). In addition, although linear computers must handle information one piece at a time, neural networks-just like humans-integrate information. When posed with a complex decision, such as whether to buy the red or the black sports car, humans do not individually scrutinize each factor involved in making the dccision but rather integrate the information and reach a decision without conscious processing. An example may help to explain how information may be processed and stored in a neural network. Consider 1000 students in a study hall, each with a battery, switch, and ammeter that is calibrated to an arbitrary scale ranging from one to 10. Each student’s