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1.
Gynecol Oncol ; 156(2): 400-406, 2020 02.
Article in English | MEDLINE | ID: mdl-31813586

ABSTRACT

OBJECTIVE: Blood-based biomarkers are attractive due to ease of sampling and standardized measurement technology, reducing obstacles to clinical implementation. The objective of this study was to evaluate a clinically available method of steroid hormone measurement for its prognostic potential in endometrial cancer. METHODS: We quantified seven steroid hormones by liquid chromatography-tandem mass spectrometry in 100 endometrial cancer patients from a prospective cohort. Abdominal fat distribution was assessed from abdominal computed tomography (CT) scans. Steroid hormone levels were compared to clinical characteristics, fat distribution and gene expression in primary tumor samples. RESULTS: Low levels of 17OH-progesterone, 11-deoxycortisol and androstenedione were associated with aggressive tumor characteristics and poor disease specific survival (p = .003, p = .001 and p = .02 respectively). Adjusting for preoperative risk based on histological type and grade, low 17OH-progesterone and 11-deoxycortisol independently predicted poor outcome with hazard ratios of 2.69 (p = .033, 95%CI: 1.09-6.68) and 3.40 (p = .020, 1.21-9.51), respectively. Tumors from patients with low steroid level displayed increased expression of genes related to mitosis and cell cycle progression, whereas high steroid level was associated with upregulated estrogen signaling and genes associated with inflammation. Estrone and estradiol correlated to abdominal fat volume in all compartments (total, visceral, subcutaneous, p < .001 for all), but not to the visceral fat proportion. Patients with higher levels of circulating estrogens had increased expression of estrogen signaling related genes. CONCLUSION: Low levels of certain endogenous steroids are associated with aggressive tumor traits and poor survival and may provide preoperative information independent of histological biomarkers already in use.


Subject(s)
17-alpha-Hydroxyprogesterone/blood , Androstenedione/blood , Cortodoxone/blood , Endometrial Neoplasms/blood , Estrogens/blood , Biomarkers, Tumor/blood , Carcinoma, Endometrioid/blood , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/mortality , Chromatography, Liquid , Cohort Studies , Endometrial Neoplasms/genetics , Endometrial Neoplasms/mortality , Estradiol/blood , Estrone/blood , Female , Gene Expression , Humans , Norway/epidemiology , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Signal Transduction , Tandem Mass Spectrometry
2.
Neurology ; 56(8): 997-1008, 2001 Apr 24.
Article in English | MEDLINE | ID: mdl-11339244

ABSTRACT

MEDLINE searches identified epidemiologic, experimental, and clinical studies on the genetics of cerebrovascular disease and stroke, including the following topics: genetic epidemiology of stroke; genetics of systemic disorders that cause ischemic stroke, including coagulation disorders, connective tissue disorders, vasculopathies, metabolic disorders, and disorders of unknown etiology; and genetics of systemic disorders that cause hemorrhagic stroke. Recent discoveries in stroke genetics involve the genetic basis of monogenic disorders such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy and sickle cell disease. Reproducing similar advances in other forms of cerebrovascular disease and stroke will be more difficult because their inheritance is complex, multigenic, and heterogeneous. However, the future is promising with the application of molecular genetic approaches such as linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses as well as the transmission/disequilibrium test--a statistical method for detection of linkage between a marker and a disease-susceptibility locus.


Subject(s)
Intracranial Arteriovenous Malformations/genetics , Mutation/genetics , Stroke/genetics , Cerebral Hemorrhage/genetics , Cerebrovascular Disorders/genetics , Genetic Linkage/genetics , Humans , Multifactorial Inheritance/genetics , Subarachnoid Hemorrhage/genetics
3.
JAMA ; 283(23): 3102-9, 2000 Jun 21.
Article in English | MEDLINE | ID: mdl-10865305

ABSTRACT

OBJECTIVE: To develop recommendations for the establishment and operation of primary stroke centers as an approach to improve the medical care of patients with stroke. PARTICIPANTS: Members of the Brain Attack Coalition (BAC), a multidisciplinary group of representatives from major professional organizations involved with delivering stroke care. Supplemental input was obtained from other experts involved in acute stroke care. EVIDENCE: A review of literature published from 1966 to March 2000 was performed using MEDLINE. More than 600 English-language articles that had evidence from randomized clinical trials, meta-analyses, care guidelines, or other appropriate methods supporting specific care recommendations for patients with acute stroke that could be incorporated into a stroke center model were selected. CONSENSUS PROCESS: Articles were reviewed initially by 1 author (M.J.A.). Members of the BAC reviewed each recommendation in the context of current practice parameters, with special attention to improving the delivery of care to patients with acute stroke, cost-effectiveness, and logistical issues related to the establishment of primary stroke centers. Consensus was reached among all BAC participants before an element was added to the list of recommendations. CONCLUSIONS: Randomized clinical trials and observational studies suggest that several elements of a stroke center would improve patient care and outcomes. Key elements of primary stroke centers include acute stroke teams, stroke units, written care protocols, and an integrated emergency response system. Important support services include availability and interpretation of computed tomography scans 24 hours everyday and rapid laboratory testing. Administrative support, strong leadership, and continuing education are also important elements for stroke centers. Adoption of these recommendations may increase the use of appropriate diagnostic and therapeutic modalities and reduce peristroke complications. The establishment of primary stroke centers has the potential to improve the care of patients with stroke. JAMA. 2000.


Subject(s)
Hospital Departments/organization & administration , Hospitals, Special/organization & administration , Neurology/organization & administration , Stroke/therapy , Clinical Protocols , Diagnostic Imaging , Education, Medical, Continuing , Emergency Medical Services , Emergency Service, Hospital , Humans , Neurology/education , Neurosurgery , Patient Care Team , Patient Education as Topic , Quality Control
5.
Wis Med J ; 92(6): 289-90, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8342290
6.
Wis Med J ; 87(4): 5, 1988 Apr.
Article in English | MEDLINE | ID: mdl-3388881
7.
Wis Med J ; 87(2): 5-6, 1988 Feb.
Article in English | MEDLINE | ID: mdl-3348045
8.
J Neurol Sci ; 52(2-3): 305-25, 1981.
Article in English | MEDLINE | ID: mdl-7310437

ABSTRACT

Scapuloperoneal syndrome is a more or less clinically distinct neurologic entity with predominant involvement of scapular and peroneal muscles. The disease shows a variable mode of inheritance. Electromyography and muscle biopsy has shown the presence of denervation and dystrophic changes, sometimes both in the same patient. Cardiac manifestations when present add a graver prognosis to an otherwise relatively benign disease. Study of two cases in this report, one with significant sensory changes and another with cardiopathy, showed degeneration of peripheral nerve and mixed features in muscle biopsy. It is postulated that the myopathic or dystrophic features in the muscle of these cases and other patients with scapuloperoneal syndrome is likely to be secondary to slow denervation and reinnervation.


Subject(s)
Neuromuscular Diseases/genetics , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Muscle Denervation , Muscles/innervation , Muscles/pathology , Neural Conduction , Neuromuscular Diseases/pathology , Pedigree , Syndrome
10.
Science ; 167(3916): 280-1, 1970 Jan 16.
Article in English | MEDLINE | ID: mdl-17734448

ABSTRACT

N-(1,1-Dimethylpropynyl)-3,5-dichlorobenzamide is representative of a group of benzamides that are herbicidally active on annnual and perennial grasses with potential agricultural uitility in forage legumes, certain turf grasses, and clultivated crops.

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