tbuckley/cabot-search huggingface dataset:
Postmenopausal Hormone Therapy and Risk of Cardiovascular Disease by Age and Years Since Menopause
Authors: Jacques E. Rossouw, Ross L. Prentice, JoAnn E. Manson, LieLing Wu, David Barad, Vanessa M. Barnabei, Marcia Ko, Andrea Z. LaCroix, Karen L. Margolis, Marcia L. Stefanick
Journal: JAMA (2007)

The timing of initiation of hormone therapy may influence its effect on cardiovascular disease.To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began.Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10,739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16,608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate (CEE + MPA) or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998.Statistical test for trend of the effect of hormone therapy on coronary heart disease (CHD) and stroke across categories of age and years since menopause in the combined trials.In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 370 [corrected] cases of CHD and 239 cases of stroke in the placebo group. For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76 (95% confidence interval [CI], 0.50-1.16); 10 to 19 years, 1.10 (95% CI, 0.84-1.45); and 20 or more years, 1.28 (95% CI, 1.03-1.58) (P for trend = .02). The estimated absolute excess risk for CHD for women within 10 years of menopause was -6 per 10,000 person-years; for women 10 to 19 years since menopause began, 4 per 10,000 person-years; and for women 20 or more years from menopause onset, 17 per 10,000 person-years. For the age group of 50 to 59 years, the HR for CHD was 0.93 (95% CI, 0.65-1.33) and the absolute excess risk was -2 per 10,000 person-years; 60 to 69 years, 0.98 (95% CI, 0.79-1.21) and -1 per 10,000 person-years; and 70 to 79 years, 1.26 (95% CI, 1.00-1.59) and 19 per 10,000 person-years (P for trend = .16). Hormone therapy increased the risk of stroke (HR, 1.32; 95% CI, 1.12-1.56). Risk did not vary significantly by age or time since menopause. There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women (HR of 0.70 for 50-59 years; 1.05 for 60-69 years, and 1.14 for 70-79 years; P for trend = .06).Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion for statistical significance. A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms.clinicaltrials.gov Identifier: NCT00000611.
EVIDENCE FOR THE EXPRESSION OF Ia (<i>H-2</i>-ASSOCIATED) ANTIGENS ON THYMUS-DERIVED LYMPHOCYTES
Authors: Jeffrey A. Frelinger, John E. Niederhuber, C. S. David, Donald C. Shreffler
Journal: The Journal of Experimental Medicine (1974)

We have demonstrated in an anti-Ia serum the presence of specific antibodies reacting with T cells, as well as with B cells, using a highly sensitive dye exclusion test. This antiserum reacts with both spleen and lymph node in a characteristic biphasic titration curve killing up to 70% of these cells. It also reacts with cortisone-resistant thymocytes. The A.TH-α-A.TL serum can be absorbed with spleen, lymph node, cortisone-resistant thymus, or normal thymus cells. Further in vivo absorptions in BALB/c nude cannot remove all of the cytotoxic activity for normal BALB lymph node lymphocytes, while completely removing the activity for nude cells. A Thy-1 positive cell line derived from a C57Br leukemia is reactive with this anti-Ia serum.
Combined Aspirin and Cortisone Treatment of Acute Rheumatic Fever: A Controlled Trial in Young Men
Authors: J D Slater
Journal: Annals of the Rheumatic Diseases (1961)

For many years large doses of salicylate have been used in the treatment of acute rheumatic fever (Coburn, 1936(Coburn, , 1943;;Manchester, 1946).Although the acute manifestations of the disease are partially suppressed (Illingworth, Burke, Doxiadis, Lorber, Philpott, and Stone, 1954), there is no convincing evidence that chronic damage to the heart is prevented (Bywaters, 1950).However, the introduction of the adrenocortical hormones in 1948 brought hope of a more radical form of treatment (Hench, Kendall, Slocumb, and Polley, 1949).Anecdotal studies have emphasized the value of steroid therapy in acute rheumatic fever (Massell, 1954; Debr6, Mozziconacci, and Caramanian, 1955), and there is evidence that carditis is less likely to develop if large doses of cortisone are given at an early enough stage in the disease (Roy and Massell, 1956).Nevertheless, two well-controlled therapeutic trials comparing the effects of aspirin, cortisone, and adreno-cortico- trophic hormone in children (M.R.C. and A.H.A., 1955) and in American airmen (Houser, Clark, and Stolzer, 1954) have shown that when used singly each of these drugs has a similar effect on the course of the acute disease.These trials have not, how- ever, assessed the effect of cortisone, because there were no untreated controls and no patients treated with both aspirin and steroids.The present paper describes a controlled therapeutic trial in 28 young men designed to assess the response to cortisone.The course of acute rheumatic fever was followed when using high doses of salicylate, either alone or combined with cortisone. MethodsIn the British Army many patients with doubtful or mild rheumatic fever are admitted to hospital so that the diagnostic criteria laid down by Duckett Jones (1944) have been modified and made more rigid.These are described in detail elsewhere on July 18,
Significance of nuclear immunofluorescent patterns.
Authors: C.A Dorsch, C.B Gibbs, M.B Stevens, L.E Shulman
Journal: Annals of the Rheumatic Diseases (1969)

techniques havebeenused extensively todetect thepresence ofantinuclear factors (ANF)inserafrompatients withsystemic lupuserythematosus andrelated disorders. Furthermore, morphological differences inthecharacter ofnuclear immunofluorescence havebeenconsidered tobeofclinical aswellasimmunological significance (Casals, Friou, andTeague,1963; Burnham, Fine, andNeblett, 1966). Fourpatterns ofnuclear staining havebeen described, namely, homogeneous, peripheralt, speckled, andnucleolar. Thehomogeneous andperipheral patterns, reflecting antibodies tonucleoprotein anddesoxyribonucleic acidrespectively, have beencorrelated primarily withtheclinical diagnosis ofsystemic lupuserythematosus (SLE)(Friou, 1958; Casals andothers, 1963). Lesswelldefined arethespecific antigen-antibody systems responsible forspeckled fluorescence andpreferential staining ofnucleoli. Moreover, these latter twoimmunofluorescent patterns havebeencorrelated forthe mostpartwithdisorders other thanSLE,notably progressive systemic sclerosis andSj6gren's syndrome(Beck, 1963; Burnham andothers, 1966). Inthepresent study, theclinical significance of immunofluorescent patterns and factors which influence themorphology ofnuclear staining have beenevaluated inserafrom76patients withSLE, 34patients with rheumatoid arthritis, and39patients withmiscellaneous disorders. Nopattern ofnuclear immunofluorescence
European Collaborative Group on Prostate Brachytherapy: Preliminary Report in 1175 Patients
Authors: S. Langley, R. Laing, A. Henderson, S. Aaltomaa, V. Kataja, J.-E. Palmgren, F. Bladou, N. Salem, G. Serment, L. Nava, A. Losa, G. Guazzoni, F. Guedea, F. Aguilo, J.F. Suarez
Journal: European Urology (2004)
Taste perception in cirrhosis: Its relationship to circulating micronutrients and food preferences
Authors: A M Madden, W Bradbury, M Y Morgan
Journal: Hepatology (1997)

Impairment of gustatory acuity may influence nutrient intake and hence nutritional status. The aim of this study was to evaluate gustatory acuity in patients with cirrhosis and its relationship to circulating concentrations of micronutrients, and food preferences. Gustatory evaluation was undertaken, using a rinsing technique, in 75 cirrhotic patients and 75 comparable healthy volunteers. Circulating concentrations of magnesium, zinc, vitamin A, and alpha- and beta-carotene were measured, and food preferences were assessed by questionnaire. The cirrhotic patients showed impaired gustatory function with significantly higher (less sensitive) median thresholds for detection of salt, sweet, and sour and for recognition of bitter, salt, sweet, and sour, together with a higher overall median gustatory score (P < .0001). Mean circulating concentrations of magnesium, zinc, vitamin A, and alpha- and beta-carotene were significantly lower in the patient population. Serum magnesium was significantly negatively associated with detection of salt (P = .02) and gustatory score (P = .02). Patients' subjective assessment of taste acuity did not correspond with objective measurements. Overall, no differences were observed in food preferences between the two groups, nor was any association found between food preferences and gustatory acuity. Patients with cirrhosis have impaired gustatory acuity that is associated with hypomagnesemia but apparently does not affect food selection.
Basophil Hyporesponsiveness To Peanut Following Immunotherapy May Be Transient and Correlates With Clinical Response
Authors: Mark Gorelik, Satya Narisety, Kristin Chichester, Anja Bieneman, Corinne Keet, Robert A. Wood, John T. Schroeder, Pamela Frischmeyer Guerrerio
Journal: Journal of Allergy and Clinical Immunology (2014)
S125 A retrospective study characterising ciliary ultrastructure, light microscopy and sputum microbiology associations with lung function decline in a large adult primary ciliary dyskinesia cohort
Authors: A Shah, A Rogers, A Shoemark, D Bilton, R Wilson, MR Loebinger
Journal: Thorax (2013)

<h3>Background</h3> Primary ciliary dyskinesia (PCD) is an inherited disease related to ciliary dysfunction, with heterogeneity in clinical presentation, prognosis and ciliary ultrastructure. Our study aimed to comprehensively characterise a large cohort with respect to ciliary ultrastructure, beat frequency, sputum microbiology, mortality and lung function decline. <h3>Method</h3> A cohort of 100 adult PCD patients was identified at a tertiary respiratory centre. A retrospective analysis of clinical age at presentation and diagnosis alongside ciliary ultrastructure, nasal nitric oxide, beat frequency, sputum microbiology, lung function at diagnosis and follow-up and mortality were recorded. Non-parametric multi-parameter analysis of variance and Spearman rank correlation statistical analysis was performed to identify significant associations with decline in lung function (FEV1%/year). Median duration of follow-up was 7.5years (range 2–30years). <h3>Results</h3> Overall mortality was 4% (median age of death 55years). 12% of patients had a central pair/transposition defect, 37% missing outer dynein arms, 15% missing inner dynein arms, 28% no arms, and 3% had normal ultrastructure. There was no significant correlation between ciliary ultrastructure, beat frequency (range 0–13.9Hz) and nasal nitric oxide with clinical age at presentation (range 1–26 years) and diagnosis (range 1–72 years) or lung function at presentation and decline with follow-up. There was additionally no significant association between sputum isolation including Pseudomonas aeruginosa with lung function decline. 44% of patients had Pseudomonas aeruginosa chronic infection. The incidence of NTM colonisation was low (4%). Aspergillus species colonisation was additionally low (5%). The average lung function decline in the cohort was 1.45% FEV1/year. <h3>Conclusions</h3> Comprehensive characterisation of an adult PCD cohort with ciliary ultrastructure, light microscopy, clinical presentation and follow-up data shows a relatively favourable outcome with optimum care. Ciliary ultrastructure, beat frequency and nasal nitric oxide does not predict prognosis. Contrary to parallel diagnoses such as cystic fibrosis and adult idiopathic bronchiectasis, microbiological isolation of Pseudomonas aeruginosa is not associated with a more rapid decline in lung function with optimal prophylaxis and care. Contrary to recent suggestion of low ciliary beat frequency and low nasal nitric oxide association with NTM susceptibility, we did not find a high incidence of NTM or Aspergillus species within this cohort.
Cuirass respirator treatment of chronic respiratory failure in scoliotic patients.
Authors: P W Wiers, R Le Coultre, O T Dallinga, W van Dijl, A F Meinesz, H J Sluiter
Journal: Thorax (1977)

The results are reported of domiciliary cuirass respirator treatment, using tailor-made shells, in four patients with severe thoracic scoliosis. Three of the patients had suffered from poliomyelitis. All complained of increasing dyspnoea on exertion, ultimately interfering with almost every activity of daily life; three patients had severe acute respiratory failure necessitating urgent admission to the Respiratory Care Unit. Right heart failure was present in two. Two patients required mechanical treatment via an endotracheal tube. All the patients were discharged home with a cuirass respirator. Standard type shells were used initially with low efficiency due to the poor fit of the cuirass shell to the deformed thoracic cage. Tailor-made shells were constructed from polyester reinforced with glass fibre, modelled on plaster casts of the thoracic cage. Subjectively the patients improved greatly and were able to resume and increase many activities. One patient committed suicide for reasons unconnected with treatment but the other three patients have been doing well from the time the cuirass respirator treatment was started, respectively, 3, 6, and 10 years ago. This treatment seems particularly effective in younger patients with severe paralytic scoliosis and cardiorespiratory failure, although the possibility of using it in older patients suffering from scoliosis of other aetiology should certainly be explored.
Melanoma reporting to central cancer registries by US dermatologists: An analysis of the persistent knowledge and practice gap
Authors: Todd V. Cartee, Seema P. Kini, Suephy C. Chen
Journal: Journal of the American Academy of Dermatology (2011)

Every state requires diagnosing physicians to report new cases of melanoma to its central cancer registry. Previous regional studies and anecdotal experience suggest that few dermatologists are cognizant of this obligation. This oversight could result in a large number of unreported melanomas annually and, in turn, US melanoma statistics that markedly underestimate the true incidence of the disease.We sought to quantify the percentage of dermatologists who are unaware of melanoma reporting requirements (the knowledge gap) and who are not reporting melanoma diagnoses (the practice gap). We also sought to delineate factors predictive of reporting knowledge and behavior.A survey was administered to attendees of the Cutaneous Oncology Symposium at the 2010 American Academy of Dermatology annual meeting.In all, 104 of 419 eligible attendees completed surveys (response rate 26%). Fifty percent of respondents do not believe they are required to report melanomas and 56% do not actively report their diagnoses to a registry. Practice duration of less than 10 years was significantly associated with both a knowledge gap (P = .047) and practice gap (P = .056). Similarly, dermatologists who diagnosed fewer than 10 melanomas per year were more likely to possess a knowledge gap (P = .096) and a practice gap (P = .087) than those who diagnosed more than 10.Limitations include small sample size and low response rate.A majority of dermatologists are not reporting melanomas they diagnose to a cancer registry, and half of those surveyed were not aware that diagnosing physicians are required to report melanoma.
IL-4-deficient Balb/c mice resist infection with Leishmania major.
Authors: M Kopf, F Brombacher, G Köhler, G Kienzle, K H Widmann, K Lefrang, C Humborg, B Ledermann, W Solbach
Journal: The Journal of Experimental Medicine (1996)

Mice with a genetically engineered deficiency for either IL-4 or IFN-gamma R1 (single mutants), and IL-4/IFN-gamma R1 (double mutants) on the Balb/c and 129Sv background were used to study the course of infection with Leishmania major. In contrast to genetically resistant 129Sv wildtype mice, IL-4/IFN-gamma R1 double mutant mice developed fetal disease with parasite dissemination to visceral organs similar to mice lacking IFN-gamma R1 only. Balb/c mice, which are exquisitely susceptible to L. major, were rendered resistant to infection by disruption of the IL-4 gene. As compared to homozygous IL-4+/- mice, heterozygous IL-4+/- mice, heterozygous IL-4+/- animals consistently developed smaller lesions with less ulceration and necrosis, indicating the likelihood of gene-dosage effects. This implicates that the magnitude of the IL-4 response determines the severity of disease. CD4+ T cells of IL-4-deficient mice showed impaired Th2 cell development, as assessed by quantitative RT-PCR of characteristic cytokines. Development of resistance is not explained by default Th1 development, because this was observed only at very late stages of infection. Moreover, the induction of inflammatory cytokines (e.g., IL-1 alpha, IL-1 beta, TNF-alpha, IL-12) together with iNOS in the lesion and draining lymph nodes was not altered in the absence of IL-4.
Declining Into Failure
Authors: Sandra A. Jones, Mark R. Boyett, Matthew K. Lancaster
Journal: Circulation (2007)

Background— The spontaneous activity of pacemaker cells in the sinoatrial (SA) node controls heart rate under normal physiological conditions. Clinical studies have shown the incidence of SA node dysfunction increases with age and occurs with peak prevalence in the elderly population. The present study investigated whether aging affected the expression of Ca v 1.2 channels and whether these changes could affect pacemaker activity, in turn leading to age-related SA node degeneration. Methods and Results— The SA node region was isolated from the right atrium of guinea pigs between birth and 38 months of age. Immunofluorescence studies showed Ca v 1.2 protein was present as punctate labeling around the outer membrane of atrial cells but was absent from the center of the SA node. The area lacking Ca v 1.2-labeled protein progressively increased from 2.06±0.1 (mean±SEM) mm 2 at 1 month to 18.72±2.2 mm 2 at 38 months ( P &lt;0.001). Western blot provided verification that Ca v 1.2 protein expression within the SA node declined during aging. Functional measurements showed an increased sensitivity to the L-type calcium blocker nifedipine; SA node preparations stopped beating in 100 μmol/L nifedipine at 1 day old, compared with 30 μmol/L at 1 month and 10 μmol/L at 38 months of age. Furthermore, the amplitude of extracellular potentials declined within the center and periphery of the SA node during aging. Conclusions— The present data show Ca v 1.2 channel protein decreases concurrently with reduced spontaneous activity of the SA node with increased age, which provides further evidence of mechanisms underlying the age-related deterioration of the cardiac pacemaker.
P51 Tuberculosis outcome following pre-treatment assessment for directly observed or self-administered therapy: still room for improvement?
Authors: J. C. Barrett, S. Dart, A. Solamalai, C. Snook, M. Lipman
Journal: Thorax (2011)

<h3>Setting and Methods</h3> London has high rates and large numbers of TB notifications. Treatment completion is generally &lt;85% (the figure recommended by the WHO to achieve effective control). NICE TB guidelines (2011) advise using risk assessment to identify those individuals most likely to non-adhere to therapy and hence who require enhanced case management, including directly observed therapy (DOT), to complete treatment successfully. The North Central London TB Network piloted a risk assessment tool, derived from reported risk factors predisposing to non-adherence plus information from a patient profile study undertaken across London, in a cohort of 306 TB patients starting treatment between June and December 2008. On the basis of the individual9s risk of non-adherence score they were broadly allocated to DOT or self-administered therapy (SAT). Here we evaluate treatment outcomes (completion and need for re-treatment) using the London TB register (LTBR) and individual case records. <h3>Results</h3> Subjects receiving SAT had excellent treatment completion rates (91%), with 3% lost to TB service follow-up (Abstract P51 table 1). Those on DOT had a lower completion rate—which at 80% was less than the international standard. Ten per cent of DOT subjects were lost to follow-up (all after transfer out of NCL TB service care). Death rates were threefold higher in the DOT group. After 20 months median follow-up post treatment completion, 3 SAT and 0 DOT patients had been re-treated for TB. <h3>Conclusions</h3> The risk assessment tool appears to discriminate those patients who can receive SAT; though it should be noted that re-treatment was only required in this group—suggesting possible poor adherence with therapy in some individuals. Subjects on DOT did well within NCL TB service, but were too often lost to follow-up if transferred elsewhere. It is unclear whether this reflects inadequate local data collection and communication by, and with, our service, or genuine loss from healthcare. Either way, this requires urgent attention. The planned introduction of enhanced case management within the London TB model of care may improve this.
Cognitive function and <sup>99m</sup>Tc-ECD brain SPECT are significantly correlated in patients with primary Sjögren syndrome: a case–control study
Authors: V Le Guern, C Belin, C Henegar, C Moroni, D Maillet, C Lacau, J L Dumas, N Vigneron, L Guillevin
Journal: Annals of the Rheumatic Diseases (2009)

To assess subclinical central nervous system (CNS) involvement in primary Sjögren syndrome (pSS), by comparing standard brain MRI, in-depth neuropsychological testing and (99m)Tc-ECD brain single-photon emission computed tomography (SPECT) of patients with pSS with matched controls.10 women (<55 years old), with pSS defined using European-American criteria, presence of anti-SSA and/or anti-SSB antibodies and no history of neurological involvement were prospectively investigated, and compared with 10 age- and sex-matched controls. All subjects underwent, within 1 month, brain MRI, neuropsychological testing, including overall evaluation and focal cognitive function assessment, and (99m)Tc-ECD brain SPECT.(99m)Tc-ECD brain SPECT abnormalities were significantly more common in patients with pSS (10/10) than controls (2/10; p<0.05). Cognitive dysfunctions, mainly expressed as executive and visuospatial disorders, were also significantly more common in patients with pSS (8/10) than controls (0/10; p<0.01). Notably, between-group comparisons enabled a significant correlation to be established between neuropsychological assessment and (99m)Tc-ECD brain SPECT abnormalities in patients with pSS (r(s) = 0.49, p<0.01). MRI abnormalities in patients and controls did not differ significantly.Neuropsychological testing and (99m)Tc-ECD brain SPECT seem to be the most sensitive tools to detect subclinical CNS dysfunction in pSS. The strong correlation between cortical hypoperfusion in (99m)Tc-ECD brain SPECT and cognitive dysfunction suggests an organic aetiology of CNS dysfunction in pSS. These data should be confirmed in a larger study.