tbuckley/cabot-search huggingface dataset:
Factors Predicting the Age When Type 2 Diabetes Is Diagnosed in Hong Kong Chinese Subjects
Authors: Shao C. Lee, Gary T.C. Ko, June K.Y. Li, Chun C. Chow, Vincent T.F. Yeung, Julian A.J.H. Critchley, Clive S. Cockram, Juliana C.N. Chan
Journal: Diabetes Care (2001)

OBJECTIVE—To examine the factors predicting age at diagnosis of type 2 diabetes in Hong Kong Chinese. RESEARCH DESIGN AND METHODS—The relationships between age at diagnosis and parental history of diabetes as well as an array of clinical and metabolic factors were examined using a hospital clinic-based diabetes registry involving 3,414 index patients with type 2 diabetes. Patterns of age at diagnosis in successive generations were also examined using 21 affected child-parent pairs and 7 affected child-parent-grandparent trios. RESULTS—Approximately 29% of the index patients were diagnosed with type 2 diabetes at ≤35 years of age (hereby defined as early-onset). Compared with the patients diagnosed at &amp;gt;35 years of age (hereby defined as late-onset), the early-onset patients had higher rates of positive paternal (16 vs. 5%) and maternal (22 vs. 12%) history of diabetes (both at P &amp;lt; 0.01) and had poorer metabolic profiles. In the overall index patients, male sex, higher HbA1c, waist-to-hip ratio (WHR), and systolic blood pressure (sBP); lower HDL cholesterol level; and a positive paternal as well as maternal history of diabetes predicted younger age at diagnosis. More senior age and higher BMI and diastolic blood pressure predicted older age at diagnosis. Predictors for younger age at diagnosis in the male patients were higher HbA1c and sBP and a positive paternal history of diabetes. Predictors for younger age at diagnosis in the female patients were higher HbA1c, WHR, and sBP and a paternal as well as maternal history of diabetes. In the affected child-parent pairs and child-parent-grandparent trios, there was a decrease in age at diagnosis in successive generations. CONCLUSIONS—Our data indicate that both familial (possibly genetic) and metabolic factors affect the age of onset of type 2 diabetes in the Chinese population. The results also suggest an onset and progression pattern of the disease that is compatible with the phenomenon of anticipation.
Doctors' leaders reject "immoral" proposals to close thousands of beds
Authors: A. O'Dowd
Journal: BMJ (2010)

Doctors’ leaders have reacted angrily to proposals that around 30 000 NHS hospital beds in England should be closed to save money and improve patient care.

The radical proposal came in a report published on 17 March by public services and economic think tank Reform, which believes much of the overall deficit in the public sector is caused by increased spending on the NHS in recent years.

The report says that the NHS has overinvested in the wrong facilities and far more care could and should be provided in the community hence the need to reduce the number of hospital beds by around a third …
S91 Aspergillus fumigatus sensitisation in patients with chronic obstructive pulmonary disease
Authors: M. Bafadhel, J. Agbetile, A. Fairs, D. Desai, M. Pancholi, V. Mistry, I. D. Pavord, A. J. Wardlaw, C. H. Pashley, C. E. Brightling
Journal: Thorax (2011)

<h3>Background</h3> Bacteria and viruses have been implicated in exacerbations of chronic obstructive pulmonary disease (COPD) and bacteria are often isolated in stable state. Whether fungi are also commonly present and associated with clinical and pathological features of disease is uncertain. <h3>Objectives</h3> To determine the frequency of filamentous fungal culture and sensitisation to <i>Aspergillus fumigatus</i> in COPD and its relationship to clinical outcomes. <h3>Methods</h3> Subjects with COPD were recruited from a single centre into a 1-year observational study. Assessments of lung function, allergen testing, and sputum analysis for inflammation, bacterial and fungal cultures were undertaken in COPD subjects and in smoking healthy controls. <h3>Results</h3> Fungi were cultured at baseline in 63/128 subjects of which 47/63 were <i>A fumigatus</i>. <i>A fungus</i> was cultured in 2/11 controls (both were <i>A fumigatus</i>). The total sputum cell count, sputum neutrophil % and inhaled corticosteroid dosage were significantly increased in COPD patients with a positive fungal culture compared to those without a fungal culture (p&lt;0.05), but the within subject repeatability of fungal culture between stable visits was low (K=−0.04). Sensitisation to <i>A fumigatus</i> was present in 13% of COPD subjects and was associated with worse lung function (FEV<sub>1</sub> % predicted 39% vs 51%; p=0.01), but not related to fungal culture. Positive fungal cultures were present in 42/110 exacerbations and were not associated with bacterial culture or severity of exacerbation. <h3>Conclusions</h3> <i>A fumigatus</i> sensitisation is related to poor lung function. Positive fungal culture is a common feature of COPD. The clinical significance of this remains uncertain.
Effects of long-term nocturnal nasal ventilation on spontaneous breathing during sleep in neuromuscular and chest wall disorders
Authors: A.J. Piper, C.E. Sullivan
Journal: European Respiratory Journal (1996)

Nocturnal nasal intermittent positive pressure ventilation (NIPPV) is an effective means of normalizing awake blood gases in patients with respiratory insufficiency due to neuromuscular or chest wall dysfunction. However, little attention has been paid to the effects of long-term ventilation on spontaneous breathing during sleep in such patients. The purpose of this study was to determine whether spontaneous breathing during sleep improved after long-term nasal ventilation. Fourteen patients with documented nocturnal respiratory failure, who had been treated with nocturnal NIPPV for at least 6 months, were reviewed with an all night polysomnograph on a night without ventilatory support. The severity of nocturnal desaturation both in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep without nocturnal ventilation was compared to desaturation measured during the initial diagnostic study. Spontaneous daytime blood gas values (mean +/- SD) were significantly improved at follow-up compared to values obtained prior to nasal ventilation: arterial oxygen tension (Pa,O2): 7.5 +/- 1.2 to 10.2 +/- 1.3 kPa (p &lt; 0.005); arterial carbon dioxide tension (Pa,CO2) 8.2 +/- 1.6 to 6.4 +/- 0.7 kPa (p &lt; 0.001). Significant improvements in inspiratory muscle strength were also observed with maximal inspiratory pressure (Pl, max) increasing from a baseline value of 41 +/- 18 to 65 +/- 26% predicted measured prior to the night of ventilation withdrawal (p &lt; 0.003). Spontaneous breathing during sleep after long-term treatment was markedly improved although still abnormal. During NREM sleep without ventilatory support, oxygen desaturation was significantly less severe compared to the initial study (arterial oxygen saturation (Sa,O2) 88 +/- 4 vs 78 +/- 8%; p &lt; 0.001). Minimum Sa,O2 during REM sleep similarly improved from a mean value of 49 +/- 14% during the diagnostic night to 73 +/- 10% at review follow-up (p &lt; 0.001). In 12 patients, transcutaneous carbon dioxide was measured continuously during sleep on both occasions and demonstrated significantly less CO2 retention during follow-up compared to control studies both in NREM (p &lt; 0.003) and REM sleep states (p &lt; 0.004). Long-term nocturnal ventilation produces improved respiratory drive both asleep and awake and improved arousal responses to abnormal blood gases.
Porphyromonas gingivalis Manipulates Complement and TLR Signaling to Uncouple Bacterial Clearance from Inflammation and Promote Dysbiosis
Authors: Tomoki Maekawa, Jennifer L Krauss, Toshiharu Abe, Ravi Jotwani, Martha Triantafilou, Kathy Triantafilou, Ahmed Hashim, Shifra Hoch, Michael A Curtis, Gabriel Nussbaum, John D Lambris, George Hajishengallis
Journal: Cell Host & Microbe (2014)
Impact of diabetes mellitus on functional capacity and cardiac autonomic control: Spectral and non linear indices analysis
Authors: Daniela Dutra, Vivian Arakelian, Renata Mendes, Flávia Caruso, Luís Carlos Bonjorno, Glaucio Dutra, Claudio Oliveira, Milena Sperling
Journal: European Respiratory Journal (2013)

Background:  Heart rate variability (HRV) is a non-invasive method to measure cardiac autonomic function.  Diabetes Mellitus  (DM) is a chronic disease is one of the most important risk factors for developing cardiovascular disease.  Objective:  To evaluate and correlate functional capacity and HRV in DM patients.  Materials and Methods:  16 patients (49.4±6.2 years) were evaluated. R-R intervals (RRi) were obtained by the Polar S810i heart rate (HR) monitor on rest. Linear (mean heart rate, mean HR, standard deviation of RRi, mean RR, triangular index, RR-Tri, standard deviation of RR, STD-RR and nonlinear (short-term correlation properties of RRi, DFAα2, approximate entropy- AE and Shannon entropy- SE) indices of HRV were analyzed. Pulmonary gas exchange breath-by-breath was measured during an incremental exercise testing on a cycle. Oxygen uptake (VO 2 ), carbon dioxide production (VCO 2 ), minute ventilation (V E ), end tidal carbon dioxide tension (PetCO 2 ) and V E /VCO 2  were compared. Data analysis was used to test for normality Shapiro-Wilk test and Pearson correlation.  Results:  We found that VO 2  peak presented correlation with mean RRi (r=0.59) and with mean HR (r=0.60). In addition, VCO 2  was correlated with mean RR (r=0.65) and mean HR (r=-0.65). PetCO 2  was correlated with STD-RR (r=-0,54), RR-Tri (r=-0.56), DFAα2 (r=-0.63), SE (r=0.64) and AE (r=0.67). Finally, we observed correlation between V E /VCO 2  with STD-RR (r=0.54), RR-Tri (r=0.58) and DFAα2 (r=0.59), SE (r=-0.63) and AE (r=-0.79).  Conclusion:  The results suggest that linear and nonlinear analyses of HRV are associated to maximal functional capacity in DMII.  Financial support: CNPq and FAPESP 2009/01842-0.
Diagnosis and monitoring of central nervous system involvement in systemic lupus erythematosus: value of F-18 fluorodeoxyglucose PET
Authors: S M Weiner
Journal: Annals of the Rheumatic Diseases (2000)

To investigate prospectively abnormalities of brain glucose utilisation in relation to major or minor neuropsychiatric symptoms in systemic lupus erythematosus (SLE).Positron emission tomography (PET) using F-18-labelled fluorodeoxyglucose was performed in 28 patients with SLE. Patients were classified as having severe neuropsychiatric manifestations (seizures, focal neurological deficits, acute confusional states, mood disorders) (n=12), or mild neuropsychiatric manifestations (headache, reactive depression, cognitive dysfunction, anxiety disorders) (n=11) and five patients without signs of central nervous system (CNS) involvement. Ten clinically and neurologically healthy volunteers served as controls. In 26 patients magnetic resonance imaging (MRI) was performed and autoantibodies against CNS tissue, ribosomal P protein and cardiolipin were measured. In 14 patients follow up PET scans were performed after a mean (SD) period of 11.6 (9.5) months.PET scans showed hypometabolism in at least one brain region in all patients with severe or mild CNS symptoms (100%) as compared with patients without cerebral symptoms (40%) (p<0.0025). Parieto-occipital regions were most commonly affected (96%), followed by parietal regions (32%). In contrast, MRI images were abnormal in only 11 of 22 patients (50%) with neuropsychiatric symptoms and in one of four patients (25%) without symptoms. In 12 of 14 patients examined in follow up PET scans persistence, improvement or worsening of cerebral symptoms were associated with unchanged, decreased or increased brain hypometabolism, respectively. No significant correlation was found between PET or MRI findings and autoantibody profiles.PET imaging represents a sensitive tool to detect manifest or subclinical CNS involvement in SLE and PET findings correlate well with the clinical course of disease.
Membrane versus Soluble Isoforms of TNF-α Exert Opposing Effects on Tumor Growth and Survival of Tumor-Associated Myeloid Cells
Authors: Shidrokh Ardestani, Bin Li, Desirae L. Deskins, Huiyun Wu, Pierre P. Massion, Pampee P. Young
Journal: Cancer Research (2013)

TNF-α, produced by most malignant cells, orchestrates the interplay between malignant cells and myeloid cells, which have been linked to tumor growth and metastasis. Although TNF-α can exist as one of two isoforms, a 26-kDa membrane tethered form (mTNF-α) or a soluble 17-kDa cytokine (sTNF-α), the vast majority of published studies have only investigated the biologic effects of the soluble form. We show for the first time that membrane and soluble isoforms have diametrically opposing effects on both tumor growth and myeloid content. Mouse lung and melanoma tumor lines expressing mTNF-α generated small tumors devoid of monocytes versus respective control lines or lines expressing sTNF-α. The lack of myeloid cells was due to a direct effect of mTNF-α on myeloid survival via induction of cell necrosis by increasing reactive oxygen species. Human non-small cell lung carcinoma expressed varying levels of both soluble and membrane TNF-α, and gene expression patterns favoring mTNF-α were predictive of improved lung cancer survival. These data suggest that there are significant differences in the role of different TNF-α isoforms in tumor progression and the bioavailability of each isoform may distinctly regulate tumor progression. This insight is critical for effective intervention in cancer therapy with the available TNF-α inhibitors, which can block both TNF-α isoforms.
Dopamine Increases the Efficacy of Anticancer Drugs in Breast and Colon Cancer Preclinical Models
Authors: Chandrani Sarkar, Debanjan Chakroborty, Uttio Roy Chowdhury, Partha Sarathi Dasgupta, Sujit Basu
Journal: Clinical Cancer Research (2008)

Because neurotransmitter dopamine inhibits vascular permeability factor/vascular endothelial growth factor (VEGF)-induced angiogenesis and as anti-VEGF agents act synergistically with anticancer drugs, we therefore investigated whether dopamine can increase the efficacies of these drugs.The effect of dopamine was investigated in human breast cancer-(MCF-7) and colon (HT29) cancer-bearing mice. Experimental groups received either dopamine or doxorubicin or dopamine plus doxorubicin in MCF-7 tumor-bearing mice, and either dopamine or 5-fluorouracil or dopamine plus 5-fluorouracil in HT29-bearing mice. Thereafter, tumor growth, angiogenesis, tumor cell apoptosis, life span, and the effect of dopamine on the growth and survival of tumor cells in vitro were determined. Finally, the effects of dopamine on tumor vascular permeability; on VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation; and also on the proliferation and migration of tumor endothelial cells were investigated.Dopamine, in combination with anticancer drugs, significantly inhibited tumor growth and increased the life span when compared with treatment with dopamine or anticancer drugs alone. Dopamine had no direct effects on the growth and survival of tumor cells. The antiangiogenic action of dopamine was mediated by inhibiting proliferation and migration of tumor endothelial cells through suppression of VEGF receptor-2, mitogen-activated protein kinase, and focal adhesion kinase phosphorylation.Our study shows that dopamine significantly enhances the efficacies of commonly used anticancer drugs and also indicates that an inexpensive drug like dopamine, which is being extensively used in the clinics, might have a role as an antiangiogenic agent for the treatment of breast and colon cancer.
Oxidative Stress and Platelet Activation in Homozygous Homocystinuria
Authors: G. Davì, G. Di Minno, A. Coppola, G. Andria, A.M. Cerbone, P. Madonna, A. Tufano, A. Falco, P. Marchesani, G. Ciabattoni, C. Patrono
Journal: Circulation (2001)

Severe hyperhomocysteinemia due to cystathionine beta-synthase deficiency (CbetaSD) is associated with early atherothrombotic vascular disease. Homocysteine may exert its effects by promoting oxidative damage. In the present study, we investigated whether in vivo formation of 8-iso-prostaglandin (PG) F(2alpha), a platelet-active product of arachidonic acid peroxidation, is enhanced in CbetaSD and whether it correlates with in vivo platelet activation, as reflected by thromboxane (TX) metabolite excretion.Urine and blood samples were obtained from patients with homozygous CbetaSD (n=13) and age-matched healthy subjects. Urinary 8-iso-PGF(2alpha) excretion was significantly higher in CbetaSD patients than in control subjects (640+/-384 versus 213+/-43 pg/mg creatinine; P=0.0015) and correlated with plasma homocysteine (rho=0.398, P=0.0076). Similarly, urinary 11-dehydro-TXB(2) excretion was enhanced in CbetaSD (1166+/-415 versus 324+/-72 pg/mg creatinine; P=0.0015) and correlated with urinary 8-iso-PGF(2alpha) (rho=0.362, P=0.0153). Vitamin E supplementation (600 mg/d for 2 weeks) was associated with a statistically significant increase in its plasma levels (from 16.6+/-4.6 to 40.4+/-8.7 micromol/L, P=0.0002) and with reductions in 8-iso-PGF(2alpha) (from 790+/-159 to 559+/-111 pg/mg creatinine, P=0.018) and 11-dehydro-TXB(2) (from 1273+/-383 to 913+/-336 pg/mg creatinine, P=0.028). A statistically significant inverse correlation was found between urinary 8-iso-PGF(2alpha) and plasma vitamin E levels (rho=-0.745, P=0.0135).The results of the present study suggest that enhanced peroxidation of arachidonic acid to form bioactive F(2)-isoprostanes may represent an important mechanism linking hyperhomocysteinemia and platelet activation in CbetaSD patients. Moreover, they provide a rationale for dose-finding studies of vitamin E supplementation in this setting.
Ejection fraction response to exercise in patients with chest pain, coronary artery disease and normal resting ventricular function.
Authors: R J Gibbons, K L Lee, F R Cobb, R E Coleman, R H Jones
Journal: Circulation (1982)

We studied the ejection fraction (EF) response to upright exercise using first-pass radionuclide angiography (RNA) in 281 patients with chest pain, significant coronary artery disease and normal resting ventricular function. A wide range of resting function (heart rate and EF) and exercise function (heart rate, EF and peak work load) was measured in this population. The EF response to exercise (delta EF) varied widely, ranging from a decrease of 36% to an increase of 26%. Twenty-eight clinical, catheterization and RNA variables were examined to determine their relationship to delta EF. Considered individually, the variables showing the strongest relationship were resting pulse pressure, positive exercise ECG changes and adequate exercise. Multivariable analysis identified resting pulse pressure, adequate exercise, resting EF, the change in end-diastolic volume index with exercise, positive exercise ECG changes and, to a lesser degree, the number of diseased vessels as variables that were significant independent predictors of delta EF. These observations indicate that delta EF is a complex response that is influenced by many pathophysiologic variables in the presence of coronary artery disease. Several of these variables are not related to the extent of coronary artery disease.
Expression of CD4+CD25+ marker and CXCR3, CCR4 chemokine receptors on peripheral blood lymphocytes during rush venom specific immunotherapy (VIT) in children
Authors: E. Cichocka-Jarosz, G. Lis, T. Szczerbinski, E. Zuba-Surma, M. Majka
Journal: Journal of Allergy and Clinical Immunology (2005)
FUNCTIONAL FACTORS IN "ORGANIC" BRAIN SYNDROME
Authors: HERBERT S. GREENSPAN
Journal: American Journal of Psychiatry (1964)

A patient was treated for symptoms of toxic psychosis, a form of organic brain syndrome, induced by tetanus antitoxin; her personal history showed an unstable emotional background, plus immediate emotional stress, prior to the onset of the overt psychotic behavior. The resultant lack of conviction about diagnosis and etiology led to other considerations, including pathology and treatment. Review of the pertinent literature revealed: 1. Support for the influence of pre-morbid background on the nature of toxic reactions; 2. The absence of any case of toxic psychosis caused by tetanus antitoxin; and 3. Evidence indicating the role of situational stress in the production of so-called toxic reactions. The conclusions reached were that a close scrutiny is indicated in the toxic psychoses before the application of such a diagnosis, and further scientific investigation into the "organic" nature of this disorder seems warranted.
Serum Proprotein Convertase Subtilisin/Kexin Type 9 and Cell Surface Low-Density Lipoprotein Receptor
Authors: Hagai Tavori, Daping Fan, John L. Blakemore, Patricia G. Yancey, Lei Ding, MacRae F. Linton, Sergio Fazio
Journal: Circulation (2013)

Background— Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates low-density lipoprotein (LDL) receptor (LDLR) degradation, thus influencing serum cholesterol levels. However, dysfunctional LDLR causes hypercholesterolemia without affecting PCSK9 clearance from the circulation. Methods and Results— To study the reciprocal effects of PCSK9 and LDLR and the resultant effects on serum cholesterol, we produced transgenic mice expressing human (h) PCSK9. Although hPCSK9 was expressed mainly in the kidney, LDLR degradation was more evident in the liver. Adrenal LDLR levels were not affected, likely because of the impaired PCSK9 retention in this tissue. In addition, hPCSK9 expression increased hepatic secretion of apolipoprotein B–containing lipoproteins in an LDLR-independent fashion. Expression of hPCSK9 raised serum murine PCSK9 levels by 4.3-fold in wild-type mice and not at all in LDLR −/− mice, in which murine PCSK9 levels were already 10-fold higher than in wild-type mice. In addition, LDLR +/− mice had a 2.7-fold elevation in murine PCSK9 levels and no elevation in cholesterol levels. Conversely, acute expression of human LDLR in transgenic mice caused a 70% decrease in serum murine PCSK9 levels. Turnover studies using physiological levels of hPCSK9 showed rapid clearance in wild-type mice (half-life, 5.2 minutes), faster clearance in human LDLR transgenics (2.9 minutes), and much slower clearance in LDLR −/− recipients (50.5 minutes). Supportive results were obtained with an in vitro system. Finally, up to 30% of serum hPCSK9 was associated with LDL regardless of LDLR expression. Conclusions— Our results support a scenario in which LDLR represents the main route of elimination of PCSK9 and a reciprocal regulation between these 2 proteins controls serum PCSK9 levels, hepatic LDLR expression, and serum LDL levels.