tbuckley/cabot-search huggingface dataset:
Impact of Diabetic Nephropathy on Pharmacodynamic and Pharmacokinetic Properties of Insulin in Type 1 Diabetic Patients
Authors: Klaus Rave, Tim Heise, Andreas Pfützner, Lutz Heinemann, Peter T. Sawicki
Journal: Diabetes Care (2001)

OBJECTIVE—To quantify pharmacokinetic and pharmacodynamic properties of regular insulin and insulin lispro in type 1 diabetic patients with and without overt diabetic nephropathy. RESEARCH DESIGN AND METHODS—In this double-blind, two-way cross-over, euglycemic (5 mmol/l) glucose clamp study, we investigated the metabolic response to subcutaneous injections of regular insulin and insulin lispro (0.2 U/kg) in 12 type 1 diabetic patients with overt diabetic nephropathy (proteinuria &amp;gt;500 mg/24 h and/or serum creatinine &amp;gt;1.5 mg/dl; NP group) and in a control group of 12 type 1 diabetic patients with normal renal function (DC group). RESULTS—Peak plasma free insulin levels with insulin lispro (359 [NP] vs. 254 pmol/l [DC]) were higher and time to maximal insulin concentrations (85 [NP] vs. 99 min [DC]) shorter than with regular insulin (213 [NP] vs. 144 pmol/l [DC]; 118 [NP] vs. 153 min [DC]) in both patient groups. Overall insulin levels for regular insulin and for insulin lispro were higher in patients with overt diabetic nephropathy compared with control patients. Time to maximal metabolic effect was shorter with insulin lispro than with regular insulin in both patient groups (102 vs. 191 min [NP]; 105 vs. 172 min [DC]). The overall metabolic effect of regular insulin but not of insulin lispro was lower in patients with diabetic nephropathy than in diabetic control patients (967 vs. 1,510 mg/kg, respectively). CONCLUSIONS—Although insulin levels are higher in patients with overt diabetic nephropathy, the metabolic response to regular insulin is reduced. Insulin lispro maintains its characteristic pharmacokinetic and pharmacodynamic properties in patients with overt diabetic nephropathy.
Follicular miniaturization in female pattern hair loss: clinicopathological correlations
Authors: A.G. Messenger, R. Sinclair
Journal: British Journal of Dermatology (2006)

Background The pathology of female pattern hair loss (FPHL) is characterized by an increase in the proportion of vellus follicles, manifest as a low terminal/vellus ratio. This is conventionally thought to be due to a progressive miniaturization of terminal hair follicles. There is also a prolongation of the latent period of the hair cycle (kenogen) in both male pattern hair loss and FPHL and follicles in kenogen may be difficult to classify histologically. Therefore, a low terminal/vellus ratio could be due to a preferential increase in the number of terminal follicles in kenogen rather than to a true increase in the number of vellus follicles. Objectives To establish whether there is an increase in the absolute number of vellus follicles during the progression of FPHL, indicating a process of follicular miniaturization. Methods We studied 42 women complaining of hair loss. The severity of the hair loss was graded clinically on a five-point scale from 1 (no obvious hair loss) to 5 (severe hair loss). Three 4-mm punch biopsies were taken from the frontal scalp of each patient, sectioned horizontally and stained with haematoxylin and eosin. Two levels were studied on each biopsy: through the mid-infundibular region and through the mid-isthmus. The following were counted: total follicles, terminal follicles, vellus follicles, anagen and telogen/catagen follicles. The results from the three biopsies from each subject were averaged and statistical evaluations performed on the mean values. Results There was a progressive decline in mean total follicle count with increasing grade of hair loss (grade 1, 317 cm−2; grade 5, 243 cm−2) and a more pronounced reduction in terminal follicle counts (grade 1, 263 cm−2; grade 5, 96 cm−2). The absolute number of vellus follicles increased from 33 cm−2 (grade 1) to 71 cm−2 (grade 4), declining to 51 cm−2 at grade 5. The terminal/vellus ratio fell from 12·8 (grade 1) to 2·3 (grade 4) and remained at this level thereafter. The proportion of follicles in telogen increased from 13·7% (grade 1) to 31·4% (grade 5). Conclusions Our results show that there is an increase in vellus follicle numbers with increasing severity of hair loss in women with FPHL, suggesting that terminal follicles do indeed miniaturize. It is possible that there is also an increase in the number of follicles in a latent stage of telogen but this was difficult to assess from our data. The fall in total follicle counts with stabilizing of the terminal/vellus ratio in severe hair loss suggests that miniaturization does not stop with a vellus follicle but progresses to follicular deletion.
IMPACT OF OPTIMAL HEART FAILURE MEDICAL THERAPY AFTER DRUG-ELUTING STENT IMPLANTATION FOR THE PATIENTS WITH SEVERE LEFT VENTRICULAR DYSFUNCTION ON LONG TERM MORTALITY
Authors: Shinichi Shirai, Takeshi Kimura, Takeshi Morimoto, Kenji Ando, Yoshimitsu Soga, Kyohei Yamaji, Takeshi Arita, Makoto Hyodo, Koyu Sakai, Katsuhiro Kondo, Masashi Iwabuchi, Hiroyoshi Yokoi, Masakiyo Nobuyoshi, Kazuaki Mitsudo
Journal: Journal of the American College of Cardiology (2011)
The U.S. Health Insurance Marketplace: Are Premiums Truly Affordable?
Authors: Ilana Graetz, Cameron M. Kaplan, Erin K. Kaplan, James E. Bailey, Teresa M. Waters
Journal: Annals of Internal Medicine (2014)

The Patient Protection and Affordable Care Act requires that individuals have health insurance or pay a penalty. Individuals are exempt from paying this penalty if the after-subsidy cost of the least-expensive plan available to them is greater than 8% of their income. For this study, premium data for all health plans offered on the state and federal health insurance marketplaces were collected; the after-subsidy cost of premiums for the least-expensive bronze plan for every county in the United States was calculated; and variations in premium affordability by age, income, and geographic area were assessed. Results indicated that-although marketplace subsidies ensure affordable health insurance for most persons in the United States-many individuals with incomes just above the subsidy threshold will lack affordable coverage and will be exempt from the mandate. Furthermore, young individuals with low incomes often pay as much as or more than older individuals for bronze plans. If substantial numbers of younger, healthier adults choose to remain uninsured because of cost, health insurance premiums across all ages may increase over time.
Loss of E-Cadherin Promotes Metastasis via Multiple Downstream Transcriptional Pathways
Authors: Tamer T. Onder, Piyush B. Gupta, Sendurai A. Mani, Jing Yang, Eric S. Lander, Robert A. Weinberg
Journal: Cancer Research (2008)

Abstract Loss of the epithelial adhesion molecule E-cadherin is thought to enable metastasis by disrupting intercellular contacts—an early step in metastatic dissemination. To further investigate the molecular basis of this notion, we use two methods to inhibit E-cadherin function that distinguish between E-cadherin's cell-cell adhesion and intracellular signaling functions. Whereas the disruption of cell-cell contacts alone does not enable metastasis, the loss of E-cadherin protein does, through induction of an epithelial-to-mesenchymal transition, invasiveness, and anoikis resistance. We find the E-cadherin binding partner β-catenin to be necessary, but not sufficient, for induction of these phenotypes. In addition, gene expression analysis shows that E-cadherin loss results in the induction of multiple transcription factors, at least one of which, Twist, is necessary for E-cadherin loss–induced metastasis. These findings indicate that E-cadherin loss in tumors contributes to metastatic dissemination by inducing wide-ranging transcriptional and functional changes. [Cancer Res 2008;68(10):3645–53]
Lansley's NHS "reforms"
Authors: A. McLellan, J. Middleton, F. Godlee
Journal: BMJ (2012)

Something like this must never happen again

As the editors of the BMJ , Health Service Journal , and Nursing Times , we have divergent views on the government’s NHS reforms and its beleaguered Health and Social Care Bill. But on one thing we are agreed—that the resulting upheaval has been unnecessary, poorly conceived, badly communicated, and a dangerous distraction at a time when the NHS is required to make unprecedented savings. Worse, it has destabilised and damaged one of this country’s greatest achievements: a system that embodies social justice and has delivered widespread patient satisfaction, public support, and value for money. We must make sure that nothing like this ever happens again.

Health professional groups differ in their stance on whether to oppose the bill outright—as the BMA, the royal colleges of nursing and midwives, and the chartered physiotherapists have done—or whether to work with the government to try to improve the bill, as the NHS Confederation and the medical and surgical royal colleges have opted to do. But there can be no doubting the deep distress and lack of confidence in the government’s plans among those who must deliver the service.

A chief executive of a primary care trust cluster admitted to one of us last week that the breakdown of the relationships between commissioners and hospital trusts caused by the structural mayhem had left him with no way of knowing for sure “if I’ve got another Mid Staffs on my doorstep.” He was only reassured by the fact that “nothing much happens up here, so the local paper does a lot on health.” One commentator told the …
Points from Letters: Schonlein versus Henoch
Authors: S. R. Meadow
Journal: BMJ (1974)

poem.I was particularly interested as there is a current neglect of medals as a source of medical history.May I make some observations on the medal itself?The object under the lancet on the reverse is a vaccine point, perhaps of ivory, on which the material, fresh or dry, would be conveyed to the scarified area.Ampoules were not used for biological material until sterilization was understood.Incidentally, the goddess has a bandage round her left arm as though she had been recently vaccinated, surely a work of supererogation. . Schonlein versus Henoch
Association of Acanthosis Nigricans With Hyperinsulinemia Compared With Other Selected Risk Factors for Type 2 Diabetes in Cherokee Indians
Authors: Martha L. Stoddart, Kathleen S. Blevins, Elisa T. Lee, Wenyu Wang, Piers R. Blackett
Journal: Diabetes Care (2002)

OBJECTIVE—To report prevalence rates of acanthosis nigricans (AN) and hyperinsulinemia and the association of AN with hyperinsulinemia compared with other known or suspected risk factors for type 2 diabetes in young American Indians. RESEARCH DESIGN AND METHODS—A random sample of Cherokee Nation members aged 5–40 years was invited to participate in the Cherokee Diabetes Study, a cross-sectional study of type 2 diabetes and its risk factors in a young American Indian population. Data were collected by personal interview, medical history, physical examination (including anthropometric and blood pressure measurements and examination of the neck for AN), and laboratory analyses of blood specimens. Levels of insulin, lipids, and glucose were measured on fasting blood specimens. Diabetes status was determined according to the American Diabetes Association criteria. RESULTS—A total of 2,205 participants were examined. Overall prevalence rates for AN and hyperinsulinemia were 34.2 and 47.2%, respectively. In general, the rates for both increased with age and degree of Indian heritage and were higher in female subjects, overweight/obese individuals, those with type 2 diabetes, and those with a parental history of type 2 diabetes. In addition, both had significantly higher age- and sex-adjusted means for selected known or suspected risk factors for type 2 diabetes. AN remained significantly associated with hyperinsulinemia (P = 0.0001) in multivariate analysis. CONCLUSIONS—AN is independently associated with hyperinsulinemia and therefore may be useful as an early indicator of high risk for diabetes.
The Common Health — Centenary at St. Mary's Hospital — The Doctor and His Car
Authors: John Lister
Journal: New England Journal of Medicine (1955)

EVER since 1901, when King Edward VII graciously consented to become patron of the British Medical Association, the Association has been honored by the patronage of each successive sovereign. Today, it rejoices in the patronage of Her Majesty, the Queen, and at a recent Council Dinner the Duke of Edinburgh, the principal guest, graciously accepted honorary membership in the Association. In conferring this membership on the Duke, the chairman of the Council, Dr. E. A. Gregg, recalled how His Royal Highness had continually shown his interest in the welfare of the people and in the practical application of scientific knowledge. . . .
Sex hormones in postmenopausal women with primary biliary cirrhosis
Authors: Ulrik Becker, Thomas Almdal, Erik Christensen, Christian Gluud, Stense Farholt, Paul Bennett, Birgit Svenstrup, Finn Hardt
Journal: Hepatology (1991)

To evaluate serum sex hormone profiles in nonalcoholic postmenopausal women with liver disease, 25 women with primary biliary cirrhosis (11 in cirrhotic stage) and 46 healthy controls were studied. The patients had significantly (p less than 0.05) elevated serum concentrations of estrone and androstenedione and significantly (p less than 0.05) lower concentrations of estrone sulfate, dehydroepiandrosterone sulfate and 5 alpha-dihydrotestosterone compared with the 46 controls. Serum concentrations of sex hormone binding globulin, testosterone, non-sex hormone binding globulin-bound testosterone and non-protein-bound testosterone did not differ significantly (p greater than 0.05) between primary biliary cirrhosis patients and controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher concentrations of sex hormone binding globulin than did controls. Patients in the cirrhotic stage had significantly (p less than 0.05) higher sex hormone binding globulin and estrone sulfate levels compared with noncirrhotic patients with primary biliary cirrhosis. Otherwise, no significant differences were observed between cirrhotic and noncirrhotic patients. The observed changes in steroid concentrations may be a consequence of hepatic dysfunction.
Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease
Authors: Behzad Yeganeh, Emilia Wiechec, Sudharsana R. Ande, Pawan Sharma, Adel Rezaei Moghadam, Martin Post, Darren H. Freed, Mohammad Hashemi, Shahla Shojaei, Amir A. Zeki, Saeid Ghavami
Journal: Pharmacology & Therapeutics (2014)
ASSOCIATION OF GENOME WIDE LOCI FOR CAD WITH DISTRIBUTION OF CORONARY DISEASE
Authors: Atif Qasim, Lena Matthews, Liming Qu, Rajesh Movva, Kambiz Parcham-Azad, Stephanie DerOhannessian, Jane Ferguson, Mingyao Li, Daniel J. Rader, Muredach P. Reilly
Journal: Journal of the American College of Cardiology (2010)
Decreased proliferation, interleukin 2 synthesis, and interleukin 2 receptor expression are accompanied by decreased mRNA expression in phytohemagglutinin-stimulated cells from elderly donors.
Authors: J E Nagel, R K Chopra, F J Chrest, M T McCoy, E L Schneider, N J Holbrook, W H Adler
Journal: Journal of Clinical Investigation (1988)

Using cDNA probes to human interleukin 2 (IL2) and interleukin 2 receptor (IL2R), the amount of IL2 and IL2R mRNA produced by PHA stimulated peripheral blood mononuclear cells from young (less than 40 yr) and old (greater than 60 yr) donors was quantitated. Stimulated cell cultures from each individual were also examined for proliferative ability, expression of membrane IL2R, membrane IL2R density, and for the amount of IL2R shed into the culture supernatant. Induction of IL2 and IL2R mRNAs were decreased in cells from elderly individuals, as were the levels of IL2 secretion, the percentage of IL2R+ T cells and the density of membrane IL2R per cell. The results suggest that decreased expression of both IL2 and IL2R mRNA contributes to the low synthesis of IL2 and membrane IL2R, respectively, and is partially responsible for the diminished proliferative activity observed in lymphocytes from the elderly.
Incubation period of coronary heart disease.
Authors: G Rose
Journal: BMJ (1982)

Serum cholesterol concentrations and blood pressure were measured during 1958-64 among men aged 40-59 who took part in the Seven Countries Study. In the present study these measurements were related to the national mortality from coronary heart disease in the periods 1959-61, 1964-6, 1969-71, and 1974-6. The correlations increased with time (r = +0.86, 0.90, 0.93, and 0.96 respectively for serum cholesterol concentration and r = +0.48, 0.56, 0.57, and 0.64 for systolic blood pressure), suggesting that the "incubation period" between exposure to major coronary risk factors and the maximum effects on mortality may be 10 years or more.
Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome
Authors: Y Sagami
Journal: Gut (2004)

Background and aims: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of α-helical CRH (αhCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. Methods: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of αhCRH (10 μg/kg). Results: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of αhCRH. Administration of αhCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. αhCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by αhCRH. Conclusion: Peripheral administration of αhCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.
257 Liver transplantation (OLT), compared to percutaneous ethanol injection (PEI), assures better survival in patients with “early HCC”: a controlled, multicenter study
Authors: A ANDRIULLI, I DESIO, L SOLMI, S ORSOLAMALPIGHI, V FESTA, E CATURELLI, A GRASSO, A BURROUGHS, R TROISI, B DEHEMPTINNE
Journal: Hepatology (2003)
260. ITRs Necessary for IL-10 Encoding Naked Plasmid Induced Reversal of Chronic Pain State in Rat
Authors: T.S. Hughes, S.J. Langer, E.M. Sloane, J. Mahoney, B. Jekich, K.W. Johnson, R.E. Chavez, E.D. Milligan, L.R. Watkins, L.A. Leinwand
Journal: Molecular Therapy (2006)

Controlling chronic pain in humans is a major unresolved problem. Spinal cord astrocytes and microglia are critically involved in the creation and maintenance of diverse enhanced pain states via the release of proinflammatory cytokines. Interluekin-10 (IL-10), a potent anti-inflammatory cytokine, suppresses proinflammatory cytokine production and activity. Control of chronic neuropathic pain such as sensitivity to light touch (allodynia) requires chronic spinal delivery of IL-10. Chronic pain can be surgically induced in rats by loose ligature of chromic cat gut around the sciatic nerve in four places. This creates a chronic constriction injury (CCI) as the nerve bundle swells against the irritating ligature. The CCI model produces an enhanced pain phenotype for 3 months. We have demonstrated that this pain is reversed transiently (4hrs.) through intrathecal injection of recombinant IL-10 protein and that two temporally spaced injections of an IL-10 expression vector containing inverted terminal repeats (ITRs) reverses this pain long term (3+ months, Milligan et al., these proceedings). The role of ITRs in gene expression is not well known, however there is evidence that they possess transcription promoter and enhancer activity (Flotte et al., 1992 Am J Respir Cell Mol Biol. 7:p349-56 and 1993 J Biol Chem. 268: p3781-90). Based on this and other evidence in the literature we sought to determine if the ITRs in our expression vector, which are located 5|[prime]| of the CMV enhancer and Chicken |[beta]|-actin promoter (5|[prime]| ITR) and 3|[prime]| of the SV 40 poly A tail sequence (3|[prime]| ITR), influence reversal of pain in the CCI model. To this end we deleted both ITR's from the expression vector and found that it was incapable of producing pain reversal. We next asked if one or both ITRs are necessary for pain reversal. We found that plasmids containing just the 3|[prime]| or 5|[prime]| ITR are not as robust in reversing chronic pain. We have also found that ITRs are required on the first injection but not on a second injection for long-term pain relief. In other words, initial injection of a plasmid containing ITRs seems to |[ldquo]|prime|[rdquo]| the system making the second injection of the expression vector vastly more efficacious. Ongoing studies seek to further characterize the role of ITRs on gene expression and pain reversal in the CCI model.
327 Opioid dependent modulation of liver fibrogenesis: A role for hepatic redox state
Authors: M.R. Ebrahimkhani, S. Kiani, T. Kendall, S.M. Tavangar, A. Shariftabrizi, E. Oakley, A.R. Mani, A.R. Dehpour, D.A. Manna, K.P. Moore
Journal: Journal of Hepatology (2006)
Effect of Quinidine on Digoxin Concentration in Skeletal Muscle and Serum in Patients with Atrial Fibrillation
Authors: Karin Schenck-Gustafsson, Tomas Jogestrand, Rolf Nordlander, Rune Dahlqvist
Journal: New England Journal of Medicine (1981)

Medical Intelligence from The New England Journal of Medicine — Effect of Quinidine on Digoxin Concentration in Skeletal Muscle and Serum in Patients with Atrial Fibrillation — Evidence for Reduced Binding of Digoxin in Muscle