tbuckley/cabot-search huggingface dataset:
Chest Physical Therapy Management of Patients with Cystic Fibrosis: A Meta-analysis
Authors: J. Thomas, D.J. Cook, D. Brooks
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The purpose of this overview is to quantitatively assess the conflicting body of literature concerning the efficacy of physical therapy modalities for clearing bronchial secretions in the treatment of patients with cystic fibrosis (CF). The modalities examined included positive expiratory pressure (PEP) mask, forced expiratory technique (FET), exercise (EX), autogenic drainage (AD), and standard physical therapy (STD), consisting of postural drainage, percussion, and vibration. Computerized searches of the MEDLINE and Cumulative Index for Nursing and Allied Health databases were performed for the years from 1966 to 1993. The authors of relevant papers were contacted for unpublished information. Studies were considered relevant if they met the following criteria: randomized trials in patients with a definite diagnosis of CF; an intervention of any combination of PEP, FET, STD, AD, or EX; and an outcome of FEV1, sputum weight, or sputum clearance. A review of 456 citations yielded 65 potentially relevant trials and 8 review articles; of these, 35 met the inclusion criteria and were incorporated into the overview. These studies evaluated different combinations of physical therapy modalities; therefore, we performed seven separate meta-analyses comparing the independent techniques using the pooled effect size technique. Standard physical therapy resulted in a significantly greater sputum expectoration than no treatment (effect size of 0.61 SD units, p < 0.0001). The combination of standard therapy with EX was associated with a statistically significant increase in FEV1 over STD alone (effect size of 0.48 SD units, p = 0.04). No other differences between physical therapy modalities were found.
Erythrocyte G Protein as a Novel Target for Malarial Chemotherapy
Authors: Sean C Murphy, Travis Harrison, Heidi E Hamm, Jon W Lomasney, Narla Mohandas, Kasturi Haldar
Journal: PLoS Medicine (2006)

Malaria remains a serious health problem because resistance develops to all currently used drugs when their parasite targets mutate. Novel antimalarial drug targets are urgently needed to reduce global morbidity and mortality. Our prior results suggested that inhibiting erythrocyte Gs signaling blocked invasion by the human malaria parasite Plasmodium falciparum.We investigated the erythrocyte guanine nucleotide regulatory protein Gs as a novel antimalarial target. Erythrocyte "ghosts" loaded with a Gs peptide designed to block Gs interaction with its receptors, were blocked in beta-adrenergic agonist-induced signaling. This finding directly demonstrates that erythrocyte Gs is functional and that propranolol, an antagonist of G protein-coupled beta-adrenergic receptors, dampens Gs activity in erythrocytes. We subsequently used the ghost system to directly link inhibition of host Gs to parasite entry. In addition, we discovered that ghosts loaded with the peptide were inhibited in intracellular parasite maturation. Propranolol also inhibited blood-stage parasite growth, as did other beta2-antagonists. beta-blocker growth inhibition appeared to be due to delay in the terminal schizont stage. When used in combination with existing antimalarials in cell culture, propranolol reduced the 50% and 90% inhibitory concentrations for existing drugs against P. falciparum by 5- to 10-fold and was also effective in reducing drug dose in animal models of infection.Together these data establish that, in addition to invasion, erythrocyte G protein signaling is needed for intracellular parasite proliferation and thus may present a novel antimalarial target. The results provide proof of the concept that erythrocyte Gs antagonism offers a novel strategy to fight infection and that it has potential to be used to develop combination therapies with existing antimalarials.
Variation in barrier impairment and inflammation of human skin as determined by sodium lauryl sulphate penetration rate
Authors: C.M. de Jongh, I. Jakasa, M.M. Verberk, S. Kezic
Journal: British Journal of Dermatology (2005)

Skin irritability after a brief exposure to the model skin irritant, sodium lauryl sulphate (SLS), is known to vary considerably between individuals. A difference in the skin barrier to SLS may contribute to this variation. To date, no human in vivo data have been available on SLS penetration into the skin.We studied whether the SLS penetration rate into the stratum corneum (SC) is related to impairment of the water barrier function and inflammation of the skin.The penetration of SLS into the SC was assessed using a noninvasive tape-stripping procedure in 20 volunteers after a 4-h exposure to 1% SLS. Additionally, the effect of a 24-h exposure to 1% SLS on the skin water barrier function was assessed by measuring the transepidermal water loss (TEWL). The accompanying inflammation was quantified by measuring erythema.The mean +/- SD diffusivity of SLS (D) and the SLS permeability coefficient (Kp) were 1.4 +/- 0.6 x 10(-8) cm2 h(-1) and 1.5 +/- 0.7 x 10(-3) cm h(-1), respectively. A multiple regression analysis showed that the baseline TEWL, SC thickness and SLS penetration parameters K (SC/water partition coefficient) and D clearly influenced the increase in TEWL after the 24-h irritation test (explained variance: r2 = 0.80). Change in erythema was mainly influenced by SC thickness.We found that variation in the barrier impairment and inflammation of human skin depends on the SLS penetration rate, which was mainly determined by SC thickness.
Financial Hardship: A Consequence of Survivorship?
Authors: Cathy J. Bradley
Journal: Journal of Clinical Oncology (2012)

Despite this success on the treatment front, we have done little in a concerted and well-planned fashion to investigate and address the problems of survivors.It is as if we have invented sophisticated techniques to save people from drowning, but once they have been pulled from the water, we leave them on the dock to cough and splutter on their own in the belief that we have done all that we can.-Fitzhugh Mullan, MD, physician, survivor of cancer, and founding president of the National Coalition for Cancer Survivorship. 1(p273) Medicare and other insurers are paying for ever-increasing costs for chemotherapy treatment for cancer. 2Depending on the regimen, these costs can exceed $30,000 for an 8-week regimen.Bach 3 reported that Medicare spending on cancer drugs administered in the doctor's office was $11 billion in 2004.By 2020, the cost for the management of colorectal cancer alone in the United States is expected to increase to more than $14 billion. 4In a provocatively titled article, "When Will the U.S. Flinch at Cancer Drug Prices?," Vanchieri 5 interviewed physicians who discussed the societal costs of these drugs and the trade-offs purchasers make to supply these drugs in their treatment centers.In this article, Robert Wittes, physician-in-chief at Memorial Sloan-Kettering, noted that "nothing will happen [about rising costs] until patients start yelling when they are denied treatment or have to mortgage their homes to get it." 5(p626) This last point brings us to the research by Shankaran et al 6 published in the article that accompanies this editorial.Shankaran et al 6 report findings from an exploratory study of financial hardships experienced by patients who received adjuvant chemotherapy for the treatment of colon cancer.These authors shine a light on a serious problem facing many patients with cancer and their families.In their study, 38% of the analytic sample had one or more financial hardships as defined by fairly extreme measures: sold or refinanced a home, borrowed money, or experienced a 20% or greater decline in annual income.Most of us would consider these types of expenses as overly burdensome and nearly impossible to overcomeespecially if employment were no longer an option for the survivor of cancer.Risk factors associated with financial hardship are, as one would expect, younger age and low annual income (less than $50,000).These same characteristics are also associated with greater symptom burden, perhaps not coincidentally, 1 year after diagnosis, 7 echoing what is known about survivorship and who does well and who does not.Had Shankaran et al cast a wider net to the diagnosed population, the researchers might also have found patients who decided against treatment for financial reasons.
Weapons of Mass Destruction
Authors: Jerome P. Kassirer
Journal: JAMA Internal Medicine (2012)

While our national leaders agonize about the threats in the Middle East from missiles, bombs, and automatic weapons that might fall into terrorist hands, they have remained eerily silent about the unlimited access to weapons of mass destruction in our own backyard. In a sickening recapitulation of terror wrought in schools, movie theaters, and malls, our nation grieves for the large number of innocents murdered in a few minutes by a single American gunman. Yet the gun lobby has successfully muzzled political debate about guns, shut down federal research on gun-related injuries, and promoted legislation that prevents physicians from asking patients about gun-related risks. In the last few years, Supreme Court cases resulted in judgments that affirmed the right to keep guns in the home for protection. Recently, a federal appeals court ruled that our citizens even have a constitutional right to carry loaded guns outside their homes.1 Although legal scholars have questioned the current relevance of the Second Amendment, now that men no longer have to bring their private weapons to join the local militia,2 the Supreme Court has spoken, and for now we must live with its interpretation. Our sense of security, already seriously shaken by the launching of long-range missiles by rogue countries, by attacks on our citizens abroad, and by brazen terrorist assaults at home, now has us looking over our shoulders when we send our children to school or go to Macy's to buy a shirt. This state of chronic anxiety over safety is new; it is damaging individually and to our national psyche, and we must ameliorate the threats. We must not tolerate a situation in which some irrational, seriously disturbed person with a grudge can quickly blow us to bits along with dozens of others. Many approaches to prevent this kind of mayhem have been proposed. Some have suggested arming the public: the more guns, they argue, the greater the likelihood that someone will be able to “take down” a shooter. But imagine asking school nurses, librarians, sales clerks, and movie ushers to “pack heat.” Would they kill the shooter or, accidentally, each other? If we judge by recent experiences, this strategy is wanting. In Florida, a “neighborhood watch coordinator” killed an unarmed boy who was acting suspiciously; and near the Empire State Building, police fire injured 9 pedestrians while they were subduing 1 shooter. Would “more guns” lead to fewer gun deaths? Unlikely....[excerpt] Language: en
Cumulative Absolute Breast Cancer Risk for Young Women Treated for Hodgkin Lymphoma
Authors: Lois B. Travis, Deirdre Hill, Graça M. Dores, Mary Gospodarowicz, Flora E. van Leeuwen, Eric Holowaty, Bengt Glimelius, Michael Andersson, Eero Pukkala, Charles F. Lynch, David Pee, Susan A. Smith, Mars B. Van't Veer, Timo Joensuu, Hans Storm, Marilyn Stovall, John D. Boice, Ethel Gilbert, Mitchell H. Gail
Journal: JNCI Journal of the National Cancer Institute (2005)

Many women develop breast cancer after treatment for Hodgkin lymphoma (HL) at a young age. We estimated this future risk, taking into account age and calendar year of HL diagnosis, HL treatment information, population breast cancer incidence rates, and competing causes of death.Relative risks of breast cancer for categories defined by radiation dose to the chest (0, 20- < 40 Gy, or > or = 40 Gy) and use of alkylating agents (yes or no) were estimated from a case-control study conducted within an international population-based cohort of 3817 female 1-year survivors of HL diagnosed at age 30 years or younger from January 1, 1965, through December 31, 1994. To compute cumulative absolute risks of breast cancer, we used modified standardized incidence ratios to relate cohort breast cancer risks to those in the general population, enabling application of population-based breast cancer rates, and we allowed for competing risks by using population-based mortality rates in female HL survivors.Cumulative absolute risks of breast cancer increased with age at end of follow-up, time since HL diagnosis, and radiation dose. For an HL survivor who was treated at age 25 years with a chest radiation dose of at least 40 Gy without alkylating agents, estimated cumulative absolute risks of breast cancer by age 35, 45, and 55 years were 1.4% (95% confidence interval [CI] = 0.9% to 2.1%), 11.1% (95% CI = 7.4% to 16.3%), and 29.0% (95% CI = 20.2% to 40.1%), respectively. Cumulative absolute risks were lower in women treated with alkylating agents.Breast cancer projections varied considerably by type of HL therapy, time since HL diagnosis, and age at end of follow-up. These estimates are applicable to HL survivors treated with regimens of the past and can be used to counsel such patients and plan management and preventive strategies. Projections should be used with caution, however, in patients treated with more recent approaches, including limited-field radiotherapy and/or ovary-sparing chemotherapy.
Mesenchymal Stem Cells Are Renotropic, Helping to Repair the Kidney and Improve Function in Acute Renal Failure
Authors: Marina Morigi, Barbara Imberti, Carla Zoja, Daniela Corna, Susanna Tomasoni, Mauro Abbate, Daniela Rottoli, Stefania Angioletti, Ariela Benigni, Norberto Perico, Malcolm Alison, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2004)

Injury to a target organ can be sensed by bone marrow stem cells that migrate to the site of damage, undergo differentiation, and promote structural and functional repair. This remarkable stem cell capacity prompted an investigation of the potential of mesenchymal and hematopoietic stem cells to cure acute renal failure. The model of renal injury induced in mice by the anticancer agent cisplatin was chosen. Injection of mesenchymal stem cells of male bone marrow origin remarkably protected cisplatin-treated syngeneic female mice from renal function impairment and severe tubular injury. Y chromosome-containing cells localized in the context of the tubular epithelial lining and displayed binding sites for Lens culinaris lectin, indicating that mesenchymal stem cells engraft the damaged kidney and differentiate into tubular epithelial cells, thereby restoring renal structure and function. Mesenchymal stem cells markedly accelerated tubular proliferation in response to cisplatin-induced damage, as revealed by higher numbers of Ki-67-positive cells within the tubuli with respect to cisplatin-treated mice that were given saline. Hematopoietic stem cells failed to exert beneficial effects. These results offer a strong case for exploring the possibility that mesenchymal stem cells by virtue of their renotropic property and tubular regenerative potential may have a role in the treatment of acute renal failure in humans.
PREDISPOSING LOCUS FOR ALZHEIMER'S DISEASE ON CHROMOSOME 21
Authors: AlisonM. Goate, MichaelJ. Owen, LouiseA. James, MichaelJ. Mullan, MartinN. Rossor, AndrewR. Haynes, Martin Farrall, LawrenceY.C. Lai, Penelope Roques, Robert Williamson, JohnA. Hardy
Journal: The Lancet (1989)
A Multicenter Randomized Controlled Trial of Motivational Interviewing in Teenagers With Diabetes
Authors: Sue J. Channon, Michelle V. Huws-Thomas, Stephen Rollnick, Kerenza Hood, Rebecca L. Cannings-John, Carol Rogers, John W. Gregory
Journal: Diabetes Care (2007)

OBJECTIVE—We sought to examine the efficacy of motivational interviewing with teenagers aged 14–17 years with type 1 diabetes. RESEARCH DESIGN AND METHODS—In a randomized controlled trial analyzed by intention to treat, 66 teenagers with type 1 diabetes attending diabetes clinics in South Wales, U.K., were randomly assigned to the intervention group (38) and control group (28). Teenagers in the intervention group received motivational interviewing, and the control group received support visits. All participants received individual sessions over 12 months. The main outcome measures assessed at baseline, 6, 12, and 24 months were serum A1C and psychosocial self-report questionnaires including quality of life and well-being measures. RESULTS—At 12 months, 60 patients had complete data. At the end of the intervention (12 months), the mean A1C in the motivational interviewing group was significantly lower than in the control group (P = 0.04), after adjusting for baseline values. At 24 months (when n = 47), this difference in A1C was maintained (P = 0.003). There were differences in psychosocial variables at 12 months, with the motivational interviewing group indicating more positive well-being, improved quality of life, and differences in their personal models of illness (all P &amp;lt; 0.01). Some of these differences were maintained at 24 months. CONCLUSIONS—Motivational interviewing can be an effective method of facilitating behavioral changes in teenagers with type 1 diabetes with subsequent improvement in their glycemic control.
Modulation of iron transport proteins in human colorectal carcinogenesis
Authors: M J Brookes
Journal: Gut (2006)

<b>Background and aims:</b> Total body iron and high dietary iron intake are risk factors for colorectal cancer. To date there is no comprehensive characterisation of iron transport proteins in progression to colorectal carcinoma. In this study, we examined expression of iron import (duodenal cytochrome b (DCYTB), divalent metal transporter 1 (DMT1), and transferrin receptor 1 (TfR1)) and export (hephaestin (HEPH) and ferroportin (FPN)) proteins in colorectal carcinoma. <b>Methods:</b> Perl's staining was used to examine colonocyte iron content. Real time polymerase chain reaction (PCR) and western blotting were used to examine mRNA and protein levels of the molecules of interest in 11 human colorectal cancers. Semiquantitative immunohistochemistry was used to verify protein levels and information on cellular localisation. The effect of iron loading on E-cadherin expression in SW480 and Caco-2 cell lines was examined by promoter assays, real time PCR and western blotting. <b>Results:</b> Perl's staining showed increased iron in colorectal cancers, and there was a corresponding overexpression of components of the intracellular iron import machinery (DCYTB, DMT1, and TfR1). The iron exporter FPN was also overexpressed, but its intracellular location, combined with reduced HEPH levels, suggests reduced iron efflux in the majority of colorectal cancers examined. Loss of HEPH and FPN expression was associated with more advanced disease. Iron loading Caco-2 and SW480 cells caused cellular proliferation and E-cadherin repression. <b>Conclusions:</b> Progression to colorectal cancer is associated with increased expression in iron import proteins and a block in iron export due to decreased expression and aberrant localisation of HEPH and FPN, respectively. This results in increased intracellular iron which may induce proliferation and repress cell adhesion.
Therapeutic Approaches for Women Predisposed to Breast Cancer
Authors: Katherine L. Nathanson, Susan M. Domchek
Journal: Annual Review of Medicine (2010)

The medical management of women at an increased risk of breast cancer has substantially changed over the past few years, with improvements in screening, cancer prevention, and treatment, and is best defined for women with mutations in BRCA1 and BRCA2. Screening techniques, such as breast magnetic resonance imaging, enable early detection of cancers in high-risk women. Prophylactic salpingo-oophorectomy has been demonstrated to decrease the risk of breast and ovarian cancers, as well as mortality in BRCA1/2 mutation carriers. Most recently, there have been considerable strides in the treatment of cancers in BRCA1/2 mutation carriers. Breast cancer patients with BRCA1/2 mutations treated with systemic therapy do not appear to have excess toxicity, and have similar relapse-free and overall survival compared to noncarriers. Preclinical and early clinical research suggests that specific classes of chemotherapy may be more effective in mutation carriers. PARP inhibitors represent a novel therapeutic strategy that exploits the weaknesses of BRCA1/2-associated malignancies.
Differential Activation of Cardiac c-Jun Amino-Terminal Kinase and Extracellular Signal-Regulated Kinase in Angiotensin II–Mediated Hypertension
Authors: Masahiko Yano, Shokei Kim, Yasukatsu Izumi, Shinya Yamanaka, Hiroshi Iwao
Journal: Circulation Research (1998)

Two subgroups of mitogen-activated protein kinases, c-jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), are thought to be involved in cultured cardiac myocyte hypertrophy and gene expression. To examine the in vivo activation of these kinases, we measured cardiac JNK and ERK activities in conscious rats subjected to acute or chronic angiotensin II (Ang II) infusion, by using in-gel kinase methods. About 50 mm Hg rise in blood pressure by Ang II (1000 ng . kg-1 . min-1) infusion caused larger activation of left ventricular JNK than ERK, via the AT1 receptor. In spite of short duration (about 30 minutes) of maximal blood pressure elevation by Ang II, JNK sustained the peak value (more than 5-fold increase) from 15 minutes up to at least 3 hours. Similar activation of JNK was seen in the right ventricle. Thus, cardiac JNK activation by Ang II seems to be in part mediated by its direct action via the AT1 receptor. The dose-response relationships for Ang II-induced rises in blood pressure and cardiac JNK and ERK activation indicated that cardiac JNK or ERK was not activated by a mild increase in blood pressure and that cardiac JNK was activated by Ang II-mediated hypertension in a more sensitive manner than ERK. Cardiac hypertrophy, induced by chronic Ang II infusion, was preceded by JNK activation without ERK activation. Furthermore, gel mobility shift analysis showed that cardiac JNK activation was followed by increased activator protein-1 DNA binding activity due to c-Fos and c-Jun. These results provided the first evidence for the preferential activation of cardiac JNK in Ang II-induced hypertension and suggested that JNK might play some role in Ang II-induced cardiac hypertrophic response in vivo. However, further study is needed to elucidate the role of JNK in cardiac hypertrophy in vivo.