tbuckley/cabot-search huggingface dataset:
Long-Term Therapy of IDDM With an Implantable Insulin Pump
Authors: Fredrick L Dunn, David M Nathan, Marina Scavini, Jean-Louis L Selam, Theresa G Wingrove
Journal: Diabetes Care (1997)

OBJECTIVE To examine the long-term benefits and risks of treatment of IDDM with an implantable programmable insulin pump. RESEARCH DESIGN AND METHODS Seventy-six patients with IDDM were studied at nine clinical centers. After 3–4 months of intensive subcutaneous therapy, the Infusaid Model 1000 pump was implanted, and insulin was delivered either intraperitoneally or intravenously for an average of 39.6 ± 10 months (251 patient-years). Data was collected for glycemic control, lipid levels, weight gain, insulin requirements, adverse events, and quality of life. Sixty-three patients were also followed for 8.5 ± 6.3 months (45 patient-years) after pump therapy was discontinued. RESULTS Mean quarterly HbA1c fell with subcutaneous intensive therapy and remained stable on implantable pump therapy between 6.9 and 7.5%. Severe hypoglycemia was relatively rare, with only 4 episodes/100 patient-years of implantable pump therapy. This rate was significantly less than with subcutaneous intensive therapy before implantable pump initiation (33 episodes/100 patient-years) or after discontinuation of implantable pump therapy (36/100 patient-years) (P &amp;lt; 0.003). Weight did not increase significantly in the 1st year of therapy, but increased by 2.0 ± 4.3 kg after 3 years of therapy. There were no significant differences in metabolic control or adverse events between intraperitoneal and intravenous insulin therapy except for minor differences in lipid levels and the more frequent development of catheter obstruction with intravenous delivery. Most pump slow-downs and catheter occlusions were corrected noninvasively. Quality of life, as measured by the Diabetes Control and Complications Trial instrument, showed high satisfaction and improved impact scores. CONCLUSIONS Long-term implantable pump therapy maintained HbA1c in a range similar to intensive subcutaneous therapy, but with fewer episodes of severe hypoglycemia. Although pump and catheter occlusions remain a limitation, patient satisfaction with implantable pump therapy remains high.
Primary hepatic angiosarcoma with multifocal metastases in the gastrointestinal tract
Authors: J. Chou, K. Cheng, S. Chen
Journal: Endoscopy (2013)

A 64-year-old man presented with a 2-month history of melena. He also had a history of chronic renal disease, hypertension, and diabetes mellitus, and he had worked at a leather factory for decades. He was diagnosed as having primary hepatic angiosarcoma and had undergone right lobectomy 4 months before this admission. Esophagogastroduodenoscopy and colonoscopy failed to detect the bleeding source. Capsule endoscopy showed multiple small hemorrhagic spots in the small intestine. Anterograde double-balloon enteroscopy (DBE) demonstrated multiple ulcerative, sessile polyps with oozing in the small intestine and a 2.5-cm tumor with hemorrhage in the distal jejunum ([Fig. 1 a, b]). The tumor was resected by polypectomy; however, intermittent melena was still present. Retrograde DBE demonstrated a 2.5-cm ulcerative tumor with hemorrhage in the ascending colon ([Fig. 1 c]), which was also removed by polypectomy. Histopathological examination of the ulcerative polyps and tumors showed spindle tumor cells arranged in solid sheets rich in minute vascular channels ([Fig. 2 a]). Immunohistochemical study of tumor cells showed positivity for CD31 ([Fig. 2 b]) and CD34 ([Fig. 2 c]). A diagnosis of metastatic angiosarcomas was made. Although thalidomide was prescribed for the patient, he died within 3 months of the diagnosis.
Antidepressants for Bipolar Depression: A Systematic Review of Randomized, Controlled Trials
Authors: Harm J. Gijsman, John R. Geddes, Jennifer M. Rendell, Willem A. Nolen, Guy M. Goodwin
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: This study reviewed the evidence from randomized, controlled trials on the efficacy and safety of antidepressants in the short-term treatment of bipolar depression. METHOD: The authors performed a systematic review and meta-analysis of randomized, controlled trials. They searched the Cochrane Collaboration Depression, Anxiety, and Neurosis Controlled Trials Register, incorporating results of searches of MEDLINE, EMBASE, CINAHL, PsycLIT, PSYNDEX, and LILACS. The main outcome measures were the proportion of patients who clinically responded to treatment and the rate of switching to mania. RESULTS: Twelve randomized trials were included, with a total of 1,088 randomly assigned patients. Five trials compared one or more antidepressants with placebo: 75% of these patients were receiving a concurrent mood stabilizer or an atypical antipsychotic. Antidepressants were more effective than placebo. Antidepressants did not induce more switching to mania (the event rate for antidepressants was 3.8% and for placebo, it was 4.7%). Six trials allowed comparison between two antidepressants. The rate of switching for tricyclic antidepressants was 10%, and for all other antidepressants combined, it was 3.2%. CONCLUSIONS: Antidepressants are effective in the short-term treatment of bipolar depression. The trial data do not suggest that switching is a common early complication of treatment with antidepressants. It may be prudent to use a selective serotonin reuptake inhibitor or a monoamine oxidase inhibitor rather than a tricyclic antidepressant as first-line treatment. Given the limited evidence, there is a compelling need for further studies with longer follow-up periods and careful definition and follow-up of emerging mania and partial remission.
Airborne particulates and hospital admissions for cardiovascular disease: a quantitative review of the evidence.
Authors: R D Morris
Journal: Environmental Health Perspectives (2001)

This is a quantitative review of studies characterizing the relationship between exposure to airborne particulates and hospital admissions for cardiovascular disease. A MEDLINE search and a review of reference lists were conducted to identify time-series studies that considered particles less than 10 microm or 2.5 microm in diameter (PM(10) and PM(2.5), respectively) and their association with day-to-day variation in cardiovascular admissions. The results of these studies were standardized to give estimates of the percentage increase in hospital admissions associated with an increase in ingestion of ambient particles of 10 microg/m3. The results were grouped and compared on the basis of the specific outcomes and exposure measures. When studies that considered the association between PM(10) exposure and specific cardiovascular outcomes were pooled (after exclusion of outliers), a 10-microg/m(3) increase in PM(10) was associated with increases in admission rates of 0.8% (95% confidence interval [CI]: 0.5, 1.2%) for congestive heart failure, 0.7% (95% CI: 0.4, 1.0%) for ischemic heart disease, and 0.2% (95% CI: -0.2, 0.6%) for cerebrovascular accidents. These effects tended to diminish substantially when gaseous co-pollutants were considered. The extent to which these effects are due to fine particles is unclear. The available studies indicate that exposure to airborne particles is associated with hospital admissions for cardiovascular disease; but the magnitude of this effect depends strongly on the specific disease category being considered, the time lag used in the analysis, and the type and amount of co-pollutants. Future studies should include careful consideration of the role of co-pollutants in this association, the interaction of particles with temperature, the impact of particle size on this effect, and the extent to which the observed effect involves short-term "harvesting."
TUBERCULOSIS OF THE TONGUE
Authors: HOWARD MORROW
Journal: JAMA (1924)

Tuberculosis of the tongue is considered one of the rare manifestations of tuberculosis in the human body. Medical literature contains a few good articles on this subject. Dermatologic textbooks ignore it. A perusal of the indexes of our standard dermatologic textbooks does not reveal the name. In the differential diagnosis of other tongue conditions, it is not mentioned. We think that it is not as rare as the literature would lead us to believe, and we feel certain that the difficulties encountered in the diagnosis of tuberculosis of the tongue, especially in primary tuberculosis of the tongue, warrant some space and thought in dermatologic textbooks. The first authentic case of this disease was reported by Portal,<sup>1</sup>in 1804. Morgagni,<sup>2</sup>in 1761, described a patient with tubercles on the tongue, but he does not define the word "tubercle" as he uses it. It is with considerable pride that we
Science commentary: Behaviour of hepatitis C virus
Authors: A. Berger
Journal: BMJ (1998)

Hepatitis C virus was identified in 1989 in the United States. Parenteral and sexual transmission is responsible for most hepatitis C infection worldwide. There is a difference in carriage rate between hepatitis B and C. For example, over 80% of people infected with hepatitis C virus become chronic carriers compared with up to 20% of those infected with hepatitis B virus.

One possible explanation for this difference between the two viruses is that hepatitis C evades the …
An Antiviral Mechanism of Nitric Oxide
Authors: Marta Saura, Carlos Zaragoza, Audrey McMillan, Richard A Quick, Christine Hohenadl, John M Lowenstein, Charles J Lowenstein
Journal: Immunity (1999)

Although nitric oxide (NO) kills or inhibits the replication of a variety of intracellular pathogens, the antimicrobial mechanisms of NO are unknown. Here, we identify a viral protease as a target of NO. The life cycle of many viruses depends upon viral proteases that cleave viral polyproteins into individual polypeptides. NO inactivates the Coxsackievirus protease 3C, an enzyme necessary for the replication of Coxsackievirus. NO S-nitrosylates the cysteine residue in the active site of protease 3C, inhibiting protease activity and interrupting the viral life cycle. Substituting a serine residue for the active site cysteine renders protease 3C resistant to NO inhibition. Since cysteine proteases are critical for virulence or replication of many viruses, bacteria, and parasites, S-nitrosylation of pathogen cysteine proteases may be a general mechanism of antimicrobial host defenses.
Focus: Westminster: Ministers begin a drive on effectiveness
Authors: J Warden
Journal: BMJ (1994)

Whether state medicine in the style of the NHS is compatible with clinical freedom is a question more suited to academic discussion than practical politics - though in Britain it is never far from the surface and is about to rise to the top again. Twice at critical junctures in the history of the NHS doctors' leaders have had to press for government assurances on the issue. In 1990 a formal agreement was reached with the medical royal colleges that clinical standards would not be compromised by the current NHS reforms. This in turn had echoes of Lord Moran's crucial mediation in 1948 to avert Bevan's threat of a full time salaried service.

These initiatives were assumed to satisfy the profession on matters of clinical freedom. For their part governments have by and large respected the principle of clinical freedom. Ministers who do not …
Treating neurodegenerative diseases
Authors: L. J Findley
Journal: BMJ (2002)

Parkinson's disease is an excellent example of the challenges of caring posed by people with neurodegenerative disorders. It is insidious in onset, inexorably progressive, of unknown cause, incurable, yet amenable to management with pharmacological and other interventions. With the ageing of the population the prevalence of Parkinson's disease and other such disorders is projected to increase in the years ahead.1 Thus all doctors must be prepared to provide diagnostic and management strategies for this growing population of patients. Medical practitioners must understand the expectations of patients and their families and introduce these perspectives within the framework of scientific understanding and evidence based practice. Conventional medical education has set a tradition of practice based on science, basic and clinical, cemented by a period of postgraduate training in the conventional apprenticeship mode. This has ensured that practices are generally competent and safe and grounded in the best available information. But is this approach consistent with the mission of …
Abstract C45: Somatostatin receptor activation by agonist-like antibodies can reverse neuroendocrine tumor BON cell dedifferentiation and increase cell death
Authors: Frank Leu, Minesh Nandi, Chung Wong
Journal: Cancer Research (2009)

Abstract The somatostatin receptors (SSTR) are effective therapeutic targets for treating neuroendocrine tumors, primarily achieved through the inhibition of both cellular proliferation and hormone secretion. SSTR are comprised of five major subtypes, namely subtypes 1, 2 (A and B), 3, 4 and 5. The somatostatin signaling also works as a determinant in the TGF-β dependent neuroendocrine-mesenchymal transition (NMT) process. NMT is similar to the epithelial-mesenchymal transition (EMT), but has the opposite cellular differentiation response to TGF-β. For instance, TGF-β promotes cell dedifferentiation in EMT but promotes cell differentiation in NMT. The process of EMT is a critical morphogenic event during the progression of epithelial tumors. Recently, in epithelial tumors, the micro RNA 200c (miR-200c) has been found to negatively regulate E-cadherin's transcriptional repressor ZEB1 and capable of keeping the EMT invasiveness in check. In our study, the miR-200c repressor (Oligoengine Inc. designed by Todd Hauser) has been successful in up-regulating ZEB1 and ultimately driving the neuroendocrine tumor BON cells into the dedifferentiated mesenchymal state. The miR-200c repressor induces changes in the tumor metastasis markers, such as the ZEB1 increase, E-cadherin decrease, and ultimately with both Vimentin and Twist increases. Our anti-SSTR antibodies raised against receptor's ectodomain region (anti-SSTR ECL2 antibodies) were able to reverse the BON cell from its mesenchymal state back to the differentiated neuroendocrine state. Our results suggest that similar to EMT, both miR-200c and ZEB1 are also involved in the NMT dedifferentiation programming. In summary, we conclude that miR-200c/ZEB1 signaling can be regulated by the SSTR activation. This is evident because anti-SSTR agonist-like SSTR2, 3 and 5 antibodies are capable of overcoming neuroendocrine tumor's miR-200c commitment to metastasis. Furthermore, we also found that these anti-SSTR antibodies can sensitize tumor cells to death. Citation Information: Cancer Res 2009;69(23 Suppl):C45.
Mortality and smoking in Hong Kong: case-control study of all adult deaths in 1998
Authors: T H Lam, S Y Ho, A J Hedley, K H Mak, R Peto
Journal: BMJ (2001)

Chronic liver injury characteristically results in hepatic inflammation, which represents a prerequisite for organ fibrosis. Although NKT cells are abundantly present in liver and involved in hepatic inflammation, molecular mechanisms of their recruitment in liver fibrosis remained elusive. We hypothesized that chemokine receptor CXCR6 and its ligand CXCL16 control NKT cell migration and functionality in liver fibrosis. In patients with chronic liver diseases (<i>n</i> = 58), <i>CXCR6</i> and <i>CXCL16</i> expression was intrahepatically upregulated compared with controls. In murine liver, <i>Cxcl16</i> was strongly expressed by endothelium and macrophages, whereas lymphocyte populations (NKT, NK, CD4 T, CD8 T cells) expressed CXCR6. Intravital two-photon microscopy imaging of <i>Cxcr6<sup>+/gfp</sup></i> and <i>Cxcr6<sup>gfp/gfp</sup></i> mice and chemotaxis studies in vitro revealed that CXCR6 specifically controls hepatic NKT cell accumulation during the early response upon experimental liver damage. Hepatic invariant NKT cells expressed distinct proinflammatory cytokines including IFN-γ and IL-4 upon injury. CXCR6-deficient mice were protected from liver fibrosis progression in two independent experimental models. Macrophage infiltration and protein levels of inflammatory cytokines IFN-γ, TNF-α, and IL-4 were also reduced in fibrotic livers of <i>Cxcr6<sup>−/−</sup></i> mice, corroborating that hepatic NKT cells provide essential cytokine signals perpetuating hepatic inflammation and fibrogenesis. Adoptive transfer of NKT cells, but not CD4 T cells, isolated from wild type livers restored hepatic fibrosis in <i>Cxcr6<sup>−/−</sup></i> mice upon experimental steatohepatitis. Our results demonstrate that hepatic NKT cells accumulate CXCR6-dependent early upon injury, thereby accentuating the inflammatory response in the liver and promoting hepatic fibrogenesis. Interfering with CXCR6/CXCL16 might therefore bear therapeutic potential in liver fibrosis.
Will Pharmac become a victim of its own success?
Authors: R. H. Foster, N. Wilson
Journal: BMJ (2011)

Moynihan’s article summarises well the issues surrounding New Zealand’s drug funding authority Pharmac and the Trans-Pacific Partnership trade agreement currently being negotiated with the US.1 Why are US drug companies lobbying against Pharmac when the New Zealand drug market is insignificant in global terms? Pharmac’s success has probably made it a target.

Pharmac operates within a …
In intracranial artery stenosis, adding angioplasty and stenting to medical therapy increased stroke or death
Authors: Graeme J. Hankey
Journal: Annals of Internal Medicine (2014)

Source Citation Derdeyn CP, Chimowitz MI, Lynn MJ, et al; Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis Trial Investigators. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet. 2014;383:333-41. 24168957
T cell activation, from atopy to asthma: more a paradox than a paradigm
Authors: M. El Biaze, S. Boniface, V. Koscher, E. Mamessier, P. Dupuy, F. Milhe, M. Ramadour, D. Vervloet, A. Magnan
Journal: Allergy (2003)

During the last 15 years, it was largely shown that allergic inflammation was orchestrated by activated Th2 lymphocytes, leading to IgE production and eosinophil activation. Indeed, Th2 activation was shown to be necessary to induce allergic sensitization in animal models. In humans, a Th2 skewing was shown in atopic children soon after birth. In asthma, descriptive studies showed that Th2 cells were more numerous in patients than in controls. In addition, during specific allergen stimulation, an increase of Th2 cells was described in most cases. According to this Th2 paradigm, it was proposed that early avoidance of microbial exposure could explain the increase of atopic diseases seen in the last 20 years in developed countries, as the ‘hygiene hypothesis’. Recently, it was proposed that early exposure to lipopolysaccharide (LPS) could be protective against atopic diseases. However, it is well established that exposure to LPS can induce asthma symptoms, both in animals and humans, although it induces a Th1 inflammatory response. In addition, most infections induce asthma exacerbations and Th1 responses. Recently, some studies have showed that some Th1 cells were present in asthmatic patients, which could be related to bronchial hyperreactivity. There is therefore an ‘infectious paradox’ in asthma, which contributes to show that the Th2 paradigm is insufficient to explain the whole inflammatory reaction of this disease. We propose that the Th2paradigm is relevant to atopy and inception of asthma albeit a Th1 activation would account at least in part for bronchial hyperreactivity and asthma symptoms.
Fms-like Tyrosine Kinase 3 Ligand Stimulation Induces <i>MLL</i>-Rearranged Leukemia Cells into Quiescence Resistant to Antileukemic Agents
Authors: Yoshiyuki Furuichi, Kumiko Goi, Takeshi Inukai, Hiroki Sato, Atsushi Nemoto, Kazuya Takahashi, Koshi Akahane, Kinuko Hirose, Hiroko Honna, Itaru Kuroda, Xiaochun Zhang, Keiko Kagami, Yasuhide Hayashi, Kenichi Harigaya, Shinpei Nakazawa, Kanji Sugita
Journal: Cancer Research (2007)

Abstract Fms-like tyrosine kinase 3 (FLT3) is highly expressed in acute lymphoblastic leukemia with the mixed-lineage leukemia (MLL) gene rearrangement refractory to chemotherapy. We examined the biological effect of FLT3-ligand (FL) on 18 B-precursor leukemic cell lines with variable karyotypic abnormalities, and found that nine of nine MLL-rearranged cell lines with wild-type FLT3, in contrast to other leukemic cell lines, are significantly inhibited in their proliferation in a dose-dependent manner by FL. This inhibition was due to induction of the G0-G1 arrest. A marked up-regulation of p27 by suppression of its protein degradation and an abrogation of constitutive signal transducers and activators of transcription 5 phosphorylation were revealed in arrested leukemia cells after FL stimulation. Importantly, FL treatment rendered not only cell lines but also primary leukemia cells with MLL rearrangement resistant to chemotherapeutic agents. MLL-rearranged leukemia cells adhering to the bone marrow stromal cell line, which expresses FL as the membrane-bound form, were induced to quiescent state resistant to chemotherapeutic agents, but their chemosensitivity was significantly restored in the presence of neutralizing anti-FL antibody. The FL/FLT3 interaction between leukemia cells and bone marrow stromal cells expressing FL at high levels should contribute, at least in part, to persistent minimal-residual disease of MLL-rearranged leukemia in bone marrow. [Cancer Res 2007;67(20):9852–61]
Fixing the NHS: We need fewer and better managers
Authors: P. L Thorpe
Journal: BMJ (2006)

I just wanted to be a doctorWe need to be more than "just" doctors Editor-Hunt articulates the feelings of many doctors on discovering that the effective practice of modern medicine requires a range of skills beyond the provision of direct clinical care. 1 Her slightly delayed entry into medicine may explain why this issue is troubling her now, rather than later in her career: certainly these are sentiments I hear more commonly from consultant colleagues than juniors.However, to imagine that good medical practice is confined to the delivery of care to one patient at a time is to overlook the role of doctors in organising healthcare systems and delivery in the wider context.It is disappointing that Hunt's appraiser chose to frame the process in terms of her trust's participation in the clinical negligence scheme, since most junior doctors value well conducted appraisals.Nevertheless, cheaper insurance premiums for hospitals mean more money to spend on health care, and also indicate that organisations that carry out effective appraisal make fewer clinical errors: presumably these are both outcomes that Hunt would approve of.Furthermore, research and audit without the active participation of doctors will soon become clinically irrelevant or ineffective.We have a wider responsibility for patient care that is served by informed participation in these and many other activities, such as teaching and continuous quality improvement (which also seem to get irritatingly in the way of a narrowly focused approach to patient care).However, all is not lost.Hunt appears well placed to fall into the "Modernising Medical Careers" vacuum that currently threatens to swallow those junior doctors who are too old for a foundation programme yet too young to have secured a specialist registrar post.If this does indeed curtail all opportunities for career progression she may end up as "just" a doctor after all.