tbuckley/cabot-search huggingface dataset:
Incidence of skin cancer in 5356 patients following organ transplantation
Authors: B. Lindelöf, B. Sigurgeirsson, H. Gäbel, R.S. Stern
Journal: British Journal of Dermatology (2000)

Skin cancer following solid organ transplantation is an important cause of morbidity in long-term survivors. This risk is well known but imprecisely quantified.We aimed to determine: (i) the skin cancer risks in transplant patients more precisely; (ii) whether the risk of malignant melanoma is altered; and (iii) whether the risk of epithelial cancers occurring at non-exposed sites is comparable with that seen in sun-exposed sites.We linked a population-based cohort of 5356 patients who had received organ transplants in Sweden between 1970 and 1994 with the compulsory Swedish Cancer Registry, to identify all cancer cases except basal cell carcinomas, which are not registered.After a mean follow-up of 5.6 years post-transplantation, 172 of 5356 patients developed 325 non-melanoma skin cancers (excluding basal cell carcinomas) and six malignant melanomas. The relative risk of non-melanoma skin cancer was 108.6 [95% confidence interval (CI) 94.6-123.1] for men and 92.8 (95% CI 73.2-116.0) for women. The highest risks were noted for upper limbs, and the risk increased with time. No significant increase in malignant melanomas was noted: the relative risk was 1.6 (95% CI 0.5-3.7) for men and 0.5 (95% CI 0. 0-2.6) for women. Except for the lip, which is also sun-exposed, other epithelial sites did not show comparable increases in cancer risk.We conclude that organ transplant recipients are at a highly increased risk for non-melanoma skin cancer and must be closely followed throughout their lives. Cancer risk associated with transplantation is higher for sun-exposed than for non-sun-exposed epithelial tissues, even among populations living in regions with low solar insolation.
THE EFFECT OF UNDERNOURISHMENT ON THE SUSCEPTIBILITY OF THE RABBIT TO INFECTION WITH VACCINIA
Authors: Douglas H. Sprunt
Journal: The Journal of Experimental Medicine (1942)

Experiments are reported in which it is shown that if rabbits are deprived of food, the lesions resulting from injection of vaccinia are either fewer or smaller; presumably this is partially explainable on reduction of available nutrients in the cell. The number and character of the lesions are also modified by the state of hydration of the interstitial tissues: If the amount of interstitial fluid is increased by permitting the animal to drink water, the lesions are even less numerous; but if the interstitial tissues are dehydrated either by withholding water or by injecting physiological saline solution into the peritoneal cavity, then the lesions are more numerous. The increase in interstitial fluids in these experiments was not due to decreased plasma proteins, for these were normal. In this respect, therefore, the rabbit differs from man, for unless the plasma proteins are reduced, simple starvation in man results in dehydration rather than edema of the tissues. From these experiments it is concluded that the virus is less able to multiply in the poorly nourished cell than in the well nourished one, and that hydration of the tissues increases the resistance of the tissue to infection while dehydration has the opposite effect. It is suggested that this is because hydration tends to localize the virus in situ, with result that fewer cells are exposed to it, while dehydration has the opposite effect. However, actual changes in cell susceptibility consequent upon altered water balance may be responsible for the effect.
DR-02 * TEMOZOLOMIDE SENSITIZES GLIOMA STEM CELLS TO TRAIL-INDUCED APOPTOSIS THROUGH UPREGULATION OF c-CBL
Authors: Z. Jing, L. Li, J. Liu, M. Wang, Y. Ban, A. Wu
Journal: Neuro-Oncology (2014)

TRAIL-induced apoptosis is inhibited in GSCs. In this study, we investgated whether or not the widely used chemotherapeutic agent-TMZ can sensitize TRAIL treatment in GSCs, related mechanism was investigated in cultured glioma stem cells (GSCs) and primary glioma cells (PGCs) from patients. We found that the expression of c-Fas-associated death domain-like interleukin 1-converting enzyme-like inhibitory protein long and short isoforms (c-FLIPL and c-FLIPS, respectively) was significantly higher in GSCs than in PGCs, and was associated with greater tolerance to TRAIL treatment in the former. Application of the chemotherapeutic drug temozolomide (TMZ) induced the upregulation of casitas B-lineage lymphoma(c-Cbl) and downregulation of c-FLIPL and c-FLIPS expression in GSCs, and when combined with TRAIL promoted GSC apoptosis. These results suggest that combination therapy with TMZ and TRAIL may have clinical applicability for glioma treatment.
How US politicians are playing the health card
Authors: M. McCarthy
Journal: BMJ (2012)

Michael McCarthy looks at how the health debate is unfolding in the run up to the US elections 

When the US Supreme Court, in a narrow five to four decision, upheld President Barack Obama’s 2010 health reform law in June, many Republicans, though disappointed with the ruling, felt the court had handed them a winning election issue.

The law, the Patient Protection and Affordable Care Act (ACA), remains unpopular with many voters, and Republicans saw the court’s decision as an opportunity to make the upcoming election a referendum on the act, which they had dubbed derisively as Obamacare.

“If we want to get rid of Obamacare, we will have to get rid of Obama,” said Mitt Romney, the Republican candidate for president, after the court’s decision. Romney has repeatedly promised to act to repeal the law on the day he takes office, should he be elected.

Since the court’s decision, the Republican strategy has been “to just hammer on the unpopular aspects of the ACA and deflect any questions about what they would do in place of the law,” said Bradley Herring, associate professor in the Johns Hopkins Bloomberg School of Public Health’s department of health policy and management in Baltimore. “You talk about the law taking money out of Medicare; you talk about death panels; you talk about the unpopular individual mandate.”

The Democrats’ defense had been hampered because the law is complicated and because many of its important provisions that Democrats believe will be popular do not come into effect until 2014.

In the meantime, the Democrats’ strategy has been to focus on the popular provisions that have been implemented, said Herring, such as provisions that guarantee coverage for children with pre-existing conditions, allow young adults to remain on their parents’ health plans until they turn 26, and …
El Niño and the dynamics of vectorborne disease transmission.
Authors: S Hales, P Weinstein, Y Souares, A Woodward
Journal: Environmental Health Perspectives (1999)

The objective of the study was to investigate the relationship between reported incidence of dengue fever and El Niño southern oscillation (ENSO) in 14 island nations of the South Pacific. Using a mixed ecological study design, we calculated correlations between annual averages of the southern oscillation index (SOI), local temperature and rainfall, and dengue fever. We also calculated temporal correlations between monthly reports of dengue fever cases on different islands. There were positive correlations between SOI and dengue in 10 countries. In five of these (including all of the larger islands) there were also positive correlations between SOI and estimates of local temperature and/or rainfall. There were temporal correlations between monthly reports of dengue cases within two groups of countries. Climate changes associated with ENSO may trigger an increase in dengue fever transmission in larger, more populated islands where the disease is endemic. There was also evidence of propagation of infection from larger islands to smaller neighbors. Unlike the initiation of epidemics, this transfer between islands appears to be independent of interannual climate variations, pointing to the importance of modulating factors in dengue transmission such as population density and travel. In the future, models of the impact of climate change must attempt to account for these factors.
Consultants could give patients a letter summarising their consultation
Authors: C. Essex
Journal: BMJ (1998)

EDITOR—Burkey et al state that patients in outpatient clinics value a clear message when they are being discharged, being given written and verbal information about their condition, and knowing that their general practitioner has this information.1 I suggest that one way to address these is to write to the patient or the parents.

After every consultation I write only one letter, to the parent(s), with a copy to other parties. This includes (examples in brackets) whether I have discharged the …
Metagenomics and the case of the deadly hamster
Authors: Andrew L. Mason, Karen Doucette, Gane Ka-Shu Wong
Journal: Hepatology (2008)

Background: Three patients who received visceral-organ transplants from a single donor on the same day died of a febrile illness 4 to 6 weeks after transplantation. Culture, polymerase-chain-reaction (PCR) and serologic assays, and oligonucleotide microarray analysis for a wide range of infectious agents were not informative. Methods: We evaluated RNA obtained from the liver and kidney transplant recipients. Unbiased high-throughput sequencing was used to identify microbial sequences not found by means of other methods. The specificity of sequences for a new candidate pathogen was confirmed by means of culture and by means of PCR, immunohistochemical, and serologic analyses. Results: High-throughput sequencing yielded 103,632 sequences, of which 14 represented an Old World arenavirus. Additional sequence analysis showed that this new arenavirus was related to lymphocytic choriomeningitis viruses. Specific PCR assays based on a unique sequence confirmed the presence of the virus in the kidneys, liver, blood, and cerebrospinal fluid of the recipients. Immunohistochemical analysis revealed arenavirus antigen in the liver and kidney transplants in the recipients. IgM and IgG antiviral antibodies were detected in the serum of the donor. Seroconversion was evident in serum specimens obtained from one recipient at two time points. Conclusions: Unbiased high-throughput sequencing is a powerful tool for the discovery of pathogens. The use of this method during an outbreak of disease facilitated the identification of a new arenavirus transmitted through solid-organ transplantation.
Phase Ib Trial of Mutant Herpes Simplex Virus G207 Inoculated Pre-and Post-tumor Resection for Recurrent GBM
Authors: James M Markert, Peter G Liechty, Wenquan Wang, Shanna Gaston, Eunice Braz, Matthias Karrasch, Louis B Nabors, Michael Markiewicz, Alfred D Lakeman, Cheryl A Palmer, Jacqueline N Parker, Richard J Whitley, George Y Gillespie
Journal: Molecular Therapy (2008)

We have previously demonstrated safety of G207, a doubly mutated (deletion of both γ134.5 loci, insertional inactivation of UL39) herpes simplex virus (HSV) for patients stereotactically inoculated in enhancing portions of recurrent malignant gliomas. We have now determined safety of two inoculations of G207, before and after tumor resection. Inclusion criteria were histologically proven recurrent malignant glioma, Karnofsky score ≥70, and ability to resect the tumor without ventricular system breach. Patients received two doses of G207 totaling 1.15 × 109 plaque-forming units with 13% of this total injected via a catheter placed stereotactically in the tumor. Two or five days later, tumor was resected en bloc with catheter in place. The balance of G207 dose was injected into brain surrounding the resection cavity. Six patients with recurrent glioblastoma multiforme were enrolled. Two days after the second G207 inoculation, one patient experienced transient fever, delirium, and hemiparesis, which entirely resolved on high-dose dexamethasone. No patient developed HSV encephalitis or required treatment with acyclovir. Radiographic and neuropathologic evidence suggestive of antitumor activity is reported. Evidence of viral replication was demonstrated. G207 appears safe for multiple dose delivery, including direct inoculation into the brain surrounding tumor resection cavity. We have previously demonstrated safety of G207, a doubly mutated (deletion of both γ134.5 loci, insertional inactivation of UL39) herpes simplex virus (HSV) for patients stereotactically inoculated in enhancing portions of recurrent malignant gliomas. We have now determined safety of two inoculations of G207, before and after tumor resection. Inclusion criteria were histologically proven recurrent malignant glioma, Karnofsky score ≥70, and ability to resect the tumor without ventricular system breach. Patients received two doses of G207 totaling 1.15 × 109 plaque-forming units with 13% of this total injected via a catheter placed stereotactically in the tumor. Two or five days later, tumor was resected en bloc with catheter in place. The balance of G207 dose was injected into brain surrounding the resection cavity. Six patients with recurrent glioblastoma multiforme were enrolled. Two days after the second G207 inoculation, one patient experienced transient fever, delirium, and hemiparesis, which entirely resolved on high-dose dexamethasone. No patient developed HSV encephalitis or required treatment with acyclovir. Radiographic and neuropathologic evidence suggestive of antitumor activity is reported. Evidence of viral replication was demonstrated. G207 appears safe for multiple dose delivery, including direct inoculation into the brain surrounding tumor resection cavity.
Storm forecasting: additional lessons from the CD28 superagonist TGN1412 trial
Authors: Christopher Horvath, Laura Andrews, Andreas Baumann, Lauren Black, Diann Blanset, Joy Cavagnaro, Kenneth L. Hastings, David L. Hutto, Timothy K. MacLachlan, Mark Milton, Theresa Reynolds, Stan Roberts, Mark Rogge, Jennifer Sims, George Treacy, Garvin Warner, James D. Green
Journal: Nature reviews. Immunology (2012)
Laevadosin in Treatment of the Duchenne Type of Muscular Dystrophy: Preliminary Results of a Double-blind Controlled Trial
Authors: J. M. S. Pearce, S. S. Gubbay, J. Hardy, R. J. T. Pennington, D. J. Newell, J. N. Walton
Journal: BMJ (1964)

Many drugs have been advocated for the treatment of muscular dystrophy, but all have been shown eventually to lack any significant therapeutic effect.Among the remedies subjected to extensive clinical trials have been glycine, leucine, multiple vitamins, mixed amino-acids, vitamin E and its analogues, and anabolic steroids.The difficulties in the assessment of drug therapy in this condition are considerable.The enthusiastic response of a parent, distressed by the pro- gressive disability seen in his child, to the offer of a new preparation renders more difficult a critical evaluation of the response to treatment.A good example of this situation is afforded by the claims for clinical improvement following uncontrolled treatment with anabolic steroids (De Toni, 1959; Bekeny, Kraft, and Lang, 1959; Hantschmann, Matzelt, Mertens, and Nowakowski, 1962 ; Dowben, 1963).Only when subjected to a carefully planned controlled trial (Barwick, Newell, and Walton, 1963) was it demonstrated that two particular drugs of this type were of no more value during the period of assessment than a placebo.During the past few years yet another drug has been introduced for the treatment of muscular dystrophy.The preparation, named Laevadosin, is a nucleotide-nucleoside mixture, and was first used by Beckmann (1959Beckmann ( , 1964)), who noted no functional improvement in patients with rapidly progressive muscular dystrophy with irreversible muscle damage, but benefit was derived from this treatment in other instances.The results of a course of Laevadosin therapy have been reported recently in six patients with the Duchenne type of muscular dystrophy and in one with the limb-girdle type (Thomson and Guest, 1963).In this trial the patients were used as their own controls, and the drug was given paren- terally to each patient for approximately 40 days.The authors claim to have shown amelioration of the dystrophic process, as judged by increase in muscle power and by diminution in the activity of serum aldolase and trans- aminases.More recently, Guest and McLay (1964) claim improvement in 19 cases treated for between 5 and 28 months.These trials have been criticized as lacking control groups, and the disadvantages of using the patient as his own con- trol have been clearly outlined (Lancet, 1963).We believed that a similar trial, rigidly designed and strictly controlled, was necessary before the widespread administration of this preparation could be recommended; we report below the preliminary findings of such a trial. Material and MethodsThe detailed administration of the trial was purposely designed to replicate closely that of Thomson and Guest (1963) so that valid comparison was possible.Twenty subjects were selected, and 14 of these were ambulant when the trial began.All but one (a patient in the
Association Between Acute-Phase Reactants and Advanced Glycation End Products in Type 2 Diabetes
Authors: Kathryn C.B. Tan, Wing-Sun Chow, Sidney Tam, Richard Bucala, John Betteridge
Journal: Diabetes Care (2004)

OBJECTIVE—Type 2 diabetes is associated with chronic low-grade inflammation, but the underlying mechanism(s) is not well understood. Because in vitro studies have shown that advanced glycation end products (AGEs) can trigger inflammatory responses, the present study has investigated whether serum concentration of AGEs is an important determinant of circulating levels of inflammatory markers, like C-reactive protein (CRP), in type 2 diabetic patients. RESEARCH DESIGN AND METHODS—Diabetic patients (n = 210) and healthy control subjects (n = 110) of similar BMI were recruited. Serum AGEs were assayed by competitive enzyme-linked immunosorbent assay using a polyclonal rabbit anti-sera raised against AGE-RNase. Plasma high-sensitivity CRP was measured by an immunoturbidimetric assay and interleukin (IL)-6 by enzyme-linked immunosorbent assay. RESULTS—Serum AGEs were increased in diabetic patients compared with control subjects (4.24 ± 0.88 vs. 3.15 ± 0.81 unit/ml, respectively, P &amp;lt; 0.01). Both plasma CRP (1.55 [0.81–2.95] vs. 0.88 mg/dl [0.51–1.89], respectively, P &amp;lt; 0.01; median [interquartile range]) and IL-6 (0.80 [0.68–0.97] vs. 0.69 pg/ml [0.48–0.84], respectively, P &amp;lt; 0.01) were also higher in diabetic patients than in control subjects. In the diabetic patients, log(CRP) correlated with AGEs (r = 0.22, P = 0.002) and with log(IL-6) (r = 0.29, P &amp;lt; 0.001). Forward stepwise linear regression analysis showed that BMI, log(IL-6), and AGEs were significant independent determinants of log(CRP) in the diabetic patients, accounting for 17, 12, and 10% of the variation in log(CRP), respectively. CONCLUSIONS—Serum concentration of AGEs is increased in patients with diabetes and is an independent determinant of plasma CRP levels. Subclinical inflammation in these patients may therefore be partly due to activation of the inflammatory response by AGEs.
Prognostic value of radionuclide angiography in medically treated patients with coronary artery disease. A comparison with clinical and catheterization variables.
Authors: K L Lee, D B Pryor, K S Pieper, F E Harrell, R M Califf, D B Mark, M A Hlatky, R E Coleman, F R Cobb, R H Jones
Journal: Circulation (1990)

To evaluate the usefulness of multiple measures from rest and exercise radionuclide angiography (RNA) in predicting cardiovascular death and cardiovascular events (death or nonfatal myocardial infarction) and to assess the prognostic usefulness of the RNA relative to clinical and catheterization data, we studied 571 stable patients with symptomatic coronary artery disease who had upright rest/exercise first-pass RNA within 3 months of catheterization and were medically treated. With a median follow-up of 5.4 years, 90 patients have died from cardiovascular causes, and 147 patients have either died or suffered a nonfatal myocardial infarction. Using the Cox regression model and a preselected group of RNA variables, the most important RNA predictor of mortality was exercise ejection fraction (chi 2 = 81, p less than 0.00001). Neither rest ejection fraction nor the change in ejection fraction from rest to exercise contributed additional predictive information. Two other RNA study variables, the change in heart rate from rest to exercise and rest end-diastolic volume index, did contribute additional prognostic information to the exercise ejection fraction (chi 2 = 23, p less than 0.0001). Compared with noninvasive clinical data (history, physical examination, electrocardiogram, and chest radiograph), RNA variables were considerably more predictive of mortality (chi 2 = 71 [clinical variables] versus chi 2 = 104 [RNA]). Remarkably, the strength of the relation of RNA variables with mortality was equivalent to that of the set of catheterization variables previously demonstrated in our large angiographic population to be prognostically important (chi 2 = 104 [RNA] versus chi 2 = 102 [catheterization variables]). The RNA contained 84% of the information provided by clinical and catheterization descriptors combined. Furthermore, the RNA contributed significant additional prognostic information to the clinical and catheterization data (chi 2 = 13.6, p = 0.0035). For cardiovascular events, the relative prognostic usefulness of the RNA was similar, although relations with this outcome were generally weaker. Descriptors from the rest/exercise RNA exhibit a powerful relation with long-term outcomes and can be useful in defining risk, even when clinical and catheterization data are available.
Heme Oxygenase-1 Is an Anti-Inflammatory Host Factor that Promotes Murine Plasmodium Liver Infection
Authors: Sabrina Epiphanio, Sebastian A. Mikolajczak, Lígia A. Gonçalves, Ana Pamplona, Silvia Portugal, Sónia Albuquerque, Michael Goldberg, Sofia Rebelo, Daniel G. Anderson, Akin Akinc, Hans-Peter Vornlocher, Stefan H.I. Kappe, Miguel P. Soares, Maria M. Mota
Journal: Cell Host & Microbe (2008)
Overdrive suppression of conduction at the canine Purkinje-muscle junction.
Authors: R F Gilmour, J R Davis, D P Zipes
Journal: Circulation (1987)

We have shown previously that overdrive suppression of conduction in depolarized His-Purkinje tissue requires conduction asymmetry. In this study we examined whether overdrive suppression of conduction can occur at the Purkinje-muscle junction, where natural asymmetry of conduction exists. Canine Purkinje-muscle preparations were superfused with hyperkalemic Tyrode's solution (KCl 8 to 12 mM), and action potentials were recorded from Purkinje, junctional, and muscle cells. Initially, the Purkinje fiber was paced at the shortest cycle length at which 1:1 anterograde Purkinje-muscle conduction occurred. The papillary muscle then was paced for 10 to 50 beats at shorter cycle lengths during which, because of conduction asymmetry at the Purkinje-muscle junction, 1:1 retrograde muscle-Purkinje conduction also occurred. After overdrive papillary muscle pacing, Purkinje fiber pacing at the same cycle length that previously resulted in 1:1 conduction now produced transient Purkinje-muscle conduction block (overdrive suppression of conduction). The degree and duration of overdrive suppression of conduction were proportional to the rate and duration of overdrive pacing. After overdrive pacing, Purkinje cell action potential amplitude and Vmax recovered within 300 msec, yet conduction block persisted for up to 7 sec. In contrast, excitability in papillary muscle cells near the Purkinje-muscle junction increased continuously after overdrive pacing. These data suggest that rapid activation of Purkinje cells during overdrive pacing was not required for overdrive suppression of conduction and that restoration of conduction after overdrive pacing was determined primarily by recovery of excitability in papillary muscle cells. Transient Purkinje-muscle conduction block after periods of rapid ventricular rates might account for overdrive-induced conduction disturbances normally attributed to bundle branch block.