tbuckley/cabot-search huggingface dataset:
S85 Initiation of long-term non-invasive ventilation enables successful weaning from prolonged mechanical ventilation
Authors: R Parker, G Sunderland, V Ford, K Ward, H Ashcroft, V Molyneux, J Cheney, B Chakrabarti, J O'Reilly, N Duffy, R Angus
Journal: Thorax (2013)

<h3>Introduction</h3> Prolonged mechanical ventilation is an increasing workload for intensive care units (ICU). Units distinct from ICU can provide step-down care for stable slow-to-wean patients and facilitate weaning by the use of long-term non-invasive ventilation (NIV). Development has been limited in the UK despite being recommended by the NHS Modernisation Agency in 2002 and reiterated by the NHS Commissioning Board in 2013. A unit opened at our hospital in September 2010 as part of a comprehensive complex home ventilation service. <h3>Methods</h3> Review of completed in-patient episodes of transfers for weaning from invasive mechanical ventilation (IMV) from September 2010 to December 2012. Transfers following neurosurgery were compared with allcomers. <h3>Results</h3> Thirty-nine patients were identified, mean age 54.2 (17.9) years, 24 male. Average length of stay (LOS) on the referring ICU was 49 days. Six had neuromuscular disease, nine COPD, 7 were obese or had chest wall disease, 14 ICU-acquired weakness and 3 used NIV prior to ICU admission. Thirty-five patients survived to hospital discharge. Thirty-one patients were successfully decannulated and weaned from IMV, including the use of nocturnal NIV. Twelve required no ventilatory support, 19 were discharged using nocturnal NIV and 5 continued nocturnal IMV (one of own choice). Twenty-two were discharged directly home, 7 to rehabilitation or the referring hospital and 6 to long-term nursing care. Thirty-four patients were alive 6 months after hospital discharge. Seven transfers had undergone neurosurgery, five having posterior fossa surgery. Compared with allcomers they were significantly more likely to have permanent bulbar dysfunction, require feeding gastrostomy, tracheostomy on discharge, have a longer LOS (106 vs 51 days) and were less likely to be discharged home. Long-term NIV was used in two neurosurgical patients compared with 17 allcomers. <h3>Conclusions</h3> Patients with weaning failure can be effectively managed outside ICU. NIV enabled weaning in 50% of cases; consistent with published experience<sup>1</sup>. Six month survival is good and most are discharged directly home. Patients after neurosurgery present a specific challenge. NIV may not possible, and ongoing bulbar dysfunction may necessitate the retention of a tracheostomy for ventilation, airway protection and suction. <h3>References</h3> Pilcher <i>et al.</i><i>Thorax</i> 2005:187–192.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Ivan L. Bennett, Paul B. Beeson
Journal: The Journal of Experimental Medicine (1953)

Further studies on fever production by injection of leukocyte extracts or cell-free supernatant fluids from peritoneal exudates in rabbits are reported. Granulocytes collected from peripheral blood or from pleural exudates contain a heat-labile pyrogenic substance. The material in extracts of leukocytes and in peritoneal fluids, which causes fever, is destroyed by heating for 30 minutes at 90 degrees C. at pH 7.2 and at 70 degrees C. at pH 4.5. It is active in producing fever over a pH range of 2.0 to 10.5 and maintains potency for as long as 6 months at 4 degrees C. The fever-producing substance in leukocyte extracts is not dialyzable. Its activity is not destroyed by trypsin, chymotrypsin, or ribonuclease. No evidence of plasma activator or inhibitor was detected. Significant temperature elevation in the rabbit was effected by a quantity of leukocyte extract containing 0.76 mg. protein and 0.054 mg. polysaccharide. The febrile response produced by the material under study was compared with that of Menkin's pyrexin as well as with that of bacterial pyrogens. Several significant differences were noted. The properties of pyrexin are similar to those of bacterial pyrogens. Amidopyrine suppressed the febrile response to injection of leukocyte extracts, whereas neither amidopyrine nor cortisone influenced the appearance of pyrogenic material in induced peritoneal exudates. Peritoneal fluids collected from rabbits made leukopenic by HN(2) were found to contain a fever-promoting substance. Its character has yet to be determined. It is concluded that there is present in polymorphonuclear leukocytes of rabbits a heat-labile factor capable of producing fever in rabbits and that the leukocyte is probably not the only source of such a factor.
A Subset of Liver NK T Cells Is Activated during<i>Leishmania donovani</i>Infection by CD1d-bound Lipophosphoglycan
Authors: Joseph L. Amprey, Jin S. Im, Salvatore J. Turco, Henry W. Murray, Petr A. Illarionov, Gurdyal S. Besra, Steven A. Porcelli, Gerald F. Späth
Journal: The Journal of Experimental Medicine (2004)

Natural killer (NK) T cells are activated by synthetic or self-glycolipids and implicated in innate host resistance to a range of viral, bacterial, and protozoan pathogens. Despite the immunogenicity of microbial lipoglycans and their promiscuous binding to CD1d, no pathogen-derived glycolipid antigen presented by this pathway has been identified to date. In the current work, we show increased susceptibility of NK T cell-deficient CD1d(-/-) mice to Leishmania donovani infection and Leishmania-induced CD1d-dependent activation of NK T cells in wild-type animals. The elicited response was Th1 polarized, occurred as early as 2 h after infection, and was independent from IL-12. The Leishmania surface glycoconjugate lipophosphoglycan, as well as related glycoinositol phospholipids, bound with high affinity to CD1d and induced a CD1d-dependent IFNgamma response in naive intrahepatic lymphocytes. Together, these data identify Leishmania surface glycoconjugates as potential glycolipid antigens and suggest an important role for the CD1d-NK T cell immune axis in the early response to visceral Leishmania infection.
Absence of peripheral blood T cell responses to `shared epitope' containing peptides in recent onset rheumatoid arthritis
Authors: G. J McColl, J. Hammer, L. C Harrison
Journal: Annals of the Rheumatic Diseases (1997)

<h3>OBJECTIVES</h3> To determine if peptides containing the 'shared epitope' sequence, QKRAA, from either endogenous, HLA-DRβ1(0401), or exogenous, <i>Escherichia coli</i> dnaJ, sources activate T cells in recent onset rheumatoid arthritis (RA). <h3>METHODS</h3> Peripheral blood mononuclear cell (PBMC) proliferative and whole blood cytokine responses to shared epitope containing peptides from DRβ1(0401) and <i>E coli</i> dnaJ, to control peptides from DRβ1(0402) and hsp40 and to the recall antigen, tetanus toxoid, were tested in 20 untreated, recent onset RA subjects, 20 HLA, age, and sex matched healthy controls and 18 other subjects with inflammatory arthritis. PBMC proliferative responses to a second<i>E coli</i> dnaJ peptide (with the shared epitope at the N-terminus) and two peptides from type II collagen with high affinity for DR4(0401) were tested in a further 16 recent onset RA and 17 control subjects. <h3>RESULTS</h3> PBMC proliferation and whole blood interferon γ or interleukin 10 production in response to the shared epitope containing and control peptides were not different between the disease and control groups. On the other hand, compared with controls, RA subjects had significantly higher proliferation to a collagen II (aa 1307-1319) peptide, but significantly lower proliferation and interferon γ production to tetanus toxoid. <h3>CONCLUSION</h3> Recent onset RA subjects had no demonstrable increase in peripheral blood T cell reactivity to shared epitope containing peptides. However, a proportion had increased T cell reactivity to a peptide of similar length from a candidate RA autoantigen, collagen type II. Their impaired responses to tetanus are in keeping with evidence for general T cell hyporesponsiveness in RA.
Ventricular Response to Increased Outflow Resistance in Absence of Elevated Intraventricular End-Diastolic Pressure
Authors: MATTHEW N. LEVY, ELIAS S. IMPERIAL, HARRISON ZIESKE, Nelson Geraldine
Journal: Circulation Research (1963)

In the isolated, supported, canine heart preparation, the response of the left ventricle to augmented outflow resistance was compared under conditions in which ventricular end-diastolic pressure and volume were increased and in which the pressure and volume remained virtually constant. The compensatory changes were much greater when end-diastolic pressure and volume were increased, even if these alterations in pressure and volume subsequently returned to or toward control levels. Immediately after resistance was augmented, peak ventricular power and stroke work diminished to less than control values. Within a very few beats, however, both of these parameters rose to exceed control levels. However, definite adaptive changes were also observed under conditions in which ventricular dimensions and pressures did not change appreciably, even temporarily. After a similar initial reduction in peak power and work after resistance was increased, peak power rose progressively to a value still significantly below control, while stroke work attained control levels by the end of a mean interval of 32 seconds of increased resistance. The intrinsic adaptation of the ventricle to increased resistance per se undoubtedly contributes to the total compensatory response, even under conditions in which diastolic stretch of the ventricle plays a major role.
Therapists’ Reactions to Patients’ Suicides
Authors: H Hendin, A Lipschitz, J T Maltsberger, A P Haas, S Wynecoop
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: The authors wished to obtain information from therapists about their reactions to the suicides of patients in their care. METHOD: Therapists for 26 patients who committed suicide completed a semistructured questionnaire about their reactions, wrote case narratives, and participated in a workshop to discuss their cases. The therapists discussed what they would do differently, the impact of the death on their treatment of suicidal patients, their interaction with patients' relatives after the suicides, and the reactions of their colleagues and supervisors. RESULTS: Shock, grief, guilt, fear of blame, self-doubt, shame, anger, and betrayal were the major emotional reactions. In 21 out of 26 cases, therapists identified at least one major change they would have made in their patients' treatments; most frequently mentioned were changes in medication, hospitalization of the patients, and consultation with the patients' previous therapists. Nineteen of the therapists saw the patients' relatives after the suicides; in almost all cases the relatives were not critical of them. Some of the therapists were reluctant to accept subsequent suicidal patients into their practices. Although colleagues were supportive, institutional responses and case reviews were rarely helpful, offering either blame or false reassurance that the suicide was inevitable. CONCLUSIONS: Clinicians felt they learned from participating in the project and that it was therapeutic for them. Review of such cases by a disinterested independent group with no institutional ties to the therapists seems desirable.
Targeting pulmonary metastases of renal cell carcinoma by inhalation of interleukin-2
Authors: O. Merimsky, E. Gez, R. Weitzen, H. Nehushtan, R. Rubinov, H. Hayat, T. Peretz, M. Ben-Shahar, H. Biran, R. Katsenelson, V. Mermershtein, D. Loven, N. Karminsky, A. Neumann, D. Matcejevsky, M. Inbar
Journal: Annals of Oncology (2004)
Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer
Authors: Bao-Hong Guo, Yan Feng, Rong Zhang, Li-Hua Xu, Man-Zhi Li, Hsiang-Fu Kung, Li-Bing Song, Mu-Sheng Zeng
Journal: Molecular Cancer (2011)

Abstract Background B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT) and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs), whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs). Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time. Results Bmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M) and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these observations, the repression of Bmi-1 in highly metastatic breast cancer cells remarkably reduces cellular motility, invasion and transformation, as well as tumorigenesis and lung metastases in nude mice. In addition, the repression of Bmi-1 reverses the expression of EMT markers and inhibits the Akt/GSK3β/Snail pathway. Conclusions This study demonstrates that Bmi-1 promotes the invasion and metastasis of human breast cancer and predicts poor survival.
Oesophageal stricture: a late complication of endoscopy?
Authors: G E Holdstock, M J Wiseman, C A Loehry
Journal: BMJ (1978)

6 MAY 1978MAY 1183 stopping all medication the concentration fell to 1-89 mmol/l (1-3 mg/100 ml)and on the fifth day it was 0 28 mmol/l (0 19 mg/100 ml).She recovered rapidly, and there were no neurological sequelae.
Homo Sapiens - a Species too Successful
Authors: R Gordon Booth
Journal: Journal of the Royal Society of Medicine (1990)

Our species has been more successful than any other in its ability to  adapt itself to available food supplies.  The result of this success  combined with a reduction in war and an increase in medical technology  has resulted in a large population growth.  Current population is 5.2  billion and is expected to double in 30-40 years.  But there is no  indication that the food supply is going to double in the same time  period.  Current food production is energy intensive and as a species  we put more calories into food production than we get out.  The result  of this type of activity is the consumption of finite resources such as  water soil and land.  Fresh water is being used up faster than it is  being replenished soil is eroding faster than it is being replaced  and land is being used for non-agricultural purposes such as housing  and industry.  Also in the West only 8% of the population makes their  living from food related labor such as production processing  transportation.  The author sums up the problem our species is having  by stating that there are too many people on this planet.  The carrying  capacity of the planet is already questionably being exceed and  doubling the population without doubling the food supply will only lead  to famine and war.
Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade
Authors: Virginia Pascual, Florence Allantaz, Edsel Arce, Marilynn Punaro, Jacques Banchereau
Journal: The Journal of Experimental Medicine (2005)

Systemic onset juvenile idiopathic arthritis (SoJIA) encompasses ∼10% of cases of arthritis that begin in childhood. The disease is unique in terms of clinical manifestations, severity of joint involvement, and lack of response to tumor necrosis factor blockade. Here, we show that serum from SoJIA patients induces the transcription of innate immunity genes, including interleukin (IL)-1 in healthy peripheral blood mononuclear cells (PBMCs). Upon activation, SoJIA PBMCs release large amounts of IL-1β. We administered recombinant IL-1 receptor antagonist to nine SoJIA patients who were refractory to other therapies. Complete remission was obtained in seven out of nine patients and a partial response was obtained in the other two patients. We conclude that IL-1 is a major mediator of the inflammatory cascade that underlies SoJIA and that this cytokine represents a target for therapy in this disease.
Rapid Loss of Insulin Secretion in a Patient With Fulminant Type 1 Diabetes Mellitus and Carbamazepine Hypersensitivity Syndrome
Authors: Nobuo Sekine
Journal: JAMA (2001)

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Large quantities of low molecular weight IgM in mixed cryoglobulinaemia.
Authors: P J Roberts-Thomson, A Kennedy, L Y Koh
Journal: Annals of the Rheumatic Diseases (1988)

Low molecular weight (LMW) IgM is the monomeric subunit of pentameric IgM. It was not found in the sera of 20 healthy subjects but was detected in all six patients with mixed cryoglobulinaemia with a mean value of 1.4 g/l, representing 34% of the total IgM. In three of four patients studied LMW IgM was monoclonal and of the same light chain type (kappa) as the pentameric monoclonal IgM rheumatoid factor (RF) observed in the cryoprecipitate. LMW IgM was proportionately under-represented, however, in the cryoprecipitate compared with the corresponding serum, possibly because of the lower valency of the LMW molecule. Immunoblot analysis of sera showed the presence of other oligomers of IgM in addition to monomeric IgM, suggesting that a disorder of IgM assembly was responsible for its occurrence, and this was supported by the secretion of large proportions of LMW IgM in vitro by peripheral blood mononuclear cells (PBMC) from one patient with this disorder but not from healthy controls. In conclusion, the occurrence of large quantities of monoclonal LMW IgM in mixed cryoglobulinaemia was observed, and it is suggested that this is unlikely to have a direct pathogenic significance. It is postulated that its presence reflects a disturbance of assembly of the monomeric IgM subunits that occurs during the polymerization of the pentameric molecule.
Dermatophytes can trigger cooperative (CAMP-like) haemolytic reactions
Authors: P. Schaufuss, J. Brasch, U. Steller
Journal: British Journal of Dermatology (2005)

Dermatophytes usually grow on skin that is also colonized by bacteria. Therefore, a possible interaction between dermatophytes and bacteria is of potential relevance for the pathogenesis of skin infections. Cell membranes contribute substantially to epidermal barrier function. Erythrocyte haemolysis is a model commonly used to study membrane-damaging effects of microbial factors. Cooperative (CAMP-like) haemolytic reactions are known from distinct bacteria, but not from dermatophytes and bacteria.To investigate CAMP-like reactions of dermatophytes.Species of dermatophytes representing the genera Microsporum, Trichophyton and Epidermophyton, erythrocytes from sheep, horse and cattle, cultures of Staphylococcus aureus, S. intermedius, Listeria ivanovii, S. hyicus and S. epidermidis, and cell-free supernatants of bacterial cultures were used to search for cooperative haemolytic effects in in vitro agar diffusion assays.A cooperative (CAMP-like) haemolytic reaction was identified for all dermatophytes tested. Using erythrocytes from sheep and cattle, pretreated with a sphingomyelinase from S. aureus, S. intermedius or L. ivanovii, the fungi induced a distinct zone of complete haemolysis on solid media and in a diffusion test. No CAMP reaction could be detected using S. hyicus or S. epidermidis as a first-step agent or with equine erythrocytes. The lytic reaction of the CAMP-cohaemolysin derived from dermatophytes was always separate from the zone of complete haemolysis, indicating two different cytolytic factors.Our results show, for the first time, that in principle a CAMP-like effect can occur with dermatophtyes. This is a new observation of potential relevance for the pathogenesis of skin infections. The membrane-damaging factors released by dermatophytes should be further analysed.