tbuckley/cabot-search huggingface dataset:
Autoantibodies to B Lymphocytes in a Patient with Hypoimmunoglobulinemia
Authors: Thomas Tursz, Jean-Louis Preud'Homme, Sylvaine Labaume, Claude Matuchansky, Maxime Seligmann
Journal: Journal of Clinical Investigation (1977)

In a young woman with ulcerative colitis, hypoimmunoglobulinemia, and humoral immunodeficiency, lymphocyte counts vary between 600 and 1,000 per mm3 with 0.5-1.5% bone marrow-derived (B) cells and 98-99% thymus-derived (T) cells. Anti-lymphocyte antibodies were detected by immunofluorescence and by microlymphocytotoxicity with increased reactivity at +4°C. They belonged to the IgM class and were polyclonal. Studies performed with various normal lymphocyte subpopulations, several lymphoblastoid cell lines and lymphocytes from immunodeficiency patients showed that these antibodies reacted with B cells. The corresponding antigen(s) is distinct from membrane-bound immunoglobulins, is not an alloantigen, and is probably unrelated to the la-like molecules. Pokeweed mitogen stimulated B cells appear to lose this antigen. Cells from various lymphoproliferative disorders were tested. T-derived and “non T-non-B” leukemic cells did not react with the antibody. Malignant cells from B-derived lymphomas and prolymphocytic leukemias were reactive. The incidence of positivity of the leukemic cells among patients with common B chronic lymphocytic leukemia was surprisingly low (one-third of the patients).
Quantitative Exfoliative Cytology of Normal Oral Squames: An Age, Site and Sex-Related Survey
Authors: J G Cowpe, R B Longmore, M W Green
Journal: Journal of the Royal Society of Medicine (1985)

This study describes the development of quantitative cytological techniques and their application to oral smears. Nuclear and cell size has been measured and matched with age, sex and site in an attempt to produce a baseline for comparison with identical measurements carried out on pathological smears. The results displayed a significant variation in nuclear and cytoplasmic area between different sites. Nuclear size varied significantly with advancing age; however, this was not the case for cytoplasmic area. There was no significant variation in either criterion between males and females.
Efficacy of biologics in the treatment of moderate to severe psoriasis: a network meta-analysis of randomized controlled trials
Authors: K. Reich, A.D. Burden, J.N. Eaton, N.S. Hawkins
Journal: British Journal of Dermatology (2011)

Ustekinumab, a novel monoclonal antibody for the treatment of moderate to severe plaque-type psoriasis, has recently received regulatory approval in Europe, bringing the total number of biologic agents licensed in this indication to five. To assist treatment selection in daily practice it is essential to understand the benefit/risk profile of these agents and in the absence of a clinical trial comparing all available biologics a number of reviews have used statistical techniques to generate estimates of the comparative effectiveness of these therapies through the available network of randomized clinical trials. These estimates have previously been published for a limited range of psoriasis biologic treatments, although, to date no review has compared all the currently available agents in Europe.To estimate the comparative effectiveness of all biologic agents indicated in the treatment of moderate to severe psoriasis currently available in Europe based on the primary trial endpoints.A number of databases were searched for details of randomized controlled trials of available biologics in the treatment of plaque-type psoriasis in adults. Comparative effectiveness was estimated based on the reported Psoriasis Area and Severity Index (PASI) 50, 75 and 90 response rates. A network meta-analysis conducted on the ordered probit scale and implemented as a Bayesian hierarchical model provided estimates for the probability of response and relative risk vs. placebo, based on all observed comparisons.Twenty trials were included in the meta-analysis including patients with a mean disease duration of 18-22years. Based on the indirect comparison and given a placebo PASI 50 response of 13%, infliximab had the highest predicted mean probability of response at PASI levels 50 (93%), 75 (80%) and 90 (54%), followed by ustekinumab 90 mg at 90%, 74% and 46%, respectively, and then ustekinumab 45mg, adalimumab, etanercept and efalizumab.The ordered probit model allowed a quantitative comparison of all currently licensed biologics, providing estimates on comparative effectiveness and a suggested ranking of treatments that is of potential use to decision-makers. However, the analysis is based on indirect comparisons of the primary endpoint reported from short-term randomized trials.
Peristomal lichen sclerosus: the role of occlusion and urine exposure?
Authors: F. Al-Niaimi, C. Lyon
Journal: British Journal of Dermatology (2012)

Lichen sclerosus (LS) is a chronic inflammatory skin disorder that typically affects the anogenital area. It presents with ivory-white atrophic patches or plaques with associated telangiectasia and occasional purpura. It has rarely been described as affecting abdominal stomas.To investigate possible aetiological factors responsible for the development of this condition.All patients with peristomal LS were identified at a specialist stoma dermatology clinic and studied using a standardized pro forma.We identified 12 patients with peristomal LS. The mean age was 72·3 years (range 47-85 years). With the exception of one patient, all our other patients had urostomies. Treatment was effective in the majority of cases.Peristomal LS, in our experience, is most commonly found around urostomies, and we speculate that in addition to the possible role of local trauma and occlusion, certain - as yet unidentified - constituents in the urine possibly play a role in its aetiology. It tends to respond well to corticosteroids and has not been associated with malignant transformation.
LSC 2014 abstract - Endotracheal intubation triggers neutrophil extracellular traps
Authors: Davide Scozzi, Carlos Puyo, Daniela Peruzzi, Kelsey Toth, Salvatore Mariotta, Andrew Gelman
Journal: European Respiratory Journal (2014)

Background:  We have previously reported endotracheal intubation induces upper airway injury that leads to neutrophil recruitment in the absence of any evidence of infection. Neutrophil Extracellular Traps (NETs) are thought to play role in containing infection but it remains unclear if tissue injury stimulate NETs. Here we ask if endotracheal intubation can induce trachea-infiltrating neutrophils to produce NETs.   Methods:  Lavage above the tracheal cuff and peripheral blood was obtained from 3 healthy surgical patients that have undergone endotracheal intubation for general anesthesia. At the end of surgery tracheal lavage and peripheral blood neutrophils were cultured for 3 hrs with or without 25nM phorbol 12-myristate 13-acetate (PMA). NET formation was analyzed by fluorescence microscopy using antibodies specific for the NET components neutrophils elastase and histone protein H2b along with the DNA stain Hoescht 33342.   Results:  Both peripheral blood and tracheal lavage neutrophils produced NETs in response to PMA (Figure 1.A) However, unlike neutrophils in the peripheral blood tracheal lavage neutrophils spontaneously produced NETs in culture (Figure 1.B).   Conclusions:  Human infiltrating tracheal neutrophils in response to endotracheal intubation produce NETs. These data suggest that mechanically induced tissue injury is sufficient to promote NET formation.
Adjunctive systemic corticosteroid treatment in hospitalized patients with community-acquired pneumonia
Authors: Shigeo Hanada, Shinko Suzuki, Hironori Uruga, Hisashi Takaya, Atsushi Miyamoto, Nasa Morokawa, Atsuko Kurosaki, Kazuma Kishi
Journal: European Respiratory Journal (2012)

Rationale: Although steroids potentially modulate the activation of the immune system in patients with pneumonia, the clinical benefit of adjunctive corticosteroid therapy in patients with community-acquired pneumonia (CAP) remains controversial.  Objective: The present study evaluated the effects of adjunctive corticosteroid therapy on hospitalized patients with CAP.  Methods: We retrospectively studied 98 patients with CAP having definitive etiologies who visited the Toranomon Hospital between April 2006 and April 2010.  Results: The patients included 49 men and 49 women with a mean age of 64 years (range: 19-100). Underlying diseases included diabetes mellitus (n=23), malignancy (n=21) and chronic obstructive pulmonary diseases (n=7). The Pneumonia Severity Index (PSI) was I in 20 patients, II in 25, III in 21, IV in 30, and V in 2. Causative pathogens were  Streptococcus pneumoniae  (n=33),  Haemophilus influenzae  (n=25),  Mycoplasma pneumoniae  (n=22), and others (n=17). Of the 98 patients, 67 were treated with standard antimicrobial therapy and 31 were treated antibiotics and systemic steroids (prednisolone 15-60 mg/day). Clinical characteristics were similar between the steroid and nonsteroid groups, except that PSI was higher in the steroid group. In the steroid group, the number of patients with a clinical cure at days 7 and the median length of hospital stay were 11 (35%) and 15.1 days, respectively, while those in the nonsteroid group were 36 (55%) and 14.5 days, respectively (p = 0.08, and p = 0.43, respectively).  Conclusion: Adjuncive corticosteroid therapy along with antibiotics does not improve the outcome of CAP in hospitalized patients.
OX-22high CD4+ T cells induce wasting disease with multiple organ pathology: prevention by the OX-22low subset.
Authors: F Powrie, D Mason
Journal: The Journal of Experimental Medicine (1990)

Congenitally athymic rats injected with CD45RBhigh CD4+ T cells from congenic euthymic donors developed a severe wasting disease with inflammatory infiltrates in liver, lung, stomach, thyroid, and pancreas. In contrast, recipients of CD45RBlow CD4+ T cells remained well and continued to gain weight. Animals given unfractionated CD4+ T cells, i.e., a mixture of approximately two-thirds CD45RBhigh and one-third CD45RBlow, were protected from the wasting disease, and the incidence of organ-specific inflammation was much reduced compared with that found in recipients of CD45RBhigh cells alone. The data suggest that this latter subset of CD4+ T cells has autoaggressive potential that is inhibited in normal animals by cells of the CD45RBlow CD4+ phenotype. The possible consequences of a breakdown in this immunoregulatory mechanism are briefly discussed.
Practice based primary care research networks
Authors: L. A Green
Journal: BMJ (2001)

Primary care p 588 

Practice based research networks are research laboratories as essential to advancing the scientific understanding of medical care as bench laboratories are to advancing knowledge in the basic sciences. The medical establishment has been slow to realise patients' needs for a robust research enterprise in family practice and primary care. But a paper in this week's BMJ adds to evidence that research networks in primary care have come of age and deserve sustained support (p 588).1

For much of the past century the prevailing view was that the problems faced in family practice could be resolved by research carried out by others in other settings. The failure to implement research findings in daily practice raised some researchable questions about knowledge transfer, but it did not engender a spirit of excitement about the research needs and opportunities intrinsic to family practice. The notion that there were important questions, fundamental to the origins of health and disease, that could be investigated best or only in family practice proved elusive.

Countries rich enough …
Detection of TB by smear microscopy and GeneXpert MTB/RIF assay in non expectorating pulmonary TB suspects and pleural TB in high prevalent low income setting
Authors: Saifullah Baig, Shahina Qayyum, Nausheen Saifullah, Nadeem Ahmed
Journal: European Respiratory Journal (2014)

Introduction  Pakistan is 4 th  among the 12 countries with 75% of 2.9 million missing TB cases. Not expectorating pulmonary TB cases are often missed. Gastric aspirate is obtained in these cases for AFB smear and culture. Diagnoses of extra pulmonary TB especially the pleural TB is difficult. GeneXpert MTB/RIF (Xpert) Assay has shown promising results in diagnosis of TB.  The purpose of this study was to test the efficiency and reliability Xpert system for the detection of  M. tuberculosis  bacteria in gastric aspirate and pleural fluids  Method  Gastric aspirated were taken from all non expectorating TB suspects attending Ojha institute of chest diseases Karachi In 2013. Pleural tap was obtained from pleural TB suspects. Specimens were tested for Mycobacterium by smear microscopy and Xpert assay.  Result  Out of 521 specimens tested 110, 113 and 38 were gastric aspirate, pleural fluid and pleural pus. Among these 57(51.8%), 17(44.7%) and 64(90.1%) of gastric aspirate, pleural pus and pleural fluid tested respectively were new cases.  Smear was positive in 65(59.1%), 16(42.1%) and 7(9.1%) of gastric aspirate, pleural pus and pleural fluid respectively. TB was detected in 66(60%), 21(55.3%) and 8(11.3%) of gastric aspirate, pleural pus and pleural fluid with Xpert respectively. Rifampacin(R) resistance was detected in 8 gastric aspirates and 1 pleural pus.  Conclusion  Xpert shows additional detection of 1%, and 2% by gastric aspirate and pleural fluid but 12% additional detection in pleural pus. R resistance was detected in 7.2% gastric aspirates and 2.6% pleural pus. Therefore Xpert should be more frequently used.
Comparison of CT-based lobar ventilation models with 3He MRI ventilation measurements in asthmatics
Authors: Bilal Tahir, Cedric Van Holsbeke, Rob Ireland, Andy Swift, Felix Horn, Helen Marshall, Juan Parra-Robles, Ruth Hartley, Richard Kay, Chris Brightling, Jan De Backer, Wim Vos, Jim Wild
Journal: European Respiratory Journal (2014)

Introduction CT models of ventilation can be computed from expiratory and inspiratory scans by means of the relative lobar expansion. This model has been validated against SPECT [1].

Objective To compare models of lobar ventilation from CT with 3He MRI using multi-modal image registration in a population of asthma patients.

Methods 29 patients with moderate-to-severe asthma underwent breath-hold CT at TLC and FRC. CT was used to segment the lobes at FRC and TLC by identification of major fissures and these were used to calculate percentage lobar ventilation [1]. 1H and 3He MRI were acquired in the same breath at FRC+1L [2], and the 1H MRI to CT registration was applied directly to 3He MRI allowing direct comparison of lobar CT ventilation with 3He.

Results 3He MRI was successfully warped to inspiration CT using the transform from the 1H MRI and CT registration. The mean absolute difference between CT and 3He MRI ventilation across lobes was 4.8% (mean±SD for each lobe: RUL+RML=6.1±4.6%; RLL=5.0±5.7%; LUL=4.0±4.1%; LLL=4.6±3.7%).

![Figure][1] 



Conclusion This study compares percentage lobar ventilation from CT models with a direct measure of gas ventilation using 3He MRI. In so doing we validate the CT ventilation model and demonstrate that multi-modal registration allows the regional interpretation of 3He MR images on top of the underlying anatomy of the CT.

References [1]Radiol 2010;257:854-62 [2]NMR Biomed 2011;24:130-34.

 [1]: pending:yes
Viruses detected by systematic multiplex polymerase chain reaction in adults with suspected community-acquired pneumonia attending emergency departments in France
Authors: D. Das, H. Le Floch, N. Houhou, L. Epelboin, P. Hausfater, A. Khalil, P. Ray, X. Duval, Y.-E. Claessens, C. Leport
Journal: Clinical Microbiology and Infection (2015)
Lymphoproliferative disorders after renal transplantation in patients receiving triple or quadruple immunosuppression.
Authors: B Melosky, M Karim, A Chui, M McBride, E C Cameron, C K Yeung, D Landsberg, C Shackleton, P A Keown
Journal: Journal of the American Society of Nephrology (1992)

A retrospective review of 478 renal transplant recipients receiving cyclosporin A (CsA) was conducted to determine the incidence, relative risk, and outcome of lymphoproliferative disease after transplantation. Cases of neoplasm were identified by linking the computerized databases of the British Columbia (B.C.) Transplant Society and the B.C. Cancer Agency. B.C. Cancer Statistics for 1988 were used to determine relative risk. Patients were monitored for a total of 1,054 patient years with a mean follow-up time of 26 months (range, 0.1 to 63 months). A total of 334 patients were treated with triple immunosuppression (CsA), azathioprine, and prednisone), and 144 received adjunctive antilymphocyte globulin as induction immunosuppression. Sixty-nine patients received OKT3 for the treatment of transplant rejection. Twenty-two patients developed 23 malignancies (4.8%) at a mean interval of 16 months (range, 3 to 45 months) after transplantation. Non-Hodgkins lymphoma occurred in five patients, of whom two received triple (0.6%) and three received quadruple (2.1%) therapy. All five patients, in addition, received OKT3 for the treatment of graft rejection. The relative risk of developing a neoplasm among the defined sample adjusted for age and sex was 3.08 overall, increasing to 26.9 (P less than 0.005) for lymphoma. Six of the 22 patients (27%), including all 5 patients with lymphoma, died as a result of their tumor. Renal transplant recipients receiving CsA have a significantly elevated risk of developing a de novo lymphoreticular malignancy, which is comparable to that reported for those receiving azathioprine treatment, and which appears to be increased by the use of quadruple immunosuppression and the administration of OKT3 for the treatment of acute graft rejection.
Phase I study of single-agent perifosine for recurrent pediatric solid tumors.
Authors: O. J. Becher, T. M. Trippett, J. Kolesar, S. Gilheeney, Z. Jiang, Y. Khakoo, D. Lyden, C. Sima, E. C. Holland, I. J. Dunkel
Journal: Journal of Clinical Oncology (2010)

9540 Background: Perifosine is a synthetic alkylphospholipid which inhibits Akt activity and also has been reported to affect the JNK and MAPK signaling pathways. Single agent trials of perifosine in adults have demonstrated responses in patients with renal cell carcinoma, advanced brain tumors, soft-tissue sarcomas, hepatocellular carcinoma, as well as in hematologic malignancies including multiple myeloma and Waldenstrom's macroglobulinemia. We sought to determine the safety of perifosine in children with recurrent solid tumors Methods: Pediatric patients with recurrent solid tumors were enrolled in a phase I, open-label, dose-escalating study to assess pharmacokinetics (PK), and to identify the maximally tolerated dose (MTD). Cohorts of 3 pts were treated at three dose levels: 25mg/m2/day, 50mg/m2/day and 75mg/m2/day using 50mg tablets of perifosine after a loading dose on D#1 Results: 9 pts (4 male, 5 female) with high-grade glioma (n=5), medulloblastoma (n=2) or neuroblastoma (n=2) have been treated to date. Their median age was 13 years (range 5-18), most were heavily pretreated, with a median of 3 prior treatment regimens (range 1-10). No DLTs were observed. No ≥ grade 3 toxicities or adverse events have been encountered. Grade 2 toxicities that were possibly related to perifosine include asthenia (22%), asymptomatic transaminase elevation (22%), neutropenia (33%), leukopenia (11%), hyperglycemia (22%), hypomagnesemia (22%), hypophosphatemia (11%), and colitis which resolved despite drug continuation (11%). Preliminary PK data resulted in the following steady state serum levels: 14.1±4μ M for dose level 1, 32.8±8.1 μ M for dose level 2, and 31.6 ±7.8μ M for dose level 3. Conclusions: Perifosine is well tolerated in children with advanced solid tumors. No significant financial relationships to disclose.
Fusidic Acid Monotherapy
Authors: V Vassiliou, A K Demetriades, G Scott
Journal: Journal of the Royal Society of Medicine (2002)

Dr Biswas and colleagues (February 2002 JRSM1) present two cases of hypocalcaemia arising during fusidic acid therapy. We agree that this could represent a rare side-effect of fusidic acid. However, we would like to focus on a different aspect—that of antimicrobial resistance selection. In both patients fusidic acid was used as monotherapy (for more than one month in case 2, unspecified for case 1). The general view is that fusidic acid should not be used alone because natural mutants with an alteration in the elongation factor G are harboured even at low rates of 106 staphylococci2. This leads to a rapid spontaneous mutation rate, seen when the organism is grown in increasing concentrations of the drug. Therefore, combination with another antistaphylococcal antibiotic such as flucloxacillin or vancomycin will decrease the risk of resistance emergence1,2,3, particularly if the infection is with methicillin-resistant Staphylococcus aureus or chronic4. The British National Formulary (BNF) recommends ‘clindamycin alone or flucloxacillin+fusidic acid’ for the treatment of osteomyelitis5.

Both patients were taking aspirin during treatment with fusidic acid. There is some evidence that this too could promote the emergence of resistance6, and one might consider replacing aspirin with a different antiplatelet agent. In case 1 the patient was concurrently taking aspirin and ciprofloxacin. According to the BNF such a combination can increase the risk of convulsions even in patients with no previous history5 and ciprofloxacin resistance might also increase in the presence of salicylates7.

In conclusion, fusidic acid should be used only in combination with another antistaphylococcal agent, and interactions with even as ‘benign’ a drug as aspirin should be considered.
Ultraviolet Microscopy of X-Irradiated Intestine&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Yevette S. Lewis, Henry Quastler, George Svihla
Journal: JNCI Journal of the National Cancer Institute (1958)

The color-translating ultraviolet microscope was used to study radiation effects in the mouse intestine. Generative cells showed pronounced changes in light absorption at 263 mµ; the light-absorbing clumps normally present in the nucleus disappeared. Later, diffuse, strong absorption was seen in cytoplasm and nucleus; still later, there was very little absorption. The earlier changes occurred uniformly in all generative cells and thus cannot be related to a stage in the mitotic cycle; the late changes were independent of resumption of mitosis. The principal cells had similar but much less pronounced changes in 263 mµ absorption. Later, changes occurred that were related to abnormal development. The Paneth cells showed similar changes in 263 mµ absorption. In addition, they showed early degeneration of a specific (secretory) cytoplasmic structure, followed by speedy recovery.