tbuckley/cabot-search huggingface dataset:
Human myeloma IgA half-molecules.
Authors: H L Spiegelberg, B G Fishkin
Journal: Journal of Clinical Investigation (1976)

A lambda, IgAl myeloma protein that formed two chain half-molecules was obtained from a patient who had typical multiple myeloma. His serum contained 1.3 g/100 ml of an IgA paraprotein of gamma-1 electrophoretic mobility, his urine predominantly lambda Bence Jones protein, and only small amounts of IgA paraprotein. Analytical ultracentrifugation of the isolated serum IgA protein showed 7.0S and 4.5S protein peaks but no IgA polymers. When the 7.0S and 4.5S protein peaks were tested with an antiserum specific for alpha chain, both fractions were antigenically deficient compared to control IgA myeloma proteins but showed a line of identity to their F(ab')2 fragments. The serum and 7.0S protein fraction showed double precipitin lines in IgA radial immunodiffusion plates and in immunoelectrophoretic analysis, one line being formed by the myeloma protein and the other by residual normal IgA. The myeloma protein did not form a precipitin line with antisera specific for the IgA Fc fragment. Sodium dodecylsulfate-urea-polyacrylamide gel electrophoresis demonstrated that both the 7.0S and 4.5S fractions of the myeloma protein consisted of covalently linked heavy and light chains, 4.5S fraction being apparently the half-molecule of the 7.0S protein. The heavy chain had a mol wt of 46,500 daltons compared to 55,000 daltons for normal alpha chains. Reduction and alkylation in aqueous solutions resulted in dissociation of the 7.0S myeloma protein fractions into smaller units, probably half-molecules, suggesting that the noncovalent interactions between the alpha chains were substantially weakened or absent, presumably as a result of a deletion in the Fc portion of the alpha chain. The catabolic rates of the radio-labeled 7.0S and 4.5S protein in rhesus monkeys were similar to those of control IgA myeloma proteins; the excretion of protein-bound radioactivity of the IgA half-molecules into the urine was no greater than that of the 7.0S or of control IgA myeloma proteins. It is suggested that the myeloma IgA half-molecule is probably derived from an IgAl mutant that is carried in the human genome and that it is unlikely a representative of a rare IgA subclass or an IgA l allotypic variant.
Endothelial Perturbation in Children and Adolescents With Type 1 Diabetes
Authors: Mario Romano, Mariapina Pomilio, Sergio Vigneri, Angela Falco, Pierluigi Lelli Chiesa, Francesco Chiarelli, Giovanni Davì
Journal: Diabetes Care (2001)

OBJECTIVE—The progression of diabetic angiopathy is, in most cases, unpredictable. The aim of this study was to investigate early events that could influence the development of diabetic angiopathy. RESEARCH DESIGN AND METHODS—Circulating levels of von Willebrand factor (vWF) and tissue-plasminogen activator (tPA), defining endothelial perturbation, were measured in 40 young patients with type 1 diabetes. Patients were divided into two groups according to the duration of diabetes (group A, &amp;lt;1 year; group B, &amp;gt;1 year) and compared with a control group of age- and sex-matched healthy individuals. Prothrombin fragment 1 and 2 (F1+2), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) levels were also determined as markers of a prothrombotic state and inflammatory response. A total of 16 of the 20 children in group A were re-examined after 12 months. RESULTS—Compared with either normal subjects or patients in group B, children in group A showed increased levels of vWF, tPA, F1+2, TNF-α, and CRP. Significant direct correlations between TNF-α or CRP and either vWF, tPA, or F1+2 were observed. Endothelial perturbation was shown in 70% of group A and 20% of group B. After 1 year, 16 of the 20 patients in group A showed a significant reduction in vWF, tPA, F1+2, TNF-α, and CRP levels, whereas endothelial perturbation was reversed in 5 of these patients. CONCLUSIONS—Endothelial perturbation represents an early and, in some cases, reversible event in the chronology of type 1 diabetes in children. A correlation might exist between the initial inflammatory reaction and the appearance of endothelial perturbation.
A 45 year old man with an ulcerated nodule on his right leg
Authors: P. Fernandez-Crehuet, R. Ruiz-Villaverde
Journal: BMJ (2014)

<h3>Objective</h3> To compare physical function scales of the Multi-Dimensional Health Assessment Questionnaire (MDHAQ) to the Health Assessment Questionnaire Disability Index (HAQDI) in patients with psoriatic arthritis (PsA), and examine whether either questionnaire is less prone to ‘floor effects’. <h3>Methods</h3> Data were collected prospectively from 2018 to 2019 across three UK hospitals. All patients completed physical function scales within the MDHAQ and HAQDI in a single clinic visit. Agreement was assessed using medians and the Bland-Altman method. Intraclass correlation coefficients (ICCs) were used to assess test-retest reliability. <h3>Results</h3> 210 patients completed the clinic visit; one withdrew consent thus 209 were analysed. 60.0% were male, with mean age of 51.7 years and median disease duration of 7 years. In clinic, median MDHAQ and HAQDI including/excluding aids scores were 0.30, 0.50 and 0.50 respectively. Although the median score for HAQDI is higher than MDHAQ, the difference between the two mostly lies within 1.96 standard deviations from the mean suggesting good agreement. The ICCs demonstrated excellent test-retest reliability for both HAQ questionnaires. Similar numbers of patients scored ‘0’ on the MDHAQ and HAQDI including/excluding aids (48, 47, and 49 respectively). Using a score of ≤0.5 as a cut-off for minor functional impairment, 23 patients had a MDHAQ ≤0.5 when their HAQDI including aids &gt;0.5. Conversely, 4 patients had a MDHAQ &gt; 0.5 when the HAQDI including aids ≤0.5. <h3>Conclusion</h3> Both HAQ questionnaires appear to be similar in detecting floor effects in patients with PsA.
Effect of Ventilator Mode on Sleep Quality in Critically Ill Patients
Authors: Sairam Parthasarathy, Martin J. Tobin
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

To determine whether sleep quality is influenced by the mode of mechanical ventilation, we performed polysomnography on 11 critically ill patients. Because pressure support predisposes to central apneas in healthy subjects, we examined whether the presence of a backup rate on assist-control ventilation would decrease apnea-related arousals and improve sleep quality. Sleep fragmentation, measured as the number of arousals and awakenings, was greater during pressure support than during assist-control ventilation: 79 +/- 7 versus 54 +/- 7 events per hour (p = 0.02). Central apneas occurred during pressure support in six patients; heart failure was more common in these six patients than in the five patients without apneas: 83 versus 20% (p = 0.04). Among patients with central apneas, adding dead space decreased sleep fragmentation: 44 +/- 6 versus 83 +/- 12 arousals and awakenings per hour (p = 0.02). Changes in sleep-wakefulness state caused greater changes in breath components and end-tidal CO2 during pressure support than during assist-control ventilation. In conclusion, inspiratory assistance from pressure support causes hypocapnia, which combined with the lack of a backup rate and wakefulness drive can lead to central apneas and sleep fragmentation, especially in patients with heart failure.
Ethics on the London Underground
Authors: P. Bruggen
Journal: BMJ (2010)

As I let myself fall into the only vacant seat in the London Underground carriage, I caught sight of something to my left. I closed my eyes to recapture detail. The occupant of the seat to my left had been holding a piece of paper titled with the name of someone I knew, and halfway down was a heading, “Mr X’s schooling.” Did I really know that Mr X? No, but it was not a usual name, and it was that of a friend of my parents long ago.

A rustle on my left, and I allowed myself to glance in that direction. The page that I had …
Diagnosis of pancreatic cancer by 2[18F]-fluoro-2-deoxy-D-glucose positron emission tomography.
Authors: H Friess, J Langhans, M Ebert, H G Beger, J Stollfuss, S N Reske, M W Buchler
Journal: Gut (1995)

The detection of pancreatic cancer or the discrimination between pancreatic cancer and chronic pancreatitis remains an important diagnostic problem. The increased glucose metabolism in malignant tumours formed the basis for this investigation, which focused on the role of positron emission tomography (PET) with 2[18F]-fluoro-2-deoxy-D-glucose (FDG) in the detection of pancreatic cancer and its differentiation from chronic pancreatitis. Eighty patients admitted for elective pancreatic surgery received preoperatively 250-350 mBq FDG intravenously and emission scans were recorded 45 minutes later. Intense focal activity in the pancreatic region was taken at the time of scanning as showing the presence of pancreatic cancer. The presence of cancer was later confirmed by histological examination of the surgical specimens and histological findings were compared with the preoperative PET results. Forty one patients with pancreatic cancer (group I: n = 42) had a focally increased FDG uptake in the pancreatic region. Two patients with a periampullary carcinoma (group II: n = 6) failed to develop FDG accumulation. In 28 patients with chronic pancreatitis (group III: n = 32) no FDG accumulation occurred. Overall sensitivity and specificity of PET for malignancy (group I + II) were 94% (45 of 48) and 88% (28 of 32), respectively. The standard uptake value of the patients with pancreatic carcinoma was significantly higher than in patients with chronic pancreatitis (3.09 (2.18) v 0.87 (0.56); p &lt; 0.001; median (interquartile range)). These findings show that FDG-PET represents a new and non-invasive diagnostic procedure for the diagnosis of pancreatic cancer and to differentiate pancreatic cancer from chronic pancreatitis. However, the diagnostic potential of this technique requires further evaluation.
Urban Violence in Los Angeles-Reply
Authors: C. Boyd James
Journal: JAMA (1994)

<h3>In Reply.</h3> —We appreciate the kind words of our colleague Dr Silfen. His observations and references will be useful to our future undertakings. With regard to the letter from Dr Gorsuch, we are indeed troubled by his situating our appeal for a more equitable distribution of health care services and other social resources within the arena of "social engineering." Nonetheless, we will continue to be guided by Rudolph Virchow's principle of 130 years ago, when he argued that it was incongruous to treat a patient with tuberculosis if it meant returning the patient to the customary squalor and filth from which his misfortune sprung. We here who labor within the arid vineyards of the dispossessed are not acquainted with Gorsuch's sector of sufferers who had chosen this deprived and sullen existence. Indeed, every day we encounter all kinds of people desperately clamoring and working toward an escape from the condition
Doxorubicin release is not a prerequisite for the in vitro cytotoxicity of HPMA-based pharmaceuticals: In vitro effect of extra drug-free GlyPheLeuGly sequences
Authors: B. Říhová, J. Strohalm, O. Hovorka, V. Šubr, T. Etrych, P. Chytil, R. Pola, D. Plocová, J. Bouček, K. Ulbrich
Journal: Journal of Controlled Release (2008)
Thrombin receptor expression is increased by angiotensin II in cultured and native vascular smooth muscle cells
Authors: B Fisslthaler
Journal: Cardiovascular Research (1998)

Objective: The factors involved in restenosis after balloon angioplasty are poorly characterized but the local concentration of the potent mitogens angiotensin II (AII) and thrombin is known to be increased at sites of vascular injury. We investigated the possibility of a synergistic interaction between AII and thrombin by studying the effects of AII on the expression of the thrombin receptor in rat aortic smooth muscle cells (VMSC). Methods: Thrombin receptor mRNA expression was studied by Northern blot analysis and RT-PCR using total RNA extracted from VMSC or from endothelium-denuded rat aortae. As a measure of thrombin receptor protein expression, we assessed either the thrombin-stimulated release of 6-keto-prostaglandin F1α from VMSC or the contraction of endothelium-denuded rat aortic rings. Results: The thrombin receptor mRNA was expressed at a low level in both cultured and native VMSC. AII concentration- and time-dependently increased expression of thrombin receptor mRNA in VSMC and augmented the thrombin-induced release of 6-keto-prostaglandin F1α as well as the thrombin-induced contraction. Blockade of the angiotensin subtype 1 (AT1) receptor by EXP3174 or D8731 prevented the AII-mediated increase in thrombin receptor expression. The effect of AII on the increase in thrombin receptor mRNA expression was enhanced by the protein kinase C inhibitor Ro 31-8220, but was unaffected by prolonged incubation with phorbol myristate acetate or the tyrosine kinase inhibitors genistein and erbstatin A. Conclusion: These results demonstrate that AII enhances the expression of thrombin receptor in cultured and native VMSC. In cultured cells, this effect is mediated by the activation of the AT1 receptor subtype. This synergistic effect between AII and the thrombin receptor may promote the extensive proliferation of smooth muscle cells in response to vascular injury.
Proposal for GPs to take back some out of hours care sparks debate
Authors: I. Torjesen
Journal: BMJ (2013)

A row has erupted over a suggestion by the Royal College of General Practitioners that GPs in England could potentially take back responsibility for providing out of hours primary care services for some of their patients.

The row stems from an article published in the Guardian newspaper on 4 June, in which the college’s chairwoman, Claire Gerada, was reported as saying that GPs could take back responsibility for the out of hours care of patients who were heavy users of NHS services.1 These would include frail, elderly people; people at the end of their lives; people with complex medical problems; and people with certain mental health problems. Together they would equate to about 5% of the total population or roughly three million people.

Instead of these patients seeking help through existing urgent care services or turning up at hospital emergency departments in difficulties, the proposal was that …
Detection of inflammatory bowel disease in adults and children: evaluation of a new isotopic technique.
Authors: D J Dawson, A N Khan, V Miller, J F Ratcliffe, D R Shreeve
Journal: BMJ (1985)

The distribution of radioactivity after the oral administration of sucralfate labelled with technetium-99m was studied in 33 patients with Crohn9s disease (13 adults, 20 children), 10 with ulcerative colitis (four adults), and 29 controls (23 with upper intestinal disease, four irritable bowel, one hypolactasia, and one malrotation of the gut). Positive scans were obtained in all patients with ulcerative colitis and 29 of 31 with active Crohn9s disease. The scans of two patients with inactive Crohn9s disease were negative. There were two false negative scans in patients with Crohn9s colitis and one false positive scan. Overall, sensitivity was 95% and specificity 97%. Comparison with radiology in 39 patients showed similar distribution of disease in 24 and more extensive disease in 12. The scan was inexpensive, simple to perform, well tolerated, allowed small and large bowel to be visualised simultaneously, and used a lower dose of radiation than barium studies. It may prove useful as a screening test for inflammatory bowel disease and in the serial assessment of disease activity.
Constitutionality of Exemption Laws on Guarantee of Purity for Blood Transfusions and Tissue and Organ Transplants
Authors: William J. Curran
Journal: New England Journal of Medicine (1973)

THERE has been much controversy and concern among hospitals, physicians (especially transplant surgeons and blood banks about decisions of certain state supreme courts imposing "strict liability without fault," or requiring a guarantee of purity in the furnishing of blood products to hospital patients. The most famous recent decision of this type was passed down in 1970 by the Illinois Court in Cunningham vs. MacNeal Memorial Hospital.1 The other two leading cases in this period were decided in Pennsylvania2 and New Jersey.3 The reaction of hospital associations, insurance carriers, blood banks and medical societies to these decisions has been to seek . . .
ON MEMBRANES DISCHARGED FROM THE UTERUS.
Authors: EMIL RIES
Journal: JAMA (1896)

The gynecologist often receives for examination membranes which, he is told, have been discharged from the uterus. Unfortunately he often receives them in a stage of decomposition which makes them hardly fit for microscopic examination. The cause of this may be that the membrane has been retained in the vagina for some time before it was discharged, or that after discharge it has not been preserved with sufficient care. If the membranes are kept in water or in weak solutions of alcohol the decomposition may go so far that the epithelium is thrown off from the surface and from the glands, and the cells of the interstitial tissue stain very badly or not at all. Let me draw your attention to the importance of the careful preservation of such membranes in concentrated alcohol or in a 20 per cent. solution of formol. The shrinking which may be caused by the
240 SUSTAINED VIROLOGICAL RESPONSE IMPROVES SURVIVAL IN HCV-RELATED LIVER CIRROSIS WITH PORTAL HYPERTENSION
Authors: B.E. Annicchiarico, M. Siciliano, A. Iacobellis, A.W. Avolio, G. Caracciolo, A. Andriulli, G. Bombardieri
Journal: Journal of Hepatology (2010)
PHYSICIAN-PATIENT RELATIONSHIP
Authors: Henry C. Eichelmann
Journal: JAMA (1952)

To the Editor.—  From day-to-day conversations with patients, it is my impression that the average patient does not favor government medicine, but he at times is disgusted with the average physician. On this account, some patients feel that government intervention in the field of medicine might help matters (how  do not know).  The chief gripe, especially in the larger cities, is that, owing to specialization, the physician never really gets to know his patient. As one woman told me, I had been going regularly to an obstetrician for about seven months when  suddenly developed severe gallbladder colic, which  recognized, having had it before.  called the obstetrician and asked for assistance, giving my name, etc. His first question was 'Are you pregnant?' When assured in the affirmative, and that he had been attending me for seven months, he referred me to another specialist. We are starved for
The Effectiveness of Multimedia Nursing Education on Reducing Illness-Related Anxiety and Depression in Coronary Care Unit's Patients
Authors: Muhammed Bora Demirçelik, Derya Yigit, Esra Sentepe, Mevlude Keklık, Mustafa Cetın, Zehra Cetın, Beyhan Eryonucu
Journal: Journal of the American College of Cardiology (2013)
Meta-analysis: testing for reporting bias
Authors: P. Sedgwick
Journal: BMJ (2015)

Researchers undertook a meta-analysis to evaluate the effectiveness of oral decontamination on the incidence of ventilator associated pneumonia in mechanically ventilated adults. Randomised controlled trials that recruited mechanically ventilated adults and compared the effects of a daily oral application of antibiotics or antiseptics with no prophylaxis were included.1

In total, 11 trials involving 3242 patients met the inclusion criteria. When the results of these trials were pooled, rates of ventilator associated pneumonia were significantly lower in patients who received oral decontamination than in those who received no prophylaxis (relative risk 0.61, 95% confidence interval 0.45 to 0.82). The researchers constructed the funnel plot for the primary outcome of ventilator associated pneumonia, and visual inspection suggested that it was asymmetrical, indicating the existence of reporting bias. A formal statistical test did not, however, support the presence of reporting bias (Egger’s test, P=0.111). Subgroup analysis showed that the incidence of ventilator associated pneumonia was significantly reduced with a daily oral application of antiseptics (0.56, 0.39 to 0.81) but not with antibiotics (0.69, 0.41 to 1.18).

The researchers concluded that oral decontamination of mechanically ventilated adults with a daily oral application of antiseptics is associated with a lower risk of ventilator associated pneumonia.

Which of the following types of bias, if any, would have contributed to reporting bias for the results of the meta-analysis?

Answers a , b , c , and d are all true.

In total, 11 trials that compared the effects of a daily oral application of antibiotics or antiseptics with no prophylaxis on the incidence of ventilator associated pneumonia in mechanically ventilated adults were identified. However, as is often the case, the results of the different trials …
Burkitt cell leukemia following treatment of Hodgkin's disease: Report of a case and review of the literature
Authors: S. H. Krikler, G. O. Bain, P. A. Gordon
Journal: American Journal of Hematology (1984)

Abstract The development of Burkitt cell leukemia (FABL3) [1] in a patient 7 years after successful treatment of Hodgkin's disease (HD) by combined modality (chemotherapy and radiotherapy) therapy is described. The B‐cell nature of the leukemic blasts is shown by immunologic surface marker studies. While L3 leukemia is very rarely seen following therapy for HD, diffuse lymphoma of small noncleaved cells (LSNC)— resembling the Burkitt tumor—is more common in this setting.
Abstract A55: Tumor-associated fibroblasts: A new target for cancer treatment
Authors: Chase Hamilton, Shary Shelton, Kiran Kakarala, Sufi Mary Thomas
Journal: Cancer Research (2015)

Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with a 50% rate of local failure with current standard of care. We recently reported that patient-derived tumor associated fibroblasts (TAF) facilitate HNSCC proliferation and metastasis to the cervical lymph node and lung of mice. Although the paracrine molecular interactions between HNSCC and TAFs have not been fully described, we demonstrated that TAFs (and not HNSCC) secrete hepatocyte growth factor (HGF), a ligand for the c-Met receptor on HNSCC cells. Further, activation of the HGF-c-Met pathway increased HNSCC growth and invasion. In addition, we demonstrated that HNSCC cells induce the expression of HGF from TAFs. We hypothesized that inhibition of TAF-secreted HGF would reduce HNSCC proliferation, invasion and migration. We tested the efficacy of ficlatuzumab (AV-299) a humanized HGF inhibitory immunoglobulin G1 (IgG1) monoclonal antibody in mitigating TAF-induced HNSCC progression. . Ficlatuzumab exhibits antitumor effects in xenograft models as a single agent and has been tested in patients with non-small cell lung cancer in a phase I setting. The antitumor efficacy of HGF neutralization has not been tested in the context of TAFs in HNSCC. Our data demonstrate that ficlatuzumab is effective in mitigating TAF-induced HNSCC proliferation, migration and invasion through inhibition of the c-met pathway in HNSCC. Citation Format: Chase Hamilton, Shary Shelton, Kiran Kakarala, Sufi Mary Thomas. Tumor-associated fibroblasts: A new target for cancer treatment. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A55. doi:10.1158/1538-7445.CHTME14-A55