tbuckley/cabot-search huggingface dataset:
Interactions between Antibiotics and Human Neutrophils in the Killing of Staphylococci
Authors: Richard K. Root, Raul Isturiz, Abdolghader Molavi, Julia A. Metcalf, Harry L. Malech
Journal: Journal of Clinical Investigation (1981)

Normal and antibiotic-pretreated staphylococci were incubated with human neutrophils to determine the interactions between cells and antimicrobials in the killing of the organisms. Staphylococcus aureus 502A pretreated during log-phase growth with subinhibitory ((1/4) minimum inhibiting concentration) (MIC) concentrations of penicillin G were more susceptible to killing by normal neutrophils than untreated bacteria (intracellular survival 0.17+/-0.04 vs. 1.5+/-0.38%, mean+/-SEM, respectively, at 35 min in 14 experiments; P < 0.01 by t test). Furthermore, this enhanced susceptibility to killing was observed even when phagosome formation was inhibited by cytochalasin B (65.6+/-4.6% pencillintreated vs. 30.5+/-4.5% untreated killed at 30 min in 14 experiments, P < 0.001). Pretreatment of S. aureus with vancomycin similarly enhanced susceptibility to killing by cytochalasin B-treated polymorphonuclear leukocytes (PMN), whereas pretreatment with gentamicin did not. The enchancement of killing by pretreatment with cell wall-active antibiotics was present in a dose-response fashion to 1/16th the MIC. It required specific antimicrobial activity; i.e., penicillin activity was inhibited by penicillinase or by incubation with bacteria at 4 degrees C. It also required active cellular metabolism and intact neutrophils. For antibiotic-pretreated bacteria to be killed by normal and cytochalasin B-treated cells, phagocytosis or binding to the cells was essential via a serum opsonindependent mechanism. In experiments with the cytochalasin B-treated cells, all bound penicillin-treated bacteria were killed vs. only a fraction (70%) of the bound untreated bacteria. Penicillin in 10 times the MIC had no direct effects on PMN phagocytic, metabolic, or microbicidal functions against a nonsusceptible organism, Candida albicans. The results indicate a cooperative effect between cell wall-active antibiotics at low concentrations and human PMN in the killing of staphylococci. The model establishes conditions for the study of the mechanisms involved in the cooperation of these bactericidal systems.
Hepatocyte Growth Factor and Keratinocyte Growth Factor in the Pulmonary Edema Fluid of Patients with Acute Lung Injury
Authors: G. M. VERGHESE, K. McCORMICK-SHANNON, R. J. MASON, MICHAEL A. MATTHAY
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Hepatocyte growth factor (HGF) and keratinocyte growth factor (KGF) are among the most potent mitogens identified for alveolar type II epithelial cells and may have other important functions in repair of the alveolar epithelium in acute lung injury (ALI). However, neither growth factor has been identified in the distal air spaces or plasma of patients with ALI. The goals of this study were to determine: (1) whether HGF and KGF are present in pulmonary edema fluid from patients with ALI and control patients with hydrostatic pulmonary edema; (2) whether HGF and KGF are biologically active in pulmonary edema; and (3) whether HGF or KGF levels are associated with clinical outcome. Pulmonary edema and plasma samples were obtained within 48 h of onset of acute pulmonary edema requiring mechanical ventilation in 26 patients with ALI and 11 control patients with hydrostatic edema. HGF and KGF concentrations were measured with enzyme-linked immunosorbent assays (ELISAs). The median (25th to 75th percentiles) concentration of HGF in pulmonary edema fluid was 21.4 (8.3 to 41.3) ng/ml in ALI and 6.6 (4.8 to 11.4) ng/ml in hydrostatic edema fluid (p < 0.01). The HGF concentration was 7-fold higher in the edema fluid than in the plasma of patients with ALI. In contrast, KGF was detected in low concentrations in edema fluid of patients with ALI and hydrostatic pulmonary edema; the concentration of KGF did not differ in ALI edema (0.6 [0.3 to 2.1] ng/ml) and hydrostatic edema fluid (0.2 [0.0 to 2.6] ng/ml) (p = NS). HGF and KGF were partly purified from four edema-fluid samples by heparin–Sepharose chromatography. Partly purified edema fluids were potent stimuli of DNA synthesis in cultured rat type II alveolar cells; addition of neutralizing antibodies to HGF and KGF attenuated this increase in DNA synthesis by 66% and 53%, respectively. Interestingly, higher edema-fluid levels of HGF were associated with higher mortality in patients with ALI. These novel results show that HGF and KGF are active in the alveolar space early in ALI, probably mediating early events in lung repair, and that increased levels of HGF in edema fluid may have prognostic value early in ALI.
Soundings: No sweet surrender
Authors: Imre Loefler
Journal: BMJ (2005)

Sugar is as dangerous as tobacco and, in terms of world health, far more important. Although the ill effects of tobacco are manifold (from memory loss to poor semen, damage to the fetus, and wrinkled skin) it kills either through cancer or vascular disease, and it usually does so from the sixth decade of life onwards. Sugar is an enormous burden throughout life: it destroys children's teeth, it leads to obesity, and it exacerbates diabetes, a disease that eventually destroys every organ.

In the West there will soon be more people with diabetes than smokers. In the developing world tobacco use is increasing but sugar consumption is increasing as well, not least because of the proliferation of soft drinks.

The campaign for the cessation of sugar consumption must not repeat the mistakes of the antitobacco crusade. It is not just a case of education, persuasion, and lawsuits—sugar should be classified as a hard drug, for it is addictive and harmful. Sugar production, trade, possession, and consumption should be legislated against internationally. In the spirit of coercive healthism sugar should be eradicated. German and French farmers can be compensated for leaving their sugar beet fields fallow. The sugar plantations in the tropics should be converted into rubber plantations to meet the growing need for condoms.

Non-compliance should be punishable by sanctions and through the destruction of sugar cane, if necessary by aerial spraying. It is likely that as soon as these measures are in place there will be an illegal trade in sugar. Inevitably the price of sugar will rise.

Sugar is currently the cheapest calorie in the developing world. This in itself drives consumption. Illegal sugar will become too expensive for the poor, yet it will be coveted, if for no other reason than because it will be illegal. Criminalisation of the sugar trade will mean the creation of antisugar agencies. The benefits of such bureaucracies will include not only curtailing illegal production and trade, but also adding to the price of sugar.

It is high time that the world learned how to deal with the risks associated with such an unhealthy diet. There will be a considerable cost attached to the cessation of sugar consumption, but this will be negligible in comparison with the cost of the disease burden attributable to sugar.
The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare-associated infections and antimicrobial use
Authors: P Zarb, B Coignard, J Griskeviciene, A Muller, V Vankerckhoven, K Weist, M M Goossens, S Vaerenberg, S Hopkins, B Catry, D L Monnet, H Goossens, C Suetens, Collective National Contact Points for the ECD, Collective Hospital Contact Points for the ECD
Journal: Eurosurveillance (2012)

A standardised methodology for a combined point prevalence survey (PPS) on healthcare-associated infections (HAIs) and antimicrobial use in European acute care hospitals developed by the European Centre for Disease Prevention and Control was piloted across Europe. Variables were collected at national, hospital and patient level in 66 hospitals from 23 countries. A patient-based and a unit-based protocol were available. Feasibility was assessed via national and hospital questionnaires. Of 19,888 surveyed patients, 7.1% had an HAI and 34.6% were receiving at least one antimicrobial agent. Prevalence results were highest in intensive care units, with 28.1% patients with HAI, and 61.4% patients with antimicrobial use. Pneumonia and other lower respiratory tract infections (2.0% of patients; 95% confidence interval (CI): 1.8-2.2%) represented the most common type (25.7%) of HAI. Surgical prophylaxis was the indication for 17.3% of used antimicrobials and exceeded one day in 60.7% of cases. Risk factors in the patient-based protocol were provided for 98% or more of the included patients and all were independently associated with both presence of HAI and receiving an antimicrobial agent. The patient-based protocol required more work than the unit-based protocol, but allowed collecting detailed data and analysis of risk factors for HAI and antimicrobial use. .
Quality of life improvement in patients with Hashimoto thyroiditis and other goiters after surgery: A prospective cohort study
Authors: Vladan R. Zivaljevic, Branka R. Bukvic Bacotic, Sandra B. Sipetic, Dejana M. Stanisavljevic, Jadranka M. Maksimovic, Aleksandar D. Diklic, Ivan R. Paunovic
Journal: International Journal of Surgery (2015)
Bacterial cultures in bronchoalveolar lavage fluid in children with chronic respiratory conditions
Authors: Pedro Mondejar-Lopez, Mª Dolores Pastor-Vivero, Esther Bragado-Alcaraz, Virginia Perez-Fernandez, Manuel Sanchez-Solis, Luis Garcia-Marcos
Journal: European Respiratory Journal (2011)

Background: The role of bacteria has usually been underestimated in children with chronic respiratory symptoms.

Aims: To describe the incidence of positive (+) bacterial cultures (BC) in bronchoalveolar lavage (BAL) fluid in children with chronic symptoms, and to assess differences between children with and without bronchiectasis (BCE).

Methods: We carried out a review of all BAL performed from 2007 to 2010 in outpatients of our respiratory clinic. We defined 2 groups (gr): 1) BCE of unknown etiology; 2) Other chronic respiratory conditions. Patients with cystic fibrosis or receiving antibiotic treatment at the moment of the BAL were excluded. Chi2 test was used to assess differences between both gr and the association between gr 1 and the presence of purulent airway (AW) secretions. A multivariate logistic regression was built using gr as dependent variable; and gender, age, AW malacia and gastroesophageal reflux (GER) as independent ones.

Results: The final sample consisted of 70 children (56% male; gr 1: 23, gr 2: 47) who underwent a BAL at a median age 51.7±35 mo. BC was + in 48 (69%) children: 19 (83%) in gr 1 and 29 (62%) in gr 2 (p=0.077). Among + BC, the most common bacteria were H influenzae (n=26) and S pneumoniae (n=18), followed by S aureus (n=5), P aeruginosa (n=4) and K pneumoniae (n=2). A very significant association was found between gr 1 and purulent secretions (p<0.0001).

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Conclusion: Although a + BC in BAL fluid is more common in children with BCE, the role of bacteria in other non-suppurative lung diseases should be taken into account.
Role of Bcl‐3 in the Development of Follicular Helper T Cells and in the Pathogenesis of Rheumatoid Arthritis
Authors: Kazuyuki Meguro, Kotaro Suzuki, Junichi Hosokawa, Yoshie Sanayama, Shigeru Tanaka, Shunsuke Furuta, Kei Ikeda, Hiroaki Takatori, Akira Suto, Akemi Sakamoto, Osamu Ohara, Hiroshi Nakajima
Journal: Arthritis & Rheumatology (2015)

Objective We have previously shown that expression of the Bcl‐3 gene, a member of the IκB family, is down‐regulated in CD4+ T cells from patients with rheumatoid arthritis (RA) following tocilizumab therapy. The objective of this study was to examine the role of Bcl‐3 in the pathogenesis of RA. Methods DNA microarray analysis was used to compare the signal intensity of Bcl‐3 in CD4+ T cells from untreated RA patients and healthy controls. We examined the roles of interleukin‐6 (IL‐6)/STAT‐3 signaling in the induction of Bcl‐3. In addition, we analyzed the gene expression profiles of Bcl‐3–transduced CD4+ T cells by RNA sequencing. The effects of enforced expression as well as gene silencing of Bcl‐3 on the development of follicular helper T (Tfh) cells were evaluated. Finally, we examined correlations between the signal intensities of Bcl‐3 and Tfh cell–related genes in CD4+ T cells from untreated RA patients. Results Bcl‐3 levels were significantly higher in RA patients than in healthy controls. IL‐6 induced Bcl‐3 expression in CD4+ T cells in a STAT‐3–dependent manner. Transcriptome analysis revealed that the expression of Bcl‐6, a master regulator of Tfh cell differentiation, was significantly up‐regulated by the enforced Bcl‐3 expression. The enforced Bcl‐3 expression increased, but Bcl‐3 silencing decreased, the numbers of IL‐21–producing Tfh‐like cells. Bcl‐3 levels in CD4+ T cells from RA patients correlated positively with the levels of Tfh cell–related genes CXCR5, inducible costimulator, and achaete‐scute homolog 2. Conclusion Bcl‐3 is involved in the development of Tfh cells and the pathogenesis of RA, presumably by inducing IL‐21 production.
A survey to assess smoking awareness and attitudes of staff at a local hospital
Authors: Joelle Azzopardi, Sarah Degiovanni, Luisa Farrugia, Neville Calleja, Charmaine Gauci, Anne Buttigieg, Stephen Montefort
Journal: European Respiratory Journal (2012)

Background : Rising smoking-related morbidity and mortality would be expected to lead to increased awareness among hospital staff regarding the harmful effects of cigarettes.   Aims and Objectives:  The aim is to assess the smoking habits of individuals working within a hospital setting who are directly or indirectly exposed to patients with smoking-related illnesses. The survey addresses health issues and attitudes towards smoking. The timing is opportune in that Mater Dei Hospital Malta is to be declared a totally smoke-free hospital.   Methods:  A questionnaire was compiled, based on various tools validated in the literature. These were distributed to all members of staff at our General Hospital, targeting more than 3600 individuals.   Results : 27.1% of male and 24.8% of female staff are active smokers. Males were significantly (p = 0.001) more likely to have started smoking at a younger age than females. Almost half find difficulty in refraining from smoking in forbidden areas. Only 22.2% of smokers refrain from smoking in hospital.The highest percentage of smokers are in the youngest age group (18-25 years). 10.4% of doctors and 23.6% of nurses are active smokers. 25.7% of non-smokers had previously smoked, the greatest incentive for quitting being for health reasons. Most members of staff are aware of the adverse effects of smoking and a number have symptoms suggestive of smoking-related pathology.   Conclusions : Hospital staff mirror the general population with respect to smoking habits and comorbidities. This is unacceptable and emphasizes the need to implement harsher measures whilst educating our hospital staff so that these in turn may serve as educators to patients and hospital visitors.
Long term follow-up of BL22 in cladribine-resistant hairy cell leukemia
Authors: R. J. Kreitman, W. H. Wilson, M. Stetler-Stevenson, P. Noel, I. Pastan
Journal: Journal of Clinical Oncology (2004)

6624 Background: Hairy cell leukemia (HCL) is effectively treated although not cured with cladribine and the likelihood and durability of response decrease after each relapse. BL22 is a recombinant anti-CD22 immunotoxin containing a truncated form of Pseudomonas exotoxin which kills CD22 positive cells. Methods: A total of 36 patients with cladribine-resistant hairy cell leukemia (HCL) have received BL22, 31 on a phase I trial, 2 patients by single patient exemption and 3 in a recently opened phase II trial. Results: In the phase I trial, complete remission (CR) was observed in 19 patients, with CR rates of 43% (6/14), 69% (9/13), and 100% (3/3) in patients enrolled at 30, 40 and 50 ug/Kg every other day for 3 days (QOD x3), respectively. CR was achieved after cycle 1 in 11 and after cycles 2–14 in 8 patients. Of the 19 CRs, 8 (42%) have remained in CR for 14–47 (median 27) months, and the median CR duration is 26 months. Hematologic remission (HR), defined as minimum platelets 100,000/ul, absolute neutrophil count 1500/ul, and hemoglobin 11 g/dl, was achieved in 21 out of 29 (72%) patients. Of 21 in HR, 11 (52%) have remained in HR for 14–46 (median 37) months, and the median HR duration is 26 months. BL22 was nontoxic to CD4+ lymphocytes; the median CD4 count in 17 evaluable patients was 288 prior to and 345 at 3–8 months after BL22. A total of 5 HCL patients had hemolytic uremic syndrome (HUS), 2 after cycle 2 of 30, 2 after cycle 3 of 40, and 1 after cycle 2 of 50 ug/Kg QOD x3 of BL22. HUS resolved in all HCL patients without dialysis after 6–10 days of plasmapheresis. All HUS patients benefited from BL22, with independence from pre-BL22 transfusions, and HR in 5 out of 5 patients. Conclusions: The risk-benefit ratio of BL22 is favorable even in those with HUS because of response to BL22 and reversibility of HUS. BL22 is currently undergoing phase II testing in patients with HCL where 3 of 3 patients have achieved reversal of cytopenias. The true incidence and durability of HR to one cycle of BL22 is being examined by delaying retreatment for 8 weeks after cycle 1, and observing rather than retreating patients in HR after one cycle. This should greatly diminish the incidence of HUS, which in HCL occurred only during retreatment. No significant financial relationships to disclose.
Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensive-stage small-cell lung cancer: a North Central Cancer Treatment Group study.
Authors: K M Rowland, C L Loprinzi, E G Shaw, A W Maksymiuk, S A Kuross, S H Jung, J W Kugler, L K Tschetter, C Ghosh, P L Schaefer, D Owen, J H Washburn, T A Webb, J A Mailliard, J R Jett
Journal: Journal of Clinical Oncology (1996)

PURPOSE Megestrol acetate has been reported to improve appetite and quality of life and to decrease nausea and vomiting in patients with cancer anorexia/cachexia. The present trial was formulated to evaluate the impact of megestrol acetate on quality of life, toxicity, response, and survival in individuals with extensive-stage small-cell lung cancer who received concomitant chemotherapy. PATIENTS AND METHODS Patients were randomized to receive megestrol acetate 800 mg/d orally or placebo. In addition, all patients were scheduled to receive a maximum of four cycles of cisplatin and etoposide chemotherapy. Quality of life was self-assessed at entry onto study, with every cycle of chemotherapy, and 4 months thereafter with a linear visual analog scale. Toxicity was evaluated by patient questionnaire and investigator reports. RESULTS A total of 243 eligible patients were randomized. Those who received megestrol acetate had increased nonfluid weight gain (P = .004) and significantly less nausea (P = .0002) and vomiting (P = .02). Significant thromboembolic phenomena occurred more often in patients who received megestrol acetate versus placebo (9% v 2%, P = .01). Patients who received megestrol acetate had more edema (30% v 20%, P = .002), an inferior response rate to chemotherapy (68% v 80%, P = .03), and a trend for inferior survival duration (median, 8.2 v 10.0 months, P = .49). These findings may have been influenced by a poorer quality of life of the megestrol acetate group at study initiation. There were no significant changes in quality of life scores over time between either of the study arms. CONCLUSION Megestrol acetate cannot be routinely recommended for all patients with small-cell lung cancer at the time of chemotherapy initiation. Rather, its therapeutic ratio may be more favorable for patients with problematic cancer anorexia/cachexia.
Human rabies - Québec, Canada, 2000.
Authors: N. Turgeon, M. Tucci, J. Teitelbaum, D. Deshaies, P. A. Pilon, J. Carsley, L. Valiquette, H. Arruda, L. Alain, A. C. Jackson, A. Wandeler
Journal: MMWR Morbidity and Mortality Weekly Report (2000)
Episodic Postoperative Oxygen Desaturation: The Value of Added Oxygen
Authors: J G Jones, C Jordan, C Scudder, D A Rocke, M Barrowcliffe
Journal: Journal of the Royal Society of Medicine (1985)

Six patients were studied following general anaesthesia for cholecystectomy or hip replacement. Intravenous morphine was given for postoperative pain relief. Continuous measurements were made of breathing pattern and arterial oxygen saturation for a 12-hour period postoperatively. The effect of breathing either air or 28% oxygen for alternate 2-hour periods was examined. There was no significant effect of oxygen on the number of periods of central apnoea, obstructive apnoea or partial upper airways obstruction. The number of episodes of decreases in oxygen saturation to below 80%, associated with these breathing disturbances, was reduced from 59 to zero by the administration of oxygen. There was a gradual improvement in oxygenation whilst breathing air during the 12-hour postoperative period. The administration of oxygen had a beneficial effect on average arterial oxygen saturation.
Hemodynamic and respiratory assessement of an ex vivo perfused rat lung model
Authors: Jeremie Reeb, Anne Olland, Melanie Burban, Cyril Auger, Valérie Schini-Kerth, Laurence Kessler, Florence Toti, Pierre-Emmanuel Falcoz, Gilbert Massard
Journal: European Respiratory Journal (2014)

We describe a simple and cost-effective small animal experimental to study the field of ischemia reperfusion. We present an ex vivo perfused and ventilated rat lung model and report the results of its hemodynamic initial assessment.  Murine lung blocks were placed in a pleural chamber following harvest under general anethesia. The perfusion was realized during 60 minutes by cannulas connected to the pulmonary artery and the left atrial. The perfusion flow (Q) was 7mL/min. Lungs were ventilated with a tracheal catheter (TV=4mL/min, RR=70bpm, FiO 2 =21%).We recorded the mean pulmonary artery pressure (mPAP), the left atrial pressure (LAP), and the peak airway pressure (pPAW). The pulmonary vascular resistances (PVR) were calculated according to the formula: PVR=(sPAP-LAP)x80/Q. PaO 2  was maesured from the left atrial effluent. At the end of perfusion lungs were weighed and dried to calculate wet/dry weight ratio.  We harvested the lungs blocks of 6 male Wistar rats (300-400g). At the initiation of the perfusion, mPAP, PVR, and pPAW, were 4.8±1.8 mmHg, 95785.5±34610.2dyn.sec.cm -5 , and 9.3±2.2mmHg respectively. After the 60 minutes period, mPAP, PVR, and pPAW were 8.4±4.1mmHg, 143618.2±13,7931.0dyn.sec.cm -5 , and 12.2±6.1mmHg, respectively. Left atrial effluent PaO 2  after 10, 30, and 60minutes of reperfusion were 140±2, 134±5, and 140±9mmHg, respectively. No hemodynamic or respiratory differences between the beginning and the end of the perfusion were observed (p>0,05). The mean wet/dry weight ratio was 13±3.  This experimental model used without ischemia is stable. We will be able to vary the times of ischemia and the perfusion flows to study the ischemia reperfusion injuries and to define optimal perfusion values.
Does the GMC think it's immune to its own guidance regarding candour?
Authors: C. Lees
Journal: BMJ (2015)

Dean has established the true degree of independence and transparency of the GMC’s Greenaway report.1 That this hasn’t sent shock waves through the medical establishment attests to the nature of the relations between the GMC, the Department of Health, and medical education quangos. Dean’s findings may reflect a pattern of behaviour at the GMC that does not favour candour.

The recent report on deaths of doctors while under investigation, commissioned by the GMC, was in fact an internal …