tbuckley/cabot-search huggingface dataset:
Abstract 3466: Mitochondrial targeting photosensitizer-lipophilic cation conjugates for photodynamic therapy
Authors: Pallavi Rajaputra, Gregory Nkepang, Youngjae You
Journal: Cancer Research (2012)

Abstract Mitochondrion of a living cell plays a pivotal role in apoptosis. Targeting the mitochondria of cancer cell for the induction of apoptosis in photodynamic therapy (PDT) has gained importance. Cancer cells have higher plasma and mitochondrial membrane potential compared to normal cells, consequently delocalized lipophilic cations (DLCs) tend to accumulate more in them than in normal cells. In PDT photosensitizers can be specifically delivered to the mitochondria of cancerous cell by conjugating them with DLCs. Three conjugates: CMP-TPP (a porphyrin-triphenyl phosphene monocation conjugate) and CMP-(TPP)2 (a porphyrin- triphenyl phosphene dication conjugate), CMP-Rh (a porphyrin -rhodamine monocation conjugate) were synthesized as mitochondria targeting photosensitizers. The conjugates were synthesized by conjugating a core modified porphyrin (CMP-TPP) to either 1 or 2 triphenyl phosphene (TPP) molecules or rhodamine B (Rh B) respectively via a saturated hydrocarbon linker. To evaluate the efficiency of the conjugates, the photophysical properties like fluorescence resonance energy transfer (FRET in CMP-Rh) and singlet oxygen generation was compared to that of the unconjugated CMP. Potent in vitro photodynamic activity was observed in Colon 26 cells upon treatment with CMP conjugates and exposure to 690 nm diode laser light source (5.6 mW/cm2 for 30 min, 10.8 J/cm2). No significant darktotoxicity was observed in cells treated up to 5 μM of the conjugates. The conjugates showed approximately 12-14 times higher uptake in Colon 26 cells compared to unconjugated porphyrin. Further, sub-cellular localization, comparison of preferential uptake by cancerous cells versus normal cells, in vivo bio-distribution, PDT in BALB/c mice will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3466. doi:1538-7445.AM2012-3466
Herpes Zoster After Irradiation
Authors: F. Ellis, B. A. Stoll
Journal: BMJ (1949)

Since 1935 one of us (F.E.) has been of the opinion that clinically typical zoster occurring in patients who had received radiotherapy probably resulted from the treat- ment.The numerical incidence of zoster generally in the population is not known, so that statistically the point is difficult to prove; we believe, however, that there is pre- sumptive evidence of such correlation.Although the virus nature of zoster is now accepted, there is still a considerable difference of opinion on the importance of various factors predisposing to attack by the virus.Apart from the idiopathic type of disease occurring especially in adults, the infection may also arise after contact with a case of varicella, during the course of
Comparison of Cardiorespiratory Effects of Isoprenaline and Salbutamol in Patients with Bronchial Asthma
Authors: D. A. Warrell, D. G. Robertson, J. N. Howes, M. E. Conolly, J. W. Paterson, L. J. Beilin, C. T. Dollery
Journal: BMJ (1970)

The effects of isoprenaline and salbutamol administered orally, by inhalation, or by intravenous infusion were compared in 13 asthmatic patients. Bronchodilator activity was assessed by serial measurement of specific airways conductance (SGaw). Log-dose response curves were obtained for both drugs and showed them to be equipotent as bronchodilators. Cardiovascular effects were variable, but in general, isopenaline caused greater rise in pulse rate and a greater change in blood pressure than the same dose of salbutamol.Cardiorespiratory measurements during continuous intravenous infusion of increasing doses of both drugs suggested a greater effect of isoprenaline than the same dose of salbutamol on metabolic rate, pulmonary ventilation, pulmonary gas exchange, cardiac output, and heart rate. The effect of salbutamol on the heart rate was about 10 times less than that of isoprenaline but lasted longer.
Effect of a "Lean" intervention to improve safety processes and outcomes on a surgical emergency unit
Authors: P. McCulloch, S. Kreckler, S. New, Y. Sheena, A. Handa, K. Catchpole
Journal: BMJ (2010)

Emergency surgical patients are at high risk for harm because of errors in care. Quality improvement methods that involve process redesign, such as “Lean,” appear to improve service reliability and efficiency in healthcare.Interrupted time series.The emergency general surgery ward of a university hospital in the United Kingdom.Seven safety relevant care processes.A Lean intervention targeting five of the seven care processes relevant to patient safety.969 patients were admitted during the four month study period before the introduction of the Lean intervention (May to August 2007), and 1114 were admitted during the four month period after completion of the intervention (May to August 2008). Compliance with the five process measures targeted for Lean intervention (but not the two that were not) improved significantly (relative improvement 28% to 149%; P<0.007). Excellent compliance continued at least 10 months after active intervention ceased. The proportion of patients requiring transfer to other wards fell from 27% to 20% (P<0.000025). Rates of adverse events and potential adverse events were unchanged, except for a significant reduction in new safety events after transfer to other wards (P<0.028). Most adverse events and potential adverse events were owing to delays in investigation and treatment caused by factors outside the ward being evaluated.Lean can substantially and simultaneously improve compliance with a bundle of safety related processes. Given the interconnected nature of hospital care, this strategy might not translate into improvements in safety outcomes unless a system-wide approach is adopted to remove barriers to change.
Occurrence of Non-Hodgkin's Lymphoma after Therapy for Hodgkin's Disease
Authors: John G. Krikorian, Jerome S. Burke, Saul A. Rosenberg, Henry S. Kaplan
Journal: New England Journal of Medicine (1979)

We studied the clinical and pathological features of six cases of non-Hodgkin's lymphoma (diffuse undifferentiated in four cases and diffuse histiocytic in two cases) occurring in patients treated for Hodgkin's disease. All six patients had received both radiation therapy and chemotherapy. Abdominal or gastrointestinal involvement was present in five of the six cases. None of the patients had evidence of Hodgkin's disease when the diagnosis of non-Hodgkin's lymphoma was made. Five of the six patients were among a study group of 579 patients with Hodgkin's disease, prospectively followed since diagnosis. At 10 years the actuarial risk of development of non-Hodgkin's lymphoma in this study group is 4.4 per cent (1.2 to 15.0) (per cent probability with 95 per cent confidence limits) and is similar to that of developing acute leukemia: 2.0 per cent (0.3 to 12.9). Non-Hodgkin's lymphoma is a second tumor that may occur late in the course of patients treated for Hodgkin's disease — particularly in patients who have received both radiation therapy and chemotherapy. Like acute leukemia, non-Hodgkin's lymphoma may be another cancer that represents a substantial late risk of combined-modality therapy. (N Engl J Med 300:452–458, 1979)
Anti-immunoglobulin E treatment decreases worm burden and egg production in Schistosoma mansoni-infected normal and interferon gamma knockout mice.
Authors: P Amiri, M Haak-Frendscho, K Robbins, J H McKerrow, T Stewart, P Jardieu
Journal: The Journal of Experimental Medicine (1994)

The immunoglobulin E (IgE) response is generally considered an essential component of the host defense against parasitic helminths such as Schistosoma mansoni. In contrast, work on antischistosome vaccines suggests that interferon gamma (IFN-gamma) is the critical immune mediator for vaccine-induced immunity to the parasite. In this study, the total IgE response to a primary S. mansoni infection was suppressed by anti-IgE treatment in both normal mice and in mice with defective IFN genes (gene knockout [GKO]). Reduction of the IgE response resulted in decreased worm burden and a decrease in the number of eggs produced per worm in both normal and GKO mice. Whereas anti-IgE treatment also resulted in reduced hepatosplenomegaly, granulomas around existing schistosome eggs showed normal cellularity. Serum interleukin 4 levels fell in response to the reduction in serum IgE as well. The data suggest that IgE plays a detrimental, rather than beneficial, role for the host in schistosomiasis. Furthermore, the absence of IFN-gamma was found to be of little consequence to the host-response to adults or eggs in a primary schistosome infection.
Suspected Cushing's syndrome.
Authors: K C McHardy
Journal: BMJ (1984)

If assaulted again I shall be reluctant to fight back. I now know that I can't defend myself very effectively anyway. The risks of severe personal injury are great if knives or other weapons are wielded. The ego trip of foiling a robbery or the deterrent effect of failure on those trying to commit a crime is not worth the risk. It is too easy to apportion all the blame for crime statistics on to social, financial, and environmental factors. A glance at any newspaper underlines the fact that man is a violent and primitive animal and is likely to remain that way. Misfits, as arbitrarily defined by the society of the time, will always tend to congregate together and the stronger will always prey on the weak. Inner city general practice is the most exciting and depressing, stimulating and humbling, rewarding and heartrending experience that I know. The News of the World encapsulated this experience with its slogan All Human Life is Here and who picks up the Guardian, the Telegraph, or The Times when the News of the World is lying around?
Laryngeal Papillomavirus Infection during Clinical Remission
Authors: Bettie M. Steinberg, William C. Topp, Patricia S. Schneider, Allan L. Abramson
Journal: New England Journal of Medicine (1983)

Biopsy samples from 20 patients with a history of laryngeal papillomas were analyzed by Southern blot hybridization for the presence of human papillomavirus DNA. All papillomas examined contained papillomavirus DNA sequences. Four samples from uninvolved sites in two patients with active disease and eight samples from patients in remission also contained viral DNA. No human papillomavirus DNA was detected in a third patient seen during remission. These results explain the clinical pattern of frequent recurrences even after long-term remission in laryngeal papillomatosis.
The thinking doctor’s guide to placebos
Authors: Rudiger Pittrof, Ian Rubenstein
Journal: BMJ (2008)

Tapasin organizes the peptide-loading complex (PLC) by recruiting peptide-receptive MHC class I (MHC-I) and accessory chaperones to the N-terminal regions of the TAP subunits TAP1 and TAP2. Despite numerous studies have shown that the formation of the PLC is essential to facilitate proper MHC-I loading, the molecular architecture of this complex is still highly controversial. We studied the stoichiometry of the PLC by blue native-PAGE in combination with Ab-shift assays and found that TAP/tapasin complexes exist at steady state as a mixture of two distinct oligomers of 350 and 450 kDa. Only the higher m.w. complex contains MHC-I and disulfide-linked tapasin/ER60 conjugates. Moreover, we show for the first time to our knowledge that the fully assembled PLC comprises two tapasin, two ER60, but only one complex of MHC-I and calreticulin. Based hereon we postulate that the TAP subunits alternate in the recruitment and loading of a single MHC-I.
Identification of two single base substitutions in the UGT1 gene locus which abolish bilirubin uridine diphosphate glucuronosyltransferase activity in vitro.
Authors: L T Erps, J K Ritter, J H Hersh, D Blossom, N C Martin, I S Owens
Journal: Journal of Clinical Investigation (1994)

Accumulating evidence indicates that mutations in the human UGT1 gene locus abolish hepatic bilirubin UDP-glucuronosyltransferase activity and cause the subsequent accumulation of bilirubin to toxic levels in patients with Crigler-Najjar type 1 (CN-I). Genetic and biochemical criteria are required to link CN-I with mutations in UGT1. Here we present analysis of mutations at the UGT1 locus in three individuals that were clinically diagnosed with CN-I (two related and one unrelated). Each patient carries a single base substitution that alters conserved residues in the transferase enzyme molecule, serine to phenylalanine at codon 376 and glycine to glutamic acid at codon 309. Each was homozygous for the defect as demonstrated by sequencing and RFLPs. Mutant cDNAs, constructed by site-directed mutagenesis, inserted into expression vectors, and transfected into COS-1 cells, supported the synthesis of the bilirubin transferase protein but only cells transfected with the wild-type cDNA expressed bilirubin UDP-glucuronosyltransferase activity. The data provide conclusive evidence that alterations at Gly 309 and Ser 376 are the genetic basis for CN-I in these families. These results suggest that the two codons, located in conserved regions of the molecule, are part of the active site of the bilirubin enzyme.
Communication Skills for Medicine
Authors: M. R Partridge
Journal: BMJ (1996)

Margaret Lloyd, Robert Bor Churchill Livingstone, £15, pp 180 ISBN 0 443 05168 2

In 1978 the late Charles Fletcher wrote a superb book entitled Talking with Patients: A Teaching Approach. This was distributed to medical schools by the Nuffield Provincial Hospitals Trust and it made a lasting impression on many doctors. Communication training has subsequently been introduced into all undergraduate curriculums. Lloyd and Bor have produced a text to go with these courses, but the content is not specific to medical students and is aimed at all who wish to improve their communication skills.

The book uses a combination of factual …
Transmission and Clinical Features of Enterovirus 71 Infections in Household Contacts in Taiwan
Authors: Luan Yin Chang, Kou Chien Tsao, Shao Hsuan Hsia, Shin Ru Shih, Chung Guei Huang, Wing Kai Chan, Kuang Hung Hsu, Tsui Yen Fang, Yhu Chering Huang, Tzou Yien Lin
Journal: JAMA (2004)

Although enterovirus 71 has caused epidemics associated with significant morbidity and mortality, its transmission has not been thoroughly investigated.To investigate enterovirus 71 transmission and determine clinical outcomes within households.Prospective family cohort study to investigate patients at a children's hospital in Taiwan and family members of these patients who had signs and symptoms suggestive of enterovirus 71 between February 2001 and August 2002. Patients and household members underwent clinical evaluations, virological studies, questionnaire-based interviews, and were followed up for 6 months.Enterovirus 71 infection, defined as a positive viral culture from a throat or rectal swab, or the presence of IgM or a 4-fold increase in neutralizing antibody in serum; and clinical syndromes, defined as asymptomatic; uncomplicated symptomatic; and complicated; with unfavorable outcomes of sequelae or death.Ninety-four families (433 family members) had at least 1 family member with evidence of enterovirus 71 infection. The overall enterovirus 71 transmission rate to household contacts was 52% (176/339 household contacts). Transmission rates were 84% for siblings (70/83); 83%, cousins (19/23); 41%, parents (72/175); 28%, grandparents (10/36); and 26%, uncles and aunts (5/19). Of 183 infected children, 11 (6%) were asymptomatic and 133 (73%) had uncomplicated illnesses (hand, foot, and mouth disease, herpangina, nonspecific febrile illness, upper respiratory tract infection, enteritis, or viral exanthema). Twenty-one percent (39/183) experienced complicated syndromes including the central nervous system or cardiopulmonary failure. During the 6-month follow-up, 10 died and 13 had long-term sequelae consisting of dysfunction in swallowing, cranial nerve palsies, central hypoventilation, or limb weakness and atrophy. Age younger than 3 years was the most significant factor associated with an unfavorable outcome in children (P =.004). Among 87 infected adults, 46 (53%) were asymptomatic, 34 (39%) had nonspecific illnesses of fever, sore throat, or gastrointestinal discomfort, and 7 (8%) had hand, foot, and mouth disease. There were no complicated cases in adults.Enterovirus 71 household transmission rates were high for children in Taiwan and severe disease with serious complications, sequelae, and death occurred frequently. In contrast, adults had a much lower rate of acquisition of the infection and much less adverse sequelae.
Prognostic Indices for Older Adults
Authors: Lindsey C. Yourman, Sei J. Lee, Mara A. Schonberg, Eric W. Widera, Alexander K. Smith
Journal: JAMA (2012)

To better target services to those who may benefit, many guidelines recommend incorporating life expectancy into clinical decisions.To assess the quality and limitations of prognostic indices for mortality in older adults through systematic review.We searched MEDLINE, EMBASE, Cochrane, and Google Scholar from their inception through November 2011.We included indices if they were validated and predicted absolute risk of mortality in patients whose average age was 60 years or older. We excluded indices that estimated intensive care unit, disease-specific, or in-hospital mortality.For each prognostic index, we extracted data on clinical setting, potential for bias, generalizability, and accuracy.We reviewed 21,593 titles to identify 16 indices that predict risk of mortality from 6 months to 5 years for older adults in a variety of clinical settings: the community (6 indices), nursing home (2 indices), and hospital (8 indices). At least 1 measure of transportability (the index is accurate in more than 1 population) was tested for all but 3 indices. By our measures, no study was free from potential bias. Although 13 indices had C statistics of 0.70 or greater, none of the indices had C statistics of 0.90 or greater. Only 2 indices were independently validated by investigators who were not involved in the index's development.We identified several indices for predicting overall mortality in different patient groups; future studies need to independently test their accuracy in heterogeneous populations and their ability to improve clinical outcomes before their widespread use can be recommended.
938-55 Effect of Residual Infarct Artery Stenosis on Flow Reserve After Reperfusion: Implications for Assessing Myocardial Viability Using Myocardial Contrast Echocardiography
Authors: Flordeliza S. Villanueva, Martin C. Fallon, Prudencio C. Lucero
Journal: Journal of the American College of Cardiology (1995)
Adenosine-receptor subtypes: their relevance to adenosine-mediated responses in asthma and chronic obstructive pulmonary disease
Authors: R. Polosa
Journal: European Respiratory Journal (2002)

Adenosine administration by inhalation elicits concentration-related bronchoconstriction in subjects with asthma and chronic obstructive pulmonary disease (COPD). The mechanisms of adenosine-induced bronchoconstriction appear to involve a selective interaction with activated mast cells with subsequent release of preformed and newly-formed mediators. Further evidence linking adenosine signalling to asthma and COPD comes from the finding that many cell types that play important roles in the exacerbation of these conditions express adenosine receptors and demonstrate relevant effects through stimulation of these receptors. Therefore, blockade of these receptors may be a valuable approach to the treatment of asthma and chronic obstructive pulmonary disease. Promising adenosine-receptor targets for novel therapeutics of asthma and chronic obstructive pulmonary disease have recently been identified in a number of inflammatory cell types, including mast cells, eosinophils, lymphocytes, neutrophils, and macrophages. The recent characterisation of the A 2B receptors indicates the human lung mast cell as one of the most strategic cellular targets.
Immunodeficiency Virus Slowly Yields Secrets
Authors: Timothy F. Kirn
Journal: JAMA (1988)

A TECHNICAL INNOVATION that allows investigators to select particular marrow cells from aspirate taken from the iliac crest of living subjects and the vertebral columns of cadavers has led to two discoveries about the human immunodeficiency virus (HIV). Investigators from the National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Md, say that they have been able to infect normal hematopoietic progenitor cells with HIV in vitro. The implication: marrow may be a "potent" reservoir for the virus in the body. Moreover, Jan Marc Orenstein, MD, PhD, an associate professor of pathology at George Washington University Medical Center, Washington, DC, discovered through electron microscopy that the progenitor cells can produce new virions without budding them off the membrane. Rather, he says, oftentimes the cell will accumulate "scores" of virus in "internal compartments" deep within the cytoplasm. If that is occurring regularly in the human body, the progenitor cells theoretically could
Technique for Endoscopic Hemostasis of a Bleeding Peptic Ulcer in a Gastrostomy Patient
Authors: C. Choi, P. Chiu, P. Kwong, S. Lam
Journal: Endoscopy (2004)

Gastric ulcers induced by gastrostomy are usually located on the posterior wall of the gastric body, and they may result in upper gastrointestinal bleeding [1] [2]. A suggested mechanism for the way in which a percutaneous endoscopic gastrostomy (PEG) is capable of inducing gastric ulcers is prolonged contact between the tapered tip of the gastrostomy tube and the posterior wall [3]. The design of the gastrostomy tube has also been reported to be a factor in ulcer bleeding [4]. Esophagogastroduodenoscopy (EGD) is the standard method of establishing the diagnosis, but it involves difficult tangential viewing of gastric ulcers on the posterior wall. We present here a case in which an alternative route was used to manage this problem.
Immunological state of patients with carcinoma of the bronchus before and after radiotherapy.
Authors: A M Savage, J A Pritchard, T J Deeley, B H Davies
Journal: Thorax (1980)

The immunological state of 30 patients with carcinoma of the bronchus was assessed before and after radiotherapy by lymphocyte response to PHA and E and EAC rosette formation. The results were compared with those from age-matched patients with benign chest disease and a group of healthy control subjects. Differences were found between the three groups and decreased immunological responses were found to correlate with shorter survival times for patients with cancer of the bronchus. These differences were not associated with the extent of the disease, or with the smoking habits of the patients. Significant differences in percentage EAC cell rosetting were demonstrated between lymphocytes from patients with malignant disease (31.3 +/- 2.0) and those for control groups (21.5 +/- 1.9 and 24.0 +/- 2.2). Cancer patients and benign chest disease patients both had significantly decreased mean E rosetting values (59.3% and 55.6%) compared with healthy control subjects (69.7%). The group of cancer patients with a normal percentage of T lymphocytes and total number of lymphocytes after radiotherapy, or those with low percentage EAC cell rosettes, had a greater than 80% survival after seven months compared with less than 50% for the rest of the patients with carcinoma of the bronchus.