tbuckley/cabot-search huggingface dataset:
Long term treatment with luteinising hormone releasing hormone agonists and maintenance of serum testosterone to castration concentrations.
Authors: F Labrie, A Dupont, A Belanger, R Lachance, M Giguere
Journal: BMJ (1985)

Serum concentrations of luteinising hormone and testosterone were measured by radioimmunoassay one, two, four, seven, and 24 hours after the subcutaneous administration of 500 micrograms of the luteinising hormone releasing hormone agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide or [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide in patients who had previously received daily treatment with these peptides for 0, 1, 6, 12, 18, and 24 months. No increase in the serum concentrations of luteinising hormone or testosterone were detected at any time between one and 24 months' treatment. The data show that daily subcutaneous administration of the two luteinising hormone releasing hormone agonists used at the appropriate dose can maintain concentrations of serum androgens equivalent to those after castration during long term treatment.
Dutch agree budget for expensive anticancer drugs
Authors: T. Sheldon
Journal: BMJ (1997)

The Dutch government has announced a £12m ($19m) annual budget to meet the cost of the expensive anticancer drugs paclitaxel (Taxol) and docetaxol (Taxotere) for an estimated 2500 women patients. The drugs are used to treat patients with breast and ovarian cancer.



Having cancer has made women feel like political footballs



Each hospital has had to …
House dust mite allergen in pillows
Authors: T J Kemp, R W Siebers, D Fishwick, G B O'Grady, P Fitzharris, J Crane
Journal: BMJ (1996)

For many years asthmatic patients have been told to avoid using feather filled pillows on their beds, although there is no evidence to support this practice. Strachan and Carey's case-control study is the first to have directly challenged this assumption.1 This study showed that, after exclusion of asthmatic subjects whose bedding had been changed because of their disease, pillows with synthetic fillings were a risk factor for severe asthma. In the light of this finding, we have compared pillows with synthetic and feather fillings for their content of Der p I, the major allergen of the house dust mite Dermatophagoides pteronyssinus.

In December 1995 we took dust samples from nine pairs of pillows and analysed them for Der p I. Each pair consisted of one feather filled pillow and one …
Mediums of the nineteenth century
Authors: John H. Raach
Journal: JAMA (1963)

This two-volume work was originally published 60 years ago with the title<i>Modern Spiritualism</i>. Podmore, the author, was an English civil servant who devoted much of his life to the questions of spiritualism. As a member of the Council of the Society for Psychical Research he knew many of the mediums personally. He interpreted the system of beliefs as "partly religious and partly scientific... based upon a number of obscure phenomena," in which not only living but also deceased persons participated. Podmore traced the origins back to the witchcraft proceedings of the 17th century and discussed the historical development of psychic phenomena as discussed in the works of Swedenborg and Mesmer, among many others. Related topics, such as poltergeists, somnambulists, and clairvoyance, are also discussed. Although there is a certain amount of biographical material included, Podmore's narrative is based almost exclusively on interviews, obscure reports, certain spiritualist publications, and letters.
Quantitative Assessment of the Complex Dynamics of G1, S, and G2-M Checkpoint Activities
Authors: Paolo Ubezio, Monica Lupi, Davide Branduardi, Paolo Cappella, Edoardo Cavallini, Valentina Colombo, Giada Matera, Claudia Natoli, Daniela Tomasoni, Maurizio D'Incalci
Journal: Cancer Research (2009)

Although studies of cell cycle perturbation and growth inhibition are common practice, they are unable to properly measure the activity of cell cycle checkpoints and frequently convey misinterpretation or incomplete pictures of the response to anticancer treatment. A measure of the strength of the treatment response of all checkpoints, with their time and dose dependence, provides a new way to evaluate the antiproliferative activity of the drugs, fully accounting for variation of the cell fates within a cancer cell line. This is achieved with an interdisciplinary approach, joining information from independent experimental platforms and interpreting all data univocally with a simple mathematical model of cell cycle proliferation. The model connects the dynamics of checkpoint activities at the molecular level with population-based flow cytometric and growth inhibition time course measures. With this method, the response to five drugs, characterized by different molecular mechanisms of action, was studied in a synoptic way, producing a publicly available database of time course measures with different techniques in a range of drug concentrations, from sublethal to frankly cytotoxic. Using the computer simulation program, we were able to closely reproduce all the measures in the experimental database by building for each drug a scenario of the time and dose dependence of G(1), S, and G(2)-M checkpoint activities. We showed that the response to each drug could be described as a combination of a few types of activities, each with its own strength and concentration threshold. The results gained from this method provide a means for exploring new concepts regarding the drug-cell cycle interaction.
CONCEPTS IN THE PATHOGENESIS OF ROSACEA
Authors: R. MARKS
Journal: British Journal of Dermatology (1968)

SUMMARY. Ninety‐two patients with rosacea have been studied in order to test, where necessary against control subjects, certain widely accepted hypotheses concerning its cause. No evidence was found that bacteria are implicated as a factor in papular rosacea. Rosacea patients were not found to have a personality disorder, but when tested by a neuroticism proforma were found to be more depressed than control subjects. The depression was regarded as a reaction to the cosmetic disability. There was no evidence that rosacea is linked to disorder of the gastrointestinal tract. Rosacea is not related to the seborrhoeic diathesis. There is no evidence of any important structural or functional abnormality of the small blood vessels of the face. Rosacea patients were not found to be more exposed than controls to climatic extremes. Histologically rosacea appears not to be primarily a folliculitis. Solar elastosis is often conspicuous and disorganization and atrophy of the upper dermis are frequent. The significance of these changes is uncertain. The cause of rosacea remains unknown.
Estrogen Receptor Mutations Found in Breast Cancer Metastases Integrated With the Molecular Pharmacology of Selective ER Modulators
Authors: V. Craig Jordan, Ramona Curpan, Philipp Y. Maximov
Journal: JNCI Journal of the National Cancer Institute (2015)

The consistent reports of mutations at Asp538 and Tyr537 in helix 12 of the ligand-binding domain (LBD) of estrogen receptors (ERs) from antihormone-resistant breast cancer metastases constitute an important advance. The mutant amino acids interact with an anchor amino acid, Asp351, to close the LBD, thereby creating a ligand-free constitutively activated ER. Amino acids Asp 538, Tyr 537, and Asp 351 are known to play a role in either the turnover of ER, the antiestrogenic activity of the ER complex, or the estrogen-like actions of selective ER modulators. A unifying mechanism of action for these amino acids to enhance ER gene activation and growth response is presented. There is a range of mutations described in metastases vs low to zero in primary disease, so the new knowledge is of clinical relevance, thereby confirming an additional mechanism of acquired resistance to antihormone therapy through cell population selection pressure and enrichment during treatment. Circulating tumor cells containing ER mutations can be cultured ex vivo, and tumor tissues can be grown as patient-derived xenografts to add a new dimension for testing drug susceptibility for future drug discovery.
C'1 ESTERASE EFFECT ON ACTIVITY AND PHYSICOCHEMICAL PROPERTIES OF THE FOURTH COMPONENT OF COMPLEMENT
Authors: Hans J. Müller-Eberhard, Irwin H. Lepow
Journal: The Journal of Experimental Medicine (1965)

Highly purified C'1 esterase of human serum is capable of inactivating isolated fourth component of human complement (beta(1E)-globulin). Inactivation is accompanied by changes in electrophoretic and ultracentrifugal properties of beta(1E)-globulin. If non-sensitized sheep erythrocytes are present during the action of C'1 esterase on beta(1E)-globulin, a complex is formed consisting of cells and cytolytically active fourth component (EC'4). Thus, inactivation of beta(1E)-globulin by C'1 esterase appears to be preceded by a state of activation enabling beta(1E)-molecules to combine with cell membrane receptors. Acceptor groups appear to be present also in 7S gamma-globulin and in beta(1E)-globulin itself, since C'1 esterase can induce the formation of beta-beta and of beta(1E)-7S gamma-globulin complexes.
Child sexual abuse--children and families referred to a treatment project and the effects of intervention.
Authors: A Bentovim, P Boston, A van Elburg
Journal: BMJ (1987)

The characteristics of a series of 274 families who were referred to a sexual abuse treatment programme were analysed. Information was obtained on 411 abused children and 362 non-abused children. Different forms of sexual abuse were noted, with 77% of girls and 23% of boys affected. Boys tended to be abused at a younger age, more severely, and for longer periods than girls. There was a predominance of lower social class groups among the parents, and a wide variety of family structures, with reasonable stability over time. Ninety six per cent of perpetrators were men, and biological and step-parents predominated. Contributing factors in both the family history and the current perpetrators and their wives included sexual abuse, violence, chaotic families, marital problems, sexual difficulties, alcoholism, and subnormality. Follow up of 120 families, 180 victims, and 226 siblings showed that prosecution occurred in 60% of cases, with a high percentage of perpetrators being imprisoned. Treatment was offered to 87% of families, but because the treatment programme was in the early stages of development a variable number of children and parents were offered family treatment or treatment in groups for parents and children separately. There was an improvement in the victim9s circumstances in 61% of cases, and a noticeable reduction in "sexualised" and general emotional difficulties among victims, but there was reabuse rate of 16%. Protection of children was achieved through changes of family attitude and changes in family structure including divorce and separation: 14% of victims were rehabilitated to both parents, 33% to mothers only, and 26% to new families or other residences. Consensus in the family that abuse had occurred was seen as an important factor in determining which children could be rehabilitated with both their parents, with their mothers only, or with new families; which families could be offered or accepted treatment; and whether positive changes in the family occurred.
Oral Rehydration
Authors: Charles C. J. Carpenter
Journal: New England Journal of Medicine (1982)

The median life expectancy hovers around 15 years throughout large segments of the developing world, which includes over two thirds of the world's population. Current estimates indicate that in the most densely populated areas of the world, about half the childhood mortality is caused by acute diarrheal illnesses, either directly or as a result of the vicious diarrhea–malnutrition cycle.1 Thus, acute diarrheal illnesses are probably the major cause of death on a global scale.2 The microorganisms responsible for such acute diarrheal diseases were poorly defined before the 1970s. It is now clear that rotavirus and enterotoxigenic Escherichia coli are the . . .
Drug misuse is soaring worldwide warns control board
Authors: L Dillner
Journal: BMJ (1994)

Drug misuse is increasing dramatically in almost every country in the world, says a report from the International Narcotics Control Board. Organised and violent drug trafficking syndicates are exploiting the growing number of politically unstable countries to cultivate and store drugs. “More and more governments are beginning to realise that international cooperation in drug control has now become a matter of urgent self defence,” says the report. Trafficking organisations are bartering different drugs among themselves and using each other's routes to increase their profits.

The board was set up in 1968 as an independent body to implement United Nations policies on drug misuse. It reports annually on drug …
Rheumatoid synovial cells from intact joints. Morphology, growth, and polykaryocytosis.
Authors: B J Clarris, J R Fraser, C J Moran, K D Muirden
Journal: Annals of the Rheumatic Diseases (1977)

Synovial cell lines were isolated by instillation of trypsin or chymotrypsin into intact knee joints of patients with persistent rheumatoid effusions resistant to conventional therapy. Morphology and growth in the primary phase were compared with rheumatoid cells isolated from excised synovium and nonrheumatoid synovial cells obtained from intact joints of cadavers or amputated limbs. Cell populations from all sources included varying proportions of macrophage-like and fibroblast-like cells, with only 1-3% multinucleated cells. In medium supplemented with calf serum alone, rheumatoid cells from intact joints showed negligible changes in morphology. However, in the presence of nonrheumatoid, autologous rheumatoid or homologous rheumatoid serum a rapid increase occurred in size of the macrophage-like cells and numbers of polykaryocytes, including some giant syncytial cells. These effects were directly proportional to serum concentration and were identical in fresh or heat-inactivated serum. In most of these rheumatoid cell lines no multiplication occurred, regardless of serum type or concentration. In rheumatoid synovial cells from excised synovium, human serum induced both polykaryocytosis and rapid growth of fibroblasts. Nonrheumatoid synovial cells grew rapidly but few polykaryocytes developed, mostly with less than 6 nuclei. Evidence of viral infection in rheumatoid synovial cells was sought by electron microscopy after stimulation of polykaryocytosis by human serum. In one of the cultures many cells were found with intranuclear particles possessing characteristics of the adenovirus group.
Airway Eosinophilia Is Associated with Wheeze But Is Uncommon in Children with Persistent Cough and Frequent Chest Colds
Authors: PETER G. GIBSON, JODIE L. SIMPSON, ANITA C. CHALMERS, RUTH C. TONEGUZZI, PETER A. B. WARK, AMANDA J. WILSON, MICHAEL J. HENSLEY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The role of eosinophilic airway inflammation in the variant asthma syndromes of cough and chest colds is not well defined. We tested the hypothesis that children with persistent cough and chest colds have increased sputum eosinophils, similar to those with wheeze. The parents of 390 primary school children completed a symptoms questionnaire. Children with wheeze (n = 28), cough (n = 12), recurrent chest colds (n = 17), and no symptoms (control subjects, n = 26), underwent allergy skin prick tests, spirometry, hypertonic saline inhalation challenge, and sputum induction, and then completed a peak expiratory flow (PEF) and symptoms diary over a 2-mo period. Children with wheeze had significantly reduced PEF (p = 0.001) and higher sputum eosinophils when compared with the cough, chest cold, and control groups (3.1% versus 0.5%, 0%, 0%; p = 0.03). The prevalence of eosinophilic bronchitis (sputum eosinophils > 2.5%) was 45% in the wheeze group, which was significantly higher than the control group (9.35%, p = 0.04). Eosinophilic bronchitis was present in two children with cough (20%) and two with chest colds (15%, p > 0.05 versus control). In these groups, eosinophilic bronchitis was not associated with airway hyperresponsiveness (AHR) to hypertonic saline (p > 0.05). Children with cough and chest colds reported greater exposure to environmental tobacco smoke. In conclusion, this community-based survey of children with chronic respiratory symptoms has shown that wheeze is a good discriminator for the presence of eosinophilic bronchitis, and that persistent cough and recurrent chest colds without wheeze should not be considered a variant of asthma. Eosinophilic bronchitis did occur in a significant minority of these "variant asthma" syndromes.
Permeability characteristics of the guinea pig biliary apparatus†
Authors: Nicola Tavoloni, Herman R. Wyssbrod, Mary Jane T. Jones
Journal: Hepatology (1986)

To determine the mechanism and pathway of entry of polar nonelectrolytes into bile, we studied first the permeation of [3H]H2O, [14C]urea, [14C]erythritol, [14C]mannitol, [3H]sucrose, [3H]inulin and [3H]dextran across an isolated, in situ perfused segment of the guinea pig's extrahepatic bile duct. All of these molecules, except [3H]dextran, permeated the bile duct. The diffusive permeability coefficients (cm per sec per 10(6) ranged from 248 for [3H]H2O to 1.2 for [3H]inulin. On the basis of these results, we formulated two models of solute biliary excretion. In Model I, permeation across both the canaliculus and ductule/duct was assumed to be by simple diffusion. In Model II, solute was assumed to enter the canaliculus by convection and diffusion, and the ductule/duct by diffusion. Reflection coefficients and/or permeability coefficients for the canalicular membrane were then determined by fitting the equations describing these processes to the bile-to-plasma ratios of [14C] erythritol, [14C]mannitol, [3H]sucrose and [3H]inulin observed at different rates of bile flow produced by partially clamping the bile duct cannula and subsequently infusing taurodehydrocholate. Only when convection was included as a mechanism of canalicular permeation (Model II) was excellent fitting observed. In such a case, the reflection coefficients and permeability coefficients for the carbohydrates in question were similar to those reported for other transporting epithelia. Cholestasis produced by taurolithocholate (10 to 40 mumoles per kg, i.v.) was associated with an irreversible increase in both the sieving coefficient and permeability coefficient for [3H]sucrose and [3H]inulin, even when the inhibition of bile flow was fully reversible. The permeability to [14C] erythritol and [14C]mannitol was either not affected or minimally increased. These findings suggest that, in the guinea pig: solutes as large as [3H]inulin enter the biliary tree both at the canaliculus and bile ductule/duct; [14C]erythritol and [14C]mannitol gain access into the canalicular lumen primarily by convection, whereas [3H]sucrose and [3H]inulin permeate mainly by diffusion; distal permeation of these carbohydrates is small, and accounts for 1 to 11% of their total biliary entry; the canalicular membrane permeability to [3H]sucrose and [3H]inulin is not functionally important in bile secretion, and a fraction of canalicular bile flows through the transjunctional shunt pathway.
Part time consultants scheme
Authors: J Cumberlege
Journal: BMJ (1994)

EDITOR, - Anne Edwards's letter contains several misunderstandings about the part time consultants scheme.1 As the scheme is centrally funded by the Department of Health bids could not be invited until the availability of funds was assured, and government accounting does not allow funds made available for a particular year to be carried forward. Nevertheless, every effort was made to ensure that as much of the funding as possible was available for use. The executive letter announcing the scheme was issued on 30 April 1993 and bids were invited by …
Pulmonary edema induced by phagocytosing neutrophils. Protective effect of monoclonal antibody against phagocyte CD18 integrin.
Authors: R A Kaslovsky, M J Horgan, H Lum, B K McCandless, N Gilboa, S D Wright, A B Malik
Journal: Circulation Research (1990)

We studied the changes in pulmonary hemodynamics and lung wet weight induced with opsonized zymosan (OZ) in isolated guinea pig lungs perfused with Ringer-albumin solution containing neutrophils (PMNs). Addition of OZ to the PMN-perfused lungs caused pulmonary vasoconstriction and weight gain; neither OZ nor PMNs added individually to the perfusate altered pulmonary vasomotor tone or wet weight. The steady gain in lung weight by 1,588 +/- 464 mg over the 45-minute study period was associated with pulmonary capillary hypertension and an increase in the capillary filtration coefficient, indicative of increased lung vascular permeability. These responses may not be due to generation of oxygen radicals, because the alterations in pulmonary hemodynamics and lung weight were not reduced by addition of superoxide dismutase, catalase, or superoxide dismutase plus catalase. We examined the basis of the PMN-mediated effects by layering PMNs on bovine pulmonary artery endothelial monolayers. Challenge with OZ resulted in increased endothelial permeability to 125I-albumin. The monoclonal antibody IB4 (directed against CD18, the common beta-subunit of structurally related adhesion receptors on phagocytes, LFA-1, Mac-1, and P150,95) prevented the OZ-mediated increase in PMN adherence to endothelial cells and the increase in endothelial permeability to 125I-albumin. IB4 also inhibited the lung weight gain mediated by the OZ-stimulated PMNs in intact lungs. The protective effect of IB4 could be ascribed neither to inhibition of uptake of OZ by PMNs nor to inhibition of release of oxygen radicals, myeloperoxidase, and elastase.(ABSTRACT TRUNCATED AT 250 WORDS)