tbuckley/cabot-search huggingface dataset:
An Additional Basic Science for Clinical Medicine: II. The Limitations of Randomized Trials
Authors: ALVAN R. FEINSTEIN
Journal: Annals of Internal Medicine (1983)

Although highly successful in investigating remedial therapy, randomized clinical trials have sometimes created rather than clarified controversy when the treatments were given for the complex problems involved in studying either the primary prevention of disease or the secondary prevention of adverse progression for an established disease. Another source of difficulty has been the inevitable conflicts created by two legitimate and justifiable but opposing policies regarding the fastidious or pragmatic goals of the trials. These problems limit the scope of clinical questions that can be answered successfully by randomized trials, but other limitations are produced by problems in logistics or ethics. Randomized trials are unfeasible for studying multiple therapeutic candidates, minor changes in therapy, "instabilities" due to rapid technologic improvements in available treatment, long-term adverse effects, studies of etiologic or other suspected "noxious" agents, and the diverse clinical roles of diagnostic technology. Consequently, despite the magnificent scientific achievements of randomized clinical trials, the foundation for a basic science of patient care will also require major attention to the events and observations that occur in the ordinary circumstances of clinical practice.
Corrigendum to: “Reply from Authors re: Christian Doehn. Immunotherapy of Prostate Cancer. Eur Urol 2008;53:681–3” [Eur Urol 2008;53:684–5]
Authors: Andrea Kiessling, Susanne Füssel, Rebekka Wehner, Michael Bachmann, Manfred P. Wirth, E. Peter Rieber, Marc Schmitz
Journal: European Urology (2008)
Mutant Prpf31 causes pre-mRNA splicing defects and rod photoreceptor cell degeneration in a zebrafish model for Retinitis pigmentosa
Authors: Jun Yin, Jan Brocher, Utz Fischer, Christoph Winkler
Journal: Molecular Neurodegeneration (2011)

Abstract Background Retinitis pigmentosa (RP) is an inherited eye disease characterized by the progressive degeneration of rod photoreceptor cells. Mutations in pre-mRNA splicing factors including PRPF31 have been identified as cause for RP, raising the question how mutations in general factors lead to tissue specific defects. Results We have recently shown that the zebrafish serves as an excellent model allowing the recapitulation of key events of RP. Here we use this model to investigate two pathogenic mutations in PRPF31 , SP117 and AD5, causing the autosomal dominant form of RP. We show that SP117 leads to an unstable protein that is mislocalized to the rod cytoplasm. Importantly, its overexpression does not result in photoreceptor degeneration suggesting haploinsufficiency as the underlying cause in human RP patients carrying SP117. In contrast, overexpression of AD5 results in embryonic lethality, which can be rescued by wild-type Prpf31. Transgenic retina-specific expression of AD5 reveals that stable AD5 protein is initially localized in the nucleus but later found in the cytoplasm concurrent with progressing rod outer segment degeneration and apoptosis. Importantly, we show for the first time in vivo that retinal transcripts are wrongly spliced in adult transgenic retinas expressing AD5 and exhibiting increased apoptosis in rod photoreceptors. Conclusion Our data suggest that distinct mutations in Prpf31 can lead to photoreceptor degeneration through different mechanisms, by haploinsufficiency or dominant-negative effects. Analyzing the AD5 effects in our animal model in vivo , our data imply that aberrant splicing of distinct retinal transcripts contributes to the observed retina defects.
Parallel reasoning in structured connectionist networks: Signatures versus temporal synchrony
Authors: Trent E. Lange, Michael G. Dyer
Journal: Behavioral and Brain Sciences (1996)

Shastri &amp; Ajjanagadde (1993) (S&amp;A) argue convincingly that both structured connectionist networks and parallel dynamic inferencing are necessary for reflexive reasoning - a kind of inferencing and reasoning that occurs rapidly, spontaneously, and without conscious effort, and which seems necessary for everyday tasks such as natural language understanding. As S&amp;A describe, reflexive reasoning requires a solution to the dynamic binding problem , that is, how to encode systematic and abstract knowledge and instantiate it in specific situations to draw appropriate inferences. Although symbolic artificial intelligence systems trivially solve the dynamic binding problem using computers' registers and pointers, it has remained a difficult problem for connectionist systems (see Fodor &amp; Pylyshyn 1988). S&amp;A's temporal synchrony solution to the dynamic binding problem using synchronous firing of argument units and the entities that are bound to them illustrates one way in which connectionist networks can do thisusing a constrained but important class of long-term knowledge rules. Their structured connectionist solution allows dynamic inferencing to proceed in parallel and therefore has a number of advantages for reflexive reasoning over most other connectionist and symbolic systems.
AN EXPERIMENTAL STUDY OF OPSONIC IMMUNITY TO STAPHYLOCOCCUS AUREUS
Authors: J. C. Meakins
Journal: The Journal of Experimental Medicine (1910)

1. The administration of Staphylococcus aureus, killed by heat (vaccine), produces a high degree of opsonic immunity in rabbits. 2. Such increase of opsonin affords protection against living virulent staphylococcus in direct proportion to the amount of opsonins present in the serum and complete recovery may follow subsequent inoculation, if the opsonic power be high. 3. Frequent administration of vaccines may produce a diminution of the opsonic power of the serum. 4. Immune opsonins are most active against the homologous strain of Staphylococcus aureus, but are only slightly less active against heterologous strains. 5. Infections of the human body by Staphylococcus aureus may cause great increase of opsonins. 6. Vaccines prepared from Staphylococcus aureus may produce a high degree of opsonic immunity in man.
Hypertrophied Thyroid Tissue in a Thyroglossal Duct Remnant
Authors: IRWIN M. FEUERSTEIN, JOHN C. HARBERT
Journal: Clinical Nuclear Medicine (1986)

A 37-year-old woman was evaluated for a neck mass. This was located in the midline below the hyoid bone. Thirty-three years had elapsed since she had undergone subtotal thyroidectomy for hyperthyroidism. Eight years prior to examination, the patient had discontinued her thyroid maintenance medications. She had discovered the mass eight months prior to examination. Thyroid scan (Fig. 1) showed intense uptake in the mass. At operation the mass was attached to the midportion of the hyoid bone by a small fibrous band, as is usual in a thyroglossal duct remnant. Biopsy results showed diffuse thyroid hyperplasia. Thyroglossal duct remnants are known to harbor cysts or thyroid carcinoma, but growths of compensatory hyperplastic tissue are unusual.
Rotavirus vaccine could prevent thousands of deaths a year in India, study finds
Authors: S. Bagcchi
Journal: BMJ (2014)

Introducing a rotavirus vaccine to India’s national vaccination programme could prevent around 27 000 deaths a year from rotavirus gastroenteritis, a new study has indicated. The vaccine would also substantially reduce numbers of outpatient visits and admissions to hospital each year for rotaviral diarrhoea, the study concluded.1

Published online on 2 August in Vaccine , the study, led by Jacob John of Christian Medical College, Vellore, noted that acute gastroenteritis was a leading cause …
Hookworm Infection in Great Britain
Authors: H. G. Jenkins
Journal: BMJ (1965)

heights of children of parents whose mean height was 69.5 in.-that is, above average stature.In the frequency series 1, 16, 4, 17, 27, 20, 33, 25, 20, 11, 4, 5, which he quotes, there are three prominent peaks.These he ignores, saying no one has paid any attention to them, that such variation is " natural with such small numbers " (actually the chance of this being so is less than 1: 100), and possibly because they were not what he was looking for.I contend that he should have been look- ing for multimodality, and in 1963 I tested this contention on the heights of 760 univer- sity students and their parents.The results, which supported the view put forward here, were published in the Lancet' in a column adjacent to a letter from Sir George and under the same heading.It is interesting that these results find no place in his recent lecture and bibliography.
Risk of hepatitis B virus infection in patients with eczema or psoriasis of the hand.
Authors: V Guadagnino, F Ayala, A Chirianni, L Picciotto, D Tiseo, M Piazza
Journal: BMJ (1982)

A month later he was readmitted complaining of fever, malaise, and lethargy.Intravenous pyelography disclosed a non-functioning left kidney, and retrograde studies on the left side showed a stricture of the ureter at the level of L4.Laparotomy confirmed continued blockage of the ureter by dense fibrous tissue and also a small abscess at the site of the T-tube ureterostomy.Left nephrectomy was performed.Histological examination of the kidney showed severe acute pyelonephritis secondary to ureteric obstruction.This was considered to be a complication of the T-tube ureterostomy.
Herman W. Mudgett alias H. H. Holmes.
Authors: John Madden
Journal: JAMA (1896)

Milwaukee, Wis., Aug. 20, 1896. The article of Dr. Eugene S. Talbot in ourJournalfor August 1, reminds me that I may say something about Holmes which may be of interest to members of the medical profession. Holmes was a member of my class, which graduated in 1884, and he received his degree of Doctor of Medicine with the other successful members. A few failed in their examinations but Holmes was not among them. I was not intimately acquainted with him but knew him as well as I did any member of the class, excepting my immediate associates. What manner of man he was I remember distinctly and as distinctly recall several conversations I had with him. Holmes was a mild-mannered young man, with a diffident air, possessing no characteristics in any direction which would attract attention. He evidently had not much in the way of pecuniary means, for
Treatment with cimetidine of atypical fasciitis panniculitis syndrome.
Authors: J.E Naschitz, D Yeshurun, I Rosner, J.E Abrahamson, I Misselevitch, J.H Boss
Journal: Annals of the Rheumatic Diseases (1990)

Three patients presented with septal fasciitis and panniculitis, associated with clinical and laboratory features which precluded straight-forward classification into eosinophilic fasciitis, localised scleroderma, or lupus erythematosus profundus. Treatment with cimetidine caused the remission of cutaneous manifestations and the extracutaneous abnormalities, such as nailfold capillary disturbances and the presence of antithyroid antibodies, improved. It is concluded that features of eosinophilic fasciitis or localised scleroderma and certain additional atypical elements should be categorised as atypical fasciitis-panniculitis syndrome.
Association of B. coli Infection and Rheumatoid Arthritis
Authors: G. Slot, P. M. Deville
Journal: BMJ (1936)

NS{z similar to those of the cases now under medical care."-Thismortality must-have conmrenced sub- sequent to the journey of the first case and his medical attendant.Thereafter the epidemic assumed greater proportions, so that up to October 12th, 1911, sixty-six cases had been reported,' up to-September 30th, 1912, ninety-'three, and at the end of that year the total was 108.In 1913 the figures rose to 153, whilst at the end of 1915 there had been 240.Thereafter the epidemic 'seems to have died out gradually.A parallel instance of anepidemic directly traceable to a human carrier is afforded in an uilpublished report written in 1910 by a' German, Dr. Woolf, dealing with sleeping sickness along the valley of the Rovuma River in Tanganyika 'Territory.Early in 1910 a native, Mnyao by name, was found ill with symptoms suggestive of trypanosomiasis, a diagnosis which was later confirmed.He had come from his village at the junction of the Upper Rovuma and Sawasaru Rivers.Following the discovery of this patient numerous cases of the same disease occurred along the route on which, it was definitely ascertained, the native had travelled.In 1911 a segregation camp was established at Sawasaru -to deal with the outbreak, and between 1911 and 1913 seventy- two cases were isolated.From this area the disease spread northward, and in 1917 it had reached the hinter- land of Kilwa. ConclusionsThis case may well afford an affirmative answer to the question: Can T. brucei, occurring in areas where human trypanosomiasis is unknown, infect man?Its impor- tance lies in the fact that the spread of sleeping sickness is, in-all probability, mainly due to the movements of human carners of a strain of trypanosome which, while not immediately pathogenic, may become so after more than one passage through man.It emphasizes the need for examination *of the whole population when sleeping sickness arises apparently de novo.The investigation §hould include the examina- tion of the blood of even the apparently healthy and of material obtained by puncture of the lymph glands.Summary 1.The modern theories on the epidemiology of try- panosomiasis are reviewed.2. The existence of a reservoir host in man is emphasized.3. The case of such an individual is presented.4. The spread of sleeping sickness through the agency of a human host is described.5.The results which would follow the liberation of the case under reference are suggested.6.The location of the reservoir host is made the crucial point in the investigation of future outbreaks of this disease.The thanks of the writers are due
HLA antigens and Langerhans cell density in contact dermatitis
Authors: S.I. WHITE, P.S. FRIEDMANN, A. STRATTON
Journal: British Journal of Dermatology (1986)

Journal Article HLA antigens and Langerhans cell density in contact dermatitis Get access S.I. WHITE, S.I. WHITE University Department of Dermatology, University of Newcastle upon Tyne, U.K. Dr S.I. White, Department of Dermatology, University of Glasgow, Anderson College Building, 56 Dumbarton Road, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar P.S. FRIEDMANN, P.S. FRIEDMANN University Department of Dermatology, University of Newcastle upon Tyne, U.K. Search for other works by this author on: Oxford Academic Google Scholar A. STRATTON A. STRATTON Regional Transfusion Centre, Newcastle upon Tyne, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 115, Issue 4, 1 October 1986, Pages 447–452, https://doi.org/10.1111/j.1365-2133.1986.tb06239.x Published: 01 October 1986 Article history Accepted: 14 March 1986 Published: 01 October 1986
Cross-talk between phosphatidylinositol 3-kinase (PI3-K) and the NA+/H+ exchanger in hepatic stellate cells (HSC): effect of canrenone
Authors: A. Caligiuri, F. Marra, P. Failli, R.M.S. DeFranco, R.G. Romanelli, P. Gentilini, M. Pinzani
Journal: Journal of Hepatology (2001)
Assessment of platelet production with 75Se selenomethionine
Authors: D. G. Penington
Journal: BMJ (1969)

Incorporation of intravenously injected <sup>75</sup>Se selenomethionine into platelets has been found to vary with alterations in the rate of platelet production. It appears to label newly produced platelets during their formation in megakaryocytes and provides a method by which thrombopoiesis may be studied in vivo. This technique may be applicable to clinical studies of disordered platelet production.
Requests for cosmetic genitoplasty: how should healthcare providers respond?
Authors: Lih Mei Liao, Sarah M Creighton
Journal: BMJ (2007)

Demand for cosmetic genitoplasty is increasing. <b>Lih Mei Liao and Sarah M Creighton</b> argue that surgery carries risks and that alternative solutions to women9s concerns about the appearance of their genitals should be developed
Effects of corn oil and benzyl acetate on number and size of azaserine-induced foci in the pancreas of LEW and F344 rats.
Authors: D S Longnecker, B D Roebuck, T J Curphey, E Lhoste, C I Coon, D MacMillan
Journal: Environmental Health Perspectives (1986)

The response of LEW and F344 strain rats to the pancreatic carcinogen azaserine was compared using the size and number of azaserine-induced acidophilic acinar cell foci and nodules as parameters in a 4-month experiment. A second experiment compared the effect of corn oil intake by gavage and dietary routes on the growth of azaserine-induced pancreatic lesions in LEW rats. A third experiment tested the activity of benzyl acetate in regard to its ability to induce acinar cell foci or to promote the growth of such foci in azaserine-treated rats. The results showed that equivalent doses of azaserine induce two to seven times more foci in LEW than in F344 rats, and that LEW rats have a higher incidence of
Leprosy elimination---a virtual phenomenon or a reality?
Authors: D. N J Lockwood
Journal: BMJ (2002)

Why are evidence based policies not guiding the World Health Organization's leprosy elimination campaign, asks Diana Lockwood

Leprosy is an infectious disease but it has many features in common with neurodegenerative disorders. It results in a chronic neurological illness, which is progressive unless treated; frequently produces long term disability; and is associated with high levels of stigma. As it has a known infective agent, Mycobacterium leprae , there is the possibility of disease control. Multidrug treatment with the antibiotic combination rifampicin, dapsone, and clofazimine is highly effective in curing infection, with relapse rates of 1%.1 It was hoped that having effective antibiotics would permit disease control and thus the concept of leprosy elimination developed. “Leprosy elimination by the year 2000” was first proposed in 1986 and at the 44th World Health Assembly in 1991 modified by the addendum “as a public health problem,” defined as less than one case per 10 000 population.2 The leprosy elimination campaign has had some notable successes but also illustrates the epidemiological, medical, and political problems of the elimination concept.

#### Summary points

Leprosy is a leading cause of neurological disability

The World Health Organization's leprosy elimination campaign has treated 11 million patients, but case numbers are still rising in the major countries where leprosy is endemic

New methods for diagnosis and treatment proposed by the WHO risk missing disease and undertreating patients, and an opportunity for implementing evidence based policies may be missed

Leprosy is a complex mycobacterial disease whose manifestations and complications are determined by the immune response. Many patients experience immune mediated nerve damage, which may occur before, during, or after treatment. Recent field based cohort studies have shown that at diagnosis many patients already have established nerve damage; rates vary from 20% in Bangladesh to 56% in Ethiopia, 3 4 and these …
Use of the rendezvous technique to treat a nonhealing biliary cutaneous fistula
Authors: J. Nasr, P. Orons, A. Slivka
Journal: Endoscopy (2012)

A 32-year-old man with a history of gunshot wound to the liver was referred for management of a biliocutaneous fistula. Previously, a biloma had been drained percutaneously and an endoscopic retrograde cholangiogram (ERC) demonstrated a bile leak, which was treated with a stent. The fistula persisted despite three additional stent changes.
Identification of arthritis promoting non-obese diabetic genes in the<i>Cia9</i>locus using different genetic strategies
Authors: Dorota Klaczkowska, Diana Ekman, Rikard Holmdahl, Kutty Selva Nandakumar
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> In the gene segregation experiment between susceptible B10.Q and protective NOD.Q mice strains, two strong loci associated with collagen-induced arthritis (CIA) were found, disease-promoting locus on chromosome 1 named <i>Cia9</i> and a disease-protective locus on chromosome 2, named <i>Cia2</i>. NOD allele on <i>Cia9</i> locus promotes arthritis whereas on <i>Cia2</i> locus it inhibits arthritis development. <h3>Materials and methods</h3> The authors used both the classic congenic approach and heterogeneous stock mice to identify arthritis promoting genes in the <i>Cia9 locus.</i> The authors dissected the original <i>Cia9</i> locus into three minimal fragments namely, <i>Cia9b</i> (165–172.6 Mbp), <i>Cia9c</i> (173–175Mbp) and <i>Cia9i</i> (170.9–173.4 Mbp) by generating three congenic lines. <h3>Results</h3> Fragments <i>Cia9b</i> and <i>Cia9c</i> had no effect on CIA and collagen-antibody induced arthritis (CAIA). On the other hand, <i>Cia9i</i> fragment containing a cluster of FcγR genes promoted CIA and, CAIA induced by a monoclonal antibody cocktail containing four antibodies of γ2a and γ2b isotypes. Interestingly, IgG subclass dependency of <i>Cia9i</i> gene segment in arthritis development was ascertained using CII-specific γ2a or γ2b subclass antibodies. Furthermore, the significance of FcγR locus controlling CIA could be confirmed by analysis of the Northport heterogeneous stock cohort, a cross between eight inbred strains involving higher recombinant resolution. <h3>Conclusions</h3> The data from congenic approach and HS cross thus suggest increased susceptibility to arthritis of <i>Cia9</i> locus is due to polymorphisms in the FcγR region.
Treatment of Lung Cancer with an ALK Inhibitor After EML4-ALK Fusion Gene Detection Using Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration
Authors: Takahiro Nakajima, Hideki Kimura, Kengo Takeuchi, Manabu Soda, Hiroyuki Mano, Kazuhiro Yasufuku, Toshihiko Iizasa
Journal: Journal of Thoracic Oncology (2010)
Watchdog group says "massive lobbying effort" by medical device industry threatens public health
Authors: J. Lenzer
Journal: BMJ (2012)

A watchdog group says that the medical device industry has lavished millions of dollars on US politicians in a “massive lobbying effort” to promote legislation that will weaken oversight of the industry and endanger the public.

The charges were made on 15 February by Public Citizen, a non-profit watchdog organisation based in Washington, DC, during a Congressional hearing on the Medical Device User Fee Act. Consumer groups and industry representatives clashed during the hearing on the proposed legislation, which was hammered out after a year of negotiations between the industry and the Food and Drug Administration.

The current act will expire on 30 September. If the proposed legislation is adopted, fees paid by industry to the FDA will more than double from $287m (£180m; €215m) …