tbuckley/cabot-search huggingface dataset:
Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study
Authors: Jeppe Frederiksen, Klaus Juul, Peer Grande, Gorm B. Jensen, Torben V. Schroeder, Anne Tybjærg-Hansen, Børge G. Nordestgaard
Journal: Blood (2004)
Letter: Disodium cromoglycate and DNA-ase in treatment of bronchial asthma.
Authors: A A Demin
Journal: BMJ (1976)

the convulsion rate.No such evidence has been published, and indeed in Thorn's paper the recurrence rate was 12 00% in those with mean serum phenobarbitone levels over 61 umol (14 mg)/l and 12 80o in those with lesser concentrations.Further, we do not like the concept that some children may be protected by phenobarbitone and others not, without evidence that we were treating two types of patient.Even if there is a reduction in febrile convulsion recurrence rates on phenobarbitone the cost must be counted.There is no evidence that the risk of later recurrent afebrile seizures ("epilepsy") is reduced,6 while the incidence of adverse effects is unacceptably high, even at lower blood concentrations.3Although a recent publication7 indicates that sodium valproate may reduce the recur- rence rate of febrile convulsions without the side effects often associated with phenobarbitone, we must reiterate our point that the really serious complication, febrile status epilepticus, usually occurs with the first convulsion.The resultant brain damage must be prevented by a research-based country- wide emergency treatment service.In this field there is much anecdotal but little scientific evidence.Recommendations include paraldehyde, parenteral phenobarbitone, fever reduc- tion, and diazepam intravenously, rectally, or intramuscularly with hyalase, chlormethiazole, and lignocaine.If other authors do have clear evidence of the relative value of one or other therapy or management of febrile status, then we and many of your readers would like to know where this evidence is to be found.
Incidence of HIV-1 infection in a rural region of Uganda
Authors: M J Wawer, N K Sewankambo, S Berkley, D Serwadda, S D Musgrave, H R Gray, M Musagara, Y R Stallings, K J Konde-Lule
Journal: BMJ (1994)

<h3>Abstract</h3> <b>Objective</b> : To determine the incidence of infection with HIV-1 and the risk factors associated with seroconversion in three geographical strata of a rural Ugandan district. <b>Design</b> : Serological, sociodemographic, and behavioural surveys of everyone aged 13 or more in 21 randomly selected communities at baseline and 20 one year later. <b>Setting</b> : Rural population of Rakai district, south-western Uganda, residing in main road trading centres, secondary trading villages, and agricultural villages. <b>Subjects</b> : In 1989, 1292 adults provided a blood sample and interview data; one year later, 778 survivors (77%) who had been seronegative at baseline provided follow up data. <b>Main outcome measures</b> : Incidence of HIV infection in relation to individual characteristics and risk factors, including place of residence. <b>Results</b> : Incidence of HIV infection in all adults was 2.1/100 person years of observation (SE 0.5 (95% confidence interval 1.1 to 3.1)); in people aged 15-39 the incidence was 3.2/100 person years. Incidence was highest in men and women aged 20-24 (9.2/100 person years (3.9) and 6.8/100 person years (2.9) respectively). Risk factors significantly associated with seroconversion were age 24 and under and two or more sexual partners. Between the surveys the proportion of all respondents reporting high risk behaviour (two or more partners) significantly increased from 8.9% to 12.3%. <b>Conclusions</b> : Despite preventive programmes and substantial knowledge about AIDS the incidence of HIV infection remains high in this rural population. Prevention aimed at vulnerable rural communities is urgently needed to contain the HIV epidemic.
Quantitative aspects of chemical carcinogenesis and tumor promotion in liver.
Authors: H W Kunz, H A Tennekes, R E Port, M Schwartz, D Lorke, G Schaude
Journal: Environmental Health Perspectives (1983)

Chronic exposure of rodents to high dose levels of drugs, food additives and environmental chemicals frequently results in liver enlargement. Several of these compounds have been found to enhance the incidence of liver tumors in animals briefly exposed previously to hepatocarcinogens. Accordingly, it has been advanced that these agents act as tumor promoters. This contention has remained subject of controversy following reports that these substances may also cause liver tumors in noncarcinogen-treated rodents, particularly in those characterized by a relatively high incidence of "spontaneous" liver tumors. Since many of these chemicals are in common use, a crucial question would seem to be whether such effects are due to facilitation of the expression of pre-existing oncogenic potential, i.e., to tumor promotion, or to the synergistic action of weakly carcinogenic agents. As a result of mechanistic differences tumor promotion and syn-carcinogenesis must exhibit different dose-time-response characteristics, and, accordingly, it should be possible, in principle, to discriminate between these phenomena. However, since tumor manifestation periods in low-dose groups frequently exceed the animals average lifespan, this approach may not always yield conclusive data, unless a sensitive early marker of carcinogenic activity can be employed. There is evidence that enzyme-deficient preneoplastic areas in liver can be used for this purpose. A strong quantitative correlation between carcinogen dose, the extent of ATPase deficient areas, and the subsequent appearance of tumors has now been established for a number of hepatocarcinogens. Experimental data are consistent with the concept that two critical events (hits) are required for induction of ATPase deficiency in hepatocytes. The first hit is carcinogen-dependent, whereas the second hit would seem to be due to time-dependent event(s). Tumor-promoters, such as phenobarbital, were found to accelerate and increase formation of preneoplastic islets. This evidence, together with data indicating that the compound is devoid of carcinogenic potential, suggests that phenobarbital may be operative at relatively early stages of hepatocarcinogenesis by increasing the probability of the occurrence of the time-dependent second hit. Such effects are dose-dependent and appear to be related to the induction of liver enlargement. The changes in hepatocellular ploidy status and atypical nuclear figures observed during phenobarbital treatment and cessation thereof, suggest that this compound might induce abnormal redistributions of genetic material. It is postulated that these cytological changes may result in phenotypical manifestation of recessive oncogenic information.
Elevated Serum Levels of Estrogen and Prolactin in Daughters of Patients with Breast Cancer
Authors: Brian E. Henderson, Veeba Gerkins, Iris Rosario, John Casagrande, Malcolm C. Pike
Journal: New England Journal of Medicine (1975)

Demographic risk factors In sisters and daughters of 150 patients with breast cancer were compared to those of controls. Plasma hormone levels in 36 teen-age daughters of patients and 31 controls were also studied to ascertain whether an "abnormal" hormone pattern underlies these risk factors. The patients' sisters had, on the average, menarche four months earlier and first full-term pregnancy 12 months later than the controls. The patients' daughters did not show these differences — apparently owing to low fertility in the patients with early menarche. The patients' daughters had higher 22d-day estradiol-plus-estrone levels than controls (24.4 vs. 19.1 ng per 100 ml, P <0.05). Sixth-day prolactin was also elevated (19.0 vs. 14.2 ng per 100 ml, P <0.05). About half the patients' daughters could clearly be distinguished from the controls' daughters by means of the sixth-day information on both estrogens and prolactin. Hypersecretion of these hormones may be important factors in breast cancer. (N Engl J Med 293:790–795, 1975)
The Learning Curve
Authors: Robert Matz
Journal: JAMA (1994)

To the Editor.  —The article1and Editorial2regarding The Learning Curve raises an issue with which all physicians and institutions are wrestling.  However, there is an even more vexing concern out there. Namely, for the many complex (and not so complex) procedures learned in the past, how many need to be successfully done and over what period of time to maintain skills and credentialing? Should it be once credentialed, always credentialed?  This is the other side of the learning curve—the retention curve—and it may prove an even tougher nut to crack!
A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis
Authors: Arun J. Sanyal, Pouneh S. Mofrad, Melissa J. Contos, Carol Sargeant, Velimir A. Luketic, Richard K. Sterling, R. Todd Stravitz, Mitchell L. Shiffman, John Clore, Alan S. Mills
Journal: Clinical Gastroenterology and Hepatology (2004)
Jaundice during cyproheptadine treatment.
Authors: D A Henry, J M Lowe, T Donnelly
Journal: BMJ (1978)

Jaundice during cyproheptadine treatmentCyproheptadine is a potent antagonist of histamine and serotonin and is widelv used as an appetite stimulant, for symptomatic relief of pruritus, and in Cushing's syndrome.'Although it has a similar structure to the phenothiazine antihistamines (see fig), we know of no previous reports of jaundice attributable to the drug. Case reportA 25-vear-old Iraqi woman had had intermittent pruritus for several years.In October 1975, while temporarily resident in the United Kingdom, symptoms recurred and she consulted one of us (TD).She had received no drug treatment except for oral contraceptives, which had been discontinued one year previously for non-medical reasons.No clinical abnormality was detected and cyproheptadine hydrochloride (Periactin) 12 mg day was prescribed.In November 1975, one month after starting the drug, she developed right upper abdominal discomfort and jaundice with pale stools and darkened urine.The liver was non-tender and enlarged 2 cm, and the spleen was impalpable.Liver function tests confirmed cholestatic jaundice: serum bilirubin 112 Mumol 1 (6 5 mg 100 ml); serum aspartate transaminase (SGOT) 107 U 1; serum alanine transaminase (SGPT) 210 Ull; serum alkaline phosphatase 2400 U 1 (normal range for our laboratory 80-280 U/1).Cyproheptadine was discontinued and chlorpheniramine (Piriton) 16 mg/day substituted.One month later she was still jaundiced, though the liver was impalpable.Serum bilirubin was 130 kmol 1 (7 6 mg 100 ml); SGOT 120 U 1; SGPT 201 U 1; and alkaline phosphatase 418 U 1. Coagulation
Skipped exon in<i>COL7A1</i>determines the clinical phenotypes of dystrophic epidermolysis bullosa
Authors: E. Toyonaga, W. Nishie, M. Komine, S. Murata, S. Shinkuma, K. Natsuga, H. Nakamura, M. Ohtsuki, H. Shimizu
Journal: British Journal of Dermatology (2014)

Fig S1. A schematic of COL7A1 shows the database of exon skipping in COL7A1 that results in recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Exons 1–28 encode the NC-1 domain, exons 29–112 encode the triple-helical domain and exons 112–118 encode the NC-2 domain. Those above the COL7A1 schema represent DDEB, whereas those below it represent RDEB. RDEB-sev gen, RDEB severe generalized (previously called Hallopeau–Siemens); REDB-lo, RDEB localized; RDEB-o, RDEB other; RDEB-pt, RDEB pretibial; RDEB-ac, RDEB acral; DDEB-pr, DDEB pruriginosa; DDEB-pt, DDEB pretibial. Table S1. Most of the dominant dystrophic epidermolysis bullosa (DDEB) that was caused by exon skipping presented a pruriginosa phenotype. Table S2. Exon-skipping mutations in the COL7A1 of patients with recessive dystrophic epidermolysis bullosa (RDEB) are found both in the collagenous and the noncollagenous domains. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
New anti-asthma therapies: suppression of the effect of interleukin (IL)‐4 and IL‐5
Authors: J.C. Kips, K.G. Tournoy, R.A. Pauwels
Journal: European Respiratory Journal (2001)

Asthma is currently defined as a chronic inflammatory disorder of the airways. The central role of allergen-specific Th2 cells in the regulation of this mucosal airway inflammation has been highlighted. Hence, there is large interest in the therapeutic potential of an anti-Th2 cell approach. One of the strategies which has been developed, is to inhibit the effect of interleukin (IL)-4 or IL-5, two main Th2 cell derived cytokines. Interleukin-4 is pivotal in the pathogenesis of allergic disorders through its wide range of effects. An important observation, especially during secondary antigen exposure, is the possible redundancy with IL-13. Both cytokines share common elements in their receptor and intracellular signalling pathway. As a result, compounds can be developed that selectively inhibit the effect of either IL-4 or IL-13, or alternatively, by interfering with the common pathway, inhibit the effect of both cytokines. Eosinophils are generally seen as a particularly harmful element in the allergic inflammation. The importance of IL-5 on eosinophil biology has clearly been established. Conversely, in man, the biological effects of IL-5 are largely limited to eosinophil function. Therefore, IL-5 antagonists offer the unique opportunity of selectively neutralizing the effect of eosinophils. Several strategies have now been developed that successfully inhibit the biological effect of interleukin-4 or interleukin-5. Some of these compounds have proven to be biologically active in man. The challenge now is to establish their therapeutic role in asthma.
Proposals to charge migrants for NHS care are unworkable, says BMA
Authors: G. Iacobucci
Journal: BMJ (2013)

The UK government’s plans to charge migrants and short term visitors to use the NHS are fraught with problems and risk damaging the NHS, the BMA has warned.

The government recently outlined plans to make temporary residents from outside of the European Economic Area (EEA) contribute to the cost of their healthcare and end free access to primary care for all visitors and tourists.1

But in its response to a consultation on the plans the BMA said that the changes would be burdensome to enforce, uneconomic, and could lead to doctor shortages if skilled migrants were dissuaded from coming to work in the United Kingdom.2

It also warned of public health risks if migrants were deterred from using the NHS and urged the government to instead focus on making improvements within the current …
Postural hypotension in elderly patients given carvedilol
Authors: H Krum, E L Conway, J H Broadbear, L G Howes, W J Louis
Journal: BMJ (1994)

and early afternoon.4As suicide and attempted suicide have different psychological causes and epidemiological risk factors, these data support the hypothesis that chronobiologically determined changes influence suicidal behaviour.The acrophases of important biological variables such as temperature, heart rate, and cortisol secretion vary in people with affective disorders compared with control subjects and may affect behaviour in addition to diurnal changes in mood and social activities.Increased adrenergic activity and lowered serotoninergic activity5 in the afternoon might play a part in mood changes.It could also be argued, however, that people who attempt suicide by minor self poisoning often do not want to die and their cry for help is more likely to be heard in the hours of the day when social and psychiatric services are available.In conclusion, a specific temporal risk, defined as the point of confluence of many factors (hormonal, environmental, and behavioural), probably plays a part in suicidal behaviour.Treatment of depressive disorders might therefore be improved by aiming for peak drug concentrations at vulnerable times.
Diethylstilbestrol increases risk of breast cancer death
Authors: Roger Dobson
Journal: BMJ (2006)

Women who took the drug diethylstilbestrol during pregnancy have an increased risk of death from breast cancer ( British Journal of Cancer 2006;95:107-11).

Results from the largest study to date of mortality outcomes in women who were exposed to the drug also show increased mortality from all causes. Diethylstilbestrol is a powerful non-steroidal oestrogen that was used to prevent pregnancy loss and complications for almost 30 years.

The highest rates of breast cancer mortality were in women who had been in clinical trial with the drug and …
Mechanisms of Gene Evolution
Authors: Philip Leder
Journal: JAMA (1982)

<h3>The Underlying Thread</h3> The evolutionary continuity of all organisms, including man, is plainly read in the continuity of biochemical and molecular processes in all living things. The fundamental threads of organization and of structure are seen again and again. Fundamental processes in simple bacteria, yeasts, or algae are the same fundamental processes that occur in man. The genetic code is virtually unchanged from<i>Escherichia coli</i>to man. The DNA molecule that incorporates genetic information is the same molecule, based on the same biochemistry, in the simplest and in the most complex organisms. The differences that exist between the species are written in the sequences of nucleotides that encode their genes, but the language in which the sequences are written and the biochemical properties of their cells are very similar. The paths of evolution can be easily traced today in the DNA of living organisms. As a molecular geneticist, I view
Surveillance and management of all types of <i>Staphylococcus aureus</i> bacteraemia
Authors: John Paul
Journal: BMJ (2006)

Electrogenic (Cl-) secretion was measured as the short circuit current (Isc, microA/cm2) across muscle-stripped sheets of jejunum and ileum incubated in vitro after removal from fed rats, rats starved for three days, and chronically undernourished rats (50% of fed control intake for 21 days). Concentration and Isc response curves for serially-added mucosal Escherichia coli STa enterotoxin showed that the rats which had undergone dietary deprivation had a larger secretory Isc maximum but the ED50 values were unchanged compared with fed animals. In fed intestine the action of STa was transient, with an Isc peak and subsequent decay to the baseline over 60 minutes but in the undernourished intestine the response consisted of a significantly greater peak than that of the fed state (jejunum = 94%; ileum = 168%) and the Isc was maintained at or near the peak for at least 60 minutes. The starved intestine had a less well developed maintenance of its enhanced peak Isc. Serosal tetrodotoxin (1 microM) had no effect on the initial peak Isc values but caused a decay of the maintained Isc down to the basal or fed levels in the starved and, especially, in the undernourished intestines. Thus, dietary deprivation, especially chronic undernutrition, enhances the maximum electrogenic secretion due to STa and creates a new neural path in the submucosal plexus that, when activated by STa, maintains its enhanced secretory action. Its putative role in exacerbating secretory diarrhoea in malnourished human subjects could be an important component underlying the known relation between malnourishment and the increased severity of diarrhoea.
Ads: The new NHS smoking campaign
Authors: J. Foulds
Journal: BMJ (2000)

The UK government's 1998 white paper on tobacco promised that £60m would be spent over three years to set up smoking cessation services in the NHS and that these services would be backed up by an advertising campaign. The campaign—“Don't give up giving up”—was launched in December 1999. This initial £5m media campaign comprises posters and six weeks of television advertising; it offers tips on giving up, testimonials from people with smoking related diseases, and a video diary of nicotine addicts trying to quit. All the advertisements feature genuine smokers: there is not an actor in sight.

The testimonials are particularly powerful. It would be surprising if the story of a 43 year old woman who died of lung cancer three weeks after filming didn't prompt many smokers to think again. The video diaries provide a day by day account of smokers' efforts to quit. They seem partly to …
Use of Gene Signatures to Improve Risk Estimation in Cancer
Authors: Chiang-Ching Huang
Journal: JAMA (2008)

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WHO accused of stifling debate about infant feeding
Authors: A. Ferriman
Journal: BMJ (2000)

International specialists in infant feeding expressed concern that the policy of WHO of establishing partnerships with private industry has gone too far, with the result that debate about the infant food industry's role in marketing breast milk substitutes is being stifled. Specialists, who want the WHO to recommend exclusive breast-feeding to babies up to 6 months, claim that at a recent joint meeting on infant feeding they were prevented from discussing the issue. In addition, some papers intended for the meeting were edited so that they were less critical to the infant food industry. Although 20 of the 28 consultants signed a statement saying that scientific evidence was now sufficient to warrant changing of the current WHO recommendation on the introduction of complementary feeding from age 4-6 months to about 6 months, no discussion was allowed. In response, a spokesman for the WHO stated that the current recommendation of WHO on the duration of exclusive breast-feeding was excluded in the discussion because of the WHO¿s research that is under way in this connection. As far as the alleged censorship of the background papers is concerned, he explained that WHO documents have to conform to a high standard of scientific objectivity and balance. Lastly, WHO cited that the food industry continues to play an important and constructive role in relation to infant feeding.