tbuckley/cabot-search huggingface dataset:
Migrants should not be forced to have TB and HIV screening
Authors: S. Mayor
Journal: BMJ (2003)

Compulsory health screening for tuberculosis and HIV infection in asylum seekers and migrants would cause more problems than it solved, argues a report published in the United Kingdom last week.

The report found that screening of migrants was likely to be ineffective and costly and might have negative consequences. It was written by the Institute for Public Policy Research, an independent think tank on social policy, in response to the UK government's current deliberations on health screening for migrants arriving in the country.

The report acknowledged that the United Kingdom was experiencing increases in tuberculosis and HIV that were associated with immigration, and that these …
Paediatric mastocytosis: a systematic review of 1747 cases
Authors: C. Méni, J. Bruneau, S. Georgin-Lavialle, L. Le Saché de Peufeilhoux, G. Damaj, S. Hadj-Rabia, S. Fraitag, P. Dubreuil, O. Hermine, C. Bodemer
Journal: British Journal of Dermatology (2015)

Paediatric mastocytosis was previously considered to be a benign and spontaneously regressing disease. However, this evolution is impossible to predict. To clarify the characteristics and course of paediatric mastocytosis, we performed a literature review of 1747 cases published between 1950 and April 2014. Lesions occurred before the age of 2 years in 90% of cases, and presented as urticaria pigmentosa (75% of cases), mastocytoma (20%) or diffuse cutaneous mastocytosis (5%). The male‐to‐female ratio was 1·4. KIT D816V mutation was detected in 34% of 215 tested patients. Clinical regression (complete or partial) occurred in 67% of cases and stabilization in 27%. However, the outcome was fatal in 2·9% of patients.
Cutaneous Sporotrichosis in Forestry Workers
Authors: Kenneth E. Powell
Journal: JAMA (1978)

In December 1975 and January and February 1976, an epidemic of cutaneous sporotrichosis occurred in Mississippi among forestry workers and other persons exposed to sphagnum moss used in packing pine seedlings. Seventeen cases were identified, 15 of which were from patients who had been exposed to sphagnum moss from a single source. Attack rates were significantly higher among workers exposed to this moss than among those not exposed.<i>Sporothrix schenckii</i>was cultured from the implicated batch of sphagnum moss but not from other batches. The source of contamination of the sphagnum moss that caused this epidemic and sphagnum moss associated with similar epidemics is unknown. One worker without cutaneous sporotrichosis may have had asymptomatic pulmonary sporotrichosis. (<i>JAMA</i>240:232-235, 1978)
The NEDD8-Activating Enzyme Inhibitor MLN4924 Disrupts Nucleotide Metabolism and Augments the Efficacy of Cytarabine
Authors: Steffan T. Nawrocki, Kevin R. Kelly, Peter G. Smith, Mignon Keaton, Hetty Carraway, Mikkael A. Sekeres, Jaroslaw P. Maciejewski, Jennifer S. Carew
Journal: Clinical Cancer Research (2014)

Abstract Purpose: New therapies are urgently needed for patients with acute myelogenous leukemia (AML). The novel NEDDylation inhibitor MLN4924 (pevonedistat) has demonstrated significant preclinical antileukemic activity and preliminary efficacy in patients with AML in a phase I trial. On the basis of its antimyeloid and DNA-damaging properties, we investigated the ability of MLN4924 to augment conventional cytarabine (ara-C) therapy. Experimental Design: The effects of MLN4924/ara-C on viability, clonogenic survival, apoptosis, DNA damage, and relevant pharmacodynamic targets were determined. The efficacy and pharmacodynamics of MLN4924/ara-C were assessed in an AML xenograft model. Results: Cotreatment of AML cell lines and primary patient specimens with MLN4924 and ara-C led to diminished clonogenic survival, increased apoptosis, and synergistic levels of DNA damage. RNAi demonstrated that stabilization of CDT-1, an event previously shown to mediate the DNA-damaging effects of MLN4924, was not a key regulator of sensitivity to the MLN4924/ara-C combination. Global metabolic profiling revealed that MLN4924 disrupts nucleotide metabolism and depletes intracellular nucleotide pools in AML cells. Subsequent experiments showed that MLN4924 promoted increased incorporation of ara-C into the DNA of AML cells. This effect as well as the therapeutic benefit of the MLN4924/ara-C combination was antagonized by supplementation with the nucleotide building block ribose. Coadministration of MLN4924 and ara-C to mice bearing FLT3-ITD+ AML xenografts stably inhibited disease progression and increased DNA damage in vivo. Conclusions: Our findings provide strong rationale for clinical investigation of the MLN4924/ara-C combination and establish a new link between therapeutic inhibition of NEDDylation and alterations in nucleotide metabolism. Clin Cancer Res; 21(2); 439–47. ©2014 AACR.
Infliximab in the Treatment of Crohn Disease and Type 1 Diabetes
Authors: Katharina Timper, Petr Hruz, Christoph Beglinger, Marc Y. Donath
Journal: Diabetes Care (2013)

Inhibition of tumor necrosis factor (TNF)-α is an effective treatment for Crohn disease. It is recommended as a second-line therapy in steroid-dependent or -refractory disease, although first-line treatment may improve chances of intestinal mucosal healing (1). In the context of diabetes, TNF-α has been implicated in the development of insulin resistance during obesity (2) and in autoimmune destruction of pancreatic β-cells in an animal model of type 1 diabetes (3), and a recent study demonstrated some preservation of insulin secretion in children with new-onset type 1 diabetes upon TNF-α inhibition (4).

Here, we report a case of a 29-year-old Caucasian man who was diagnosed with type 1 diabetes at the age of 27 years on the basis of rapid onset of hyperglycemia, a lean BMI of 22.7 kg/m2, signs of β-cell autoimmunity (autoantibodies to GAD 476 IU/mL [normal value <10] and islet-cell autoantibodies 125 units/mL [normal value <1.5]), and a negative family history of diabetes. Upon treatment with insulin glargine …
The hibernator heart ? Nature's model of resistance to ventricular fibrillation
Authors: B JOHANSSON
Journal: Cardiovascular Research (1996)

During hibernation animals decrease their body temperature down to a few degrees above 0 degrees C. This means that when entering into and arousing from hibernation their body temperature passes through the critical level of 20 degrees C, a temperature region where nonhibernating mammals develop circulatory arrest, usually ventricular fibrillation (VF). The hibernator heart is resistant to VF, not only induced by hypothermia, but also when induced by local application of aconitine on the epicardium, and other ways of inducing VF in nonhibernators. Several mechanisms may explain this resistance to VF of the hibernator heart. The factors of greatest importance seem to be the different adrenergic innervation pattern, the different physico-chemical properties with a lower melting point of the lipids in the hibernator, the different enzyme temperature activity curves in the hibernator and the different handling of intracellular calcium, which results in protection against calcium overload in the hibernator heart, when compared with the nonhibernator heart.
Safety of Minibikes-Reply
Authors: Lee N. Hames
Journal: JAMA (1975)

<h3>In Reply.—</h3> Mr Amidon's letter accusesThe Journal(232:55; 58, 1975) of misleading the medical community. Specifically, Mr Amidon writes that it is unfair to apply the number of minibike and motorcycle injuries and deaths in Wilmington, Del, to the country as a whole. However, had the extrapolation been made from statistics taken from areas in California, Texas, or New York, where motorcycle registrations and, presumably, the number of minibikes are highest, the extrapolation might have suggested a worse picture nationally. Mr Amidon also objects to the use of "epidemic" in describing minibike and motorcycle injuries. Perhaps, in a strict, narrow interpretation, 21 cases in Wilmington do not constitute an epidemic, a term the authors used only to emphasize a serious and rapidly growing problem. Nevertheless, in the face of a nationwide accumulation of thousands of areas such as Wilmington, Del, with deaths totaling more than 3,000 and an estimated 350,000
Inhaling heroin during pregnancy: effects on the baby
Authors: J E M Gregg, D C Davidson, A M Weindling
Journal: BMJ (1988)

margin of the umbilicus.The direction of skin splitting was vertical in all cases.Secondly, full thickness skin biopsy specimens were taken from beside the umbilical incisions of six patients (three horizontal and three vertical incisions).Routine histological sections showed that in all cases collagen was aligned vertically at the lower umbilical verge.Furthermore, when a vertical incision was made 68% fewer blood vessels were transected (means of 14-6 with vertical incisions and 46 with horizontal incisions per field at 25 objective magnification).Clinically this was shown by less bleeding after operation.
Premature termination codons in PRPF31 cause retinitis pigmentosa via haploinsufficiency due to nonsense-mediated mRNA decay
Authors: Thomas Rio Frio, Nicholas M. Wade, Adriana Ransijn, Eliot L. Berson, Jacques S. Beckmann, Carlo Rivolta
Journal: Journal of Clinical Investigation (2008)

Dominant mutations in the gene encoding the mRNA splicing factor PRPF31 cause retinitis pigmentosa, a hereditary form of retinal degeneration. Most of these mutations are characterized by DNA changes that lead to premature termination codons. We investigated 6 different PRPF31 mutations, represented by single-base substitutions or microdeletions, in cell lines derived from 9 patients with dominant retinitis pigmentosa. Five of these mutations lead to premature termination codons, and 1 leads to the skipping of exon 2. Allele-specific measurement of PRPF31 transcripts revealed a strong reduction in the expression of mutant alleles. As a consequence, total PRPF31 protein abundance was decreased, and no truncated proteins were detected. Subnuclear localization of the full-length PRPF31 that was present remained unaffected. Blocking nonsense-mediated mRNA decay significantly restored the amount of mutant PRPF31 mRNA but did not restore the synthesis of mutant proteins, even in conjunction with inhibitors of protein degradation pathways. Our results indicate that most PRPF31 mutations ultimately result in null alleles through the activation of surveillance mechanisms that inactivate mutant mRNA and, possibly, proteins. Furthermore, these data provide compelling evidence that the pathogenic effect of PRPF31 mutations is likely due to haploinsufficiency rather than to gain of function.
Transdermal delivery of levonorgestrel
Authors: David R. Friend
Journal: Medicinal Research Reviews (1991)

This review of the research and development of transdermal delivery systems for levonorgestrel and combinations of levonorgestrel and estrogens also contains explanatory material on skin structure and absorption of drugs by diffusion and partition, permeability and use of enhancers to facilitate absorption, use of pro-drugs and derivatives, and cutaneous side effects. Drug absorption entails diffusion through the lipophilic stratum corneum and the hydrophilic epidermis, and between the two layers. Diffusion of levonorgestrel is driven by the saturated solution in the medium, such as ethanol, but the rate was insufficient. The target delivery rate for levonorgestrel used alone as a contraceptive is 35 mcg/day for transdermal use, which would require a delivery rate of 0.3 mcg/sq.cm. Ethyl acetate was found to be the best "penetration enhancer," speeding absorption 17-fold in rat skin. Levonorgestrel in ethyl acetate diffused through human cadaver skin at a rate requiring a patch of 7.5 sq. cm. Use of pro-drugs and derivatives is based on the theory that even though the derivative may diffuse more slowly because of its larger size, it is more soluble in both lipophilic and hydrophilic media. The best pro-drug was levonorgestrel-glycidol, with a 32-fold increase in penetration. Pro-drugs have the drawback of requiring complete FDA approval. They are hydrolyzed in skin to the native steroid, however. The type of transdermal delivery system needed for levonorgestrel is a membrane-based patch with a reservoir. Ethylene vinyl acetate copolymer systems have been tested or rabbits and in Phase I clinical trials. The micro-reservoir systems has been marketed for estradiol in a 3.5-day patch. A similar system has been developed experimentally using levonorgestrel and estradiol combined. Most transdermal systems cause mild skin irritation in a high proportion of users, but the likelihood of contact allergy or urticaria with levonorgestrel is minimal. Development of a transderm system with levonorgestrel and ethyl acetate, which is generally recognized as safe (GRAS), would be feasible as soon as the stability of levonorgestrel in ethyl acetate is defined.
INTERMITTENT TREATMENT OF TRICHOPHYTON RUBRUM INFECTIONS WITH GRISEOFULVIN.
Authors: M. A. COWAN
Journal: British Journal of Dermatology (1960)

Journal Article INTERMITTENT TREATMENT OF TRICHOPHYTON RUBRUM INFECTIONS WITH GRISEOFULVIN. Get access M. A. COWAN, M.B., Ch.B., M.R.C.P. (Lond.). M. A. COWAN, M.B., Ch.B., M.R.C.P. (Lond.). Registrar, The Rupert Hallam Department of Dermatology, Royal Infirmary, Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 72, Issue 5, 1 May 1960, Pages 185–187, https://doi.org/10.1111/j.1365-2133.1960.tb13872.x Published: 01 May 1960
An epidemiologic study of early biologic effects of benzene in Chinese workers.
Authors: N Rothman, M T Smith, R B Hayes, G L Li, R D Irons, M Dosemeci, R Haas, W S Stillman, M Linet, L Q Xi, W E Bechtold, J Wiemels, S Campleman, L Zhang, P J Quintana, N Titenko-Holland, Y Z Wang, W Lu, P Kolachana, K B Meyer, S Yin
Journal: Environmental Health Perspectives (1996)

Benzene is a recognized hematotoxin and leukemogen, but its mechanisms of action in humans are still uncertain. To provide insight into these processes, we carried out a cross-sectional study of 44 healthy workers currently exposed to benzene (median 8-hr time-weighted average; 31 ppm), and unexposed controls in Shanghai, China. Here we provide an overview of the study results on peripheral blood cells levels and somatic cell mutation frequency measured by the glycophorin A (GPA) gene loss assay and report on peripheral cytokine levels. All peripheral blood cells levels (i.e., total white blood cells, absolute lymphocyte count, platelets, red blood cells, and hemoglobin) were decreased among exposed workers compared to controls, with the exception of the red blood cell mean corpuscular volume, which was higher among exposed subjects. In contrast, peripheral cytokine levels (interleukin-3, interleukin-6, erythropoietin, granulocyte colony-stimulating factor, tissue necrosis factor-alpha) in a subset of the most highly exposed workers (n = 11) were similar to values in controls (n = 11), suggesting that benzene does not affect these growth factor levels in peripheral blood. The GPA assay measures stem cell or precursor erythroid cell mutations expressed in peripheral red blood cells of MN heterozygous subjects, identifying NN variants, which result from loss of the GPA M allele and duplication of the N allele, and N phi variants, which arise from gene inactivation. The NN (but not N phi) GPA variant cell frequency was elevated in the exposed workers compared with controls (mean +/- SD, 13.9 +/- 8.4 mutants per million cells versus 7.4 +/- 5.2 per million cells, (respectively; p = 0.0002), suggesting that benzene produces gene-duplicating but not gene-inactivating mutations at the GPA locus in bone marrow cells of exposed humans. These findings, combined with ongoing analyses of benzene macromolecular adducts and chromosomal aberrations, will provide an opportunity to comprehensively evaluate a wide range of early biologic effects associated with benzene exposure in humans.
Identification of Risk Factors in Hypertensive Patients
Authors: François Gueyffier, Jean-Pierre Boissel, Stuart Pocock, Florent Boutitie, John Coope, Jeffrey Cutler, Tord Ekbom, Robert Fagard, Lawrence Friedman, Karla Kerlikowske, Mitchell Perry, Ronald Prineas, Eleanor Schron
Journal: Circulation (1999)

Background —Predicting individual risk is needed to target preventive interventions toward people with the highest probability of benefit over a given time period. We assessed which prognostic factors should be used in predicting risk for hypertensive patients and in searching for treatment modifiers. Methods and Results —Data from 24 390 hypertensive participants who constituted the control groups from 8 controlled trials (1726 deaths over 5 years) were analyzed in multivariate survival models. Outcomes were coronary heart disease death, stroke death, and cardiovascular death. We explored systematically the heterogeneity of results between trials. Left ventricular hypertrophy was electrocardiographically confirmed to be a powerful risk factor and should be included in risk scoring. Height, glomerular filtration rate, and serum uric acid deserve further exploration. Body mass index and heart rate were not confirmed as independent cardiovascular risk factors in this population. The association between male sex and coronary heart disease death was significantly stronger in British cohorts. The lack of prognostic value of diastolic blood pressure was explained by an interaction with age, with a positive association before 65 years and a negative association thereafter. Previous antihypertensive treatment was a significant risk factor. Conclusions —Clinical trials provide valuable information for risk prediction. Carefully exploring the heterogeneity among trials is a way to assess the generalizability of findings. This approach, if systematically performed, should increase the ability to identify risk modifiers and to predict individual therapeutic benefit.
Waldenstrom's macroglobulinaemia: three cases in shoe repairers.
Authors: L. M. Williamson, M. Greaves, J. R. Worters, C. C. Harling, J. R. Waters
Journal: BMJ (1989)

68p) and the patient (80p).The two home tests were of comparable cost to the NHS (49p for blood spots, 45p for strips).Costs ofmaterials for all three methods were similar (20p).Blood spots cost the patient 19p in postage, but strips brought to the clinic did not cost the patient anything.PC was funded by Boehringer Mannheim.We thank
TICAGRELOR VERSUS CLOPIDOGREL IN ELDERLY PATIENTS WITH ACUTE CORONARY SYNDROMES: A SUBANALYSIS FROM THE PROSPECTIVE RANDOMIZED PLATELET INHIBITION AND PATIENT OUTCOMES (PLATO) TRIAL
Authors: Steen Husted, Stefan James, Richard C. Becker, Jay Horrow, Hugo Katus, Robert F. Storey, Christopher P. Cannon, Magda Heras, Renato D. Lopes, Joao Morais, Kenneth W. Mahaffey, Richard Bach, Daniel M. Wojdyla, Lars Wallentin
Journal: Journal of the American College of Cardiology (2011)
INJURY TO THE PERINAeUM: RUPTURE OF THE URETHRA, WITH EXTRAVASATION OF URINE: WITH REMARKS
Authors: J. S. Fletcher
Journal: BMJ (1855)

ComxvuwIcATioxs for the Journal may be addressed to 87, Russell Square, s formerly, till an Editor is appointed.THz EDwTor.has not on hand a single " OrigiQal Communication" for the Journal.Members are requested to forward contributions at ouce,as by their present apathy the value of the Journal may be impaired.Letters on the York Mleeting form a thin and acid food for the many: but if nothing else be reoeived, what can we give?
Detection of urinary interleukin-8 in glomerular diseases
Authors: Takashi Wada, Hitoshi Yokoyama, Naohisa Tomosugi, Yukimasa Hisada, Satoshi Ohta, Takero Naito, Ken-ichi Kobayashi, Naofumi Mukaida, Kouji Matsushima
Journal: Kidney International (1994)
The effect of Tuftsin on the nitrous blue tetrazolium reduction of normal human polymorphonuclear leukocytes.
Authors: Z Spirer, V Zakuth, A Golander, N Bogair, M Fridkin
Journal: Journal of Clinical Investigation (1975)

The influence of Tuftsin, the synthetic phagocytosis-stimulating tetrapeptide (L-threonyl-L-lysyl-L-prolyl-L-arginine), on the nitrous blue tetrazolium (NBT) reduction by human polymorphonuclear leukocytes was investigated. It was found that this substance increases the NBT reduction by approximately as much as endotoxin. Other tetrapeptides do not share this property. When Tuftsin analogs are added to the cell suspension and incubated, they prevent the action of both Tuftsin and endotoxin but not of methylene blue. When washed of the analogs, the cells regain the property to be activated by both Tuftsin and endotoxin. It appears that methylene blue on one hand and Tuftsin and endotoxin on the other hand have different sites for their actions. We suggest that whereas methylene blue diffuses into the cell and acts directly upon the hexosemonophosphate shunt activation, Tuftsin and endotoxin appear to act on the cell membrane binding to specific receptors. By treating the cells with Tuftsin analogs, we probably block these receptors.
Patterns of intrahepatic recurrence after curative resection of hepatocellular carcinoma
Authors: Takashi Matsumata, Takashi Kanematsu, Kenji Takenaka, Yasuhiro Yoshida, Takashi Nishizaki, Keizo Sugimachi
Journal: Hepatology (1989)

Using selective angiograms of the liver, we analyzed the patterns of intrahepatic recurrence of hepatocellular carcinomas following curative surgery. In 33 patients with intrahepatic recurrences, seven patients (21%) had a recurrence near the resected hepatic stump. The remaining 26 had either a nodular recurrence in segments away from the resected margin or a widespread multinodular recurrence in the liver remnant. There was a recurrence within the first postoperative year in five of 16 patients with a nodular recurrence and in eight of 10 patients with a widespread multinodular recurrence. In these patients, particularly those with a widespread multinodular recurrence, tumor thrombi in the portal vein present before the operation and/or disseminated during operation from such an advanced main tumor seemed to be the most important and significant factor related to the early recurrence in the remnant liver. This evidence suggests that in cases of surgery for hepatocellular carcinoma it is important to establish a technique to prevent dissemination of cancer cells due to operative manipulation and also adequate adjuvant therapy rather than attempting to obtain an ample resection margin.
Individualized short-course cyclosporin therapy in psoriasis
Authors: A.F. FINZI
Journal: British Journal of Dermatology (1996)

The efficacy and side-effects of cyclosporin in psoriasis, namely hypertension and renal dysfunction, are dose-related. An initial dose of 3 mg/kg per day has a better risk/benefit ratio than 5 mg/kg per day. Maximum efficacy is usually reached after 2-3 months, and effects of the drug remain even after treatment stops. We therefore suggest that periodic short-term use of cyclosporin in order to combine persisting therapeutic effect with safety. Psoriatic erythroderma and arthropathy also respond rapidly to oral cyclosporin. Once patients have been successfully treated, the drug should be discontinued. Treatment must not exceed 6 months, but in the case of relapse a new cycle of the previously effective and tolerated dose can be given. The concomitant use of other therapies has been assessed in an attempt to reduce the dose of cyclosporin. There are no significant cyclosporin-sparing effects when etretinate or UVB are used adjunctively, and currently no convincing data on the risk of combining low-dose cyclosporin with immunosuppressive therapy (including methotrexate, UVB, and PUVA) in dermatological indications. The addition of topical corticosteroids or calcipotriol leads to more rapid clearing of psoriasis plaques, although relapse rates remain unchanged. Individualized short-course cyclosporin therapy is useful in controlling acute psoriasis flares and/or inducing remission; less potent agents can then be used for maintenance therapy. Short courses of low-dose cyclosporin may almost completely eliminate the risks of renal dysfunction from this drug.