tbuckley/cabot-search huggingface dataset:
Treatment of the carcinoid syndrome with the longacting somatostatin analogue lanreotide: a prospective study in 39 patients.
Authors: P Ruszniewski, M Ducreux, J A Chayvialle, J Blumberg, D Cloarec, H Michel, J M Raymond, J L Dupas, H Gouerou, R Jian, E Genestin, P Bernades, P Rougier
Journal: Gut (1996)

BACKGROUND: Somatostatin analogues effectively control flushing and diarrhoea in patients with the carcinoid syndrome. The octapeptide lanreotide is available in slow release form, which could eliminate the necessity of twice a day injections as with octreotide. PATIENTS AND METHODS: 39 patients with carcinoid syndrome were included in a prospective multicentre study. Patients received lanreotide 30 mg intramuscularly every 14 days for six months. The number and intensity of flushing episodes and bowel movements, urinary 5 hydroxy-indolacetic acid (5 HIAA) concentrations, and variations of tumour mass were recorded. RESULTS: After one month of treatment, flushing episodes (median (range)) decreased significantly (3 (0.3-24) episodes per day v 1 (0-15), p = 0.04) and completely resolved in 39% of the patients. A significant decrease was seen in the number of bowel movements and discomfort related to diarrhoea. Urinary 5 HIAA concentrations were unchanged in 57% of the patients and decreased in 18%. After six months of treatment, the actuarial proportions of patients with at least a 50% decrease in the number of flushing episodes and bowel movements were 54% and 56%, respectively. Forty two per cent of the patients who were treated for six months had at least a 50% reduction in 5 HIAA values. No clear signs of regression of tumours were seen in any of the patients. Lanreotide was well tolerated despite transient mild pain or erythema at the injection site in 25% of the patients. Biliary lithiasis appeared in two patients after six months of lanreotide. CONCLUSION: Lanreotide, 30 mg intramuscularly every other week, is an effective and convenient treatment in patients with the carcinoid syndrome.
Incidence of restenosis after successful coronary angioplasty: a time-related phenomenon. A quantitative angiographic study in 342 consecutive patients at 1, 2, 3, and 4 months.
Authors: P W Serruys, H E Luijten, K J Beatt, R Geuskens, P J de Feyter, M van den Brand, J H Reiber, H J ten Katen, G A van Es, P G Hugenholtz
Journal: Circulation (1988)

Data from experimental, clinical, and pathologic studies have suggested that the process of restenosis begins very early after coronary angioplasty. The present study was performed to determine prospectively the incidence of restenosis with use of the four National Heart, Lung, and Blood Institute and the 50% or greater diameter stenosis criteria, as well as a criterion based on a decrease of 0.72 mm or more in minimal luminal diameter. Patients were recatheterized at 30, 60, 90, or 120 days after successful percutaneous transluminal coronary angioplasty (PTCA). After PTCA all patients received 10 mg nifedipine three to six times a day and aspirin once a day until repeat angiography. Of 400 consecutive patients in whom PTCA was successful (less than 50% diameter stenosis), 342 underwent quantitative angiographic follow-up (86%) by use of an automated edge-detection technique. A wide variation in the incidence of restenosis was found dependent on the criterion applied. The incidence of restenosis proved to be progressive to at least the third month for all except NHLBI criterion II. At 4 months a further increase in the incidence of restenosis was observed when defined as a decrease of 0.72 mm or more in minimal luminal diameter, whereas the criteria based on percentage diameter stenosis showed a variable response. The lack of overlap between the different restenosis criteria applied affirms the arbitrary nature of angiographic definitions currently in use. Restenosis should be assessed by repeat angiography, and preferably ascertained according to the change in absolute quantitative measurements of the luminal diameter.
Bowenoid papulosis with amyloid deposition
Authors: B.K. Koh, S.T. Oh, J.Y. Lee, B.K. Cho
Journal: British Journal of Dermatology (2002)

Sir, Localized cutaneous amyloidosis may be primary, as in lichen, macular and nodular amyloidosis, or secondary to a number of skin lesions, particularly tumours. The secondary form has most commonly been reported in association with various skin lesions of epithelial origin.1 We report a Korean man who had bowenoid papulosis (BP) with amyloid deposition on the penis and scrotum. A 69‐year‐old man presented with an 8‐month history of multiple painless penile and scrotal skin lesions. He denied any preceding penile eruption such as herpes simplex or condyloma acuminatum, but had a history of prostatic carcinoma and had undergone radical prostatectomy 2 years before. He had had no sexual contacts for a few years. Physical examination revealed multiple brownish papules and patches with erosions on the penis and scrotum (Fig. 1a). No cutaneous lesions were noted on other areas including the anal mucosa. Histopathology revealed mild hyperkeratosis, epidermal hyperplasia with keratinocytes showing various degrees of cellular atypia, loss of polarity, and atypical mitoses (Fig. 1b). The papillary dermis contained a mild perivascular lymphocytic inflammatory cell infiltrate, and amorphous deposits of an eosinophilic material that stained with Congo red (Fig. 1c). A histopathological diagnosis of BP with amyloid deposition was made. A limited surgical excision for polymerase chain reaction analysis with probes specific for the DNA of human papillomavirus (HPV) types 16 and 18 showed the presence of HPV‐16. The remaining lesions were treated with liquid nitrogen, but the patient returned 1 month later with new lesions, which were treated by wide excision. There has been no recurrence for 8 months of follow‐up.
P263 Reducing Investigation Time For the Diagnosis of the Obstructive Sleep Apnoea Syndrome (OSAS) by Combining Oximetry with a Screening Algorithm
Authors: JA Benjamin
Journal: Thorax (2012)

<h3>Introduction</h3> Oximetry and limited channel sleep studies (LCSS) for the diagnosis of OSAS have sensitivities of 87% and 82–94% respectively and specificities of 65% and 82–100% respectively¹. Our centre finds oximetry useful for confirming OSAS in high probability patients but not at ruling it out. LCSS seems useful for both. The average time taken for oximetry is 15 minutes compared with 75 minutes for LCSS (times were pooled from 5 Welsh sleep centres). We proposed an investigative approach that combined a screening algorithm that would allocate high probability patients to oximetry and low probability patients to LCCS. High probability subjects with negative oximetry also proceeded to LCSS. This 2-step approach has been recently tested with a subsequent sensitivity of 97% and specificity of 87%<sup>2</sup>. The aim of our study was to assess if our interpretation of this approach reduced investigation time for the diagnosis of OSA. <h3>Methods</h3> We recruited consecutive sleep referrals over a 5 month period. A screening algorithim was employed. The following risk factors were used to score referrals(1) Snoring, Apnoea (2) Daytime somnolence (3) Hypertension, Obesity, Large neck size 0.2/3 positive factors made the referral high probability; 2/3 negative-low probability. A referral with inadequate information went straight to LCSS. A high probability patient with subsequent negative oximetry proceeded to LCSS. We compared the total and average time taken with our algorithm against a strategy (control arm) of LCSS for every patient. The study was powered for 50 patients. <h3>Results</h3> N=50. Median age 53 years, 34 were male. See figure 1 for outcomes. For the control arm, assuming every patient had LCSS, the total investigation time for the 50 patients was 3750 minutes with an average time of 75 minutes per patient. For the algorithm arm, the total time was 2715 minutes with an average time of 54.3 minutes per patient. Average time saving – 20.7 minutes per patient. <h3>Conclusion</h3> We propose that allocating high probability subjects to oximetry and using LCSS for low probability subjects and for oximetry negative high probability subjects results in significant time and resource savings. <h3>References</h3> Thorax 2005; 60 (ii):37. Thorax 2011; 66.
Castration for the Cure of Hypertrophied Prostrate
Authors: J. W. White
Journal: BMJ (1895)

THE reception by the medical profession here and elsewhere of the suggestion made by me in June, 1893, that castration might be an effectual remedy for prostatic hypertrophy has been increasingly favourable.Up to that time no reference existed in surgical literature to the possibility of affecting the overgrowth by the removal of the testes.Since then, twelve more or less successful cases have been published.It is not too much to say that, in connection with the further corroborative evidence that has been brought forward, they serve to establish the operation as a rational and justifiable procedure.I have already reviewed' the history of eight of these cases.2The other four may be briefly summarised as follows:Mayer and Haenel3 operated, May 16th, 1894, on a man about 70, with a much enlarged prostate, cystitis, and ammoniacal urine, tenesmus and toxuemia, in whom catheterism was becoming impossible on account of the pain it excited.There were several ounces of residual urine.Some improvement was noted in a few days; after two weeks the tonicity of the bladder began to return; in three weeks the urine was nearly nor- -mal; and in six weeks the prostate had shrunk to its proper dimen- -sions, the bladder emptied itself completely, no catheter being required; ,urination was performed only once in four hours, and the urine was timpid and of acid reaction.
Medicinal uses of tobacco in history
Authors: A. Charlton
Journal: Journal of the Royal Society of Medicine (2004)

The tobacco plant, Nicotiana, has probably been responsible for more deaths than any other herb. At present, tobacco smoking is causing over 3 million deaths a year worldwide, and if current smoking trends continue the annual mortality will exceed 10 million by around 2030.1 Add to this the mortality from cancers caused by oral uses and the death toll becomes still higher. Undoubtedly, tobacco is the most important avoidable cause of premature death and disease in the world.2

Tobacco leaves and the smoke generated when they are burned contain over 4 thousand chemicals,3 the best known of which is nicotine, first isolated from tobacco leaves in 1828 by Posselt and Reimann.4 It is the nicotine that causes smokers to become addicted to tobacco, and the chemical itself is lethal in small doses.5 When tobacco smoke is inhaled, the nicotine passes quickly to every organ of the body. The brain and nervous system are stimulated by small doses and depressed by larger ones.5 Nicotine increases the heart rate and the blood pressure, and may contribute directly to the excess of thrombosis and atheroma in smokers. Nevertheless, nicotine replacement therapy is used in helping people to stop smoking, because it spares them the many other harmful contents of tobacco smoke—for example, the carcinogenic polycyclic aromatic hydrocarbons and N-nitroso compounds; irritant substances such as acrolein; benzene; formaldehyde; ammonia; acetone; acetic acid, and carbon monoxide.3

The evidence that tobacco causes cardiovascular disease and lung disease took several hundred years to emerge. In the 15th century, when the use of Nicotiana by the indigenous populations in the New World was first observed by Columbus and the plant was brought to Europe, all herbs were considered to have potential therapeutic properties and this new one was used to treat a wide range of conditions. Indeed, Nicotiana acquired a reputation as a panacea, to the extent of being called the ‘holy herb’ and ‘God's remedy’.6 To understand the enthusiasm of Tudor doctors for this newly discovered herb, it is useful to look at the background.
Bmp in Podocytes Is Essential for Normal Glomerular Capillary Formation
Authors: Hiroyuki Ueda, Yoichi Miyazaki, Taiji Matsusaka, Yasunori Utsunomiya, Tetsuya Kawamura, Tatsuo Hosoya, Iekuni Ichikawa
Journal: Journal of the American Society of Nephrology (2008)

Bone morphogenetic protein (BMP) 4 exerts multiple biological effects on kidney and ureter development. To examine the role of BMP4 in glomerular morphogenesis, we generated transgenic mice with altered BMP4 function in podocytes by conferring tissue-specificity with the nephrin (Nphs1) promoter. At birth, Tg(Nphs1-Nog) mice, which had loss of BMP4 function in podocytes, were found to have glomerular microaneurysms, collapsed glomerular capillary tufts, enlarged Bowman's capsules, and fewer normal proximal tubules. Conversely, Tg(Nphs1-Bmp4) mice, which had increased BMP4 function in podocytes, demonstrated defects in glomerular capillary formation, but podocytes were not appreciably affected. The Tg(Nphs1-Nog) and Tg(Nphs1-Bmp4) mice shared morphological characteristics with the previously reported podocyte-specific Vegf-A over-expressing and knockout mice, respectively. Consistent with the morphological similarity, in situ hybridization revealed an intense signal for podocyte expression of Vegf in Tg(Nphs1-Nog) mice, whereas the signal was markedly suppressed in Tg(Nphs1-Bmp4) mice. However, in vitro studies with metanephroi failed to demonstrate a direct interaction between BMP4 or Noggin and VEGF in podocytes. Instead, immunostaining showed that phosphorylated Smads, the mediators of BMP signaling, are present in endothelial and/or mesangial cells, but not in podocytes, within the developing glomeruli. Therefore, this study suggests that podocyte-derived BMP plays an important role in glomerular capillary formation, perhaps by acting on non-podocyte glomerular cells in a paracrine fashion.
Effects of Choice Architecture and Chef-Enhanced Meals on the Selection and Consumption of Healthier School Foods
Authors: Juliana F. W. Cohen, Scott A. Richardson, Sarah A. Cluggish, Ellen Parker, Paul J. Catalano, Eric B. Rimm
Journal: JAMA Pediatrics (2015)

Little is known about the long-term effect of a chef-enhanced menu on healthier food selection and consumption in school lunchrooms. In addition, it remains unclear if extended exposure to other strategies to promote healthier foods (eg, choice architecture) also improves food selection or consumption.
Mutations in Drosophila sec15 Reveal a Function in Neuronal Targeting for a Subset of Exocyst Components
Authors: Sunil Q. Mehta, P. Robin Hiesinger, Slobodan Beronja, R. Grace Zhai, Karen L. Schulze, Patrik Verstreken, Yu Cao, Yi Zhou, Ulrich Tepass, Michael C. Crair, Hugo J. Bellen
Journal: Neuron (2005)
Signal Transduction by Cell Adhesion Receptors and the Cytoskeleton: Functions of Integrins, Cadherins, Selectins, and Immunoglobulin-Superfamily Members
Authors: R. L. Juliano
Journal: The Annual Review of Pharmacology and Toxicology (2002)

Cellular interactions with the extracellular matrix and with neighboring cells profoundly influence a variety of signaling events including those involved in mitogenesis, survival, and differentiation. Recent advances have provided insights into mechanisms underlying the ability of integrins, cadherins, selectins, and other cell adhesion molecules to regulate signal transduction cascades. These mechanisms often involve the ability of cell adhesion molecules to initiate the formation of organized structures or scaffolds that permit the efficient flow of information in signaling pathways.
Tumor necrosis factor/cachectin stimulates peritoneal macrophages, polymorphonuclear neutrophils, and vascular endothelial cells to synthesize and release platelet-activating factor.
Authors: G Camussi, F Bussolino, G Salvidio, C Baglioni
Journal: The Journal of Experimental Medicine (1987)

Murine tumor necrosis factor (mTNF) stimulates production of platelet-activating factor (PAF) by cultured rat peritoneal macrophages in amounts comparable to those formed during treatment with the calcium ionophore A23187 or phagocytosis of zymosan. The cell-associated PAF that was released into the medium was identical to synthetic PAF, as determined with physicochemical, chromatographic, and enzymatic assays. Furthermore, de novo synthesis of PAF by macrophages was demonstrated by the incorporation of radioactive precursors such as [3H]acetyl-coenzyme A or [3H]2-lyso-PAF. Macrophages incubated with mTNF for 4 h synthesized PAF only during the first h of treatment. At this time, the amount of cell-associated PAF was approximately equal to that released into the medium. The cell-associated PAF decreased afterwards, whereas that in the medium did not correspondingly increase, suggesting that some PAF was being degraded. The response of rat macrophages to different doses of mTNF and human TNF (hTNF) was examined. Maximal synthesis of PAF was obtained with 10 ng/ml of mTNF and 50 ng/ml of hTNF. This finding may be explained by a lower affinity of hTNF for TNF receptors of rat cells. The hTNF stimulated production of PAF by human vascular endothelial cells cultured from the umbilical cord vein. The time course of PAF synthesis was slower than that observed with macrophages, with maximal production between 4 and 6 h of treatment. Optimal synthesis of PAF was obtained with 10 ng/ml of hTNF. Only 20-30% of the PAF synthesized by endothelial cells was released into the medium, even after several hours of incubation. Synthesis of PAF in response to TNF was also detected in rat polymorphonuclear neutrophils, but not in human tumor cells and dermal fibroblasts. Therefore, production of PAF is a specialized response that is transient in macrophages continuously treated with TNF, and that appears to be controlled by unidentified regulatory mechanisms.
Serum fibrosis markers to predict clinical and histological progression in hepatitis C non-responders
Authors: R. Malik, D. Schuppan
Journal: Gut (2010)

As in other chronic liver diseases, the clinically relevant end point for patients with chronic hepatitis C infection who have failed antiviral therapy, is progressive hepatic fibrosis and finally cirrhosis; with impending hepatic decompensation, liver failure and the development of hepatocellular carcinoma.1–3 Of note, the natural history of liver fibrosis progression has been studied in greatest detail in the hepatitis C population. The course is variable with decades of viraemia causing mild fibrosis in some patients to post-transplant hepatitis C, where cirrhosis can develop within a few years post transplant. Percutaneous liver biopsy has been the reference standard for liver fibrosis staging since its general introduction by Menghini in the 1950s. The liver biopsy has the additional benefit of providing information on A. aetiology, B. grading of inflammation, C. steatosis and D. iron overload, making it a valuable diagnostic test. However, there are important limitations with liver biopsy that include a small but significant morbidity and mortality rate, which creates anxiety in patients, but most importantly a significant sampling variability coupled with intraobserver and interobserver variation in pathology reporting.1 3 4

Serum markers were originally developed to identify the degree of liver fibrosis as an alternative to liver biopsy. The idea of developing a simple blood test to identify and stage liver fibrosis, and to act as a surrogate marker of clinical severity of liver disease superior to conventional liver function tests has enormous potential. There have been many different serum marker panels studied in the hepatitis …
Cyclin D1 Is Transcriptionally Regulated by and Required for Transformation by Activated Signal Transducer and Activator of Transcription 3
Authors: Kenneth Leslie, Cynthia Lang, Geeta Devgan, Janeen Azare, Marjan Berishaj, William Gerald, Young Bae Kim, Keren Paz, James E. Darnell, Christopher Albanese, Toshiyuki Sakamaki, Richard Pestell, Jacqueline Bromberg
Journal: Cancer Research (2006)

Signal transducers and activators of transcription 3 (STAT3) is a transcription factor that is aberrantly activated in many cancer cells. Constitutively activated STAT3 is oncogenic, presumably as a consequence of the genes that it differentially regulates. Activated STAT3 correlated with elevated cyclin D1 protein in primary breast tumors and breast cancer-derived cell lines. Cyclin D1 mRNA levels were increased in primary rat-, mouse-, and human-derived cell lines expressing either the oncogenic variant of STAT3 (STAT3-C) or vSrc, which constitutively phosphorylates STAT3. Mutagenesis of STAT3 binding sites within the cyclin D1 promoter and chromatin immunoprecipitation studies showed an association between STAT3 and the transcriptional regulation of the human cyclin D1 gene. Introduction of STAT3-C and vSrc into immortalized cyclin D1(-/-) and cyclin D1(-/+) fibroblasts led to anchorage-independent growth of only cyclin D1(-/+) cells. Furthermore, knockdown of cyclin D1 in breast carcinoma cells led to a reduction in anchorage-independent growth. Phosphorylation of the retinoblastoma (Rb) protein [a target of the cyclin D1/cyclin-dependent kinase 4/6 (cdk4/6) holoenzyme] was delayed in the cyclin D1(-/-) cells relative to cyclin D1(-/+) cells. The E7 oncogene, whose activity includes degradation of Rb and dissociation of Rb from E2F, did not confer anchorage-independent growth to the cyclin D1(-/-) cells but, in conjunction with vSrc, resulted in robust growth in soft agar. These results suggest both a cdk-dependent and cdk-independent role for cyclin D1 in modulating transformation by different oncogenes.
Molecular Evolution of the tprC, D, I, K, G, and J Genes in the Pathogenic Genus Treponema
Authors: R. Gray
Journal: Molecular Biology and Evolution (2006)

We investigated the evolution of 6 genes from the Treponema pallidum repeat (tpr) gene family, which encode potential virulence factors and are assumed to have evolved through gene duplication and gene conversion events. The 6 loci (tprC, D, G, J, I, and K) were sequenced and analyzed in several members of the genus Treponema, including the 3 subspecies of human T. pallidum (T. pallidum subsp. pallidum, pertenue, and endemicum), Treponema paraluiscuniculi (rabbit syphilis), and the unclassified Fribourg-Blanc (simian) isolate. Phylogenetic methods, recombination analysis, and measures of nucleotide diversity were used to investigate the evolutionary history of the tpr genes. Numerous instances of gene conversion were detected by all 3 methods including both homogenizing gene conversion that involved the entire length of the sequence as well as site-specific conversions that affected smaller regions. We determined the relative age and directionality of the gene conversion events whenever possible. Our data are also relevant to a discussion of the evolution of the treponemes themselves. Higher levels of variation exist between the human subspecies than within them, supporting the classification of the human treponemes into 3 subspecies. In contrast to published theories, the divergence and diversity of T. pallidum subsp. pertenue relative to the other subspecies does not support a much older origin of yaws at the emergence of modern human, nor is the level of divergence seen in T. pallidum subsp. pallidum consistent with a very recent (<500 years) origin of this subspecies. In general, our results demonstrate that intragenomic recombination has played a significant role in the evolution of the studied tpr genes and emphasize that efforts to infer evolutionary history of the treponemes can be complicated if past recombination events are not recognized.
The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes
Authors: James W. Vardiman, Jüergen Thiele, Daniel A. Arber, Richard D. Brunning, Michael J. Borowitz, Anna Porwit, Nancy Lee Harris, Michelle M. Le Beau, Eva Hellström-Lindberg, Ayalew Tefferi, Clara D. Bloomfield
Journal: Blood (2009)