tbuckley/cabot-search huggingface dataset:
Identical p53 gene mutation in malignant proliferating trichilemmal tumour of the scalp and small cell carcinoma of the common bile duct: the necessity for therapeutic caution?
Authors: N. Nakai, H. Takenaka, S. Hamada, S. Kishimoto
Journal: British Journal of Dermatology (2008)

Conflicts of interest: none declared. Sir, Malignant proliferating trichilemmal tumour (MPTT) is a rare neoplasm derived from the outer root sheath of the hair follicle. The tumour has a high metastatic rate and preferentially arises on the scalp in elderly people.1, 2 Primary small cell carcinoma (SCC) is usually seen in the lung in elderly people and SCC of organs other than the lung is extremely rare.3 We report a 32‐year‐old man who died of SCC of common bile duct (CBD) origin 1 year after combination chemotherapy and radiation therapy for primary MPTT on the scalp. A 32‐year‐old man presented with a 1‐year history of a large tumour on his scalp that had enlarged rapidly. Neither his family nor medical history was of significance. Physical examination at the first visit (day 0) showed a dome‐shaped reddish nodule with ulceration on the scalp, measuring 25 mm in diameter (Fig. 1a). Clinically, the tumour was suggestive of MPTT. A magnetic resonance imaging scan of the scalp and neck revealed a mass that had almost infiltrated the periosteum of the head and slight enlargement of the left two cervical lymph nodes, respectively. A whole‐body computed tomographic (CT) scan excluding the head and neck and a routine laboratory examination including blood tests were normal. Preoperative combination chemotherapy of intramuscular injection of peplomycin (5 mg daily) for 5 days and intravenous injection of mitomycin C (6 mg daily) for 1 day was performed. On day 15, the tumour was completely excised with wide margins and complete left neck dissection of cervical lymph nodes was also performed because of metastatic sentinel lymph nodes.
Adult Psychiatric Outcomes of Girls With Attention Deficit Hyperactivity Disorder: 11-Year Follow-Up in a Longitudinal Case-Control Study
Authors: Joseph Biederman, Carter R Petty, Michael C Monuteaux, Ronna Fried, Deirdre Byrne, Tara Mirto, Thomas Spencer, Timothy E Wilens, Stephen V Faraone
Journal: American Journal of Psychiatry (2010)

Objective Few follow-up studies have been conducted of girls with ADHD, and none have followed girls into adulthood. The authors sought to estimate the prevalence of psychopathology in girls with and without ADHD followed into young adulthood. Method The authors conducted a longitudinal case-control study of 6- to 18-year-old girls with (N=140) and without (N=122) ADHD ascertained from psychiatric and pediatric sources. At the 11-year follow-up, 96 (69%) of the girls with ADHD and 91 (75%) of the comparison girls were reassessed (mean age=22 years). Participants were blindly assessed by structured diagnostic interviews. Results Lifetime and 1-year risks for all composite categories of psychopathology were significantly greater in girls with ADHD grown up relative to comparison girls; lifetime hazard ratios were 7.2 (95% CI=4.0–12.7) for antisocial disorders, 6.8 (95% CI=3.7–12.6) for mood disorders, 2.1 (95% CI=1.6–2.9) for anxiety disorders, 3.2 (95% CI=2.0–5.3) for developmental disorders, 2.7 (95% CI=1.6–4.3) for addictive disorders, and 3.5 (95% CI=1.6–7.3) for eating disorders. For lifetime psychopathology, all six composite categories remained statistically significant after controlling for other baseline psychopathology. Except for addictive disorders, significant 1-year findings remained significant after controlling for baseline psychopathology. The 1-year prevalences of composite disorders were not associated with lifetime or 1-year use of ADHD medication. Conclusion By young adulthood, girls with ADHD were at high risk for antisocial, addictive, mood, anxiety, and eating disorders. These prospective findings, previously documented in boys with ADHD, provide further evidence for the high morbidity associated with ADHD across the life cycle.
BMA moves to full opposition on healthcare reforms
Authors: A. O'Dowd
Journal: BMJ (2011)

The BMA has changed its official policy to one of full opposition to the Health and Social Care Bill and its proposed reforms of the NHS. The change of stance was agreed at a BMA council meeting on 24 November. 

At the meeting, a motion—that the BMA council publicly announce its opposition to the whole health bill and that there be “rapid” organisation of a public campaign of opposition to the bill—was narrowly passed after much discussion.

The BMA also issued a briefing paper on 7 December outlining its new stance. In its paper it said that, despite several successful amendments to the bill, major areas of concerns had still not been dealt with sufficiently, such as a continuing over-reliance on market forces to shape care and concerns about the future delivery of public health and medical education. …
Serum 7 alpha-hydroxy-4-cholesten-3-one concentrations in the evaluation of bile acid malabsorption in patients with diarrhoea: correlation to SeHCAT test.
Authors: S Eusufzai, M Axelson, B Angelin, K Einarsson
Journal: Gut (1993)

The synthesis of bile acids is regulated by a homeostatic mechanism in which bile acids returning to the liver from the intestine inhibit their own synthesis. Serum concentrations of the bile acid intermediate 7 alpha-hydroxy-4-cholesten-3-one reflect the rate of bile acid synthesis whereas bile acid malabsorption can be determined by the SeHCAT test. This study was done to evaluate the correlation between the two tests in humans. Twenty eight patients with chronic diarrhoea were included in the study. Fasting serum was collected for the determination of 7 alpha-hydroxy-4-cholesten-3-one, and on the same day the gamma emitting bile acid analogue SeHCAT was given orally and its fractional catabolic rate assessed by repeated external counting over the upper abdomen during the next seven days. There was a highly significant positive correlation between the two tests (Rs = 0.80, p &lt; 0.001). The results show a close relation between intestinal loss and hepatic synthesis of bile acids and imply that analysis of 7 alpha-hydroxy-4-cholesten-3-one in serum should now be evaluated as a possible convenient method for assessing bile acid malabsorption in patients with diarrhoea.
Are these patients indeed resistant to treatment with C1 inhibitor concentrate?
Authors: L. Varga, G. Füst, H. Farkas
Journal: British Journal of Dermatology (2011)

Funding sources: none. Conflicts of interest: none declared. Madam, Bouillet et al.1 report two remarkable cases of patients with type I hereditary angio‐oedema (HAE) who developed ‘resistance against C1 inhibitor concentrate’. In our view, however, the authors failed to substantiate the statement made in the title of their article (‘… patients with hereditary angio‐oedema type I resistant to treatment with C1 inhibitor concentrate’). The severity of HAE fluctuates during the lifetime of afflicted patients, regardless of permanent C1 inhibitor deficiency. External factors are known potential inducers of oedematous attacks, the frequency of which may increase in their presence. However, variations of attack frequency can occur both in untreated patients and in those on a stable prophylactic regimen. This was the case in patient 1, who began to experience breakthrough attacks despite unchanged treatment, and whose attacks could not be eliminated even by increasing the dose of C1 inhibitor concentrate to the standard level recommended for prophylaxis (see the U.S. Food and Drug Administration package insert of Cinryze®2). The authors mention breakthrough attacks, but do not provide any information on the frequency and duration of these episodes.
Effect of Target Dynamics on Pharmacokinetics of a Novel Therapeutic Antibody against the Epidermal Growth Factor Receptor: Implications for the Mechanisms of Action
Authors: Jeroen J. Lammerts van Bueren, Wim K. Bleeker, Henrik O. Bøgh, Mischa Houtkamp, Janine Schuurman, Jan G.J. van de Winkel, Paul W.H.I. Parren
Journal: Cancer Research (2006)

The epidermal growth factor receptor (EGFR) is overexpressed on many solid tumors and represents an attractive target for antibody therapy. Here, we describe the effect of receptor-mediated antibody internalization on the pharmacokinetics and dose-effect relationship of a therapeutic monoclonal antibody (mAb) against EGFR (2F8). This mAb was previously found therapeutically active in mouse tumor models by two dose-dependent mechanisms of action: blockade of ligand binding and induction of antibody-dependent cell-mediated cytotoxicity. In vitro studies showed 2F8 to be rapidly internalized by EGFR-overexpressing cells. In vivo, accelerated 2F8 clearance was observed in cynomolgus monkeys at low doses but not at high doses. This enhanced clearance seemed to be receptor dependent and was included in a pharmacokinetic model designed to explain its nonlinearity. Receptor-mediated clearance was also found to affect in situ antibody concentrations in tumor tissue. Ex vivo analyses of xenograft tumors of 2F8-treated nude mice revealed that relatively high antibody plasma concentrations were required for maximum EGFR saturation in high-EGFR-expressing human A431 tumors, in contrast to lower-EGFR-expressing human xenograft tumors. In summary, receptor-mediated antibody internalization and degradation provides a saturable route of clearance that significantly affects pharmacokinetics, particularly at low antibody doses. EGFR saturation in normal tissues does not predict saturation in tumor tissue as local antibody concentrations in EGFR-overexpressing tumors may be more rapidly reduced by antibody internalization. Consequently, antibody saturation of the receptor may be affected, thereby affecting the local mechanism of action.
Angiotensin-Converting Enzyme Inhibitors, Angiotensin II Receptor Antagonists and Calcium Channel Blocking Agents: A Review of Potential Benefits and Possible Adverse Reactions
Authors: Marvin Moser
Journal: Journal of the American College of Cardiology (1997)

A review of recent studies suggests that the use of angiotensin-converting enzyme (ACE) inhibitors may be preferred (usually along with a diuretic drug) as initial therapy in several subsets of hypertensive patients (i.e., those with diabetes and nephropathy or with diminished left ventricular function with or without symptoms of heart failure). Limited long-term data are available for the angiotensin II receptor antagonists. The use of nondihydropyridine calcium channel blocking agents (CCBs) appears to reduce reinfarction in patients with ischemic heart disease (however, mortality is not reduced). Long-acting formulas of CCBs appear to decrease congestive heart failure in patients with dilated, but not ischemic, cardiomyopathy and to decrease strokes and arrhythmias in hypertensive subjects. Short-acting agents (primarily those that increase heart rate) may increase coronary heart disease events in hypertensive patients. There is little evidence at present that CCBs offer a major advantage over other antihypertensive agents or that they should be recommended as initial therapy, except in special situations.
Semen retrieval by penile vibratory stimulation in men with spinal cord injury
Authors: N. Brackett
Journal: Human Reproduction Update (1999)

Traumatic spinal cord injury resulting from car accidents, falls, violence or sport-related activities is a common occurrence throughout the world. Spinal cord injuries occur most often to young men in their parenting years. Among the medical challenges facing many of these men is the inability to ejaculate via sexual intercourse. To achieve biological fatherhood, their semen may be retrieved by methods of assisted ejaculation. This paper discusses the use of penile vibratory stimulation in men with spinal cord injury, and includes the topics: patient selection and management; proper placement and timing of stimulation; appropriate use of low-amplitude, high-amplitude or dual vibrators; and factors influencing ejaculatory success rate. Also summarized are recent data on semen quality in men with spinal cord injury. When performed properly, penile vibratory stimulation is a safe and easy method of obtaining semen from anejaculatory men with spinal cord injury. Semen quality is better when obtained by penile vibratory stimulation compared with electroejaculation, an alternative method of semen retrieval. For these reasons, and because of the low investment of time and money, it is recommended that penile vibratory stimulation be used as the first line of treatment for anejaculation in men with spinal cord injury.
Markedly Increased FDG Uptake in a Vocal Cord After Medialization With Teflon: PET/CT Findings
Authors: Dharmesh Modi, Michael J Fulham, Armin Mohamed, Thomas E Havas
Journal: Clinical Nuclear Medicine (2004)

An FDG PET scan was requested for a 73-year-old man who had been previously diagnosed and treated for esophageal carcinoma and mediastinal nodal involvement with chemoradiotherapy. He originally presented with a hoarse voice and dysphagia. The PET scan was requested to assess treatment response, although a baseline scan had not been done. Two weeks prior to the PET scan the patient fell and fractured his left clavicle. On the PET scan there was no evidence for residual esophageal disease but there was marked focal FDG uptake in the left larynx and moderate FDG uptake at the sites of the recent fractures (clavicle and ribs). The PET findings prompted further review. It was noted that 6 months prior to the PET scan, and a month after the initial diagnosis, there had been a left vocal cord medialization with Teflon to treat the left vocal cord paresis.
Starting Insulin Therapy in Type 2 Diabetic Patients
Authors: Mayer B. Davidson
Journal: Diabetes Care (2005)

Type 2 diabetic patients failing oral antidiabetes medications need insulin. If used appropriately and with patient cooperation, almost all patients can be well controlled. There is no agreed upon optimal mode of initiating insulin in this situation. In recent years, adding NPH insulin at bedtime (1–3) or 70/30 premixed insulin at suppertime (4) to the oral medications have been studied. Adding NPH insulin at bedtime has yielded similar improvements in control as two or more injections of insulin for 3 (1), 6 (2), or 12 (3) months. Recently, several studies have compared the peakless insulin, glargine, with bedtime NPH insulin and showed similar levels of control but less nocturnal hypoglycemia (5–7).

Two reports in this issue of Diabetes Care pertain to this matter. In the first, Janka et al. (8) compared adding a morning injection of glargine insulin to type 2 diabetic patients failing oral medications with discontinuing the pills and starting premixed 70% NPH insulin/30% regular insulin twice a day. The patients receiving glargine insulin during the 24-week study were also taking 3 or 4 mg of glimepiride and 850 mg or more of metformin. A weekly forced-titration algorithm was used to achieve a target fasting glucose concentration of ≤100 mg/dl in both groups and ≤100 mg/dl before supper in the patients taking premixed insulin. Patients in the glargine group had a statistically greater fall in A1c levels (−1.6 vs. −1.3%) and less …
MicroRNA-21 Promotes Fibrosis of the Kidney by Silencing Metabolic Pathways
Authors: B. Nelson Chau, Cuiyan Xin, Jochen Hartner, Shuyu Ren, Ana P. Castano, Geoffrey Linn, Jian Li, Phong T. Tran, Vivek Kaimal, Xinqiang Huang, Aaron N. Chang, Shenyang Li, Aarti Kalra, Monica Grafals, Didier Portilla, Deidre A. MacKenna, Stuart H. Orkin, Jeremy S. Duffield
Journal: Science Translational Medicine (2012)

MicroRNA-21 contributes to fibrosis in the kidney by posttranscriptionally regulating lipid metabolism genes.
Detection in life of confirmed Alzheimer's disease using a simple measurement of medial temporal lobe atrophy by computed tomography
Authors: A.D. Smith, K.A. Jobst, M. Szatmari, A. Jaskowski, E. King, A. Smith, A. Molyneux, M.E. Esiri, B. McDonald, N. Wald
Journal: The Lancet (1992)
THE SIGNIFICANCE OF INTRADERMAL TUBERCULIN TESTS: A PRELIMINARY NOTE ON AN INVESTIGATION IN PROGRESS BY THE MEDICAL STAFF OF THE WELSH NATIONAL MEMORIAL ASSOCIATION
Authors: S. L. Cummins
Journal: BMJ (1929)

231 FR& 13-10.91BIGNIPOA)CS OCF INTUADTIMAL TUBBOUIJN TBSTRO [ li 2 these cases little food can be absorbed, such sources of enuergy as are available must be conserved by keeping the patient thoroughly warm-in bed for preference-and by limiting exercise as far as possible.The ultimate fate of the majority of " coeliac " cases is recovery, but even after what may be regarded as complete recovery there is always a tendency to recidivism, aind some dilatation of the intestines usually persists.Type S.As I hiave already indicated, the symptoms of certpiui forms of dyspepsia are so remote anid geineral that they are liable to be attributed to tuberculosis or other con- stitutional ti:ouble, rather than to actual (lefects in the digestive processes.The kind of case wlhichi I am about to describe is essentially of this character in its most typical form.It occurs in children between 2 and 16 years of age.It is chronic and remittent in character.Children suffering fromii this form of dyspepsia are never really well, neither do they look well.They usually do not complain of feeling ill, but they have little energy, are easily tired, and have capricious appetites.There is often a continued temperature, usually under 100°F.,
Long term benefits of rehabilitation at home on quality of life and exercise tolerance in patients with chronic obstructive pulmonary disease.
Authors: P J Wijkstra, E M Ten Vergert, R van Altena, V Otten, J Kraan, D S Postma, G H Koeter
Journal: Thorax (1995)

BACKGROUND--Pulmonary rehabilitation has been shown to have short term subjective and objective benefits for patients with chronic obstructive pulmonary disease (COPD). However, appropriately controlled studies have not previously been performed, nor have the benefits of different types of continuation programme for rehabilitation been investigated. Both these problems have been addressed in a single study of the long term effects of once monthly physiotherapy versus once weekly physiotherapy at home after a comprehensive home rehabilitation programme on quality of life and exercise tolerance in patients with COPD. METHODS--Thirty six patients with severe airways obstruction (mean SD) forced expiratory volume in one second (FEV1) 1.3(0.4) 1, FEV1/inspiratory vital capacity (IVC) 37.2(7.9)%) were studied. Twenty three patients followed a rehabilitation programme at home for 18 months consisting of physiotherapy and supervision by a nurse and general practitioner. During the first three months all 23 patients visited the physiotherapist twice a week for a 0.5 hour session. Thereafter, 11 patients (group A) received a session of physiotherapy once weekly while 12 patients (group B) received a session of physiotherapy once a month. The control group C (13 patients) received no rehabilitation at all. Quality of life was assessed by the Chronic Respiratory Questionnaire, exercise tolerance by the six minute walking distance, and lung function by FEV1 and IVC. Outcome measures were assessed at baseline and at three, six, 12, and 18 months. RESULTS--Long term improvements in quality of life were found in patients in groups A and B, but not in those in group C compared with baseline, but these only reached significance in group B at all time points. Patients in group B had a higher quality of life than those in group C only at three and 12 months. There was a decrease in both six minute walking distance (at 12 and 18 months) and IVC (at three, 12, and 18 months) in patients in group C compared with the baseline measurement. Between groups analysis showed no differences for six minute walking distance, FEV1, and IVC. CONCLUSIONS--This study is the first to show that rehabilitation at home for three months followed by once monthly physiotherapy sessions improves quality of life over 18 months. The change in quality of life was not associated with a change in exercise tolerance.
High-dose carboplatin, thiotepa, and etoposide with autologous stem cell rescue for patients with previously irradiated recurrent medulloblastoma
Authors: I. J. Dunkel, S. L. Gardner, J. H. Garvin, S. Goldman, W. Shi, J. L. Finlay
Journal: Neuro-Oncology (2010)

Recurrent medulloblastoma is highly lethal in previously irradiated patients. Previously irradiated patients with M-0-M-3 recurrences who achieved a minimal disease state prior to protocol enrollment received carboplatin (Calvert formula with area under the curve = 7 mg/mL min, maximum 500 mg/m(2)/day) on days -8 to -6, and thiotepa (300 mg/m(2)/day) and etoposide (250 mg/m(2)/day) on days -5 to -3, followed by autologous stem cell rescue (ASCR) on day 0. Twenty-five patients, aged 7.6-44.7 years (median 13.8 years) at ASCR, were treated. Three (12%) died of treatment-related toxicities within 30 days of ASCR, due to multiorgan system failure (n = 2) and aspergillus infection with veno-occlusive disease (n = 1). Tumor recurred in 16 at a median of 8.5 months (range 2.3-58.5 months). Six are event-free survivors at a median of 151.2 months post-ASCR (range 127.2-201.6 months). The Kaplan-Meier estimate of median overall survival is 26.8 months (95% CI: 11.9-51.1 months) and of event-free survival (EFS) and overall survival are both 24% (95% CI: 9.8%-41.7%) at 10 years post-ASCR. M-0 (vs M-1 + ) recurrence prior to protocol, lack of tissue confirmation of relapse, and initial therapy of radiation therapy (RT) alone (vs RT + chemotherapy) were not significantly associated with better EFS (P = .33, .34, and .27, respectively). Trends toward better EFS were noted in patients (n = 5) who received additional RT as part of their retrieval therapy (P = .07) and whose recurrent disease was demonstrated to be sensitive to reinduction chemotherapy (P = .09). This retrieval strategy provides long-term EFS for some patients with previously irradiated recurrent medulloblastoma. The use of additional RT may be associated with better outcome.
The Collaborative Cross, a community resource for the genetic analysis of complex traits
Authors: Gary A Churchill, David C Airey, Hooman Allayee, Joe M Angel, Alan D Attie, Jackson Beatty, William D Beavis, John K Belknap, Beth Bennett, Wade Berrettini, Andre Bleich, Molly Bogue, Karl W Broman, Kari J Buck, Ed Buckler, Margit Burmeister, Elissa J Chesler, James M Cheverud, Steven Clapcote, Melloni N Cook, Roger D Cox, John C Crabbe, Wim E Crusio, Ariel Darvasi, Christian F Deschepper, R W Doerge, Charles R Farber, Jiri Forejt, Daniel Gaile, Steven J Garlow, Hartmut Geiger, Howard Gershenfeld, Terry Gordon, Jing Gu, Weikuan Gu, Gerald de Haan, Nancy L Hayes, Craig Heller, Heinz Himmelbauer, Robert Hitzemann, Kent Hunter, Hui-Chen Hsu, Fuad A Iraqi, Boris Ivandic, Howard J Jacob, Ritsert C Jansen, Karl J Jepsen, Dabney K Johnson, Thomas E Johnson, Gerd Kempermann, Christina Kendziorski, Malak Kotb, R Frank Kooy, Bastien Llamas, Frank Lammert, Jean-Michel Lassalle, Pedro R Lowenstein, Lu Lu, Aldons Lusis, Kenneth F Manly, Ralph Marcucio, Doug Matthews, Juan F Medrano, Darla R Miller, Guy Mittleman, Beverly A Mock, Jeffrey S Mogil, Xavier Montagutelli, Grant Morahan, David G Morris, Richard Mott, Joseph H Nadeau, Hiroki Nagase, Richard S Nowakowski, Bruce F O'Hara, Alexander V Osadchuk, Grier P Page, Beverly Paigen, Kenneth Paigen, Abraham A Palmer, Huei-Ju Pan, Leena Peltonen-Palotie, Jeremy Peirce, Daniel Pomp, Michal Pravenec, Daniel R Prows, Zhonghua Qi, Roger H Reeves, John Roder, Glenn D Rosen, Eric E Schadt, Leonard C Schalkwyk, Ze'ev Seltzer, Kazuhiro Shimomura, Siming Shou, Mikko J Sillanpää, Linda D Siracusa, Hans-Willem Snoeck, Jimmy L Spearow, Karen Svenson, Lisa M Tarantino, David Threadgill, Linda A Toth, William Valdar, Fernando Pardo-Manuel de Villena, Craig Warden, Steve Whatley, Robert W Williams, Tim Wiltshire, Nengjun Yi, Dabao Zhang, Min Zhang, Fei Zou
Journal: Nature Genetics (2004)