tbuckley/cabot-search huggingface dataset:
Mumps Epididymitis without Orchitis
Authors: Arnold G. Coran, Alan D. Perlmutter
Journal: New England Journal of Medicine (1965)

ORCHITIS occurs in about 18 per cent of patients with mumps — rarely before puberty.1 Epididymitis without orchitis in mumps has not been described, to our knowledge.Case ReportP.S. (P.B.B.H. 3–70–33), a 17-year-old Negro, was hospitalized after 4 days of severe pain in the left scrotum and fever. Ten days before admission he had a mild upper-respiratory-tract infection. Eight days later he noted urinary urgency and frequency. He denied recent sexual contact.His mother had had a mumps infection 1 month earlier.Physical examination showed a well developed, well nourished boy in mild distress, with a temperature of 105°F. . . .
Care of asthma in general practice: Author's reply
Authors: C. R Martys
Journal: BMJ (1992)

asthma need to be appraised critically.For example, the number of admissions to hospital is often used as evidence of bad care of asthma in general practice.Admission to hospital may, however, often be appropriate.If we can remove the stigma attached to admissions for acute asthma generated by general practitioners junior hospital doctors may take our referrals for admission more seriously.
The induction of P450-mediated oxidation of all-trans retinoic acid by retinoids in head and neck squamous cell carcinoma cell lines
Authors: Sang Yoon Kim, In Suk Han, Hwa Kyung Yu, Hye Rim Lee, Jong Woo Chung, Jee-Ho Choi, Sun Hee Kim, Youngbro Byun, Thomas E. Carey, Kwang-Sun Lee
Journal: Metabolism (1998)
Genetic Alterations at 5p15: a Potential Marker for Progression of Precancerous Lesions of the Uterine Cervix
Authors: A. B. Mitra, V. V. V. S. Murty, R.-G. Li, R. S. K. Chaganti, V. Singh, M. Pratap, P. Sodhani, U. K. Luthra
Journal: JNCI Journal of the National Cancer Institute (1995)

Background: Development of uterine cervical cancer is preceded by preneo-plastic proliferative changes in the cervical epithelium called "intra-epithelial neoplasia" or "dysplasia." The genetic basis of the origin and progression of such preneoplastic lesions is not known. By analysis of carcinomas for loss of constitutional heterozygosity (LOH), we have previously shown a high frequency of allelic loss in the short arm of chromosome 5 (5p), suggesting loss of a candidate tumor suppressor gene located in 5p and associated with the development of this tumor. Purpose: To further understand the role of genetic alterations that affect 5p in cervical carcinogenesis, we evaluated the status of microsatellite polymorphisms at five loci mapped to 5pl4-ter in precancerous and cancerous lesions. Methods: Biopsy specimens from two groups of patients were analyzed for genetic alterations affecting 5p. One group comprised 14 cases of precancerous lesions (i.e., dysplasias) and five cases of carcinoma in situ (CIS); the second group comprised 46 previously untreated patients with invasive carcinoma. Tumor and normal DNAs were analyzed by polymerase chain reaction for genetic losses and instability at five polymorphic micro-satellite loci (D5S392, D5S406, D5S208, D5S117, and D5S432) mapped to 5p. Results: LOH was observed in 25 (55.6%) of 45 informative invasive carcinomas, one (20%) of five cases of CIS, and three (21%) of 14 precan-cerous lesions. Among the loci tested, D5S406 (5pl5.1–15.2) exhibited LOH in 12 (48%) of 25 invasive carcinomas, one (33%) of three cases of CIS, and three (60%) of five precancerous lesions, suggesting this to be the site in 5p of the novel candidate tumor suppressor gene. In addition, replication error-type alterations were noted in the 5pl4-ter region in six (13%) of 46 invasive carcinomas, two (40%) of five cases of CIS, and three (21%) of 14 precancerous lesions. Instability affected D5S406 in eight (66.7%) of 12 instances that showed microsatellite instability. Conclusion: These observations suggest that allelic loss and microsatellite instability in the region of D5S406 may play a role early in the development of cervical carcinoma and identify the site of a candidate tumor suppressor gene. These genetic markers (allelic loss and microsatellite instability) may also define CIS and precancerous lesions at high risk for progression to invasive cancer. Implications: The future molecular cloning of the candidate tumor suppressor gene at 5p15.1–15.2 may provide new insights into the genetic mechanisms of cervical carcinogenesis. Analysis and clinical follow-up of a large cohort of prospectively ascertained cases of precancerous lesions would help to validate the usefulness of these markers. [J Natl Cancer Inst 87: 742–745, 1995]
Choice of Antipsychotic Drugs
Authors: LEO E. HOLLISTER
Journal: American Journal of Psychiatry (1970)

Antipsychotic drugs are the most useful treatment available for the most serious psychiatric disorders. Despite the plethora of available drugs, a rational choice of few will provide a full range of therapeutic effects. One must always choose drugs in relation to the special needs of individual patients. A properly chosen drug may be preferable to polypharmacy; as in architecture, "less may be more."
Activation of Signal Transducer and Activator of Transcription 3 through a Phosphomimetic Serine 727 Promotes Prostate Tumorigenesis Independent of Tyrosine 705 Phosphorylation
Authors: Haiyan R. Qin, Han-Jong Kim, Joon-Young Kim, Elaine M. Hurt, George J. Klarmann, Brian T. Kawasaki, Maria A. Duhagon Serrat, William L. Farrar
Journal: Cancer Research (2008)

Abstract Aberrantly activated signal transducer and activator of transcription 3 (Stat3) is implicated in the development of various human cancers. Y705 phosphorylation is conventionally thought to be required for Stat3 signal-dependent activation and seems to play an essential role in some malignancies. Recently, it was shown that Stat3 is activated through novel and noncanonical mechanisms, including phosphorylation at S727. Here, we investigate S727 phosphorylation of Stat3 and its subsequent effects in prostate cancer development, independent of Y705 phosphorylation, using mutated Stat3 in the human prostate cancer cell line LNCaP. We show mutation of S727 to the phosphomimetic residue Glu, and inactivation of Y705 (Y705F/S727E) resulted in a remarkable growth advantage in low-serum, enhanced anchorage-independent growth in soft agar, and increased tumorigenicity in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice, possibly by direct activation of downstream proto-oncogenes c-myc, mcl-1, and survivin. Y705F/S727E mutant cells were more invasive than Y705F/S727A (inactivation of Y705 and S727) mutant cells, and more Y705F/S727E mutant Stat3 was localized in the nuclei relative to Y705F/S727A mutant Stat3 at the steady state. Furthermore, the Y705F/S727E but not the Y705F/S727A mutant induced anchorage-independent growth of noncancerous prostate epithelial cells (RWPE-1). We further show that Stat3 is phosphorylated at S727 in 65% of malignant prostate tissues (n = 20) relative to 25% of normal prostate tissues (n = 4). Moreover, there is a positive correlation between phosphoS727-Stat3 expression and Gleason score in these prostate cancer tissues (P = 0.05). Our data suggest for the first time that S727 phosphorylation is sufficient to activate Stat3, thereby driving prostate tumorigenesis independent of Y705 phosphorylation. [Cancer Res 2008;68(19):7736–41]
Basic Exploratory Research versus Guideline-Compliant Studies Used for Hazard Evaluation and Risk Assessment: Bisphenol A as a Case Study
Authors: Rochelle W. Tyl
Journal: Environmental Health Perspectives (2009)

Myers et al. [Environ Health Perspect 117:309-315 (2009)] argued that Good Laboratory Practices (GLPs) cannot be used as a criterion for selecting data for risk assessment, using bisphenol A (BPA) as a case study. They did not discuss the role(s) of guideline-compliant studies versus basic/exploratory research studies, and they criticized both GLPs and guideline-compliant studies and their roles in formal hazard evaluation and risk assessment. They also specifically criticized our published guideline-compliant dietary studies on BPA in rats and mice and 17beta-estradiol (E(2)) in mice.
ORTHOPEDIC SURGERY BETWEEN TWO WARS
Authors: AMES A. DICKSON
Journal: JAMA (1942)

At a time when human energy and resources are being consumed on a scale never before imagined in the frenzied production of instruments of destruction, carnage and chaos, it is easy to agree with the cynics and pessimists who contend that there is no real progress in the world and that what we call civilization is completely doomed. But if we ponder more carefully the things we know best and the changes that have been wrought in our thinking as well as the environment in which we live, we know that this is not true. Change is eternal, the law of life, and those changes that endure are always for the better. Sometimes progress is so gradual that we are not aware of it; sometimes it is hastened by spectacular and stimulating events. It is well, especially when immediate happenings are conducive of despair, to stop and give our attention
Compound heterozygosity for mutations in the hairless gene causes atrichia with papular lesions
Authors: M. Indelman, R. Bergman, G.G. Lestringant, G. Peer, E. Sprecher
Journal: British Journal of Dermatology (2003)

Congenital atrichias represent a complex and heterogeneous group of genodermatoses, which have been shown in several consanguineous families to result from homozygous mutations in the hairless gene (HR).To identify the molecular basis of congenital atrichia in a non-consanguineous family.Genetic analysis was carried out in a two-generation family with two children with congenital atrichia and one healthy child.We established a diagnosis of atrichia with papular lesions based on clinical and histopathological data. We identified a heterozygous 11-bp deletion (189-199del) in the two affected children and their mother. In addition, the two affected children and their father were shown to carry a non sense mutation (Q478X), which has previously been described in a Pakistani family. Haplotype analysis revealed that mutation Q478X occurred independently in the two families.We have identified the first case of compound heterozygosity for mutations in HR as well as the first instance of a recurrent mutation in this gene. These data further expand our understanding of the molecular pathomechanisms underlying congenital atrichias.
NK cell survival mediated through the regulatory synapse with human DCs requires IL-15Rα
Authors: Fabienne Brilot, Till Strowig, Susanne M. Roberts, Frida Arrey, Christian Münz
Journal: Journal of Clinical Investigation (2007)

DCs activate NK cells during innate immune responses to viral infections. However, the composition and kinetics of the immunological synapse mediating this interaction are largely unknown. Here, we report the rapid formation of an immunological synapse between human resting NK cells and mature DCs. Although inhibitory NK cell receptors were polarized to this synapse, where they are known to protect mature DCs from NK cell lysis, the NK cell also received activation signals that induced mobilization of intracellular calcium and CD69 upregulation. The high-affinity component of the receptor for IL-15, IL-15Rα, accumulated at the synapse center on NK cells, and blocking of IL-15Rα increased NK cell apoptosis and diminished NK cell survival during their interaction with DCs. Furthermore, IL-15Rα–deficient NK cells, obtained from donors with a history of infectious mononucleosis, showed diminished survival in culture with DCs. Synapse formation was required for IL-15Rα–mediated NK cell survival, because synapse disruption by adhesion molecule blocking decreased DC-induced NK cell survival. These results identify what we believe to be a novel regulatory NK cell synapse with hallmarks of spatially separated inhibitory and activating interactions at its center. We suggest that this synapse formation enables optimal NK cell activation by DCs during innate immune responses.
Low density lipoprotein apheresis therapy for steroid-resistant nephrotic syndrome
Authors: Eri Muso, Masatoshi Mune, Yasuhiro Fujii, Enyu Imai, Naohiko Ueda, Kazuhiro Hatta, Akio Imada, Shozo Miki, Takashi Kuwahara, Yoshihiro Takamitsu, Tsukasa Takemura, Yoshiharu Tsubakihara
Journal: Kidney International (1999)
Working in Spain
Authors: E. Duncan
Journal: BMJ (1998)

Spain's a great place - it's hot nearly all the time, and people hardly do any work. Both are true, and both are a double edged sword for British doctors seeking employment. For example, you wish to appear calm as you approach your local medical college for the fourth time in your attempt to register. With the temperature at 30½ C you arrive, instead, hot and sweaty to be told that the person processing your application has left for the day (at 1.40 pm) and will not be back for six days because of public holidays, the weekend, and other unspecified absence; and it only gets more bizarre.

Surprisingly, Spain is one of the countries in Europe whose health service most closely resembles the British NHS in structure: universal coverage free at point of access with general practitioners acting as gatekeepers. This familiarity makes it initially appealing to British doctors when set against the mysteries of insurance based systems: general practitioners have geographically based lists and are paid through various permutations of fixed salary, capitation, and incentives, although, like hospital doctors (who receive a fixed salary), they are health service employees. General practitioners should also note that primary care for children is often provided by hospital trained paediatricians working as part of the primary healthcare team.

So how can a shivering Brit, fed up with freezing fog and lane closures on the M6, make the switch from blood and bitter to sangre and sangria?

Entry to the system can occur at three levels: undergraduate, after qualifying, or as a trained specialist, but transferring part way through any of these stages is not practicable.

After six years at university, Spanish medical graduates sit a national competitive exam, the MIR, to obtain a training post in their chosen specialty (see 1). This …
PTU-123 Use Of Rituximab In Resistant Autoimmune Hepatitis – Birmingham Experience
Authors: N Gautam, NN Than, M Nizamuddin, D Adams, YH Oo
Journal: Gut (2014)

<h3>Introduction</h3> Autoimmune hepatitis (AIH) is due to breakdown in immunological self-tolerance. Sustained remission in AIH is crucial to prevent the progression to end stage liver disease.<sup>1</sup> Around 9% of the patients are refractory/intolerant to the standard therapy with prednisolone (Pred) ± azathioprine (AZA). High levels of immunoglobulin are typical of AIH and plasma cells are frequently observed in liver histology. Rituximab is an anti-CD20 monoclonal antibody that depletes B-cells and has been used to treat other autoimmune conditions such as systemic lupus erythematosus. However, little has been reported on the role of B cells depletion and its outcome in AIH. The aim of the study was to evaluate the safety and efficacy of rituximab in the treatment of refractory AIH. <h3>Methods</h3> A retrospective case note review of well-defined and biopsy proven type-1 AIH (simplified scoring &gt;6). 5 patients out of 200 who were intolerant/refractory to standard therapy were given Rituximab and the responses were followed up for 72 weeks. Efficacy was measured by biochemical and immunological parameters (bilirubin, AST, ALT and Immunoglobulin every 12 weeks. The dose of Prednisolone as well as UKELD/MELD score pre and post treatment was also evaluated. <h3>Results</h3> All 5 patients were female and mean age was 45 (range 35–66 yrs). The rituximab dose used was 1000 mg and the total number of doses received varied between 2 and 4 (Mean 3.2). Three patients had other concomitant autoimmune conditions (endocrine, rheumatological and renal related autoimmune diseases). The mean dose of prednisolone used pre-rituximab was 19mg (±SD 12.57) and this was reduced to 12.5mg (± SD 5.0) post treatment (statistically not significant=NS). There was a slight improvement of IgG pre and post Rituximab treatment (NS), with no improvement in UKELD score. There was an improvement in biochemical profile but this was not statistically significant throughout the observation period. All five patients were alive and rituximab was well tolerated without any serious adverse events. <h3>Conclusion</h3> Rituximab is well-tolerated and safe to use in resistant AIH. It can cause some biochemical and immunological improvement. Current evidence for its use in AIH patients is not well proven. The study numbers are too small to detect the actual outcome of the therapy. A multicenter larger cohort prospective study with longitudinal immunological, biochemical and histological profile assessment is warranted to assess its efficacy in resistant AIH patients. <h3>Reference</h3> Czaja AJ. Current and future treatments of AIH.<i> Expert Rev Gastroenterology Hepatol</i> 2009:3: 269–91 <h3>Disclosure of Interest</h3> None Declared.
Lessons from history: Be cautious when choosing your specialty
Authors: G. McGreal
Journal: BMJ (1998)

“Men die of the diseases which they have studied most … it's as if the morbid condition was an evil creature which, when it found itself closely hunted, flew at the throat of its pursuer.” 1 This warning introduces a tale by Sir Arthur Conan Doyle (ophthalmologist, historian, creator of Sherlock Holmes), wherein the fate of a neurologist, named Walker, is described. He developed locomotor ataxia, the early signs of which he noticed during a lecture on the said malady. Later, Doyle tells us …
Are Elderly Patients with Obstructive Airway Disease Being Prematurely Discharged?
Authors: DON D. SIN, JACK V. TU
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Despite the temporal trend toward decreasing length of hospital stay for all medical conditions in North America, the effect of different lengths of hospitalization on short-term outcomes such as readmission or mortality has not been well studied. However, there is growing concern that very short stays in hospital may result in premature discharges, which may lead to worse outcomes for patients. We conducted a population-based study of elderly patients with obstructive airway disease in Ontario, Canada to test the hypothesis that very short initial hospital stays increase the short-term risk for readmission and mortality. Using a cohort of 32,384 elderly patients 65 yr of age or older, we compared 15-d rates of readmission and mortality among patients with different lengths of stay. Although patients with hospital stays of less than 4 d were younger and had fewer comorbidities, they were 39% (95% confidence interval [CI], 20% to 61%) more likely to be readmitted and 45% (95% CI, 9% to 92%) more likely to die within 15 d postdischarge compared with those who stayed 4 to 6 d. The risk was highest among patients whose stay was less than or equal to 1 hospital day; they had a 69% (95% CI, 32% to 117%) excess risk of readmission and a 2.08 (95% CI, 1.23 to 3.45) -fold increase in mortality compared with those who stayed in hospital for 2 d. This suggests that some elderly patients with obstructive airway disease may be being prematurely discharged.
"Supernormal" Bone Image in a Case of Waldenstr??m Macroglobulinemia
Authors: EDWARD LUBAT, ELISSA LIPCON KRAMER, JOSEPH J. SANGER
Journal: Clinical Nuclear Medicine (1986)

A case of Waldenstrom macroglobulinemia, a rare cause of diffusely increased skeletal uptake and relatively diminished renal uptake of bone seeking radiopharmaceutical, is presented. This pattern has been described in a variety of disorders. An important observation to be made in these cases is the skeletal distribution of the radiopharmaceutical. In diffuse bone metastases from carcinoma, which is the most common cause of these findings, the increased activity is primarily in the axial skeleton. In some of the more uncommon causes, including certain hematologic disorders, however, the increased skeletal uptake is more homogeneous in distribution, with prominent uptake in the Avethe skull and distal extremities.
Mitochondrial Complex I Deficiency Increases Protein Acetylation and Accelerates Heart Failure
Authors: Georgios Karamanlidis, Chi Fung Lee, Lorena Garcia-Menendez, Stephen C. Kolwicz, Wichit Suthammarak, Guohua Gong, Margaret M. Sedensky, Philip G. Morgan, Wang Wang, Rong Tian
Journal: Cell Metabolism (2013)
Prediagnostic Serum Concentrations of Organochlorine Compounds and Risk of Testicular Germ Cell Tumors
Authors: Mark P. Purdue, Lawrence S. Engel, Hilde Langseth, Larry L. Needham, Aage Andersen, Dana B. Barr, Aaron Blair, Nathaniel Rothman, Katherine A. McGlynn
Journal: Environmental Health Perspectives (2009)

Recent findings suggest that exposure to organochlorine (OC) compounds, chlordanes and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) in particular, may increase the risk of developing testicular germ cell tumors (TGCTs).To further investigate this question, we conducted a nested case-control study of TGCTs within the Norwegian Janus Serum Bank cohort.The study was conducted among individuals with serum collected between 1972 and 1978. TGCT cases diagnosed through 1999 (n = 49; 27-62 years of age at diagnosis) were identified through linkage to the Norwegian Cancer Registry. Controls (n =51) were matched to cases on region, blood draw year, and age at blood draw. Measurements of 11 OC insecticide compounds and 34 polychlorinated biphenyl (PCB) congeners were performed using gas chromatography/high-resolution mass spectrometry. Case-control comparisons of lipid-adjusted analyte concentrations were performed using the Wilcoxon signed-rank test. Odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles of analyte concentration were calculated using conditional logistic regression.TGCT cases had elevated concentrations of p,p'-DDE (tertile 3 vs. tertile 1 OR (OR(T3)) 2.2; 95% CI, 0.7-6.5; p(Wilcoxon) = 0.07), oxychlordane (OR(T3) 3.2; 95% CI, 0.6-16.8; p(Wilcoxon) = 0.05), trans-nonachlor (OR(T3) 2.6; 95% CI, 0.7-8.9; p(Wilcoxon) = 0.07), and total chlordanes (OR(T3) 2.0; 95% CI, 0.6-7.2; p(Wilcoxon) = 0.048) compared with controls, although no ORs were statistically significant. Seminoma cases had significantly lower concentrations of PCB congeners 44, 49, and 52 and significantly higher concentrations of PCBs 99, 138, 153, 167, 183, and 195.Our study provides additional but qualified evidence supporting an association between exposures to p,p'-DDE and chlordane compounds, and possibly some PCB congeners, and TGCT risk.