tbuckley/cabot-search huggingface dataset:
An 11-year-old high-level competitive gymnast with back pain
Authors: Charlotte Nusman, Rick van Rijn, Liesbeth Lim, Mario Maas
Journal: British Journal of Sports Medicine (2012)

An 11-year-old high-level competitive female gymnast presented with back pain. Approximately 10 months earlier, she experienced acute pain in the (thoracic-lumbar) mid-spine during a training camp, on the uneven bar. She reported no acute trauma. The pain was located at the paravertebral right side and was provoked by rotation movements to the right. Night-time pain existed. She went to a physiotherapist, who at physical examination found a movement with typical local fixation in the spine (paradox movement). There were no neurological symptoms. The pain was mainly felt when her posture changed from anterior flexion to extension of the spine and with rotation to the right. At this first presentation of symptoms, she trained 20 h a week.

Although physiotherapy, manual therapy and a period of rest slightly improved the situation, a setback occurred after another intensive training camp, now with continuous pain, increasing during jumping (like dismounts from the gymnastics apparatus) and running.

On examination, there was a painful right straight leg raise without neurological symptoms. There was painful limited range of motion during extension of the spine; anterior flexion was only slightly painful. The pain was again located on the right side (paravertebral) and on palpation of the vertebra in the proximal lumbar spine.

The patient was first referred for conventional radiography (figure 1) and 1 month later for MRI of the lumbar spine (figures 2 and 3).



Figure 1 
Lateral conventional radiography of the lumbar spine.





Figure 2 
Sagittal T1-weighted MRI at the level of the lumbar spine.





Figure 3 
Sagittal STIR MRI at the level of the lumbar spine.



### Diagnosis

Avulsion of the anterior ring apophysis of L1 vertebral body.

### Imaging findings

Conventional lateral radiography of the lumbar spine (figure 4) showed an irregular anterior superior …
Damage to the bases in DNA induced by stimulated human neutrophils.
Authors: J H Jackson, E Gajewski, I U Schraufstatter, P A Hyslop, A F Fuciarelli, C G Cochrane, M Dizdaroglu
Journal: Journal of Clinical Investigation (1989)

Leukocyte-induced DNA damage may partially account for the known association between chronic inflammation and malignancy. Since elucidation of the chemical nature of leukocyte-induced DNA damage may enhance our understanding of the mechanisms underlying leukocyte-induced DNA damage and the carcinogenesis associated with inflammation, the present study was undertaken to characterize the chemical modifications that occur in DNA exposed to stimulated human neutrophils. Calf thymus DNA was exposed to phorbol myristate acetate (PMA)-stimulated neutrophils in the presence or absence of exogenously added iron ions. DNA samples were subsequently hydrolyzed, derivatized and analyzed by gas chromatography-mass spectrometry with selected-ion monitoring. A variety of base modifications including cytosine glycol, thymine glycol, 4,6-diamino-5-formamidopyrimidine, 8-hydroxyadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 8-hydroxyguanine were identified. The yield of these various base products was increased by the addition of iron ions. Specifically, in the presence of physiologic quantities of iron ions, approximately 7 of every 1,000 DNA bases were modified. Addition of the superoxide anion scavenger, superoxide dismutase, the hydrogen peroxide scavenger, catalase, the hydroxyl scavenger, dimethylsulfoxide, or the iron chelator, deferoxamine, to DNA mixtures containing PMA, neutrophils, and iron ions, greatly decreased the yield of the damaged DNA base products. Our results indicate that stimulated human neutrophils can damage each of the four bases in DNA. It is likely that hydroxyl radical, generated via an iron catalyzed Haber-Weiss reaction, mediates neutrophil-induced DNA base damage, since: (a) the chemical structure of neutrophil-induced DNA base damage is consistent with a hydroxyl radical-mediated mechanism, (b) hydroxyl radical generated via ionizing radiation in aqueous solution produces DNA base modifications that are identical to neutrophil-induced DNA base modifications, (c) iron ions increase neutrophil-induced DNA base damage, and (d) iron chelators or scavengers of superoxide anion, hydrogen peroxide or hydroxyl radical decrease neutrophil-induced DNA base damage.
Pro-arrhythmogenic potential of immature cardiomyocytes is triggered by low coupling and cluster size
Authors: T DEBOER, M VANDERHEYDEN, M ROOK, R WILDERS, R BROEKSTRA, B KOK, M VOS, J DEBAKKER, T VANVEEN
Journal: Cardiovascular Research (2006)

Cell transplantation strategies to regenerate compromised myocardium take advance of in vitro generated cardiomyocytes. Common in those immature myocytes is spontaneous impulse formation and a restricted ability to establish proper electrical interaction. Spontaneous impulse formation and impaired cell-to-cell coupling have been shown to be arrhythmogenic. To investigate whether these features harbour a pro-arrhyhmogenic potential for cell transplantation, a co-culture of spontaneously active neonatal rat cardiomyocytes (NRC) and quiescent adult dog cardiomyocytes (ADC) was used.ADCs and NRCs were isolated and cultured on laminin-coated substrates. Connexin43, N-cadherin and alpha-actinin expression was evaluated with immunohistochemistry. Intercellular coupling was measured in cell pairs using the dual voltage clamp technique and fluorescent dye injection.One day after isolation, NRCs were beating spontaneously, while ADCs remained quiescent in monoculture. ADC resting membrane potential was -80.3+/-0.2 mV (mean+/-SEM, N=24) and did not change significantly over time. NRCs had a maximal diastolic potential of -65.0+/-2.8 mV (N=4). After one day of co-culture, pseudopodia-like extensions developed at the former intercalated discs of ADCs, contacting the NRCs. Only ADCs that contacted three or more NRCs started to beat in synchrony. Expression of connexin43 and N-cadherin indicated presence of electrical and mechanical junctions at the interface between the two cell-types. Transfer of Lucifer Yellow demonstrated junctional permeability between ADCs and NRCs. Junctional conductance between ADC-ADC (31.9+/-5.1 nS, N=10) and NRC-NRC (35.0+/-9.6 nS, N=6) pairs was significantly higher compared to ADC-NRC pairs (9.7+/-2.9 nS, N=8). Gap-junctional blockade with halothane reversibly abolished NRC-triggered beating of ADCs. Computer simulations demonstrated that within a delicate 'window' of gap junctional conductance small clusters of spontaneously active cells are able to induce triggered activity in quiescent mature myocytes but also in a two-dimensional sheet of ventricular cells.Spontaneously active immature cardiomyocytes are able to trigger mature cardiomyocytes depending on their level of electrical coupling and the amount of coupled immature myocytes.
The Importance of the Normality Assumption in Large Public Health Data Sets
Authors: Thomas Lumley, Paula Diehr, Scott Emerson, Lu Chen
Journal: Annual Review of Public Health (2002)

▪ Abstract It is widely but incorrectly believed that the t-test and linear regression are valid only for Normally distributed outcomes. The t-test and linear regression compare the mean of an outcome variable for different subjects. While these are valid even in very small samples if the outcome variable is Normally distributed, their major usefulness comes from the fact that in large samples they are valid for any distribution. We demonstrate this validity by simulation in extremely non-Normal data. We discuss situations in which in other methods such as the Wilcoxon rank sum test and ordinal logistic regression (proportional odds model) have been recommended, and conclude that the t-test and linear regression often provide a convenient and practical alternative. The major limitation on the t-test and linear regression for inference about associations is not a distributional one, but whether detecting and estimating a difference in the mean of the outcome answers the scientific question at hand.
Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy
Authors: Carl Persson
Journal: European Respiratory Journal (2014)

To the Editor: 

I read with interest the report by Davis et al. [1] on epithelial injury-shedding in vivo caused by tobacco smoke. Their model involves airways equipped with human-like subepithelial microvessels carrying systemic blood. By contrast, mice lack a bronchial microcirculation. Severe bronchial epithelial damage is induced with widespread cell loss from an apparently intact epithelial basement membrane. By weeklong pre-treatment with simvastatin, the smoke-induced epithelial derangement and associated inflammation are largely prevented. Although a high dose was used, the drug effect is impressive. The authors apparently excluded: 1) involvement of oxidative stress, as reflected by haem oxidase-1, in the smoke-induced epithelial desquamation; and 2) mevalonate-dependent mechanisms in the “therapeutic” effect of simvastatin. They discuss the possibility that simvastatin inhibits granulocyte-induced epithelial injury but also mention that the drug may target epithelial cells directly. Most previously reported anti-inflammatory actions of simvastatin are dependent on the mevalonate pathway, making the authors’ observations stand out. Incidentally, mevalonate independence is compatible with direct epithelial effects of simvastatin involving inhibition of interferon regulatory factor 3 [2]. By this mechanism, simvastatin reduces epithelial production of select cytokines/mediators, but there is no known link with epithelial cytoprotection. Perhaps the bronchoalveolar fluid collected by Davis et al. [1] can provide further information on released epithelial factors? For example, to what extent did the drug preserve epithelial innate immunity function?

During recent decades the epithelial field has, to a large extent, been addressed by cell culture approaches, hiding the in situ epithelium’s interaction opportunities. Particularly important is the supply of bioactive molecules and cells from a profuse subepithelial microcirculation. The in vivo approach taken by Davis et al. [1] is, therefore, commendable. However, they fail to mention that mere loss of epithelial lining cells, without inflammatory …
A CLINICAL STUDY OF ENCEPHALITIS LETHARGICA, Based on Sixty-two Cases
Authors: A. G. Gullan
Journal: BMJ (1925)

ENCEPHALITIS LETHAGIOA.2'IC BumO LETHA'.IITI1A E XIDICAL JoUUNAL were packed with gamgee tissue and towels, some tightly, others loosely, and among the contents of each drum one or more of the control tubes were enclosed.Beside each control tube was placed a small glass tube containing a sl)oring broth culture of Bacillus subtilis.The drums were tr^ated at various pressures for different times in a pressure steam sterilizer and then opened.The control tubes were matched against a colour scale prepared from tubes heated at 2390 F. for known times, and the culture tubes were opened under aseptic conditions and subcultured to test for sterility.In all, 47 comparisons were carried out, the results of which are summarized in Table I.TABLE I. Subculture ReEults.Numliber Group. of Tests.Sterile.Growth of B. subtilis.
Prognostic factors for survival of patients treated systemically for disseminated melanoma.
Authors: O Eton, S S Legha, T E Moon, A C Buzaid, N E Papadopoulos, C Plager, A M Burgess, A Y Bedikian, S Ring, Q Dong, A B Glassman, C M Balch, R S Benjamin
Journal: Journal of Clinical Oncology (1998)

The current American Joint Commission on Cancer (AJCC) staging system distinguishes between soft tissue and visceral metastases in advanced (stage IV) melanoma. We sought to verify these staging criteria and to identify prognostic variables that could be used to evaluate the impact of systemic therapy on long-term survival during the prior decade.We conducted a retrospective study of patients with advanced cutaneous melanoma enrolled in clinical trials between 1979 and 1989 at The University of Texas M.D. Anderson Cancer Center. Pretreatment age, sex, number of organs with metastases, serum levels of lactate dehydrogenase (LDH) and albumin, and period of enrollment were analyzed using a Cox proportional hazards model of survival.In univariate and multivariate analyses that involved 318 stage IV patients, normal serum levels of LDH and albumin, soft tissue and/or single visceral organ metastases (especially lung), female sex, and enrollment late in the decade were independent positive predictors for survival. In multivariate analyses, the current AJCC criteria did not significantly predict outcome. Systemic treatment response did not bias these results, and only 4% of patients had a complete response. Patients who lived more than 2 years (11%) had a mix of favorable prognostic characteristics and a high frequency of systemic or surgically induced complete response.This study supports the use of stratification parameters that reflect the favorable prognostic impact of soft tissue or single visceral organ metastases and normal serum levels of LDH and albumin at time of enrollment in advanced melanoma trials. Improved survival over the prior decade probably reflects advances in diagnostic and palliative interventions.
Studies of Vascular Patterns in Living Tumors With a Transparent Chamber Inserted in Hamster Cheek Pouch2
Authors: C. M. Goodall, A. G. Sanders, P. Shubik
Journal: JNCI Journal of the National Cancer Institute (1965)

A new transparent tissue chamber devised for in vivo microscopic study of the hamster cheek-pouch membrane is described. The morphology of the microcirculation in 4 transplantable hamster tumors has been studied in grafts made into the chamber. Grafts from several transplant generations of 2 pigmented melanomas that had the same vascular pattern, an anaplastic carcinoma of the breast, and a hemangiopericytoma without exception reproduced vascular patterns characteristic for each type of tumor. The 3 different patterns observed were distinctive and typical examples are illustrated. The possible ontogenetic significance of the characteristic anatomy of the microcirculation in these tumors is discussed.
Life-Threatening Sepsis Associated With Adjuvant Doxorubicin Plus Docetaxel for Intermediate-Risk Breast Cancer
Authors: Etienne G C Brain, Thomas Bachelot, Daniel Serin, Sylvie Kirscher, Yvon Graic, Jean-Christophe Eymard, Jean-Marc Extra, Martin Combe, Emmanuelle Fourme, Catherine Noguès, Jacques Rouëssé
Journal: JAMA (2005)

ContextAdjuvant chemotherapy with new cytotoxic agents for breast cancer must be properly assessed for toxicity.ObjectiveTo describe adverse events associated with adjuvant chemotherapy for breast cancer, which led to premature termination of a clinical trial.Design, Setting, and PatientsWe conducted a prospective randomized multicenter study (Reposant sur des Arguments Pronostiques et Prédictifs [RAPP]-01) to compare the effectiveness of 2 chemotherapy regimens. Patients (women aged 18-70 years) had primary unilateral breast cancer and either a moderate number of positive axillary lymph nodes (≤3) or no positive axillary lymph nodes (N0), but were at a high risk of relapse. Patients were treated at 11 French cancer referral centers from June 1999 through January 2003. Primary prophylaxis for febrile neutropenia was not recommended in the study protocol.InterventionsDoxorubicin, 50 mg/m2, plus docetaxel, 75 mg/m2, or doxorubicin, 60 mg/m2, plus cyclophosphamide, 600 mg/m2, given postoperatively for 4 courses.Main Outcome MeasuresThe main end point was the disease-free survival rate at 5 years, as estimated using the Kaplan-Meier product limit method. Secondary end points included safety, which is the focus of this article, and overall survival.ResultsA total of 627 women were enrolled. Median follow-up is currently too short (24 months) to analyze the primary end point. The trial was terminated prematurely when 2 deaths related to drug toxicity and 1 case of perforative peritonitis occurred among patients with febrile neutropenia, all in the doxorubicin-docetaxel group. The incidence of febrile neutropenia was significantly higher with the doxorubicin-docetaxel regimen (40.8%) than with the doxorubicin-cyclophosphamide regimen (7.1%) (P<.001).ConclusionsA high risk of life-threatening complications associated with the doxorubicin-docetaxel regimen was found in this open-label controlled trial. The doxorubicin-docetaxel combination should not be considered as an alternative to the doxorubicin-cyclophosphamide regimen outside carefully designed studies that include primary prophylaxis for febrile neutropenia.
The efficacy of medical and surgical treatment of endometriosis-associated infertility: arguments in favour of a medico-surgical aproach
Authors: J. Donnez
Journal: Human Reproduction Update (2002)

This review discusses the efficacy of a combined, medical (GnRH agonist) and surgical, therapy in endometriosis-associated infertility. Because of the limited information currently available on the activity of lesions in minimal and mild endometriosis, any absolute statement is inappropriate at this time, although some arguments exist in favour of treating endometriosis at laparoscopy. In moderate and severe endometriosis, this review provides arguments in favour of a medico-surgical approach and discusses the possibility of combining medical and surgical therapy.
Prospective Study of Pre-Gravid Sugar-Sweetened Beverage Consumption and the Risk of Gestational Diabetes Mellitus
Authors: Liwei Chen, Frank B. Hu, Edwina Yeung, Walter Willett, Cuilin Zhang
Journal: Diabetes Care (2009)

Consumption of sugar-sweetened beverages (SSBs) was related to an elevated risk of type 2 diabetes and insulin resistance in several recent studies among middle- or older-aged populations. Studies on SSB consumption and glucose intolerance among pregnant women, however, are lacking. We therefore examined the association between regular SSB consumption before pregnancy and the risk of gestational diabetes mellitus (GDM).This was a prospective study among 13,475 U.S. women who reported at least one singleton pregnancy between 1992 and 2001 in the Nurses' Health Study II. GDM was self-reported and validated by medical record review in a subsample. Cox proportional hazards models with multivariate adjustments were applied to examine the association of SSB consumption with GDM risk.During 10 years of follow-up, 860 incident GDM case subjects were identified. After adjustment for age, parity, race, physical activity, smoking, alcohol intake, prepregnancy BMI, and Western dietary pattern, intake of sugar-sweetened cola was positively associated with the risk of GDM, whereas no significant association was found for other SSBs and diet beverages. Compared with women who consumed <1 serving/month, those who consumed >or=5 servings/week of sugar-sweetened cola had a 22% greater GDM risk (relative risk 1.22 [95% CI 1.01-1.47]).Findings from this study suggest that prepregnancy higher consumption of sugar-sweetened cola (>or=5 servings/week) is associated with an elevated GDM risk, whereas no significant association with GDM risk was observed for other SSBs and diet beverages.
Expanding role for pharmacists
Authors: J G. Roberts
Journal: BMJ (1978)

suggest that this discrepancy may be due to our Japanese patients having "concomitant medical problems" or "taking various medications"leading surprisingly to a normal CO2 response.To explain their own observations Dr Griffith and his colleagues suggest a functional disorder of the brain vessels in their hypertensive patients.Inhalation of CO2 in acute experimental hypertension causes an extreme rise in cerebral blood flow (CBF).'The finding of a normal rise in CBF in a hypertensive patient during CO, inhalation signifies structural and func- tional adaptation of the resistance vessels to the hypertensive state.This is analogous to the adaptation of CBF autoregulation to high blood pressure demonstrated in hypertensive patients.;The finding of a decreased response or even a decrease in CBF during CO2 inhalation, on the other hand, may be caused by stenosing atherosclerosis of the major brain vessels.Thus experimental carotid occlusion in the baboon diminishes the rise in CBF caused by CO2 inhalation by exhausting the arteriolar dilatatory capacity in the resting state.4Our Japanese patients had bilateral carotid angiography as part of their clinical investiga- tion and were included in the CO2 reactivity study only if no significant cerebral athero- sclerosis or other abnormality was present.Further, they were as a group somewhat younger than the patients of Dr Griffith and his colleagues (mean age 43 v 50 years), who were not investigated for atherosclerosis.It may also be mentioned that the extracerebral compartment of CBF, as measured by the 13'Xe-inhalation method used by them, would be expected to decrease during CO2 inhalation.Hypercapnia causes a generalised vasocon- striction (and thereby a rise in blood pressure) and has a dilatatory effect only in limited areas such as the cerebral and coronary circulations.In conclusion, the discrepancy between the results of Dr Griffith and his colleagues and our own may be due to more pronounced atherosclerosis in the British hypertensive patients or it may be due to differences in methodology.
Concerted evolution of the immunoglobulin VH gene family.
Authors: T Gojobori, M Nei
Journal: Molecular Biology and Evolution (1984)

With the aim of understanding the concerted evolution of the immunoglobulin VH multigene family, a phylogenetic tree for the DNA sequences of 16 mouse and five human germ line genes was constructed. This tree indicates that all genes in this family have undergone substantial evolutionary divergence. The most closely related genes so far identified in the mouse genome seem to have diverged about 6 million years (MY) ago, whereas the most distantly related genes diverged about 300 MY ago. This suggests that gene duplication caused by unequal crossing-over or gene conversion occurs very slowly in this gene family. The rate of occurrence of gene duplication in the VH gene family has been estimated to be 5 x 10(-7) per gene per year, which seems to be at least about 100 times lower than that for the rRNA gene family. This low rate of concerted evolution in the VH gene family helps retain intergenic genetic variability that in turn contributes to antibody diversity. Because of accumulation of destructive mutations, however, about one-third of the mouse and human VH genes seem to have become nonfunctional. Many of these pseudogenes have apparently originated recently, but some of them seem to have existed in the genome for more than 10 MY. The rate of nucleotide substitution for the complementarity-determining regions (CDRs) is as high as that of pseudogenes. This suggests that there is virtually no purifying selection operating in the CDRs and that germ line mutations are effectively used for generating antibody diversity.