tbuckley/cabot-search huggingface dataset:
Pathology of the formalin-treated heterograft porcine aortic valve in the mitral position
Authors: A. G. Rose
Journal: Thorax (1972)

The mitral valve was replaced by a pig aortic valve in 33 patients at Groote Schuur Hospital. Eleven of the failed heterograft aortic valves were examined at intervals of from 2 to 32 months after insertion. Fourteen control pig aortic valves were also examined. Electron microscopy was performed on two of the failed heterograft valves and three control pig valves. Failure of the heterograft was due to stretching and deformation of the cusps with resultant valvular incompetence. Stretching of the cusp was a result of reduction in the amount of its collagen content. The elastic tissue appeared little altered. A microscopic layer of fibrin thrombus was present on the surface of 8 of the 11 valves. Only 2 of the 11 valves showed invasion of the graft by immunologically competent cells. No valve showed any sign of infection or calcification. The denatured collagen of the heterograft has a low antigenicity and also, infortunately, a limited durability.
Associated changes of lipid peroxidation and transforming growth factor beta1 levels in human colon cancer during tumour progression
Authors: F Biasi
Journal: Gut (2002)

Background: During neoplastic progression, alterations in transforming growth factor β1 (TGF-β1) dependent control of cell growth may be an important mechanism of selective proliferation of transformed cellular clones. Defective regulation of TGF-β1 receptors has been reported to occur in a number of human malignant tumours while little is known of the actual levels of this growth inhibitory cytokine in cancer. On the basis of the demonstrated ability of major lipid peroxidation products such as 4-hydroxynonenal to modulate TGF-β1 expression and synthesis, we speculated that decreased lipid oxidation, as frequently observed in neoplastic tissues, would contribute to the selective promotion of tumour growth through decreased expression of the cytokine within the tumour mass. Aims: To seek a possible association between steady state levels of major aldehydic end products of lipid peroxidation and TGF-β1 content in human colon cancer at different stages of growth. Patients and methods: Tissue biopsies from 15 adult patients with colon adenocarcinoma of different TNM and G stagings were compared with regard to lipid peroxidation aldehydes and net TGF-β1 levels. For a more comprehensive analysis, cytokine type I and II receptors were measured in tumour biopsies. In one set of experiments, to support the conclusions, the apoptotic effect of TGF-β1 was evaluated in a human colon cancer cell line, CaCo-2, retaining receptor changes consistent with those observed in cancer patients. Results: With the exception of two extremely advanced cases (T4/G3) in which tissue levels of lipid peroxidation were within the normal range, 4-hydroxynonenal was significantly decreased in all other cancer specimens. Consistent with lipid peroxidation levels, TGF-β1 protein was markedly decreased or even negligible compared with the corresponding normal tissue surrounding the tumour in all tested biopsies except for the two T4/G3 colon cancers in which cytokine content was again within the normal range. As regards TGF-β1 receptors, both in tumour sections and CaCo-2 cells, downregulation was greater for TGF-β1 receptor I than for receptor II. Of note, in CaCo-2 cells, incubation with appropriate doses of TGF-β1 led to marked nuclear fragmentation and apoptosis. Conclusions: Evasion of human colon cancer cells from TGF-β1 mediated growth inhibition appears to be due not only to downregulation of TGF-β1 receptors, which is inconsistent and unrelated to cancer development, but also to the constant low concentration of this cytokine in the tumour mass. The associated levels of lipid peroxidation aldehydes, much lower than in control tissue, probably represent a lower stimulus for TGF-β1 production in the neoplastic area and thus a favourable condition for neoplastic progression.
Peripartum Cardiomyopathy as a Part of Familial Dilated Cardiomyopathy
Authors: Karin Y. van Spaendonck-Zwarts, J. Peter van Tintelen, Dirk J. van Veldhuisen, Rik van der Werf, Jan D.H. Jongbloed, Walter J. Paulus, Dennis Dooijes, Maarten P. van den Berg
Journal: Circulation (2010)

Anecdotal cases of familial clustering of peripartum cardiomyopathy (PPCM) and familial occurrences of PPCM and idiopathic dilated cardiomyopathy (DCM) together have been observed, suggesting that genetic factors play a role in the pathogenesis of PPCM. We hypothesized that some cases of PPCM are part of the spectrum of familial DCM, presenting in the peripartum period.We reviewed our database of 90 DCM families, focusing specifically on the presence of PPCM patients. Then, in a reverse approach, we reviewed 10 PPCM patients seen in our clinic since the early 1990s and performed cardiological screening of the first-degree relatives of 3 PPCM patients who did not show a full recovery. Finally, we analyzed the genes known to be most commonly involved in DCM in the PPCM patients. We identified a substantial number (5 of 90, 6%) of DCM families with PPCM patients. Second, cardiological screening of first-degree relatives of 3 PPCM patients who did not show full recovery revealed undiagnosed DCM in all 3 families. Finally, genetic analyses revealed a mutation (c.149A>G, p.Gln50Arg) in the gene encoding cardiac troponin C (TNNC1) segregating with disease in a DCM family with a member with PPCM, supporting the genetic nature of disease in this case.Our findings strongly suggest that a subset of PPCM is an initial manifestation of familial DCM. This may have important implications for cardiological screening in such families.
Abnormal sweating patterns associated with itching, burning and tingling of the skin indicate possible underlying small-fibre neuropathy
Authors: S. Flores, M.D.P. Davis, M.R. Pittelkow, P. Sandroni, A.L. Weaver, R.D. Fealey
Journal: British Journal of Dermatology (2015)

Itching, burning, numbness and tingling of the skin are frequent reasons for dermatology consultation. We hypothesized that these sensations may be attributable to a small-fibre neuropathy. Sweating, which is mediated by small nerve fibres, may be a surrogate marker of small-fibre neuropathy.To investigate the results of thermoregulatory sweat testing (TST), which depicts and estimates whole-body sweating, in patients with itching, burning, numbness and tingling sensations.We retrospectively reviewed the medical records of 227 patients with itching, burning, numbness and tingling sensations involving the skin who were seen at our institution during 2008 and also underwent TST.The mean age of the cohort was 54 years (range 3-89), and 58% were female. In all, 149 patients (66%) had abnormal TST results; in 119 (80%) of these patients the areas of anhidrosis on TST corresponded to their symptomatic areas. For each symptom analysed separately, the area of anhidrosis correlated with the area of symptoms in most patients.Patients with burning, itching, numbness and tingling have abnormal sweating patterns and often do not sweat in the symptomatic areas. These novel findings suggest that a small-fibre neuropathy may underlie many cutaneous symptoms and that the neuropathy can be estimated using TST.
Quality of Life in Operable Colon Cancer Patients Receiving Oral Compared With Intravenous Chemotherapy: Results From National Surgical Adjuvant Breast and Bowel Project Trial C-06
Authors: Jacek A. Kopec, Greg Yothers, Patricia A. Ganz, Stephanie R. Land, Reena S. Cecchini, H. Samuel Wieand, Barry C. Lembersky, Norman Wolmark
Journal: Journal of Clinical Oncology (2007)

Purpose We compared health-related quality of life (HRQL), symptoms, and convenience of care (COC) in patients with stage II/III carcinoma of the colon who received either oral uracil/ftorafur (UFT) plus leucovorin (LV) or standard intravenous (IV) fluorouracil (FU) plus LV as adjuvant chemotherapy. Patients and Methods We measured HRQL with the Functional Assessment of Cancer Therapy–Colorectal (FACT-C) questionnaire, Short Form-36 Vitality Scale (SF-36), and a Quality of Life Rating Scale (QLRS) at baseline, once during chemotherapy, and at 1 year. We used the Symptom Distress Scale (SDS) and treatment-specific Symptom Checklist (SCL) to assess symptoms and a modified Burden of Care form to assess COC at baseline, on day 1 of each treatment cycle, and at 1 year. Repeated measures analyses controlling for demographic variables and baseline scores were used for statistical comparisons. Results The study accrued 1,608 patients, 803 to the FU arm and 805 to the UFT arm. There were no differences between the arms in overall FACT-C scores, FACT-C scores within the subscales of colon-specific, physical, emotional, social, and functional health, or QLRS scores. Patients taking UFT reported substantially higher COC. Statistically significant but small differences were observed for SF-36, favoring FU, and for SDS and SCL, both favoring UFT. Conclusion Patients perceive adjuvant treatment with UFT + LV as more convenient than standard IV treatment with FU + LV. Both regimens are well tolerated and do not differ in their impact on HRQL.
Lung function 5 yrs after allogeneic bone marrow transplantation conditioned with busulphan and cyclophosphamide
Authors: M.B. Lund, L. Brinch, J. Kongerud, J. Boe
Journal: European Respiratory Journal (2004)

Long-term data on lung function after bone marrow transplantation (BMT) are inconclusive. Previously, a persistent reduction in gas transfer 1 yr after allogeneic BMT with busulphan and cyclophosphamide conditioning was reported by the current authors. In the present study this reduction was examined to see if it was permanent, transient or progressive. Prospectively, 43 consecutive adult patients with malignant blood disorders undertook lung function measurements prior to BMT, at 3 month intervals during the 1st yr after BMT and finally after 5 yrs. Mean baseline lung function values were &gt;90% predicted. Within the 1st yr after BMT a transient decline in lung volumes and a persistent reduction in gas transfer were observed. After 5 yrs, baseline values were restored for all variables, except in four patients who developed obliterative bronchiolitis. Acute leukaemia and smoking were independently associated with gas transfer reductions at baseline and during the 1st yr after BMT. Allogeneic bone marrow transplantation with busulphan and cyclophosphamide conditioning was associated with a reduction in gas transfer 1 yr after bone marrow transplantation but baseline values were usually restored after 5 yrs. Since recovery may be gradual and slow, an observation period &gt;1 yr is required before drawing conclusions concerning the development of a permanent reduction in lung function after allogeneic bone marrow transplantation conditioned with busulphan and cyclophosphamide.
Are anorexic tendencies prevalent in the habitual runner?
Authors: G D Wheeler, S R Wall, A N Belcastro, P Conger, D C Cumming
Journal: British Journal of Sports Medicine (1986)

To investigate whether runners displayed any of the abnormalities characteristic of patients with anorexia nervosa, we conducted a cross sectional study of 31 high mileage, 18 low mileage runners and 18 non-running controls. Subjects completed a personal data questionnaire, the Jackson Personality Inventory (JPI) and the Eating Attitudes Questionnaire (EAT), underwent a body image test and a blood sample was obtained for measurement of reproductive, thyroid and adrenal hormones. High mileage runners scored significantly higher infrequency scores on the JPI than sedentary controls but there was no evidence of psychopathology. The high mileage runners also significantly overestimated waist width and there were small but statistically significant differences in EAT scores between controls and the runner groups. Ten of 49 runners had EAT scores beyond two standard deviations above the mean of non-running controls. Serum total, free and non-specifically bound testosterone and prolactin levels were significantly lower in high mileage runners than controls. LH, FSH, cortisol and thyroid hormones were not significantly different. There were no significant differences in any hormone between low mileage runners and controls. displayed no clear abnormalities characteristic of patients with anorexia The results suggested that running may have a chronic effect on serum testosterone and prolactin levels in high mileage but not low mileage runners. Although there was no significant evidence of anorexia nervosa on testing the runners with EAT, the overestimation of waist size provided some evidence of a distortion of body image in the high mileage runners. Runners displayed no clear abnormalities characteristic of patients with anorexia nervosa.
Ethics and Regulation of Clinical Research.
Journal: Annals of Internal Medicine (1986)

Research with human subjects is an essential part of modern medicine. Since the 1960s, when knowledge of research abuses surfaced and federal regulation of human subject research began, it has been a focus of ethical and regulatory controversy. Today, a regulatory system of prior review by mixed-peer bodies, called institutional review boards (IRBs), is firmly in place in every hospital, medical school, and research facility in the country.  Robert Levine's Ethics and Regulation of Clinical Research is an excellent summary of the key ethical and regulatory issues that arise in running the IRB system. The author draws on his wide experience in human subject research as chair of the Human Use Committee of the Yale University School of Medicine, as consultant and member of various national commissions, as editor of Clinical Research and IRB: A Review of Human Subject Research , and as a prolific writer and speaker on the subject.
Hugh Lister McMullen
Authors: W. M. D. McMullen
Journal: BMJ (2014)

Protection from yearly recurring, highly acute infections with a pathogen that rapidly and continuously evades previously induced protective neutralizing Abs, as seen during seasonal influenza virus infections, can be expected to require a B cell response that is too highly variable, able to adapt rapidly, and able to reduce morbidity and death when sterile immunity cannot be garnered quickly enough. As we outline in this <i>Brief Review</i>, the influenza-specific B cell response is exactly that: it is multifaceted, involves both innate-like and conventional B cells, provides early and later immune protection, employs B cells with distinct BCR repertoires and distinct modes of activation, and continuously adapts to the ever-changing virus while enhancing overall protection. A formidable response to a formidable pathogen.
Spiral Waves and Reentry Dynamics in an In Vitro Model of the Healed Infarct Border Zone
Authors: Marvin G. Chang, Yibing Zhang, Connie Y. Chang, Linmiao Xu, Roland Emokpae, Leslie Tung, Eduardo Marbán, M. Roselle Abraham
Journal: Circulation Research (2009)

Reentry underlies most ventricular tachycardias (VTs) seen postmyocardial infarction (MI). Mapping studies reveal that the majority of VTs late post-MI arise from the infarct border zone (IBZ).To investigate reentry dynamics and the role of individual ion channels on reentry in in vitro models of the "healed" IBZ.We designed in vitro models of the healed IBZ by coculturing skeletal myotubes with neonatal rat ventricular myocytes and performed optical mapping at high temporal and spatial resolution. In culture, neonatal rat ventricular myocytes mature to form striated myocytes and electrically uncoupled skeletal myotubes simulate fibrosis seen in the healed IBZ. High resolution mapping revealed that skeletal myotubes produced localized slowing of conduction velocity (CV), increased dispersion of CV and directional-dependence of activation delay without affecting myocyte excitability. Reentry was easily induced by rapid pacing in cocultures; treatment with lidocaine, a Na(+) channel blocker, significantly decreased reentry rate and CV, increased reentry path length and terminated 30% of reentrant arrhythmias (n=18). In contrast, nitrendipine, an L-type Ca(2+) channel blocker terminated 100% of reentry episodes while increasing reentry cycle length and path length and decreasing reentry CV (n=16). K(+) channel blockers increased reentry action potential duration but infrequently terminated reentry (n=12).Cocultures reproduce several architectural and electrophysiological features of the healed IBZ. Reentry termination by L-type Ca(2+) channel, but not Na(+) channel, blockers suggests a greater Ca(2+)-dependence of propagation. These results may help explain the low efficacy of pure Na(+) channel blockers in preventing and terminating clinical VTs late after MI.
Chemotherapy for Cancer by Perfusion in the U.S.A
Authors: A. L. Abel
Journal: BMJ (1960)

Could I ask one more question, I think of Dr. Suzman again, who has experi- ence of these things in Johannesburg ?It is said there that emboli commonly occur in 50% of the cases.How, in fact, do they come ?Is thrombosis in the ventricle a common feature ?Dr. DONIACH: It was present in the ventricle in the one or two recorded cases.Dr. SuzmAN: I showed a case like this with Dr. Evan Bedford in 1943 or 1944.It was a young man, and we eventually made this clinical diagnosis of so-called endomyocardial fibrosis.He ultimately died.We also thought he was, a traumatic case, that he might have bad an injury to his heart during a boxing bout.He died under an anaesthetic while receiving thiopentone.They quite commonly die suddenly during a minor operation.At necropsy he had a large area of fibrosis with thrombosis in the ventricle; he was a man in his early twenties, a white man.Professor McMicHAEL: We now thank Dr. Campbell for leading this discussion.His clinical approach was splendid, as nobody really knows the answer, either clinically or pathologically.
Implementation of self management support for long term conditions in routine primary care settings: cluster randomised controlled trial
Authors: A. Kennedy, P. Bower, D. Reeves, T. Blakeman, R. Bowen, C. Chew-Graham, M. Eden, C. Fullwood, H. Gaffney, C. Gardner, V. Lee, R. Morris, J. Protheroe, G. Richardson, C. Sanders, A. Swallow, D. Thompson, A. Rogers
Journal: BMJ (2013)

<b>Objective</b> To determine the effectiveness of an intervention to enhance self management support for patients with chronic conditions in UK primary care. <b>Design</b> Pragmatic, two arm, cluster randomised controlled trial. <b>Setting</b> General practices, serving a population in northwest England with high levels of deprivation. <b>Participants</b> 5599 patients with a diagnosis of diabetes (n=2546), chronic obstructive pulmonary disease (n=1634), and irritable bowel syndrome (n=1419) from 43 practices (19 intervention and 22 control practices). <b>Intervention</b> Practice level training in a whole systems approach to self management support. Practices were trained to use a range of resources: a tool to assess the support needs of patients, guidebooks on self management, and a web based directory of local self management resources. Training facilitators were employed by the health management organisation. <b>Main outcome measures</b> Primary outcomes were shared decision making, self efficacy, and generic health related quality of life measured at 12 months. Secondary outcomes were general health, social or role limitations, energy and vitality, psychological wellbeing, self care activity, and enablement. <b>Results</b> We randomised 44 practices and recruited 5599 patients, representing 43% of the eligible population on the practice lists. 4533 patients (81.0%) completed the six month follow-up and 4076 (72.8%) the 12 month follow-up. No statistically significant differences were found between patients attending trained practices and those attending control practices on any of the primary or secondary outcomes. All effect size estimates were well below the prespecified threshold of clinically important difference. <b>Conclusions</b> An intervention to enhance self management support in routine primary care did not add noticeable value to existing care for long term conditions. The active components required for effective self management support need to be better understood, both within primary care and in patients' everyday lives. <b>Trial registration</b> Current Controlled Trials ISRCTN90940049.
Obesity in Britain: gluttony or sloth?
Authors: A. M Prentice, S. A Jebb
Journal: BMJ (1995)

The prevalence of clinical obesity in Britain has doubled in the past decade. The Health of the Nation initiative has set ambitious targets for reversing the trend in recognition of the serious health burden which will accrue, but efforts to develop prevention and treatment strategies are handicapped by uncertainty as to the aetiology of the problem. It is generally assumed that ready access to highly palatable foods induces excess consumption and that obesity is caused by simple gluttony. There is evidence that a high fat diet does override normal satiety mechanisms. However, average recorded energy intake in Britain has declined substantially as obesity rates have escalated. The implication is that levels of physical activity, and hence energy needs, have declined even faster. Evidence suggests that modern inactive lifestyles are at least as important as diet in the aetiology of obesity and possibly represent the dominant factor.
Investigation of growth, development, and factors associated with injury in elite schoolboy footballers: prospective study
Authors: A. Johnson, P. J. Doherty, A. Freemont
Journal: BMJ (2009)

Objective To investigate the differences between skeletal and chronological age and to assess the role of maturity status, anthropometric data, and football related variables in explaining injury statistics in elite schoolboy footballers. Design Prospective study of injuries in schoolboy footballers according to skeletal age. Setting Premier league football club in England. Participants 292 schoolboy players (age 9-16) registered at the club Interventions Annual x ray film of hand or wrist. Main outcome measures Data on injury 2001-7. Skeletal age determined with the Fels method. Skeletal age of more than one year above chronological age was classified as an early maturer, within one year as a normal maturer, and more than one year below normal as a late maturer. Injury and hours of training and rates of exposure to match play. Results Over six years 476 injuries were reported. The mean chronological age (11.74 (SD 2.35) years) and skeletal age defined by x ray picture (12.08 (SD 3.14) years) showed a significant mean difference of −0.344 (95% confidence interval −0.490 to −0.198; t =−4.64, df=280). Analysis of covariance showed that injury incidents did not differ significantly with maturity status after adjusting for training time, playing time, height, and position played ( F =0.32,160, P=0.73). General log linear analysis with a Poisson model showed that difference in maturity, playing hours, and training hours collectively explained 48% of the variance in injury incidents. Injury exposure rates differed considerably, with 1.44/1000 hours for training and 10.5/1000 hours for match play. Conclusion Maturity, defined by the difference between chronological age and skeletal age, plus training and playing hours together predict injury in schoolboy footballers. Injury exposure rates were higher for match play than training, which could have implications for targeting preventative interventions by academy staff. The use of skeletal age measurements to establish accurate “windows of opportunity” for training is more appropriate than the commonly used chronological age. Caution is needed when interpreting differences in injury occurrence as the factors that contribute are often complex.