tbuckley/cabot-search huggingface dataset:
Mutations in the vasopressin V2 receptor gene in two families with nephrogenic diabetes insipidus.
Authors: E J Holtzman, L F Kolakowski, O Geifman-Holtzman, D G O'Brien, M Rasoulpour, A P Guillot, D A Ausiello
Journal: Journal of the American Society of Nephrology (1994)

Congenital nephrogenic diabetes insipidus (CNDI) is a rare X-linked disorder in which the renal collecting duct is unresponsive to arginine vasopressin, and thus, the urine is consistently hypotonic to plasma. As a result, affected individuals are unable to concentrate urine and suffer from episodes of severe dehydration and hypernatremia. Recently, the association between arginine vasopressin V2 receptor gene mutations and CNDI has been demonstrated. In this report, two additional novel molecular defects of the arginine vasopressin V2 receptor gene in CNDI families are described. In one family, the affected individual demonstrated a G-->T transversion causing a nonsense mutation in codon 231. This mutation results in a glutamic acid becoming a termination codon, causing premature termination and truncation of the encoded receptor protein. This mutation causes a NciI site within the gene to be abolished and a BsaWI site to be created. In the second family, affected individuals showed a 28-basepair duplicating insertion in the very beginning of exon 2 down-stream of the splice acceptor site. It was hypothesized that an insertion mutagenesis mechanism involves the formation of a stem-loop structure within the newly synthesized DNA strand, followed by a slipped mispairing. This may be a general mechanism for the deletion or insertion of repeated sequences within the genome. Recent data show that G-protein-coupled receptors are susceptible to many different mutations that often result in the loss of function, causing a similar clinical phenotype.
Ki67 expression as a predictor for suboptimally debulked patients with advanced epithelial ovarian cancer
Authors: S. F. Adams, D. A. Levine, L. Zhang, R. Barakat, J. Boyd, P. Gimotty, G. Coukos
Journal: Journal of Clinical Oncology (2007)

5563 Objective: The death rate from ovarian cancer has not changed significantly in several decades. Additional prognostic biomarkers may allow for more tailored chemotherapy and an improved response rate. Our aim was to clarify the utility of Ki67, a nuclear protein expressed by mitotic cells, as a prognostic marker in cases of advanced epithelial ovarian cancer (EOC). Methods: We conducted a retrospective cohort study of patients undergoing primary surgery for advanced EOC between 1989 and 2003 at one institution. All were diagnosed with serous or poorly differentiated ovarian adenocarcinoma, and received platinum/paclitaxel chemotherapy. Snap-frozen surgical specimens were subjected to immunohistochemical analysis using a monoclonal antibody against human Ki67. Cases were stratified into those wtih high (&gt;25%) or low expression (&lt;25%) of Ki67 based on the percentage of postively-staining tumor cells. Kaplan-Meier curves were used to estimate five-year survival rates, and were compared using a log-rank statistic. Results: 134 cases (106 stage III; 28 stage IV) were analyzed. Average age at diagnosis was 62 (range 26–84 years); average duration of follow-up was 42 months (range 0.7 - 128.8). 61 (45%) patients were optimally debulked. The 5-year survival rates were 24.7% and 41.4% (p=0.0421) for patients with high and low Ki67 expression, respectively. Patients in these two groups did not differ significantly with regard to age, tumor grade, debulking status, histotype, or stage. Sub-group analysis indicated that the differential effect of Ki67 expression existed exclusively among patients who were suboptimally debulked, with a 5-year survival of 16% vs. 39% (p=0.027) for cases with high vs. low Ki67 expression. There was no difference in survival among optimally debulked patients based on Ki67 expression (43% vs. 48%, p=0.890). Conclusion: Ki67 immunostaining provides robust prognostic information for patients with advanced EOC who are incompletely debulked at primary surgery. This biomarker may define subgroups of patients who would be more likely to benefit from cell-cycle dependent chemotherapy regimens, and may guide the development of future therapeutic strategies. No significant financial relationships to disclose.
SPECT Imaging in the Diagnosis of Meniscal Tears
Authors: M P Grevitt, P Allen, P J Ryan, I Fogelman
Journal: Journal of the Royal Society of Medicine (1993)

Sixty patients scheduled for arthroscopy of a knee because of suspected meniscal tears had preoperative planar and single photon emission computed tomography (SPECT) radionuclide scans. A crescentic pattern of uptake on the SPECT transaxial view was used as a criterion for diagnosing a tear of a meniscus. The sensitivity of the investigation was 77%, specificity 74%, negative predictive value (NPV) 65%, positive predictive value (PPV) 83%, and accuracy 76%. Tears of the posterior horn of the cartilage were also associated with intense focal uptake on the transaxial view as well as increased equilibrium activity in the adjacent femoral condyle. When these appearances were included as additional criteria the sensitivity rose to 90%, NPV 81%, and accuracy 84%. This study confirms the usefulness of SPECT imaging in identifying meniscal tears.
Hand Hygiene—The Case for Evidence-Based Education
Authors: S P Stone
Journal: Journal of the Royal Society of Medicine (2001)

Among the priorities identified for the National Health Service (NHS) are reductions in hospital-acquired infection and in antimicrobial resistance1. These are to be achieved by improved surveillance, optimal antibiotic prescribing and strengthening of basic infection control procedures such as handwashing. According to recent figures2,3, hospital acquired infection affects 1 in 11 inpatients, carries a 13% mortality and lengthens stay by a factor of 2.5. The extra cost to the NHS is nearly £3000 per patient, and the total annual cost is nearly £1 billion. Between 15% and 30% of hospital-acquired infection is considered preventable, but even a 10% reduction would improve bed management to the tune of 47ooo extra finished consultant episodes per year. The NHS's action plan to reduce hospital-acquired infection4 holds chief executives personally accountable, and requires handwashing to be implemented in line with Department of Health guidance5,6.

Healthcare workers' compliance with handwashing is known to be poor, with doctors performing particularly badly7,8. When the Department of Health published its handwashing guidance a storm of correspondence in the BMJ excused low compliance on grounds of lack of time, poor availability of sinks and soaps, skin sensitivity and lack of evidence. This paper reviews the evidence that patient contact results in contamination of the hands by pathogens and that washing with liquid soap and water or, better, use of an alcohol handrub, greatly reduces hand contamination and infection rates, and presents the case for making hand hygiene a medical educational priority9.
Psoriasis in association with prolactinoma: three cases
Authors: M. Sánchez Regaña, P. Umbert Millet
Journal: British Journal of Dermatology (2000)

We report three women with plaque‐type psoriasis in whom increase in severity and extent of the skin lesions correlated with the development of a prolactinoma. In all three patients, administration of bromocriptine, a dopamine agonist that suppresses the secretion of prolactin, improved the therapeutic response of the psoriasis. To our knowledge, there are no reports of an association between psoriasis and prolactinoma. In recent years it has become apparent that prolactin plays an important part in the immune reactions and exerts a proliferative effect on human keratinocytes. We, therefore, discuss the part that prolactin may play in the pathogenesis of psoriasis.
The MEK1/2 Inhibitor Pimasertib Enhances Gemcitabine Efficacy in Pancreatic Cancer Models by Altering Ribonucleotide Reductase Subunit-1 (RRM1)
Authors: Francesca Vena, Eleonora Li Causi, Manuel Rodriguez-Justo, Samantha Goodstal, Thorsten Hagemann, John A. Hartley, Daniel Hochhauser
Journal: Clinical Cancer Research (2015)

Gemcitabine, a nucleoside analogue, is an important treatment for locally advanced and metastatic pancreatic ductal adenocarcinoma (PDAC) but provides only modest survival benefit. Targeting downstream effectors of the RAS/ERK signaling pathway by direct inhibition of MEK1/2 proteins is a promising therapeutic strategy, as aberrant activation of this pathway occurs frequently in PDAC. In this study, the ability of pimasertib, a selective allosteric MEK1/2 inhibitor, to enhance gemcitabine efficacy was tested and the molecular mechanism of their interaction was investigated.
Exclusive Binding of Immunoglobulin to Fcγ Receptors on Macrophages in 3-Methylcholanthrene- Induced Murine Tumors&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: J M Lindsay, L Manning, G W Wood
Journal: JNCI Journal of the National Cancer Institute (1982)

Immunogenic, chemically induced, murine tumors generally are infiltrated with large numbers of Fc gamma receptor (Fc gamma R)-positive cells, most of which are mononuclear phagocytes. This study demonstrates in inbred C3H/HeN mice that such immunogenic tumors contain large amounts of cell-bound immunoglobulin (Ig) and that, within the sensitivity limits of indirect immunofluorescence, the tumor-associated Ig is bound exclusively to host-derived Fc gamma R-positive cells. Depletion of Fc gamma R-positive cells from tumor cell suspensions removed all Ig-bearing cells. Specific competitive elution of the endogenous Ig with heterologous nonimmune IgG established that the endogenous Ig was bound through the Fc gamma R. Tumor-associated Fc gamma R-positive, Ig-bearing cells could be detected with soluble antigen-antibody complexes, and mononuclear phagocytes to which the exogenous complexes were bound expressed Fc gamma R at a level significantly above normal. The role of this macrophage-associated Ig in determining the level of interaction between host cells and the tumor remains to be determined.
LSC 2012 abstract - The protective role of Pim1 in cigarette smoke induced damage of airway epithelium
Authors: M. de Vries, R. Gras, L.E. den Boef, M. van der Toorn, A.J.M. van Oosterhout, M.C. Nawijn
Journal: European Respiratory Journal (2012)

Rationale   The main risk factor of developing COPD is exposure to cigarette smoke. CS exposure induces airway epithelial cell damage, release of DAMPs and an innate inflammatory response. We previously observed increased expression of Pim1 in vivo after sub-chronic CS exposure in mice. Pim1 is a serine/threonine kinase involved in cell growth and survival by preventing apoptosis induction through the mitochondrial pathway. We hypothesize that Pim1 plays a protective role in the airway epithelium after CS exposure by phosphorylating BAD and enhancing cell survival.   Methods   Pim1-KO mice were exposed to CS twice a day for 4 days. Inflammatory cells and KC levels in BAL were determined. Beas-2b cells were treated with CS extract (CSE) for 4 hours with(out) Pim-inhibitor. Mitochondrial membrane potential (ΨM) and apoptosis/necrosis induction were measured by flowcytometry. BAD phosphorylation was determined by Western Blotting.   Results   CS exposure induces neutrophilic airway inflammation and increases KC levels in Pim1-KO mice, but not in WT controls. CSE induces a dose-dependent loss of BAD phosphorylation, loss of ΨM and necrotic cell death in Beas-2b cells. All of these CSE-induced effects are aggravated by inhibition of Pim1.   Conclusion   Pim1 protects airway epithelial cells from CS-induced damage and cell death by phosphorylating BAD and increasing the threshold for apoptosis. In vivo, this protective effect suffices to prevent CS-induced neutrophilic airway inflammation.
Socioeconomic Status, Urine Estrogens, and Breast Cancer Risk&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Dimitri Trichopoulos, Brian MacMahon, James Brown
Journal: JNCI Journal of the National Cancer Institute (1980)

Urine estrogens were measured in 46 women students, ages 15-18, at a middle-class high school in Athens and in 40 women of the same age residing at one of three orphanages in the same city. The lower socioeconomic status (SES) of the latter group was documented by their lower mean height (by 5.2 cm) and weight (by 5.3 kg) relative to the high school students. Both in follicular and luteal phases of the menstrual cycle, the women with lower SES had 50% higher estriol ratios (ratio of the concentration of estriol to the sum of the concentrations of estrone and estradiol). In luteal specimens the concentration of all three major estrogens was higher in the group with low SES than in the women in the other group, but the concentration of estriol was most increased. There was also an indication of less frequent anovular cycles among the women with low SES. These findings are consistent with hypotheses linking either the estriol ratio or the frequency of anovular cycles to breast cancer risk.Urine estrogen levels were measured in 46 women students, ages 15-18, at a middle-class high school in Athens, Greece and in 40 women of the same age residing at 1 of 3 orphanages in the same city. The lower (SES) socioeconomic status of the latter group was documented by their lower mean height (by 5.2 cm) and weight (by 5.3 kg) relative to the high school students. Both in follicular and luteal phases of the menstrual cycle, the women with lower SES had 50% higher estriol ratios (ratio of the concentration of estriol to the sum of the concentrations of estrogens and estradiol). In luteal specimens, the concentration of all 3 major estrogens was higher in the group with low SES than in the women in the other group, but the concentration of estriol was most increased. There was also an indication of less frequent anovulan cycles among the women with low SES. These findings are consistent with hypotheses linking either the estriol ratio or the frequency of anovular cycles to breast cancer risk.
Safety of cryo-trans bronchial biopsy in diffuse lung diseases- analysis 0f 200 cases
Authors: Evgeni Gershman, Oren Fruchter, Dror Rosengarten, Benjamin Fox, B.A. El Raouf, Victoria Rusanov, Yael Raviv, Nader Abdel-Rahman, Ludmila Fridel, M.R. Kramer
Journal: European Respiratory Journal (2014)

Introduction:   Trans-bronchial biopsy (TBB) which is performed with metal forceps (forceps-TBB) has been accepted as a useful technique in establishing diagnosis of diffuse lung diseases. The use of cryo-probe to obtain alveolar tissue (cryo-TBB) is a new method which is currently used by our institute as well as others with excellent results.   Aim:   To assess the safety of cryo-TBB compared with conventional forceps -TBB.   Methods:   We performed retrospective data evaluation of 200 cryo-TBB cases at our institute and compared them with previous cases done by forceps-TBB.  The yield of both diagnostic modalities was compared based on pathological reports. The major complications-significant bleeding and pneumothorax- were compared, along with post procedural hospitalization.   Results:   Pneumothorax was observed in 11(3.6%) cases of cryo vs. 10(4.8%) of forceps TBB without significant difference (p=0.365), even when stratified according to indications for TBB: immunocompromised patients, lung transplantation and interstitial lung diseases.  In the cryo- TBB group significant bleeding was seen in 12(5.8%) cases. The incidence was 13(4.3%) in the forceps TBB group with no significant difference (p=0.52).  There was no significant difference in the hospital admission rate between groups   Conclusion :  In patients with diffuse lung diseases cryo-TBB is as safe as forceps-TBB . As we have shown previously the pathological specimen were larger and without crush artifacts, thus, providing a better specimen for the pathologist.
Neck and other muscle pains in autonomic failure: their association with orthostatic hypotension
Authors: K M Bleasdale-Barr, C J Mathias
Journal: Journal of the Royal Society of Medicine (1998)

Neck pain in the suboccipital and paracervical region ('coathanger' configuration) is often reported by patients with autonomic failure and orthostatic hypotension. The frequency of this pain, along with pains in the buttock and calf regions, was determined by questionnaire in two major groups with primary chronic autonomic failure--pure autonomic failure (PAF) and multiple system atrophy (MSA). Comparisons were made with Parkinson's disease, cerebellar degeneration and other disorders in which neurological symptoms overlap but in which there was neither autonomic failure nor orthostatic hypotension. Neck pain was present in 93% of patients with PAF, 51% of patients with MSA and 38-47% of the non-autonomic groups. Buttock pain was present in smaller but similar proportions (8-19%) of each group, like calf pain (23-37%). Neck pain in PAF and MSA differed from that in the other groups in being relieved by sitting or lying flat and in being associated with factors that lower blood pressure in these patients. Buttock pain was posturally related in PAF and MSA; for calf pain there was no difference between groups. Neck pain was related to the degree of orthostatic hypotension; in PAF patients, whose postural blood-pressure fall was greater than that in MSA, there was a greater frequency of neck pain.
Effect of Liver Transplant on Long-term Disease-Free Survival in Children With Hepatoblastoma and Hepatocellular Cancer
Authors: Thomas A. Pham, Amy M. Gallo, Waldo Concepcion, Carlos O. Esquivel, C. Andrew Bonham
Journal: JAMA Surgery (2015)

Hepatoblastoma (HBL) and hepatocellular cancer (HCC) are the most common primary hepatic malignant neoplasms in childhood. Given the rarity of these childhood tumors and their propensity to present at advanced stages, updated long-term data are needed.To determine the efficacy of liver transplant in children with HBL or HCC.This single-institution retrospective medical record review and analysis spanned from January 1, 1997, through September 17, 2014, at Stanford University School of Medicine. A total of 40 patients younger than 18 years underwent liver transplant for treatment of HBL (n = 30) or HCC (n = 10) during the study period, with follow-up until September 17, 2014. Patients who underwent transplant for HCC included those with tumors that were greater in size than what is proposed by the Milan (a single tumor measuring ≤5 cm or ≤3 nodules measuring ≤3 cm) and University of California, San Francisco (single tumor measuring ≤6.5 cm or ≤3 nodules measuring ≤4.5 cm and a total diameter of ≤8 cm), criteria.Disease-free and overall patient survival and graft survival.Using a Kaplan-Meier survival analysis, 1-, 5-, and 10-year disease-free survival after liver transplant was 93%, 82%, and 82%, respectively, for 30 patients with HBL and 90%, 78%, and 78%, respectively, for 10 patients with HCC. Risk factors associated with HBL recurrence after transplant included having pretreatment extent of disease stage IV lesions and a longer waiting list time and being older at the time of the transplant. Recurrence was found in 2 of 7 patients with HBL and pretransplant metastases, which were not found to be an independent risk factor for recurrence. Patients with HCC larger than the proposed Milan and University of California, San Francisco, criteria experienced good 5-year disease-free (82%) and overall (78%) survival after transplant. Being older at the time of transplant (18 vs 11 years; P = .04) and the presence of metastatic disease (1 patient vs none; P = .05) were associated with HCC tumor recurrence.Liver transplant combined with chemotherapy is an excellent treatment that provides long-term disease-free survival in children diagnosed with advanced HBL and HCC. Early addition to a waiting list and aggressive multimodal therapy provide excellent results. Transplant should still be considered in children with HCC larger than the Milan and University of California, San Francisco, criteria.
Suicide and guilt as manifestations of PTSD in Vietnam combat veterans
Authors: H Hendin, A P Haas
Journal: American Journal of Psychiatry (1991)

Although studies have suggested a disproportionate rate of suicide among war veterans, particularly those with postservice psychiatric illness, there has been little systematic examination of the underlying reasons. This study aimed to identify factors predictive of suicide among Vietnam combat veterans with posttraumatic stress disorder (PTSD).Of 187 veterans referred to the study through a Veterans Administration hospital, 100 were confirmed by means of a structured questionnaire and five clinical interviews as having had combat experience in Vietnam and as meeting the DSM-III criteria for PTSD. The analysis is based on these 100 cases.Nineteen of the 100 veterans had made a postservice suicide attempt, and 15 more had been preoccupied with suicide since the war. Five factors were significantly related to suicide attempts: guilt about combat actions, survivor guilt, depression, anxiety, and severe PTSD. Logistic regression analysis showed that combat guilt was the most significant predictor of both suicide attempts and preoccupation with suicide. For a significant percentage of the suicidal veterans, such disturbing combat behavior as the killing of women and children took place while they were feeling emotionally out of control because of fear or rage.In this study, PTSD among Vietnam combat veterans emerged as a psychiatric disorder with considerable risk for suicide, and intensive combat-related guilt was found to be the most significant explanatory factor. These findings point to the need for greater clinical attention to the role of guilt in the evaluation and treatment of suicidal veterans with PTSD.
Computed tomography-detected apical bullae in young men with Marfanoid phenotype
Authors: Maria Vershinina, Dmitry Skripkin, Natalia Orlova, Yuri Ignatiev, Sviatoslav Aksenov
Journal: European Respiratory Journal (2012)

Subpleural bullae in young men are often the cause of primary spontaneous pneumothorax (SP), which is one of the common thoracic surgical conditions requiring hospital admission. Screening and prevention SP have not been developed so far, because the lung bullae pathogenesis in young people is not known. One hypothesis suggests a hereditary weakness of the connective tissue, the most studied in patients with Marfan syndrome. The aim of this study was to investigate the prevalence of asymptomatic bullae among young patients with Marfanoid phenotype. High-resolution computed tomography (CT) performed 50 clinically healthy men with no episodes of primary SP in history. Marfanoid phenotype was diagnosed in identifying specific major and minor criterion (skeletal, skin, eye, vascular, and others), which together made it impossible to diagnose the full Marfan syndrome. Deficiency of alpha 1-antitrpisin was rejected after a genetic test. The average age of the surveyed was 24 years. The men were smokers with a little history of smoking. CT showed the presence of bullae in 12 men (24%). The frequent maximal size of bullae was 0.5-1cm and the average number of bullae was 1-6. In almost all of the cases bullae were located in the apex. In 5 cases bullae were spread more extensively and were found up to the level of the carina and in 2 patients also bellow the carina. Correlation analysis confirmed the association between bulls and smoking history, as well as the severity of skeletal changes. These data confirm the importance of hereditary diseases of connective tissue in the genesis of bullous emphysema.CT scan may be useful for determining the risk and prevention of primary SP.