Miracle-dz/UniFAR-FTUs huggingface dataset:
Survival analysis in families affected by hereditary non‐polyposis colorectal cancer

Previous survival studies suggested a better prognosis of hereditary nonpolyposis colorectal cancer (HNPCC) patients compared with the sporadic counterpart. In the present study we evaluated the clinical outcome of HNPCC patients with respect to that of patients with colorectal cancer recorded in a population‐based cancer registry. We assessed survival of 85 colorectal cancer patients from 24 unrelated families defined as having HNPCC according to the criteria of the International Collaborative Group, for whom adequate information on subject‐ and tumor‐related parameters and a 5‐year follow‐up (cancer diagnosis from 1980‐1989) were available. Three hundred and seventy‐seven colorectal cancer patients, registered from 1984‐1986, with a 5‐year follow‐up, were used for comparison. Colorectal cancer‐specific 5‐year survival rates were 55.2% and 42.5% for HNPCC and non‐HNPCC, respectively. Using Cox regression analysis, tumor staging and location were independently associated with survival, whereas HNPCC diagnosis was not. Stage II HNPCC cases exhibited a better prognosis than non‐HNPCC patients. By Cox regression analysis, none of the variables were significantly related to survival. Both overall and stage II HNPCC cases showed a survival advantage in comparison with non‐HNPCC patients. However, the difference disappeared when clinical and pathological variables were controlled for with a Cox regression analysis. Int. J. Cancer 71:373‐376, 1997. © 1997 Wiley‐Liss Inc.
Predicting subsequent relapse by drug‐related cue‐induced brain activation in heroin addiction: an event‐related functional magnetic resonance imaging study

Abnormal salience attribution is implicated in heroin addiction. Previously, combining functional magnetic resonance imaging (fMRI) and a drug cue‐reactivity task, we demonstrated abnormal patterns of subjective response and brain reactivity in heroin‐dependent individuals. However, whether the changes in cue‐induced brain response were related to relapse was unknown. In a prospective study, we recruited 49 heroin‐dependent patients under methadone maintenance treatment, a gold standard treatment (average daily dose 41.8 ± 16.0 mg), and 20 healthy subjects to perform the heroin cue‐reactivity task during fMRI. The patients' subjective craving was evaluated. They participated in a follow‐up assessment for 3 months, during which heroin use was assessed and relapse was confirmed by self‐reported relapse or urine toxicology. Differences between relapsers and non‐relapsers were analyzed with respect to the results from heroin‐cue responses. Compared with healthy subjects, relapsers and non‐relapsers commonly demonstrated significantly increased brain responses during the processing of heroin cues in the mesolimbic system, prefrontal regions and visuospatial‐attention regions. However, compared with non‐relapsers, relapsers demonstrated significantly greater cue‐induced craving and the brain response mainly in the bilateral nucleus accumbens/subcallosal cortex and cerebellum. Although the cue‐induced heroin craving was low in absolute measures, the change in craving positively correlated with the activation of the nucleus accumbens/subcallosal cortex among the patients. These findings suggest that in treatment‐seeking heroin‐dependent individuals, greater cue‐induced craving and greater specific regional activations might be related to reward/craving and memory retrieval processes. These responses may predict relapse and represent important targets for the development of new treatment for heroin addiction.
Spectrum and frequency of ophthalmologic manifestations in patients with inflammatory bowel disease: A prospective single‐center study

Background: The frequency and spectrum of ophthalmologic manifestations in patients with inflammatory bowel disease (IBD) has been reported to vary among studies; however, rare and silent manifestations have not been extensively studied. Methods: This was a prospective study of 60 patients diagnosed with IBD who underwent full ophthalmologic examination, including visual acuity, slit lamp examination of the anterior segments, intraocular pressure, and fundus examination accompanied by color photography. Thirty‐seven (61,7%) patients were diagnosed with ulcerative colitis (UC) and 23 (38,3%) with Crohn's disease (CD). Data from 276 control individuals were used for the determination of the prevalence of dry eye in our area. Results: Ophthalmologic manifestations were diagnosed in 26 (43%) patients (14 UC, 12 CD; 12 males and 14 females). Conjunctivitis was diagnosed in 1 patient (CD), episcleritis in 2 patients (UC), and iridocyclitis in 3 (CD). Fundus examination showed 1 patient (CD) with unilateral choroiditis, 1 (UC) with retinal vasculitis, and 1 (CD) with optic neuritis. Retinal pigment epithelium disturbances (RPED) were present in 3 patients (1 CD, 2 UC) and 2 had serous retinal detachment. In total, 13/60 patients (22%) had dry eye compared with the 11% prevalence in controls. Eight patients developed glucocorticosteroid‐induced cataracts, 2 of them treated surgically. Conclusions: This study demonstrated the prevalence of the spectrum of ophthalmologic manifestations in the IBD population, including some rare and silent findings that may merit consideration and early intervention.
Expression patterns of claudins 1, 4, and 7 and their prognostic significance in nasopharyngeal carcinoma.

PURPOSE Tight junction (TJ) proteins in the cells organize paracellular permeability, and they have a critical role in apical cell-to-cell adhesion and epithelial polarity. In our study, the expression patterns of claudins 1, 4, and 7 and their relationship with prognosis were determined in patients with nasopharyngeal carcinoma. METHODS Claudins 1, 4, and 7 were stained immunohistochemically in 18 biopsy samples of nasopharyngeal carcinomas that included non-neoplastic surface epithelium and dysplastic epithelium in addition to the tumor tissue. The files of these patients were scanned and the stage of disease and treatment received were obtained along with demographic data such as age and gender. RESULTS Overexpression of claudins 1, 4, and 7 in non-neoplastic surface epithelium was found in 14 (77.7%), 16 (88.8%), and 10 (55.5%) cases respectively; in dysplastic surface epithelium overexpression was found in 8 (44.4%), 13 (72.2%), and 4 (22.2%) cases, respectively; and in invasive tumor areas overexpression was found in 13 (72.2%), 9 (50%), and 10 (55.6%) cases respectively. Increased claudin 4 expression was related to advanced stage (p=0.014). There was a significant relationship determined between claudin 4 and 7 expression and decreased survival (p=0.018, p=0.024, respectively). CONCLUSION The fact that a statistically significant relationship was found between claudin 4 expression and advanced stage, and similarly a statistically significant relationship was found between claudin 4 & 7 expression and decreased survival gives rise to thoughts that especially claudin 4 and 7 could have different tumorigenic effects on nasopharyngeal carcinoma besides their known adhesion characteristics.
Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation.

BACKGROUND Aging is associated with oxidative stress, but underlying mechanisms remain poorly understood. OBJECTIVE We tested whether glutathione deficiency occurs because of diminished synthesis and contributes to oxidative stress in aging and whether stimulating glutathione synthesis with its precursors cysteine and glycine could alleviate oxidative stress. DESIGN Eight elderly and 8 younger subjects received stable-isotope infusions of [2H(2)]glycine, after which red blood cell (RBC) glutathione synthesis and concentrations, plasma oxidative stress, and markers of oxidant damage (eg, F(2)-isoprostanes) were measured. Elderly subjects were restudied after 2 wk of glutathione precursor supplementation. RESULTS Compared with younger control subjects, elderly subjects had markedly lower RBC concentrations of glycine (486.7 ± 28.3 compared with 218.0 ± 23.7 μmol/L; P < 0.01), cysteine (26.2 ± 1.4 compared with 19.8 ± 1.3 μmol/L; P < 0.05), and glutathione (2.08 ± 0.12 compared with 1.12 ± 0.18 mmol/L RBCs; P < 0.05); lower glutathione fractional (83.14 ± 6.43% compared with 45.80 ± 5.69%/d; P < 0.01) and absolute (1.73 ± 0.16 compared with 0.55 ± 0.12 mmol/L RBCs per day; P < 0.01) synthesis rates; and higher plasma oxidative stress (304 ± 16 compared with 346 ± 20 Carratelli units; P < 0.05) and plasma F(2)-isoprostanes (97.7 ± 8.3 compared with 136.3 ± 11.3 pg/mL; P < 0.05). Precursor supplementation in elderly subjects led to a 94.6% higher glutathione concentration, a 78.8% higher fractional synthesis rate, a 230.9% higher absolute synthesis rate, and significantly lower plasma oxidative stress and F(2)-isoprostanes. No differences in these measures were observed between younger subjects and supplemented elderly subjects. CONCLUSIONS Glutathione deficiency in elderly humans occurs because of a marked reduction in synthesis. Dietary supplementation with the glutathione precursors cysteine and glycine fully restores glutathione synthesis and concentrations and lowers levels of oxidative stress and oxidant damages. These findings suggest a practical and effective approach to decreasing oxidative stress in aging.
Differential regulation of p21 by p53 and Rb in cellular response to oxidative stress

Oxidative stress to mammalian cells causes cellular damage and triggers inducible cellular responses leading to cell death by apoptosis. In this paper, we report that p53 was required for programmed cell death induced by oxidative stress in both mouse and human cells and that p53 transactivation was involved in induction of oxidative cell death. Furthermore, we show that p21 was highly responsive to oxidative stress in a p53‐dependent manner and that ectopic expression of p21 could increase cellular susceptibility to oxidative stress in the absence of p53. However, p21 was not required for p53‐directed oxidative cell death because mouse embryo fibroblasts MEFs lacking p21(p21–/– MEFs) were still susceptible to oxidative cell death. Interestingly, bax, a cell‐death mediator regulated by p53, was overexpressed in p21–/– MEFs that underwent cell death by oxidative stress, suggesting a compensation for loss of p21 that may be responsible for the existence of cell‐death responses in p21‐knockout mouse fibroblasts. Finally, we provide evidence that the retinoblastoma gene product (Rb) is a negative regulator of p21 and a repressor of the cellular apoptotic process. Because p21 is regulated by p53 positively and by Rb negatively, p21 may be a link between p53 and Rb in determining cell fate after oxidative damage. Mol. Carcinog. 24:15–24, 1999. © 1999 Wiley‐Liss, Inc.
Effect of Experimental Diabetes Mellitus on Plasma Lactate Dehydrogenase and Glutamic Oxaloacetic Transaminase Levels in Rabbits

Hyperglycemia was induced in 20 male, white, New Zealand rabbits (2-3 kg) (Oryctolagus cuniculus huxley) by alloxan (100 mg/kg body weight, I.V.) and maintained for 16 weeks without insulin treatment. Blood samples were taken from both diabetic and non-diabetic rabbits at the same time for measurement of plasma enzymes. Levels of glutamic oxalacetic transaminase (GOT) and lactate dehydrogenase (LDH) were determined after treatment. The levels of LDH and GOT were 155.6 ± 41.9 U/L and 47.0 ± 20.4 U/L in the control group respectively. These parameters were 286.9 ± 142.9 U/L and 93.9 ± 62.5 U/L in the diabetic group respectively. It was observed that LDH (p < 0.05) was significantly increased, whereas GOT was not significantly increased (p > 0.05) in the diabetic group. In conclusion, we agree that routine use of LDH measurement to monitor diabetic status may be useful, but the characteristic parameters of diabetes mellitus are better indicators.
Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study.

OBJECTIVE To examine the efficacy and safety of the humanized anti-interleukin-6 receptor antibody tocilizumab combined with conventional disease-modifying antirheumatic drugs (DMARDs) in patients with active rheumatoid arthritis (RA). METHODS A total of 1,220 patients were randomized (2:1 ratio) in the phase III, double-blind, placebo-controlled, multicenter TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy) study. Patients remained on stable doses of DMARDs and received tocilizumab 8 mg/kg or placebo (control group) every 4 weeks for 24 weeks. RESULTS At week 24, the proportion of patients achieving a response according to the American College of Rheumatology criteria for 20% improvement (ACR20) was significantly greater in the tocilizumab plus DMARD group than in the control group (61% versus 25%; P<0.0001). Secondary end points including 50% or 70% improvement (ACR50/70), the Disease Activity Score in 28 joints (DAS28), DAS28 remission responses (DAS28<2.6), European League Against Rheumatism responses, and systemic markers such as the C-reactive protein and hemoglobin levels showed superiority of tocilizumab plus DMARDs over DMARDs alone. Seventy-three percent of patients in the tocilizumab group had >or=1 adverse event (AE), compared with 61% of patients in the control group. AEs leading to withdrawal from the study were infrequent (4% of patients in the tocilizumab group and 2% of those in the control group). Serious AEs occurred in 6.7% and 4.3% of patients in the tocilizumab and control groups, respectively, and serious infections occurred in 2.7% and 1.9%, respectively. Elevations in the alanine aminotransferase level, from normal at baseline to >3-fold the upper limit of normal, occurred in 4% of patients in the tocilizumab group and 1% of those in the control group, and elevated total cholesterol levels were observed in 23% and 6% of patients, respectively. Sixteen patients started lipid-lowering therapy during the study. Grade 3 neutropenia occurred in 3.7% of patients receiving tocilizumab and none of the patients in the control group, and no grade 4 neutropenia was reported. CONCLUSION Tocilizumab combined with any of the DMARDs evaluated was safe and effective in reducing articular and systemic symptoms in patients with an inadequate response to these agents.
High‐dose vincristine, fractionated total‐body irradiation and cyclophosphamide as conditioning regimen in allogeneic and autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: a 7‐year Italian multicentre study

We investigated the feasibility and efficacy of high‐dose vincristine (4 mg/m2 over 4 d) combined with fractionated total body irradiation (F‐TBI) (200 cGyx2 over 3 d) and cyclophosphamide (60 mg/kg for 2 d) as a preparative regimen in allogeneic (AlloBMT) and autologous (ABMT) bone marrow transplantation for 75 consecutive children (median age at transplant 8‐5 years) with acute lymphoblastic leukaemia in second complete remission (CR). Median duration of first CR was 26 and 25 months in the AlloBMT and ABMT group, respectively. Of the 46 patients who underwent AlloBMT, 33 had isolated or combined marrow relapse and 13 isolated extramedullary relapse. Of the 29 patients given ABMT, 23 had preBMT isolated or combined marrow relapse and six isolated extramedullary relapse. 44/75 patients are alive and in CR at a median follow‐up of 35 months (range 10‐90 months). Seven children given AlloBMT (15.8%) and two given ABMT (7%) died from transplant‐related causes. No major early organ toxicity, including vincristine‐related toxicity, was recorded. The overall 3‐year EFS estimate (95% CL) was 53.8% (42‐66%): in particular, 58.2% (40‐76%) for AlloBMT and 27.6% (9‐46%) for ABMT patients who experienced a marrow relapse before transplant. The overall 3‐year relapse rate estimate (95% CL) was 39.2% (27‐51%): in particular, 30.1% (12‐49%) in the AlloBMT group and 72% (54‐91%) in the ABMT group (P < 0.01) who presented a preBMT isolated or combined marrow relapse. We conclude that the conditioning regimen with high‐dose vincristine combined with cyclophosphamide and F‐TBI is feasible and promising, although its therapeutic advantage should be tested in larger series of patients enrolled in randomized studies.
Dynamic balance of the aortomitral junction.

OBJECTIVE The aortic and mitral valves have been studied in isolation, as if their functions were independent. We hypothesized that both valves work in synchrony on the basis of the shared myocardial pump and orifice. METHODS Six sonometric crystals (7 sheep) were placed in both trigones, the midpoint of the anterior and posterior anulus, and the lateral extremities of the posterior anulus. In a separate series of animals, 3 crystals (8 sheep) were implanted in the aortic annular base of the right, left, and noncoronary sinuses of Valsalva. In an acute, open-chest model, under stable hemodynamic conditions, geometric changes were time related to simultaneous left ventricular and aortic pressures. RESULTS From mid-diastole to end-systole, the mitral anulus area contracted by -16.1% +/- 1.9% (mean +/- SEM), whereas the aortic base area expanded by +29.8% +/- 3.3% during systole. The mitral anulus deformation was heterogeneous. In systole, the anterior mitral anulus expanded (intertrigonal distance, +11.5% +/- 2.3%) and the posterior mitral anulus contracted (distance between lateral extremities of the posterior anulus, -12.1% +/- 1.5%). The intertrigonal distance corresponded to the base of the left and noncoronary sinus of Valsalva, which expanded similarly during systole (+12.9% +/- 2.0%). The anteroposterior diameter of the mitral anulus was reduced twice that of the transverse diameter. This disparity of reduction can be explained by the posterior displacement of the intertrigonal area corresponding to the systolic aortic root expansion. CONCLUSIONS Mitral anulus deformation is closely related to aortic root dynamics. During systole, the posterior movement of the aortic curtain allows for aortic root expansion, probably to maximize ejection, whereas during diastole, aortic root reduction participates in mitral anulus dilatation. These findings should affect mitral and aortic surgical approaches.
Transgenic rootworm corn: assessing potential agronomic, economic, and environmental benefits.

The potential benefits of transgenic rootworm corn (Cry3Bb1 protein) are expected to include: increased root protection; increased intangible benefits to farmers (safety of not being exposed to insecticides, ease of use and handling, time and labor savings, better pest control); increased economic benefits to farmers ($231 million from yield gains [$25-$75/acre relative to no insecticide control, $4-$12/acre relative to control with a soil insecticide] and $58 million in reduced insecticide risks and time savings); reduced incidence of corn stalk rot; and increased yield protection (9 to 28% relative to no insecticide use, 1.5 to 4.5% relative to control with a soil insecticide). If transgenic rootworm corn is planted on 10 million acres, the annual impact will be a reduction of 5,344,462 lb a.i. (75.2%) of insecticide use; increased resource conservation (3.07 to 5.23 million gal of diesel fuel equivalents conserved that would have been consumed in the manufacture and delivery of insecticides); increased water conservation (5,657,734 gal of water not used in insecticide application); conservation of aviation fuel (68,845 gal of aviation fuel not used); reduced farm waste (1,187,035 fewer insecticide containers used); increased planting efficiency; and improved safety to wildlife and other nontarget organisms.
Primary hyperparathyroidism.

OBJECTIVE The aim of the study is to present the clinical pattern, surgical indication and management of primary hyperparathyroidism in a teaching hospital in the Kingdom of Saudi Arabia (KSA). METHODS The records of patients who underwent surgical treatment for primary hyperparathyroidism at the King Khalid University Hospital, Riyadh, KSA from March 1992 to October 2002 were reviewed for epidemiological data, biochemical, radiological investigation, operative procedures, histopathology result, preoperative localization studies included neck ultrasonogram, neck computerized tomography and thallium-technetium subtraction scan. All patients underwent surgery under general anesthesia and procedures were bilateral, unilateral neck exploration, or minimal invasive parathyroidectomy. RESULTS A total of 41 patients with diagnosis of primary hyperparathyroidism were reviewed. There were 30 females and 11 males with a mean age of 42 years (range 14-78 years). The musculoskeletal symptoms were the major symptoms in 30 patients (73%) followed by renal stone in 6 patients (14.6%), peptic ulcer in 2, acute pancreatitis in one, asymptomatic patients accounted for 5% (2 patients) and the thallium-technetium scan has the highest sensitivity rate (89%) among the preoperative localization studies. The histopathological results showed adenoma in 36 cases (87.8%), hyperplasia in 3 cases (7.3%) and no pathology found in 2 cases. CONCLUSION Almost all the patients presented with late symptoms and complications of primary hyperparathyroidism, the number of asymptomatic patients, is low due to lack of routine serum calcium check up. Owing to the high sensitivity of thallium-technetium scan and the relatively low incidence of hyperplasia (7.3%), we believe that unilateral neck exploration guided by preoperative scan is a suitable procedure for primary hyperparathyroidism.
Eosinophilic esophagitis.

Purpose of review Previously perceived as an anomaly, eosinophilic esophagitis is now frequently diagnosed by both pediatric and adult specialists including gastroenterologists, allergists, pathologists, and otolaryngologists. Research efforts initially focused on characterization of the clinical, endoscopic, and histologic features of this disorder. In the last 3 years, the research focus has evolved into understanding its immunologic and demographic features as well as the development of efficacious therapies. Recent findings Population-based demographic studies have documented the unique epidemiologic parameters of eosinophilic esophagitis, some of its natural history, and its increasing frequency. Basic research efforts have identified cytokines relevant toward development of eosinophilic esophagitis, including interleukin-5 and interleukin-13. Clinical efforts have established the efficacy of dietary and medical treatments. Some treatments result in symptomatic improvement with ongoing inflammation, so a debate is ensuing over the long-term effect of asymptomatic esophageal inflammation. Summary Understanding of eosinophilic esophagitis has evolved to a point at which patients can be appropriately diagnosed and initially treated; however, a paucity of long-term outcome data prevents the creation of uniform recommendations for the clinical care of patients with eosinophilic esophagitis.