Miracle-dz/UniFAR-FTUs huggingface dataset:
Octreotide acetate long-acting formulation versus open-label subcutaneous octreotide acetate in malignant carcinoid syndrome.

PURPOSE Subcutaneous (SC) octreotide acetate effectively relieves the diarrhea and flushing associated with carcinoid syndrome but requires long-term multiple injections daily. A microencapsulated long-acting formulation (LAR) of octreotide acetate has been developed for once-monthly intramuscular dosing. PATIENTS AND METHODS A randomized trial compared double-blinded octreotide LAR at 10, 20, and 30 mg every 4 weeks with open-label SC octreotide every 8 hours for the treatment of carcinoid syndrome. Seventy-nine patients controlled with treatment of SC octreotide 0.3 to 0.9 mg/d whose symptoms returned during a washout period and who returned for at least the week 20 evaluation constituted the efficacy-assessable population. RESULTS Complete or partial treatment success was comparable in each of the four arms of the study (SC, 58.3%; 10 mg, 66.7%; 20 mg, 71.4%; 30 mg, 61.9%; P> or =.72 for all pairwise comparisons). Control of stool frequency was similar in all treatment groups. Flushing episodes were best controlled in the 20-mg LAR and SC groups; the 10-mg LAR treatment was least effective in the control of flushing. Treatment was well tolerated by patients in all four groups. CONCLUSION Once octreotide steady-state concentrations are achieved, octreotide LAR controls the symptoms of carcinoid syndrome at least as well as SC octreotide. A starting dose of 20 mg of octreotide LAR is recommended. Supplemental SC octreotide is needed for approximately 2 weeks after initiation of octreotide LAR treatment. Occasional rescue SC injections may be required for possibly 2 to 3 months until steady-state octreotide levels from the LAR formulation are achieved.
Naturally occurring mood and learning: comment on Hasher, Rose, Zacks, Sanft, and Doren.

We comment on the article by Hasher, Rose, Zacks, Sanft, & Doren (1985) in which they failed to find mood-congruent learning (MCL). MCL occurs whenever subjects learn more about materials that are congruent with their moods (e.g., depressed subjects learn more sad material). Hasher et al. failed to observe MCL with normal college students who scored high versus low on the Beck Depression Inventory and an affect checklist; in contrast, positive MCL has been observed with clinically depressed patients and with normals given laboratory mood inductions. Hasher et al. argue that moderately depressed normal students may be qualitatively different from clinically depressed patients and mood-induced subjects. Although we accept the findings of Hasher et al., we think it is also plausible that MCL may be a general though small effect which is present among normal college students as well.
Development and Maintenance of Donor-Specific Chimerism in Semi-Allogenic and Fully Major Histocompatibility Complex Mismatched Facial Allograft Transplants

Background. The clinical application of composite tissue allograft transplants opened the discussion on the restoration of facial deformities by allotransplantation. We introduce a hemifacial allograft transplant model to investigate the rationale for the development of operational tolerance across a major histocompatibility complex (MHC) barrier. Material and Methods. Thirty rats were studied in five groups of six animals each. The composite hemiface isograft transplantations were performed in group 1. Allograft rejection controls included semi-allogenic transplantations from LBN (RT1l+n) donors (group 2) and fully allogenic transplantations from ACI (RT1a) donors (group 3) to LEW (RT1l) recipients. In the allograft treatment groups, recipients of LBN (group 4) and ACI donors (group 5) were treated with cyclosporine A monotherapy (16 mg/kg/day, tapered to 2 mg/kg/day). Face allografts were evaluated clinically and histologically. Donor-specific chimerism for MHC class I RT1n and RT1a antigens was assessed by flow cytometry. Mixed lymphocyte reaction for donor-specific tolerance in vitro was tested at day 160 posttransplant. Results. Isograft controls survived indefinitely. All nontreated allografts rejected within 5 to 8 days posttransplant. Long-term survival was achieved in 100% of LBN (up to 400 days) and ACI (up to 330 days) recipients. At day 160, posttransplant donor-specific chimerism was present in recipients of LBN (10.14% CD4/RT1n, 6.38% CD8/RT1n, 10.02% CD45RA/RT1n) and ACI (17.54% CD4/RT1a, 9.28% CD8/RT1a) transplants, and mixed lymphocyte reaction confirmed tolerance in recipients of LBN transplants and moderate reactivity in recipients of ACI allografts. Conclusion. Operational tolerance was induced in hemiface allograft transplants across an MHC barrier under cyclosporine A monotherapy protocol. It was associated directly with the presence of multilineage donor-specific chimerism.
Prostate cancer is part of the hereditary non‐polyposis colorectal cancer (HNPCC) tumor spectrum

The recognized urologic tumor spectrum in hereditary non‐polyposis colon cancer includes ureteral and renal pelvis malignancies. Here, we report a family in which the proband, who had three metachronous adenocarcinomas of the colon and rectum (at ages 54, 57, and 60), presented with an adenocarcinoma of the prostate at age 61. Immunohistochemical (IHC) staining of colonic, rectal, and prostatic tumor tissues demonstrated lack of expression of both MSH2 and MSH6. Accordingly, microsatellite instability (MSI) was found in the rectal, colonic, and prostatic tumors. The kindred complies with the Amsterdam criteria for HNPCC, as five members over three generations had colorectal cancer. Molecular investigations were initiated when the proband's son presented with an adenocarcinoma of the colon at age 35. Southern blotting analysis of genomic DNA led to identification of a novel genomic deletion encompassing exon 5 of the MSH2 gene. Although prostate cancer has occasionally been described in HNPCC families, to the best of our knowledge, this is the first report where the MSI and IHC analysis of the prostatic adenomcarcinoma clearly link its aetiology to the germline mismatch repair mutation. Hence, prostate cancer should be included in the HNPCC tumor spectrum. © 2003 Wiley‐Liss, Inc.
Respondent Reactions to Sensitive Questions

We administered debriefing probes to gauge respondent discomfort in reaction to sensitive questions. These probes assessed respondents' own reactions to being asked to report on substance use (subjective discomfort), as well as their beliefs about the reaction of others (projective discomfort). We investigated whether a sample of men from the general population were more uncomfortable with questions about drug use than a sample of men who have sex with men (MSM) surveyed from the same city (Chicago). We also investigated whether those who disclosed drug use on the survey experienced higher levels of discomfort. Contrary to opinions often expressed as research ethics committee (REC) recommendations, questions about drug use do not generate much subjective discomfort. MSM did not differ from the general population with respect to subjective discomfort. General population males did, however, report higher levels of “drug specific” projective discomfort. Respondents disclosing recent drug use reported higher levels of subjective discomfort. Implications for the REC practice, researcher and REC education, and directions for future research are discussed.
V(D)J targeting mistakes occur at low frequency in acute lymphoblastic leukemia

Translocations of proto‐oncogenes to the B‐cell or T‐cell antigen receptor loci in acute T‐ or B‐cell leukemia and lymphoma have been, in most cases, accredited to V(D)J or switch recombination depending on the location of the breakpoint at the receptor locus. Only in rare instances, the reports take into account mechanistic characteristics of the translocation mechanism. To assess the functional ability of several sites implicated in supposedly V(D)J‐mediated translocations, we tested five sites at four proto‐oncogene loci in an ex vivo recombination substrate assay for their potential to act as direct target for V(D)J recombination. Our results show that the LMO2/RBTN2/TTG2 site and one LCK/P56 site readily engage in recombination with a genuine TCR element with the majority of breakpoint junctions showing the characteristics of V(D)J recombination, which strongly supports the involvement of this mechanism in the pathogenesis of the corresponding translocations in vivo. The site at the TLX1/HOX11 locus yielded 0.8% V(D)J‐specific junctions. Sites at the LCK/P56 and TCF3/E2A proto‐oncogenes resulted in exclusively unspecific breakpoints scattered over part of or the entire proto‐oncogene region tested, marking them as unlikely V(D)J recombination targets. Our data suggest that, while being a potentially dangerous mechanism due to the introduction of DNA breaks, V(D)J recombination is a tightly controlled mechanism allowing for only few direct mistakes. © 2009 Wiley‐Liss, Inc.
The stigma of alcohol dependence compared with other mental disorders: a review of population studies.

AIMS Stigma is likely to aggravate the severe medical and social consequences of alcohol dependence. We aim to explore the characteristics of the alcohol dependence stigma by comparing it with the stigma of other conditions. METHODS On the basis of a systematic literature search, we identified 17 representative population studies published before July 2010 that examine aspects of the stigma of alcoholism and simultaneously of other mental, medical or social conditions. Seven surveys were located in Europe, five in North America, three in New Zealand and one each in Brazil and Ethiopia, respectively. RESULTS Compared with people suffering from other, substance-unrelated mental disorders, alcohol-dependent persons are less frequently regarded as mentally ill, are held much more responsible for their condition, provoke more social rejection and more negative emotions, and they are at particular risk for structural discrimination. Only with regard to being a danger, they are perceived to be at a similarly negative level to that of people suffering from schizophrenia. CONCLUSION Alcoholism is a particularly severely stigmatized mental disorder. Cultural differences are likely, but under-researched. We discuss possible reasons for the differences between the stigma of alcoholism and of other mental diseases and the consequences for targeted anti-stigma initiatives.
Active Detachment Involves Inhibition of Cell-Matrix Contacts of Malignant Melanoma Cells by Secretion of Melanoma Inhibitory Activity

Melanoma inhibitory activity (MIA) has been identified as a small protein secreted from malignant melanoma cells. Recent results revealed a direct interaction of MIA and epitopes within extracellular matrix proteins including fibronectin. The aim of this study was to analyze functional consequences mediated by this interaction. Here we show that MIA interferes specifically with attachment of melanoma cells to fibronectin, a phenomenon we refer to as active detachment. Antibodies inhibiting binding of α4β1 and α5β1 integrins to fibronectin cross-react specifically with MIA, suggesting that MIA shares significant structural homology with the binding pockets of these integrins and thereby masks the respective epitopes on extracellular matrix molecules. Several peptides derived from fibronectin and from a phage display screening were tested with respect to a potential MIA-inhibitory effect. In vitro tests identified two peptides affecting MIA function; both inhibited growth of melanoma metastases in vivo. In summary, we conclude that MIA may play a role in tumor progression and spread of malignant melanomas via mediating active detachment of cells from extracellular matrix molecules within their local milieu. Further, our results suggest that inhibiting MIA functions in vivo may provide a novel therapeutic strategy for metastatic melanoma disease.
Fever of unknown origin: a survey on 133 patients.

The hospital records of one hundred and thirty-three patients with fever of unknown origin (FUO) were studied. An etiologic diagnosis had been made in 105 patients: 41 patients had an infection, 24 had a neoplasm, 17 had a connective tissue disease, and 23 had various diseases grouped under "miscellaneous. " FUO was self-limiting in 25 of the remaining patients. Invasive procedures (arteriography, biopsy, laparoscopy, paparotomy) were necessary to establish a diagnosis in 67 patients, non-invasive tests (sero-immunologic, bacteriologic, conventional radiologic tests, clinical course and treatment response) were sufficient in 27 patients. In 11 patients, the cause of FUO was determined in necropsy. Thirty patients died of FUO: 6 patients with a neoplasm, 4 with a connective tissue disease, and 7 with diseases termed miscellaneous.
Altered Shear Stress Stimulates Upregulation of Endothelial VCAM-1 and ICAM-1 in a BMP-4– and TGF-&bgr;1–Dependent Pathway

Objective—Hemodynamics has been associated with aortic valve (AV) inflammation, but the underlying mechanisms are not well understood. Here we tested the hypothesis that altered shear stress conditions stimulate the expression of cytokines and adhesion molecules in AV leaflets via a bone morphogenic protein (BMP)- and transforming growth fact (TGF)-&bgr;1–dependent pathway. Methods and Results—The ventricularis or aortic surface of porcine AV leaflets were exposed for 48 hours to unidirectional pulsatile and bidirectional oscillatory shear stresses ex vivo. Immunohistochemistry was performed to detect expressions of the 4 inflammatory markers VCAM-1, ICAM-1, BMP-4, and TGF-&bgr;1. Exposure of the aortic surface to pulsatile shear stress (altered hemodynamics), but not oscillatory shear stress, increased expression of the inflammatory markers. In contrast, neither pulsatile nor oscillatory shear stress affected expression of the inflammatory markers on the ventricularis surface. The shear stress–dependent expression of VCAM-1, ICAM-1, and BMP-4, but not TGF-&bgr;1, was significantly reduced by the BMP inhibitor noggin, whereas the TGF-&bgr;1 inhibitor SB431542 blocked BMP-4 expression on the aortic surface exposed to pulsatile shear stress. Conclusions—The results demonstrate that altered hemodynamics stimulates the expression of AV leaflet endothelial adhesion molecules in a TGF-&bgr;1– and BMP-4–dependent manner, providing some potential directions for future drug-based therapies for AV diseases.
Cholesteryl ester transfer protein activity and cardiovascular events in patients with chronic kidney disease stage V.

BACKGROUND Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular events (CVE). Uraemic dyslipidaemia, which is characterized by low HDL-cholesterol (HDL-C) and elevated triglycerides' levels, may contribute to this elevated cardiovascular risk. Cholesteryl ester transfer protein (CETP) lowers HDL-C by transferring cholesterol esters to LDL and VLDL particles. We tested the hypothesis that CETP activity is associated with CVE in patients with CKD stage V. METHODS We measured CETP activity and cholesterol levels in 69 haemodialysis patients. CVE and death were prospectively assessed over a follow-up period of 48 months. RESULTS CETP activity was negatively correlated with HDL-C levels in patients without lipid-lowering medication (r = -0.379, P = 0.005). We found no difference in CETP activity in patients with cardiovascular disease at baseline compared to patients without cardiovascular disease. The same was true for incident CVE during the follow-up. When stratifying patients by median CETP activity, patients with high CETP activity did not have an increased risk for CVE (P = 0.901 by the log-rank test) or death (P = 0.615). Similarly, after stratifying patients by median HDL-C no increased risk for CVE (P = 0.780) or death (P = 0.838) was found in patients with low HDL-C. CONCLUSIONS In summary, although CETP activity correlated with HDL-C levels, neither high CETP activity nor low HDL-C was associated with CVE in CKD stage V patients. Thus, pharmacological modification of HDL-C by CETP inhibitors seems to be of questionable value in these patients.
The longitudinal relation between brain lesion load and atrophy in multiple sclerosis: a 14 year follow up study

Background:Studies have suggested that T2 lesion activity is prominent in early relapsing-remitting multiple sclerosis, whereas brain atrophy, while seen early, appears more evident in later progressive disease. The temporal relation between these processes remains unclear. Objective:To explore the association between changing brain lesion loads and subsequent tissue atrophy in multiple sclerosis. Methods:28 subjects with clinically probable or definite multiple sclerosis (mean age 46.0 years; 17 female and 11 male) were followed for 14 years after first onset of symptoms. T2 lesion loads were estimated soon after symptom onset and at around five, 10, and 14 years later. Disease related atrophy was estimated at the 14 year follow up by comparing brain tissue volumes (proportional to total intracranial volumes) determined in the multiple sclerosis group with data from 29 normal control subjects (mean age 36.7 years; 16 female, 13 male) using multiple linear regression analyses to allow for differences in age and sex distributions. Results:Change in lesion load in the first five years was more closely correlated to disease related brain atrophy at 14 years than later changes in lesion load, although the correlation was only moderate (Spearman correlation = −0.528, p = 0.004). Conclusions:From this, it appears that early rather than later focal lesion accumulation relates to subsequent brain atrophy, but factors unconnected directly with lesion formation probably also play a significant role in determining such atrophy.
Effects of atorvastatin on arterial stiffness in chronic kidney disease: a randomised controlled trial.

AIM Central pulse pressure and measures of arterial stiffness (augmentation index (AIx) and aortic pulse wave velocity (PWV)) predict morbidity and mortality in patients with stage 2-4 chronic kidney disease (CKD). Although statin therapy may be of vascular benefit in patients with CKD, the long-term effect of statins on central pulse pressure and arterial stiffness has not been assessed in this patient population. Hence, the aim of this study was to assess the long-term effects of atorvastatin on arterial stiffness and central blood pressure in patients with CKD. METHODS We enrolled 37 patients with serum creatinine levels > 1.36 mg/dL into a randomized, double blind trial. Patients were allocated to receive 10 mg of atorvastatin per day (19) or placebo (18) for three years. Aortic PWV, AIx, estimated central and brachial blood pressures and were determined every nine months. RESULTS At baseline, there were no significant differences in aortic PWV, AIx, central or brachial blood pressures between atorvastatin-treated and placebo-treated patients. During the trial, aortic PWV significantly (p=0.05) increased in placebo-treated, but not (p=0.10) in atorvastatin-treated patients (0.51+/-0.95 vs. 0.30+/-0.75 m/sec/yr; p=0.48). This represented a 41% (but not statistically significant) slowing of the rate of increase in aortic stiffness. There were no significant changes between groups in the rate of change of AIx (atorvastatin -0.15+/-5.65 vs. placebo 0.39+/-5.38%/yr, p=0.53) or central pulse pressure (atorvastatin -2.32+/-7.46 vs. placebo -0.36+/-6.64 mmHg/yr p= 0.61). CONCLUSION In patients with CKD arterial stiffness measured by aortic PWV showed a significant increase over time in placebo-treated patients but not in atorvastatin-treated patients.
Caffeine consumption during pregnancy and fetal growth.

BACKGROUND The purpose of this study was to examine the association between maternal caffeine consumption and low birthweight, intrauterine growth retardation, and prematurity, adjusting for multiple confounders. METHODS Data obtained from birth certificates and interviews on 1,230 women with singleton live births were analyzed to evaluate the potential influence of caffeine consumption during the first trimester on fetal growth. RESULTS The crude odds ratio for intrauterine growth retardation in infants of women reporting heavy caffeine consumption (greater than 300 mg/day) was 3.86 (95% CI = 1.80, 8.40) which decreased to 2.90 (95% CI = 1.23, 6.87) after controlling for confounding factors. The adjusted odds ratio for low birthweight and heavy maternal caffeine consumption was also elevated (OR = 2.05; 95% CI = 0.86, 4.88). Women who reduced their caffeine intake from greater than 300 mg/day to less than that early in pregnancy had lower risks of delivering infants with either intrauterine growth retardation or low birthweight than women who continued to consume that amount. Preterm delivery appeared to be unrelated to caffeine consumption. CONCLUSIONS Taken together with studies reporting similar findings, these results suggest that heavy caffeine consumption increases the risk for fetal growth retardation.
Neurocysticercosis as a cause of stroke.

Response We would like to thank Dr. Yonas and Ms. Durham for emphasizing the difficulties in interpreting different methods of assessing cerebrovascular reserve capacity. Unfortunately, we are not aware of standardization studies comparing the Doppler CO2 test with stable xenon computed tomography (CT) combined with the "acetazolamide challenge. " Therefore, to achieve fairly similar conditions, we compared our groups with pathological CO2 reactivity with groups 2 (<±5% change in cerebral blood flow) and 3 (>5% decrease) in the study of Durham et al. In this case, the stroke rate of 27% was somewhat equivalent to that in our series (24%). From our investigations, we also know the effect of a decrease in blood flow during hypercapnia, which may be explained by an intracerebral steal effect or an increase in intracranial pressure caused by the raised blood volume in the nonaffected hemisphere. In contrast to the more static evaluation of xenon CT, however, Doppler monitoring also gives dynamic information about shortterm changes of blood flow velocity, e.g., those due to ventilatory fluctuations of the intracranial pressure. Our thresholds used for defining pathological cases have to consider this and therefore differ from those taken for xenon CT. As correctly mentioned by Dr. Yonas and Ms. Durham, every method for assessing the cerebrovascular reserve capacity has its own problems. By proper use, however, we believe that xenon CT and SPECT, as well as Doppler sonography, enable identification of patients at risk for stroke because of pathological cerebral hemodynamics.