小肠肿瘤罕见原因

小肠是消化道中最长的一段,是食物消化、吸收和能量转化的主要场所,但小肠肿瘤的相关研究却鲜有报道。原发性小肠恶性肿瘤在临床少见,由于缺乏典型临床表现及有效治疗手段,导致预后极差。小肠巨大的表面积及上皮快速更新的状态与小肠肿瘤的低发病率显然相悖。小肠肿瘤较低的发病率这一科学问题已成为困扰医学科学领域的世纪之谜。本综述主要从小肠独特的生理屏障、基因调控系统、共生菌群及黏膜免疫系统四个方面剖析小肠肿瘤罕见的原因。理解小肠精密的调控机制将为研究衰老、肠道菌群及肿瘤防治提供新思路。本文基于以往研究,结合最新进展对小肠肿瘤流行病学现状、低发病率的可能原因及其对肿瘤防治的启示进行综述。     

Personality differences among black, white, and Hispanic-American male heroin addicts on MMPI content scales

Used MMPI Content Scale scores (Wiggins, 1966) to assess personality differences among black, white, and Hispanic-American heroin addicts. Ss were 423 male veterans who volunteered for the first time for treatment between 1972 and 1979 to an inpatient Drug Dependence Treatment Program (DDTP) of a Veterans Administration Medical Center. Two hypotheses were tested: First, that minority group heroin addicts (blacks and Hispanics) will show better adjustment than majority group (white) heroin addicts; second, that Hispanic-American heroin addicts will evidence personality characteristics unlike those of either whites or blacks. Both hypotheses were confirmed. Results were interpreted as supporting cultural theories of substance abuse and providing implications for diagnosis and treatment of substance abuse disorders among minority ethnic groups.     

Ixazomib with cyclophosphamide and dexamethasone in relapsed or refractory myeloma: MUKeight phase II randomised controlled trial results

The all-oral combination of ixazomib, cyclophosphamide, and dexamethasone (ICD) is well tolerated and effective in newly diagnosed and relapsed multiple myeloma (MM). We carried out MUKeight, a randomised, controlled, open, parallel group, multi-centre phase II trial in patients with relapsed MM after prior treatment with thalidomide, lenalidomide, and a proteasome inhibitor (ISRCTN58227268), with the primary objective to test whether ICD has improved clinical activity compared to cyclophosphamide and dexamethasone (CD) in terms of progression-free survival (PFS). Between January 2016 and December 2018, 112 participants were randomised between ICD (n = 58) and CD (n = 54) in 33 UK centres. Patients had a median age of 70 years and had received a median of four prior lines of therapy. 74% were classed as frail. Median PFS in the ICD arm was 5.6 months, compared to 6.7 months with CD (hazard ratio (HR) = 1.21, 80% CI 0.9–1.6, p = 0.3634). Response rates and overall survival were not significantly different between ICD and CD. Dose modifications or omissions, and serious adverse events (SAEs), occurred more often in the ICD arm. In summary, the addition of ixazomib to cyclophosphamide and dexamethasone did not improve outcomes in the comparatively frail patients enroled in the MUKeight trial.Subject terms: Drug development, Cancer therapy, Cancer therapy     

Differential regulation of type II corticosteroid receptor messenger ribonucleic acid expression in the rat anterior pituitary and hippocampus

The present study was designed to characterize the regulation of the type II corticosteroid receptor (GR) mRNA in two tissues involved in the control of the hypothalamic-pituitary-adrenal axis. We have used a solution hybridization/S1 nuclease protection assay to quantitate GR mRNA levels in the rat hippocampus and anterior pituitary after CRF, dexamethasone (DEX), or corticosterone (CORT) treatment. In general, hippocampal GR mRNA levels increased after removal of endogenous corticosteroids by surgical adrenalectomy and decreased in response to glucocorticoid treatment. More specifically, in the hippocampus 1) GR mRNA expression was decreased when adrenalectomized (ADX) animals were replaced with a relatively low dose of CORT, but not with a low dose of DEX; 2) acutely, CRF was more effective than DEX in decreasing the levels of GR mRNA in intact animals; however, under the same paradigm in ADX animals, DEX decreased the level of GR mRNA, whereas CRF was ineffective; and 3) in contrast to the decrease in GR mRNA levels observed after acute and low doses of glucocorticoid treatment, chronic treatment with either DEX or CORT did not change the level of hippocampal GR mRNA. These results suggest that in the hippocampus the decrease in GR mRNA expression after CRF treatment is probably via the release of glucocorticoids, and that this tissue is more sensitive to endogenous glucocorticoids than DEX. Anterior pituitary GR mRNA was differentially regulated compared with that in the hippocampus. In marked contrast to Gr mRNA in the hippocampus, ADX did not alter anterior pituitary GR mRNA expression, and glucocorticoid treatment led to an increase in GR mRNA levels. In the anterior pituitary 1) glucocorticoid treatment led to an increase in GR mRNA expression, when replaced with a relatively low dose of DEX, but not when replaced with a low dose of CORT; 2) acutely, neither CRF nor DEX altered levels of GR mRNA in intact animals; however, under the same paradigm DEX increased levels in ADX animals; and 3) chronic DEX or CORT treatment of intact animals elevated levels of anterior pituitary GR mRNA. In summary, these data have demonstrated tissue-specific regulation of GR mRNA in the hippocampus and anterior pituitary, which is dependent on both the dose and length of treatment and, in addition, on the glucocorticoid itself.     

Idiopathic dilated cardiomyopathy: analysis of 152 necropsy patients

Certain clinical and cardiac necropsy findings are described in 152 patients aged 16 to 78 years (mean 45) with idiopathic dilated cardiomyopathy: 109 (72%) were men and 43 (28%) were women. Compared with the women, the men had a significantly (p less than 0.05) shorter mean duration of chronic congestive heart failure (CHF) (43 vs 69 months), a higher percentage of habitual alcoholism (40 vs 24%) and a higher mean heart weight (632 vs 551 g). The male to female ratio among the 58 known alcoholics was 7.3:1 and among the 70 known nonalcoholics, 1.5:1 (p less than 0.05). The mean duration of clinical evidence of CHF was similar among the known alcoholics and the known non-alcoholics (each 50 months). Of the 152 patients, 148 (97%) had clinical evidence of chronic CHF; in 114 patients it was the initial manifestation of idiopathic dilated cardiomyopathy, and in most it became intractable and caused death. The interval from onset of chronic CHF to death (known in 120 patients) ranged from 1 to 264 months (mean 54). Comparison of the 27 patients surviving greater than 72 months after onset of chronic CHF to the 64 patients surviving less than or equal to 36 months disclosed a significantly higher frequency in the longer survival group of older patients, of women, of habitual alcoholics, of patients with chest pain syndromes, diabetes mellitus, pulmonary emboli, of patients treated with warfarin and of patients with larger hearts at necropsy. Each of the 4 patients without chronic CHF died suddenly and sudden death was the initial manifestation of idiopathic dilated cardiomyopathy in them. An additional 33 patients also died suddenly, but each of them previously had had chronic CHF. Of the 79 patients (of the 131 for whom information was available) with either pulmonary or systemic emboli or both, 67 (85%) had either right- or left-sided thrombi or mural endocardial plaques or both, whereas of the 52 patients without emboli, 36 (69%) had intracardiac thrombi or plaques (p less than (0.05). Electrocardiograms in the last 6 months of life in 101 patients disclosed atrial fibrillation in 25; complete left (41 patients) or right (6 patients) bundle branch block or indeterminate intraventricular conduction delay (4 patients) in 51 patients; QRS voltage indicative of ventricular hypertrophy in 44 patients (left ventricular in 39 patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Success of re-use of cardiac electrode catheters

The feasibility of cardiac electrode catheter re-use was prospectively evaluated over a 5-year period (1981 to 1986), during which time 178 catheters were used 1,526 times for 847 electrophysiologic procedures. Detailed records of catheter testing and use were maintained. No complications were encountered during the study period. All re-used catheters functioned for cardiac pacing and electrographic recording. Surveillance cultures and biologic indicators revealed that adequate sterilization procedures were used. Thus, electrode catheters may be safely re-used provided a thorough cleaning, testing and record-keeping system is instituted. This may result in lower patient cost (approximately $30 per re-use vs [200 per single use) for electrophysiologic catheterization.     

Calcification of healed myocardial infarcts

Clinical and necropsy findings are described in 21 patients, aged 43 to 78 years (mean 63) (19 men [90%]), who had grossly visible calcified myocardial infarcts. The interval from the first clinically apparent acute myocardial infarct to death (20 patients) ranged from 2 to 26 years (mean 12). This interval was greater than 5 years in 17 patients (85%) and greater than 10 years in 11 patients (55%). The ages at the first clinically apparent acute myocardial infarct ranged from 36 to 72 years (mean 51). Of the 21 patients, 17 (81%) had clinical evidence of chronic congestive heart failure; 12 (57%) had left ventricular aneurysms; 8 (38%) had documented episodes of ventricular tachycardia; and 5 had angina pectoris. At necropsy, the heart weight was increased (greater than 400 g) in all (mean 557 g), the left ventricular cavity was dilated in all, and at least 1 and usually 2 or 3 (86%) major epicardial coronary arteries were narrowed greater than 75% in cross-sectional area by atherosclerotic plaque. Thus, patients with calcified myocardial infarcts are usually men, they usually have a myocardial infarct that calcifies at a relatively young age, the calcified wall is usually part of an aneurysmal wall, the left ventricular cavity is almost always dilated, heart weight is increased, and progressive congestive heart failure is the usual mode of death.     

B-cell growth factor receptor expression and B-cell growth factor response of leukemic B cell precursors and B lineage lymphoid progenitor cells

The purpose of this study was to analyze the expression of B cell growth factor (BCGF) receptors and to elucidate the biologic effects of biochemically purified natural BCGF at the B cell precursor stage of human B lineage lymphoid differentiation. The specific binding of radioiodinated high-mol-wt BCGF (125I-HMW-BCGF) and low-molecular-wt BCGF (125I-LMW-BCGF) to fresh marrow blasts from B cell precursor acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated BCGF molecules bound per blast ranged from undetectable to 24.3 X 10(3) for HMW-BCGF, and from 11.5 X 10(3) to 457.8 X 10(3) for LMW-BCGF. In 3H-TdR incorporation assays, 75% of cases showed a significant response to LMW-BCGF with a median stimulation index of 9.3. By comparison, only 33% of cases showed a significant response to HMW-BCGF with a median stimulation index of 2.4. Subsequently, B cell precursor colony assays were performed to assess and compare the biologic effects of BCGF on leukemic B lineage lymphoid progenitor cells. Among 28 cases studied, 57% responded to both HMW-BCGF and LMW-BCGF, 21% responded only to LMW-BCGF, and the remaining cases showed no proliferative response to either growth factor. The response patterns of virtually pure populations of FACS- sorted leukemic B cell precursors were essentially identical to the proliferative responses of unsorted leukemic B-cell precursors. Synergistic effects between HMW-BCGF and LMW-BCGF were observed in 80% of the cases that responded to both. The numbers of cell-bound radioiodinated BCGF molecules, the stimulation indices, as well as the number of B cell precursor colonies in BCGF-stimulated cultures showed a marked interpatient variation. Patients with structural chromosomal abnormalities (SCAs) involving 12p11-13 or patients with a Philadelphia chromosome showed a greater HMW-BCGF response at the level of leukemic progenitor cells than did other patients (P = .02). The LMW-BCGF response was significantly greater for patients with SCA than for patients without SCA (P = .04). The response of leukemic progenitor cells to HMW-BCGF or LMW-BCGF did not correlate with sex, age, disease status, FAB morphology, WBC at diagnosis, or immunophenotype. To our knowledge, this study represents the first detailed analyses of BCGF receptor expression and BCGF effects in B cell precursor ALL. The data presented provide direct evidence for the expression of functional receptors for both HMW-BCGF and LMW-BCGF in B cell precursor ALL.