Pheochromocytoma presenting with severe abdominal pain and abnormal liver enzymes

Pheochromocytoma can present with right hypochondrial pain, elevated liver enzymes, and a misleading appearance on ultrasound scan mimicking hepatic mass due to the proximity of adrenal masses to the liver.     

Y染色体或将在进化中消失

美国宾夕法尼亚州立大学的2位科学家在性染色体进化变异机制的研究上取得进展。研究发现,Y染色体比X染色体的演化速率快得多,这将导致Y染色体上的基因急剧丢失,如此,Y染色体将会完全消失,人类的传宗接代将受威胁。     

Early recognition of heart failure in patients with diabetes type 2 in primary care. A prospective diagnostic efficiency study. (UHFO-DM2)

Background  

We hypothesize that the prevalence of unknown heart failure in diabetic patients aged 60 years and over is relatively high (15% or more) and that a cost-effective strategy can be developed to detect heart failure in these patients. The strategy is expected to include some signs and symptoms (such as dyspnoea, orthopnoea, pulmonary crepitations and laterally displaced apical beat), natriuretic peptide measurements (Amino-terminal B-type natriuretic peptide) and possibly electrocardiography. In a subset of patients straightforward echocardiography may show to be cost-effective. With information from our study the detection of previously unknown heart failure in diabetic patients could be improved and enable the physician to initiate beneficial morbidity and mortality reducing heart failure treatment more timely.     

Determination of cancer risk associated with germ line BRCA1 missense variants by functional analysis

Germ line inactivating mutations in BRCA1 confer susceptibility for breast and ovarian cancer. However, the relevance of the many missense changes in the gene for which the effect on protein function is unknown remains unclear. Determination of which variants are causally associated with cancer is important for assessment of individual risk. We used a functional assay that measures the transactivation activity of BRCA1 in combination with analysis of protein modeling based on the structure of BRCA1 BRCT domains. In addition, the information generated was interpreted in light of genetic data. We determined the predicted cancer association of 22 BRCA1 variants and verified that the common polymorphism S1613G has no effect on BRCA1 function, even when combined with other rare variants. We estimated the specificity and sensitivity of the assay, and by meta-analysis of 47 variants, we show that variants with <45% of wild-type activity can be classified as deleterious whereas variants with >50% can be classified as neutral. In conclusion, we did functional and structure-based analyses on a large series of BRCA1 missense variants and defined a tentative threshold activity for the classification missense variants. By interpreting the validated functional data in light of additional clinical and structural evidence, we conclude that it is possible to classify all missense variants in the BRCA1 COOH-terminal region. These results bring functional assays for BRCA1 closer to clinical applicability.     

Intradermal Vaccinations With RNA Coding for TAA Generate CD8+ and CD4+ Immune Responses and Induce Clinical Benefit in Vaccinated Patients

The aim of this phase I/II nonrandomized trial was to assess feasibility, safety as well as immunological and clinical responses of a mRNA-based vaccination in patients with stage IV renal cell cancer using granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvant. Intradermal injections of in vitro transcribed naked mRNA, which was generated using plasmids coding for the tumor-associated antigens mucin 1(MUC1), carcinoembryonic (CEA), human epidermal growth factor receptor 2 (Her-2/neu), telomerase, survivin, and melanoma-associated antigen 1 (MAGE-A1) were performed in 30 enrolled patients. In the first 14 patients (cohort A) vaccinations were administered on days 0, 14, 28, and 42 (20 µg/antigen) while in the consecutive 16 patients (cohort B) an intensified protocol consisting of injections at days 0–3, 7–10, 28, and 42 (50 µg/antigen) was used. In both cohorts, after this induction period, vaccinations were repeated monthly until tumor progression analyzed by Response Evaluation Criteria In Solid Tumors criteria (RECIST). Vaccinations were well tolerated with no severe side effects and induced clinical responses [six stable diseases (SD) and one partial response in cohort A and nine SD in cohort B]. In cohort A, 35.7% survived 4 years (median survival 24 months) compared to 31.25% in cohort B (median survival 29 months). Induction of CD4⁺ and CD8⁺ T cell responses was shown for several tumor-associated antigens (TAA) using interferon-γ (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and Cr-release assays.     

Primary Bile Duct Stones and Bacterial Activity

The results of this study suggest that infection with beta-glucuronidase active bacteria is the initial event in the nucleation of primary bile duct stones (PBDS).PBDS from five patients were morphologically fragile and “earthy” with alternating light and dark brown pigment layers with no evidence of a distinct central nucleus that may have been reminiscent of a different structure. Chemically, calcium bilirubinate and calcium palmitate were prominent throughout their structure. All bile duct biles had a positive culture and were always associated with at least one bacterial species which was beta-glucuronidase active. Moreover, fragments of PBDS nuclear areas had positive cultures that were comparable with those present in their individual bile duct bile. Microscopic examination of bile showed abundant precipitation of calcium bilirubinate granules in all samples.Thus, bile duct bile infection with beta-glucuronidase active bacteria (e.g. E. coli, C. perfringens) appears to be a key factor in PBDS pathogenesis, having a precursor role, rather than being a consequence. Bile stasis is likely to be a co-factor which must have a supportive role in subsequent stone growth.     

Chagas' disease diagnosis: evaluation of several tests in blood bank screening

Blood transfusion is one of the principal routes of transmission of Chagas' disease, a major endemic disease in Latin America. Methods for blood screening are not accurate and may yield false results that lead to high social and economic costs. This study compares two methods of diagnosing Chagas' disease (indirect immunofluorescence and hemagglutination) and several enzyme-linked immunosorbent assays (ELISAs) with regard to specificity and sensitivity, by using human sera with known serologic and parasitologic characteristics, as well as samples with discrepant results on conventional serologic tests. An ELISA using recombinant antigens showed no cross-reactivity with sera that were positive for other diseases. All evaluated ELISAs performed well, and their use may lead to a reduction of more than 50 percent in the number of discordant sera. Further improvements are needed in view of the complexity of the serologic diagnosis of Chagas' disease.     

On the adaptation in potassium excretion associated with nephron reduction in the dog

An effort to examine certain aspects of the adaptation in potassium excretion associated with nephron reduction was made in dogs with unilateral remnant kidneys. A constant intake of potassium was maintained by tube feeding and studies were performed before and after removal of the intact control kidney. The removal of the intact kidney created the need for the remaining nephrons of the remnant kidney to increase their rate of potassium excretion markedly. Sodium intake was held constant either at a normal or a low level. Mineralocorticoid hormone activity was maintained either at a high level by the administration of 0.2 mg 9-α-fluorohydrocortisone daily or at a low level by performing bilateral adrenalectomy and administering a minimal maintenance dose of deoxycorticosterone acetate (DOCA) and cortisol. Potassium excretion per nephron increased strikingly within 18 hr of contralateral nephrectomy and by 7 days, excretion rates were 600% of control values for the remnant kidney. More potassium was excreted in the first 5 hr after administration of a test dose of potassium by the remnant kidney alone in the postnephrectomy state than by both the remnant and intact kidneys in the prenephrectomy state. 24 hr excretion of potassium by the remnant kidney postnephrectomy averaged 92% of the administered load of potassium. The adaptation in potassium excretion was independent of the concurrent rate of sodium excretion and of mineralocorticoid hormone activity and persisted during constriction of the renal artery, a stimulus which presumably decreased distal delivery of sodium. The adaptation and the continued modulation of potassium excretion could not be explained adequately by an increase in impermeant anion excretion per nephron. Finally, known changes in hydrogen ion excretion per nephron associated with nephron reduction are in a direction opposite to those which would explain the acquired kaliuresis per nephron.     

Virtual colonoscopy with magnetic resonance imaging: In vitro evaluation of a new concept

BACKGROUND & AIMS: Screening for colonic polyps is desirable. A new concept based on cross-sectional and endoscopic analysis of a magnetic resonance (MR) data set is presented. METHODS: Ex vivo autopsy colonic specimens, containing artificially placed polyps, were obtained and filled with a gadolinium-containing solution. Forty-four thin-section MR images were obtained in a 1.5-T MR scanner in 28 seconds. A three- dimensional endoscopic fly-through of these images was rendered. Fly- throughs and two-dimensional cross-sectional images were analyzed by two observers for the presence of polyps. RESULTS: The average sensitivity and specificity for the detection of polyps based on three- dimensional endoscopic MR colon imaging were 87% and 96%, respectively. Analysis of cross-sectional images showed an overall sensitivity and specificity of merely 57% and 84%, respectively. The difference in the interpretation of three-dimensional MR colonoscopy and two-dimensional cross-sections was statistically significant (P < 0.001). With three- dimensional MR colonoscopy, overall sensitivity for detection of polyps measuring < or =5 mm in length and diameter was 70%; for larger polyps, it increased to 95% (P < 0.01). CONCLUSIONS: The feasibility of an MR- based endoluminal assessment of the colon is shown. Minimal invasiveness, lack of radiation exposure, and high in vitro diagnostic accuracy warrant further investigation of this novel concept. (Gastroenterology 1997 Jun;112(6):1863-70)