Safety and efficacy of controlled-release mesalamine for maintenance of remission in ulcerative colitis

This 12-month, double-blind, placebo-controlled study randomized 205 ulcerative colitis patients in remission to placebo or controlled-release mesalamine at 4 g/day for 12 months. Patients were stratified to either pancolitis or left-sided disease, based on previous diagnosis. Maintenance of remission was defined as a sigmoidoscopic index of <5, less=" than=" five=" stools=" per=" day,=" and=" the=" absence=" of=" rectal=" bleeding.=" a=" significantly=" greater=" number=" of=" patients=" maintained=" remission=" on=" mesalamine=" 4=" g/day=" than=" on=" placebo=" at=" each=" of=" five=" study=" visits,=" following=" the=" first=" one-month=" visit=">P<0.05). the=" estimated=" 12-month=" remission=" rates=" for=" the=" mesalamine=" group=" were=" 64%=" (38%=" for=">P=0.0004). Baseline subgroups (disease location, time since last flare of active disease, and previous response to oral/rectal steroids or sulfasalazine) did not influence remission rates. Treatment-related adverse events were rare. Controlled-release mesalamine is a safe and efficacious single agent for maintaining remission of ulcerative colitis.The members of the Pentasa Study Group are as follows: Austin Diagnostic Clinic, Austin, Texas: Rambie L. Briggs, MD (Chief Investigator), V. Lawlis, MD, C. Felger, MD, G. Kitzmiller, MD, T. Liebermann, MD, Robert Frachtman, MD, Cindy Fischer, RN; San Francisco General Hospital, San Francisco, California: John P. Cello, MD (Chief Investigator), James Grendell, MD, Julie Satow, RN; University of Chicago School of Medicine, Chicago, Illinois: Stephen B. Hanauer, MD (Chief Investigator), Ira Hanan, MD, Pat Schultz, RN, Debbie James, RN; Nalle Clinic, Charlotte, North Carolina: James Mertesdorf, MD (Chief Investigator), Fitzgerald Hiestand, Jr., MD, Paul Tucker, Jr., MD, Thomas Roberts, MD, Pepper Brundage, CMA, Theresa Griffin, Medical Assistant, Janet E. Beck, CMA; Gastrointestinal Association, PA, Shawnee Mission, Kansas: Gregory Rick, Jr., MD (Chief Investigator), William Hartong, MD, William Buser, MD, Stanley Brand, MD, Peggy Bryant, RN, Michelle Kliewer, RN; HCA Presbyterian Hospital, Oklahoma City, Oklahoma: Malcolm Robinson, MD (Chief Investigator), Mark Mellow, MD, Robert McFadden, MD, David Neumann, MD, Karen Helin, Connie J. Privett-Cointepas, Rosemary R. Meek; Forsyth Medical Specialists, Winston-Salem, North Carolina: Walter Roufail, MD (Chief Investigator), Robert Brice, MD, Thomas P. Hughes, MD, Michael Fina, MD, Daniel Murphy, MD, Lacole Clinard, RN, Debbie Allman, Brenda Bowen; Northwest Gastroenterologists, Arlington Heights, Illinois: Jerrold L. Schwartz, MD (Chief Investigator), Igor Jurcik, MD, Loren B. White, MD, Michael Cohen, MD, David Sales, MD, PhD, Sandra Gochnour, RN, Nora M. York, RN; Digestive Healthcare, Minneapolis, Minnesota: David Weinberg, MD (Chief Investigator), Richard A. Dubow, MD, James Pries, MD, Joseph Tombers, MD, Stephen Gilberstadt, MD, Philip Hanna, MD, Mary Jane Watson, PharmD, Michele Mattison, LPN; Greater Cincinnati Gastroenterology Associates, Cincinnati, Ohio: Michael Safdi, MD (Chief Investigator), Alan Safdi, MD, Ronald Schneider, MD, George Waissbluth, MD, Michael D. Kraines, MD, Linda Magaw, CRC, Nancy Emrath, CRC; New England Medical Center, Boston, Massachusetts: Sanjeev Arora, MD, Marshall Kaplan, MD, Augusta McKusick, RN; Gastroenterology of Lake City, Waukegan, Illinois: Fred Rosenberg, MD (Chief Investigator), E.P. Kirch, MD, Hugh A. Allen, MD, Beth Weber, RN, Valley Health Care Medical Group, Binghamton, New York: Marcelo A. Barriero, MD (Chief Investigator), Leslie Bank, MD, Linda Gitchell, RN; Scripps Clinic Medicine Group, Inc, La Jolla, California: Williamson B. Strum, MD (Chief Investigator), Leona Goodman; University of Kansas Medical Center, Kansas City, Kansas: Philip Miner, MD (Chief Investigator), Steven Matter, MD, Dace Miller, MD, Clark Antonson, MD, Roland Christian, MD, Wendy Biddle, RN, Susan Clark, RN, Dorinda S. Sutton, RN; Oregon Health Sciences University, Portland, Oregon: Ronald M. Katon, MD (Chief Investigator), Fred Smith, MD, Kent Benner, MD, Emmet Keeffe, MD, David Lieberman, MD, Clifford Melnyk, MD, Flordeliz Lindenburg, Sue Webster; Medical College of Virginia, Richmond, Virginia: Alvin Zfass, MD, Donald Kirby, MD, Alfred Lee, MD, Yuen San Yee, MD, Paula Goshgarian-Patrick; Wake Research Associates, Raleigh, North Carolina: Charles Barish, MD, Philip Ashburn, MD, Diedrich C. Waterman, MD, Patricia M. Patterson, RN; Birmingham Gastroenterology Associates, Birmingham, Alabama: W. Roger Carlisle, MD (Chief Investigator), Leonard OuTim, MD, Raymond Tobias, MBChB, J. Lynn Cochran, MD, Walter J. Bristow, III, MD, Peter D. Miller, MD, Sarah Ingle, RN; Bowman-Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina: Robert M. Kerr, MD, Donald Castell, MD, Wallace C. Wu, MD, Joel E. Richter, MD, John H. Gilliam, III, MD, Greg Stark, PA; Marion Merrell Dow Inc., Kansas City, Missouri: Ruthanna Law, BSN, MA, Neil Malone, MA, Larry Roi, PhD, Michael Coen, MA, Doug Moore, BA, Mike McPherson, PharmD, MBA.     

Secretion of the intestinotropic hormone glucagon-like peptide 2 is differentially regulated by nutrients in humans

Background & Aims: Glucagon-like peptide 21, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 (GLP-21, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33), an intestinally derived hormone, stimulates growth in rodent small and large bowel. To explore the physiology of GLP-21, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 secretion, we measured plasma GLP-2 levels in 6 healthy male volunteers, before and after test meals. Methods: Blood samples were collected over 24 hours with the subjects consuming a normal, solid mixed diet (2500 kcal) and for 4 hours after liquid test meals (400 kcal/300 mL) composed of carbohydrate, fat, or protein. All studies commenced at 9 AM. Plasma was extracted and analyzed in radioimmunoassays for N-terminal immunoreactive GLP-2 (N-IR-GLP-2; measures bioactive GLP-21, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33) as well as total IR-GLP-2 (T-IR-GLP-2), which includes GLP-21, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, GLP-23, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 (an inactive degradation product of GLP-21, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33), and the pancreatic major proglucagon fragment (an inactive precursor that contains GLP-2). Basal and nutrient-stimulated plasma samples were also analyzed by high-performance liquid chromatography to determine the levels of GLP-21, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 and GLP-23, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33. Results: N-IR-GLP-2 levels were increased 2.0 ± 0.2– to 2.8 ± 0.5–fold 40 minutes after each mixed meal (P < 0.05–0.01) and returned to basal overnight, whereas T-IR-GLP-2 levels were increased 1.3 ± 0.1–fold 40 minutes after breakfast only (P < 0.05). After ingestion of carbohydrate or fat alone, plasma N-IR-GLP-2 concentrations increased by 5.6 ± 2.0– and 2.7 ± 0.6–fold within 1 hour (P < 0.05). High-performance liquid chromatography analysis showed a relative increase in the levels of GLP-21, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 compared with GLP-23, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 (P < 0.05). Ingestion of the protein meal did not alter N-IR-GLP-2 levels, whereas T-IR-GLP-2 was increased by fat and protein (by 1.7 ± 0.2–fold for each, P < 0.01) but not by carbohydrate. Conclusions: These results show that secretion of GLP-21, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33 from the intestine is regulated in a nutrient-dependent manner in normal humans.GASTROENTEROLOGY 1999;117:99-105     

原发性高血压与脂肪肝及血脂相关性调查

目的 探讨原发性高血压与血脂代谢水平及脂肪肝发生率的关系.方法 收集海南医学院附属医院原发性高血压患者351例,以及血压正常者100例,抽血检测甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、血糖、血尿酸、尿素氮和肌酐水平,B超检测脂肪肝比率,同时测量体重及体重指数.结果 高血压患者的TG、TC、AST、血糖、血尿酸、肌酐水平及脂肪肝患病率、体重和体重指数明显高于血压正常者,HDL-C低于血压正常者,差异均有统计学意义,LDL-C、ALT、尿素氮则差异无统计学意义.结论 高血压患者的脂肪肝患病率、体重及体重指数、TG、TC、AST、血糖、血尿酸、尿素氮和肌酐水平明显高于血压正常者,其与高血压呈正相关.     

Survey of molecular profiling during human colon cancer development and progression by immunohistochemical staining on tissue microarray

AIM： To explore the molecular events taking place during human colon cancer development and progression through high-throughput tissue microarray analysis. METHODS： We constructed two separate tissue microarrays containing 1.0 mm or 1.5 mm cylindrical samples acquired from 112 formalin-fixed and paraffinembedded blocks, including carcinomas （n = 85）, adenomatous polyps （n = 18）, as well as normal paracancerous colon tissues （n = 9）. Immunohistochemical staining was applied to the analysis of the consecutive tissue microarray sections with antibodies for 11 different proteins, including p53, p21, bcl-2, bax, cyclin D1, PTEN, p-Aktl, β-catenin, c-myc, nm23-h1 and Cox-2. RESULTS： The protein expressions of p53, bcl-2, bax, cyclin D1, β-catenin, c-myc, Cox-2 and nm23-h1 varied significantly among tissues from cancer, adenomatous polyps and normal colon mucosa （P = 0.003, P = 0.001, P = 0.000, P = 0.000, P = 0.034, P = 0.003, P = 0.002, and P = 0.007, respectively）. Chi-square analysis showed that the statistically significant variables were p53, p21, bax, β-catenin, c-myc, PTEN, p-Aktl, Cox-2 and nm23-h1 for histological grade （P = 0.005, P = 0.013, P = 0.044, P = 0.000, P = 0.000, P = 0.029, P = 0.000, P = 0.008, and P = 0.000, respectively）, β-catenin, comyc and p-Akt1 for lymph node metastasis （P = 0.011, P =0.005, and P = 0.032, respectively）, β-catenin, c-myc, Cox-2 and nm23-h1 for distance metastasis （P = 0.020, P = 0.000, P = 0.026, and P = 0.008, respectively）, and cyclin D1, β-catenin, c-myc, Cox-2 and nm23h1 for clinical stages （P = 0.038, P = 0.008, P = 0.000, P = 0.016, and P = 0.014, respectively）. CONCLUSION： Tissue microarray immunohistochemical staining enables high-throughput analysis of genetic alterations contributing to human colon cancer development and progression. Our results implicate the potential roles of p53, cyclin D1, bcl-2, bax, Cox-2, β-catenin and c-myc in development of human colon cancer and that of bcl-2, nm23-h1, PTEN and p-Akt1 in pro     

Book Reviews

Book reviewed in this article: Bigby, Christine, books reviewed by, 100‐1 Blaikie, Andrew, Ageing and popular culture, reviewed, 201‐2 Butler, Robert N., Life in an older America, reviewed, 152‐3 Caldwell, John C., books reviewed by, 99 Creedy, John, Pensions and population ageing: an economic analysis, reviewed, 99–100 Dandekar, Kurnudini, The elderly in India, reviewed, 99 Gibson, Diane, books reviewed by, 202‐3 Howe, Anna, books reviewed by, 152‐3 Howe, Brian, books reviewed by, 47 Hudson, Robert B., books reviewed by, 45‐6 Jamieson, Anne, Critical approaches to ageing and later life, reviewed, 101‐2 Lanspery, Susan, Staying put: adapting the places instead of the people, reviewed, 47 Lavin, C., Older adults with developmental disabilities, reviewed, 100‐1 McCalman, Janet, books reviewed by, 201 McDermott, Justin, books reviewed by, 101‐2 Means, Robin, From poor law to community care, reviewed, 202‐3 Mears, Jane, books reviewed by, 153‐4 Neysmith, Shiela M., Critical issues for future social work practice with ageing persons, reviewed, 153‐4 Pastalan, Leon A, Shelter and service issues for ageing populations: international perspectives, reviewed, 47 Piggott, John, books reviewed by, 99–100 Policy implications of the ageing of Australia's population: conference proceedings, reviewed, 45‐6 Rajan, S. Irudaya, India's elderly: burden or challenge?. reviewed, 99 Russell, Cherry, books reviewed by, 201‐2 Thane, Pat, Old age in English history: past experiences, present issues, reviewed, 201     

First‐Step Use of Fixed‐Dose Combination Treatment in Stage 2 Hypertensive Patients: Has the Time Come?

A panel discussion was convened on February 14, 2007, to discuss the use of fixed-dose combination therapy for stage 2 hypertensive patients. The panel was moderated by Michael A. Weber, MD, Professor of Medicine, SUNY Downstate College of Medicine, New York, NY. Participants included Luis Ruilope, MD, Chief, Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain, Thomas D. Giles, MD, Professor of Medicine, Tulane University School of Medicine, Metairie, LA, and Joseph L. Izzo, Jr, MD, Professor of Medicine, Department of Medicine, State University of New York at Buffalo, Buffalo, NY.     

Myocardial infarction Changes in the concentrations of high-energy compounds and free amino acids in erythrocytes

Quantitative determination of the nucleotides AMP, ADP, ATP, GTP, NAD, NADP, 2,3-DPG and the free amino acids Lys, His, Gly, Ala, Val, Met, Phe, Tyr, Pro, Thr, Ser, Glu, Asp in erythrocytes was carried out in early and late stages of myocardial infarction. It was found that in erythrocytes, in the early stage of myocardial infarction, the concentrations of AMP, NADP and 2,3-DPG increased, whereas those of ADP, ATP, GTP and NAD decreased. In the third week of the disease the concentrations of AMP, ADP, NADP, and especially 2,3-DPG remained high, while those of ATP and GTP shifted towards the control. The concentrations of His, Gly, Ala, Val, Met, Phe, Thr and Glu increased, while those of Tyr, Ser and Asp decreased in the first stage of myocardial infarction. At the later stage of the illness (21 days) the concentrations of free amino acids returned to normal.     

The gray rat (Rattus norvegicus) as a carrier of infectious causative agents in Siberia and the Far East

Literary data and antiplague institutions' reports demonstrate that Norway rats carry over 24 nosological forms and groups of infectious diseases: plague, tularemia, pseudotuberculosis, intestinal yersiniosis, salmonellosis, erysipeloid, listeriosis, leptospirosis, pasteurellosis, brucellosis, dysentery, paratuberculosis, hemorrhagic nephroso-nephritis, Omsk hemorrhagic fever and Q fever, tick-borne and Japanese encephalitis, lymphocytic choriomeningitis, tick-borne rickettsiosis and rickettsial pox, murine typhus, tsutsugamushi disease and toxoplasmosis.     

Diagnostic Accuracy of APRI,AAR, FIB-4, FI,King, Lok,Forns, and FibroIndex Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis: A Systematic Review and Meta-Analysis

Aspartate aminotransferase-to-platelet ratio (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, FI, King, Lok, Forns, and FibroIndex scores may be simple and convenient noninvasive diagnostic tests, because they are based on the regular laboratory tests and demographic data. This study aimed to systematically evaluate their diagnostic accuracy for the prediction of varices in liver cirrhosis.All relevant papers were searched via PubMed, EMBASE, CNKI, and Wanfang databases. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated.Overall, 12, 4, 5, 0, 0, 4, 3, and 1 paper was identified to explore the diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores, respectively. The AUSROCs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of varices were 0.6774, 0.7275, 0.7755, 0.7885, and 0.7517, respectively; and those for the prediction of large varices were 0.7278, 0.7448, 0.7095, 0.7264, and 0.6530, respectively. The diagnostic threshold effects of FIB-4 and Forns scores for the prediction of varices were statistically significant. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, and Lok scores for the prediction of varices were 0.60/0.67/1.77/0.58/3.13, 0.64/0.63/1.97/0.54/4.18, and 0.74/0.68/2.34/0.40/5.76, respectively. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of large varices were 0.65/0.66/2.15/0.47/4.97, 0.68/0.58/2.07/0.54/3.93, 0.62/0.64/2.02/0.56/3.57, 0.78/0.63/2.09/0.37/5.55, and 0.65/0.61/1.62/0.59/2.75, respectively.APRI, AAR, FIB-4, Lok, and Forns scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis.     

How Is the Liver Primed or Sensitized for Alcoholic Liver Disease?

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hidekazu Tsukamoto and Yoshiyuki Takei. The presentations were (1) Tribute to Professor Rajendar K. Chawla, by Craig J. McClain; (2) Dysregulated TNF signaling in alcoholic liver disease, by Craig J. McClain, S. Joshi-Barve, D. Hill, J Schmidt, I. Deaciuc, and S. Barve; (3) The role of mitochondria in ethanol-mediated sensitization of the liver, by Anna Colell, Carmen Garcia-Ruiz, Neil Kaplowitz, and Jose C. Fernandez-Checa; (4) A peroxisome proliferator (bezafibrate) can prevent superoxide anion release into hepatic sinusoid after acute ethanol administration, by Hirokazu Yokoyama, Yukishige Okamura, Yuji Nakamura, and Hiromasa Ishii; (5) S-adenosylmethionine affects tumor necrosis factor-α gene expression in macrophages, by Rajendar K. Chawla, S. Barve, S. Joshi-Barve, W. Watson, W. Nelson, and C. McClain; (6) Iron, retinoic acid and hepatic macrophage TNFα gene expression in ALD, by Hidekazu Tsukamoto, Min Lin, Mitsuru Ohata, and Kenta Motomura; and (7) Role of Kupffer cells and gut-derived endotoxin in alcoholic liver injury, by N. Enomoto, K. Ikejima, T. Kitamura, H. Oide, Y. Takei, M. Hirose, B. U. Bradford, C. A. Rivera, H. Kono, S. Peter, S. Yamashina, A. Konno, M. Ishikawa, H. Shimizu, N. Sato, and R. Thurman.     

Improving Blood Pressure Control Rates: Is There More We Can Do?

A panel discussion was convened on November 10, 2006, to discuss methods of improving blood pressure control rates and future study focus. The expert panel was moderated by George L. Bakris, MD, Director, Hypertension Center, Endocrine Division, the University of Chicago School of Medicine, Chicago, IL, and included Matthew R. Weir, MD, Division of Nephrology, the University of Maryland School of Medicine, Baltimore, MD, and Henry R. Black, MD, Roberts Professor of Preventive Medicine, Rush University Medical Center, Chicago, IL.     

Prebiotic Synthesis of Hydrophobic and Protein Amino Acids

The formation of amino acids by the action of electric discharges on a mixture of methane, nitrogen, and water with traces of ammonia was studied in detail. The presence of glycine, alanine, alpha-amino-n-butyric acid, alpha-aminoisobutyric acid, valine, norvaline, isovaline, leucine, isoleucine, alloisoleucine, norleucine, proline, aspartic acid, glutamic acid, serine, threonine, allothreonine, alpha-hydroxy-gamma-aminobutyric acid, and alpha,gamma-diaminobutyric acid was confirmed by ion-exchange chromatography and gas chromatography-mass spectrometry. All of the primary alpha-amino acids found in the Murchison Meteorite have been synthesized by this electric discharge experiment.     

14种抗结核药物在巨噬细胞内的抗结核活性评价

目的 测定14种抗结核药物在巨噬细胞内的抗结核活性,并评价体外巨噬细胞内抗结核活性测定对新药筛选的作用。方法 采用结核分枝杆菌标准株H37Rv 感染J774.1巨噬细胞,建立体外巨噬细胞感染模型。分别检测利福平、异烟肼、左氧氟沙星、吡嗪酰胺、贝达喹啉、氯苯吩嗪、利奈唑胺、硝基咪唑类药物PA-824、氯苯吩嗪的衍生物TBI-166、利奈唑胺的同类药物OTB-658,以及苯并噻嗪类药物PBTZ-169和BTZ-043、TZY-5-84、NTB-3119H作用后的巨噬细胞中的细菌载量,评价抗结核药物的胞内活性;并采用微孔培养显色法(MABA法)测定上述药物的体外最低抑菌浓度。从中选取利福平、异烟肼、左氧氟沙星、贝达喹啉、氯苯吩嗪、利奈唑胺、TBI-166、PBTZ-169分别作用J774.1巨噬细胞3h,利用高效液相色谱-质谱/质谱联用技术测定细胞内药物浓度。结果 细胞培养基中药物浓度为0.50μg/ml时,异烟肼、PBTZ-169、贝达喹啉、BTZ-043、NTB-3119H、TZY-5-84和PA-824降低巨噬细胞内结核分枝杆菌1.60、1.33、1.31、1.25、1.13、1.01和1.00lg(CFU/ml)(CFU:菌落形成单位),胞内活性最强的是异烟肼和PBTZ-169,其次是贝达喹啉;但吡嗪酰胺、利奈唑胺、TBI-166和OTB-658仅降低巨噬细胞内结核分枝杆菌0.65、0.55、0.33 和0.31lg(CFU/ml)。经体外90%最低抑菌浓度(MIC₉₀)和胞内活性比较,发现利奈唑胺和OTB-658虽然具有良好的体外抗菌活性(MIC₉₀分别为0.25和0.05μg/ml),但是二者在细胞培养基中浓度为5μg/ml时仅降低巨噬细胞内结核分枝杆菌0.77和0.50lg(CFU/ml)。在培养基中药物浓度为20μg/ml时,PBTZ-169、贝达喹啉、氯苯吩嗪、利福平、TBI-166、异烟肼、左氧氟沙星和利奈唑胺在巨噬细胞内的浓度为1.42、2.11、4.93、1.65、0.50、0.27、1.13和0.32μg/ml,胞内药物浓度是其MIC₉₀(分别为0.0005、0.03、0.12、0.05、0.04、0.05、0.25、0.25μg/ml)的2840.00、70.33、41.08、33.00、12.50、5.40、4.52和1.28倍。结论 各药物进入巨噬细胞的能力并不相同,巨噬细胞内抗菌活性的差异提示细胞内药物浓度及与MIC₉₀ 的关系是细胞内活性的决定因素。     

瞬时弹性成像在慢性乙型肝炎肝纤维化诊断中的应用

目的：探讨瞬时弹性成像（ FS）在慢性乙型肝炎（乙肝）肝纤维化诊断中的应用价值。方法选取慢性乙肝患者165例,其中轻度肝纤维化者77例,中度肝纤维化者47例,重度肝纤维化及肝硬化者41例;另选同期健康体检者50例。采用FS扫描仪检测所有受试者肝脏硬度值;采用常规及临床生化检查检测血小板、AST、谷氨酰转肽酶及胆固醇,计算APRI指数、Forns指数。采用受试者工作特征（ ROC）曲线分析FS、APRI、Forns单独及联合诊断慢性乙肝肝纤维化的准确性。结果在诊断中度肝纤维化时,FS、Forns、APRI的ROC曲线下面积（ AUC）值分别为0．807、0．786、0．767,诊断界值分别为8．5 kPa及8．1、11．7,敏感度分别为83．3％、60．0％、73．3％,特异度分别为81．6％、92．1％、76．3％;在诊断重度肝纤维化及肝硬化时,FS、Forns、APRI的AUC值分别为0．896、0．886、0．829,诊断界值分别为16．3 kPa及8．4、9．3,敏感度分别为73．3％、80．0％、73．3％,特异度分别为90．6％、83．0％、88．7％。在诊断中度肝纤维化时,FS＋APRI ＋Frons、FS＋Frons、FS＋APRI、FS 的AUC 值分别为0．851、0．832、0．826、0．807,敏感度分别为66．7％、76．7％、70．0％、83．3％,特异度分别为97．4％、81．6％、89．5％、81．6％;在诊断重度肝纤维化及肝硬化时,FS＋APRI＋Frons、FS＋Frons、FS＋APRI、FS的AUC值分别为0．922、0．904、0．907、0．896,敏感度分别为86．7％、86．7％、80．0％、73．3％,特异度分别为88．7％、83．0％、88．7％、90．6％。结论 FS对慢性乙肝肝纤维化诊断准确性高,联合血清学检测诊断效能增高,具有良好的临床应用价值。     

Endocrine status in stage II vs. advanced premenopausal and postmenopausal breast cancer patients.

Circulating preoperative levels of DHEA-S, androstenedione and SHBG were measured in 40 premenopausal and 49 postmenopausal breast cancer patients, and in 30 and 15 age-matched healthy controls, respectively. Moreover, the levels of LH, FSH, prolactin, estradiol, progesterone, testosterone, DHEA-S, androstenedione and SHBG of Stage II breast cancer patients were compared with advanced patients and also with controls. In premenopausal patients the levels of steroid hormones were significantly low whereas those of peptide hormones were significantly high. On the contrary, in postmenopausal patients, except DHEA-S, all other hormones were significantly elevated in comparison with controls. In premenopausal patients, DHEA-S, androstenedione, estradiol, progesterone, and testosterone decreased as stage advanced with concomitant increase of SHBG, LH, FSH and prolactin when compared with hormone levels of Stage II patients. In postmenopausal advanced breast cancer patients, when compared with Stage II patients, the levels of SHBG, LH, FSH, and prolactin increased significantly, while DHEA-S, androstenedione, estradiol, and progesterone decreased as stage advanced.     

Abstracts of papers on haemophilia from other journals

Incidence of factor VIII inhibitor development in hemophilia A patients treated with less pure plasma derived concentrates. de Biasi R, Rocino A, Papa, ML, Salerno E, Mastrullo L, De Blasi D.
Rapid clearance of hepatitis C virus RNA in peripheral blood mononuclear cells of patients with clotting disorders and chronic hepatitis C treated with alpha-2b interferon is not a predictor for sustained response to treatment. Peerlinck K, Willerns M, Sheng L, Nevens F, Fevery J, Yap SH, Verrnylen J.
Factor VIII gene rearrangements in patients with severe haemophilia A. Goodeve AC, Preston FE, Peake IR.
Immune status of human immunodeficiency virus seropositive and seronegative hemophiliacs infused for 3.5 years with recombinant factor VIII. Mannucci PM, Brettler DB, Aledort LM, Lusher JM, Abildgaard CF, Schwartz RS, Hurst D and the Kogenate Study Group.
The role of platelet von Willebrand factor in platelet adhesion and thrombus formation: a study of 34 patients with various subtypes of type I von Willebrand disease. Fressinaud E, Federici AB, Castaman G, Rothschild C, Rodeghiero F, Baumgartner HR, Mannucci PM, Meyer D.
Two controlled trials of rifabutin prophylaxis against Mycobacteriurn aviurn complex infection in AIDS. Nightingale SD, Cameron DW, Gordin FM, Sullam PM, Cohn DL, Chaisson RE, Eron LJ, Sparti PD, Bihari B, Kaufman DL, Stern JJ, Pearce DD, Weinberg WG, LaMarca A, Siegal FP.
Three-year randomised study of high-purity or intermediate-purity factor VIII concentrates in symptom-free HIV-seropositive haemophiliacs: effects on immune status. Seremetis SV, Aledort LM, Bergman GE, Bona R, Bray G, Brettler D, Eyster ME, Kessler C, Lau T-S, Lusher J, Rickles F.     

The neurotoxicity of antibacterial agents

Commonly used antibacterial agents may be associated with various neurotoxic reactions. Central nervous system toxicities include seizure disorders, encephalopathy, bulging fontanelles, and neuropsychiatric symptoms. These abnormalities have been associated with the use of the penicillins, cephalosporins, sulfonamides, tetracyclines, chloramphenicol, colistin, aminoglycosides, metronidazole, isoniazid, rifampin, ethionamide, cycloserine, and dapsone. Cranial nerve toxicities, such as myopia, optic neuritis, deafness, vertigo, and tinnitus, have been associated with the use of erythromycin, sulfonamides, tetracyclines, chloramphenicol, colistin, aminoglycosides, vancomycin, isoniazid, and ethambutol. Peripheral nerve symptoms consisting of paresthesias, motor weakness, or sensory impairment have been associated with the use of the penicillins, sulfonamides, chloramphenicol, colistin, metronidazole, isoniazid, ethionamide, and dapsone. Neuromuscular blockade has been associated with the use of the tetracyclines, polymyxins, lincomycin, clindamycin, and aminoglycosides. Management generally consists of supportive therapy and immediate discontinuation of therapy with the offending drug.     

黄嘌呤氧化酶与糖代谢异常及尿酸水平的关系

目的探讨黄嘌呤氧化酶与糖代谢异常及尿酸水平的关系。 方法选取2009年6月至2010年6月浙江省湖州市第三人民医院同期收治的2型糖尿病及空腹血糖受损男性患者各50例（分别为2型糖尿病组及空腹血糖受损组）,另择同期体检健康者（血糖水平均正常）50例作为对照组。检测3组对象空腹血糖、糖化血红蛋白A1c（HbA1c）、空腹胰岛素、甘油三酯、LDL、尿素氮、血肌酐、血尿酸、ALT、AST、黄嘌呤氧化酶（xanthine oxidase,XOD）的水平。3组间所有参数先行单因素方差分析,然后再进一步行LSD分析。XOD与血尿酸、胰岛素抵抗指数（IRI）及空腹血糖的相关性采用Pearson相关分析,血尿酸与空腹血糖的相关性采用偏相关分析。 结果3组对象XOD、LDL、甘油三酯、空腹血糖、HbA1c、空腹胰岛素、血尿酸、血肌酐、尿素氮及IRI的差异均有统计学意义（F=53.803、5.476、4.957、42.596、52.477、10.582、20.014、8.883、13.138、14.947,均P<0.01）。与对照组比较,2型糖尿病组XOD及血肌酐均显著升高,差异有统计学意义（t=9.780、3.680,均P<0.01）;2型糖尿病组及空腹血糖受损组LDL、甘油三酯、空腹血糖、HbA1c、空腹胰岛素、血尿酸、尿素氮及IRI均明显升高,差异均有统计学意义（t=2.076、2.988、9.058、10.066、4.588、5.868、6.557、5.366,3.270、2.355、2.993、3.500、2.581、4.993、3.857、1.774;P<0.05或0.01）。与空腹血糖受损组比较,2型糖尿病组XOD、空腹血糖、HbA1c、空腹胰岛素、血肌酐、尿素氮及IRI均明显升高,差异均有统计学意义（t=7.866、6.065、6.636、2.007、3.621、2.236、3.592,P<0.05或0.01）。XOD与血尿酸、IRI、空腹血糖均呈显著正相关（r＝0.507、0.361、0.268,P<0.01或P=0.01）,血尿酸与空腹血糖呈明显正相关（r=0.17,P<0.05）。 结论XOD活性升高在增加尿酸代谢紊乱的同时可能加重糖代谢紊乱。     

Traditional Chinese Medicine and herbal hepatotoxicity: a tabular compilation of reported cases

Traditional Chinese Medicine (TCM) with its focus on herbal use became popular worldwide. Treatment was perceived as safe, with neglect of rare adverse reactions including liver injury. To compile worldwide cases of liver injury by herbal TCM, we undertook a selective literature search in the PubMed database and searched for the items Traditional Chinese Medicine, TCM, Traditional Asian Medicine, and Traditional Oriental Medicine, also combined with the terms herbal hepatotoxicity or herb induced liver injury. The search focused primarily on English-language case reports, case series, and clinical reviews. We identified reported hepatotoxicity cases in 77 relevant publications with 57 different herbs and herbal mixtures of TCM, which were further analyzed for causality by the Council for International Organizations of Medical Sciences (CIOMS) scale, positive reexposure test results, or both. Causality was established for 28/57 different herbs or herbal mixtures, Bai Xian Pi, Bo He, Ci Wu Jia, Chuan Lian Zi, Da Huang, Gan Cao, Ge Gen, Ho Shou Wu, Huang Qin, Hwang Geun Cho, Ji Gu Cao, Ji Xue Cao, Jin Bu Huan, Jue Ming Zi, Jiguja, Kudzu, Ling Yang Qing Fei Keli, Lu Cha, Rhen Shen, Ma Huang, Shou Wu Pian, Shan Chi, Shen Min, Syo Saiko To, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, and Zhen Chu Cao. In conclusion, this compilation of liver injury cases establishes causality for 28/57 different TCM herbs and herbal mixtures, aiding diagnosis for physicians who care for patients with liver disease possibly related to herbal TCM.