Stunning and myocardial contractile autoregulation studied on the isolated isovolumic blood-perfused dog heart

AIM: To study, for the first time, the effects of stunning on homeometric and heterometric autoregulation. METHODS AND RESULTS: Ischaemia (15 min)/reperfusion (30 min) was induced in the isovolumic blood-perfused dog heart preparation. Heart rate elevations (n = 9) from 60 to 200 beats min-1, in steps of 20 beats min-1, promoted the same inotropic stimulation in control (C) and stunning (S), indicating that ischaemia/reperfusion does not affect the changes in calcium kinetics elicited by the Bowditch effect. Sudden ventricular dilation (VD) (n = 10) evoked an instantaneous increase in developed pressure (Delta1DP) followed by a continuous slow performance increase (Delta2DP) in C and S. Delta1DP (C: 35 +/- 2.2 mmHg; S: 27 +/- 2.1 mmHg; P = 0.002) and Delta2DP (C: 20 +/- 1.6 mmHg; S: 14 +/- 1.3 mmHg; P = 0.002) decreased proportionally, while Delta2/Delta1DP (C: 0.57 +/- 0.13; S: 0.58 +/- 0.14) and slow response time course (T/2) were unchanged (C: 55 +/- 6.6 s; S: 57 +/- 7.7 s) after ischaemia/reperfusion. The reduction of Delta1DP can be understood as a decline of the myofilaments calcium responsiveness, the main pathophysiological effect of stunning. The reason for the weakening of Delta2DP, due to intracellular calcium gain, was not determined but it was supposed that its complete manifestation could be restricted by cyclic adenosine monophosphate (cAMP) myocardial content reduction. As reported by others, Delta2DP depends on myocardial cAMP, and it has been shown that myocardial cAMP is decreased after ischaemia/reperfusion. CONCLUSIONS: Contractile depression due to stunning has no effect on the inotropic stimulation generated by the Bowditch phenomenon. Immediate and time-dependent enhancements of contraction evoked by sudden VD are proportionally reduced and the slow response time course is unaffected in the stunned myocardium.     

CD4 responses to conserved HIV-1 T helper epitopes show both negative and positive associations with virus load in chronically infected subjects

Characterization of immune responses to immunodominant CD4 epitopes in HIV-1 that are associated with control of HIV infection could be used to strengthen the efficacy of polyepitope HIV vaccines. We measured both the proliferative and the CD4 interferon (IFN)-gamma and interleukin (IL)-2 cytokine responses specific for 11 previously identified HIV-1 T helper epitopes in 10 HIV-infected non-progressors (LTNPs) (infected for a median of 15 years with a stable CD4 count of >500 cells x 10(6)/l), and seven slow progressors (SPs) (infected for a median of 15 years with a CD4 count that had declined to <500 cells x 10(6)/l). Both groups were antiretroviral treatment-naive at the time of evaluation. The median virus load of SP group was higher than that of the LTNP group (P = 0.0002). The CD4 response to a peptide pool representing all potential CD4 Gag epitopes and to Gag p24 protein was also studied. Compared to SPs, LTNPs had higher numbers of Gag-specific IFN-gamma+IL-2+ CD4s (P = 0.0059). The Gag-specific cytokine and proliferative responses correlated inversely with virus load (P = 0.03 and 0.0002, respectively), highlighting the potential importance of this response in immunity to HIV. A direct correlation was noted between proliferation and the Gag-specific IL-2 (P = 0.0053) rather than IFN-gamma response (P = 0.1336), demonstrating that the proliferation assay reflected the IL-2 rather than the IFN-gamma secreting capacity of CD4 cells. Several subjects with diverse class II DRB1 alleles responded, confirming the 11 selected peptides to be both antigenic and conserved. CD4 cytokine responses to one Gag and two conserved Pol peptides correlated negatively with virus load. The cytokine response to two additional Pol peptides correlated positively with virus load. The data indicate that there is not an absolute correlation between the CD4 immune response to conserved and broadly antigenic helper T cell epitopes in HIV non-progression.     

Relationship between HLA-DRB1 and DQ alleles and the genetic susceptibility to type 1 diabetes

Objective　To study the relationship between human leukocyte antigen (HLA)-DRB1 and DQ alleles and the genetic susceptibility of type 1 diabetes in North Chinese children. Methods　Polymerase chain reaction (PCR) techniques were used to amplify the second exon of DRB1 and DQ alleles, after which sequence specific olignucleotide probe (SSOP) dot blot hybridization techniques were used to analyze the amplified products. Results　DRB1*0301, DQA1*0301, DQB1*0201 alleles and DRB1*0301-DQA1*0501-DQB1*0201 haplotype were significantly increased in patients, while DQA1*0103 and DQB1*0601 alleles were significantly increased in controls. The distribution of DR4 and DR9 haplotypes in patients and controls were not significantly different, but DR3/DR4 and DR4/DR9 heterozygotes were significantly increased in patients. Conclusions　DRB1*0301, DQA1*0301 and DQB1*0201 confer susceptibility while DQA1*0103 and DQB1*0601 confer protection to type 1 diabetes. DRB1*0301-DQA1*0501-DQB1*0201 haplotype offers a predisposition to type 1 diabetes in North Chinese. Although the distribution of DR4 and DR9 in patients and controls had no significant difference, DR3/DR4 and DR3/DR9 heterozygotes were significantly increased in patients, showing that the susceptive effects of DR3 and DR4 or DR4 and DR9 haplotypes could be added up.     

恶性肿瘤患者血清与尿液中一氧化氮含量测定

0 引言一氧化氮（Nitric oxide,NO）是一种具有活跃生物化学性质的无机小分子. NO对许多肿瘤细胞和微生物有细胞毒性［1］,为探讨NO与肿瘤的关系,我们检测了119例恶性肿瘤患者血清及尿液中的NO.     

带有蛋白转导结构域的bcr/abl癌蛋白片段表达及其跨膜转运

0　引言　人类免疫缺陷病毒 (human immunodeficiencyvirus,HIV) - 1编码的反式激活蛋白 TAT具有独特的跨膜运转方式 ,而且有转导速度快 ,效率高的特点 ,被称为蛋白转导结构域 (protein transduction domain,PTD) [1 ,2 ] .本研究用PCR扩增了慢性粒细胞白血病慢粒 bcr/ abl融合蛋白的基因片段 ,在其 5′端融合 PTD结构域的编码区后在大肠杆菌中进行了表达 .表达产物经纯化后 ,加入培养的 HL 6 0细胞 ,表达的蛋白可直接进入细胞内 .这一结果为用外源蛋白负载(L oading)免疫细胞提供了新的途径 .1　材料和方法1.1　 DNA重组　人工合…     

Continuous infusion cisplatin and etoposide chemotherapy for cancer of unknown primary site (CUPS) in Taiwan, a region with a high prevalence of endemic viral infections

BACKGROUND: To evaluate the efficacy and toxicity of cisplatin/etoposide continuous infusion chemotherapy for cancer of unknown primary site in Taiwan, a region with a high prevalence of endemic viral infections. METHOD: Between April 1994 and February 1996, 20 patients with a diagnosis of CUPS were treated, including 15 males and five females, of average age 63.3 years (range 41-83 years). Continuous intravenous infusion of etoposide 80 mg/m2 and cisplatin 25 mg/m2 was given for 3 days every 3 weeks. Pretreatment tumor marker and viral serology studies were performed for baseline evaluation. Nearly two-thirds of the patients had poorly differentiated carcinoma. The average number of metastatic sites was 2.65 (range 1-4), with liver and lymph node involvement predominating. RESULTS: The overall response rate was 25% (95% CI 17.7-32.3%); 30.7% for poorly differentiated cancers and 25% for well differentiated cancers. Median survival was 4 months (range 1-12 months), 4.8 months for patients attaining partial response. Toxicity was moderate, grade 3 and 4 neutropenia occurred in 55% and grade 3 and 4 thrombocytopenia in 40%; other toxicities were mild. CA125 and CA199 were elevated in more than 50% of patients. Viral serology studies were not significantly different from those of the indigenous population. CONCLUSION: Etoposide and cisplatin combination chemotherapy has modest activity in patients with extensive CUPS and, at the schedule and dosage given, it is associated with moderate toxicity.      

Rectal cancer in the Kingdom of Saudi Arabia: the King Faisal Specialist Hospital experience

BACKGROUND: No survival data have yet been published from the Kingdom of Saudi Arabia for patients with rectal cancer. The present paper reports experience with these patients over an 8-year period. METHODS: All patients referred to the King Faisal Specialist Hospital (KFSH) between March 1990 and February 1998 for the primary management of rectal cancer were entered into a computerized database. Prior to 1993 patients did not receive adjuvant therapy. Kaplan-Meier survival curves and the log-rank test were used to compare outcome data. RESULTS: There were 70 men (average age: 55.6 years) and 75 women (average age: 52.8 years). Twelve per cent of patients admitted a family history of colorectal carcinoma (CRC). Twenty-seven per cent of tumours were circumferential. Most tumours were larger than 4 cm and the lowest edge of the majority of tumours was less than 6 cm from the anal verge. Fifty-four per cent of tumours were fixed; 69% of patients received either pre-operative or postoperative radiotherapy. A total of 106 patients underwent 'curative' surgery. Equal numbers of patients had abdomino-perineal resection (APR) and anterior resection (AR) of the rectum. Thirty-five patients received blood peri-operatively (APR, 34%; AR, 12%). Major anastomotic leakage following AR occurred in two patients. Two patients died within 30 days of surgery. Ten patients were lost to follow-up. Following curative AR, eight patients had a distal resection margin of < 2 cm and two patients (Dukes' C) developed local recurrence (25%); 37 patients had a margin > 2 cm and seven developed local recurrence (18.9%). A total of 48 patients underwent curative APR, and four patients developed local recurrence (8.3%). Overall local recurrence was tumour stage-dependent (Dukes' B, 8.8%; Dukes' C, 29.3%). Recurrence was local in 13 patients. Pre-operative radiotherapy seemed to reduce average tumour size (3.6 vs 4.3 cm). The crude overall 5-year survival rate was 39%. The 5-year survival rate for patients with Dukes' stage C cancers following 'curative' surgery was 25%. CONCLUSION: Curative surgery can be performed with a relatively low requirement for blood transfusion, a low mortality and morbidity, and comparable outcomes to Western studies in spite of the large, low and often advanced stage of the tumours managed. Local recurrence rates following curative resection and re-anastomosis for low rectal cancers may be reduced by resisting patient pressure to avoid stomata.     

Endocyclophotocoagulation combined with phacoemulsification in surgically naive primary open-angle glaucoma: three-year results

ObjectiveTo assess the safety and efficacy of endocyclophotocoagulation with phacoemulsification (phaco-ECP) in surgically naive, primary open-angle glaucoma (POAG).MethodsA retrospective case series of patients undergoing phaco-ECP between 2007 and 2017 at a single centre in London, UK. The primary outcome was intraocular pressure (IOP). Secondary outcomes were visual acuity, visual field global indices, topical medications and surgical complications. Failure criteria were: (1) IOP > 21 mmHg or <20% reduction at two consecutive visits, (2) IOP <5 mmHg and (3) further IOP-lowering surgery.ResultsEighty-three eyes from 83 patients were eligible. Pre-operatively, mean IOP (±SD) was 18.4 ± 5.2 mmHg. The mean number of topical agents (±SD) was 2.7 ± 0.9. Mean IOP (±SD) significantly reduced to 14.3 ± 4.7 at 1 year, 14.1 ± 4.0 at 2 years and 13.6 ± 3.7 at 3 years (p < 0.0001). Topical medications were significantly reduced to 1.3 ± 1.2 at 1 year, 1.7 ± 1.2 at 2 years and 1.8 ± 1.3 at 3 years (p < 0.0001). Annual IOP ‘survival’ was 70%, 54% and 45% at year 1, 2 and 3, respectively. Complications included uveitis (6%), macular oedema (2%), IOP spikes (1%) and corneal decompensation (1%) with no episodes of hypotony or retinal detachment. One patient underwent filtration surgery within 3 years (1%).ConclusionPhaco-ECP facilitates significant IOP lowering and reduction of medication burden in surgically naive POAG requiring cataract extraction. The procedure is relatively safe and without the use of implants and their associated risks.Subject terms: Optic nerve diseases, Surgery