Coronary artery disease and arterial hypertension: clinical, angiographic and follow-up data

OBJECTIVES: To evaluate how the presence of arterial hypertension affects coronary atherosclerosis and prognosis in patients with, or at high risk of, ischaemic heart disease. DESIGN: Retrospective analysis of clinical records and follow-up data. SETTINGS: Single referral centre for ischaemic heart disease. SUBJECTS: All consecutive patients (n = 1700, 38% with hypertension) undergoing coronary angiography for the evaluation of ischaemic heart disease during 1983-92. RESULTS: On angiography, the likelihood of having three-vessel disease was higher amongst hypertensives (odds ratio = 1.41; 95% confidence interval [CI] = 1.08-1.85) after adjustment for age, sex, and angina symptoms. The sum of all visible stenoses (an index of overall atherosclerotic involvement) was 19% higher in hypertensives (262 +/- 204 vs. 220 +/- 194 units, P < 0.005). By multivariate analysis, the presence of hypertension made a modest (+ 28 units), albeit statistically significant, independent contribution to the total atherosclerosis score. On follow-up (median = 96 months), cardiovascular mortality was slightly higher in the hypertensive patients than in the normotensive group (P < 0.05 in a Kaplan-Meier analysis), but a proportional hazard analysis adjusting for age and gender showed no significant independent contribution of hypertension. Hypertensive patients, however, remained at higher risk of non-fatal myocardial infarction following discharge (adjusted odds ratio = 1.21, 95% CI = 1.03-1.46; P < 0.05). CONCLUSIONS: In this referral population, hypertension is a risk factor for presence of three-vessel disease. Distribution, severity and extension of coronary stenosis are similar to those of normotensive patients, and prognosis is only marginally affected.     

Reduction of serum matrix metalloproteinase 1 and matrix metalloproteinase 3 in rheumatoid arthritis patients following anti- tumour necrosis factor-alpha (cA2) therapy

Matrix metalloproteinase (MMP)-1 and MMP-3 levels were measured in serum samples from rheumatoid arthritis (RA) patients undergoing a double-blinded placebo-controlled trial with the chimaeric anti-tumour necrosis factor (TNF)-alpha antibody cA2. Both MMP-1 (P < 0.015), but to a larger extent MMP-3 (P < 0.001) levels were elevated in all RA patients prior to the commencement of the trial compared with normal control sera. Following cA2 therapy, MMP-1 and MMP-3 levels were assessed in the placebo, and 1 and 10 mg/kg cA2-treated groups at 7, 14, 21 and 28 days. In both the 1 and the 10 mg/kg cA2-treated groups, a significant decrease in serum MMP-3 levels at all time points was observed, reducing maximally to 41% of pre-infusion values at day 7. MMP-1 levels were also reduced, but less dramatically than MMP-3, to 85% of pre-infusion values after 14 days in the 10 mg/kg cA2 treated group. In a separate non-placebo-controlled study, we also evaluated the tissue inhibitor of metalloproteinase (TIMP)-1 levels in plasma following cA2 infusion. Pre-infusion TIMP-1 levels were above the normal control range, but were significantly reduced (P < 0.035) 14 days after infusion to 72% of pre-infusion values. This study confirms previous reports that MMP-3 levels are elevated and correlate with measures of inflammation in RA, and furthermore demonstrate that serum MMP-3 and MMP-1 levels are downmodulated following anti-TNF-alpha antibody therapy. Whilst serum MMP-3 levels correlated with C-reactive protein (CRP) both prior to and following anti-TNF-alpha antibody therapy, it remains to be demonstrated that serum MMP-3 and/or MMP-1 levels reflect the cartilage and bone resorptive processes which are evident in this disease.      

Utility of combined use of plasma levels of chromogranin A and pancreatic polypeptide in the diagnosis of gastrointestinal and pancreatic endocrine tumors

BACKGROUND: Chromogranin A (CgA) is considered the most accurate marker in the diagnosis of gastro-entero-pancreatic (GEP) endocrine tumors. Pancreatic polypeptide (PP) has also been proposed to play this role, but then not used due to its low sensitivity. The aim of the present study was to determine whether the assessment of PP would improve the diagnostic reliability of CgA in patients with GEP tumors. PATIENTS AND METHODS: Both markers were assessed in 68 patients [28 functioning (F), 40 non functioning (NF)]. Twenty-seven patients disease-free (DF) after surgery, and 24 with non-endocrine tumors (non-ETs) were used as control groups. RESULTS: CgA sensitivity was: 96% in F, 75% in NF, 74% in pancreatic, and 91% in gastrointestinal (GI) tumors. Specificity was 89% vs DF, and 63% vs non-ETs. PP sensitivity was: 54% in F, 57% in NF, 63% in pancreatic, and 53% in GI tumors. Specificity was 81% vs DF, and 67% vs non-ETs. By combining the two markers a significant gain in sensitivity vs CgA alone was obtained: overall in GEP tumors (96% vs 84%, p = 0.04), in NF (95% vs 75%, p = 0.02), and in pancreatic (94% vs 74%, p = 0.04). More specifically, a 25% gain of sensitivity was obtained in the subgroup of NF pancreatic tumors (93% vs 68%, p = 0.04). CONCLUSION: The combined assessment of PP and CgA leads to a significant increase in sensitivity in the diagnosis of GEP tumors, particularly in pancreatic NF.     

Human colonic myogenic dysfunction induced by mucosal lipopolysaccharide translocation and oxidative stress

Background

Impairment of gastrointestinal motility is frequently observed in patients with severe infection.

Aim

To assess whether exposure of human colonic mucosa to pathogenic lipopolysaccharide affects smooth muscle contractility.

Methods

Human colonic mucosa and submucosa were sealed between two chambers, with the luminal side facing upwards and covered with Krebs solution, with or without lipopolysaccharide from a pathogenic strain of Escherichia coli (O111:B4; 1000 ng/mL), and with the submucosal side facing downwards into Krebs. The solution on the submucosal side was collected following 30-min mucosal exposure to Krebs without (N-undernatant) or with lipopolysaccharide (lipopolysaccharide undernatant). Undernatants were tested for lipopolysaccharide and hydrogen peroxide levels and for their effects on smooth muscle cells in the presence of catalase, indomethacin or MG132.

Results

Smooth muscle cells incubated with N-undernatant had a maximal contraction of 32 ± 5% that was reduced by 62.9 ± 12% when exposed to lipopolysaccharide undernatant. Inhibition of contraction was reversed by catalase, indomethacin and MG132. Lipopolysaccharide levels were higher in the lipopolysaccharide undernatant (2.7 ± 0.7 ng/mL) than in N-undernatant (0.45 ± 0.06 ng/mL) as well as hydrogen peroxide levels (133.75 ± 15.9 vs 82 ± 7.5 nM respectively).

Conclusions

Acute exposure of colonic mucosa to pathogenic lipopolysaccharide impairs muscle cell contractility owing to both lipopolysaccharide mucosal translocation and production of free radicals.     

神经肽DGAVP和Org2766对神经细胞内游离Ca2+的影响

运用Ca²⁺指示剂Fura-2作为细胞内钙离子的荧光探针,利用AR—CM—MIC阳离子测定系统,检测了分离的神经细胞内游离钙及其变化,并观测了DGAVP和Org2766对蛋白质合成抑制剂茴香霉素(ANI)引起细胞内钙离子浓度([Ca²⁺]_i)变化的影响。结果表明茴香霉素可使[Ca²⁺]_i显著升高,且有量效关系;DGAVP本身并不引起[Ca²⁺]_i发生显著变化,但适当剂量的DGAVP可显著对抗一定剂量范围内ANI升高[Ca²⁺]_i的作用,提示DGAVP对抗ANI的蛋白质合成抑制效应可能是通过拮抗ANI升高[Ca²⁺]_i这一途径实现的,另一神经肽Org2766则可能不是通过这一机制发生作用。从细胞内Ca²⁺的角度看,这两种肽的作用机理显然是不同的。     

Neonatal treatment with 192 IgG-saporin produces long-term forebrain cholinergic deficits and reduces dendritic branching and spine density of neocortical pyramidal neurons

The role of basal forebrain-derived cholinergic afferents in the development of neocortex was studied in postnatal rats. Newborn rat pups received intraventricular injections of 192 IgG-saporin. Following survival periods ranging from 2 days to 6 months, the brains were processed to document the cholinergic lesion and to examine morphological consequences. Immunocytochemistry for choline acetyltransferase (ChAT) and in situ hybridization for ChAT mRNA demonstrate a loss of approximately 75% of the cholinergic neurons in the medial septum and nucleus of the diagonal band of Broca in the basal forebrain. In situ hybridization for glutamic acid decarboxylase mRNA reveals no loss of basal forebrain GABAergic neurons. Acetylcholinesterase histochemistry demonstrates a marked reduction of the cholinergic axons in neocortex. Cholinergic axons are reduced throughout the cortical layers; this reduction is more marked in medial than in lateral cortical areas. The thickness of neocortex is reduced by approximately 10%. Retrograde labeling of layer V cortico-collicular pyramidal cells reveals a reduction in cell body size and also a reduction in numbers of branches of apical dendrites. Spine densities on apical dendrites are reduced by approximately 20-25% in 192 IgG- saporin-treated cases; no change was detected in number of spines on basal dendrites. These results indicate a developmental or maintenance role for cholinergic afferents to cerebral cortical neurons.      

Melanocytic skin lesions and pregnancy: digital dermoscopy analysis

BACKGROUND: Very few studies have tried to clarify how pregnancy influences the morphology of pigmented skin lesions (PSL). Our purpose was to objectively determine, by digital dermoscopy analysis (DDA), any dermoscopic changes of acquired melanocitic nevi during pregnancy and after 1 year from delivery. METHODS: Thirty-five healthy pregnant women and 35 age-matched female controls were enrolled in the study. Nevi of pregnant women were analysed by DDA between 5 and 8 weeks of pregnancy, between 39 and 41 weeks of pregnancy and 12 months after delivery. Nevi of control women were analysed by DDA in a month of the year matching the period of recruitment of pregnant women and 21 months later. RESULTS: Multivariate analysis of variance (manova) for repeated measures revealed that dermoscopic variables SKIN-GREEN-AVERAGE, SKIN-BLUE-AVERAGE and CONTRAST changed during pregnancy but returned to non-significant values after a year from delivery. The variable ENTROPY showed significant differences between initial evaluation and 1 year after delivery. Finally, the variable VARIANCE OF BORDER GRADIENT showed a significant difference between the first and the last evaluations, in both pregnant and control subjects. CONCLUSIONS: The study showed that pregnancy leads to significant modifications in PSL, especially with regard to pigment network, globules and architectural order or disorder.     

双胸蚯蚓溶栓酶对沙鼠缺血额叶皮质超微结构及离子的影响

采用结扎沙土鼠双颈总动脉20分钟后恢复血流制做脑缺血再灌注模型。应用透射电镜对额叶皮质超微结构进行观察,并采用电镜能谱技术对神经元随机检测Na~十Ca~卄等离子含量。结果表明,缺血的对照组神经元Na~十明显增高达16.43,而缺血后腹腔注入双胸蚯蚓溶栓酶的实验组显著下降为13.02,接近正常组的11.47;Ca~卄正常组为1.03,对照组增高达3.81,而实验组下降为2.44。同时实验组超微结构的损伤性改变明显轻于对照组。     

Successful bone marrow transplantation in children with severe aplastic anemia using HLA-partially matched family donors

Bone marrow transplantation (BMT) using HLA-partially matched family donors has produced disappointing results (25–30% of long-term survivors) in patients with severe aplastic anemia. We describe two children affected by severe aplastic anemia, not responsive to immunosuppressive therapy, who underwent allogeneic bone marrow transplantation using a HLA-partially matched family donor. Both cases presented 2 first class HLA-antigens (A and B) disparity between donor and recipient. The pretransplant conditioning regimen consisted of cyclophosphamide, thoracoabdominal irradiation, cytosine-arabinoside, and antilymphocyte globulin. As graft versus host disease (GVHD) prophylaxis, Cyclosporine-A was administered at usual dosages for 6 months. A full marrow engraftment was observed in both cases. Only grade I acute GVHD, promptly responsive to corticosteroid therapy, developed with no chronic GVHD. Five months after transplant, both children progressively developed hypertension, renal function impairment, thrombocytopenia, and severe normochromic anemia, with erythropoietin serum levels lower than expected for the haematocrit. After antihypertension treatment and supportive therapy, the clinical picture progressively improved, while treatment with recombinant human erythropoietin completely corrected the long-lasting anemia. The two children are alive and well 28 months after the transplant, with a Karnofsky score of 100% and a normal peripheral blood count. The authors suggest that, once immunosuppressive therapy has failed, BMT from donors other than HLA-identical sibling is a feasible approach in children affected by severe aplastic anemia, not having an HLA-identical donor. © 1993 Wiley-Liss, Inc.