Segmental aortic wall stiffness from intravascular ultrasound at normal and subnormal aortic pressure in pigs.

Segmental aortic wall stiffness was calculated from intravascular ultrasound images and intravascular pressures in six pigs at normal and subnormal aortic pressures (21 sequences of pressures and areas before and after boli of intravenous nitroglycerin). The wall stiffness was expressed as the pressure-strain elastic modulus (Ep). The Ep was calculated from the formula: Ep = delta PR delta R-1 (P, pressure; R, radius) in two different ways. First from maximal and minimal values of pressure and area. Second as the slope of linear regression line of delta PR as a function of delta R from 29 simultaneous recorded pressures and images. The average Ep value for all sequences in the different segments was 0.58 +/- 0.55 10(5) Pa (Method 1) and 0.50 +/- 0.40 10(5) Pa (Method 2). Ep increased with the distance from the heart at normal aortic pressures. At subnormal aortic pressures after intravenous nitroglycerin this relationship was not so evident. At subnormal aortic pressures the calculated Ep values were significantly reduced in the lower half of the abdominal aorta. The phase lag, i.e. hysteresis, between pressure and diameter was demonstrated. Our study shows the applicability of intravascular ultrasound as a tool to evaluate arterial wall stiffness.     

Catheter ablation by low energy DC shocks for successful management of atrial flutter.

OBJECTIVE--To assess the effects of low energy ablation of the substrate for atrial flutter. DESIGN--Initial retrospective analysis of patients undergoing low energy ablation of the atrioventricular node for refractory atrial flutter (group 1) was followed by a prospective assessment of low energy ablation in the posterio-inferior right atrium for the same condition (group 2). SETTING--Tertiary referral centre for management of cardiac arrhythmias. PATIENTS--Seven men (aged 50-67 years) with refractory atrial flutter. INTERVENTIONS--Multiple (3-10) low energy DC shocks with a cumulative energy of 100-245 J in the region of the atrioventricular node in group 1 and 12-15 low energy DC shocks (cumulative energy 110-235 J) guided by the anatomical landmarks of the triangle of Koch and applied directly to the atrial wall. MAIN OUTCOME MEASURE--Freedom from recurrence of atrial flutter. RESULTS--In group 1 despite initial complete atrioventricular block in three patients, atrioventricular conduction had resumed in all by one month. All four, however, were in sinus rhythm at follow up six to 13 months later. Two of the three patients in group 2 were free of atrial flutter at follow up three to four months after ablation. CONCLUSION--Ablation of the atrial flutter substrate with low energy DC shocks is feasible. Precise electrophysiological mapping is not necessary.     

Thrombotic microangiopathies in the 1980s: clinical features, response to treatment, and the impact of the human immunodeficiency virus epidemic.

We reviewed the medical records of 44 adults with 50 consecutive episodes of thrombotic thrombocytopenia purpura (TTP) or hemolytic uremic syndrome (HUS) seen at the University of California, San Francisco affiliated hospitals during the past decade. Patients were treated according to a uniform plan in which initial therapy included daily large volume plasmapheresis using fresh frozen plasma. Patients not responding completely to initial therapy were treated with a salvage regimen including splenectomy, dextran, and corticosteroids. At the time of diagnosis, the lactate dehydrogenase (LDH) was elevated in 98% of cases, with a median value of 1,208 U/L. Other clinical features were present inconsistently, and only 34% of "TTP" episodes involved the classic pentad of hemolytic anemia, thrombocytopenia, neurologic disorders, noninfectious fever, and renal impairment. Primary treatment with plasma exchange produced complete remission in 56% (27 of 48) of the episodes. Previously splenectomized patients uniformly responded to plasma therapy (12 of 12). In patients not responding completely to primary therapy, salvage splenectomy produced complete responses in 81% (13 of 16) of the cases. The pattern of clinical response to therapy was consistent, with initial resolution of neurologic dysfunction (median, 3 days) followed by normalization of LDH levels (5 days) and platelet count (7 days). Normalization of renal function occurred significantly later (15 days). Although short-term responses to plasma therapy in human immunodeficiency virus (HIV)-seropositive patients did not differ from other patients, no HIV-positive patient survived more than 2 years from diagnosis of thrombotic microangiopathy (TMA). We conclude that the diagnosis of TMA requires a high degree of clinical suspicion and that the diagnostic criteria should consist of microangiopathic hemolytic anemia, thrombocytopenia, and an elevated LDH. Initial therapy with plasma exchange leads to disease control in the majority of cases, but an optimal treatment strategy requires the use of alternative methods if initial remission is transient or not achieved. Salvage therapy with splenectomy, steroids, and dextran is highly effective in this setting.     

乳腺管状小叶癌

乳腺管状小叶癌（Tubulolobular carcinoma，TLC）最初是被作为小叶癌的管状变型。作者总结了27例TLC的组织学、免疫表型和临床特征，并与纯小管癌和经典型小叶癌进行了比较。此组患者年龄43-79岁（中位年龄60岁）。1例双侧乳腺受累，5例病变为多灶性。肿瘤直径0．5-2．5cm，色灰褐，质硬。组织学观察：TLC的肿瘤细胞形成管状和条索状两种结构模式并相互混杂，且两者比例相当（统称为管状小叶模式）。     

Germline mutations of the CDKN2 gene in UK melanoma families

Germline mutations in CDKN2 on chromosome 9p21, which codes for the cyclin D kinase inhibitor p16, and more rarely, mutations in the gene coding for CDK4, the protein to which p16 binds, underlie susceptibility in some melanoma families. We have sequenced all exons of CDKN2 and analysed the CDK4 gene for mutations in 27 UK families showing evidence of predisposition to melanoma. Five different germline mutations in CDKN2 were found in six families. Three of the mutations (Met53Ile, Arg24Pro and 23ins24) have been reported previously. We have identified two novel CDKN2 mutations (88delG and Ala118Thr) which are likely to be associated with the development of melanoma, because of their co-segregation with the disease and their likely functional effect on the CDKN2 protein. In binding assays the protein expressed from the previously described mutation, Met53Ile, did not bind to CDK4/CDK6, confirming its role as a causal mutation in the development of melanoma. Ala118Thr appeared to be functional in this assay. Arg24Pro appeared to bind to CDK6, but not to CDK4. No mutations were detected in exon 2 of CDK4, suggesting that causal mutations in this gene are uncommon. The penetrance of these mutant CDKN2 genes is not yet established, nor is the risk of non-melanoma cancer to gene carriers.      

Classification of heart failure in population based research: An assessment of six heart failure scores

Several scores based on symptoms and signs have been developed to assess the presence of heart failure. The goal of this study was to compare six heart failure scores in non-hospitalised subjects and to determine their usefulness in population based research. The scores were applied to 54 participants of a population based study. All underwent a complete medical examination, including chest X-ray, electrocardiography and Doppler echocardiography. Using all information available, a cardiologist, unaware of the results of the scores, clinically classified participants as having no, possible or definite heart failure. Sensitivity, specificity, predictive values and receiver operating characteristics were calculated, using the cardiologist's assessment as a gold standard. The cardiologist judged definite or possible heart failure to be present in 17 persons. All scores had a high sensitivity for the detection of definite heart failure, whereas the study of men born in 1913 and Walma's score had the highest sensitivity for the combination of possible and definite heart failure. Gheorgiade's and the Boston score had the highest positive predictive values. In conclusion, five of the six scores we studied are broadly similar in the detection of heart failure. The men born in 1913 score relies heavily on the assessment of dyspnea, resulting in a relatively large number of false positives. Although the scores are useful in detecting manifest heart failure, objective measurements of cardiac function appear necessary to reduce the false positive rate and accurately detect early stages of heart failure.     

Alcohol ablation of atrioventricular conduction

Transcoronary ablation of atrioventricular conduction by dehydrated alcohol was attempted in 14 patients with refractory atrial arrhythmias. Alcohol (0.5 or 1.0 ml) was delivered after selective catheterisation of the atrioventricular nodal artery in the 10 patients in whom the artery could be identified by cineangiography. The other four patients underwent electrical ablation when the nodal artery could not be catheterised. Temporary atrioventricular block induced by dilute contrast and cold saline (0.9%) confirmed that the catheter was in the correct position before the alcohol was delivered. In all 10 patients complete atrioventricular block developed after alcohol ablation. The block persisted in all four patients given 1.0 ml alcohol but not in four of the six given 0.5 ml. The mean (SD) creatine kinase (MB fraction) at four to six hours after ablation was 76.5 (49.5) IU after 1.0 ml and 75.5 (43.1) IU after 0.5 ml alcohol (normal less than 20 IU). The overall success rate of alcohol ablation in the whole group on an "intention to treat" basis was 43%. The procedure was a technical success in six of the 10 patients in whom the nodal artery was identified. Transcoronary alcohol ablation of atrioventricular conduction should be considered in patients in whom electrical techniques have been unsuccessful.