Catheter Ablation of Typical Atrial Flutter in Severe Pulmonary Hypertension

Atrial Flutter and Pulmonary Hypertension. Background: Radiofrequency ablation is first‐line therapy for atrial flutter (AFL). There are no studies of ablation in patients with severe pulmonary arterial hypertension (PAH). Methods: Consecutive patients with severe PAH (systolic pulmonary artery pressure >60 mmHg) and AFL referred for ablation were evaluated. Patients with complex congenital heart disease were excluded. Results: A total of 14 AFL ablation procedures were undertaken in 12 patients. A total of 75% of patients were female; mean age 49 ± 12 years. SPAP prior to ablation was 99 ± 35 mmHg. Baseline 6‐minute walk distance was 295 ± 118 m. ECG demonstrated a typical AFL pattern in only 42% of cases. Baseline AFL cycle length was longer in PAH patients compared to controls (295 ± 53 ms vs 252 ± 35 ms, P = 0.006). Cavotricuspid isthmus dependence was verified in 86% of cases. Acute success was obtained in 86% of procedures. SPAP decreased from 114 ± 44 mmHg to 82 ± 38 mmHg after ablation (P = 0.004). BNP levels were lower postablation (787 ± 832 pg/mL vs 522 ± 745 pg/mL, P = 0.02). Complications were seen in 14%. A total of 80% (8/10) of patients were free of AFL at 3 months; 75% (6/8) at 1 year. Conclusion: Ablation of AFL in severe PAH patients is feasible, with good short‐ and intermediate‐term success rates. The ECG pattern is not a reliable marker of isthmus dependence. The SPAP and BNP levels may decrease postablation. AFL may be a marker of poor outcomes in patients with PAH with a 1‐year mortality rate of 42% in this study. This rate is higher than expected in the general PAH population. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1185–1190, November 2012)     

Mature liver stages of cloned Plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages

The liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. Investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. In addition, only a low proportion of cells are obtained in vivo, the parasites from Cebus and Aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by contamination with the natural mosquito flora copurified with the sporozoites used for seeding the liver cultures. In our study, mature liver schizonts were shown to possess many of the antigenic determinants recognized by MoAbs and sera specific for defined sporozoite and blood-stage antigens. We employed an immunofluorescence procedure based on evaluating parasites in cryosections prepared from infected chimpanzee liver. Sufficient numbers of sectioned parasites were evaluated with each antibody to assure the reproducibility of the results, and the fixation procedure used was sufficiently non-destructive to parasite antigens so that clear differences between reactions of specific antibodies and negative controls were observed. Our evidence for sharing of epitopes by liver merozoites and sporozoites or by liver merozoites and asexual blood-stage parasites raises the possibility that immune responses elicited against sporozoites or asexual stage antigens being considered as vaccine candidates may also act against this important, little-studied stage of the parasite.     

Megakaryocytopoiesis in Experimentally Induced Immune Thrombocytopenia

The hypothesis that in immune thrombocytopenia, platelet antibody maynot only cause destruction of the circulating platelets but also depress plateletproduction by injuring the megakaryocytes of the bone marrow, was testedexperimentally.

Sustained thrombocytopenia was produced in rats by titrated injections ofa potent heteroimmune antiplatelet serum and megakaryocytopoiesis wasthen studied by the use of tritiated thymidine and bone marrow autoradiography. Rats in which the platelet count was maintained at a lower thannormal level by repeated thrombocytophereses, and other rats injected withplatelet antiserum previously absorbed with rat platelets, served as controls.

Profoundly altered patterns of megakaryocytopoiesis were found in the ratsin which thrombocytopenia was produced by the antiplatelet serum. The dataindicated a severely impaired and depressed megakaryocyte maturation and,possibly, destruction of some of the megakaryocytes during their maturationprocess. In the rats in which the platelet level was maintained low by repeatedthrombocytophereses, the pattern of megakaryocytopoiesis indicated accelerated maturation and there was also an increased megakaryocyte mass. Nodifference from normal was found in the rats receiving the platelet-adsorbed antiserum. It was concluded that the platelet antibody produced aninjurious effect on the megakaryocytes in the bone marrow, thereby depressing platelet production, and that the immune thrombocytopenia was theresult of both increased platelet destruction and defective platelet production.

Submitted on November 22, 1968 Accepted on October 3, 1969     

Hereditary Spherocytosis: Observations on Hemolytic Mechanisms and Iron Metabolism

1. Two healthy patients with hereditary spherocytosis were phlebotomizeduntil they developed iron deficiency and the erythrocytes became hypochromic.The hereditary spherocytes were no longer spheroidal: they became thin, andthe fragility tests improved. However, the life span of the cells in the circulation was not improved. Later, splenectomy corrected the hemolytic disease.

2. In both patients, prior to the experiment, the hemolytic disease wascompensated. There was no anemia despite the rapid turnover of red cells.In one of the patients, whose average red cell life span was only five days, theoutput of hemoglobin must have been exceedingly high. It was computed tobe 135 Gm. per day, or 20 times the normal rate.

3. Some aspects of iron metabolism in hereditary spherocytosis are discussed.

4. The shape of the red cell in HS does not appear to be responsible for itspremature destruction by the spleen. Iron deficiency corrects the spherocytosis,but it does not correct the hemolytic disease. Splenectomy corrects the hemolytic disease, but it does not correct the spherocytosis.

     

REPEATED DELIBERATE SELF-HARM IN THE ELDERLY

Previous reports on deliberate self-harm (DSH) in old age are reviewed and the lack of any study on repetition in this group is pointed out. The study then describes 39 patients over the age of 60 who presented after repeated self-harm at a district general hospital between 1973 and 1993. They made up 1% of all DSH cases, 28 were female and 11 were male, seven were multiple repeaters. Thirty were suffering from depressive illnesses, six showed significant cognitive impairment, while five (four of them women) gave a history of alcohol abuse. A trend emerged for women to score higher than men on a measure of suicidal intent. Two patients committed suicide during the study period. These findings are discussed together with their implications for the management and prevention of suicidal behaviour in the elderly.     

An Alzheimer's Disease-Relevant Presenilin-1 Mutation Augments Amyloid-Beta-Induced Oligodendrocyte Dysfunction

研究表明,家族性阿尔茨海默病(FAD)患者处于无症状或临床前阶段时,脑白质即出现病理改变.此种改变在髓鞘破坏及阿尔茨海默病(AD)病理生理中的作用有待进一步研究阐明.笔者前期研究证实,三重转基因AD小鼠(人淀粉前体蛋白基因的Swedish突变,早老素-1 M146V (PS1M146V)敲入突变及tauP301L突变)...     

TREATMENT OF PERNICIOUS ANEMIA BY A SPECIAL DIET

The dietetic treatment of pernicious anemia is of more importance than hithertogenerally recognized.

Forty-five patients with pernicious anemia observed essentially in sequence arecontinuing to take a special diet that they have now been living on for from aboutsix weeks to two years but which was temporarily omitted by three. This diet iscomposed especially of foods rich in complete proteins and iron—particularly liver—and containing an abundance of fruits and fresh vegetables and relatively low infat.

Following the diet, all the patients showed a prompt, rapid and distinct remission of their anemia, coincident with at least rather marked symptomatic improvement, except for pronounced disorders due to spinal cord degeneration. Improvement was often striking, so that where the red blood cell count averaged for allbefore starting the diet 1,470,000 per cubic millimeter, one month afterward itaveraged 3,400,000; and for the twenty-seven cases observed from four to sixmonths after the diet was begun, the average count was 4,500,000 per cubic millimeter.

Patients having had two or more relapses showed on the average slightly lowerred blood corpuscle counts about one and two months after commencing the dietthan did those who had started it in their first or second relapse.

Change in the frequency of bowel movements, temporary increase of reticulocytes in the peripheral blood, and decrease of the icterus index of the blood serumwere among the earliest signs that heralded the patient’s better health.

All the patients have remained to date in a good state of health except three, whodiscontinued the diet; two rapidly improved on resuming it and the other has justcommenced it again. As the diet was advised for most of the patients less than eightmonths ago, enough time has not yet elapsed to determine whether or not the remissions will last any longer than in other cases.