Pulmonary arterial hypertension as leading manifestation of methylmalonic aciduria: clinical characteristics and gene testing in 15 cases / 北京大学学报(医学版)

Objective:To deepen our understanding of Methylmalonic aciduria (MMA) associated pulmonary hypertension (PH) by analyzing the characteristics of clinical presentation,pulmonary high resolusion CT(HRCT),treatment response and gene mutation.Methods:This study includes 15 cases of pediatric patients with MMA associated PH diagnosed and treated in Peking University First Hospital pediatric department between May 2012 and May 2016 with symptoms of PH as their leading presentation.Clinical symptoms and signs were recorded,Routine blood laboratory examinations was done including arterial blood gas analysis.Plasma total homocysteine (Hcy) and brain natriuretic peptide (BNP) level were measured.MMA gene mutation was analyzed.Chest HRCT was done in most of the patients.Standard treatment strategy to MMA and PH was given and follow up study was done,and the related literature was reviewed.Statistical analysis was done.The diagnosis of MMA was made by methylmalonic acid level ＞ 100 times the normal value in the urine.The diagnosis of PH was made by pulmonary arterial systolic pressure (PASP) ＞ 40 mmHg,which was estimated by the measurement of tricuspid regurgitation velocity through Doppler Echocardiography.Results:(1) Patient characteristics:There were 10 male and 5 female patients diagnosed as MMA associated PH,aged 0.5 to 13.8 years,with an average of (5.0 ± 4.3) years.The age of onset of PH was (3.7 ± 3.5) years,with an early onset type MMA in 5 cases and late-onset type in 10 cases.(2) Clinical presentation:Among the 15 cases of MMA,the first symptoms were associated with PH in 10 cases,so PH and MMA were diagnosed at the same time,and PH was diagnosed 3 to 72 months post MMA presentation in the other 5 cases.The main presentations of PH were techypnea/dyspnea and cyanosis in 11 cases each,weakness and fatigue on exertion in 6 cases,and edema in 4 cases.PH WHO functional classification (WHO FC) was Class Ⅱ in 4,Class Ⅲ in 5 and Class Ⅵ in 6 cases,with an average of Class 3.1 ± 0.8.Multi-system involvements were common with the highest frequency in the kidney (14 cases).Macrocytic anemia was present in 8 cases and subclinical hypothyroidism in 5 cases,and mild to moderate mental retardation in 4 cases.(3) Laboratory examination:PASP of the 15 patients was from 49 to 135 mmHg,with an average of (90.3 ±23.9) mm Hg.Total blood Hcy level was severely elevated to (121.2 ± 48.2) μmol/L (range:35.0-221.0 μmol/L),and Hcy ＞ 100 μmoL/L within 11 cases.Plasma BNP level was also elevated,median 794 ng/ L (range:21.0-4 995.0 ng/L) with 12 cases ＞ 300 ng/L.Blood gas analysis showed low arterial blood oxygen saturation between 70％ and 94％,with an average of 81.4％ ±8.4％.(4) Chest HRCT:chest HRCT showed a diffuse ground-glass centrilobular nodular opacities with septal line thickening in the lungs in 9 cases,and with associated mediastinal lymph node enlargement in 1 case,which indicated pulmonary veno-occlusive disease (PVOD),a rare type of pulmonary arterial hypertension (PAH).There was lung infection or edema in 3 cases,and interstitial infiltration and mesh-like feature in other 3 cases,which was inferred to interstitial lung disease.(5) Gene mutation:Genetic testing was done in 10 cases,totally 5 reported disease-causing mutations were found.There were 100％ presence of MMACHC c.80A ＞ G mutation in all the 10 patients tested,with the allelic genes of c.609G ＞ A mutation in 6 patients,including a sister and a brother from the same parents.(6).Treatment and follow up:Intramus cular hydroxocobalamin or vitamin B12 was given to all of the patients,together with betaine,levocarnidtine,folinic acid and vitamin B6.According to the severity of PH,single or combined PAH targeted drugs was given to 11 cases.By an average of (20.0 ± 13.5) days of in-hospital treatment in 13 patients (excepting 1 case treated as outpatient),symptoms remarkably resolved,WHO FC reduced to an average of Class 2.4 ±0.9,PASP dropped to (69.4 ±21.3) mmHg,and plasma Hcy and BNP level were decreased to (74.9 ± 25.9) μmol/L and (341.6 ± 180.2) ng/L,respectively.The above values all reached statistical significance (P ＜ 0.05) compared with each related value before treatment.Therewere 2 patients who expired during hospitalization despite of treatment.At the end of 3 months' follow up,all of the 13 patients disposed oxygen,and PASP significantly dropped to 38.7 ± 7.9 mmHg,and plasma BNP returned to normal,but plasma Hcy level showed no further decline.At the last follow up of 27.5 ± 19.0 (range:11-64) months,all the patients' PASP remained normal except for the 13.8-year-old boy with 6 years-long history of MMA and almost 3.6 years' history of PH still having PASP 58 mmHg.Conclusion:PH is a severe complication of MMA combined type,especially cblC type,it is more often happens in late-onset type of male patients and can be the first and leading manifestations of MMA.Its clinical symptoms are urgent and severe,characterized by tachypnea/dyspnea and cyanosis,and sometimes right heart failure,hypoxemia is usually present,chest HRCT is often indicative of PVOD,lung edema and interstitial lung disease may occur.Rapid diagnosis and targeted treatment of MMA with appropriate anti-PAH mcdication can reverse PH and save life.MMACHC gene c.80A ＞ G mutation may be the hot point of MMA cblC type associated PH.

Combined use of occluder plus bare stent in the treatment of aortic dissection with tear at the area of visceral branches / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the novel method of combinedly use of occluder and bare stent in the treatment of aortic dissection with distal tear at visceral branches.</p><p><b>METHODS</b>From April 2010 to September 2012, 6 patients (5 male and 1 female patients, aged from 29 to 62 years, mean 47.2 years) were diagnosed as Stanford type B aortic dissection that been revealed by CT angiography. The main tears were sealed with stent-grafts firstly, and then the tears at the visceral branch area were evaluated that impossible to close spontaneously. Atrium septal defect occluder and ventricular septal defect were implanted at the tears with the anterior disc in false lumen, while the posterior disc in the true lumen. After that, the bare stents were implanted in the true lumen to pull the occluders on the aortic wall.</p><p><b>RESULTS</b>Among the 6 procedures, occluders were successfully implanted in 5 cases, and 1 failed anchoring at the tear, and the alternative method of coils embolization was applicated. After all the procedures, the immediate aortogrophy revealed that the false lumen disappeared in the 5 cases that occluders were used, and the visceral branches were all patent. No paraplegia, lesion of visceral organs or other complications occurred. All the cases were followed at least 5 months. There was one endoleak due to a non-sealed tear at the descending aorta, one new-occurred small tear in the descending aorta but with no communication to the false lumen.</p><p><b>CONCLUSIONS</b>The combinedly use of occluder and bare stent in the treatment of aortic dissection with tears at the visceral branch area is a sum of two simple technique plus each other. It is easily to master. The lesions at the aortic that ordinary stent-grafting incapable to seal are successfully solved then. The huge trauma of open or hybrid procedures are avoided.</p>

Effect of Health Education Intervention on the Recovery of First Onset Schizophrenia / 中国康复理论与实践

@#ObjectiveTo investigate the short-term effect of health education intervention on the recovery of new schizophrenia patients. Methods82 patients were randomly divided into observation group, in which patients accepted routine antipsychotic medication, general nursing and system health education intervention, and control group, in which patients accepted antipsychotic medication and general nursing. Brief psychiatric Rating Scale (BPRS) and Positive And Negative Syndrome Scale (PANSS) were used to assess the effects. ResultsThere was no difference in the score of every factor before intervention (P>0.05), but it became different after intervention (P<0.01 or P<0.05). ConclusionHealth education intervention can improve the effect on schizophrenia.

Change of platelet count and P-selectin in preserved platelet concentrates / 中国实验血液学杂志

To observe the change of quantity and quality of platelets preserved in a full-sealed bag, and explore the difference of platelets preserved in oscillating and static conditions at (22 +/- 2) degrees C, the platelet concentrates were prepared with a CS-3000-plus blood cell separator, the platelet counts were performed with automatic blood cell analyzer and P-selectin in supernatant of platelet concentrates was detected by ELISA. The results showed that both of platelet count and P-selectin content in the platelet concentrates had no significant difference between oscillating and static preservation condition. With prolongation of preserved time, the platelet count decreased and P-selectin content increased gradually in both preserved conditions. There was no difference in the platelet counts during 0 - 72 hours preservation in both conditions, and significant difference was seen in 96 - 120 hours preservation. It was concluded that the expired date for platelet product preserved in CS-3000-plus blood cell separator full-sealed system should be 3 days. Under the condition of (22 +/- 2) degrees C, the quality of the platelet preserved in oscillating state is not superior to static preservation.