ThromCat血栓切除导管系统在急性冠状动脉综合征介入治疗中的应用

目的:评价ThromCat血栓切除导管系统(ThromCat Thrombectomy Catheter System,TTC)在急性冠状动脉综合征(ACS)介入治疗应用中的安全性、工作性能及有效性.方法:入选14例ACS患者进行经皮冠状动脉介入治疗(PCI),分析TTC操作的成功率、TTC应用的临床成功率、术中并发症和术后随访30 d心脏不良事件.结果:TTC操作成功11例,TTC临床成功10例,PCI成功13例,并不伴有心脏不良事件.在PCI中,心肌梗死溶栓治疗(TIMI)血流由使用TIC前的0.5(2.0)升高至使用后的2.0(1.0),心肌灌注分级(MBG)由使用前的1.0(2.0)升高至使用后的2.0(1.0),差异均有统计学意义(均P<0.01).结论:在ACS患者中行PCI,TTC能安全有效地去除非严重钙化的冠状动脉内的血栓.并发症少,操作简单易行,减少PCI手术引起的并发症.     

甲状腺术中喉返神经监测技术的标准化

目的在甲状腺手术中缺少术中神经监测(intra operative neuromonitoring,IONM)的标准化操作可导致结果变异性强,这些结果可产生错误信息并增加喉返神经损伤的危险性。因此有必要进行IONM操作的标准化。方法本研究共招募了289例进行过甲状腺切除术的患者(435根神经有危险),均由一位外科医师实施手术。每例患者均由同一位麻醉师使用EMG气管导管进行插管。每例患者均进行标准化IONM操作。该操作包括术前和术后对声带运动进行录像监测、保证电极在正确位置、喉返神经剥离前后刺激迷走神经并记录EMG信号,并摄像记录暴露的喉返神经。结果5例患者出现IONM波形异常,是由于电极错位所致,这一问题被立刻监测到。监测到1例患者在手术较早阶段出现非喉返神经损伤。甲状腺剥离时18例患者的神经失去了EMG信号,使用我们的标准化IONM操作后神经损伤的原因得以清楚阐明。结论标准化IONM操作不仅在消除错误的IONM结果方面有用且有帮助,而且有助于阐明喉返神经损伤的机制。在确定外科手术的缺陷并提高外科手术技巧后,本研究显著降低了神经麻痹的发生率。     

Detection of reactive oxygen species (ROS) and apoptosis in human fragmented embryos

In human in-vitro fertilization (IVF)-embryo transfer, the in-vitro culture environment differs from in-vivo conditions in that the oxygen concentration is higher, and in such conditions the mouse embryos show a higher concentration of reactive oxygen species (ROS) in simple culture media. ROS are believed to cause damage to cell membranes and DNA fragmentation in somatic cells. This study was conducted to ascertain the level of H2O2 concentration within embryos and the morphological features of cell damage induced by H2O2. A total of 62 human oocytes and embryos (31 fragmented, 15 non-fragmented embryos, 16 unfertilized oocytes) was obtained from the IVF-embryo transfer programme. The relative intensity of H2O2 concentrations within embryos was measured using 2',7'-dichlorodihydrofluorescein diacetate by Quanti cell 500 fluorescence imaging and DNA fragmentation was observed with transmission electron microscopy and an in-situ apoptosis detection kit. The H2O2 concentrations were significantly higher in fragmented embryos (72.21 +/- 9.62, mean +/- SEM) compared to non-fragmented embryos (31.30 +/- 3.50, P < 0.05) and unfertilized oocytes (30.75 +/- 2.67, P < 0.05). Apoptosis was observed only in fragmented embryos, and was absent in non-fragmented embryos. Electron microscopic findings confirmed apoptotic bodies and cytoplasmic condensation in the fragmented blastomeres. We conclude that there is a direct relationship between increased H2O2 concentration and apoptosis, and that further studies should be undertaken to confirm these findings.      

De novo 16p13.11 microdeletion identified by high-resolution array CGH in a fetus with increased nuchal translucency

Objective  We investigated the application of high-resolution microarray-based comparative genomic hybridisation (array CGH) on a fetus showing increased nuchal translucency (NT).
Design  Case study.
Setting  Tertiary referral obstetrics unit.
Sample  Pregnant woman attended the antenatal clinic.
Methods  Conventional karyotyping and genetic test was carried out for the alpha-globin gene. High-resolution array CGH using the high-density 244K Agilent microarray was performed on fetal blood sample by cordocentesis to investigate the possibility of any genomic imbalance.
Main outcome measures  Detection of chromosomal abnormality.
Results  Karyotyping analysis showed 46,XY. Molecular genetic diagnosis confirms the fetus has Hb-H constant spring disease but cannot explain the increased NT to 3.2 mm. Array CGH analysis discovered a 1.32-Mb microdeletion on chromosome 16p13.11. Deletion at 16p13.11 has been implicated to predispose to autism and/or mental retardation. Baby was delivered at 40 weeks of gestation, and follow up was carried out at 3 months of age without sign of mental retardation/developmental delay.
Conclusions  This case study demonstrated that array CGH can accurately calibrate the size and identify de novo interstitial chromosome imbalances. However, the presence of chromosome copy variants with unknown clinical significance currently limits its wider scale application in prenatal diagnosis and needs further investigations.     

Is homozygous α-thalassaemia a lethal condition in the 1990s?

Two cases of homozygous α-thalassaemia who received active treatment in accordance with parental wishes are reported. One infant survived and the other, although successfully weaned off mechanical respiratory support, unexpectedly developed portal vein thrombosis and died. Homozygous a-thalassaemia, a condition previously considered to be universally fatal, and an indication for therapeutic abortion, is now potentially curable with advances in diagnostic technology and treatment. However, active management of these cases raises serious ethical questions and has major financial implications on the health-care system. Invasive prenatal and intensive postnatal interventions should remain experimental and cannot be recommended as routine clinical practice until the questions of long-term neurodevelopmental outcome, and the morbidity and mortality associated with bone-marrow transplantation have been fully addressed. As a result of advances in information technology, more and more parents of affected foetuses are likely to request active treatment.     

Vitamin D status and hyperparathyroisism in postmenopausal osteoporotic patients in Cipto Mangunkusumo hospital Jakarta

Aim: to determine the profile of vitamin D and parathyroid hormone (PTH) and the proportion of vitamin D inadequacy in a population of postmenopausal osteoporotic patients from a rheumatologic outpatient clinic. Methods: a cross sectional study was conducted between October and December 2006 in the Rheumatology Clinic, Cipto Mangunkusumo Hospital with osteoporosis confirmed by bone mineral densitometry (T score less than -2.5 at the lumbar spine or hip). Patients were excluded if there was a history of oral glucocorticoid treatment within 30 days, vitamin D supplementation, and have renal and/or liver function impairments. Forty-two postmenopausal osteoporotic patients aged 51-77 years old who had been postmenopausal for 5-28 years were included in this study. Vitamin D inadequacy was defined as the plasma levels of 25(OH)D less than 50 nmol/L whereas hyperparathyroidism was defined as the PTH level more than 69 pg/dL. Results: vitamin D inadequacy was found in 61.9% of patients and 34.6% of them or 23.8% of total patients were also having high PTH level. There was an inverse correlation between 25(OH)D with PTH levels and positive correlation between duration of menopause and PTH level. Vitamin D inadequacy is common (61.9%) in postmenopausal osteoporotic patients who visited Rheumatology outpatient clinic of Cipto Mangunkusumo Hospital Jakarta. Conclusion: the low concentration of 25(OH)D was correlated with PTH level and duration of menopause. This finding should be confirmed in a larger epidemiological study, either hospital-or community-based to assess vitamin D status among postmenopausal women in Indonesia.     

Intrauterine insemination: effect of the temporal relationship between the luteinizing hormone surge, human chorionic gonadotrophin administration and insemination on pregnancy rates

The optimal time period for intrauterine insemination (IUI) in relation to either luteinizing hormone (LH) surge or human chorionic gonadotrophin (HCG) administration leading to the best pregnancy rates has not been determined. In this study, 856 consecutive human menopausal gonadotrophin (HMG)-stimulated and 49 natural unstimulated IUI cycles carried out at a reproductive medicine unit affiliated with a tertiary centre were analysed in a retrospective fashion. There were three scenarios in the temporal relationship of the LH surge, HCG administration and artificial insemination. These were (group A) subjects who had an endogenous LH surge but were not given HCG; (group B) subjects who were given HCG after an observed LH surge, and (group C) subjects who were given HCG before the LH surge. The overall pregnancy rate (PR) was 16% per cycle. The PR was 9% in group A, 20% in group B and 14% in group C. The PR in group B was significantly better than group C (P = 0.04). In group B, the longer the time interval between the LH surge and HCG administration, the better the PR up to 20 h (P = 0.025); the timing of IUI based on the LH surge was not critical to the achievement of pregnancy within 3 days. In group C, PR improved with the increasing interval between HCG and IUI from <28 h up to 60 h. We conclude that a better PR is achieved if a spontaneous LH surge occurs before HCG administration, especially where the administration of HCG is delayed 8-20 h after an observed LH surge; the timing of IUI based on the LH surge is not critical to the achievement of pregnancy within 3 days.      

A diagnostic microdosing approach to investigate platinum sensitivity in non‐small cell lung cancer

The platinum‐based drugs cisplatin, carboplatin and oxaliplatin are often used for chemotherapy, but drug resistance is common. The prediction of resistance to these drugs via genomics is a challenging problem since hundreds of genes are involved. A possible alternative is to use mass spectrometry to determine the propensity for cells to form drug‐DNA adducts—the pharmacodynamic drug‐target complex for this class of drugs. The feasibility of predictive diagnostic microdosing was assessed in non‐small cell lung cancer (NSCLC) cell culture and a pilot clinical trial. Accelerator mass spectrometry (AMS) was used to quantify [¹⁴C]carboplatin‐DNA monoadduct levels in the cell lines induced by microdoses and therapeutic doses of carboplatin, followed by correlation with carboplatin IC₅₀ values for each cell line. The adduct levels in cell culture experiments were linearly proportional to dose (R² = 0.95, p < 0.0001) and correlated with IC₅₀ across all cell lines for microdose and therapeutically relevant carboplatin concentrations (p = 0.02 and p = 0.01, respectively). A pilot microdosing clinical trial was conducted to define protocols and gather preliminary data. Plasma pharmacokinetics (PK) and [¹⁴C]carboplatin‐DNA adducts in white blood cells and tumor tissues from six NSCLC patients were quantified via AMS. The blood plasma half‐life of [¹⁴C]carboplatin administered as a microdose was consistent with the known PK of therapeutic dosing. The optimal [¹⁴C]carboplatin formulation for the microdose was 10⁷ dpm/kg of body weight and 1% of the therapeutic dose for the total mass of carboplatin. No microdose‐associated toxicity was observed in the patients. Additional accruals are required to significantly correlate adduct levels with response.