High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus

Bogdanova NV, Antonenkova NN, Rogov YI, Karstens JH, Hillemanns P, Dörk T. High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital‐based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first‐degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first‐degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non‐carriers. Taken together, these results identify three BRCA1 founder mutations as key components of inherited breast and ovarian cancer susceptibility in Belarus and might have implications for cancer prevention, treatment and genetic counselling in this population.     

In vivo optical coherence tomography imaging of human skin: norm and pathology

Background/aims: Since the majority of skin diseases are known to be accompanied by structural alterations, research efforts are focused on the development of various novel diagnostic techniques capable of providing in vivo information on the skin structure. An essential parameter here is spatial resolution. In this paper we demonstrate the capabilities of optical coherence tomography (OCT) in detecting in vivo specific features of thin and thick skin. A particular focus is made on the identification of OCT patterns typical of certain pathological processes in skin, by performing parallel histological and tomographical studies. Methods: To obtain images of the skin, we used a compact fiber OCT system developed at the Institute of Applied Physics of the Russian Academy of Sciences. A low coherence source (superluminescent diode) operated at a wavelength of 1280 nm; the output power was 0.5–2 mW. This power is low enough to conform to the ANSI safety standards for light exposure. The in‐depth resolution limited by the spectral bandwidth (40–50 nm) of the probing light was ～20 μm. The lateral resolution determined by the probe light focusing ranged from 15 to 30 μm. In this series of experiments the maximum depth of imaging did not extend beyond 1.5 mm. Obtaining images of skin regions 2–6 mm long took 2–4 s. OCT capabilities for imaging normal skin of different localization and some skin diseases were studied in 12 healthy volunteers and 24 patients. Results: OCT imaging of the skin can detect in vivo such general pathological reactions of the human body as active inflammation and necrosis. OCT is useful for in vivo diagnosis of some specific processes in the skin, including hyperkeratosis, parakeratosis and formation of intradermal cavities. OCT imaging is noninvasive and therefore allows frequent multifocal examination of skin without any adverse effects. OCT can perform monitoring of disease progress and recovery in the course of therapy. Morphometric studies, measurements of the depth and extension of skin pathology within the human body can be easily performed by OCT. Conclusions: OCT allows imaging of subsurface soft tissues with the spatial resolution of 15–20 μm, a resolution one order of magnitude higher than that provided by other clinically available noninvasive diagnostic techniques. An imaging depth of up to 1.5–2 mm, given by current OCT technology, is sufficient to examine the skin. Real time OCT imaging can provide information not only on the structure, but also on some specific features in the functional state, of tissues. OCT imaging is a noninvasive technique, i.e., OCT does not cause trauma and has no side effects since it utilizes radiation in the near infrared wavelength range at a power as low as 1 mW.     

Neurodevelopmental outcome in high-risk preterm infants treated with inhaled nitric oxide

Inhaled nitric oxide (iNO) is used to treat preterm infants with hypoxaemic respiratory failure. In this study we describe the long-term survival and neurodevelopmental status of high-risk preterm infants enrolled into a randomized controlled trial of iNO therapy. Information regarding long-term outcome was available for all 25 children enrolled in the original trial who survived until discharge from hospital. Formal, blinded, developmental assessment and neurological examinations were performed in 21 out of 22 children still alive at 30 mo of age, corrected for prematurity. No significant differences were found in long-term mortality (12/20 vs 8/22, RR 1.65, 95% CI 0.87-3.3), neurodevelopmental delay (4/7 vs 9/14, RR 0.89, 95% CI 0.37-1.75), severe neurodisability (0/7 vs 5/14, p = 0.12) or cerebral palsy (0/7 vs 2/14, p = 0.53) between iNO-treated and control infants. CONCLUSION: In this study there was no evidence of a significant effect on either survival or long-term neurodevelopmental status in infants treated with iNO.     

杂交技术在法洛四联症中的应用

目的:总结杂交技术镶嵌治疗儿童法洛四联症(TOF)的经验。方法:外科术前介入治疗:3例有巨大体肺侧支(APCAs)的重症TOF在根治术前予以侧支血管堵塞术。外科术后镶嵌治疗:6例TOF根治术后残余分流,其中4例残余膜周部室间隔缺损,1例残余左室右房通道室间隔缺损,1例残余房间隔缺损,分别予以经导管残余心脏缺损封堵术。结果:3例有巨大APCAs的重症TOF在根治术前予以侧支血管堵塞术后随即进行外科手术,皆获得满意效果。6例TOF根治术后残余分流者行经导管封堵术封堵成功,随访无残余分流及心脏瓣膜异常,未出现心律失常。结论:杂交技术镶嵌治疗伴有巨大APCAs及术后存在残余分流的TOF安全、有效。     

Osteoarthropathy in beta-thalassemia

A total of 45 patients with beta-thalassemia and 30 patients with thalassemia intermedia underwent clinical and x-ray examinations. Electron microscopy was used to examine biopsy specimens of the synovial membrane from 6 patients with homozygous thalassemia intermedia. It has been revealed that damage to the osseous system and joints is of systemic nature and depends on the clinical form of the pathological process. Morphological methods have demonstrated abnormal metabolism of iron with its deposition in the tissues and impairment of the vessels of the microcirculatory bed.     

The serum neopterin level in acute rheumatic fever]

Acute rheumatic fever (ARF) is a systemic inflammatory disease etiologically related to infection with group A streptococcus characterized by a broad spectrum of disorders of cellular and humoral immunity. To estimate the activity of the immunopathological process and to forecast myocardial derangement in ARF patients, measurements were made of neopterin in the serum of ARF patients. Nine men with ARF serving in the armed forces were examined. The control group comprised 24 donors. The reference group included 13 patients with dilated cardiomyopathy and 14 with chronic myocarditis. The mean level of neopterin in ARF patients was equal to 14.5 +/- 12.2 nM/l and was significantly higher than in the donors (5.0 +/- 2.0 nM/l). In patients with dilated cardiomyopathy and chronic myocarditis, it was 9 +/- 6 and 16 +/- 11 nM/l, respectively. On more careful clinical analysis the highest level of neopterin was recorded in 3 patients with impairment of the valvular apparatus of the heart. That level was observable during the whole period of the follow-up of the patients. In other patients, no impairment of the valves was detected, whereas the concentration of neopterin fell to normal. Therefore, the rise of the level of neopterin was described for the first time in patients with ARF. Besides, a relationship was found between the high level of neopterin and impairment of the valvular apparatus of the heart.     

A new method of determining the bactericidal activity of the skin

This method, making use of Coli-bacterin, simplifies the preparation of bacterial test culture, cuts down the time of the test by 24 hrs, and standardizes its technique. The method is convenient for mass screening in a field setting.