Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes

We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common.     

Coincidental diagnosis of tuberculous lymphadenitis: a case report

The aim of this case report was to present a case of multiple calcified tuberculous lymph nodes found on a panoramic radiograph coincidently diagnosed in an endodontic clinic. A detailed discussion on the differential diagnosis of similar such calcification found in the same region is also presented. A 14‐year‐old girl was referred to our department with the complaint of painless swelling in the left side of the lower jaw. Clinical and radiographical examinations were performed, leading to the initial diagnosis of chronic periapical abscess. The patient's medical history was re‐evaluated. Advanced imaging and excisional biopsy were performed in order to confirm the final diagnosis. Regarding the presenting signs and symptoms of bilateral carious mandibular molars, a periapical inflammatory process was considered in the provisional diagnosis. A thorough examination and investigations were suggestive of cervical tuberculous lymphadenitis (scrofula), and the patient underwent excision of the same. The clinician should consider the possibility of chronic granulomatous inflammatory lesions in the differential diagnosis of radiopaque lesions.     

术中胆道造影在腹腔镜胆囊切除术中发现胆道损伤的作用

目的：评估术中胆道造影（IOC）在早期发现腹腔镜胆囊切除术（LC）术中胆道损伤的作用。方法：回顾分析31例LC术后胆道损伤的部位，机理，诊断时间，治疗方法及结果，并对是否行IOC进行评估。结果：胆道错认引起胆道损伤共19例，其中12例IOC显示胆道错认，致胆道部分切开损伤，腹腔镜下行I期修复或开腹修复，T管引流，但无并发症。19例中3例IOC误读及4例未行IOC患者中发生迷走胆管损伤2例，胆总管完全离断1例，胆总管完全离断合并胆道缺损2例，本组有2例损伤发生于IOC后，结论：行IOC并正确阅读可及时发现腹腔镜胆囊切除术中胆道错认所致的胆道损伤，从而防止随之可能发生的严重并发症。     

Evaluation of SNPs in miR‐146a,miR196a2 and miR‐499 as low‐penetrance alleles in German and Italian familial breast cancer cases

Recently, the SNPs rs11614913 in hsa‐mir‐196a2 and rs3746444 in hsa‐mir‐499 were reported to be associated with increased breast cancer risk, and the SNP rs2910164 in hsa‐mir‐146a was shown to have an effect on age of breast cancer diagnosis. In order to further investigate the effect of these SNPs, we genotyped a total of 1894 breast cancer cases negative for disease‐causing mutations or unclassified variants in BRCA1 and BRCA2, and 2760 controls from Germany and Italy. We compared the genotype and allele frequencies of rs2910164, rs11614913 and rs3746444 in cases versus controls of the German and Italian series, and of the two series combined; we also investigated the effect of the three SNPs on age at breast cancer diagnosis. None of the performed analyses showed statistically significant results. In conclusion, our data suggested lack of association between SNPs rs2910164, rs11614913 and rs3746444 and breast cancer risk, or age at breast cancer onset. © 2009 Wiley‐Liss, Inc.     

MLPA screening in the BRCA1 gene from 1,506 German hereditary breast cancer cases: novel deletions, frequent involvement of exon 17, and occurrence in single early-onset cases

We present a comprehensive analysis of 1,506 German families for large genomic rearrangements (LGRs) in the BRCA1 gene and of 450 families in the BRCA2 gene by the multiplex ligation-dependent probe amplification (MLPA) technique. A total of 32 pathogenic rearrangements in the BRCA1 gene were found, accounting for 1.6% of all mutations, but for 9.6% of all BRCA1 mutations identified in a total of 1,996 families, including 490 with small pathogenic BRCA1/2 mutations. Considering only high risk groups for hereditary breast/ovarian cancer, the prevalence of rearrangements is 2.1%. Interestingly, deletions involving exon 17 of the BRCA1 gene seem to be most frequent in Germany. Apart from recurrent aberrations like del ex17, dupl ex13, and del ex22, accounting for more than 50% of all BRCA1 LGRs, we could fully characterize 11 novel deletions. Moreover, one novel deletion involving exons 1-7 and one deletion affecting the entire BRCA1 gene were identified. All rearrangements were detected in families with: 1) at least two breast cancer cases prior to the age of 51 years; 2) breast and ovarian cancer cases; 3) ovarian cancer only families with at least two ovarian cancer cases; or 4) a single breast cancer case prior to the age of 36 years, while no mutations were detected in breast cancer only families with no or only one breast cancer case prior to the age of 51 years. Analysis for gross rearrangements in 412 high-risk individuals, revealed no event in the BRCA2 gene and only two known CHEK2 mutations. However, in an additional 38 high-risk families with cooccurrence of female breast/ovarian and male breast cancer, one rearrangement in the BRCA2 gene was found. In summary, we advise restricting BRCA1 MLPA screening to those subgroups that revealed LGRs and recommend BRCA2 MLPA screening only for families presenting with cooccurrence of female and male breast cancer.     

Oocyte morphology on day 0 correlates with aneuploidy as detected by polar body biopsy and FISH

Purpose

For better selection of oocytes and embryos, preimplantation genetic screening (PGS) was introduced. As from the beginning of IVF, morphology was used as selection criteria; we investigated the combination of both. If there was a correlation between phenotype and genotype, invasive PGS might be replaced.

Method

Therefore, 104 cycles with PGS were done by biopsy of the first polar body and FISH with five chromosomes. Morphology of the oocyte was recorded digitally and noted for 12 categories in 4–13 values; evaluation of the chromosomes was noted for five chromosomes in five values. Morphology and genetics were correlated to each other.

Result

Correlations between morphology and genetics for day 0 were found: oocytes with an irregular or dark zona are less probable to have a normal chromosome 13 (80 vs. 53 %, p = 0.001). A medium amount of detritus in the perivitelline space makes it more probable to have a normal chromosome 18 (94 vs. 78 %, p = 0.001). A halo in the cytoplasm makes it less probable to be euploid for chromosome 22 (56 vs. 75 %, p = 0.018). For day 1, pattern “1, 2, 3 and fine” in the pronuclei makes it more probable to be euploid for chromosome 22 (78 vs. 63 %, p = 0.002).

Conclusion

There are correlations between the oocyte genome and its morphology also on day 0. These correlations are not sufficient to replace PGS.     

Decision Aids for Preventive Treatment Alternatives for BRCA1/2 Mutation Carriers: a Systematic Review

Introduction Women with a pathogenic BRCA1/2 mutation have a markedly increased lifetime risk of developing breast and/or ovarian cancer. The current preventive treatment alternatives that are offered are an intensified breast cancer screening programme and risk-reducing operations. Before deciding on one option, medical and personal factors such as life situation and individual preferences must be weighed carefully. Decision aids are used internationally to support BRCA1/2 mutation carriers during their decision-making process. In this study these are analysed structurally for the first time and their applicability to the German context is examined. Material and Methods A systematic literature search in five electronic databases and a manual search were performed. The identified decision aids were evaluated with regard to formal criteria, medical content and quality. The qualitative assessment used the criteria of the International Patient Decision Aid Standards Collaboration (IPDASi v4.0), which examined various dimensions (e.g., information, probabilities, values). Results Twenty decision aids, which were published between 2003 and 2019 in Australia (n = 4), the United Kingdom (n = 3), Canada (n = 2), the Netherlands (n = 2) and the USA (n = 9), were included. Nine focus on BRCA1/2 mutation carriers and eleven include other risk groups. Eighteen include risk-reducing operations as decision options, 14 list screening methods for breast and/or ovarian cancer, and 13 describe the possibility of pharmacological prevention by means of selective oestrogen receptor modulators or aromatase inhibitors. Nine of the 20 decision aids meet fundamental quality criteria (IPDASi v4.0 qualification criteria). Conclusion International decision aids can serve formally as a basis for a German decision aid for BRCA1/2 mutation carriers. Some of them differ markedly in content from the recommendations of German guidelines. Only a few achieve a high quality. Key words: BRCA1, BRCA2, decision aid, familial breast cancer, familial ovarian cancer     

Ambroxol inhibits the release of histamine, leukotrienes and cytokines from human leukocytes and mast cells

OBJECTIVES AND DESIGN: The effects of the mucolytic agents ambroxol and N-acetylcystein (NAC) were studied on the release of histamine, leukotrienes, cytokines and superoxide anions from a variety of cells involved in the pathogenesis of allergic inflammation. SUBJECTS: Mast cells were isolated from human adenoids and skin (n = 5-6). Basophils, monocytes and granulocytes were obtained from Buffy-coat blood obtained from healthy blood donors (n = 4-7) and enriched by density centrifugation. TREATMENT AND METHODS: Ambroxol or NAC were added to the cells for different periods before stimulation with various immunological and non-immunological secretagogues. Histamine release from mast cells, basophils and monocytes was assayed either by radioimmunoassay or spectrofluorometrically. LTC4 (basophils), LTB4 (neutrophil/eosinophil granulocytes or monocytes), IL-4 and IL-13 (basophils) were measured by ELISA. RESULTS: Ambroxol inhibited histamine release by more than 50% from human adenoidal mast cells (1000 microM ambroxol) and skin mast cells (100 microM ambroxol) stimulated by Con A and compound 48/80, respectively. Ambroxol (100 microM) strikingly inhibited anti-IgE induced release of both histamine, LTC4, IL-4 and IL-13 from basophils and reduced both histamine and LTB4 release induced by C5a or Zymosan in monocytes. The drug also reduced LTB4 and superoxide anion production in granulocytes stimulated by zymosan or fMLP. In all cell types studied, ambroxol was more efficacious following a short preincubation (5-15 min) of the drug with the cells before stimulation. In contrast, NAC produced no clear effects on any of the different cell types studied, regardless of the preincubation period, the concentration or the stimulus employed. CONCLUSIONS: Unlike NAC, ambroxol is able to not only inhibit acute mediator release from mast cells and leukocytes but also reduce immunomodulatory cytokine generation from basophils and may have beneficial effects in the treatment of allergic respiratory diseases.     

The assessment of the effect of different intraabdominal pressures used for laparoscopic cholecystectomy surgery on optic nerve sheath diameter: a prospective observational cohort study

Background/aimDuring laparoscopic cholecystectomy operations, increases in intraabdominal, intrathoracic, and intracranial pressures (ICP) can be seen after pneumoperitoneum created for surgical imaging. Orbital ultrasonography (USG), which has been developed in recent years, is a method that can evaluate the ICP by measuring the optic nerve sheath diameter (ONSD) from the eyeball.In our study, we aimed to evaluate whether different intraabdominal pressure values created during laparoscopic cholecystectomy operations correlate with ICP by measuring ONSD.Materials and methodsThe study included a total of 90 patients with American Society of Anesthesiologists (ASA) physical status classification I (ASA I) and II (ASA II) and ages from 18 to 65 years with laparoscopic cholecystectomy planned.After the patients were intubated, at the 5th min, bilateral ONSD measurements were performed. The same measurements were performed at the 15th and 30th min after CO2 insufflation and additionally 10 min after CO2 was released at the end of the operation. During intrabdominal CO2 insufflation, patients with 10 mmHg pressure applied comprised Group 1, patients with 12 mmHg pressure applied comprised Group 2, and patients with 14 mmHg pressure applied comprised Group 3.Results The study was completed with 89 patients, 51 female and 38 males. One patient was excluded from the study due to erroneous values. The variations in ONSD measured in the right-left eye before pneumoperitoneum and at the 15th and 30th min after abdominal CO2 insufflation were observed to be statistically significant (p < 0.01). In all three groups, the right and left eye ONSD values were not identified to be statistically significantly different (p > 0.01).A significant increase was observed in ONSD values in direct proportion to the increase in intraabdominal pressure in patients undergoing laparoscopic cholecystectomy surgery.Conclusion USG-guided ONSD measurements appear be a guide to ensure optimization of intraabdominal pressures and safe anesthesia administration for patients, especially those at risk of ICP increase, during laparoscopic surgery.