Preimplantation genetic diagnosis using combined strategies on a breast cancer patient with a novel genomic deletion in BRCA2

Purpose

To perform Preimplantation Genetic Diagnosis (PGD) on a paternal Brca2 unknown mutation carrier with early-onset breast cancer, whose paternal grandmother and mother had breast cancer at 60s.

Method

Elucidating the linkage via single sperm haplotyping on patient''s carrier brother, and identifying the genomic deletion via BLAST followed by PCR screening. PGD was subsequently conducted.

Result

The mutant allele was found by using 4 microsatellite and 2 intragenic SNP markers. Recombination was detected in 8 % of sperms. BLAST was utilized to locate putative hairpin structure(s), followed by PCR screening with seven sets of primers. A novel 2,596 bp deletion containing exon 15 ~ 16 was identified. Due to the severity of phenotype and the integrity of exon 11 encoding RAD51 binding domain, and the fact that the patient''s mother also had breast cancer at her 60s, we speculate a possible coexistence of maternal breast cancer risk allele(s). Embryo biopsy was performed on day 3. Unaffected morula and blastocyst were replaced on day 5, resulting in a singleton livebirth. A breast lump appeared in the patient after delivery without the presence of malignant cells.

Conclusion

Concerning the assisted reproductive option for breast cancer patients, the possibility of coexistence of multiple familial risk alleles and the significance of each mutation to the phenotype should be evaluated. To eliminate misdiagnosis resulting from recombination and/or allelic drop-out, both direct mutation detection and linkage analysis approaches may be necessary. BLAST is a very useful and cost-effective tool for identifying large genomic deletion.     

Exhaled air dispersion and removal is influenced by isolation room size and ventilation settings during oxygen delivery via nasal cannula

Background and objective: We compared the exhaled air dispersion distances during oxygen delivery via nasal cannula to a human‐patient simulator (HPS) in two different isolation rooms. Methods: Airflow was marked with intrapulmonary smoke for visualization. Oxygen flow was gradually increased from 1 to 5 L/min, with the HPS sitting at 45°. The leakage jet plume was revealed by laser light‐sheet and images captured by high‐definition video. Smoke concentration in the plume was estimated from the light scattered by smoke particles. The experiments were conducted at a double‐door, negative pressure isolation room with a dimension of 4.1 × 5.1 × 2.6 m, pressure of ?7.4 Pa and 16 air exchanges/h (ACH) (room A). Results were compared with experiments repeated in a smaller isolation room with a dimension of 2.7 × 4.2 × 2.4 m, pressure of ?5 Pa and 12 ACH (room B). Results: Room A: an exhalation jet spread almost horizontally outward from the nostrils of the HPS to 0.66 m and 1 m towards the end of bed when oxygen flow was increased from 1 to 5 L/min respectively. Room B: there was interaction between the downward ceiling ventilation current and the exhaled air from the HPS, leading to deflection of exhaled smoke towards the head of the HPS at an oxygen flow rate of 1 L/min. As oxygen flow was increased gradually to 5 L/min, more room contamination with smoke was noted. Conclusions: Substantial exposure to exhaled air occurs within 1 m towards the end of the bed from patients receiving oxygen via nasal cannula. Room dimension and air exchange rate are important factors in preventing contamination in isolation rooms.     

Aesthetic management of severely fluorosed incisors in an adolescent female

BACKGROUND: Dental fluorosis is a condition of enamel hypomineralization due to the effects of excessive fluoride on ameloblasts during enamel formation. Delayed degradation of enamel matrix proteins or inhibited protein removal results in impaired and incomplete crystal growth, producing hypomineralized and porous enamel. Severely fluorosed teeth may undergo post-eruptive surface breakdown and post-eruptive dark brown to black staining. METHODS: A 13 year old girl presented with severely discoloured maxillary central incisors. Initial aesthetic management of these teeth was conservative, including in-office tooth whitening, microabrasion and take-home whitening. RESULTS: Dark brown to black staining of the teeth was reduced successfully without the need for gross mechanical preparation of the enamel. Further improvement of aesthetics was achieved with composite veneers. CONCLUSIONS: Conservative treatment options such as tooth whitening and microabrasion can dramatically improve severely discoloured fluorosed teeth. This can provide a satisfactory interim outcome or minimize the removal of discoloured enamel and dentine prior to the provision of composite veneers. The use of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) may enhance remineralization and decrease postoperative sensitivity following tooth whitening and microabrasion procedures in hypomineralized teeth.     

Agenesis of the corpus callosum is associated with feeding difficulties

Our objective was to characterize the common occurrence of feeding and swallowing disorders noticed by our speech therapy department among patients with agenesis of the corpus callosum. All patients with suspected or presumed agenesis of the corpus callosum undergoing therapy for feeding and/or swallowing disorders, including oral and/or pharyngeal dysphagia and oral-sensory disorder, were identified. Their brain magnetic resonance imaging (MRI) studies and charts were reviewed in detail. Seven patients with striking oral-motor and oral-sensory disorder met the criteria for agenesis of the corpus callosum. Particular difficulties noted include oral-sensory defensiveness in five of these seven patients, oral dysphagia/weakness in all seven patients, and pharyngeal dysphagia with risk of aspiration in three of these seven patients. The oral-motor weakness observed in all of the patients affected the strength and coordination necessary for functional oral-phase swallowing. We conclude that feeding and swallowing disorders are significant in children with agenesis of the corpus callosum. Although the pathophysiologic mechanism is not known, recognition of this phenomenon is important because early detection and intervention can facilitate functional feeding and swallowing patterns earlier in these patients, therefore avoiding the adverse and more severe disorders that can arise when dysphagias and/or oral-sensory disorder persist over extended periods of time.     

双能量X线骨质密度测量仪监测小儿下肢骨延长骨矿物质的变化

目的　在儿童骨延长的患儿中 ,为了能够有效地控制骨延长的速率 ,达到骨延长的目的 ,采用双能量X线骨质密度测量仪 (dualenergyX Rayabsorptiometry ,DEXA)监测延长断端骨矿含量 (bonemineralcontent,BMC)的变化。方法　 30例患儿中有 5 0处下肢作了骨延长术 ,平均年龄10 .9岁 (5～ 17岁 ) ,引起短肢的病因不同。术后 7～ 10d开始行骨延长 ,每次延长 0 .2 5mm ,每天 4次。牵引延长期间每周扫描一次 ,拆除外固定器后每 2周扫描一次到术后 2年。DEXA扫描的分辨率是 1mm× 1mm ,扫描速度 30mm/s。比较不同延长时期中骨矿含量的变化。分析不同病因和不同外固定器之间骨矿含量变化的差别。结果　不同固定器之间骨矿含量的差别无著性意义。根据骨延长区BMC增加速率 ,将患儿分为快速组、一般组和慢速组。快速组每日BMC增加速率为 0 .3%～ 0 .6 % ,新骨生长快速 ;一般组每日BMC增加 0 .1%～ 0 .3% ,新骨中速生长 ;慢速组每日增加 <0 .1% ,新骨生成缓慢。骨矿化速率与原发病因相关。结论　DEXA能动态监测骨延长中新生骨的骨矿含量的变化 ,根据骨矿含量变化的程度 ,能够调整骨延长的速率 ,从而达到预期骨延长的目的。     

Flow turbulence or twinkling artifact? A primary observation on the intrarenal color Doppler sonography

ObjectiveThe objective of this report was to describe and potentially explain differences of intrarenal color Doppler sonography (CDUS) manifestations between blood flow turbulence and twinkling artifact.MethodsWe retrospectively reviewed 32 cases with appearance of focally increased color Doppler signal on intrarenal CDUS from May 1, 2007, to February 28, 2009. Indications for intrarenal CDUS in 32 cases were suspicion of renovascular hypertension, investigation of complications related to renal biopsy, or hematuria. Characteristics of the color Doppler signal, relationship between color Doppler signal and renal vessels, and the spectral Doppler sampled at the anatomic site of the focal color signal were analyzed. The value and pitfall of color Doppler in the diagnosis of the intrarenal vascular abnormality and detection of renal calculus are discussed.ResultsThirty-two cases with focally increased color Doppler during sonography of native or transplanted kidneys were classified into two groups: (1) turbulent blood flow—intrarenal vascular abnormalities including intrarenal arteriovenous fistula (15 cases) and intrarenal artery stenosis (eight cases); and (2) color Doppler artifact—twinkling produced by renal calculus (nine cases). There were differences in the characteristics of the color Doppler signal, the relationship between the color signal and renal vessel, and the spectral waveform on CDUS between flow turbulence and twinkling.ConclusionFlow turbulence and twinkling artifact on intrarenal CDUS are distinguishable by analyzing the manifestations on intrarenal CDUS. Proper color Doppler setting and spectral Doppler play important roles in differentiation between flow turbulence in renal vascular abnormalities and twinkling produced by renal stones.     

Management of postoperative Crohn's disease

Three-quarters of the patients with Crohn's disease (CD) require surgery involving a resection in the course of their disease. Even if all macroscopically involved bowel is removed, the disease usually recurs proximal to, and at, the anastomosis. This often leads to the recurrent need for treatment of active disease, complications, and reoperation. Ileocolonoscopy has an important place in the assessment of postoperative Crohn's recurrence. The limited available data regarding drug therapy in the postoperative setting suggest that optimal management should include identification of high-risk patients earlier and more widespread use of immunosuppressive therapy than was previously recommended, and colonoscopic monitoring. Such strategies to prevent recurrence then need to be prospectively evaluated. This article examines the evidence for medical prophylaxis of postoperative CD, and proposes a treatment strategy based on current evidence.     

Towards improved fat intake and nutrition for Malaysians

An examination of the fat composition of the diet of a Malaysian urban hostel population obtained by chemical analysis of representative meals prepared by a 7-day rotation menu, revealed both nutritional attributes and limitations when compared against the dietary messages contained in the American Heart Association (AHA) and World Health Organisation (WHO) models. The Malaysian diet supplies 26% kcal i.e. 66 g total fat (51 g vegetable fats, 15 g animal fats) and contains <300 mg cholesterol, which are below the upper limits for these dietary constituents in the AHA and WHO models and conflicts with the perception that Malaysians in general, may be consuming too much fat and cholesterol. The supply of essential fatty acids (EFA), however, appears sub-optimal at 3.2% kcal mainly due to the comparatively low content of both the omega-6 (linoleic acid) and omega-3 [alpha-linolenic, eicosapentaenoate (EPA) and docosahexaenoate (DHA)] fatty acids in the Malaysian diet. The estimated omega-6/omega-3 fatty acid ratio of 10 further reflects an imbalance of these two families of polyunsaturated fatty acids (PUFA), which can be corrected to a ratio of 5 to 7 by moderate increases in the consumption of fish, soyabean-based foods, and pulses and nuts. Considering the current status of knowledge on the health effects of the different families of fatty acids, the ratio of 2:3:1 for the saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and PUFA in the diet is judged to improve fat intake and nutrition in Malaysians. Such a dietary fatty acids ratio can be satisfied by the use of a cooking oil containing 28% SFA, 53% MUFA, and 19% PUFA, which may obtained by the judicious blending of palm olein with MUFA-rich and PUFA-rich vegetable oils. Alternatively, moderate increases in the consumption of marine fish, pulses, nuts, soybean-based foods and their products would also serve the same end.