Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia

Fifty percent of Diamond-Blackfan anemia (DBA) patients possess mutations in genes coding for ribosomal proteins (RPs). To identify new mutations, we investigated large deletions in the RP genes RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26. We developed an easy method based on quantitative-PCR in which the threshold cycle correlates to gene copy number. Using this approach, we were able to diagnose 7 of 27 Japanese patients (25.9%) possessing mutations that were not detected by sequencing. Among these large deletions, similar results were obtained with 6 of 7 patients screened with a single nucleotide polymorphism array. We found an extensive intragenic deletion in RPS19, including exons 1-3. We also found 1 proband with an RPL5 deletion, 1 patient with an RPL35A deletion, 3 with RPS17 deletions, and 1 with an RPS19 deletion. In particular, the large deletions in the RPL5 and RPS17 alleles are novel. All patients with a large deletion had a growth retardation phenotype. Our data suggest that large deletions in RP genes comprise a sizable fraction of DBA patients in Japan. In addition, our novel approach may become a useful tool for screening gene copy numbers of known DBA genes.     

Impact of combined assessment of coronary artery calcium score, carotid artery plaque score, and brachial-ankle pulse wave velocity for early coronary revascularization in patients with suspected coronary artery disease

Coronary artery calcium score (CACS) measured by multi-detector computed tomography, carotid plaque score (CPS) measured by carotid artery ultrasound, and brachial-ankle pulse wave velocity (baPWV) are noninvasive screening tools for coronary artery disease. The aim of this study was to determine whether the combination of CACS, CPS, and baPWV improves the prognostic value for future cardiac events. CACS, CPS, and baPWV were assessed in 77 patients (mean age, 65 years, 49 males) undergoing invasive coronary angiography. ECG-triggered MSCT was used to assess CACS. CPS was defined as the sum of all plaque heights in bilateral carotid arteries. The highest baPWV was used for analysis. Cardiac events were defined as cardiac death, nonfatal myocardial infarction, or coronary revascularization. Thirty-two cardiac events (41.6%) occurred during follow-up (23.6 ± 20.8 months), consisting of 28 PCIs and 4 CABGs. The best cutoff values of positive CACS, CPS, and baPWV for predicting cardiac events were ≥ 50, ≥ 5, and ≥1.6 m/second, respectively. For the combination of the 3 modalities, the positive test was defined as having at least 1 positive result by each method. The negative predictive value of all 3 modalities combined was better than that of CACS alone. The event-free rate was higher in patients with negative results for all 3 parameters compared with those that were positive (100% versus 44.8%, P < 0.0001). The prognostic value of using combined assessment of CACS, CPS, and baPWV is more effective for predicting cardiac events than CACS alone.     

Case with metastatic cutaneous malignant melanoma that developed Vogt–Koyanagi–Harada-like uveitis following pembrolizumab treatment

Documenta Ophthalmologica - The study reports a case with metastatic cutaneous malignant melanoma that developed Vogt–Koyanagi–Harada-like uveitis during pembrolizumab treatment. The...     

Case of cystoid macular edema induced by systemic administration of paclitaxel: evaluations with electroretinograms

Purpose

To report abnormal full-field electroretinograms (ERGs) in a patient with cystoid macular edema (CME) induced by systemic paclitaxel.

Methods

This is an observational case report. Full-field ERGs were recorded to evaluate the retinal function using the RETeval system and conventional ERGs using contact lens electrodes with built-in white light-emitting diodes. Optical coherence tomography (OCT) was also used to assess the retinal morphology.

Results

A 70-year-old man, who was diagnosed with gastric cancer, had undergone gastrectomy. Subsequently, systemic paclitaxel was administered once a week as an adjuvant therapy. After the tenth course of paclitaxel, he experienced blurred vision in both eyes and visited our department of ophthalmology. OCT revealed the presence of CME in both eyes, and the RETeval flicker ERGs showed a marked reduction in the amplitudes and a prolongation of the implicit times in both eyes. Conventional ERGs showed that the amplitudes of the oscillatory potentials (OPs) were also severely attenuated. The abnormal OCT findings and reduced visual acuity recovered to normal at 1 and 2 months, respectively, after the discontinuation of paclitaxel. However, the flicker ERGs did not recover to normal values until 4 months after the discontinuation of paclitaxel.

Conclusion

These results suggest that the ERGs can be used to monitor the changes in the overall retinal function in patients receiving paclitaxel.

     

Early abnormality detected by speckle-tracking echocardiography in a patient with suspected cardiac sarcoidosis

A 56-year-old female was admitted to our hospital because of respiratory symptoms. Her admission ECG showed normal sinus rhythm and standard echocardiographic evaluation showed no structural or functional abnormalities. She was diagnosed as having sarcoidosis by imaging modalities and mediastinum lymph node biopsy. In this case, 2-dimensional speckle-tracking echocardiography (STE) demonstrated abnormal regional myocardial function and delayed enhancement cardiac magnetic resonance imaging revealed a high intensity area in the same segments. This case suggests that STE is potentially useful for the detection of cardiac sarcoidosis in the early phase.     

Clinical reappraisal of the segmental pectoralis major turn-over flap for coverage of the local mediastinal wound

The viability of a long and narrow pectoralis major turn-over flap based on one intercostal muscle perforator was supported by the result of our cadaveric injection study. This flap preserves the muscular strength and aesthetic contour of the anterior axillary line, and is attractive for reconstruction of the mid-sternum.     

Cytotoxic effects of acrylic acid, methacrylic acid, their corresponding saturated carboxylic acids, HEMA, and hydroquinone on fibroblasts derived from human pulp

The purpose of this study was to evaluate the cytotoxicity of acrylic and methacrylic acid (AA and MA), propanoic acid and isobutylic acid (PRA and IBA) which were the corresponding saturated carboxylic acids, 2-hydroxylethyl methacrylate and acrylate (HEMA and HEA), and hydroquinone (HQ). The growth of the fibroblast when exposed to AA decreased with increase of the acid, and was less than when exposed to MA. The growth when exposed to their corresponding saturated acids, PRA and IBA, showed a similar tendency to AA and MA. The growth of fibroblasts exposed to 5 mmol/L HEMA after 4 days and 3 mmol/L HEMA after 6 days was significantly different compared with that without HEMA. The growth in 1, 3, and 5 mmol/L of HEA after 2 days was markedly decreased compared with that without HEA, and the cells were probably lifeless. The growth when exposed to HQ was extremely lower than their acids.