Contiguous ABCD1 DXS1357E deletion syndrome: Report of an autopsy case

Contiguous ABCD1 DXS1357E deletion syndrome (CADDS) is a contiguous deletion syndrome involving the ABCD1 and DXS1357E/BAP31 genes on Xq28. Although ABCD1 is responsible for X‐linked adrenoleukodystrophy (X‐ALD), its phenotype differs from that of CADDS, which manifests with many features of Zellweger syndrome (ZS), including severe growth and developmental retardation, liver dysfunction, cholestasis and early infantile death. We report here the fourth case of CADDS, in which a boy had dysmorphic features, including a flat orbital edge, hypoplastic nose, micrognathia, inguinal hernia, micropenis, cryptorchidism and club feet, all of which are shared by ZS. The patient achieved no developmental milestones and died of pneumonia at 8 months. Biochemical studies demonstrated abnormal metabolism of very long chain fatty acids, which was higher than that seen in X‐ALD. Immunocytochemistry and Western blot showed the absence of ALD protein (ALDP) despite the presence of other peroxisomal proteins. Pathological studies disclosed a small brain with hypomyelination and secondary hypoxic‐ischemic changes. Neuronal heterotopia in the white matter and leptomeningeal glioneuronal heterotopia indicated a neuronal migration disorder. The liver showed fibrosis and cholestasis. The thymus and adrenal glands were hypoplastic. Array comparative genomic hybridization (CGH) analysis suggested that the deletion was a genomic rearrangement in the 90‐kb span starting in DXS1357E/BACP31 exon 4 and included ABCD1, PLXNB3, SRPK3, IDH3G and SSR4, ending in PDZD4 exon 8. Thus, the absence of ALDP, when combined with defects in the B‐cell antigen receptor associated protein 31 (BAP31) and other factors, severely affects VLCFA metabolism on peroxisomal functions and produces ZS‐like pathology.     

Mesenteric panniculitis: sonographic findings

BACKGROUND: Mesenteric panniculitis (MP) is a relatively rare disease, and sonographic (US) and color Doppler findings have been infrequently reported. METHODS: We reviewed the clinical data and US and Doppler results of three cases of MP to determine the role and limitations of these techniques. RESULTS: The sole presenting clinical sign was a soft mass. On US the lesion was imaged as a poorly margined echogenic mass with hypoechoic areas. Color Doppler US visualized the nondeviated mesenteric vessels within the mass, which enabled us to perform a safe guided biopsy. CONCLUSIONS: US is useful as an initial diagnostic tool, but its results must be interpreted carefully. Color Doppler US is very useful in demonstrating fine vessels and helps in performing a safe needle biopsy.     

Clinical application of a new method that segments the region of interest into multiple layers for RF amplitude histogram analysis in the cirrhotic liver

Purpose We used texture analysis in conjunction with an alternative method of analyzing the amplitude histogram using a radiofrequency (RF) signal to differentiate ultrasonograms of normal and cirrhotic livers. This method segments the region of interest (ROI) into multiple layers (sub-ROIs). In each sub-ROI of a homogeneous medium, the histogram of enveloped-amplitude of RF backscattered echoes resembles a Rayleigh distribution. Theoretically, the values of the signal-to-noise ratio (SNR), skewness, and kurtosis for Rayleigh statistics are constant and independent of the mean scattering intensity, which is contributed by such undesirable effects as tissue attenuation, beam diffraction, and incident waveforms. These values, which averaged overall sub-ROI, should provide an unbiased estimator.Methods We studied 36 normal livers and 28 cirrhotic livers, all confirmed by clinical findings including laboratory and pathology data; the SNR, skewness, and kurtosis values of the disease groups were compared. At the same time, these values were estimated using the conventional method, which did not segment the ROI into multiple sub-ROIs. The unpaired t-test was used to determine statistical significance.Results With the new method, all values obtained from cirrhotic livers differed significantly from those obtained from normal livers, and the standard deviation of these values was smaller than those obtained using the conventional method.Conclusions These results suggest that the new method can be used to diagnose the cirrhotic liver objectively.This article is translated from the Japanese version, which was published in J Med Ultrasonics 2001;28:J25–33     

Influence of response to prior docetaxel on sensitivity to cabazitaxel in prostate cancer patients with PTEN alterations

The purpose of this study was to investigate factors predicting the sensitivity to cabazitaxel therapy in metastatic castration‐resistant prostate cancer (mCRPC) patients with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) alterations. This single‐institution, retrospective study included 12 mCRPC patients with PTEN alterations who had received cabazitaxel therapy. Five patients (41%) responded to cabazitaxel therapy with a prostate‐specific antigen (PSA) level decline of ≥30% from baseline, and all of them had responded to prior docetaxel therapy with a PSA decline of ≥30%. None of the patients with a poor response to prior docetaxel therapy responded well to cabazitaxel therapy. Of the seven patients who did not respond to cabazitaxel and whose PSA declined from baseline was <30%, five (71%) were also refractory to prior docetaxel therapy. The PSA responses to docetaxel and cabazitaxel were significantly correlated (p = 0.027). Kaplan–Meier analysis revealed that progression‐free survival (PFS) for cabazitaxel was significantly shorter for prior docetaxel nonresponders (3.3 versus 9.1 months, p = 0.028). Multivariate analysis revealed that a poor response to prior docetaxel (PSA decline < 30%) (hazard ratio [HR] = 6.382, 95% confidence interval [CI] 1.172–34.750, p = 0.032) and baseline PSA of ≥20 ng/ml (HR = 33.584, 95% CI 2.332–483.671, p = 0.010) were independent prognostic factors for PFS with cabazitaxel therapy. These results demonstrate cross‐resistance between docetaxel and cabazitaxel. The response to prior docetaxel therapy can influence the sensitivity to cabazitaxel therapy in mCRPC patients with PTEN alterations.     

Venovenous Extracorporeal Membrane Oxygenation in Diffuse Alveolar Hemorrhage Secondary to Anti-neutrophil Cytoplasmic Autoantibody-associated Vasculitis: Starting without Systemic Anticoagulation

Regarding extracorporeal membrane oxygenation (ECMO) support against hemorrhagic conditions, there seems to be a dilemma when deciding between maintaining the circuit patency by systemic anticoagulation and increasing the risk of bleeding. We herein report two cases of diffuse alveolar hemorrhage (DAH) caused by myeloperoxidase (MPO) anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) successfully treated with venovenous (VV)-ECMO support, both initially started without systemic anticoagulation. Under anticoagulation-free ECMO management, we should consider the shortcomings of frequent circuit exchange and hemorrhagic diathesis related to circuit-induced disseminated intravascular coagulation (DIC).     

Muscle Biopsy-proven Drug-induced Microscopic Polyangiitis in a Patient with Tuberculosis

We herein report a case of muscle biopsy-proven microscopic polyangiitis (MPA) in a patient with tuberculosis. The patient had developed a persistent fever after the initiation of treatment for tuberculosis and was positive for myeloperoxidase-antineutrophil cytoplasmic antibody (ANCA). However, because conventional symptoms were lacking, determination of the biopsy site was difficult. Based on the findings of a biopsy of the biceps femoris, which confirmed small vessel vasculitis, the patient was diagnosed with MPA. The fever was alleviated by glucocorticoids. Tuberculosis and antituberculosis drugs can cause ANCA-associated vasculitis (AAV). A muscle biopsy is useful for the diagnosis of AAV.     

The interrelationship between three-dimensional foot mobility and bodyweight bearing

[Purpose] To clarify the three-dimensional nature of foot mobility and its interrelationships within the foot due to bodyweight bearing. [Participants and Methods] Data regarding left foot mobility due to body weight bearing were collected from 31 healthy adults. Foot shape differences while sitting and standing, and their interrelationship were examined. The same examiner reapplied the landmark stickers when misaligned during measurement position changes. [Results] The foot length, heel width, forefoot width, hallux valgus angle, and calcaneus eversion angle were significantly larger in the standing than in sitting position. The digitus minimus varus angle was significantly smaller in the standing than in sitting position. The medial and lateral malleoli, navicular, and dorsum of the foot were displaced medially and inferiorly; the other indices, except for the midfoot, were displaced anteriorly. The interrelationships within the foot showed a positive correlation between the calcaneus eversion angle and the medial displacement of the medial and lateral malleoli, navicular, and dorsum of the foot points. There was a negative correlation between the calcaneus eversion angle and inferior displacement of the medial malleolus, navicular, and dorsum of the foot. [Conclusion] The intra-foot coordination relationship in response to bodyweight bearing was clarified.