Phospholamban p.Arg14del Cardiomyopathy: A Japanese Case Series

Phospholamban p.Arg14del is reported to cause hereditary cardiomyopathy with malignant ventricular tachycardia (VT) and advanced heart failure. However, the clinical courses of Japanese cardiomyopathy patients with phospholamban p.Arg14del remain uncharacterized. We identified five patients with this variant. All patients were diagnosed with dilated cardiomyopathy (DCM), developed end-stage heart failure and experienced VT requiring implantable cardioverter defibrillator discharge. Four patients survived after implantation of a left ventricular assist device (LVAD), while one patient who refused LVAD implantation died of heart failure. Based on the severe course of the disease, we propose genetic screening for phospholamban p.Arg14del in DCM patients.     

Is there any benefit of preservation of the spleen in distal pancreatectomy?

For a pancreatic body or tail tumor, distal pancreatectomy with splenectomy (DPS) is a standard operation. Spleen-preserving distal pancreatectomy (SPDP) was introduced in order to preserve the organ and thus provide the patient with a better quality of life. Clinical data were compared between 38 Japanese patients with DPS and 9 with SPDP for benign tumors or tumor-like lesions at the body or tail of the pancreas at preoperative, early postoperative (< 3 months after operation), and late postoperative periods (>6 months after operation). The preoperative findings were not different between the two groups except for the significantly higher serum amylase levels in the SPDP group. Operation time, operative blood loss, and length of postoperative hospital stay were not different between the two groups. Pancreatic fistula occurred in 3 (8%) of the 38 patients in the DPS group and in 1 (11%) of the 9 patients in the SPDP group, abdominal abscess in 5 (13%) of the 38 patients in the DPS group and none (0%) in the 9 patients in the SPDP group. At short-term, clinical findings were not different between the two groups except for a significantly greater platelet count in the DPS group than in the SPDP group (46.8 x 10(4)/microl versus 29.6 x 10(4)/microl, P = 0.0081). At long-term after the operation, clinical findings, including the platelet count, were not different between the two groups. Computed tomography revealed a pseudocyst in 9 (53%) of 17 patients examined in the DPS group and in 3 (75%) of 4 patients examined in the SPDP group at short-term after operation. All patients with pseudocysts were asymptomatic. Two asymptomatic patients (one in the DPS group and one in the SPDP group) first developed a pseudocyst at long-term after the operation. The alteration of glucose tolerance was similar between the two groups. Postoperative pancreatic exocrine function (the N-benzol-L-tyrosyl-p-aminobenzoic acid test) was not different between the two groups. These data suggest that SPDP with preservation of the splenic vessels can be satisfactorily performed without elongating operative time and postoperative hospital stay or increasing risk of postoperative complications, with the exception of increased platelet count in the DPS group at short-term after the operation. Thus, SPDP is worth considering as one of the options for the treatment of benign lesions of the body or tail of the pancreas.     

A new parameter in decision making for transurethral electroresection of benign prostate hyperplasia

OBJECTIVE: In this study, the clinical usefulness of transition zone (TZ) volume (TZV) measured by transrectal ultrasonography (TRUS) was investigated as a new parameter for the preoperative prediction of the treatment efficacy of transurethral resection of the prostate (TURP). METHODS: Fifty-six men with symptomatic benign prostatic hyperplasia (BPH; age 68.6 +/- 9.7 years) underwent TURP and were evaluated based on ordinary BPH parameters such as the international prostatic symptom score (I-PSS), quality of life (QOL) score, peak urine flow and entire prostate volume (PV), as well as the new TZV parameters and calculation of the TZ index. Relative risks were adjusted simultaneously for potentially confounding variables by multiple logistic regression analysis after adjustment for age, QOL, I-PSS, Qmax and residual urine. RESULTS: The adjusted relative risk for TURP at a TZ index of 0.1 increased to 4.5 (95% confidence interval 2.3-8.78). In general, poor responses were observed in patients with less symptomatic scores or lower values prior to operation, but there was a weak correlation between treatment outcome and preoperative scores or values of ordinary parameters. The volume parameters of BPH and PV did not predict treatment efficacy preoperatively, but TZV and the TZ index correlated with the treatment efficacy of TURP. CONCLUSION: TZV and the TZ index seem to be useful new parameters in preoperative decision-making with regard to TURP.     

The efficiency of performing ultrasound-guided fine-needle aspiration biopsy following mass screening for thyroid tumors to avoid unnecessary surgery

Thyroid masses are a common clinical finding, and their management remains controversial. The purpose of this study was to evaluate the clinical effect of performing routine ultrasound (US) examinations and US-guided fine-needle aspiration biopsy (US-FNAB) in the management of diffuse or nodular goiter diagnosed by mass screening. Mass screening carried out from 1993 to 1996 revealed 444 women with goiter, 322 of whom had diffuse goiter and 122 had nodular goiter. All of these patients underwent US examination, the results of which determined that 169 should undergo US-FNAB to confirm an accurate diagnosis of their thyroid tumors. Histological examinations after surgical resection revealed that 12 of the 322 patients with diffuse goiter (3.7%) and 23 of the 122 with nodular goiter (18.9%) had malignant tumors. Among the 61 thyroid tumors surgically verified, US-FNAB yielded a sensitivity rate of 93%, a specificity rate of 81%, and an accuracy rate of 90%. Insufficient aspiration was obtained from 5%. Performing US-FNAB-resulted in an elevation in the percentage of malignant tumors yielded at surgery of up to 72%. Thus, ultrasonography followed by US-guided-FNAB could be a useful routine method of evaluating thyroid tumors detected by mass screening. Moreover, a greater number of unnecessary thyroid operations can be avoided by performing US-FNAB rather than FNAB alone.     

Reversible posterior leukoencephalopathy in a patient with Wegener granulomatosis

A 14-year-old girl with rapidly progressive glomerulonephritis was transferred to our hospital because of acute renal failure. A diagnosis of Wegener granulomatosis was made according to the symptom triad of a renal biopsy demonstrating crescentic glomerulonephritis, severe sinusitis, and serological findings of raised proteinase 3 anti-neutrophil cytoplasmic antibody level. In spite of combination therapy with methylprednisolone, cyclophosphamide, and plasma exchange, her renal function gradually deteriorated. Thereafter, she suffered a severe headache and generalized seizures. Brain computed tomography (CT) scan revealed bilateral low-density areas in the parieto-occipital lobes. Magnetic resonance imaging (MRI) disclosed a high-intensity area on T2-weighted images and a low-signal intensity area on T1-weighted images in the same lesion. Follow-up brain CT scan 3 weeks and MRI 2 months after the first studies showed complete resolution of the abnormal lesions, which indicated reversible posterior leukoencephalopathy syndrome. In addition to renal failure, hypertension, and cyclophoshamide, the primary disease may have played a role in the development of this uncommon syndrome in our patient.     

Comparison of 99mTc-hexakis 2-methoxy-2-isobutyl isonitrile and 201Tl SPECT imaging for evaluation of coronary artery disease

To evaluate clinical value of 99mTc-hexakis 2-methoxy-2-isobutyl isonitrile (MIBI) imaging for assessing coronary artery disease (CAD), 99mTc-MIBI SPECT imaging at post-exercise and at rest was compared with 201Tl SPECT imaging at post-exercise and 3 hours redistribution in 27 patients suspected with CAD. The sensitivities for detecting CAD patients were 94% (17/18) by both studies. The specificities were 71% (5/7) by 99mTc-MIBI and 57% (4/7) by 201Tl (p = NS). The sensitivities for detecting stenosed coronary arteries (greater than or equal to 75% stenosis) were also similar between 99mTc-MIBI (78%) and 201Tl (74%) (p = NS). The similar specificity values were obtained by 99mTc-MIBI (84%) and by 201Tl (82%) (p = NS). The patterns of abnormality (normal, ischemia and scar) were similar between 99mTc-MIBI and 201Tl images in 22 of the 25 cases (88%) and 117 of the 125 segments (94%). However, these patterns were occasionally different particularly in patients who received PTCA or CABG. Thus, 99mTc-MIBI SPECT imaging seems to be as accurate as 201Tl SPECT imaging for the detecting and evaluating CAD.     

Four novel mutations in the thiazide-sensitive Na-Cl co-transporter gene in Japanese patients with Gitelman's syndrome.

BACKGROUND: Gitelman's syndrome (GS) is an autosomal recessive disorder resulting from inactivating mutations in the thiazide-sensitive Na-Cl co-transporter (NCCT) gene. To date, almost 90 mutations have been identified. It is possible that there is a population-specific distribution of mutations. In this study, we analysed mutations in the NCCT gene of seven Japanese patients with GS. METHODS: Peripheral blood mononuclear cells were isolated from patients with GS, their family members and healthy control subjects. A mutation analysis of the NCCT gene was performed completely by direct automated sequencing of polymerase chain reaction-amplified DNA products. In patients with a deletion or splice site mutation, we undertook cDNA sequence analysis. RESULTS: We identified nine mutations. Five of them [c.185C>T (Thr60Met), c.1712C>T (Ala569Val), c.1930C>T (Arg642Cys), c.2552T>A (Leu849His) and c.1932delC] have been reported in Japanese patients, but not in GS patients from other ethnic groups. The remaining four mutations [c.7A>T (Met1Leu), c.1181_1186+20del26, c.1811_1812delAT and IVS16+1G>A] were novel. In cDNA derived from a patient with c.1181_1186+20del26, a deletion of exon 9 and a frameshift at the start of exon 10 were observed. In cDNA derived from patients with IVS16+1G>A, an additional 96 bp insertion between exons 16 and 17 was observed. Six out of seven patients were compound heterozygotes, and the remaining one carried a single heterozygous mutation. CONCLUSIONS: We found four novel mutations in the NCCT gene in seven Japanese patients with GS. Moreover, our study suggests that the distribution of mutations in the NCCT gene in Japanese GS patients potentially differs from that in other populations.     

Surgical anatomy of the cervical carotid artery for carotid endarterectomy

Carotid endarterectomy (CEA) is the main treatment for atherosclerotic plaque of the cervical internal carotid artery. The surgical anatomy of the carotid arteries was studied in the carotid triangle of 49 cadavers. The carotid bifurcation was located at the level of the lower third of C-3. The superior thyroid artery arose from the anterior wall of the external carotid artery in 70% of specimens and from the distal portion of the common carotid artery in 30%. The lingual artery arose as a separate trunk between the origins of the superior thyroid and facial arteries in 81% of specimens, with the facial artery from a common trunk in 18%, and with the superior thyroid artery in 1%. The occipital artery arose from the posterior aspect of the external carotid artery above the level of origin of the facial artery in 57% of specimens, between the origins of the facial and lingual arteries in 32%, and below the origin of the lingual artery in 11%. The origin of the occipital artery was positioned low and the distal portion of the occipital artery was crossed by the hypoglossal nerve in 20%. The ascending pharyngeal artery arose from the posterior wall of the external carotid artery above the level of origin of the lingual artery in 66% of specimens, below the origin of the lingual artery in 9%, from the proximal portion of the occipital artery in 19%, from the carotid bifurcation in 2%, and from the internal carotid artery in 2%. The branches of the external carotid artery are the key landmarks for adequate exposure and appropriate placement of cross-clamps on the carotid arteries. It is necessary to understand the surgical anatomy of the carotid arteries to carry out successful removal of plaque and minimize postoperative complications in a bloodless surgical field.     

Anisotropic diffusion in kidney: apparent diffusion coefficient measurements for clinical use

The purpose of this study was to evaluate anisotropy of the kidney by measurements of the apparent diffusion coefficient (ADC) using commercially available magnetic resonance (MR) imaging. Fifty-one consecutive patients underwent diffusion-weighted echoplanar MR imaging of the upper abdomen with five different strengths of motion probing gradients (b = 1.51, 55.3, 36.6, 317, and 932 sec/mm2) applied along the z-axis. Four ADC values for the upper pole and central portion of the kidney were calculated from four different b-value ranges and compared. The ADCs for the kidney calculated in the lower b-value ranges were significantly higher than those in the higher ranges. The ADCs for the upper pole portion were significantly higher than those for the central portion except for one in the highest b-value range. Diffusion in the kidney is anisotropic, probably due to the kidney's radially oriented structures such as renal vessels and tubules.     

Internalization of antibodies by endothelial cells via fibronectin implicating a novel mechanism in lupus nephritis

BACKGROUND: One of the crucial events in lupus nephritis is the glomerular deposition of immunoglobulins (Igs), of which pathogenic properties have been proposed mostly to be either type IIor type III allergic reactions. Some of IgG3-producing hybridoma clones established from an MRL/MpTn-gld/gld (MRL/gld) lupus mouse generate wire loop-like lesions in glomeruli resembling lupus nephritis when injected into SCID mice. These clones are useful for analyzing the mechanisms of glomerular deposition of antibodies in lupus nephritis at the monoclonal level. METHODS: Glomerular lesions of SCID mice injected with the hybridoma clones, 17H8a or 1G3 as control were analyzed by light and electron microscopy. Interaction of the antibodies with human glomerular endothelial cells (HGECs) and human umbilical vein endothelial cells (HUVECs) in vitro was studied by fluorescence microscopy, electron microscopy, and flow cytometry. RESULTS: Both antibodies did not show any antigen specificity for mouse glomeruli. The glomerular lesions generated by 17H8a, but not by 1G3, contained electron-dense deposits not only in subendothelial regions but also in the cytoplasm of endothelial cells, suggesting internalization of the 17H8a antibodies by endothelial cells. In cell culture studies, internalization of only 17H8a antibodies by HGECs and HUVECs was observed, but the antibodies did not have antigen specificity for both types of endothelial cells. The internalization by HUVECs was mediated by actin polymerization, and it was inhibited by RGDS (Arg-Gly-Asp-Ser) tetrapeptide, antihuman fibronectin and antihuman integrin beta1 monoclonal antibodies. CONCLUSION: The interaction between particular antibodies and endothelial cell surface integrins via fibronectin may be involved in their subsequent internalization by endothelial cells leading to antibody deposition in glomeruli. This may be one of the mechanisms of glomerular injury in lupus nephritis.