A case of WHIM syndrome associated with diabetes and hypothyroidism

Abstract: The WHIM syndrome is a rare immunological disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. We hypothesized that immunological or genetic mechanisms may link WHIM syndrome and type 1 diabetes. We report that the young girl with WHIM syndrome developed diabetes and transient hypothyroidism. A nonsense mutation (C→T) truncating the CXC chemokine receptor 4 (CXCR4) C-terminal cytoplasmic tail domain occurred at nucleotide position 1000(R334X) of the CXCR4 gene in one allele of the patient was identified, and the person was diagnosed as having WHIM syndrome. Recent observation suggested that the CXCR4, a G-protein-coupled receptor with a unique ligand, CXCL12, might be involved in the pathogenesis for type 1 diabetes. Taken into consideration the concurrent prevalence of the two disorders and the speculated common pathogenesis associated with the CXCR4, our patient may enable us to understand the genetic damage related to accelerated apoptosis.     

Combined cuff and suture technique for orthotopic whole intestinal transplantation in rats

For the purpose of immunological study on small intestinal transplantation (SIT), rat SIT models using direct suture technique widely have been used, which requires at least several months of training for microsurgery. Alternatively, a simple cuff technique for SIT has been mainly used by us, which reduces warm-ischemic time and the training period, but the entire intestinal grafts usually obtain a limited blood supply. This report describes a modification of a combined cuff and suture technique for rat SIT to aid beginning microsurgical transplantation researchers. The advantages are 1) use of only arterial suturing, making it easier for beginners, with the cuff technique applied to the more difficult vein anastomosis; 2) achievement of better arterial inflow and graft survival than when the arterial cuff technique is used; and 3) doing only partial clamping of the aorta, which improves animal survival and success of the procedure. A very high successful rate in orthotopic whole SIT was achieved even by beginners.     

Usefulness of self-expandable metallic stent with an antireflux mechanism as a palliation for malignant strictures at the gastroesophageal junction

BACKGROUND: Patients with unresectable malignant gastroesophageal strictures often are troubled with reflux esophagitis after stent placement. METHODS: A self-expandable metallic stent (SEMS) without an antireflux mechanism was placed in seven patients with unresectable malignant gastroesophageal strictures (group A), and SEMS with an antireflux mechanism was placed in five patients (group B). After we obtained monitoring systems, two patients in group A and all the patients in group B underwent measurement of bilirubin and pH in the esophagus using a 24-h bilirubin and pH monitor. RESULTS: The mean percentage of total time less than 0.14 for use of the bilirubin absorbance unit was 12.4% in group B and 64.0% in group A. The mean percentage of total time for a pH less than 4 was 2.9% in group B and 37.8% in group A. CONCLUSION: The placement of SEMS with the antireflux mechanism can be effective not only for palliation of gastroesophageal stricture, but also for prevention of reflux.     

Three-dimensional analysis of nystagmus in benign paroxysmal positional vertigo. New insights into its pathophysiology

Nystagmus is a rhythmical rotation of the eyeball. Its characteristics can be defined mathematically by the axis of rotation and the angular velocity around this axis. We analysed the axis of rotation for the nystagmus in benign paroxysmal positional vertigo (BPPV) to elucidate its pathophysiology. Thirteen patients with typical unilateral BPPV participated in the present study. The axis of rotation for the nystagmus was calculated from images recorded on digital videotape with an infrared CCD camera, using an algorithm that we developed. The patients' responsiveness to Semont's liberatory maneuver was also assessed. The results showed that patients could be assigned to one of two groups based on the rotation axis of the nystagmus. In one group of patients (n = 7; Group A), the axis of rotation was almost vertical to the plane containing the posterior semicircular canal (PSC) on the presumed affected side. In the other group of patients (n = 6; Group B), it was clustered around the naso-occipital axis. These results suggest that in the patients in Group A the responsible lesion is confined to the PSC, whereas the pathogenesis underlying the conditions in those in Group B is considered to be more complicated. This speculation was reinforced by the difference in responsiveness to Semont's liveratory maneuver. All of the patients in Group A showed remission of vertigo within 10 days (mean, 2.4 days) after onset of treatment using Semont's liberatory maneuver, whereas the patients in Group B required much longer periods of time for remission to occur (mean, 25.7 days). Our findings lead to the conclusion that by considering the spatial orientation of individual semicircular canals, in the patients in Group B the pathophysiology is not confined to the PSC, but most probably all three semicircular canals are involved. Received: 16 January 2002, Received in revised form: 22 May 2002, Accepted: 6 June 2002 Correspondence to Yujiro Hayashi, MD     

Biological characteristics in bladder cancer depend on the type of genetic instability.

PURPOSE: Malignant tumors show an inherent genetic instability that can be classified as microsatellite instability (MSI) or chromosomal instability (CIN). To elucidate the differences in biological characteristics of bladder cancer between the two types of genetic instability, the expression of the mismatch repair (MMR) proteins, Aurora-A and p53 proteins, the number of centrosomes, numerical aberrations of chromosomes and 20q13, and DNA ploidy were examined in 100 human urothelial carcinomas of the bladder. EXPERIMENTAL DESIGN: Expressions of the MLH1, MSH2, Aurora-A, and p53 proteins and the numbers of centrosomes were immunohistochemically assessed. Numerical aberrations of chromosomes 7, 9, 17, and 20q13 spots were evaluated by fluorescence in situ hybridization, and DNA ploidy was assessed by laser scanning cytometry. RESULTS: The expression levels of the MMR related-proteins decreased in 9 of 100 tumors. Tumors with low MLH1 or MSH2 expression (designated as MSI cancers) were not linked with centrosome amplification, Aurora-A overexpression, increased p53 immunoreactivity, 20q13 gain, DNA aneuploidy, and disease progression. MSI cancers showed a favorable prognosis. CIN cancers (49 cases), defined as tumors with a large intercellular variation in centromere copy numbers, were associated more frequently with centrosome amplification, Aurora-A overexpression, increased p53 immunoreactivity, and 20q13 gain than the others (51 cases). Tumors with disease progression were included in the CIN cancer group. CONCLUSIONS: The present observations suggest that there are differences in the biological characteristics of the two types of genetic instability.     

Receiver operating characteristic (ROC) analysis of images reconstructed with iterative expectation maximization algorithms

PURPOSE: The quality of images reconstructed by means of the maximum likelihood-expectation maximization (ML-EM) and ordered subset (OS)-EM algorithms, was examined with parameters such as the number of iterations and subsets, then compared with the quality of images reconstructed by the filtered back projection method. METHODS: Phantoms showing signals inside signals, which mimicked single-photon emission computed tomography (SPECT) images of cerebral blood flow and myocardial perfusion, and phantoms showing signals around the signals obtained by SPECT of bone and tumor were used for experiments. To determine signals for recognition, SPECT images in which the signals could be appropriately recognized with a combination of fewer iterations and subsets of different sizes and densities were evaluated by receiver operating characteristic (ROC) analysis. The results of ROC analysis were applied to myocardial phantom experiments and scintigraphy of myocardial perfusion. RESULTS: Taking the image processing time into consideration, good SPECT images were obtained by OS-EM at iteration No. 10 and subset 5. CONCLULSION: This study will be helpful for selection of parameters such as the number of iterations and subsets when using the ML-EM or OS-EM algorithms.     

Clinical features of poorly differentiated thyroid papillary carcinoma

Objective

To investigate the clinical feature of the poorly differentiated thyroid papillary carcinoma.

An elder case of neurosarcoidosis associated with brain infarction]

A 75-year-old woman with sarcoidosis developed sudden weakness of the left upper and lower limbs. Neurological examination revealed left-sided hemiplegia, hyperreflexia with pathological reflexes and hypesthesia. She was disoriented and euphoric. Diffusion-weighted brain MRI showed high intensity lesions in the right parietooccipital lobes. Electroencephalogram showed diffuse slowing of the background activity. Serum lysozyme increased to 18.4 mg/ml, CSF protein to 51 mg/dl. After admission, she presented psychotic manifestation followed by a progressive disturbance of consciousness. Epithelioid granulomas without caseous necrosis were present in the biopsied lymph node and specimens from the occipital cortex, indicating neurosarcoidosis. Necrosis was also present in the sampled brain tissue. The psychotic symptoms and consciousness disturbance rapidly ameliorated after the treatment with oral prednisolone, 40 mg/day. Neurosarcoidosis should be considered even in an elder case of sarcoidosis complicated with a stroke.