Varied appearance of cornea of patients with corneal dystrophy associated with R124H mutation in the BIGH3 gene.

PURPOSE: To evaluate the corneal phenotype of patients with corneal dystrophy and the R124H mutation in the BIGH3 gene. METHODS: We examined the corneas of 24 unrelated Japanese individuals who had an R124H mutation in the BIGH3 gene. Large, discrete, granular deposits were present in the anterior stroma of all patients. They were subdivided into two types according to the appearance of the cornea. Histologic examination of the cornea after Masson trichrome and Congo red staining also was performed in specimens from patients who underwent keratoplasty. RESULTS: The first and the most common type of corneal findings on slit-lamp examination (20 of 24 patients) were discrete granular deposits in the anterior stromal layer and star-shaped opacities in the mid-to-deep stroma. The central subepithelial diffuse opacity increased with age. Amyloid deposits were seen mainly in the mid-to-deep stroma in five of the seven such patients evaluated. The second type of corneal appearance (four of 24 patients) was the presence of diffuse subepithelial opacities in the anterior stroma predominantly, rather than granular or linear opacities. Amyloid deposits were present in the anterior cornea of three of these four patients. CONCLUSION: The corneal lesions documented in patients with the R124H mutation were not unique to that disease but could be divided into two types, which likely represent a disease continuum. The lesion location, amount of amyloid deposition, or an interaction between the granular materials and amyloid may influence the varied appearance of the corneal lesion in patients with this disease.     

Focal distribution of p16/CDKN2 gene mutations within individual prostate carcinomas

To examine the potential role of pl6/CDKN2 gene mutations in prostate tumorigenesis, focal areas within individual tumors were investigated. Eleven cases of histologically heterogeneous prostate carcinomas obtained by radical prostatectomy were subjected to analysis of p16/CDKN2 gene mutations. DNA was extracted from 5 to 10 separate areas of each tumor with different growth or histological patterns. Exons 1 through 3 of the p16/CDKN2 gene were amplified using the polymerase chain reaction (PCR) and screened for homozygous deletions and mutations of this gene by single-strand conformation polymorphism (SSCP) analysis. No homozygous deletions were observed in any of the prostate carcinomas, but two of the eleven tumors demonstrated mutations in exon 2 of p16/CDKN2 gene. Missense mutations were detected in only one and two foci, respectively, out of six ana ten selected tumor areas. The present results suggest that p16/CDKN2 gene mutations, although they occur at a low incidence, are involved in prostate tumorigenesis, indicating a mutational heterogeneity in addition to morphological heterogeneity.     

A case of ductal carcinoma in situ (DCIS; non-comedo type) detected by ultrasonography: Demonstration of occult multiple foci

We report a case of ductal carcinoma in situ (DCIS) of the breast detected by ultrasonographic mass screening in a 51-year-old woman. In a mass screening program for breast cancer, physical examination with inspection and palpation, and ultrasonography (US) were performed. A hypoechoic mass with a slightly irregular margin was detected by US in the lateral upper quadrant of the right breast, at a distance 2 cm from the edge of the nipple. The mass was not detected by physical examinations or by mammography (MMG). The mass, which measured 0.8 x 0.5 cm and was examined by fine needle aspiration biopsy (FNAB) under US guidance, was cytologically diagnosed as class X. Modified radical mastectomy (Auchincloss method) was performed with the patient's consent. Pathological examination of the resected specimen revealed DCIS (noncomedo type) and occult multiple foci of malignancy which was considered tracking centripetally underneath the nipple. This case suggests that US and FNAB performed under US guidance are useful in the detection and diagnosis, respectively, of a breast mass. We should take multifocality into consideration, particularly with tendency tracking to the nipple, in the treatment of small breast cancers such as DCIS.     

Glycogen-rich clear cell carcinoma of the breast: A case report and review of the literature

A case of glycogen-rich clear cell carcinoma (GRCC) which arose in the right breast of a 35-year-old Japanese woman is reported. Light microscopic examination of the tumor revealed solid alveolar proliferation of clear cells containing abundant glycogen. Electron microscopy identified aggregates of glycogen particles and numerous empty glycogen lakes. This case is reported with a discussion on the other 42 GRCC cases reported in the international literature.     

Delayed image of iodine-123 iomazenil as a relative map of benzodiazepine receptor binding: The optimal scan time

Delayed single-photon emission tomograpic (SPET) images after an intravenous bolus injection of iodine-123 iomazenil have been used as a relative map of benzodiazepine receptor binding. We determined the optimal scan time for obtaining such a map and assessed the errors of the map. SPET and blood data from six healthy volunteers and five patients were used. A three-compartment kinetic model was employed in simulation studies and analyses of actual data. The simulation studies suggested that, in the normal brain, the scan time at which a single SPET image best represented the relative receptor binding was 3.0–3.5 h post-injection. This finding was supported by actual data from the volunteers. The simulation studies also suggested that the optimal scan time was not greatly changed by the variability of the input functions, and that the error in the SPET image contrast in the vicinity of the optimal scan time was not increased by changes in the tracer kinetics in the entire brain. The SPET image contrast in the patients at 3.0 h post-injection agreed well with the reference receptor binding estimated by kinetic analysis, with a mean error of 3.6%. These findings support the use of a single SPET image after bolus injection of [¹²³I]iomazenil as a relative map of benzodiazepine receptor binding. For this purpose, a SPET scan time of 3.0-3.5 h post-injection is recommended.     

Attentional modulation of parieto-occipital cortical responses: implications for hemispatial neglect

Functional magnetic resonance imaging (fMRI) was used to examine whether preattentive and attentive visual processing, the cognitive psychological dichotomy on normal vision, indeed activate the parieto-occipital systems differentially as suggested by recent neuropsychological research. The activation paradigms consisted of feature detection and discrimination of line orientation, and visual fixation, which corresponded to preattentive, attention-requiring, and baseline conditions, respectively. The detection versus fixation contrast revealed activation sites in the right lateral prefrontal cortex and bilateral occipital lobes, whereas the discrimination versus fixation contrast showed broader bilateral activations extending from the occipital lobes through the parietal lobes, prefrontal cortex, thalamus, basal ganglia and upper brainstem. In the discrimination versus detection contrast, significant activations were observed in the right superior and inferior parietal lobules as well as in the subcortical structures. These findings were consistently demonstrated both at intra- and inter-subject levels. The present study provides further evidence to delineate neural substrate for the two distinct modes of visual processing and helps us to understand the neuropsychological mechanism underlying visual attention disorders.     

Curative Resection of Microgastrinomas Based on the Intraoperative Secretin Test

The intravenous secretin injection test (secretin test) has been used for the differential diagnosis of gastrinoma. In this study we report that the intraoperative secretin test (IOS test) is also useful for determining the extent of curability in patients with Zollinger-Ellison syndrome (ZES). Twelve patients with ZES underwent surgical exploration and the IOS test. The results of the IOS test were obtained by rapid radioimmunoassay of the serum gastrin level (IRG) within 60 minutes. The test was diagnosed as negative when the maximum increase of serum IRG was less than 80 pg/ml and also less than 20% of the basal serum IRG level. Three of the twelve patients underwent pancreatoduodenectomy (PD), and two patients underwent distal pancreatectomy. Extirpation of duodenal tumors with dissection of regional lymph nodes was performed in seven patients. In two of the seven patients the IOS test remained positive after extirpation of the duodenal tumors and the dissection of regional lymph nodes. In one patient PD was performed on the basis of the positive results, and the IOS test became negative after PD. In the other patient, two tiny metastatic liver tumors were identified and were resected, but the IOS test did not become negative. We closed the abdomen in 11 patients when we obtained negative results from the IOS test. The results of the IOS test were almost identical to the data obtained by the standard assay postoperatively. The serum IRG levels of all but one patient fell to the normal level, and the secretin test became negative postoperatively. The IOS test is thus useful and indispensable for curative resection of microgastrinomas in patients with ZES.     

An experimental study of the effects of nerve root retraction on the posterior ramus

STUDY DESIGN: The histologic and ultrastructural changes in the posterior ramus after posterior lumbar surgery were studied in rabbits. OBJECTIVE: To investigate the structural changes in the posterior ramus after posterior lumbar surgery that may cause injury to the posterior ramus after the procedure. SUMMARY OF BACKGROUND DATA: Investigators in previous studies have pointed out that low back discomfort after lumbar discectomy relates to neurogenic changes and/or myogenic changes of paravertebral muscle. However, no previous study has demonstrated the effects of excessive nerve root retraction on spinal posterior rami. METHODS: Eighteen male Japanese White rabbits were used. The posterior ramus arising from the S1 nerve root was examined after exposure of the lamina only, fenestration, or retraction of the S1 nerve root, with light microscopy and transmission electron microscopy at 2, 4, and 6 weeks after the procedure. Results were compared with a those in control specimens that did not undergo the procedure. RESULTS: In the exposed group, no distinct difference was found compared with the control specimen. In the fenestration group, especially at 6 weeks, some attenuation and splitting of myelin sheaths was observed. In the retraction group, the structural alteration was most severe. Even at 2 weeks, fragmentation of many myelin sheaths was detected. Examination of specimens by electron microscopy indicated phagocytosis of myelinated fibers at 4 and 6 weeks. CONCLUSIONS: Findings showed that posterior lumbar procedures, including retraction of paravertebral muscle, fenestration of the lamina, and retraction of the nerve root affect the posterior ramus. Excessive retraction of the nerve root has an especially disastrous effect on the posterior ramus. Such a violent maneuver within the spinal canal must be avoided.     

Spreading patterns of hilar bile duct cancer

Spreading patterns of hilar bile duct cancer were investigated based on cases resected in our institution and reported cases in Japan. Forty-seven patients underwent resection in our institution during the past 20 years. Three patients(12%) survived for more than 5 years. The depth of tumor invasion was m or fm in 4 and se or si in 26 patients. Positive cancer invasion in the cut end was classified as hm2 or dm2 in 8 patients and em2 in 13. Twenty-four (60%) of 40 patients investigated histologically had positive lymph node metastases. Invasion of the ss layer or deeper perineural invasion occurred in 92.5%. In terms of direct invasion of the liver, hinf1 occurred in 20(42.6%). Fourteen(29.8%) han invasion of the portal vein(more than vs1). Patients with invasion of the hepatic artery were not resected. The 5-year survival rate by cancer stage was 38% in stage I, 20% in stage II, 16% in stage III, and 0% in stage IV. Surgery was assessed as Cur A in 19 patients (46.3%), Cur B in 7 (17.1%), and Cur C in 15 (36.6%). In Cur A patients the 5-year survival rate was 18%, while that for our Cur B and Cur C patients was 0%. Our patient series was more advanced in terms of cancer stage than the statistical Japanese series and both included a significant number of noncurative cases. Hepatic resection of the right or left lobe, medial segment, and S4a and S5, combined resection of the caudal lobe, and combined portal vein resection are important as radical surgery in the treatment of this cancer.     

Difference of visual attention between smokers and never-smokers]

Nicotine is known to improve cognitive performance such as attention, concentration and working memory in humans and animals. Previous research suggests that nicotine enhances visuospatial attention. But it could be hypothesized that nicotine intake alleviate a withdrawal-induced deficit in smokers. To evaluate the cognitive performance in smokers and never-smokers, we investigate eye movement while 4-points saccade task is performed. 5 smokers and 6 never-smokers are matched for age and education. Eye movement was investigated by using TKK2920 (Takei Co.) which determines the direction of gaze over a two-dimensional visual field without attachments to the eye. We found that a tendency which Mean Gazing Time is prolonged in smokers. These data suggest that impairment of visual attention in smokers is not significant.