Recovery of postural stability following conscious sedation with midazolam in the elderly

Purpose. To investigate the differences in recovery of postural stability, after obtaining similar intravenous sedation levels with midazolam, in elderly and younger patients undergoing dental surgery. Methods. We studied 15 elderly patients (>65 years) and 15 younger patients (<55 years) after intravenous sedation. Midazolam was carefully titrated over 4–5 min until slow response to verbal commands, ptosis of the eyelid, or slight slurring of speech was obtained. Parameters were postural balance tests and an addition test, as a psychomotor function test. Results. The dose of midazolam in the elderly group (0.045 ± 0.012 mg·kg⁻¹) was 62% of that in the younger group (0.074 ± 0.026 mg·kg⁻¹). In evaluation of the percentile rank of a balance test with a visual feedback system, which contained a dynamic balance element, recovery at 60 min in the elderly group was significantly slower than that in the younger group. However, the recovery times for the balance test and the addition test, at which the significantly changed values were restored to the baseline values, were 120 min and 90 min, respectively, in both groups. Conclusion. In the recovery from sedation, elderly patients had more difficulty in acquiring postural adjustment during movement than in maintaining a standing posture. If the dose is carefully administered, however, even elderly patients might be able to return home 2 h after midazolam administration, as could the younger patients. Received: November 6, 2001 / Accepted: April 22, 2002     

Functional Mediastinal Parathyroid Cyst: Report of a Case

We report herein a rare case of a functional mediastinal parathyroid cyst. A mediastinal tumor was detected by a chest X-ray film and subsequent computed tomography (CT) scan in a 68-year-old woman who was asymptomatic. Biochemical examination revealed that her serum calcium and intact-parathyroid hormone (i-PTH) levels were above the normal range. The findings of chest CT and magnetic resonance imaging suggested a cystic mass. The mass, which adhered tightly to its surrounding structures, was resected through a median sternotomy. The patient had an uneventful postoperative course, and her serum calcium and i-PTH levels rapidly returned to within the normal range. Received: March 21, 2001 / Accepted: September 11, 2001     

Increased vulnerability to focal ischemic brain injury in human apolipoprotein E4 knock-in mice

Accumulating evidence suggests that among the 3 human apolipoprotein E (apoE) isoforms encoded by the human APOE gene, the e4 allele may act to exacerbate brain damage in humans and animals. This study aimed to compare the isoform-specific vulnerability conferred by human apoE to ischemic brain damage, using mice expressing human apoE isoforms (apoE2, apoE3, or apoE4) in place of mouse apoE, produced by the gene-targeting technique in embryonic stem cells (knock-in, KI). Homozygous human apoE2 (2/2), apoE3 (3/3), or apoE4 (4/4) KI mice were subjected to permanent focal cerebral ischemia by a modified intraluminal suture method. Twenty-four h thereafter, brain damage, (as estimated by infarct volume and neurologic deficit) was significantly worse in 4/4 KI mice versus 2/2 or 3/3 KI mice (p < 0.001 for each comparison), with no significant differences between 2/2 and 3/3 KI mice. Immunohistochemistry for human apoE expression revealed similar apoE distribution with no significant difference in the immunostaining intensity among the 3 lines of KI mice. Notably. increased expression of human apoE was detected in neurons and astrocytes in the peri-infarct area, and a punctate expression pattern was evident in the border between the infarct and peri-infarct areas in all KI mice subjected to ischemia. Taken together, our results show that apoE affects the outcome of acute brain damage in an isoform-specific fashion (apoE4 > apoE3 = apoE2) in genetically engineered mice.     

A novel approach for the detection of proteolytically activated transglutaminase 1 in epidermis using cleavage site-directed antibodies

It has been suggested that transglutaminase 1 is proteolytically activated upon the terminal differentiation of the keratinocyte, but the mechanisms are not well understood. We have established two mouse hybridoma cell lines producing monoclonal antibodies that specifically detect proteolytically cleaved transglutaminase 1. One detects the amino-terminus of the fragment produced by cleavage between Arginine 93 and Glycine 94, and the other detects the amino-terminus of the fragment produced by cleavage between Arginine 573 and Glycine 574. Using these two antibodies, immunohistochemical analyses of the epidermis revealed that the cleavages of the transglutaminase 1 protein occur early in the terminal differentiation of keratinocytes in the basal layer of the epidermis, that the cleavage between Arginine 573 and Glycine 574 (producing the 574G fragment) precedes the cleavage between Arginine 93 and Glycine 94 (producing the 94G fragment), that the 94G fragment is localized to the plasma membrane of keratinocytes and has cross-linking activity, whereas the 574G fragment is dispersed in the cytosol and does not have detectable levels of activity on in situ transglutaminase assay, and that 1-alpha-25-dihydroxycholecalciferol or all-trans retinoic acid treatment and ultraviolet B exposure disturb the localization of the transglutaminase 1 fragments with changes in the morphology of differentiating keratinocytes. All these results demonstrate that the antibodies generated in this work are useful to dissect the mechanism by which transglutaminase 1 is activated, and would provide us with novel insights into the biogenesis of the epidermis.     

Genetic alterations in adenoma-carcinoma sequencing of intraductal papillary-mucinous neoplasm of the pancreas

We investigated the adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm from the aspect of genetic changes. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from patients with 16 intraductal papillary-mucinous adenoma of the pancreas (IPMA) and 10 intraductal papillary-mucinous carcinoma of the pancreas (IPMC) were provided for DNA extraction after microdissection. SSCP-DNA sequencing analysis demonstrated K-ras mutations at codon 12 in 75% of IPMA and 70% of IPMC, while those at codon 13 were observed neither in IPMA nor IPMC. There were no characteristic K-ras mutation types in IPMA and IPMC and no significant differences in incidence of K-ras mutations between the two categories. The frequencies of p53 mutations analyzed by SSCP-DNA sequencing were not high in IPMA (18.8%) and IPMC (30%), showing no significant difference between them. LOHs of APC in IPMA and IPMC were infrequent (6.3 and 20%, respectively) and showed no significant difference in incidence between the two categories. The LOH frequencies of DCC in IPMA and IPMC were 31.3 and 40%, respectively, and were not statistically different from each other. Taken together, genetic changes such as K-ras, p53, APC and DCC mutations may not be associated with adenoma-carcinoma sequence in intraductal papillary-mucinous neoplasm of pancreas.     

Very low incidence of microsatellite instability in intraductal papillary-mucinous neoplasm of the pancreas

Intraductal papillary-mucinous carcinoma (IPMC) of the pancreas, a new entity of pancreatic cancer with a favorable prognosis, has shown a gradual increase in the number of reported cases. Patients with high-frequency microsatellite instability (MSI-H) tumors have been shown to survive longer than those with low-frequency MSI (MSI-L) or microsatellite stable (MSS) tumors in colorectal and gastric cancer. We investigated whether MSI-H in patients with IPMC can contribute to a good prognosis. The formalin-fixed paraffin-embedded tumors and surrounding normal pancreatic tissues from 10 patients with IPMCs and 16 with intraductal papillary-mucinous adenomas (IPMAs) were provided for DNA extraction after microdissection. Polymerase chain reaction (PCR) was carried out using 8 microsatellite primer marker sets. The mixed PCR samples were analyzed using a genetic analyzer. MSI-H was determined by assessment of microsatellite variations in 3 or more of the 8 tested markers. Immunohistochemical staining of the MSI-responsible proteins hMLH1 and hMSH2 was conducted for both the IPMC and IPMA samples. Ten percent of IPMC harbored MSI-H tumors, whereas no MSI-H tumors were detected in the IPMAs. Thirty percent of IPMC tumors and 25% of IPMA tumors showed MSI-L. All IPMCs and IPMAs showed normal expression of both hMLH1 and hMSH2. MSI-H and loss of hMLH1 and hMSH2 are very rare events in both IPMCs and IPMAs. We conclude that a good prognosis for patients with IPMC is not associated with MSI-H.     

A pectin glucuronyltransferase gene is essential for intercellular attachment in the plant meristem

Intercellular attachment is an essential process in the morphogenesis of multicellular organisms. A unique mutant, nolac-H18 (nonorganogenic callus with loosely attached cells), generated by T-DNA transformation using leaf-disk cultures of haploid Nicotiana plumbaginifolia, lost the ability to form tight intercellular attachments and adventitious shoots. The gene tagged with T-DNA, named NpGUT1 (glucuronyltransferase 1), was similar to the gene for the catalytic domains of animal glucuronyltransferases and was expressed predominantly in shoot and root apical meristems. The transformation of NpGUT1 complemented the nolac-H18 mutation, and the expression of antisense NpGUT1 RNA produced crumbled shoots. The mutation caused defects in the glucuronic acid of rhamnogalacturonan II of pectin, which drastically reduced the formation of borate cross-linking of rhamnogalacturonan II. NpGUT1, which encodes a unique glucuronyltransferase, is a glycosyltransferase gene identified in pectin biosynthesis and is essential for intercellular attachment in plant meristems and tissues.     

Improvement of both psychotic symptoms and Parkinsonism in a case of dementia with Lewy bodies by the combination therapy of risperidone and L-DOPA

A 69-year-old female of dementia with Lewy bodies (DLB) with fluctuating cognitive impairment, visual and auditory hallucinations, persecutory delusions and Parkinsonism was treated by the combination of 1 mg/day risperidone and 300-750 mg/day L-DOPA. By this combination therapy, both the psychotic symptoms and Parkinsonism improved, while cognitive function did not deteriorate. This report suggests that the combination therapy of risperidone and L-DOPA may be worth considering in the special cases of DLB.     

Outcomes following staged bilateral pallidotomy in advanced Parkinson's disease

The authors assessed clinical outcome for up to one year after staged bilateral pallidotomy in 14 patients with advanced PD. One year after surgery, dyskinesias were virtually abolished and there were significant reductions in "off" time (67%) and activities of daily living "off" scores (24%), as well as nonsignificant reduction in "off" motor score (39%); "on" scores were unchanged. One patient developed a visual field deficit; two had transient confusion. Staged bilateral pallidotomy improves motor function in selected patients with advanced PD.     

The relationship of p53 Protein and lymph node metastases in invasive breast cancer

The p53 expression in invasive breast cancers from 106 patients was correlated with clinicopathological variables to ascertain its usefulness for estimating prognosis. The p53 expression was significantly associated with the number of axillary lymph node metastases and the presence of internal mammary lymph node metastases; however, it was not associated with age, menopausal status, histologic type, or tumor size. Although p53 expression was a significant prognostic factor according to univariate analysis, it did not appear to be an independent prognostic factor according to multivariate analysis. Thus, the prognostic power of p53 expression is likely to be weak and therefore probably of limited clinical value. Nevertheless, the number of patients in our study was small, and we believe that an investigation of a larger series of patients is indicated.