Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr virus infection

Two girls (a 5 year old and a 21 month old) experiencing mononucleosis syndrome with coincidental human herpesvirus (HHV)-7 and Epstein-Barr virus (EBV) infections are described. One patient had primary HHV-7 infection and reactivated EBV infection. The other had primary HHV-7 and EBV infections. These cases indicated that HHV-7 is capable of inducing infectious mononucleosis-like illness. Multiple herpesvirus infection in one of the patients also suggests that interaction among herpesviruses can occur in vivo. The consequence of this interaction may have clinical implications.     

Comparative diagnostic utility of different MR modalities in mild cognitive impairment and Alzheimer's disease

This study compares the diagnostic accuracy of magnetic resonance (MR)-based hippocampal volumetry, single voxel (1)H MR spectroscopy ((1)H MRS) and MR diffusion-weighted imaging (DWI) measurements in discriminating patients with amnestic mild cognitive impairment (MCI), Alzheimer's disease (AD) and normally aging elderly. Sixty-one normally aging elderly, 24 MCI and 22 AD patients underwent MR-based hippocampal volumetry, (1)H MRS and DWI. (1)H MRS voxels were placed over both of the posterior cingulate gyri, and N-acetyl aspartate (NAA)/creatine (Cr), myoinositol (MI)/Cr and NAA/MI ratios were obtained. Apparent diffusion coefficient (ADC) maps were derived from DWI, and hippocampal borders were traced to measure hippocampal ADC. At 80% specificity, the most sensitive single measurement to discriminate MCI (79%) and AD (86%) from controls was hippocampal volumes. The most sensitive single measurement to discriminate AD from MCI was posterior cingulate gyrus NAA/Cr (67%). At high specificity (>85-90%), combinations of MR measures had superior diagnostic sensitivity compared with any single MR measurement for the AD vs. control and control vs. MCI comparisons. The MR measures that best discriminate more from less affected individuals along the cognitive continuum from normal to AD vary with disease severity. Selection of imaging measures used for clinical assessment or monitoring efficiency of therapeutic intervention should be tailored to the clinical stage of the disease.     

Colchicine suppresses osteopontin expression and inflammatory cell infiltration in chronic cyclosporine nephrotoxicity

BACKGROUND: Colchicine (Col) is beneficial to renal injury because of its anti-inflammatory effect, but its mechanism has yet to be elucidated. The present study was designed to evaluate the inhibitory effects of colchicine on osteopontin (OPN) expression and the macrophage accumulation in chronic cyclosporine (CsA) nephrotoxicity in rats. METHODS: Male adult Sprague-Dawley rats on a low salt diet (LSD, 0.05% sodium) were treated daily with Col (30 microg/kg), CsA (15 mg/kg), and both CsA and colchicine or vehicle (olive oil 1 ml/kg) for 4 weeks. The effects of colchicine on chronic CsA nephrotoxicity were evaluated by examining renal function, histopathology, and ED-1 positive cells. The expressions of OPN mRNA and protein were estimated respectively by Northern blot and immunohistochemistry. RESULTS: Compared with vehicle-treated rats, CsA-treated rats showed an increase in serum creatinine, a decline in creatinine clearance rate, and tubulointerstitial fibrosis (all p < 0.01). Concomitant administration of colchicine reversed all of the above parameters (all p < 0.01). Of note, the upregulated expression of osteopontin mRNA and protein seen in CsA-treated rats was significantly decreased after colchicine treatment. Furthermore, the expression of osteopontin mRNA was strongly correlated with the number of ED-1 positive cells (r = 0.712, p < 0.001) and the tubulointerstitial fibrosis score (r = 0.586, p = 0.007). CONCLUSION: Colchicine is capable of abrogating the upregulation of chemotactic OPN expression and macrophage influx, and this is associated with improved renal tubulointerstitial fibrosis in chronic CsA nephrotoxicity.     

A phase II trial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia

Purpose. The incidence of adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia has been rising in the face of limited treatment options for patients with metastatic disease. With the emergence of data to suggest that single agent docetaxel and irinotecan carry antineoplastic effects in this setting, we determined the response rate of these agents when given in combination. Patients and Methods. Forty-six patients with metastatic adenocarcinoma of the lower third of the esophagus, esophagogastric junction, and gastric cardia were evaluated. Patients received docetaxel 50 mg/m²/d and irinotecan 130 mg/m²/d intravenously at 21-d intervals with a tumor assessment after 2 cycles. Because of unacceptable toxicity among the first 13 patients, dosing was reduced to docetaxel 40 mg/m²/d and irinotecan 100 mg/m²/d intravenously at 21-d intervals. Results. The response rate for the entire cohort was 26% (95% confidence interval: 14%, 41%) with 12 confirmed partial responses. Five of these 12 responses were observed in patients treated at the higher chemotherapy dose. However, because 8 of 13 patients suffered grade 4 neutropenia and fevers, a dose reduction was incorporated into the protocol, and the remainder of the cohort was treated at the lower dose. All except 4 of the 15 observed grade 4 toxicities occurred at the higher dose, and these toxicities included nausea and vomiting, dyspnea, hypotension, dysrhythmias, and diarrhea in addition to neutropenia and fevers. There were no grade 5 toxicities. The median survival for the entire cohort was 7.3 mo. Conclusion. The combination of docetaxel and irinotecan provides modest antineoplastic activity among patients with adenocarcinoma of the esophagus, esophagogastric junction, and gastric cardia. Doses of docetaxel 40 mg/m²/d and irinotecan 100 mg/m²/d at 21-d intervals provide an acceptable safety profile, but higher doses appear to result in unacceptable toxicity.     

beta-Cell dysfunction rather than insulin resistance is the main contributing factor for the development of postrenal transplantation diabetes mellitus

BACKGROUND: Our study was undertaken to investigate the pathogenesis and possible risk factors for postrenal transplantation diabetes mellitus (PTDM). METHODS: We recruited 114 patients with normal glucose tolerance (NGT) and performed both 75-g oral glucose tolerance tests (OGTT) and short insulin tolerance tests 1 week before and 9-12 months after transplantation. RESULTS: The subjects were classified into three groups by World Health Organization criteria on the basis of OGTT after transplantation: (a) 36 (31.6%) subjects with normal glucose tolerance; (b) 51 (45.7%) subjects with impaired glucose tolerance (IGT); and (c) 27 (23.7%) subjects with postrenal transplantation diabetes mellitus. Dosages of steroid and cyclosporine were equivalent among the three groups. Before transplantation, the fasting and 2-hr plasma glucose and proinsulin/insulin (PI/I) ratios were significantly higher in the IGT and PTDM groups than in the NGT group, but the insulin sensitivity index (ISI) was not significantly different among the three groups. In addition, the area under the curve-insulin on OGTT was significantly lower in the PTDM group than in the NGT group. After transplantation, however, the ISI was increased in all groups. Furthermore, the ISI and PI/I ratios revealed significantly higher values in the PTDM group than in the NGT group after transplantation. CONCLUSIONS: These results revealed that fasting and 2-hr plasma glucose levels, as well as the proinsulin/insulin ratio before transplantation, are both possible indicators of beta-cell dysfunction and may be predictors for the development of PTDM. Furthermore, beta-cell dysfunction, rather than insulin resistance, was proven to be the main factor for the pathogenesis of PTDM.     

Reduced oral wound healing in the NOD mouse model for type 1 autoimmune diabetes and its reversal by epidermal growth factor supplementation

Using the NOD mouse, a model for type 1 diabetes, we examined how reduced concentrations of epidermal growth factor (EGF) in the saliva, after onset of type 1 diabetes, affect oral wound healing. Diabetic NOD/LtJ mice on insulin therapy, prediabetic NOD/LtJ, and age- and sex-matched BALB/cJ mice were given a cutaneous tongue punch and allowed to undergo normal healing. With diabetes onset and a reduction in saliva-derived growth factor levels, the rate of tongue wound healing was reduced compared with nondiabetic NOD/LtJ and healthy BALB/cJ mice. Addition of exogenous EGF to the drinking water did not accelerate the rate of healing in BALB/cJ or prediabetic NOD/LtJ; however, diabetic NOD/LtJ mice exhibited accelerated wound healing similar to healthy mice. These results demonstrate that loss of growth factors from saliva is associated with profoundly reduced oral wound healing, suggesting that therapeutic treatment with topical delivery may be beneficial to patients with type 1 diabetes and oral wound complications.     

Age-related changes in the distribution of Kv1.1 and Kv1.2 channel subunits in the rat cerebellum

We have revealed age-related changes in the expression patterns of Kv1.1 and Kv1.2 in the rat cerebellum for the first time. In the aged rat, immunoreactivity for Kv1.1 was increased in the cell bodies of Purkinje cells, while the staining intensity was significantly decreased in the granule cells. The cell bodies of cerebellar output neurons showed strong Kv1.1 immunoreactivity in the nucleus medialis, interpositus and lateralis of the aged rat. Kv1.2 immunoreactivity was found in some interneurons with their processes in this region of the aged rat. Image analysis demonstrated that immunoreactivities for Kv1.1 and Kv1.2 were increased specifically in the cell bodies of cerebellar output neurons of the aged rat. This study may provide useful data for future investigations on the channels that cause brain diseases and age-related disorders.     

Aldosterone, a new appreciation of its role in heart failure

Understanding of the role, triggers, and impact of the renin-angiotensin-aldosterone system in cardiovascular disease has significantly broadened. In recent years substantial discoveries have been made regarding the pathophysiology of heart failure, particularly in the area of neurohormonal activation. New interest in therapy with aldosterone antagonists was stimulated by results of a 2-year study of 1663 patients with heart failure that showed a 30% relative risk reduction of death among patients given a subhemodynamic dosage of spironolactone, a nonselective aldosterone antagonist, compared with placebo, in addition to standard therapy of diuretics, angiotensin-converting enzyme inhibitors, beta-blockers, and digitalis.