Current concept and future research directions of mild cognitive impairment

Alzheimer's disease (AD) generally begins with mild memory problems which occur in an insidious manner and progresses to the development of multiple cognitive impairments. There is a ‘gray’ area between what is classified as ‘normal’ and what is classified as ‘dementia’, currently called mild cognitive impairment (MCI). In this article, a case of MCI is described, and the diagnosis, assessment, subclassification (pre‐Alzheimer type and white matter lesion type) and future therapeutic plans for MCI are reviewed.     

Iron deficiency down-regulates the Akt/TSC1-TSC2/mammalian Target of Rapamycin signaling pathway in rats and in COS-1 cells

Iron deficiency (ID) is one of the most commonly known forms of nutritional deficiencies. Low body iron is thought to induce neurologic defects but may also play a protective role against cancer development by cell growth arrest. Thus, ID may affect cellular pathways controlling cell growth and proliferation, the mechanism of which is still not fully understood. The serine/threonine protein kinase Akt and its downstream target, the mammalian Target of Rapamycin (mTOR), is known to play a crucial role in the regulation of cell growth and survival. Therefore, we hypothesized that Akt/mTOR pathway could be influenced by ID. Three-week-old male Wistar-strain rats were divided into 3 groups and the 2 groups had free access to a control diet (C group) or an iron-deficient diet (D group). The third group (PF group) were pair-fed the control diet to the mean intake of the D group. After 4 weeks, rats were killed and their brains were sampled. In separate experiments, COS-1 cells were cultured with or without the iron chelator deferoxamine. Western blots of brain samples and COS-1 lysates were used to analyze the expression and phosphorylation state of Akt, TSC2, mTOR, and S6 kinase proteins implicated in the Akt/mTOR pathway. Using 2 different ID models, we show for the first time that iron deficiency depresses Akt activity in rats and in COS-1 cells, leading to a decrease in mTOR activity.     

Juvenile-onset dystonia with bilateral atrophy of the basal ganglia on MRI]

A 40-year-old man was hospitalized for tremor of the right upper limb, gait disturbance and dysarthria. His course of development had been normal until the age of 14, when difficulties in speaking and walking, and tremor of the upper limb became evident following an episode of fever. His symptoms have been gradually worsening for the past 25 years. His elder sister showed similar clinical symptoms and progressive course of illness. The patient showed no indication of mental retardation. Neurological examination showed dysarthria, slow dyskinetic movement of the tongue, dystonic posture of the left hand, tremor of irregular frequency of the right upper limb, diminished tendon reflex, positive Romberg's sign, diminished vibratory and position sense in the lower limbs and pyramidal signs. Cystometry indicated defective voiding of the bladder. Magnetic resonance imaging of the brain showed bilateral atrophy of the putamina, globus pallidus, caudate nuclei and substantia nigra. MRI showed similar findings in her sister. By electrophysiological and pathological examination, disorders of other systems were evident, such as upper motor neurons, and sensory tract. GM1 and GM2 gangliosidosis appeared the most likely diagnosis, but were ruled out on the basis of the result of lysozomal enzyme assay and rectal biopsy. The present patient's condition may possibly be the result of an unknown metabolic disorder, or a new disease entity affecting various components of the nervous system.     

Carpentier-Edwards pericardial aortic valve in middle-aged patients comparison with the St. Jude medical valve

Objective The objective of the present study was to compare long-term results of single aortic valve replacement (AVR) with mechanical (St. Jude Medical valves: standard) and biologic (the Carpentier-Edwards pericardial) prostheses. Method: Between 1995 and 2002, 95 patients who underwent single AVR with mechanical (n=46) or biologic (n=49) prostheses were enrolled in this study. The mean age at the operation was 54.0±9.6 years (range: 20 to 69 years) with the mechanical and 68.8±7.1 years (range: 44 to 85 years) with the biologic prosthesis. Results: The 9-year actuarial survival rate, which was calculated by taking perioperative mortality into account, was 90.3±4.6% for patients with mechanical valves and 87.6 ±4.8% for patients with bioprostheses, with no difference between the two groups (p=0.342). The 9-year freedom rate from thromboembolism, reoperation, endocarditis was 94.8+3.6%, 100% and 97.8 ±2.2% for patients with mechanical valves and 98.0 ±2.0%, 97.5 ±3.4% and 95.0 ±3.4% for those with bioprostheses, respectively. After 9 years, freedom from cardiac death averaged 97.8% in the group with mechanical valves compared with 95.3% in those with bioprostheses (p=0.541). Conclusion: We conclude that the mid-term durability of the Carpentier-Edwards pericardial valve in the aortic position for the elderly is excellent. Nevertheless, the risk of tissue valve reoperation progressively increases with time, and a longer follow-up may be necessary to provide its value compared with the mechanical valves in a country like Japan with a high life expectancy. (Jpn J Thorac Cardiovasc Surg 2005; 53:465-469)     

Expression profile of chemokines and chemokine receptors in epithelial cell layers of oral lichen planus

BACKGROUND: To understand the immunopathological features of oral lichen planus (OLP), we analyzed the expression of chemokines in the epithelial cell layers. Methods: Epithelia from OLP or healthy gingiva were collected by laser microdissection. The chemokine and chemokine receptor expressions in the epithelia were analyzed by DNA microarray. RESULTS: High levels of MIP-3alpha/LARC/CCL20 and its receptor CCR6 were expressed in the lesional epithelia. Furthermore, DC-CK1/CCL18, ELC/CCL19, SDF-1/CXCL12 and CXCR4 expressions were also increased. Immunohistologial analysis showed that high numbers of Langerhans cells (LCs) were present in the epithelia of OLP. Lesional epithelia also expressed high levels of the ligands specific for CXCR3 (e.g. MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11) and CCR5 (e.g. RANTES/CCL5). CONCLUSIONS: Infiltration of LCs is orchestrated by CCR6. Further, LCs residing in the lesional epithelia may be a mature phenotype. Moreover, infiltration of T cells in OLP could be mediated by signaling pathways through CXCR3 and CCR5.     

Dorsal inlay graft urethroplasty for primary hypospadiac repair

OBJECTIVE: Tubularized incised plate urethroplasty has become a popular technique for repairing distal and proximal hypospadias in many institutions. Dorsal inlay graft urethroplasty has been used in our institution since 2003 to reduce the risk of meatal stenosis. In the present study, we evaluated the results of the dorsal inlay graft procedure. METHODS: A total of 28 patients with no deep groove and no severe curvature underwent one-stage urethroplasty using an inner preputial-based dorsal inlay graft. The medical records of all patients were retrospectively reviewed with regard to complication rate and cosmetic appearance. RESULTS: Mean patient age at surgery was 21 months (range, 14 months to 4.6 years). Preoperatively the urethral meatus was coronal in two cases, distal shaft in 17, proximal shaft in six and penoscrotal in three. Nine patients required testosterone therapy before surgery. Mean operative time was 200 min (range, 154-249 min). Mean length of inlay graft was 20.9 mm (range, 12-30 mm). In all patients, a straight penis was achieved without dorsal plication of the corposa cavernosa, and the neomeatus with a slit-like appearance was positioned at the glans tip. At a mean of 22 months of follow up, a urethrocutaneous fistula developed in only one patient (3.6%), requiring repair surgery 6 months after urethroplasty. No patient had meatal stenosis, neourethral stricture or urethral diverticulum along the inlay graft. CONCLUSION: Dorsal inlay graft urethroplasty is an effective method for hypospadiac repair and leads to good cosmetic outcome with low risk of complications.     

Effects of Increasing Concentrations of Propofol on Jugular Venous Bulb Oxygen Saturation in Neurosurgical Patients under Normothermic and Mildly Hypothermic Conditions

Background: Recent evidence suggested that propofol can deteriorate the cerebral oxygen balance compared with inhalational anesthetics. However, dose-related influences of propofol on cerebral oxygen balances were not clearly investigated. In the current study, the authors investigated the effects of increasing concentrations of propofol on jugular venous bulb oxygen saturation (Sjo2) in neurosurgical patients under normothermic and mildly hypothermic conditions.

Methods: After institutional approval and informed consent were obtained, 30 adult patients undergoing elective craniotomy were studied. Patients were randomly allocated to either normothermic or hypothermic group (n = 15 in each group). In the normothermic and hypothermic groups, tympanic membrane temperature was maintained at 36.5[degrees] and 34.5[degrees]C, respectively. Sjo2 was measured at predicted propofol concentrations of 3, 5, and 7 [mu]g/ml using a target-controlled infusion system in both groups.

Results: At a predicted propofol concentration of 3 [mu]g/ml, there were no significant differences in Sjo2 values between the normothermic and hypothermic groups, although the incidence of desaturation (Sjo2 < 50%) was significantly higher in the normothermic group than in the hypothermic group (30% vs. 13%; P < 0.05). Sjo2 values and the incidence of desaturation remained unchanged during the changes in predicted propofol concentration from 3 to 7 [mu]g/ml both in the normothermic and hypothermic groups.     

Human Tumor–infiltrating Lymphocytes Transfected with Tumor Necrosis Factor Gene Could Augment Cytotoxicity to Autologous Tumor Cells

Human tumor–infiltrating lymphocytes (TILs) derived from pleural or ascitic fluid were incubated with recombinant interleukin 2 and transfected with human tumor necrosis factor (TNF) a gene by the lipofection procedure. The resulting TILs secreted significant amounts of TNF in the culture supernatant and exhibited cytotoxicity against established cell lines, such as K562 and Daudi, and autologous tumor cells. The TNF gene–transfected TILs exhibited an augmented killing of autologous tumor cells.