Intracranial deep white matter lesions (DWLs) are associated with chronic kidney disease (CKD) and cognitive impairment: a 5-year follow-up magnetic resonance imaging (MRI) study.

Stroke incidence and cognitive decline are related to progression of arteriosclerosis in intracranial DWLs. However, the relationships between DWLs and factors associated with their progression, including CKD, have not been fully elucidated using longitudinal MRI. Of 291 individuals (184 males, 107 females; age 66.9 ± 6.1 years) who had voluntarily participated in a hospital-based health check-up and underwent repeated brain MRI scans in 2003 and 2008, 273 were evaluated in this study. The DWL group included those having DWL without progression, and the DWL progression (DWLP) group included those having an increase in grade number according to the Fazekas classification. Unimpaired age-matched subjects with no brain MRI abnormalities constituted Group C. The Mini-Mental State Examination (MMSE) and verbal fluency tasks were used for objective cognitive evaluations according to the MR evaluation schedule in 2008. Associations between DWLs and vascular risk factors were examined. DWLP occurred in 9.2% of subjects. Compared to Group C subjects, DWL and DWLP group subjects had high odds ratios (ORs) for hypertension (HT) (2.23 and 2.92, respectively) and CKD (1.40 and 2.41, respectively). After adjustment for potential confounders, the ORs of CKD for DWLs remained significant (1.13 and 1.43, p<0.05). DWLs and DWLP were associated with low cognitive scale scores and increased CKD. In conclusion, CKD was associated with DWLs and DWLP as an independent risk factor and a lower level of cognitive function 5 years after CKD was identified. Successful CKD therapy may be expected to prevent DWLP.

A theoretical model for single blastocyst transfer.

OBJECTIVE: To elucidate the relationship between embryo grade and ART outcomes and determine how to decrease multiple pregnancy rates by assigning patients to single embryo transfer (SET) instead of dual embryo transfer (DET) according to embryo grade and/or availability. DESIGN: Retrospective medical record review. SETTING: IVF fertility center. PATIENTS: 247 women undergoing day 5 DET after in vitro fertilization or intracytoplasmic sperm injection treatment. METHODS: We retrospectively investigated embryo grade and outcomes on day 5 DET and calculated theoretical multiple pregnancy rates by assigning patients to SET instead of DET according to a combination of embryo grades and availability. MAIN OUTCOMES MEASURES: Implantation, pregnancy, multiple pregnancy, expected pregnancy and expected multiple pregnancy rates. RESULTS: Embryo grade affects implantation rates so that embryo transfer of at least one embryo with grade > or = 3BB resulted in high multiple pregnancy rates as well as high pregnancy rates. By performing DET, the clinical pregnancy rate was 39.9% with a multiple pregnancy rate of 33.3%; however, had SET been performed with an embryo graded 3BB or better, theoretical calculated pregnancy rates would have dropped to 35.8% but with a multiple pregnancy rate of 7.2%. CONCLUSIONS: Our model showed that cases having at least one embryo with grade > or = 3BB might serve as suitable candidates for SET.

Renal artery pseudoaneurysm occurring after laparoscopic partial nephrectomy.

Renal artery pseudoaneurysm (RAP) is rare, and has been reported after renal biopsy and percutaneous renal surgery. We report a case of RAP after laparoscopic partial nephrectomy for renal cell carcinoma.

[Carcinomatous pericarditis successfully treated with thoracoscopic pericardial fenestration; report of a case].

We report a case of malignant pericardial effusion after lung cancer surgery treated with thoracoscopic pericardial fenestration. The patient was admitted to our hospital because of dyspnea. Computed tomography (CT) and ultrasound cardiography (UCG) revealed cardiac tamponade which was diagnosed as carcinomatous pericarditis by cytology. We attempted to inject 25 mg of cisplatin (CDDP) into the pericardial space twice. The response of the treatment was unexpectedly poor for the patient. The thoracoscopic pericardial fenestration was performed and the patient was discharged without a drainage tube on the 17th postoperative day. Malignant pericardial effusion is a common complication of advanced cancers and is often associated with significant morbidity. Thoracoscopic pericardial fenestration appears to be a safe, effective and minimally invasive treatment for patients with malignant pericardial effusion. This surgery might also have a favorable effect on the improvement of the quality of life for patients with malignant pericardial effusion resistant to chemotherapy.

Retroperitoneoscopic radical nephrectomy in obese patients: outcomes and considerations.

OBJECTIVE: To determine whether obesity is associated with surgical outcome in Japanese patients undergoing retroperitoneoscopic radical nephrectomy (RRN). PATIENTS AND METHODS: Between November 1999 and March 2005, we performed 98 RRN procedures for patients with renal cell carcinoma. Patients with a body mass index (BMI) of 25.0 or more were defined as obese (group A, n=33) and those with a BMI of <25.0 were defined as non-obese (group B, n=65), in accordance with the criteria of the Japan Society for the Study of Obesity. Patient background, degree of surgical invasiveness, and period of convalescence were compared between groups A and B. RESULTS: No statistically significant differences were observed between the groups in terms of age, gender, tumor laterality, tumor size, and time until resumption of oral intake and ambulation. However group A had a significantly longer insufflation time (172.1 vs. 137.4 min), greater blood loss (195.3 vs. 48.4 ml) and higher renal specimen weight (440.0 vs. 306.0 g) than group B. CONCLUSION: Obesity is not a factor that affects patient eligibility for RRN, but is a risk factor for longer insufflation time and greater blood loss.

Increased serum resistin levels in patients with type 2 diabetes are not linked with markers of insulin resistance and adiposity.

The role of resistin in human biology remains uncertain. We measured serum resistin levels in Japanese patients with (n=111) and without (n=98) type 2 diabetes mellitus and investigated the significance of this hormone in the pathophysiology of diabetes. The levels of serum adiponectin and leptin were also measured. Resistin levels were increased significantly in patients with type 2 diabetes compared with non-diabetic subjects (24.7+/-2.6 vs. 15.0+/-1.2 ng/ml, p=0.0013). However, there was no correlation in either patient group between serum resistin levels and markers of insulin resistance, obesity or hyperlipidaemia. These results were in direct contrast to the data of leptin or adiponectin, both of which were closely related to these clinical markers of diabetes. Multivariate regression analysis on the combined data of the two groups demonstrated that the presence of diabetes and HDL cholesterol levels were significant predictors of serum resistin levels (diabetes: beta=0.159, p=0.035; HDL: beta=-0.172, p=0.039). No correlation was observed between C-reactive protein and resistin adjusted for BMI. Taken together, these findings demonstrate that serum resistin levels are increased in patients with type 2 diabetes, but this increase is not linked to markers of insulin resistance or adiposity. Further studies are necessary to elucidate the significance of serum resistin concentration in human pathophysiology.

[Large cell neuroendocrine carcinoma of the lung; report of a case].

Large cell neuroendocrine carcinoma (LCNEC) is a rare type of lung cancer and it has the least favorable prognosis. We describe our experience with a patient in whom LCNEC was diagnosed. A 65-year-old man who was pointed out abnormal shadow on a chest X-ray film in the health screening was admitted to the hospital. Chest X-ray film and computed tomography (CT) scan showed a 4 x 3 cm mass in the left-S2. Poorly differentiated adenocarcinoma of the left lung was suspected based on CT guided cytology. An upper lobectomy of the left lung and dessection of the mediastinal lymph nodes were performed. This tumor showed light microscopic and immunohistochemical evidences of neuroendocrine differentiation. Further it showed positive responses in neuronspecific enolase (NSE), synaptophysin, and chromogranin-A stainings. Pathological diagnosis was stage IB (pT2N0M0) LCNEC. There have been no findings of tumor recurrence 22 months after the operation.

Fluctuations of source locations of EEG activity during transition from alertness to sleep in Alzheimer's disease and vascular dementia.

Vascular dementia (VaD) differs from Alzheimer's disease (AD) in larger fluctuations of cognitive impairment, hypothetically because of deteriorated vigilance control. Vigilance levels are reflected by locations of EEG sources. Transition from alertness to sleep might be particularly sensitive to degradations of vigilance control. Twelve AD and 12 VaD patients (medication free, mean age 75.6 and 77.6 years, respectively, difference = n.s.), and 12 healthy elderly subjects (mean age 70.6 years), who served as controls, were studied (each group comprised 2 males and 10 females). A twenty-one-channel EEG was recorded from full alertness to the onset of sleep stage 2. Dipole source modeling, based on Fast Fourier Transform dipole approximation, yielded 3D source localizations in 7 EEG frequency bands. For each brain axis, means of source location differences between successive 20-second periods were calculated (fluctuation magnitude). EEG band-wise MANCOVAs (3 brain axes, 3 subject groups, covariate: age) showed differences in fluctuation magnitude between groups in the 10.5- to 12-Hz alpha(2) frequency band (p=0.0066). Post hoc ANCOVAs for the axes (3 subject groups, covariate: age) were significant on the superior-inferior axis: VaD patients had higher fluctuations than AD patients and controls, without significant difference between the latter two. Thus, larger source fluctuations in VaD might reflect the patients' decreased vigilance control, accounting for their increased fluctuations of cognitive impairment.

Spatial organization of EEG activity from alertness to sleep stage 2 in old and younger subjects.

In order to elucidate brain mechanisms that contribute to the increased tendency for vigilance dysregulation in the elderly, we examined the spatial organization of brain electric activity [electroencephalogram (EEG)] during decreasing vigilance from alertness to onset of sleep stage 2, comparing 7 old and 10 younger, healthy subjects (60-79 and 18-41 years old, respectively). Two features were analyzed: (1) change of location of the brain electric source gravity centers of the EEG frequency bands, and (2) magnitude of fluctuation of these locations over time. Multichannel EEG was analyzed into source gravity center localizations for seven EEG frequency bands, using fast Fourier transform (FFT) Dipole Approximation (first principal component-single source modeling in the frequency domain). Multivariate analysis of covariance (MANCOVA) showed: source localizations were more anterior in old than younger subjects for beta-1 and more superior for all three beta bands; from alertness to sleep, delta and theta EEG sources (inhibitory activity) changed to more posterior and superior areas, and alpha-1 and -2 (routine activity) and beta-1 and -2 sources (excitatory activity) towards anterior and superior areas. Fluctuations of the source locations of delta and beta-2 were larger on the superior--inferior axis, and of beta-2 smaller on the left-right axis in the old than younger subjects. The results suggest functional specifications (inhibitory, routine, excitatory) of cortical positron emission tomography (PET) changes reported in sleep. In sum, aging exhibits changes in spatial organization of EEG-generating neuronal assemblies; during the transition wakefulness-to-sleep, aging affects the spatial-temporal dynamics of this organization. The latter is suggested to contribute to the increased risk for consciousness disturbances in the elderly.

[Comparison of mediansternotomy approach vs left thoracotomy approach for distal aortic arch aneurysm, and their postoperative complications].

We performed surgery for distal arch aneurysm in 22 patients; through a mediansternotomy in 11 patients (group M), and through a left thoracotomy approach in 11 patients (group L). If the distal position of an aneurysm was located at the pulmonary hilus without severe calcification of the ascending aorta, the mediansternotomy approach was chosen, whereas if we suspected that distal anastomosis would be difficult due to severe calcification of the descending aorta or aortic dissection type B, the left thoracotomy approach was selected. The mean cardiopulmonary bypass time (min.) was 229 +/- 56 in group M and 225 +/- 47 in group L, the mean circulation arrest time (min.) was 39 +/- 19 in group M and 31 +/- 5 in group L, and the mean lowest temperature (degree C) was 22 +/- 1 in group M and 20 +/- 2 in group L. No severe cerebral or cardiac complications developed in any patients. The hospital mortality was 9% (1/11) in group M and 9% (1/11) in group L. Following discharge, 8 (73%) patients from group M and 9 (92%) from group L resumed a normal lifestyle. There were no significant differences between the 2 groups and the operative results of both approaches proved satisfactory. Therefore our indications for each surgical approach to treat distal arch aneurysm seemed appropriate.

Initial pathological events in renal dysplasia with urinary tract obstruction in utero.

Multicystic dysplastic kidneys (MCDK) and obstructive renal dysplasia (ORD) are two different phenotypes of dysplasia commonly associated with urinary tract obstruction. However, the mechanisms whereby obstruction in the developing kidney leads to each dysplasia are unknown. In the present study, 16 fetal MCDKs and 3 fetal ORDs (18-35 weeks of gestation) were analyzed with light microscopy, point-counting morphometry, immunohistochemistry with a podocyte marker, and scanning electron microscopy. Additionally, reconstructions of dysplastic nephrons were done via serial section analysis. Early stages of MCDK and ORD similarly revealed numerous cyst formations, predominantly in the subcapsular nephrogenic zone. Occasionally, glomerular tuft remnants with mature podocyte phenotypes were observed in cysts, suggesting the acquisition of filtration. Three dimensionally, basic nephron structures were installed in the cystic nephrons, namely the macula densa with a primary loop structure. Cysts developed in the once-induced nephrons due to fluid retention in both MCDK and ORD. In utero urinary tract obstruction may cause urine retention in functioning nephrons and lead to glomerular cysts in the nephrogenic zone. These findings were common to MCDK and ORD, albeit at different sites of obstruction. Expansion of glomerular cysts with tubular dilatation (cysts) disturbs the subsequent nephrogenesis and may contribute to the misdevelopment of fetal kidneys.

Development of bronchial hyperresponsiveness during childhood.

Bronchial hyperresponsiveness (BHR) produces the characteristic pathological abnormalities seen in asthma and clearly plays a central role in the pathophysiology of asthma. The presence of BHR has been demonstrated in infants with asthma, as has the possibility of BHR persisting through the childhood period. The level of BHR may not only reflect the state of the airways, as a marker of airway dysfunction, but may also predict the persistent prognosis of the disease. Thus, measurement of BHR may provide important information about the symptoms and lung function in children with asthma. In view of multiple pathophysiological mechanisms, BHR does not seem to have a single cause. Many potential confounding variables, such as age, gender and genetic status, and some environmental factors, such as allergens, infections, and pollutants, could be responsible for the establishment of childhood BHR. There may be differences between the mechanisms that induce transient BHR and the mechanisms that induce persistent BHR. Also, there may be differences between the causes that induce BHR in the infantile period and the causes that maintain persistent BHR during childhood asthma. There is also disagreement as to the most suitable method to measure BHR in children, especially in infants. The assessment of BHR in young children has not been uniformly successful, and measurements of BHR changes over the childhood period (are associated with a number of problems. To resolve these problems, there may be two ways to study childhood BHR. One is to use age-matched specific techniques to clarify the precise BHR in each age group; the other is to use simple techniques that can be performed over the childhood period on a large number of subjects. In studies of infantile respirator, dysfunction the ultimate goal is to establish a simple, noninvasive method by which measurements of respiratory function may be obtained in infants. Further investigations and acceptable methods will be needed to clarify, the mechanisms involved in the establishment of asthma throughout the childhood period.

BCG inoculation and corticosteroid sensitivity.

PURPOSE: This study was conducted to clarify the relationship between Bacille de Calmette-Guérin (BCG) inoculation and corticosteroid sensitivity. METHODS: Lewis and WKAH rats were inoculated with BCG vaccine weekly beginning at six weeks of age. At 15 weeks, spleen cells were cultured with PHA and betamethasone for 24 hours. RNA was extracted and interleukin-2 gene expression was measured using a real-time PCR method. RESULTS: BCG inoculation sensitized Lewis rats, but not WKAH rats, to PPD stimulation. In Lewis rats, IL-2 gene expression increased after BCG inoculation, while betamethasone suppressed IL-2 expression. In WKAH rats, the expression of IL-2 was not affected by repeated BCG inoculations and betamethasone had no effect on BCG-treated rats. CONCLUSION: BCG inoculation may affect steroid sensitivity in some strains of rats.

Donepezil for Alzheimer's disease: pharmacodynamic, pharmacokinetic, and clinical profiles.

Donepezil was developed in order to overcome the disadvantages of physostigmine and tacrine. Its use is based on the cholinergic hypothesis. Donepezil is a piperidine-based, reversible acetylcholinesterase inhibitor, that is chemically unrelated to other cholinesterase inhibitors. It was developed for the symptomatic treatment of Alzheimer's disease (AD). Donepezil is highly selective for acetylcholinesterase with a significantly lower affinity for butyrylcholinesterase, which is present predominantly in the periphery. Phase I and II clinical trials demonstrated donepezil's favorable pharmacokinetic, pharmacodynamic and safety profile. There is no need to modify the dose of donepezil in the elderly or in patients with renal and hepatic failure. Pivotal phase-III trials in the US, European countries, and Japan showed that donepezil significantly improved cognition and global function in patients with mild to moderate AD. In long-term trials, donepezil maintained cognitive and global function for up to 1 year prior to the resumption of gradual deterioration. Donepezil is generally well tolerated; most of its adverse events are mild, transient and cholinergic in nature. Donepezil produces no clinically significant changes in laboratory parameters, including liver function. The drug is approved for the treatment of mild to moderate Alzheimer's disease, but donepezil therapy does not have to be discontinued if a patient continues to deteriorate. Possible new indications for donepezil in psychiatric and neurologic diseases, other than AD, include dementia with Lewy bodies, brain injury, attention deficit hyperactivity, multiple sclerosis, Down's syndrome, delirium, mood disorders, Huntington's disease and sleep disorders.

Analysis of B cell epitopes of a glycoprotein porcine zona pellucida (pZP1).

The zona pellucida (ZP) of mammalian oocytes forms an extracellular matrix composed of three major glycoproteins and plays an important role in sperm-zona interactions. As ZP had a strong organ-specific but species-cross-reactive antigenicity and passive or active immunization with ZP antigens could impair fertilization, the possibility of developing a immunocontraceptive vaccine has been extensively studied. Studies on active immunization with porcine ZP (pZP) that contain B cell epitopes and T cell epitopes demonstrated that a temporary infertility could be induced along with the elevation of antibody titers, but it was always associated with ovarian failure. This could be due to the oophoritis by activation of pathogenic T cell immunity. It is the general consideration that any adverse effects by vaccination should be avoided for an immunocontraception. From this point of view, the analysis of B cell epitopes of pZP protein would be helpful for construction of a safe immunocontraceptive vaccine with zona antigens. We determined the amino acid sequence of the B epitope in the pZP1 protein by using a monoclonal antibody (MAb-5H4) that possesses a fertilization blocking ability. In addition, antiserum raised to the epitope sequence was revealed to block in vitro fertilization of homologous animal species.

Quantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer's disease.

The present study evaluated the clinical course of patients with mild cognitive impairment (MCI), the pattern of electroencephalography (EEG) changes following cognitive deterioration, as well as the potential of neurophysiological measures in predicting dementia. Twenty-seven subjects with MCI were followed for a mean follow up period of 21 months. Fourteen subjects (52%) progressed (P MCI) to clinically manifest Alzheimer's disease (AD), and 13 (48%) remained stable (S MCI). The two MCI subgroups did not differ in baseline EEG measures between each other and the healthy controls (n = 16), but had significantly lower theta relative power at left temporal, temporo-occipital, centro-parietal, and right temporo-occipital derivation when compared to the reference AD group (n = 15). The P MCI baseline alpha band temporo-parietal coherence, alpha relative power values at left temporal and temporo-occipital derivations, theta relative power values at frontal derivations, and the mean frequency at centro-parietal and temporo-occipital derivations overlapped with those for AD and control groups. After the follow-up, the P MCI patients had significantly higher theta relative power and lower beta relative power and mean frequency at the temporal and temporo-occipital derivations. A logistic regression model of baseline EEG values adjusted for baseline Mini-Mental Test Examination showed that the important predictors were alpha and theta relative power and mean frequency from left temporo-occipital derivation (T5-O1), which classified 85% of MCI subjects correctly.