Epidemiology of multi-infarct dementia

Multi-infarct dementia (MID), thought to result from the cumulative effect of repeated episodes of cerebral infarction, represents a sizable proportion of the dementia cases in the population. The frequency of MID as the cause of dementia is commonly quoted as 12-20%, but a more conservative figure on the order of 10% is suggested from prospective epidemiologic studies. Its prevalence increases steadily with advancing age, and a male predominance has been noted. Geographical variations in prevalence of MID may reflect true geographic/ethnic differences or lack of uniformity in the use of diagnostic criteria. Risk factors possibly associated with dementia after stroke include advancing age, previous cerebral or myocardial infarction, an atherothrombotic stroke mechanism, and cerebral atrophy as detected by imaging studies. In order to clarify the role of cerebrovascular disease as a cause of dementia, future epidemiologic studies should define the entity in precise terms, and place emphasis on clearly establishing the temporal relationship between stroke and dementia; new onset of dementia should be correlated with the clinical and anatomic features of the stroke.     

Does multi-vessel off-pump coronary artery bypass grafting reduce post operative morbidity compared to on-pump CABG?

Background Cardiopulmonary bypass (CPB) may contribute to the complications and it is assumed that eliminating cardiopulmonary bypass has the potential of reducing post operative morbidity after coronary artery bypass grafting (CABG). The study was carried out to compare mortality and morbidity in the off-pump and on-pump CABG groups. Methods We prospectively analysed 200 patients undergoing CABG. Group A consists of 100 patients underwent multi-vessel off-pump CABG and group B consists of 100 patients underwent CABG with CPB. The incidence of complications (mortality, re-exploration for bleeding, myocardial infarction, atrial fibrillation, neurological events, new onset renal failure (s. creatinine>1.6 mg/dL) pulmonary complications, length of ICU stay and hospital stay were recorded, analysed and compared. Results OPCAB patients received 2.73±0.61 grafts/patient and on-pump CABG patients received 3.39±0.75 grafts/patient (p value<0.00001). There was no significant statistical difference in mortality, incidence of stroke between OPCAB and CABG with CPB patients. Length of ICU stay was 32.84±4.22 vs 44.85±7.18 hrs (p value<0.00001) and hospital stay was 6.52±0.69 vs 7.94±0.92 days (p value<0.00001) between group A and group B respectively. Incidence of atrial fibrillation was less in OPCAB group 7% vs 12% although it was statistically not significant (p value 0.33). It was observed in our study that there was no significant deference in worsening of existing renal failure between on-pump CABG and OPCAB 6% vs 2% (P value 0.28). Blood utilization was significantly less in OPCAB group (p value<0.001). Conclusion There was no statistically significant difference in terms of mortality, incidence of stroke and new onset renal failure in both groups. But there was lesser incidence of post operative atrial fibrillation, worsening of existing renal failure in off-pump group though statistically not significant. There was significant reduction in blood utilization, length of ICU and hospital stay in OPCAB group.     

High human IgG levels in severe combined immunodeficient mouse reconstituted with human splenic tissues from patients with gastric cancer.

We implanted normal peripheral blood lymphocytes (PBL) from healthy donors and splenic tissues from patients with gastric cancers into the severe combined immunodeficient (SCID) mouse, demonstrating that SCID mouse with splenic tissue can produce a high level of human immunoglobulin G (IgG). The normal PBLs at 10(7) and 10(8)/mouse were implanted intraperitoneally, and three splenic tissues with a size of 3 x 3 x 3 mm from gastric cancer patients were inoculated subcutaneously into the bilateral backs of the mice. At 2, 4, 6 and 8 weeks after inoculation, mice were killed, and the human IgG was assessed by an ELISA method. SCID mice with splenic tissue revealed high human IgG levels from 2 weeks after inoculation and approximately 2 mg of IgG per ml was observed at 8 weeks post-implantation, while the IgG levels in mice treated with PBLs were limited. Since the half life of the extrinsic human IgG was 10.2 days, the high level of human IgG in the SCID mice was supposed to be produced by human plasma cells in the splenic tissue from gastric cancer patients. This model was thought to be adequate for evaluating human immunological functions in vivo.     

KT5926, a potent and selective inhibitor of myosin light chain kinase

KT5926, (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-14-n-propoxy-2,3 ,9, 10-tetrahydro-8,11-epoxy, 1H,8H, 11H-2,7b,11a-triazadibenzo[a,g]cycloocta[cde] trinden-1-one, was found to be a potent and selective inhibitor of myosin light chain kinase. The compound inhibited both Ca2+/calmodulin-dependent and -independent smooth muscle myosin light chain kinases to a similar extent. The inhibition was not affected by the concentration of calmodulin. Kinetic analyses showed that the mode of inhibition was of the competitive type with respect to ATP (Ki, 18 nM) and of the noncompetitive type with respect to myosin light chain (Ki, 12 nM). These results indicated that KT5926 directly interacted with the enzyme at the catalytic site. KT5926 also inhibited other protein kinases, but with relatively high Ki values; the values for protein kinase C, cAMP-dependent protein kinase, and cGMP-dependent protein kinase were 723, 1200, and 158 nM, respectively. Ca2(+)-ATPase, Na+/K(+)-ATPase, hexokinase, and 5'-nucleotidase were not inhibited by KT5926 at less than 10 microM. The effect of KT5926 on serotonin secretion and protein phosphorylation induced by platelet-activating factor or phorbol ester was examined in rabbit platelets. KT5926 inhibited the phosphorylation of a 20-kDa protein but had no effect on the phosphorylation of a 40-kDa protein, thereby indicating that the compound exerts its selective inhibition of myosin light chain kinase in intact cells. The compound inhibited serotonin secretion induced by platelet-activating factor, but its potency was significantly less than that of K-252a, (8R*,9S*,11S*)-(-)-9-hydroxy-9-methoxycarbonyl-8-methyl-2,3,9, 10-tetrahydro-8,11-epoxy-1H,8H,11H-2,7b, 11a-triazadibenzo[a,g]cycloocta [cde]trinden-1-one, which inhibited the phosphorylation of both the 20-kDa protein and the 40-kDa protein. Phorbol ester-induced secretion was not suppressed by KT5926. These results provide the evidence that both the 20-kDa protein phosphorylation by myosin light chain kinase and the 40-kDa protein phosphorylation by protein kinase C substantially contribute to the secretion response in platelets.     

Possible downward burster-driving neurons related to the anterior semicircular canal in the region of the interstitial nucleus of Cajal in alert cats.

It is well known that vestibular nystagmus evoked by head rotation occurs in the plane specific to that in which head rotation was applied in three-dimensional space. Although burster-driving neurons (BDN) have been demonstrated for a quick phase of horizontal nystagmus, it is not yet known where the counterpart for vertical nystagmus is located. We analyzed the activity of a class of neurons in the region within, and in the close vicinity of, the interstitial nucleus of Cajal (INC) in alert cats. Their activity gradually increased during an upward slow phase evoked by nose-down pitch. This increased activity was further followed by burst discharge shortly before and during the downward quick phase. Gradually increased activity was also evoked by contralateral roll. These results suggest that the gradually increased activity was evoked by activation of the contralateral anterior canal. Many of these cells were fired by electrical stimulation of the contralateral vestibular nerve with short latencies. These cells also showed burst discharge shortly before and during downward saccades induced by visual stimuli, and the number of spikes during bursts was correlated with saccade amplitudes. Although all had irregular resting discharges, eye-position-related activity was rarely obtained. The characteristic behavior of these cells is very similar, except for their on-directions, to the behavior of horizontal BDNs, suggesting that these INC cells are a candidate for downward BDNs related to the anterior canal.     

Coexistence of paired helical filaments and glial filaments in astrocytic processes within ghost tangles.

Ultrastructural examination of ghost tangles in an autopsy case of long-term Alzheimer's disease revealed, in addition to degenerate neurites containing paired helical filaments (PHF), astrocytic processes which included PHF. This finding suggests either that astrocytes in ghost tangles possess the capacity to produce PHF or that PHF are incorporated into astrocytes by endocytosis.     

Validity of transition-zone dosimetry at high atomic number interfaces in megavoltage photon beams

Measurement of dose or dose perturbation factors at high atomic number interfaces are usually performed with a thin-window parallel-plate ion chamber. In a transition region, under nonequilibrium conditions, accuracy of ion chamber readings for the dose measurements has often been questioned. This paper critically analyzes the factors (stopping power ratio and charge collection) for the dose measurements at interfaces. Monte Carlo simulations were performed to investigate the secondary electron spectrum produced by photon beams and to calculate the stopping power ratios at the point of measurement. The validity of dose measurements was studied for the photon beams in the range of Co-60 gamma rays to 24-MV x rays at bone and lead interfaces with polystyrene, using thermoluminescent dosimeters, extrapolation chamber and several types of commercially available parallel-plate ion chambers. It is observed that for energies greater than 10 MV most parallel-plate chambers can be used to measure dose accurately. At lower energies, however significant differences between measured doses with different detectors were noticed. It is suggested that at high-Z interfaces and lower energies, the dose measurements should be performed with ultrathin-window parallel-plate ion chambers or extrapolation chambers.