Age and stimulus dependency of visually evoked cerebral blood flow responses

BACKGROUND AND PURPOSE: During visual stimulation, the increased metabolic demand is coupled with an increase of cerebral blood flow velocity (pCBFV) in the posterior cerebral artery (PCA). Investigation of the visually evoked flow responses (VEFR, expressed as percentage of increase from baseline pCBFV values) was suggested for different conditions of vasoneuronal disorders in the absence of any systematic investigation in healthy subjects. METHODS: We investigated VEFRs from both PCAs to various increasingly complex paradigms (diffuse light, alternating checkerboard patterns, and a color video movie stimulation; 5, 10, 20, and 30-second intervals) in 60 healthy volunteers (mean age, 41.5+/-14.9 years; range, 24 to 80 years; 28 male, 32 female) at different recording sites (P1 versus P2 segments of PCAs). RESULTS: With increasing complexity of stimulation, the VEFRs increased significantly (24.3+/-10.3%, 28.5+/-13.5%, and 43.4+/-10.7%, respectively). Twenty-second stimulation intervals yielded maximal responses (41.5+/-13.2%) compared with 5-, 10-, and 30-second intervals (22.6+/-14.1%, P=0.001; 34.4+/-11.7%, P=0.0042; and 35.5+/-9.9%, P=0.0032, respectively). Significantly higher responses were gained from P2 segments than from P1 segments (42.7+/-7.2% versus 28.2+/-7.1%). Although VEFRs tended to decrease in amplitude with age (mean, 41. 7+/-10.5% [20 to 40 years], 35+/-9.2% [40 to 60 years], and 33.9+/-8.6% [60 to 80 years]); without significant sex-related differences, only the percentage decrement of the pulsatility indices during stimulation were significant (mean, 24+/-10.7% [20 to 40 years], 20+/-7.3% [40 to 60 years], and 13+/-11.2% [60 to 80 years]). CONCLUSIONS: For optimal stimulus conditions for maximum VEFRs, a colored video stimulation of 20-second intervals should be used to combine responses not only from the primary visual projection fields (V1 and V2) but also from temporal lobe areas (V3 through V5) often supplied by the PCA.     

Biliary secretion of sulindac and metabolites in man

The biliary secretion of sulindac and metabolites after a single 400 mg oral dose of the drug was studied in 3 elective gallbladder surgical patients following placement of an occludable T-tube in the common bile duct. Bile and systemic plasma were sampled at frequent intervals for up to 36 h postdose. The apparent biliary clearance (V?_cl,bilc) of the prodrug sulindac is about 25 times greater than that of the pharmacologically active sulfide metabolite. The total biliary flux of drug in normal man with an uninterrupted enterohepatic cycle, calculated from V?_cl,bile and historic mean plasma drug AUC values, averages 144 and 12·2 per cent of the dose as sulindac and the sulfide metabolite, respectively. Thus, enterohepatic recycling of the drug in man is principally in the form of the prodrug which not only limits exposure of the intestine to the active moiety but also sustains systemic concentrations of active drug upon reabsorption of the prodrug.     

Children can't fly: a program to prevent childhood morbidity and mortality from window falls.

"Children Can't Fly" is a health education program developed by the New York City Department of Health to combat the high incidence of child mortality and morbidity due to falls from windows. The success of the program, begun in 1972, in drastically reducing death and injury persuaded the New York City Board of Health to amend the Health Code in 1976 to require that landlords provide window guards in apartments where children ten years old and younger reside. The law is the first and only one of its kind in the nation. The program has four major components: 1) reporting of falls by hospital emergency rooms and police precincts, followed up by counseling, referral, and data collecting by public health nurses; 2) a media campaign to inform the public and elevate their awareness of the hazards; 3) community education for prevention through door-to-door hazard identification, counseling by outreach workers, community organization efforts with schools, tenant groups, clinics, churches, health care providers, etc; 4) provision of free, easily installed window guards to families with young children living in high-risk areas. Significant reduction in falls resulted, particularly in the Bronx, where reported falls declined 50 percent from 1973 to 1975. The program is one solution to an urgent urban problem which other cities might consider to avert the loss of life and limb, and the corollary financial burden for hospitalization, rehabilitation, and maintenance of the injured and permanently disabled.     

Marrow regeneration after mechanical depletion

The origin of marrow regeneration after mechanical depletion was reinvestigated in mouse chimeras. The results were compatible with the local origin of stem cells from remnants of incompletely removed marrow, but not with their origin from a common precursor of both bone and hemopoietic cell lines. In transplanted femurs depleted by a modified technique of in vivo evacuation of marrow, hemopoietic regeneration failed to occur. The presence of hemopoietic stem cells in the Haversian canals was thus excluded. The demonstration of ample hemopoiesis with minimal bone formation in nondepleted controls in which bone marrow initially became necrotic provided new evidence that osteogenesis was not a prerequisite of hemopoietic regeneration.     

The cholinergic deficit coincides with Abeta deposition at the earliest histopathologic stages of Alzheimer disease

Effective therapeutic intervention in Alzheimer disease (AD) will be most effective if it is directed at early events in the pathogenic sequence. The cholinergic deficit may be such an early event. In the present study, the brains of 26 subjects who had no history of cognitive loss and who were in early histopathologic stages of AD (average Braak stage less than II) were examined at autopsy to determine whether a cortical cholinergic decrement was associated with Abeta concentration or deposition. In the superior frontal and inferior temporal gyri, the choline acetyltransferase (ChAT) activity of plaque-containing cases was significantly decreased (p < 0.05, unpaired, two-tailed t-tests), measuring 70.9% and 79.5%, respectively, relative to plaque-free cases. In the inferior temporal gyrus, Spearman's rank correlation analysis showed that ChAT activity had a significant inverse correlation with Abeta concentration (p = 0.075; r = -0.3552). The results indicate that the cholinergic deficit is established at an early histopathologic stage of AD, before the onset of clinical symptoms.     

Anterior vertebral screw strain with and without solid interspace support

STUDY DESIGN: This in vitro biomechanical study examines segmental anterior vertebral screw strain and solid rod construct stiffness with and without the addition of multilevel, threaded cortical bone dowels in a bovine model. OBJECTIVE: To determine whether strain at the bone-screw interface is higher at the end levels during physiologic range loading, and whether solid interspace support decreases segmental strain on the implant. SUMMARY OF BACKGROUND DATA: Anterior instrumentation provides greater correction and preserves distal motion segments. However, nonunion and implant failure are observed more frequently than with posterior segmental instrumentation, and when observed, loss of fixation occurs at the end levels. METHODS: Eight calf spines underwent mechanical testing in the following sequence: 1) intact condition, 2) anterior release with anterior solid rod and bicortical rib grafts, and 3) anterior release with anterior solid rod and threaded cortical bone dowels (L2-L5). Instrumented vertebral screws were used to assess strain within the vertebral body by the near cortex, whereas an anterior extensometer spanning the instrumented segments was used to measure segmental displacements to calculate construct stiffness. The protocol included axial compression (-400 N), right lateral bending (4 Nm (Newton-meter), away from the implant), and left lateral bending (4 Nm, toward the implant). Statistical analysis included a one-way analysis of variance and a Student-Newman-Keuls post hoc test. A pilot study was performed using four additional specimens loaded for 4000 cycles to investigate macroscopic loosening after fatigue loading. RESULTS: In lateral bending toward the implant, the strain was higher at both end levels, with no differences between the rib and dowel reconstructions. The stiffness values were greater than the intact values for both groups. In lateral bending away from the implant, the strain also was higher at both end screws, and the dowel group had less strain at these levels than the rib group. Both groups were stiffer than the intact condition, and the dowel group was stiffer than the rib group. Axial compressive strain also was higher at the end levels, but this difference did not reach statistical significance. The rib group did not reach intact stiffness values, whereas the dowel group was stiffer than the intact condition. The fatigue study showed gross loosening at one or both end levels in all cases. CONCLUSIONS: Higher strain was observed at the bone-screw interface in both end screws of an anterior solid rod construct during lateral bending, which correlates with the clinically observed failure location. This suggests that physiologic range loading may predispose to failure at the end levels. Disc space augmentation with solid implants increased construct stiffness in all three load paths and decreased strain at the end levels in lateral bending away from the implant. Future implant modifications should achieve better fixation at the end screws, and the current model provides a means to compare different strategies to decrease strain at these levels.