Optical coherence tomography velocimetry of colloidal suspensions.

Optical coherence tomography velocimetry combined with a rheometer and optical modulation techniques provides increased sensitivity to the low shear rate motion of complex fluid systems. Optical modulation coupled with a new interferometer design yields improved signal to noise ratios and is demonstrated with optically opaque colloidal suspensions. Thus the measurable range of shear velocities with complex fluids can be as low as ∼40 µm s(-1), more than an order of magnitude improvement on the previous lower limit of ∼700 µm s(-1). Furthermore the apparatus demonstrates improved sensitivity to the measurement of velocity. The instrument was used to study two hard sphere colloidal systems, sterically stabilized PVP spheres of 1 µm radius and sterically stabilized polystyrene spheres of 600 nm radius, which display shear banding behavior due to shear induced concentration gradients. OCT velocimetry also allows the velocity fluctuations of the system to be quantified as a function of the distance across the rheometer gap to help classify underlying unsteady or turbulent phenomena.

Medical terminations of pregnancy: a viable source of tissue for cell replacement therapy for neurodegenerative disorders.

"Proof-of-principle" that cell replacement therapy works for neurodegeneration has been reported, but only using donor cells collected from fetal brain tissue obtained from surgical terminations of pregnancy. Surgical terminations of pregnancy represent an increasingly limited supply of donor cells due to the tendency towards performing medical termination in much of Europe. This imposes a severe constraint on further experimental and clinical cell transplantation research. Therefore, we explore here the feasibility of using medical termination tissue as a donor source. Products of conception were retrieved from surgical terminations over the last 7 years and from medical terminations over the last 2.5 years. The number of collections that yielded fetal tissue, viable brain tissue, and identifiable brain regions (ganglionic eminence, ventral mesencephalon, and neocortex) were recorded. We studied cell viability, cell physiological properties, and differentiation potential both in vitro and following transplantation into the central nervous system of rodent models of neurodegenerative disease. Within equivalent periods, we were able to collect substantially greater numbers of fetal remains from medical than from surgical terminations of pregnancy, and the medical terminations yielded a much higher proportion of identifiable and dissectible brain tissue. Furthermore, we demonstrate that harvested cells retain the capacity to differentiate into neurons with characteristics appropriate to the region from which they are dissected. We show that, contrary to widespread assumption, medical termination of pregnancy-derived fetal brain cells represent a feasible and more readily available source of human fetal tissue for experimental cell transplantation with the potential for use in future clinical trials in human neurodegenerative disease.

Carbon monoxide is a rapid modulator of recombinant and native P2X(2) ligand-gated ion channels.

BACKGROUND AND PURPOSE: Carbon monoxide (CO) is a potent modulator of a wide variety of physiological processes, including sensory signal transduction. Many afferent sensory pathways are dependent upon purinergic neurotransmission, but direct modulation of the P2X purinoceptors by this important, endogenously produced gas has never been investigated. EXPERIMENTAL APPROACH: Whole-cell patch-clamp experiments were used to measure ATP-elicited currents in human embryonic kidney 293 cells heterologously expressing P2X(2), P2X(3), P2X(2/3) and P2X(4) receptors and in rat pheochromocytoma (PC12) cells known to express native P2X(2) receptors. Modulation was investigated using solutions containing CO gas and the CO donor molecule, tricarbonyldichlororuthenium (II) dimer (CORM-2). KEY RESULTS: CO was a potent and selective modulator of native P2X(2) receptors, and these effects were mimicked by a CO donor (CORM-2). Neither pre-incubation with 8-bromoguanosine-3',5'-cyclomonophosphate nor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (a potent blocker of soluble guanylyl cyclase) affected the ability of the CO donor to enhance the ATP-evoked P2X(2) currents. The CO donor caused a small, but significant inhibition of currents evoked by P2X(2/3) and P2X(4) receptors, but was without effect on P2X(3) receptors. CONCLUSIONS AND IMPLICATIONS: These data provided an explanation for how CO might regulate sensory neuronal traffic in physiological reflexes such as systemic oxygen sensing but also showed that CO could be used as a selective pharmacological tool to assess the involvement of homomeric P2X(2) receptors in physiological systems.

Passive and active microrheology of hard-sphere colloids.

We performed passive and active microrheology using probe particles in a bath of well-characterized, model hard-sphere colloids in the fluid state over the whole range of volume fractions below the glass transition. The probe and bath particles have nearly the same size. Passive tracking of probe particles yields short-time self-diffusion coefficients. Comparison with literature data demonstrates that the interaction between probe and bath particles is hard-sphere-like. The short-time diffusivities yield one set of microviscosities as a function of volume fraction, which agrees with previous macrorheological measurements of the high-frequency viscosity of hard-sphere colloids. Using optical tweezers, we measure the force on a trapped probe particle as the rest of the sample is translated at constant velocity. This yields a second set of microviscosities at high Péclet numbers. These agree with previous macrorheological measurements of the high-shear viscosity of similar colloids, at shear-rates below the onset of shear-thickening.

Testing the self-efficacy-performance linkage of social-cognitive theory.

Past empirical research examining the relationship of self-efficacy perceptions and performance has had several limitations. Most studies were performed in the laboratory with tasks not directly related to individual work performance. As a consequence, many findings are not generalizable to individual work performance. This study tested the self-efficacy-performance model found in Bandura's social-cognitive theory in a work setting, with a sample of 776 American university employees, and with discriminant function analyses. Respondents indicated that performance with computers significantly predicted perceptions of high and low self-efficacy. Results provide additional support for social-cognitive theory as outlined by Bandura.

Maintaining physiological pacing in AV block using a new generation single lead VDD pacemaker.

OBJECTIVE: A prospective evaluation of patients with AV block using a single pass lead, VDD pacing system. DESIGN: Fifteen patients with AV block, eight males, seven females, average age 68.1 years (range 22.3 to 86.5) were implanted with the THERA VDD 8948 pacemaker and 5032 single pass steroid eluting lead (Medtronic, Inc). P wave sensing and ventricular thresholds were done predischarge and at one, three, and six months and subsequent six-month periods postimplant. P wave sensing was evaluated with exercise testing and other provocative tests. Twenty-four hour Holter monitoring was done before discharge. Patients were given a quality of life questionnaire pre- and postimplant. SETTING: Tertiary care hospital. RESULTS: Average follow-up was 6.4 months (1.5 to 18). Ventricular thresholds remained stable. P wave amplitude at implant (average 2.2 mV; 1.6 to 3.6) showed a significant decrease at the initial visit (average 1.1 mV, 0.5 to 2.4), however, it remained stable at subsequent visits. This initial decrease had no clinical significance as the maximum atrial sensitivity of the device is 0.18 mV. The 24 hr Holter monitoring confirmed reliable AV synchronous pacing in 14 of 15 patient pacemakers programmed in the VDD mode. The sleep function maintained AV synchrony during nocturnal bradycardia; atrial rate histograms available at follow-up imply appropriate intrinsic rate variation and provocative sensing tests and exercise protocol demonstrated reliable atrial sensing. There was a significant improvement in overall patient well-being score using a quality of life questionnaire. CONCLUSIONS: During the follow-up period, this new generation VDD pacemaker, using a single pass lead, provided reliable AV synchronous pacing for patients diagnosed with AV block and normal sinus node function, as well as improved patient well-being.

Differential performance on Taylor's Manifest Anxiety Scale by black private college freshmen, a partial report.

Distributions of scores from Taylor's 1953 Manifest Anxiety Scale administered to 295 men and 361 women, selected from the 1052 participating students, were presented in graphic form. Means were higher than those reported by Taylor and gender differences were found. Pictorial views of the polygons for both the current freshman data and those for Taylor were similar, including the positive skewness. Results were expected to contribute to refinement of college counseling interventions.

Traumatic rupture of the thoracic aorta: should one always operate immediately?

Although the traditional therapy for blunt traumatic rupture of the thoracic aorta (TRA) is immediate operative repair, there may be a selective role for delayed repair, particularly in patients with head trauma, respiratory failure, or cardiac dysfunction. The present study examines the hypothesis that TRA can be managed by selective delayed operative repair. Clinical data were collected from 59 consecutive patients with TRA at a regional trauma unit. All TRAs were at the aortic isthmus. Patients were retrospectively classified into three groups: group I (n = 12) included patients who either arrived in extremis or rapidly became unstable during triage; group II (n = 3) included patients who had no contraindications to early repair and underwent repair at the time of diagnosis; and group III (n = 44) consisted of patients who because of concomitant injuries or sepsis required initial admission and management in the intensive care unit until their clinical status had improved sufficiently to allow for deliberate delayed operative repair of the TRA. The delay ranged from 1 day to 7 months. Eight patients have yet to undergo repair and remain well at follow-up from 1 to 4 years. Overall survival rates in groups I, II, and III were 17%, 100%, and 82%, respectively. The surgery-related mortality rate in group III was 10% (three patients). Only two (4.5%) patients in group III died as a result of a ruptured aorta within 72 hours of admission. In conclusion, contrary to surgical doctrine, TRA may not require immediate operative repair in all cases, but may instead be managed selectively depending on the patient's clinical status.

Appraisal of a glycopeptide cloaking strategy for a therapeutic oligopeptide: glycopeptide analogs of the renin inhibitor ditekiren.

Among the limitations to the practical therapeutic oligopeptide are low oral availability, indifferent aqueous solubility, and an astonishing efficient sequestration and biliary elimination by a multi-capacity liver transporter. Given the purposed use of N- and O- linked saccharides as functional appendages of eukaryotic peptides and proteins, a strategy of glycopeptide mimicry was examined for the oligopeptide renin inhibitor, ditekiren. The anticipation was that the saccharide would impart significant aqueous solubility, and might impact beneficially on the remaining two limitations. Execution of this approach was achieved by the removal of the (dimethylethoxy)carbonyl amino terminus of ditekiren, and its substitution by Boc-L-asparagine N-linked mono- and disaccharides. Potent hypotensive activity, as measured by a human renin-infused rat assay, is observed for virtually all of these structures (N-linked beta-pyranose D-N-acetyglucosaminyl, D-glucosaminyl, D-N-acetylgalactosaminyl, D-mannosyl, D-galactosyl, D-maltosyl, D-cellobiosyl, D-chitobiosyl, but not L-fucosyl). The basis for this dramatic improvement (relative to ditekiren in the same assay) is the diversion of the peptide clearance from rapid liver biliary clearance to slower urinary clearance (Fisher, J. F.; Harrison, A. W.; Wilkinson, K. F.; Rush, B. R.; Ruwart, M. J. J. Med. Chem. 1991, 34, 3140). Guided by the human renin-infused rat hypertension assay, an evaluation of the linker-saccharide pairing was made. Loss of hypotensive activity is observed upon substitution of the Boc-L-asn by Boc-D-asn, and by removal of the Boc amino terminus of the glycopeptide. Potent hypotensive activity is preserved by replacement of the Boc-L-asn linker by succinate, malate, tartrate, and adipate linkers. With the longer adipate spacer, attachment of the saccharide to the P-3 phenylalanine--with omission of the P-4 proline--retains activity. These data suggest value to the glycopeptide guise for preserving the in vivo activity, and for the beneficial manipulation of pharmacodynamics, of this renin inhibitory oligopeptide. This strategy may have general applicability.

Evaluation of the bile acid transporter in enhancing intestinal permeability to renin-inhibitory peptides.

To evaluate the bile acid transporter as a means of enhancing the ability of renin-inhibitory peptides (RIPs) to penetrate the intestinal mucosa, two RIP-cholic acid conjugates and an RIP-taurocholic acid conjugate were synthesized. Conjugation was through the N-terminus of an RIP and the 3-position of the bile acid, via a six-carbon spacer. An RIP derivative containing the spacer without the bile acid moiety was also synthesized. The bile acid-RIP conjugates and the RIP derivative were shown to be potent inhibitors of human renin in vivo and to have in vivo hypotensive activity equivalent to that of the parent RIP (ditekiren) in a human renin-infused rat model. The ability of these RIP derivatives to bind to the bile acid transporter and be transported across an epithelial cell monolayer was evaluated in an in vitro model of the intestinal mucosa consisting of Caco-2 cell monolayers grown on microporous membranes. One of the RIP-cholic acid conjugate (KI = 60 +/- 10 microM) and the RIP-taurocholic acid conjugate (KI = 19 +/- 5 microM), but not the RIP derivative, were shown to be potent inhibitors of the apical (AP) to basolateral (BL) transport of [14C]-taurocholic acid ([14C]-TA). At concentrations up to 250 microM these RIP-bile acid conjugates had no effect on the diffusion of [3H]-PEG (800-1000), which is a marker of the paracellular pathway. The permeability coefficients of the RIP-bile acid conjugates, determined using Caco-2 cell monolayers, were shown to be six times less than that of [3H]-PEG (800-1000). In addition, the transport of one of the RIP-cholic acid conjugates was investigated in perfused rat ileum in which the mesenteric vein was cannulated. The conjugate was not detected in blood samples taken from the mesenteric vein, while its concentration in intestinal perfusate remained almost constant during the perfusion experiment. These results suggest that while the peptide-bile acid conjugates retain binding affinity for the intestinal bile acid transporter, the molecules are not themselves transported.

A survey of patients in a regional geriatric psychiatry inpatient unit.

The functioning is described of a regional geriatric psychiatry unit with inpatient beds supplemented by an active community team. Data were collected on 100 consecutive patients admitted between November 1985 and July 1986. Eighty-seven per cent of patients were discharged during the course of the study, the majority (66%) to their own homes or to special accommodation houses, 9% to nursing homes, 7% to general hospitals for treatment and 5% to other psychiatric hospitals for social reasons. The patients were characterized by multiple psychiatric and physical disorders, 26% receiving multiple major psychiatric diagnoses. Fifty-two per cent suffered from significant previously recognized physical disorders and 47% had significant physical illnesses diagnosed for the first time during their admission. At the conclusion of the study 7% remained in long-term wards.

Blunt liver trauma at Sunnybrook Medical Centre.

Between 1 June 1976 and 30 June 1985 Sunnybrook Medical Centre Regional Trauma Unit admitted 2,016 patients of whom 220 (11%) sustained liver injury. Of these 220 patients, 211 (96%) sustained blunt liver trauma; 175 of 176 patients who underwent open peritoneal lavage had a true positive lavage. Resuscitation was successful in 212 patients, of whom 209 underwent laparotomy and three were treated nonoperatively: 129 of 209 patients (62%) required only minor surgical treatment; the remaining 80 patients (38%) required major surgical procedures. The overall mortality was 29% (64/220). Eight patients died during resuscitation, one of them of liver hemorrhage. Of the 56 patients who died after admission, the cause of death was head injury in 31, liver hemorrhage in 11 (five intraoperatively) and 14 died of other causes. Overall, liver hemorrhage was the cause of death in 12 of 64 deaths (19%). In other words, 12 of the total of 220 patients (6%) died from liver-related mortality.

New options in the surgical management of Crohn's disease.

Conventional surgical treatment of Crohn's disease involves multiple or extensive resections or bypass procedures. These contribute to the morbidity and mortality of the disease. Minimal resection with appropriate "strictureplasty" is proposed as an alternative approach. Strictureplasty is analogous to pyloroplasty. The authors performed 15 strictureplasties in three patients, all of whom had previously undergone small-bowel resection for Crohn's disease. They presented with symptoms of chronic bowel obstruction resistant to medical therapy. There were two minor postoperative complications. Two patients were asymptomatic 20 months postoperatively; the third required reoperation for recurrent enterovesical fistula. The technique is safe. Its efficacy will be determined by long-term follow-up.

Abdominopelvic computerized tomography and open peritoneal lavage in patients with blunt abdominal trauma: a prospective study.

This prospective trial compares abdominopelvic computerized tomography and open peritoneal lavage in the diagnosis of blunt abdominal trauma. Fifteen patients (group 1) were evaluated by both methods. Another 15 patients (group 2) had only computerized tomography. Criteria for a "positive" scan were hemoperitoneum and evidence of solid organ injury. Criteria for "positive" lavage were a grossly bloody return, erythrocyte count greater than 20.0 X 10(9)/L and leukocyte count greater than 0.5 X 10(9)/L. At laparotomy, only injuries requiring repair or excision were considered "true positive". Patients who did not have laparotomy and had an uncomplicated clinical course were considered "true negative". With tomographic criteria alone for diagnosis there would have been one false-positive and three false-negative results, compared with three false positive and no false negatives for open peritoneal lavage alone. None of the three patients who had negative findings on laparotomy suffered any morbidity or died. Results of computerized tomography and open peritoneal lavage agreed in 8 of 15 patients (kappa value = 0.52), indicating a low level of agreement between the two. The authors believe that open peritoneal lavage remains the diagnostic procedure of choice in blunt abdominal trauma.

Analysis of peritoneal lavage parameters in blunt abdominal trauma.

Peritoneal lavage is the most valuable diagnostic modality presently available for the evaluation of patients with blunt abdominal trauma. A retrospective review of 523 patients who underwent open peritoneal lavage for blunt abdominal trauma over a 3 1/2-year period revealed serious intra-abdominal pathology in 83% of patients undergoing laparotomy with RBC lavage counts in the range of 20,000 to 100,000 cells/mm3, a level considered by many authors to be negative or indeterminate. Two patients with isolated small bowel perforations had an elevated amylase level as the only measured abnormality. The data indicate that the standard guidelines for RBC positivity (positive count greater than 100,000 cells/mm3 and indeterminate count 50,000 to 100,000 cells/mm3) result in missed intraperitoneal injuries in a large percentage of patients and therefore require reevaluation. Lavage amylase determinations, previously stated to be costly and of insignificant yield, should be performed on patients whose lavage would otherwise be considered negative by RBC and WBC counts.

Blunt liver trauma at the Sunnybrook Regional Trauma Unit.

Between June 1, 1976 and Mar. 31, 1983, the Sunnybrook Medical Centre Regional Trauma Unit in Toronto, Ont., admitted 145 patients with liver trauma; of these, 141 (97%) had sustained blunt liver trauma. Of 113 patients who underwent open peritoneal lavage, 112 had a true-positive lavage. Resuscitation was successful in 137 patients and 134 of these underwent laparotomy. Seventy-nine (59%) of the 134 patients required only minor surgical treatment; the other 55 (41%) required major surgical procedures. The overall mortality was 32% (47 of 145). Eight patients died during resuscitation but only one of them died of liver hemorrhage. Of the 39 patients who died after admission, the cause of death was head injury in 22, while 6 died of liver hemorrhage and 11 of other causes. Overall, liver hemorrhage was the cause of death in 15% of cases (7 of 47).

Transluminal angioplasty: results in high-risk patients with advanced peripheral vascular disease.

The role of percutaneous transluminal angioplasty in treating advanced peripheral vascular disease is unknown. The authors therefore reviewed the experience of Sunnybrook Medical Centre in Toronto with 85 consecutive patients who had rest pain, ulceration, pregangrene or gangrene as a result of peripheral vascular disease and who underwent percutaneous transluminal angioplasty. Seventy-four percent were smokers and 91% were at increased risk due to one or more of the following: coronary or cerebral ischemic disease, diabetes mellitus, obesity and hypertension. Thirty-six patients underwent dilatation of iliac lesions, 46 of superficial femoral or popliteal and 3 of more distal lesions. In nine patients angioplasty was repeated on the same lesion. In 16 patients, the procedure was technically unsatisfactory. The morbidity and 30-day mortality were 5% and 2%, respectively. When the procedure was technically satisfactory, surgery was avoided and the limb was salvaged at 1, 2 and 5 years in 69%, 62% and 54% of cases, respectively (life-table analysis). The authors conclude that percutaneous transluminal angioplasty is acceptable treatment for patients with advanced peripheral vascular disease, because the morbidity and mortality are low and the long-term results are good.