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Biomedical subjects

A Smith

Publications and source records attributed to A Smith.

At least 1,495 records · Page 83Linked to original sources

Automated donor-recipient identification systems as a means of reducing human error in blood transfusion.

Clerical and administrative errors are the most common mistakes in blood banking, with errors of sample or patient identification accounting for the majority of mistakes. In an effort to reduce the incidence of human errors, three automated donor-recipient identification systems were developed and were evaluated under clinical conditions. After two years of development and bench testing, each set of equipment was tested, along with established procedures, at a large clinical center, a medium-sized community hospital and a regional donor center. Although none of the systems, as tested, proved acceptable under clinical conditions, a great deal was learned about prototype equipment testing in the clinical setting. Future development of identification systems for clinical use should respond to carefully defined problems, apply in all areas of the hospital or donor center, and be convenient and reliable. The development of the equipment should involve established manufacturers and be subject to exacting preclinical testing.

Blood Banks↗

Lead contamination during domestic preparation and cooking of potatoes and leaching of bone-derived lead on roasting, marinading and boiling beef.

Lead concentrations were measured in boiled, mashed potatoes and in baked potatoes that had been prepared and cooked in domestic kitchens. Levels of lead in the boiled, mashed potatoes ranged from below the 1 microgram/kg limit of detection up to 18 micrograms/kg with a mean of 6 micrograms/kg (wet weight). In the large majority of cases the lead in the tap water was the predominant source of the metal. Higher amounts of lead (range 11 micrograms/kg to 56 micrograms/kg, mean 27 micrograms/kg) were present in baked potatoes and this was attributed to soil adhering to the potato skin. The extent of leaching of lead from bone during cooking has also been investigated. For beef stocks there was little evidence to suggest that significant migration of bone lead occurred. For beef casseroles, marinaded in red wine, some leaching did occur from beef joints containing elevated amounts of bone lead; however the levels were all below 350 micrograms/kg and, on average, less than double that found in casseroles prepared from normal joints where the bone lead levels were an order of magnitude less.

Animals↗

Solvent influence on spray-dried biodegradable microspheres.

Microspheres of fixed poly(D,L-lactic acid) (PDLLA) composition--Resomer R104:R202H (30:70)--containing 20% w/w rifampicin have been spray-dried from a range of acetonic, halogenated, and solvent mixtures thereof under constant process conditions to examine the influence of solvent selection on microsphere characteristics. Solubility of the polymer composite in the studied solvents determined the kinetics of polymer deposition during drying. Viscosity studies provided an indirect index of solvent power in ascending order: acetone (ACT) < dichloromethane (DCM) < chloroform (CFM) < halothane (HAL). Accordingly, poorer acetonic solvents produced a more open, porous matrix of increased mean diameter, whereas DCM, CFM and HAL generated more coherent matrices of greater density and elevated glass transition temperature, which significantly retarded drug release. Yield generally increased in parallel with solvent strength and microsphere density consistent with the proposed generalized particle formation mechanism. Residual solvent also increased with particle density, both parameters being interrelated and dictated by the inherent affinity of the polymer composite for individual solvents. In turn, the position of glass transition temperature (Tg) and the quantity of associated polymer stress-relaxation were a direct function of amount and persistence of organic residue. The magnitude of these changes determined the relative rates and extents of microsphere ageing, as measured by drug release studies. In general, rate of drug release increased with Tg, after corrections were made for specific surface area (r2 = 0.963). Overall, solvent choice for spray-drying has a remarkable influence on microsphere characteristics and, accordingly, technological as well as toxicological considerations should be paid during selection of same.

Biodegradation, Environmental↗

Modulation of rifampicin release from spray-dried microspheres using combinations of poly-(DL-lactide).

Microspheres containing 20% w/w rifampicin (RIF) with smooth morphology have been readily prepared from combinations of low, R104 (Mw, 2000) and moderate, R202H (Mw, 9000), molecular weight poly(D,L-lactide) (PDLLA) as a means to modulate drug release from either polymer when used alone. These have been characterized with respect to their drug loading, granulometry, in vitro drug release and thermal behaviour. Particle size distributions were Gaussian, whereby mean microsphere diameter was found to increase from 2.11 to 2.98 microns as the proportion of more viscous R202H increased, whilst > 95% of particles were < 10 microns, irrespective of the polymer blend used. Use of a reduced inlet temperature for spray-drying gave uncharacteristically high production yields in the range of 55.8-80.7% for the process. Encapsulation efficiencies were quantitative with the weight proportion of drug co-dissolved (p < 0.05), yielding microspheres of high and predictable RIF loading. In vitro drug release revealed a dramatic shift in release profile between 40 and 60% R104. Closer examination in this range showed the predicted pattern of increased release rate as the fraction of more hydrophilic R104 increased. However, disproportionate differences were evident between 44 and 48% R104. From the apparent temperature dependent drug release, the criticality of matrix composition was attributed to the coincidence of matrix softening with the dissolution medium temperature and consequent hydration, which, at a finite composition, resulted in a controlled auto-hydration mechanism. Dramatic dependence of release rate with dissolution methodology was accountable to the fact that drug release was considerably quicker where microspheres remained suspended and individualized with the USP paddle method as opposed to aggregated with the shaking bath methodology. In conclusion, the utility of blending racemic PDLLA to modulate drug release and the convenience of spray-drying as a technique to produce microspheres of predictable character have been demonstrated. The temperature-dependent release exhibited may have application in the site-specific delivery of drugs where local increased biochemical activity promotes drug release in response to an increased pharmacological need.

Aerosols↗

Development of an objective structured clinical examination (OSCE) for physical medicine and rehabilitation residents.

Clinical competency is poorly measured by knowledge-based written examinations. A five-station, four-interstation objective structured clinical examination (OSCE) has been developed in consultation with the National Board of Medical Examiners as a pilot study to standardize assessment methods that serve to evaluate the clinical competency of senior physical medicine and rehabilitation residents. Various stations demonstrating musculoskeletal and neurologic conditions commonly encountered in physiatric practice were included, incorporating the use of standardized patients into the OSCE format. This is a descriptive study of individual stations-evaluated history-taking, physical examination, and communication skills, whereas the interstations measured the residents' ability to write therapy and prosthetic/orthotic prescriptions, as well as interpret x-ray and electrodiagnostic data. The OSCE program development including case background, principal tasks, time allotment, evaluation objectives, performance criteria, therapeutic plan, standardized patients case descriptions, and assessment checklists as well as the training procedure is discussed. Additionally, cost analysis and scheduling issues are reviewed. This information should aid other training programs or consortiums in developing similar clinical evaluation tools.

Clinical Competence↗

Hybrid functional electrical stimulation orthosis system for the upper limb: effects on spasticity in chronic stable hemiplegia.

A new hybrid functional electrical stimulation orthosis system for the upper limb has been designed to allow for ease of use in the home as a daily treatment modality, as well as offer the opportunity for function enhancement. In a pilot study, the system was used by ten patients with chronic stable hemiparesis secondary to cerebral vascular accident and head injuries. The patients were referred by their treating physicians or therapists after meeting the inclusion criteria of good general health, being greater than one year after head injury, or being ten months post-stroke, with no observed neurologic changes in the prior six weeks. Each of these patients had received prolonged physical therapy, either continuous from the initial inpatient rehabilitation treatment or on an intermittent basis over a period of years. The baseline status for factors related to increased muscle tone, i.e., passive range of motion at the wrist and elbow, posture at rest, posture immediately following activity, and spasticity were quantified before the treatment protocol with the functional electrical stimulation orthosis. Active range of motion and tests of functional use of the involved upper limb were also assessed. The patients were instructed in the protocol, trained in the use of the system, and then used the electrical orthosis at home for up to several hours per day. Follow-up assessments were at six months. A statistically significant improvement was noted in all muscle tone/spasticity parameters measured. A separate report will describe the effects on voluntary motion and functional capabilities.

Activities of Daily Living↗

Further experience in development of an objective structured clinical examination for physical medicine and rehabilitation residents.

Since the last report, two additional objective structured clinical examinations (PGY-2, PGY-3, and PGY-4, as well as incoming PGY-2) have been administered. As a result, our curriculum has been modified to strengthen physical examination skills, including specific workshops. Interrater reliability of evaluators has been tested for the first time to verify reliability, and refinements have been made in the standardized checklist grading system. The interrater grading of history-taking had good reliability (0.73-0.96), as did neurological and spine physical examination (0.84-0.88). The interrater grading reliability of small and large joint examination was more problematic (0.46-0.62) because of examiners' inability to have full visibility, evaluator's fatigue, and confusing evaluation scoring descriptions. We now use a two-point grading scale (correct or incorrect) for history but continue a three-point scale (correct, partially correct, or incorrect) for physical examination. The examination schedule is being modified to add more encounters, give time for trainee feedback, and further refinement of grading expectations for a more efficient and reliable scoring system.

Clinical Competence↗

Acidification of endosomes is not important for the entry of rotavirus into the cell.

Rotavirus causes enteritis in both man and animals. The mechanism by which this protein-enveloped virus enters the cell to initiate infection is not known. Many viruses depend on the acidification of endosomes for entry into the cell. We studied the importance of the acidification of endosomes for the initiation of two early phases of rotavirus infection, virus RNA and peptide synthesis. Monensin, nigericin, chloroquine and ammonium chloride at a variety of concentrations caused no specific inhibition of virus RNA or peptide synthesis. We conclude that the acidification of endosomes is not important for the entry of rotavirus into the cell.

Animals↗

The study of CTLA-4 and vitamin D receptor polymorphisms in the Romanian type 1 diabetes population.

Several studies suggested that part of the genetic susceptibility for Type 1 diabetes (T1DM) is encoded by some polymorphisms of CTLA-4 gene (2q33) and of Vitamin D Receptor gene (VDR; 12q12-14). Our aim was to assess their contribution to T1DM genetic susceptibility in the Romanian population. We typed CTLA-4 49 A/G and VDR FokI (F/f), ApaI (A/a) and TaqI (T/t) polymorphisms by Sequence Specific Primer PCR (SSP-PCR) in 204 Romanian diabetic families (756 individuals: 212 T1DM probands and 544 unaffected parents and siblings). We studied alleles transmission using the Transmission Disequilibrium Test (TDT). We found an increased transmission of CTLA-4 49G allele to diabetics (54.8%, p=0.11). The transmission of F (56.1%, p=0.063), a (55.7%, p=0.061) and T (51.8%, p=0.37) alleles of VDR gene to diabetics was increased but did not reach statistical significance. In conclusion we found the same increased transmission of CTLA-4 49 G allele to diabetics as previously reported. VDR FoqI F allele seems to be predisposing while TaqI T allele seems to be protective.

Abatacept↗

An automated dosimetry data-acquisition and analysis system at the LAMPF pion therapy facility.

An automated data-acquisition and analysis system has been developed for dosimetry measurements on the pion therapy beam at the Clinton P. Anderson Meson Physics Facility Biomedical Channel in Los Alamos using a PDP-11/45 computer and CAMAC interface. Initialization, test, and monitor programs allow the user to set the physical limits of scanner travel, test the data lines, calibrate the analog signals for the scanner position, and monitor the analog versus digital values of the scanner position during operation. Data-acquisition programs scan beams in one, two, and three dimensions. Many options are available to the user in selecting the scan parameters and in changing some of these parameters during scanning. Data-analysis programs provide reproduction of stored data, comparison of linear scans, beam profiles along any line of a planar or volume scan, and isodose distributions from any planar scan or from any planar scan or from any plane of a volume scan. Other programs summarize stored data files and search for specific data according to the user's instruments.

Computers↗

Laparoscopic environmental changes during surgery enhance the invasive potential of tumours.

OBJECTIVE: The use of laparoscopic techniques in resection of malignant tumours has been proposed to offer potential benefit to the patient in the form of earlier recovery and less immune paresis; however, reported tumour seeding, both peritoneal and at port site, has put this approach into question. The biological effects of the introduction of carbon dioxide or helium to form a pneumoperitoneum on tumour invasion and dissemination are unknown. METHODS: A human colonic adenocarcinoma cell line (SW1222) was exposed to in vitro laparoscopic environment of either carbon dioxide or helium for 4 h, mimicking the duration of a laparoscopic colorectal resection. Alteration in production of matrix metalloproteinase (MMP)-2, MMP-9 and urokinase-type plasminogen activator (uPA) due to exposure to a laparoscopic environment was determined by zymography and correlated to invasive capacity by a standard Matrigel-based invasion assay. Incorporation of specific gelatinase inhibitors or antibodies directed at the uPA receptor was utilized to determine the relative importance of proteases. RESULTS: Exposure to the laparoscopic environment significantly enhanced production of the proteases MMP-2, MMP-9 and uPA. A concomitant enhancement of invasive capacity was also observed, being blocked by specific protease inhibitors. Changes in both protease production and aggression were observable for at least 24 h following the removal of the operative environment, indicating the possible long-term effects of the initial insult. CONCLUSION: Exposure to the laparoscopic environment enhances the invasive capacity of colonic adenocarcinomas via a well-defined protease-determined pathway. It therefore appears likely that tumour cells released into the operative field can be made increasingly aggressive by a laparoscopic operative environment and can thus contribute to disease dissemination.

Adenocarcinoma↗

Relative roles of plaques and tangles in the dementia of Alzheimer's disease: correlations using three sets of neuropathological criteria.

We have performed a quantitative analysis of the amyloid load (plaques), neuritic plaques and neurofibrillary tangles (NFT) in the frontal, temporal and parietal association cortices of autopsied brains from 49 prospectively evaluated patients with Alzheimer's disease (AD) diagnosed according to three sets of published pathological criteria. These patients had been assessed clinically with psychological testing of cognitive abilities within 6 months of death. Correlations were sought between severity of pathological change and cognitive status before death, duration of disease and age at death. Using Khachaturian and CERAD criteria highly positive correlations were obtained between the extent of cognitive deficit and the density of NFT in frontal and parietal lobes. The percentage area of cortex occupied by amyloid in the parietal lobe was correlated to the cognitive deficit only in the CERAD-diagnosed cases. The density of all amyloid plaques (AP) showed no correlation with the extent of cognitive deficit, but the densities of neuritic plaques did correlate with cognitive deficit. Both amyloid load and tangle densities were positively correlated with disease duration. All these correlations were reduced or absent in a subgroup of cases fulfilling the Tierney et al. A3 diagnostic criteria for AD. We found no pathological measure that correlated with the age of patients at death. Amyloid loads and NFT densities showed highly significant but selective positive correlations, the most striking being between temporal lobe NFT density and frontal and parietal lobe amyloid load and between temporal lobe NFT density and frontal and parietal lobe NFT densities. Correlations involving AP density as a measure of amyloid load were almost always less significant than those involving the percentage area of cortex occupied by amyloid, suggesting that the latter measures amyloid load more accurately. However, the highest correlations of NFT densities were with neuritic plaque densities. Overall this study highlights the relevance of neuritic changes (revealed by NFT and neuritic plaques) and the irrelevance of amyloid plaques to the dementia of AD.

Aged↗

Injuries in Junior A ice hockey. A three-year prospective study.

This 3-year prospective cohort observational analysis of elite amateur hockey players ranging in age from 17 to 20 years on a United States Hockey League team describes ice hockey injuries using a strict definition of injury, standardized reporting strategies, and diagnosis by a team physician. One hundred forty-two injuries were recorded for an on-ice injury rate of 9.4 per 1000 player hours. A player was 25 times more likely to be injured in a game (96.1 per 1000 player-game hours) than in practice (3.9 per 1000 player-practice hours). Game-related injuries were more frequent in the third period, and practice-related injuries occurred more often in the first third of the season. Collisions represented 51% of the total injuries. The most common types of injuries were strains, lacerations, contusions, and sprains. The face and the shoulder were most frequently injured. A facial laceration was the most common injury; acromioclavicular joint sprain was the second most common injury. Facial lacerations typically occurred in games and were stick related. Further research is necessary to determine if injuries in Junior A amateur ice hockey can be reduced by mandatory full facial protection, enforcement of existing rules, improvement in shoulder pad design, and by focusing more attention on stretching programs.

Adolescent↗

Functional coupling of human D2, D3, and D4 dopamine receptors in HEK293 cells.

The D2 dopamine receptor is known to be functionally coupled to the inhibition of adenylate cyclase when expressed in a number of mammalian cell lines. However, functional coupling of the recently discovered D3 and D4 dopamine receptor subtypes has been more difficult to demonstrate. In this study, human D2, D3 and D4 receptors were stably expressed separately in human embryonic kidney cells (HEK 293). In these cells, activation of D2, D3 or D4 receptors resulted in the inhibition of forskolin-stimulated adenylate cyclase activity in a dose responsive manner. This activation was prevented by pre-incubation of the cells expressing these receptors with the dopaminergic antagonist haloperidol. Radioligand binding studies using [3H]spiperone confirmed that the atypical neuroleptic clozapine has higher affinity for the human D4 receptor than the D3 or D4 receptors, although only 6-fold higher than the D2 receptor in this study. In addition, ribonuclease protection studies demonstrated the presence of D4 dopamine receptor mRNA in human brain regions.

Adenylyl Cyclases↗

Clinical practice guidelines for the management of orbital cellulitis.

PURPOSE: A retrospective study was performed to review the management of periorbital and orbital cellulitis at Miami Children's Hospital, between January 1, 1993 and February 15, 1996. RESULTS: One hundred and one patients were included in this study. The variables analyzed in this study included age, sex, length of hospital stay, imaging studies, laboratory tests, and microbiology specimens collected. Patients were classified according to the modified Chandler classification. Average length of stay for our patient population was 4.5 days. Data regarding the radiologic studies, laboratory tests, and microbiology yield of specimens were analyzed. CONCLUSIONS: The incidence of orbital infection, manifested by lid swelling alone is much more common (stages I and II) than orbital infection involving postseptal findings (stages III, IV, and V); 84.16% compared with 15.84%, respectively. An updated approach and a general guideline for the management of periorbital and orbital cellulitis according to the clinical staging of the process is presented.

Anti-Bacterial Agents↗

Cystinuria and its relationship to mental retardation.

Urine specimens from 2,073 mentally retarded children have been analysed for their amino acid content, with the aim of determing the relationship of cystinuria and mental retardation. No children homozygous for cystinuria were identified, but 50 heterozygous children were found. This heterozygote incidence is 13 times that expected in our general population.

Adolescent↗

Cystinuria.

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Adolescent↗