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Biomedical subjects

D J Smith

Publications and source records attributed to D J Smith.

At least 163 records · Page 9Linked to original sources
PubMed1996

TNF-alpha potentiates oxidant and reperfusion-induced endothelial cell injury.

Pulmonary edema following reperfusion is a major clinical problem. Changes in endothelial cell shape induced by oxidant injury may account for immediate capillary leakage associated with reperfusion injury. In these experiments we examined the role of tumor necrosis factor-alpha (TNF-alpha) in acute endothelial cell injury following ischemia-reperfusion. Sprague-Dawley rats were treated with a neutralizing antisera directed against TNF-alpha prior to production of distal ischemia. These rats demonstrated a significant reduction (P < 0.05) in acute lung edema in response to 4 hr of ischemia and 30 min of reperfusion when compared to rats undergoing the same procedure without antisera treatment. An in vitro model was developed to determine if TNF-alpha had a direct effect on endothelial cell response to ischemia-reperfusion. The effects of TNF-alpha and oxidant stress on the integrity of cultured endothelial cell monolayers was measured. Rat pulmonary artery endothelial cell monolayers reacted in vitro to oxidant stress by an increase in permeability. The cells changed shape and an increase in diffusion of 125I-albumin across cell monolayers resulted when these cells were exposed to 50 microM hydrogen peroxide (H2O2) or plasma from the ischemic hind limb of a Sprague-Dawley rat (50 microliters/ml). Pretreatment of cultured cells with low levels of recombinant mouse TNF-alpha significantly affected both the cell shape change and the increase in permeability (P < 0.05). Increased permeability of cell monolayers in vitro was not due to cell lysis as determined by media lactate dehydrogenase levels. The effect appeared to be due to cellular rounding and contraction seen using video time lapse microscopy. These data suggest a direct effect of TNF-alpha on endothelial cells, whereby the cells are rendered more susceptible to oxidant injury accompanying reperfusion.

Acute Disease↗
PubMed1996

Long-term results with the Kasai operation for biliary atresia.

OBJECTIVE: To evaluate long-term outcome in a series of children with biliary results atresia treated by portoenterostomy. DESIGN: Case series of consecutive infants with biliary atresia with 10-year follow-up. Data were obtained by retrospective chart review or phone interview. SETTING: A tertiary academic medical center and regional children's hospital. PATIENTS: A consecutive series of 104 infants diagnosed with biliary atresia more than 10 years ago were evaluated. Eighty-nine had totally obliterated extrahepatic ducts, 4 had proximal hilar cysts (correctable type), and 11 had patency of the gallbladder and distal common duct. INTERVENTIONS: Ninety-eight patients underwent biliary reconstruction and 6 had exploration only. Seventy-four infants underwent reconstruction using a Rouxen-Y with exteriorization. The 11 infants with distal patency underwent a portocholecystostomy ("gallbladder Kasai"). The remainder had various modifications of the Kasai operation. MAIN OUTCOME MEASURES: Survival, liver function, complications, growth, and development. RESULTS: The 6 patients who did not have a portoenterostomy died. Of the 98 who had a reconstruction, 63 died (mean age at death, 27 months; median, 13.4 months), 10 following liver transplantation. Twelve of the 35 survivors ultimately required liver transplants. Twenty-three children are alive more than 10 years after portoenterostomy without the need for transplantation. Two thirds have experienced some manifestation of portal hypertension (ie, variceal bleeding, hypersplenism, ascites). Nineteen patients (79%) are anicteric with normal liver synthetic function and are in an age-appropriate school grade or working and living independently. CONCLUSIONS: We found that surgical correction of biliary atresia offers long-term survival for about one quarter of patients, provides palliation until liver transplantation becomes necessary, and if surgical correction is not feasible, biliary atresia is uniformly fatal. The outlook is good for those children who survived more than 10 years and justifies continued attempts to establish bile flow in infants with biliary atresia.

Adolescent↗
PubMed1996

A non-invasive, three-dimensional, diagnostic laser imaging system for accurate wound analysis.

A PC-based laser imaging system has been developed that can accurately image and analyse three-dimensional (3D) surfaces in healing wound tissue. The device consists of a laser diode and sensor mounted to a motorized, bi-directional, X-Y table. The laser measures the distance to the wound surface as the X-Y table moves over the wound. The laser beam diameter is 1 x 2 mm and can measure distances as small as 8 microns. The distance information from the laser is used to produce the 3D image and to calculate the volume of the wound. The accuracy of this device is demonstrated by measuring rubber model wounds of 0.5, 1 and 2 ml. The per cent error for the 0.5 and 1 ml model wounds was less than 1 per cent and approximately 4 per cent for the 2 ml model. Studies were done in which full-thickness wounds were made on rats and monitored over a two week period. The rats were scanned five times during this period and the wound area and volumes calculated. The laser measurements are compared to measurements using saline and wound thickness multiplied by wound area.

Animals↗
PubMed1996

Human huntingtin derived from YAC transgenes compensates for loss of murine huntingtin by rescue of the embryonic lethal phenotype.

Huntington disease (HD) is caused by expansion of a CAG trinucleotide repeat in exon 1 of a novel gene. The HD protein (huntingtin) plays a critical role in early embryonic development since homozygous targeted disruption of the murine HD gene results in embryonic lethality by day 7.5. To rescue this phenotype by transgene based huntingtin expression it is therefore essential to express the protein early enough in development in the appropriate cells. Since YAC based transgenes are known to be regulated in an appropriate temporal and tissue-specific manner, we sought to rescue the embryonic lethality by breeding YAC transgenic mice expressing human huntingtin with mice heterozygous for the targeted disruption. We generated viable offspring homozygous for the disrupted murine HD gene but expressing human huntingtin derived from the YAC. This result clearly shows that YAC transgene based expression of huntingtin occurs prior to 7.5 days gestation. Additionally, we show that human huntingtin expression in YAC transgenic mice follows an identical tissue distribution and subcellular localisation pattern as that of the murine endogenous protein and that expression levels of 2-3 times endogenous can be achieved. This shows that human huntingtin under the influence of its native promoter, despite differences to the murine protein, is functional in a murine background and can compensate for loss of the murine protein. These results show that YAC transgenic approaches are a particularly promising route to producing an animal model for disorders associated with CAG expansion.

Animals↗
PubMed1996

Diagnosis and management of diving accidents.

Humans experience significant physiological stresses while diving, which can result in disease on occasion. With the increasing popularity of sports diving, it is critical that both physicians and divers be aware of the spectrum of illness associated with diving. An overview of common diving-related disorders is presented. After a brief discussion of relevant physics principles, the clinical presentation of ear and sinus squeeze is covered along with preventive strategies and treatment. This is followed by a discussion of the pathophysiology, clinical settings, and manifestations of pulmonary barotrauma along with a review of the pathophysiology and presentation of decompression illness. Initial emergency measures and referral procedures for decompression related disorders are addressed. A brief discussion of recompression therapy is included.

Accidents↗
PubMed1996

Comparison of critical speed determined from track running and treadmill tests in elite runners.

The purpose of this study was to compare critical speed determined from a field test of maximal effort runs between 3 and 15 min on a running track and a laboratory test of high-speed runs on a treadmill with a 10-km criterion performance. Nine highly trained male runners (VO ++(2max) 67.7 +/- 4.1 ml*kg*min(-1)) participated in the study. Critical speed was determined from three maximal runs (907, 2267.5, and 4081.5 m) on a 453.5-m indoor running track and from three high speed runs on a treadmill. The treadmill speeds were individualized so that exhaustion was reached in approximately 3, 7, and 13 min. All subjects participated in a 10-km cross-country race (measured distance 9.8 km) on a flat and dry course. Track critical speed (293 m*min(-1)) was correlated (r = 0.92, P < 0.001) with race speed (293 m*min(-1)), whereas treadmill critical speed (300 m*min(-1)) had the same correlation but over predicted race performance. It was concluded that although both tests were correlated with 9.8-km race performance, track-determined critical speed was easy to administer with highly trained runners and was very similar to 10-km race speed.

Adult↗
PubMed1996

Diagnosis of silicone gel breast implant rupture by ultrasonography.

To prospectively evaluate the efficacy of ultrasonography in the diagnosis of ruptured silicone gel breast implants, 98 patients (192 implants) underwent preoperative breast ultrasonography prior to silicone gel breast implant removal. The prevalence of implant rupture confirmed at surgery in this group of patients was 62 of the 192 implants (32 percent). Of the 60 implants diagnosed as ruptured by ultrasonography, 46 were confirmed as having visible defects at surgery (true positive) for a positive predictive value of 77 percent. Of the 132 implants diagnosed as intact by ultrasonography, 116 were confirmed as intact at surgery (true negative) for a negative predictive value of 88 percent. Overall, the sensitivity of ultrasonography for implant rupture was 74 percent, and the specificity was 89 percent. These findings demonstrate that ultrasonography is an effective imaging modality for the diagnosis of silicone gel breast implant rupture. Compared with mammography, ultrasonography appears to offer superior sensitivity and specificity without radiation exposure or discomfort. Although magnetic resonance imaging has shown considerable promise in the diagnosis of implant rupture, ultrasonography provides comparable sensitivity at a fraction of MRI's cost.

Breast↗
PubMed1996

Functional roles for granzymes in murine epidermal gamma(delta) T-cell-mediated killing of tumor targets.

Granzymes, a family of serine proteases contained in cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells, play a critical role in killing tumor targets by triggering rapid breakdown of DNA and subsequent apoptosis. We have reported previously that dendritic epidermal T cells, which are skin-specific members of the tissue-type gamma(delta) T-cell family in mice, are capable of killing selected tumor cell lines. Here we report that short-term cultured dendritic epidermal T-cell lines contain significant N-alpha-benzyloxycarbonyl-L-Lys-thiobenzyl esterase activity, produce granzyme A protein, and express constitutively mRNA for granzymes A and B. Messenger RNA expression for granzyme B was also confirmed in freshly procured Thy-1+ epidermal cells (i.e., dendritic epidermal T cells). Finally, preincubation of dendritic epidermal T cell lines with a granzyme inhibitor, dichloroisocoumarin, but not with a cysteine protease inhibitor, E-64, abrogated completely their capacity to trigger DNA breakdown in YAC-1 target cells. These results reinforce the concept that dendritic epidermal T cells represent skin-resident killer cells that share several functional properties with conventional killer leukocytes, thereby playing a local immunosurveillance role against tumor development.

Animals↗
PubMed1996

Experimental immunization of rats with a Streptococcus mutans 59-kilodalton glucan-binding protein protects against dental caries.

Glucan-binding proteins (GBPs) are theoretically important in the molecular pathogenesis of dental caries caused by Streptococcus mutans. The present study evaluated the ability of antibody induced by the S. mutans 59-kDa GBP (GBP59) to affect dental caries caused by experimental infection with S. mutans in a rodent model. Groups of 20-day-old rats were injected twice at 9-day intervals subcutaneously in the salivary gland vicinity with GBP59, glucosyltransferase (GTF), or phosphate-buffered saline (sham injection), each incorporated in an adjuvant. Two weeks after the second injection, GBP59- and GTF-injected rats contained significant levels of salivary immunoglobulin A and serum immunoglobulin G antibody to the respective injected antigens. However, cross-reacting antibody to S. mutans GTF or GBP59 was not induced by the respective antigen. Rats were then orally infected with S. mutans. After 71 days of infection, GBP59- and GTF-injected groups had smaller numbers of S. mutans on their molar surfaces, compared with the sham-injected infected group. Total, sulcal, and smooth-surface molar caries in the GBP59- and GTF-immunized S. mutans-infected groups were each significantly lower (P < or = 0.003) than the respective measures of caries in the sham injected infected group. The results of this investigation demonstrate that immunization with S. mutans GBP59 induces an immune response in rats that can interfere with the accumulation of S. mutans and can reduce the level of dental caries caused by this cariogenic streptococcus. Furthermore, the protective immunity induced by either GBP59 or GTF appears to result from antibodies to independent epitopes since these two S. mutans components do not have a close antigenic relationship.

Animals↗
PubMed1996

Erythropoietin does not demonstrate circadian rhythm in healthy men.

The hormone erythropoietin (Epo) produced in the kidneys in response to hypoxia stimulates the production of red blood cells. We measured serum Epo levels in 26 healthy men over a 24-h period to determine whether Epo is secreted according to a circadian rhythm. Samples were collected every 2-4 h, and Epo was measured by using a radioimmunoassay (INCSTAR Epo-trac). To determine whether blood collection had any effect on Epo production, one-half of the subjects began the collection period in the morning and the other half in the evening. Exercise and the use of prostaglandin inhibitors were prohibited to eliminate fluctuations in Epo production in response to discrete stimuli. The daily Epo concentration for all subjects combined was 15.5 +/- 5.3 (SD) U/l. No significant circadian variation in serum Epo concentrations was observed in either group or when both groups were combined; however, a measure of individual variance was observed (mean deviation = 0.8 +/- 0.4 U/l).

Adult↗
PubMed1996

A brief assessment of executive control dysfunction: discriminant validity and homogeneity of planning, set shift, and fluency measures.

The current study evaluated the discriminant validity and homogeneity of category fluency, Stroop interference, and planning measures of executive dysfunction and introduced a new measure of planning behavior. We compared performance of patients with schizophrenia, Parkinson's disease, and Huntington's disease, which are disorders associated with some impairment of executive function. Findings indicated that all three measures successfully discriminated between patient groups and controls. Correlational analysis suggested a strong association between test scores on these measures, which were only moderately related to performance on nonexecutive function measures. It is concluded that the three tasks are sensitive and relatively homogeneous in their recruitment of executive functions.

Journal Article↗
PubMed1996

Biochemical and pharmacological characterization of multiple beta-endorphinergic antinociceptive systems in the rat periaqueductal gray.

Based on the differential abilities of the opioid antagonists naltrexone and D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 (CTP) to antagonize the antinociceptive action of beta-endorphin and morphine in the rat periaqueducatal gray (PAG), three pharmacologically distinct mechanisms were determined to mediate the antinociceptive effect of beta-endorphin. Two of these mechanisms are unique to beta-endorphin, possess a high affinity for CTP and can be discriminated based on their differential sensitivity to naltrexone. The third mechanism displays characteristics common to that activated by morphine. The results of radioligand binding studies were consistent with these observations. [125I]-beta-Endorphin labeled a population of sites in the PAG which (compared to those labeled by [3H]morphine) displayed a significantly higher affinity for CTP. In addition, a naltrexone-insensitive binding component was identified in the [125I]-beta-endorphin, but not [3H]morphine assays. Furthermore, comparable competitor affinities were determined across assays, suggesting an interaction of the radioligands with common PAG sites. A naltrexone-insensitive component to beta-endorphin antinociception also was identified in studies which evaluated the ability of the antagonist to shift the beta-endorphin dose-response curve. Interestingly, the ability of low doses of CTP and naltrexone to inhibit increasing doses of beta-endorphin was described by a U-shaped dose effect curve. The response to low and high, but not intermediate, doses of beta-endorphin were antagonized by picomole doses of both antagonists. As there was no evidence for allosteric interactions between [125I]-beta-endorphin binding sites in the PAG, it appears that beta-endorphin also may activate pain facilitory mechanisms which counterbalance its overall antinociceptive effect.

Amino Acid Sequence↗
PubMed1996

Comparison of a rapid hepatitis B immunization schedule to the standard schedule for adults.

We report a prospective, randomized, single-blinded trial comparing immunogenicity of rapid (0, 1, and 2 months) versus standard schedule (0, 1, 6 months) hepatitis B vaccinations of healthy adults with recombinant hepatitis B vaccine (Engerix-B, 20 micrograms i.m.) (230 of 234) negative to hepatitis B were randomized and completed the study. Groups were similar in age, weight, race, and obesity rate, but the rapid schedule group had more women. Both groups reached > or = 100 mIU/mL at a similar rate, but a higher seroprotection rate at > or = 500 mIU/mL was reached by the standard schedule. No demographic variables influenced the effect of dose schedule on anti-hepatitis B titer. We conclude that rapid schedule vaccination gives a rate that is quicker than, and identical to, the rate of seroprotection of the standard schedule vaccination.

Adult↗
PubMed1996

Involvement of spinal cholecystokininB receptors in mediating neurotensin hyperalgesia from the medullary nucleus raphe magnus in the rat.

Neurotensin microinjection into the medullary nucleus raphe magnus (RMg) has been shown to both inhibit and facilitate the spinal nociceptive tail-flick reflex in a dose-dependent manner. Our study was designed to determine a potential involvement of spinal cholecystokinin octapeptide (CCK) in mediating neurotensin hyperalgesia from the RMg. Microinjection of neurotensin (50 ng) into the RMg of awake rats produced a facilitation of the tail-flick reflex that was completely inhibited by intrathecal (i.t.) administration of the nonselective CCK receptor antagonist proglumide (100 ng). Conversely, injection of a greater dose of neurotensin (5 micrograms) into the RMg produced an inhibition of the tail-flick reflex that was enhanced by i.t. proglumide. Intrathecal administration of the selective CCKB receptor antagonist L-365260 dose-dependently inhibited neurotensin hyperalgesia from the RMg (ID50 = 0.42 ng) at doses approximately 1000-fold less than that observed with the selective CCKA receptor antagonist devazepide (ID50 = 646 ng). Injection of CCK alone i.t. produced a biphasic response on the tail-flick reflex as lesser doses (0.1-0.3 ng) inhibited the reflex although greater doses (30-100 ng) facilitated it. Similar to supraspinal neurotensin hyperalgesia, the hyperalgesia observed with i.t. CCK (30 ng) was inhibited by i.t. L-365260 (ID50 = 0.59 ng) at doses approximately 1000-fold less than that observed with i.t. devazepide (ID50 = 630 ng). These data indicate that spinal CCK can both inhibit and facilitate spinal nociceptive responses. The facilitation of nociception observed with spinal CCK appears to involve CCKB receptors, which is consistent with the data in our study suggesting that spinal CCKB receptors mediate neurotensin hyperalgesia from the RMg via descending neuronal projections.

Animals↗
PubMed1996

Identification of beta-glucuronidase-resistant diastereomeric glucuronides of 3-hydroxy-3-methyloxindole formed during 3-methylindole metabolism in goats.

Goats were jugularly infused with the pneumotoxin 3-methylindole (3MI; 15 mg/kg, 0.5 microCi/kg) dissolved in cremophor-EL to characterize the urinary metabolites of 3MI in a ruminant specie. Urine was collected for 36 hr after the beginning of a 2-hr infusion period, and 3MI metabolites were purified using reversed-phase HPLC. Goats excreted 3MI as at least 11 distinct metabolites. Metabolites were characterized using a combination of UV spectroscopy, 1H- and 13C-NMR spectroscopy, and negative-ion FAB/MS. Two of the metabolites (E1 and E2), representing approximately 30% of the urinary radioactivity, were unambiguously identified as diastereomeric glucuronides of 3-hydroxy-3-methyloxindole [HMOI; 3-(beta-D-glucosiduronic acid)-3-methyloxindole]. Glucuronide conjugates were investigated using enzymatic and chemical hydrolysis. These ethereal glucuronides were unique in that they were not readily hydrolyzable with bovine beta-glucuronidase, although one of the diastereomers was hydrolyzed sparingly by beta-glucuronidase from Helix pomatia. Treatment of the glucuronides with 6 M HCI for a 2-hr period liberated unconjugated HMOI. Treatment of each diastereomer with dilute acid (pH 3) or dilute alkali (pH 10) was ineffective at hydrolyzing the conjugates. Goats form HMOI from 3MI and extensively glucuronidate the metabolite before excreting it, as opposed to mice that do not conjugate HMOI before excretion. These ethereal glucuronic acid conjugates seem to be unique in that they are essentially resistant to beta-glucuronidase-catalyzed hydrolysis.

Animals↗
PubMed1996

Outcomes research: a primer for plastic surgeons.

The growing emphasis on cost-effectiveness in the United States health care industry has highlighted the need for comprehensive outcomes research in a variety of medical specialties. Currently, there is a relative paucity of reliable data characterizing the long-term results of many medical and surgical treatments. This shortage of outcomes research is particularly acute within plastic surgery where the benefits of treatment are often intangible and notoriously difficult to measure. In evaluating the effectiveness of medical treatment, conventional clinical research has focused primarily on morbidity and mortality as the outcomes of interest. In contrast, current outcome studies assess the results of interventions from the patient's perspective, measuring the impact of medical care on physical functioning, well-being, and quality of life. The resulting data can assist consumers, providers, and payers in making more appropriate health care decisions. As the outcomes movement has matured, it has evolved into two major areas of study: effectiveness research that evaluates the relationships between specific medical interventions and outcomes of care, and quality assessment that seeks to provide the best outcomes at the most reasonable costs. This review details the origins and trends of current outcomes research, examining the implications of this movement for plastic surgery. The growing impact of outcomes data on treatment guideline formulation in both the public and private sectors is also described. Finally, a brief review of outcomes study design, including definition of variables and selection of instruments, is presented.

Cost-Benefit Analysis↗