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Biomedical subjects

L Finch

Publications and source records attributed to L Finch.

At least 19 recordsLinked to original sources
PubMed2001

Serum insulin-like growth factor-I (IGF-I) does not correlate positively with isometric strength, fatigue, and quality of life in post-polio syndrome.

OBJECTIVES AND BACKGROUND: To determine if serum insulin-like growth factor-I (IGF-I) levels are associated with strength, body mass index (BMI), fatigue, or quality of life in post-poliomyelitis syndrome (PPS). PPS is likely due to a distal disintegration of enlarged post-polio motor units as a result of terminal axonal sprouting. Age-related decline in growth hormone and IGF-I (which support terminal axonal sprouts) is proposed as a contributing factor. METHODS: As part of the North American Post-Poliomyelitis Pyridostigmine Study (NAPPS), baseline data on maximum voluntary isometric contraction (MVIC), BMI, subjective fatigue (fatigue severity scale, Hare fatigue symptom scale), health-related quality of life (short form health survey-36; SF-36), and serum IGF-I levels were gathered on 112 PPS patients. Pearson correlation coefficients were calculated to evaluate the association between serum IGF-I and MVIC in 12 muscles, BMI, two fatigue scales, and SF-36 scale scores. RESULTS: There is a significant inverse correlation of IGF-I levels with MVIC in left ankle dorsiflexors (r=-0.30, P<0.01), and left and right knee extensors (r=-0.22, -0.25, P=<0.01, 0.01), but no significant correlations in other muscles. When men and women were evaluated separately, inverse correlations of IGF-I levels with MVIC were found only in men. IGF-I correlated inversely with BMI (r=-0.32, P=0006) and age (r=-0.32, P=0.0005). IGF-I did not correlate with the fatigue or SF-36 scales. CONCLUSIONS: In this exploratory study, we found that contrary to our expectations, IGF-I did not correlate positively with strength. IGF-I correlated negatively with strength in several lower extremity muscles, BMI, and age. IGF-I is likely not an important factor in the pathogenesis of fatigue and in determining quality of life in PPS, but its role on strength should be studied further.

Adult↗
PubMed2001

A hybrid computational fluid dynamics and physiologically based pharmacokinetic model for comparison of predicted tissue concentrations of acrylic acid and other vapors in the rat and human nasal cavities following inhalation exposure.

To assist in interspecies dosimetry comparisons for risk assessment of the nasal effects of organic acids, a hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of inhaled vapors in the rat and human nasal cavity. Application to a specific vapor would involve the incorporation of the chemical-specific reactivity, metabolism, partition coefficients, and diffusivity (in both air and tissue phases) of the vapor. This report describes the structure of the CFD-PBPK model and its application to a representative acidic vapor, acrylic acid, for interspecies tissue concentration comparisons to assist in risk assessment. By using the results from a series of short-term in vivo studies combined with computer modeling, regional nasal tissue dose estimates were developed and comparisons of tissue doses between species were conducted. To make these comparisons, the assumption was made that the susceptibilities of human and rat olfactory epithelium to the cytotoxic effects of organic acids were similar, based on similar histological structure and common mode of action considerations. Interspecies differences in response were therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The results of simulations with the seven-compartment CFD-PBPK model suggested that the olfactory epithelium of the human nasal cavity would be exposed to tissue concentrations of acrylic acid similar to that of the rat nasal cavity when the exposure conditions are the same. Similar analysis of CFD data and CFD-PBPK model simulations with a simpler one-compartment model of the whole nasal cavities of rats and humans provides comparable results to averaging over the compartments of the seven-compartment model. These results indicate that the general structure of the hybrid CFD-PBPK model applied in this assessment would be useful for target tissue dosimetry and interspecies dose comparisons for a wide variety of vapors. Because of its flexibility, this CFD-PBPK model is envisioned to be a platform for the construction of case-specific inhalation dosimetry models to simulate in vivo exposures that do not involve significant histopathological damage to the nasal cavity.

Acrylates↗
PubMed2000

Preoperative embolization of cerebral arteriovenous malformations with silk sutures: analysis and clinical correlation of complications revealed on computerized tomography scanning.

OBJECT: The aim of this study was to determine the incidence and clinical significance of complications related to preoperative embolization of cerebral arteriovenous malformations (AVMs) with silk sutures as documented on postprocedure computerized tomography (CT) scans. METHODS: The CT scans were obtained within 12 to 24 hours after 221 (96%) of 230 consecutive embolizations in 70 patients. These CT scans were evaluated for the presence of ischemia, infarction, hemorrhage, or contrast agent extravasation. Adverse patient outcomes were determined after each embolization and were correlated with CT findings. New abnormalities demonstrated on CT scans were also correlated with the Spetzler-Martin AVM grade, degree of arteriovenous shunting, and location. New abnormalities, the majority of them infarcts, resulted from 29 (13%) of 221 embolization procedures. In 11 (38%) of 29 cases of new CT findings, patients were asymptomatic, including 10 with new infarcts on CT scans. New neurological deficits occurred in 20 (8.7%) of 230 total embolization procedures in 19 patients, including one death. Permanent deficits occurred in nine patients (3.9% per embolization procedure, 12.8% per patient). Of the patients with new neurological deficits, 18 (90%) of 20 embolization procedures resulted in new abnormalities on CT scans. Two patients with new transient neurological deficits had no new findings on CT scans. Spetzler-Martin grade, AVM location, degree of arteriovenous shunting, and higher numbers of procedures were not statistically associated with a higher incidence of abnormalities on CT scans or new permanent neurological deficits. CONCLUSIONS: Silk sutures are an effective and relatively safe embolic agent. After brain AVM embolization with silk sutures, new abnormalities were found on CT scans obtained in one of eight procedures. When a new CT finding occurred, the patient had roughly equal chances of having no new symptoms, having new transient neurological deficits, or having new permanent neurological deficits.

Adult↗
PubMed1999

A multicenter, randomized, double-blinded trial of pyridostigmine in postpolio syndrome.

BACKGROUND: Postpoliomyelitis syndrome (PPS) is likely due to degeneration and dysfunction of terminal axons of enlarged postpolio motor units. Age-related decline in growth hormone and insulin-like growth factor (IGF-I) may be a contributing factor. Neuromuscular junction abnormalities and decreased IGF-I levels may respond to the anticholinesterase pyridostigmine, with consequent improvement in strength, fatigue, and quality of life. OBJECTIVES: To determine the effect of pyridostigmine in PPS on health-related quality of life, isometric muscle strength, fatigue, and serum IGF-I levels; and to assess the safety of pyridostigmine in PPS. METHODS: The study was a multicenter, randomized, double-blinded, placebo-controlled trial of a 6-month course of pyridostigmine 60 mg three times per day in 126 PPS patients. The primary data analysis compared mean changes of outcomes between treatment and control groups at 6 months using an intention to treat approach. Secondary analyses included a comparison of outcomes at 6 and 10 weeks, and in compliant patients. RESULTS: The study showed no significant differences in pyridostigmine and placebo-treated patients with regard to changes in quality of life, isometric strength, fatigue, and IGF-I serum levels at 6 months in the primary analysis and in compliant patients. There were no differences in outcomes at 6 and 10 weeks between groups. However, very weak muscles (1 to 25% predicted normal at baseline) were somewhat stronger (p = 0.10, 95% CI of difference -9.5 to 73.3%), and in compliant patients IGF-I was somewhat increased (p = 0.15, 95% CI of difference -6.4 to 44.8 ng/mL) at 6 months with the medication. Pyridostigmine was generally well tolerated. CONCLUSIONS: This study showed no significant differences between pyridostigmine and placebo-treated PPS patients on measures of quality of life, isometric strength, fatigue, and serum IGF-I.

Aged↗
PubMed1998

Application of a hybrid computational fluid dynamics and physiologically based inhalation model for interspecies dosimetry extrapolation of acidic vapors in the upper airways.

This study provides a scientific basis for interspecies extrapolation of nasal olfactory irritants from rodents to humans. By using a series of short-term in vivo studies, in vitro studies with nasal explants, and computer modeling, regional nasal tissue dose estimates were made and comparisons of tissue doses between species were conducted. To make these comparisons, this study assumes that human and rodent olfactory epithelium have similar susceptibility to the cytotoxic effects of organic acids based on similar histological structure and common mode of action considerations. Interspecies differences in susceptibility to the toxic effects of acidic vapors are therefore assumed to be driven primarily by differences in nasal tissue concentrations that result from regional differences in nasal air flow patterns relative to the species-specific distribution of olfactory epithelium in the nasal cavity. The acute, subchronic, and in vitro studies have demonstrated that the nasal olfactory epithelium is the most sensitive tissue to the effects of inhalation exposure to organic acids and that the sustentacular cells are the most sensitive cell type of this epithelium. A hybrid computational fluid dynamics (CFD) and physiologically based pharmacokinetic (PBPK) dosimetry model was constructed to estimate the regional tissue dose of organic acids in the rodent and human nasal cavity. The CFD-PBPK model simulations indicate that the olfactory epithelium of the human nasal cavity is exposed to two- to threefold lower tissue concentrations of a representative inhaled organic acid vapor, acrylic acid, than the olfactory epithelium of the rodent nasal cavity when the exposure conditions are the same. The magnitude of this difference varies somewhat with the specific exposure scenario that is simulated. The increased olfactory tissue dose in rats relative to humans may be attributed to the large rodent olfactory surface area (greater than 50% of the nasal cavity) and its highly susceptible location (particularly, a projection of olfactory epithelium extending anteriorly in the dorsal meatus region). In contrast, human olfactory epithelium occupies a much smaller surface area (less than 5% of the nasal cavity), and it is in a much less accessible dorsal posterior location. In addition, CFD simulations indicate that human olfactory epithelium is poorly ventilated relative to rodent olfactory epithelium. These studies suggest that the human olfactory epithelium is protected from irritating acidic vapors significantly better than rat olfactory epithelium due to substantive differences in nasal anatomy and nasal air flow. Furthermore, the general structure of the hybrid CFD-PBPK model used for this study appears to be useful for target tissue dosimetry and interspecies dose comparisons for a wide range of inhaled vapors.

Acrylates↗
PubMed1995

Glutathione content and turnover in rat nasal epithelia.

During inhalation exposure to airborne toxicants, the nasal epithelium may be subjected to local toxicity. Since glutathione (GSH) is often involved in xenobiotic metabolism, GSH status in these tissues has been examined. GSH content and apparent first-order rate constants for GSH turnover and synthesis were determined for respiratory epithelium covering the anterior ventral septum and naso and maxillo turbinates, olfactory epithelium covering the dorsal posterior septum, and olfactory epithelium of the dorsal meatus from male Fischer-344 rats. The three tissues had GSH concentrations that ranged from 2.9 to 4.2 mumol/g tissue as determined by the Ellman's assay and by HPLC equipped with an electrochemical detector. Animals were administered [35S]cysteine (Cys) by tail vein injection and rate constants for GSH turnover were estimated, after incorporation of Cys into tissue GSH pools, by the decrease in GSH-specific activity 1-102 hr after administration. Total [35S]GSH was analyzed by HPLC with a flowthrough radioactivity detector. The respiratory epithelium had an apparent biphasic rate of GSH turnover, with a rapid-phase half-life of 4.4 hr and a slow-phase half-life of 34 hr. The other epithelia had slower rates of GSH turnover, with half-lives greater than 30 hr. When half-lives of GSH turnover and GSH concentrations for nasal epithelia, and for 14 previously evaluated tissues, were compared it was found that tissues with high concentrations of GSH generally had a more rapid turnover of GSH than did tissues with low concentrations of GSH. However, apparent GSH turnover in the two regions of the olfactory epithelium poorly followed this trend.

Animals↗
PubMed1995

Acrylic acid oxidation and tissue-to-blood partition coefficients in rat tissues.

We report rates of acrylic acid (AA) oxidation and tissue/blood partition coefficients in rat tissues. AA oxidation in Fischer 344 rat kidney and liver slices was described by saturable kinetics with maximal velocities of about 4 and 2 mumol/h/g, respectively. AA oxidation rates in 11 additional tissues were 40% or less than in liver. AA oxidation rates in Sprague-Dawley rat liver and kidney were similar to those in Fischer rats. Partition coefficients varied within a narrow range, suggesting that a tissue's contribution to systemic detoxification of AA will depend much more strongly on its rate of AA oxidation and the proportion of the cardiac output that it receives.

Acrylates↗
PubMed1995

Disposition and metabolism of acrylic acid in C3H mice and Fischer 344 rats after oral or cutaneous administration.

Acrylic acid (AA) is used in large amounts to produce acrylic esters and polymers. Here we report on the disposition and metabolism of [1-14C]AA in male C3H mice and Fischer 344 (F344) rats after oral (40 and 150) mg/kg) or cutaneous (10 and 40 mg/kg) administration. Although these and other strains of rodents have been used frequently in toxicity studies of AA, results of pharmacokinetic studies are available for only the Sprague-Dawley rat. In the current study, C3H mice rapidly absorbed and metabolized orally administered AA, with about 80% of the dose exhaled as 14CO2 within 24 h. Excretion in urine and feces accounted for approximately 3% and 1% of the dose, respectively. Elimination of 14C from plasma, liver, and kidney was rapid but was slower from fat. The disposition of orally administered AA in F344 rats was similar to the results obtained from mice. After cutaneous administration to C3H mice, about 12% of the dose was absorbed, while the remainder apparently evaporated. Approximately 80% of the absorbed fraction of the dose was metabolized to 14CO2 within 24 h. Excretion in urine and feces each accounted for less than 0.5% of the dose. Elimination of radioactivity from plasma, liver, and kidney was rapid; however, levels in fat were higher at 72 h than at 1 or 8 h. After cutaneous administration to F344 rats, 19-26% of the dose was absorbed, and the rest apparently evaporated. Disposition of the absorbed fraction of the dose was similar to results found in mice. Results from an in vitro experiment with rat skin showed that at least 60% of the applied dose evaporated and about 25% was absorbed, confirming the in vivo results. High-performance liquid chromatography (HPLC) analysis of rat urine and rat and mouse tissues indicated that absorbed AA was rapidly metabolized by the beta-oxidation pathway of propionate catabolism. In summary, rapid detoxification of systemically absorbed AA, as observed here in C3H mice and F344 rats, can explain findings that AA causes minimal systemic toxicity despite its causing irritation at portal-of-entry tissues.

Acrylates↗
PubMed1994

The regional hydrolysis of ethyl acrylate to acrylic acid in the rat nasal cavity.

Cytotoxicity is primarily limited to the olfactory epithelium of the dorsal meatus region of the nasal cavity of rodents following inhalation exposure to acrylic monomers. To investigate the biochemical basis for this effect, three regions of the Fischer F344N rat nasal cavity were evaluated for carboxylesterase activity for the representative acrylic ester, ethyl acrylate. Prior studies have indicated that the rodent olfactory epithelium is sensitive to the cytotoxic effects of short chain organic acids. In this study, no regional difference in carboxylesterase activity was observed between sensitive and non-sensitive regions of olfactory epithelium. Respiratory epithelium (resistant to cytotoxicity) was found to be have a much lower rate of carboxylesterase activity than olfactory epithelium. These results suggest that the regional distribution of cytotoxicity observed in the rat nasal cavity at high concentrations of inhaled acrylic monomers may be due in part to the amount of released organic acid following deposition. However, the observation of the same esterase activity in sensitive and nonsensitive olfactory regions suggests that nasal air flow patterns and regional deposition may also be critical factors.

Acrylates↗
PubMed1993

Metabolism of acrylic acid to carbon dioxide in mouse tissues.

Acrylic acid (AA) is acutely irritating at sites of initial contact but causes little systemic toxicity probably due to its rapid metabolism to CO2 and acetyl-CoA via a secondary pathway of propionic acid catabolism. In this study, the rate of AA oxidation in 13 tissues of C3H mice was measured by incubating tissue slices with [1-14C]AA and collecting, 14CO2. Oxidation of AA followed pseudo-Michaelis-Menten kinetics in the liver, kidney, and skin. Pseudo-Km values were similar among these tissues and averaged 0.67 mM. The maximal rate of AA oxidation in kidney, liver, and skin was 2890 +/- 436 (mean +/- SE, N = 3), 616 +/- 62, and 47.9 +/- 5.8 nmol/hr/g, respectively. The remaining organs oxidized AA at rates less than 40% of the rate in liver. Rates of metabolism in tissues from male and female mice were similar. 3-Hydroxypropionic acid was the only metabolite detected by high-performance liquid chromatographic analysis following incubation of tissues with [1-14C]AA. Kidney and liver also oxidized [2,3-14C]AA and [1-14C]acetate well, thus providing for the complete metabolism of AA carbons to CO2. These results demonstrate that the rate of AA metabolism varies significantly among mouse tissues and suggest that the kidneys and liver are major sites of detoxification of AA.

Acrylates↗
PubMed1992

Characterization of a novel rat thymocyte costimulating antigen by the monoclonal antibody 1.3.

To define membrane-associated molecules that impart signals for the activation and expansion of double negative (DN) cells, mAb were raised against in vitro-cultured rat DN cells. One such mAb, 1.3, stimulated proliferation of DN cells along with submitogenic concentrations of PMA and IL-2 without affecting the mobilization of Ca2+. The 1.3 mAb precipitated a heterodimeric protein from DN cells and kidney (130/110 kDa). Although the tissue distribution and biochemical characteristics of the 1.3 determinant resemble the neutral aminopeptidase (AP-N) first described as the thymocyte activating molecule in the mouse, other data are contradictory; AP-N message was not detected in mRNA from 1.3 positive cells and the AP-N gene was absent in the genomic DNA from rat DN hybridomas expressing high levels of 1.3 Ag. In addition, the 1.3 mAb did not affect AP-N enzyme activity suggesting that 1.3 mAb does not function through this enzyme to transduce signals for proliferation. Thus, the 1.3 mAb defines a new and important thymocyte costimulating Ag.

Animals↗
PubMed1992

Rate and route of oxidation of acrylic acid to carbon dioxide in rat liver.

Results of in vivo metabolism studies with acrylic acid (AA) have indicated that 60-80% of the administered dose is excreted as CO2 within 2-8 hr of oral dosing of rats; however, the pathway of AA metabolism to CO2 in mammals has not been determined. To define this route, rat hepatocytes were isolated and incubated with [1-14C]AA in a sealed vial modified to trap evolved 14CO2. Rapid oxidation of AA to CO2 was observed. Similar incubations conducted with rat liver homogenates fortified with ATP, ADP, coenzyme A, carnitine, and malate also resulted in oxidation of AA. Mitochondria isolated from liver homogenates were incubated with AA under the same conditions and yielded higher rates of AA oxidation than homogenates. Addition of equimolar amounts of propionic acid, 3-hydroxypropionic acid, or 3-mercaptopropionic acid significantly inhibited the oxidation of AA by mitochondria. HPLC analysis of the mitochondrial incubation mixtures indicated that a single major metabolite, which coeluted with 3-hydroxypropionate, accumulated in the solution. The results indicate that AA is rapidly incorporated into a mitochondrial pathway for propionic acid catabolism that results in the release of CO2 and possible bioincorporation as acetate. This pathway appears to be the principal route of detoxification of AA in mammals.

Acrylates↗
PubMed1991

Receptor-mediated elimination of phosphocholine-specific B cells in x-linked immune-deficient mice.

The combined expression of the M167 mu/kappa anstiphosphocholine (PC) transgenes with the x-linked immunodeficiency gene, xid, results in an almost total failure to develop B cells in the peripheral lymphoid organs of such mice. Although there is no significant difference between the normal transgene positive (TG+) female offspring and the immunodeficient TG+ xid males with respect to the number of B220+ pre-B cells and IgM+B220+B cells that develop in their bone marrow, the hemizygous xid males have 85% fewer B cells in their spleens than the phenotypically normal heterozygous F1 females. In xid M167-mu-transgenic mice, PC-specific B cells also fail to develop in the spleen; however, numerous B cells bearing the mua+VH1(+)-transgene product associated with endogenous kappa L chains that do not give rise PC-specific antibodies are present. In the phenotypically normal TG+ (B6.CBA/N x mu 243-4)F1 female mice, PC-specific B cells represent almost 10% of the total B cell population, and these B cells express an M167-Id that has been produced by association of the VH1 transgene product with an endogenous V kappa 24L chain. B cells expressing the normally dominant T15-Id are not detectable in the spleens of these M167 mu-transgenic mice. Furthermore, M167-Id+ B cells are present at a fivefold lower level in the bone marrow of mu-TG+ normal mice than in their spleens. These data suggest that the PC-specific B cells that develop in TG+ xid mice are either clonally deleted via some "IgR-directed" mechanism or they fail to receive the appropriate signals to exit the bone marrow or to enter the peripheral lymphoid tissues. This hypothesis is supported by the finding that TNP-specific B cells develop normally and do not undergo clonal deletion in xid mice carrying the Sp6 mu/kappa anti-TNP transgenes.

Animals↗
PubMed1991

Influence of body weight support on normal human gait: development of a gait retraining strategy.

The recovery of locomotion, following interactive training with graded weight support, in the adult spinal cat has led to the proposal that removal of body weight may be a therapeutic tool in human gait retraining. There would be benefits, however, in knowing normal responses of humans to partial weight bearing before applying this strategy to patients. In this study, 10 nondisabled male subjects walked on a treadmill while 0%, 30%, 50%, and 70% of their body weight was supported by a modified climbing harness. To dissociate the changes attributable to walking speed from those attributable to body weight, each subject walked at the specified body-weight-support (BWS) levels and at full weight bearing (FWB) at the same speed. Simultaneously, electromyographic data from the right leg muscles, footswitch signals, and video recording of joint motion were collected. The FWB and BWS gaits appeared similar, except at the highest level of BWS studied (ie, 70% of BWS). Significant differences among other BWS and FWB trials at comparable speeds included decreases in percentage of stance, percentage of total double-limb support time, and maximum hip and knee flexor swing angle. Other adaptations to BWS were a reduction in the mean burst amplitude of the muscles that are active during stance and an increase in the mean burst amplitude of the tibialis anterior muscle. The possible implications of this new gait retraining strategy for patients with neurological impairment are discussed. [Finch L, Barbeau H, Arsenault B. Influence of body weight support on normal human gait: development of a gait retraining strategy.

Adult↗
PubMed1988

The reaction of bisulfite with liposomal membranes.

Bisulfite has been shown to induce leakage of encapsulated substances from liposomal vesicles. The bisulfite induced leakage of either DNP-tyrosine, potassium ferricyanide, or [3H]glycine was observed to be greater with lipsomes composed of phospholipids containing unsaturated fatty acids. The leakage of encapsulated substances from liposomes was found to be concentration dependent when incubated for a constant time interval and time dependent when incubated at a constant bisulfite concentration. In addition, bisulfite caused the leakage of approximately 5 times more [3H]glycine from unilamellar liposomes than from multilamellar liposomes. These findings are consistent with the interaction of bisulfite with liposomal membranes via reaction with sites of unsaturation.

Liposomes↗
PubMed1983

Transcutaneous electrical nerve stimulation for low back pain. A comparison of TENS and massage for pain and range of motion.

Patients with acute or chronic low back pain were treated in a double-blind study that compared transcutaneous electrical nerve stimulation at intense levels and gentle, mechanically administered massage. Transcutaneous electrical nerve stimulation produced significantly greater pain relief, based on two measures of the McGill Pain Questionnaire, and significant improvement in straight leg raising. There were no significant differences between the two groups in backflexion scores. Pain-relief scores and range-of-motion scores were significantly correlated. The results indicate that pain-relief scores provide valuable information and can easily be obtained from patients for whom pain is a major symptom.

Back Pain↗