Biomedical subjects

M M Moore

Publications and source records attributed to M M Moore.

At least 55 records · Page 3Linked to original sources

PubMed1998

Mutagenicity of three disinfection by-products: di- and trichloroacetic acid and chloral hydrate in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells.

The disinfection of water, required to make it safe for human consumption, leads to the presence of halogenated organic compounds. Three of these carcinogenic 'disinfection by-products', dichloroacetic acid (DCA), trichloroacetic acid (TCA) and chloral hydrate (CH) have been widely evaluated for their potential toxicity. The mechanism(s) by which they exert their activity and the steps in the etiology of the cancers that they induce are important pieces of information that are required to develop valid biologically-based quantitative models for risk assessment. Determining whether these chemicals induce tumors by genotoxic or nongenotoxic mechanisms (or a combination of both) is key to this evaluation. We evaluated these three chemicals for their potential to induce micronuclei and aberrations as well as mutations in L5178Y/TK +/- (-)3.7.2C mouse lymphoma cells. TCA was mutagenic (only with S9 activation) and is one of the least potent mutagens that we have evaluated. Likewise, CH was a very weak mutagen. DCA was weakly mutagenic, with a potency (no. of induced mutants/microgram of chemical) similar to (but less than) ethylmethanesulfonate (EMS), a classic mutagen. When our information is combined with that from other studies, it seems reasonable to postulate that mutational events are involved in the etiology of the observed mouse liver tumors induced by DCA at drinking water doses of 0.5 to 3.5 g/l, and perhaps chloral hydrate at a drinking water dose of 1 g/l. The weight-of-evidence for TCA suggest that it is less likely to be a mutagenic carcinogen. However, given the fact that DCA is a weak mutagen in the present and all of the published studies, it seems unlikely that it would be mutagenic (or possibly carcinogenic) at the levels seen in finished drinking water.

Animals↗

PubMed1998

Human in vivo somatic mutation measured at two loci: individuals with stably elevated background erythrocyte glycophorin A (gpa) variant frequencies exhibit normal T-lymphocyte hprt mutant frequencies.

A survey of glycophorin A (gpa) in vivo somatic cell mutation in a population of 394 healthy people from 8 to 77 years of age (mean age +/- SD 41 +/- 15 years) revealed a subset of 37 individuals with stably elevated allele-loss and/or allele-loss with duplication variant erythrocyte frequencies (Vf) exceeding 30 x 10(-6). These 37 individuals with gpa outlier Vf are significantly older (P < 0.001) than the remainder of the larger study population from which they were drawn reflecting a highly significant increase in the prevalence of these individuals in the population beyond age 40 years. A study of hpt mutant frequencies (Mf) in the peripheral blood T-lymphocytes of 27 of these individuals, together with 15 matched control individuals with unremarkable gpa Vf, was undertaken to determine if these subjects also displayed elevated mutation frequencies at this independent locus indicative of globally elevated somatic mutation. The hprt Mf in these 27 subjects (geometric mean 11.5 x 10(-6)(dispersion interval 5.8 x 10(-6) to 22.8 x 10(-6)) was not significantly different from that observed in the 15 controls (geometric mean 12.1 x 10(-6)(dispersion interval 5.7 x 10(-6) to 25.5 x 10(-6)). These Mf are higher than typically reported values reflecting the older age distribution of these individuals (arithmetic mean age +/- SD 53 +/- 12 and 50 +/- 16 years for the subjects and controls, respectively). Taken together, these data suggest that several genetic mechanisms may be responsible for producing the gpa outlier Vf observed in these subjects. The observation that hprt Mf were not increased indicates that the majority did not arise by a genome-wide increased rate of somatic mutation detectable at both loci. The fixation and subsequent expansion of 'jackpot' mutations at the gpa locus occurring early in embryonic/fetal development also does not appear to be a predominant mechanism. Some cases may result from a stable over-representation of gpa variant cells, perhaps associated with a marked age-dependent decrease in the number of contributing erythroid stem cells in the bone marrow. The subset that displays elevated allele-loss with duplication Vf involving both gpa alleles may represent individuals with increased rates of somatic recombination. Elevations arising by this mechanism are not detected in the hprt assay, but could be confirmed using a autosomal locus in vivo somatic cell mutation endpoint such as the hla-a assay. Of primary biological significance, these results demonstrate that genetics/stochastic processes leading to the loss of heterozygosity of somatic cells occur ubiquitously in humans and in some individuals this level of somatic mosaicism can approach a frequency of 10(-3) at the gpa locus in erythroid lineage cells.

Adolescent↗

PubMed1998

Mapping of the nitrate-assimilation gene cluster (crnA-niiA-niaD) and characterization of the nitrite reductase gene (niiA) in the opportunistic fungal pathogen Aspergillus fumigatus.

This study reports the molecular characterization of the nitrate-assimilation gene cluster from the opportunistic fungal pathogen Aspergillus fumigatus. A genomic fragment was isolated which contained the entire structural gene encoding nitrite reductase (niiA), plus segments of the nitrate reductase (niaD) and the nitrate transporter (crnA) genes. Nitrate-assimilation genes in A. fumigatus are physically linked and transcribed in the same direction as in A. nidulans. The nitrate-assimilation gene cluster is on the largest chromosome (5.3 Mb). The nitrite reductase (niiA) gene encodes a protein of 1110 amino acids that contains regions corresponding to FAD, NADPH, FeS and siroheme binding sites. Eight small introns interrupt the niiA open reading frame. The niaD-niiA intergenic regulatory region contains promoter consensus sequences including TATA, CAAT, and binding sites for the areA and nirA gene products. Northern analysis indicated that the expression of niaD, niiA and crnA are induced by nitrate and repressed by ammonium at the transcriptional level.

Amino Acid Sequence↗

PubMed1998

Mutation and polymorphism analysis of the human homogentisate 1, 2-dioxygenase gene in alkaptonuria patients.

Alkaptonuria (AKU), a rare hereditary disorder of phenylalanine and tyrosine catabolism, was the first disease to be interpreted as an inborn error of metabolism. AKU patients are deficient for homogentisate 1,2 dioxygenase (HGO); this deficiency causes homogentisic aciduria, ochronosis, and arthritis. We cloned the human HGO gene and characterized two loss-of-function mutations, P230S and V300G, in the HGO gene in AKU patients. Here we report haplotype and mutational analysis of the HGO gene in 29 novel AKU chromosomes. We identified 12 novel mutations: 8 (E42A, W97G, D153G, S189I, I216T, R225H, F227S, and M368V) missense mutations that result in amino acid substitutions at positions conserved in HGO in different species, 1 (F10fs) frameshift mutation, 2 intronic mutations (IVS9-56G-->A, IVS9-17G-->A), and 1 splice-site mutation (IVS5+1G-->T). We also report characterization of five polymorphic sites in HGO and describe the haplotypic associations of alleles at these sites in normal and AKU chromosomes. One of these sites, HGO-3, is a variable dinucleotide repeat; IVS2+35T/A, IVS5+25T/C, and IVS6+46C/A are intronic sites at which single nucleotide substitutions (dimorphisms) have been detected; and c407T/A is a relatively frequent nucleotide substitution in the coding sequence, exon 4, resulting in an amino acid change (H80Q). These data provide insight into the origin and evolution of the various AKU alleles.

Alkaptonuria↗

PubMed1998

The mechanics underlying laparoscopic intra-abdominal surgery for obese patients.

Any surgeon experienced with a laparoscopic approach to intra-abdominal surgery on morbidly obese patients is aware of the increased difficulty associated with the patients' obesity. We present a study of the mechanics of laparoscopic surgery that explains the difficulty subjectively experienced in terms of the decreased sensitivity felt by the surgeon as a result of the increased thickness of the abdominal wall and increasing force required for the repositioning of the tip of the operating instrument. We propose that the placement and angling of the trocar in the abdominal wall are of paramount importance in the successful and safe completion of laparoscopic procedures in obese patients.

Abdomen↗

PubMed1998

Identification and chromosomal assignment of two heterozygous mutations in the Trp53 gene in L5178Y/Tk(+/-)-3.7.2C mouse lymphoma cells.

The thymidine kinase locus (Tk1) in Tk(+/-)-3.7.2C mouse lymphoma cells is widely used to identify mutagenic agents. Because Trp53 (the mouse homolog of human TP53) is located with Tk1 on chromosome 11 and is critical in regulating cellular responses following exposure to DNA damaging agents, we wanted to determine if these mouse lymphoma cells harbor mutations in Trp53. Single-stranded conformation polymorphism (SSCP) analysis of PCR-amplified exons 4-9 of Trp53 indicated mutations in both exons 4 and 5. We sequenced exons 4-9 from isolated clones of Tk(+/-)-3.7.2C cells and a Tk-/- mutant (G4). Mutant G4 has two copies of the chromosome carrying the Tk1- allele and no copy of the chromosome carrying the Tk1+ allele and thus could establish linkage of the individual Trp53 and Tk1 alleles. DNA sequence analysis revealed no mutations in exons 6-9 in any Tk(+/-)-3.7.2C or G4 clones. As suggested by SSCP, there was a nonsense mutation in exon 4 at bp 301 (codon 101) in one Trp53 allele. Tk(+/-)-3.7.2C clones have both mutant and wild-type sequences at bp 301; G4 clones have wild-type exon 4 sequence. These data allow assignment of the Trp53 exon 4 mutated allele to chromosome 11 carrying the Tk1+ allele. The exon 4 mutation leads to a stop codon early in translation, thus functionally deleting the Trp53 allele on the Tk1(+)-bearing chromosome. As previously reported, we find a missense mutation in exon 5 at bp 517 (codon 173) in one Trp53 allele. Using the G4 clones we determined that the exon 5 mutation is linked to the Tk1- allele. Thus the Tk +/-(-)3.7.2C mouse lymphoma cells have two mutant Trp53 alleles, likely accounting for their rapid cell growth and contributing to their ability to detect the major types of mutational damage associated with the etiology of tumor development. This ability to integrate across the mutational events seen in the multiple stages of tumor development further supports the use of the assay in chemical and drug safety studies and its recommendation as part of the required screening battery for regulatory agency submissions.

Alleles↗

PubMed1998

Brain volume preserved in healthy elderly through the eleventh decade.

OBJECTIVE: To determine which brain regions lose volume with aging over time in healthy, nondemented elderly. BACKGROUND: Cross-sectional studies suggest widespread loss of brain volume with aging. These studies may be biased by significant numbers of preclinically demented elderly in the oldest comparison groups. Longitudinal studies may allow closer determination of the effect of aging unaffected by dementia. METHODS: Quantitative volumetric MRI was performed annually on 46 healthy subjects older than age 65 who had maintained cognitive health a mean of 5 years. Comparisons (analysis of variance) were made of rates of volume loss (slopes) divided into 11 young-old (mean age, 70 years), 15 middle-old (mean age, 81 years), and 20 oldest-old (mean age, 87 years) subjects. Regions of interest included CSF spaces, lobar regions, and limbic-subcortical regions. RESULTS: There were significant differences between groups in intracranial, total brain, left hemisphere, right hemisphere, temporal lobe, basilar-subcortical region, and hippocampus volumes, with oldest-old subjects showing the smallest volumes, followed by middle-old and young-old subjects. Oldest-old subjects had significantly greater subarachnoid volumes than the younger groups. There were no significant differences in rates of change of regions of interest across age groups. CONCLUSIONS: After age 65 there is minimal brain volume loss observed over time in healthy elderly. Brain volume differences seen cross-sectionally, at any age, likely reflect small, constant rates of volume loss with healthy aging. Healthy oldest-old subjects do not show greater rates of brain loss compared with younger elderly, suggesting that large changes seen in cross-sectional studies reflect the presence of preclinical dementia in older groups.

Aged↗

PubMed1998

Fibrin sealant in breast surgery.

Recent research has investigated the use of fibrin sealant (FS) in axillary lymph-node dissections performed for staging carcinoma of the breast. The majority of complications of axillary dissections in breast surgery stem from the two factors that influence the formation of seromas, hematomas, and lymphedema: the oozing of small transected vessels and the creation of a reservoir due to the removal of tissue. An effective surgical adhesive could improve hemostasis and tissue adherence, thereby decreasing the frequency of these postoperative problems. This paper reviews the use of fibrin sealant in breast surgery to reduce postoperative serous drainage by improving hemostasis and tissue adherence.

Animals↗

PubMed1998

Interventions to reduce decibel levels on patient care units.

The University of Virginia Health System inpatient satisfaction survey identified noise as the most important irritant to surgical inpatients. Analysis of the level and pattern of noise on patient floors and intensive care units was done with baseline measurements followed by then two separate interventions: 1) education of nursing and physician staff 2) closing patient room doors. A decibel meter (M-27 Dosimeter) recorded the noise level over 24 hours. Patients doors were open in the initial measurements. Next, three 1-hour education sessions were conducted by a surgeon and nursing supervisor to review noise-reduction strategies with the staff. These included using pagers in vibrate mode, minimizing overhead announcements, and conducting nurse reports and physician teaching sessions in classrooms away from the nurses' station. Finally, the doors were closed except as visitors and staff entered the room. Little impact was seen from staff education. Closing patient doors on surgical floors decreased noise an average of 6.0 dB, a change that patients can readily perceive. Conversely, intensive care unit patients are exposed to more noise with closed doors, presumably because most noise emanates from equipment within the room. A policy of closing patient floor room doors may increase patient satisfaction.

Communication↗

PubMed1997

The L5178Y/tk+/- mouse lymphoma specific gene and chromosomal mutation assay a phase III report of the U.S. Environmental Protection Agency Gene-Tox Program.

The L5178Y/tk+/- (-)3.7.2C mouse lymphoma assay (MLA) which detects mutations affecting the heterozygous thymidine kinase (tk) locus is capable of responding to chemicals acting as clastogens as well as point mutagens. Improvements in the assay to enhance detection of this spectrum of genetic events are summarized, and criteria for evaluating the data are defined. Using these criteria, the Phase III Work Group reviewed and evaluated literature containing MLA results published from 1976 through 1993. The data base included 602 chemicals of which 343 were evaluated as positive, 44 negative, 18 equivocal, 54 apparently inappropriate for evaluation in this test system with the published protocols, and 142 that were inadequately tested, and thus a definitive call could not be made. The overall performance of the assay is summarized by chemical class, and the outcome of testing 260 chemicals in the MLA is compared with Gene-Tox and National Toxicology Program evaluations of rodent carcinogenesis bioassay results for the same chemicals. Based on the Work Group's evaluation of published MLA data for chemicals that were considered adequately tested, it is concluded that for most chemicals the L5178Y/tk+/- mouse lymphoma assay is eminently well suited for genotoxicity testing and for predicting the potential for carcinogenicity.

Animals↗

PubMed1997

Quantification of hprt gene deletions mediated by illegitimate V(D)J recombination in peripheral blood cells of humans.

V(D)J recombinase is normally involved in the highly regulated rearrangement of immunoglobulin and T-cell-receptor gene segments (in B and T cells, respectively) to form functional antibody genes and T-cell-receptor genes. Occasionally, this tightly controlled process acts on inappropriate places in the genome and results in deletions and translocations. Some of these illegitimate V(D)J recombinase-mediated events have been implicated in the genetic changes associated with several forms of leukemia and lymphoid malignancy. We have developed a sensitive, specific polymerase chain reaction (PCR)-based assay to quantify such events in the peripheral blood cells of humans. This assay detects a V(D)J recombinase-mediated deletion in the hprt gene, which codes for a housekeeping enzyme and is not implicated in cancer development. Alterations in this gene serve as a surrogate indicator for these illegitimate events, which may be occurring throughout the genome. The assay involves a hemi-nested PCR with two sets of primers. Multiple replicates of genomic DNA (each representing 4 x 10(5) cells) are amplified with specific primers under conditions in which a single copy will give a detectable PCR product. Poisson statistics are then used to estimate the deletion mutant frequency. The frequency of cells with the hprt deletion among 20 healthy young adults ranged from <1.3 x 10(-7) to 4.1 x 10(-7) and was compared with the frequency of t(14;18) previously determined in these same individuals. No correlation was found between the frequencies of these two measures of genomic rearrangement. The DNA sequences at the deletion junctions were determined and provided evidence for multiple independent mutations in some individuals. This assay may serve as a biomarker for the level of illegitimate V(D)J recombination occurring in peripheral blood cells of humans.

Adolescent↗

PubMed1997

Relative genotoxic potency of arsenic and its methylated metabolites.

Arsenic is one of the few identified human carcinogens that has yet to be shown to cause cancer in rodents when the standard bioassay protocols are used. The reasons for this apparent interspecies difference are unclear but may be related to differences between humans and rodents in their detoxification capabilities. Detoxification of arsenic may occur through a methylation pathway. If, in fact, methylation does detoxify arsenic, one would predict that the methylated arsenicals might be less genotoxic than the inorganic arsenicals. To evaluate the hypothesis that the inorganic arsenicals are more mutagenic than the organic arsenicals, we tested sodium arsenite, sodium arsenate, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) for their relative mutagenic and clastogenic potentials. We used the L5178Y/TK+/- mouse lymphoma assay which allows the detection of chemicals inducing a broad spectrum of different types of genetic damage. Sodium arsenite and sodium arsenate were active at concentrations of 1-2 micrograms/ml and 10-14 micrograms/ml, respectively. MMA was active between 2500-5000 micrograms/ml; while DMA required almost 10000 micrograms/ml to induce a genotoxic response. The organic arsenicals are thus much less potent as mutagenic agents than the inorganic arsenicals. All four of these arsenicals appear to act by mechanisms that cause chromosomal mutations.

Animals↗

PubMed1997

Association of breast cancer with the finding of atypical ductal hyperplasia at core breast biopsy.

OBJECTIVE: The purpose of the study is to evaluate the prevalence of occult breast carcinoma in surgical breast biopsies performed on nonpalpable breast lesions diagnosed initially as atypical ductal hyperplasia (ADH) by core needle biopsy. BACKGROUND: Atypical ductal hyperplasia is a lesion with significant malignant potential. Some authors note that ADH and ductal carcinoma in situ (DCIS) frequently coexist in the same lesion. The criterion for the diagnosis of DCIS requires involvement of at least two ducts; otherwise, a lesion that is qualitatively consistent with DCIS but quantitatively insufficient is described as atypical ductal hyperplasia. Thus, the finding of ADH in a core needle breast biopsy specimen actually may represent a sample of a true in situ carcinoma. METHODS: Between May 3, 1994, and June 12, 1996, image-guided core biopsies of 510 mammographically identified lesions were performed using a 14-gauge automated device with an average of 7.5 cores obtained per lesion. Atypical ductal hyperplasia was found in 23 (4.5%) of 510 lesions, and surgical excision subsequently was performed in 21 of these cases. In these 21 cases, histopathologic results from core needle and surgical biopsies were reviewed and correlated. RESULTS: Histopathologic study of the 21 surgically excised lesions having ADH in their core needle specimens showed seven (33.3%) with DCIS. CONCLUSIONS: In the authors' patient population, one third of patients with ADH at core biopsy have an occult carcinoma. A core needle breast biopsy finding of ADH for nonpalpable lesions therefore warrants a recommendation for excisional biopsy.

Biopsy, Needle↗

PubMed1997

Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia.

OBJECTIVE: To determine initial locus and rate of degeneration of temporal lobe structures (total lobe, hippocampus and parahippocampus) in preclinical dementia. BACKGROUND: Postmortem studies suggest that the earliest changes in Alzheimer's disease are neurofibrillary tangle formation in hippocampus and adjacent cortex. MRI volume analysis of temporal lobe structures over time in subjects prior to developing dementia may allow the identification of when these processes begin, the rate they develop, and which areas are key to symptom development. METHODS: 30 nondemented (NoD), healthy, elderly individuals enrolled in a prospective study of healthy aging evaluated annually over a mean of 42 months. Twelve subjects with subsequent cognitive decline were assigned to the preclinical dementia group (PreD). All 120 annual MRI studies analyzed by volumetric techniques assessed group differences in temporal lobe volumes and rates of brain loss. RESULTS: NoD as well as PreD subjects had significant, time-dependent decreases in hippocampal and parahippocampal volume. Rates of volume loss between the groups did not significantly differ. PreD cases had significantly smaller hippocampi when asymptomatic. Parahippocampal volume did not differ between PreD and NoD cases. Significant time-dependent temporal lobe atrophy was present only in PreD. CONCLUSIONS: Hippocampal and parahippocampal atrophy occurs at a similar rate regardless of diagnostic group. Those who develop dementia may have smaller hippocampi to begin with, but become symptomatic because of accelerated loss of temporal lobe volume. Temporal lobe volume loss may mark the beginning of the disease process within six years prior to dementia onset.

Aged↗

PubMed1997

Fibrin sealant reduces serous drainage and allows for earlier drain removal after axillary dissection: a randomized prospective trial.

Fibrin sealant (FS) has been used successfully as an effective adhesive and hemostatic agent in a variety of surgical procedures. At the University of Virginia, autologous fibrin sealant is used to reduce the potential accumulation of serous fluid after axillary dissection in patients undergoing modified radical mastectomy (MRM) for carcinoma of the breast. Unilateral MRM, including level I and II axillary lymph node dissection, was performed upon 21 patients prospectively randomized into treatment and control groups. Surgical procedures between both groups differed only by the application of autologous FS prior to axilla closure in the treatment group. Drainage was collected and measured at 24-hour intervals following the operation. Drains were removed following the measurement of 40 ml or less during a 24-hour interval. Cumulative drainage for the first 3 postoperative days in the treatment group averaged 198 +/- 83 ml compared to 467 +/- 138 ml in the control group (P < 0.0003). Day of drain removal averaged 3.9 +/- 1.7 for the treatment group and 6.9 +/- 1.2 for the control group (P < 0.0001). In the treatment group, there was a reduction in cumulative drainage over the first 3 days of 268 ml or 57 per cent, and there was a reduction in the number of days before drains can be removed of 3.0 days, or 43 per cent. We conclude that local application of FS significantly reduced the total drainage measured in patients undergoing MRM and enabled earlier drain removal.

Aged↗

PubMed1997

Immunization with bacterial antigens: edwardsiellosis.

Enteric septicaemia of catfish (ESC), caused by Edwardsiella ictaluri, is the most serious disease affecting commercial catfish culture in the United States. ESC is generally an acute septicaemia that develops very quickly, especially in the temperature range of 22-28 degrees C, with a more chronic disease presentation outside this range. The ability of E. ictaluri to avoid the host's immune system and proliferate into a systemic infection is impressive. Catfish kidney tissue cultured positive for E. ictaluri as soon as 15 minutes following gastric lavage and signs of disease are observed microscopically within two days of immersion challenge, with reported mortalities as early as five days following immersion challenge. Analysis of E. ictaluri antigens by several investigators using SDS-PAGE and colorimetric western blotting with immune catfish has identified as many as 15 immunogenic bands. Analysis using two-dimensional SDS-PAGE and chemiluminescent western blotting identified 14 bands and 25 spots as consistently immunogenic. The strongest immunodominant antigens were reported as 34-37 KD and 60 KD, depending on the study. Lipopolysaccharide is the only purified component of E. ictaluri tested for fish vaccination, and results indicated that very poor protection was induced unless Freund's Complete Adjuvant was used. Because E. ictaluri strains are serologically homogeneous, most studies on vaccination have emphasized killed whole cell preparations and have delivered equivocal results. Although antibodies are produced to a variety of preparations, a positive antibody response does not correlate with protection unless very high titres are achieved. Efficacy of killed products has been demonstrated in field trials, and an orally delivered product has been licensed. However, protection probably relies on booster exposure of the host to E. ictaluri during non-permissive temperatures. As a facultative intracellular pathogen, further studies on vaccination of catfish against E. ictaluri should target products and delivery methods that favour induction of cell mediated immunity.

Animals↗

PubMed1996

Effect of fibrinogen and thrombin concentrations on mastectomy seroma prevention.

Seroma formation remains a significant clinical problem which increases morbidity and hospital costs in patients undergoing mastectomy operations. This study evaluated the effect of varying the concentrations of fibrinogen and thrombin in fibrin sealant on successfully preventing seroma formation in a rat model. After axillary dissection, control animals (Groups I and II) had 1 ml of either normal saline or thrombin (100 U/ml) applied to the axilla while treated animals (Groups III-VIII) had increasing concentrations of 0.5 ml of fibrinogen (25, 50, or 100 mg/ml) and 0.5 ml of thrombin (10 or 100 U/ml) applied. Seroma volumes (means +/- standard deviation) were measured on Postoperative Day 5. They were largest in Group I (3.1 +/- 1.9 ml, n = 13) and Group II (3.9 +/- 2.7 ml, n = 15) and then decreased from a high in Group III (2.5 +/- 2.4 ml, n = 15) using fibrinogen, 25 mg/ml, and thrombin, 10 mg/ml, to a low in Group VIII (0.8 +/- 1.0 ml, n = 15) using fibrinogen, 100 mg/ml, and thrombin, 100 U/ml. Analysis of variance revealed a statistically significant difference in the mean seroma fluid volumes between the groups (P = 0.0021), while Scheffe's comparison showed a specific significant difference (P = 0.028) between the thrombin control (Group II) and the highest concentration fibrin sealant (Group VIII). The difference in seroma volumes for all control animals (Groups I and II), 3.5 +/- 2.4 ml, and all treated animals (Groups III-VIII), 1.7 +/- 2.1 ml, was highly significant by unpaired t test. (P < 0.0001). Thus, fibrin sealant was useful in reducing seroma formation in this rat model with the highest concentration of fibrinogen and thrombin appearing most effective. These data may be useful in guiding future clinical trials in humans.

Animals↗

PubMed1996

Excimer laser effects on human corneal endothelium. Modulation by serum factor(s).

OBJECTIVE: To determine the possibility of endothelial cell damage after excimer laser ablation. METHODS: Endothelial cell densities and morphology of human corneas after photoablations or mechanical keratectomy were compared with those of the untreated mates after 1 week of culture with or without serum. RESULTS: Corneas cultured in serum-free medium after ablation to a depth of 150 microns showed endothelial cell densities reduced to 60% of untreated, mate corneas; ultrastructural analysis showed endothelial cell damage not seen in untreated mates. Corneas ablated to the same depth and cultured in serum-enriched medium showed no endothelial cell density loss, nor did corneas cultured in serum-free medium after an ablation to a depth of 50 microns or mechanical keratectomies averaging 95 microns. CONCLUSIONS: Endothelial cell loss in deep laser resections may be prevented by factor(s) in fetal bovine serum. The apparent lack of cell loss in clinical studies may be related to the protective action of similar factors in aqueous humor.

Aged↗