Biomedical subjects

K Barton

Publications and source records attributed to K Barton.

At least 19 recordsLinked to original sources

PubMed2001

Analysis of expression of nuclear factor kappa B (NF-kappa B) in multiple myeloma: downregulation of NF-kappa B induces apoptosis.

Nuclear factor-kappa B (NF-kappa B) is an important transcription factor that regulates survival in many cells. Activated NF-kappa B has been shown to protect some haematopoietic neoplastic cells from apoptosis. In the present study, we analysed NF-kappa B status in 13 primary samples from patients with multiple myeloma (MM) and in four myeloma cell lines including U266, RPMI 8226, HS-Sultan and K620. Constitutive activation of NF-kappa B was evaluated by either immunohistochemistry or immunofluorescence using a monoclonal mouse anti-human p65 (Rel A) antibody, which recognizes the unbound, active form of p65 (Rel A). Constitutively active NF-kappa B was present in all MM patient samples as well as in all four myeloma cell lines. Inhibition of constitutively active NF-kappa B, by either proteasome inhibitors (MG132, gliotoxin) or inhibitors of I kappa B phosphorylation (Bay117082, and Bay117085), induced apoptosis as demonstrated by both flow cytometric analysis and light microscopic morphological evaluation. This chemically induced apoptosis was associated with decreased DNA binding of nuclear NF-kappa B as determined by the electrophoretic mobility shift assay. In addition, adenovirus vector with dominant negative I kappa B alpha (Ad5I kappa B) was used for inhibition of NF-kappa B in the U266 cell line. Compared with wild-type, super-repressor-treated cells showed an increased level of apoptosis. These results suggest that constitutive expression of NF-kappa B plays an important role in plasma cell survival in MM.

Adenoviridae↗

PubMed2001

A multibehavioral intervention to decrease cardiovascular disease risk factors in older men.

The purpose of this study was to compare the effectiveness of two mutibehavioral interventions: stress management (SM) (nutrition, exercise, and stress management) and education (ED) (nutrition, exercise, and education) on reduction of cardiovascular disease (CVD) risk factors in older men. A convenience sample (n = 33) of older men (66 +/- 5 years) with at least one CVD risk factor participated in this 6-month intervention. Mean receiving the SM intervention (n = 25) exercised at the facility twice weekly (at > or = 70% maximum heart rate for 40 minutes) and received 12 hours each of nutrition and stress management class instruction. Men receiving the ED intervention (n = 8) received the same exercise and nutrition protocols but received 12 hours of education without stress management. There were no significant differences in body habitus, metabolic response, exercise endurance, blood pressure, or heart rate between groups at baseline. The SM group had significant pre-post differences in weight, body mass index, intraabdominal fat, subcutaneous fat, total cholesterol, low-density lipoprotein, triglycerides, VO2, supine systolic and diastolic blood pressures. The ED group demonstrated significant pre-post differences only in supine diastolic blood pressure. There were significant change score differences between the groups in triglycerides, subcutaneous fat, VO2, and body mass index. Results suggest that a 6-month multibehavioral intervention with stress management is effective in decreasing CVD risk factors in older men.

Acute Disease↗

PubMed2001

Glaucoma filtration surgery using amniotic membrane transplantation.

PURPOSE: To investigate the potential use of amniotic membrane transplantation (AMT) in the construction of glaucoma filtering blebs. METHODS: Twenty-four albino rabbits underwent glaucoma filtration surgery in one eye. In alternate cases, the conjunctival flap was replaced with AMT. Postoperative examination data were grouped into three time points. Six animals with AMT and six filtration surgery-controls were euthanatized at each of two postoperative time points, and tissue was obtained for histologic examination. Conjunctival biopsies were explanted for estimation of fibroblast outgrowth. RESULTS: Bleb formation was observed in all eyes, and amniotic membranes were epithelialized after 11.2 +/- 2.48 (mean +/- SD) days. Throughout the study IOPs were significantly lower in operated than unoperated fellow eyes. Between postoperative days 11 and 16 (the middle time point), the percentage IOP reduction in AMT eyes was significantly greater than in filtration surgery controls (P = 0.014), though not at other time points. Filtration surgery survival was significantly longer in the AMT group (22.3 +/- 3.8 days; mean +/- SE) than in "No AMT" controls (14.0 +/- 1.6 days; P = 0.035). In tissue culture, significantly less fibroblast outgrowth occurred from AMT explants when compared with unoperated conjunctiva (P = 0.01) between postoperative days 3 and 9 (the early time point). Amniotic membrane transplants were intact on histologic examination after 14 days but were associated with considerable granulomatous inflammation. After 36 days, the ocular surfaces remained clinically intact, but lysis of AMT was noted histologically. CONCLUSIONS: AMT exhibits potential as an alternative tissue to conjunctiva in the construction of glaucoma filtration blebs. The healing response as demonstrated by fibroblast outgrowth is retarded when compared with conventional conjunctival closure. The improvement in bleb survival must be weighed against the potential for complications related to delayed healing. In rabbits, human amniotic membrane elicited a late xenograft reaction, leading to granulomatous inflammation and dissolution of the membrane.

Amnion↗

PubMed2000

Microphthalmia due to p53-mediated apoptosis of anterior lens epithelial cells in mice lacking the CREB-2 transcription factor.

CREB-2 (also called ATF4, TAXREB67, or C/ATF) is an evolutionarily conserved member of the CREB/ATF family of basic-leucine zipper transcription factors. CREB-2 is expressed ubiquitously in the adult mouse and can function as both a transcriptional activator and a repressor. However, little was understood about the normal function of CREB-2 in mammalian development or organ physiology. In this report we have used gene targeting to produce CREB-2-deficient (CREB-2-/-) mice. Adult CREB-2-/- mice displayed microphthalmia due to the complete absence of a lens. Early embryonic lens development including formation of the optic vesicle, primary lens fibers, and proliferating anterior epithelial cells occurred normally in these mice. However, beginning at ED 14.5 the CREB-2-deficient anterior epithelial lens cells underwent massive and synchronous apoptosis. This was followed by the complete resorption of the developing lens. Consistent with this defect in anterior epithelial cell survival, in situ hybridization studies showed that CREB-2 is expressed at high levels in wild-type anterior epithelial lens cells at ED 14.5. The defect in lens formation seen in the CREB-2-/- mice was not associated with qualitative defects in the expression of Pax-6, alphaA-crystallin, c-maf, or PDGF-R alpha. However, apoptosis of the anterior epithelial cells was mediated by a p53-dependent cell death pathway because ablation of the p53 gene rescued anterior epithelial cell death and allowed the formation of a lens in the absence of CREB-2. Taken together, these results identify CREB-2 as an important regulator of mammalian lens development.

Animals↗

PubMed2000

AML1 haploinsufficiency, gene dosage, and the predisposition to acute leukemia.

Hematopoiesis is the complex developmental process through which undifferentiated, pluripotent, hematopoietic stem cells come to generate mature, functional blood cells. This process is regulated in large part by specific transcription factors that control expression of genes necessary for the developmental sequence. Leukemias represent one form of disruption of this normal developmental process, and studies over the past few years have shown that many of the genes that underlay leukemogenesis are also essential for normal hematopoiesis. In an interesting recent example, Song et al.((1)) demonstrate that haploinsufficiency of the AML1 gene is the genetic basis of a form of familial thrombocytopenia which predisposes the affected individuals to the development of acute myeloid leukemia. Here we summarize Song's paper and current information describing the interesting dosage effects of this gene and other members of its gene family.

Acute Disease↗

PubMed2000

The mutation of Pro789 to Leu reduces the activity of the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA1) and is associated with Brody disease.

Brody disease is a rare inherited disorder of fast-twitch skeletal muscle function and is characterized by a lifelong history of exercise-induced impairment of skeletal muscle relaxation, stiffness, and cramps. The autosomal recessive inheritance of mutations in ATP2A1, the gene encoding SERCA1, which is the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, has been associated with Brody disease in three of six Brody families in which ATP2A1 has been sequenced. In the present analysis of the ATP2A1 gene in four unrelated families with autosomal recessive inheritance of Brody disease, three mutations were found in two families, leading to premature stop codons and truncated SERCA1. In a third family, the homozygous substitution of T for C2366 led to the missense mutation of Pro789 to Leu. The Pro789 to Leu mutant was readily expressed in HEK-293 cells, but it demonstrated an almost complete loss of Ca2+ transport activity because of reduced Ca2+ affinity. In a fourth family, the heterozygous substitution of T for C2455, mutating Arg819 to Cys, was identified. This mutation was also readily expressed in HEK-293 cells and shown to have near normal Ca2+ transport activity, indicating that it is not causal for Brody disease. These results confirm the genetic heterogeneity of Brody disease and emphasize the importance of a functional test for mutant SERCA1; immunostaining of skeletal muscle to detect the loss of SERCA1a protein is not adequate for the diagnosis of ATP2A1-linked Brody disease.

Adolescent↗

PubMed2000

Amniotic membrane transplantation for repair of leaking glaucoma filtering blebs.

PURPOSE: To compare the safety and efficacy of human preserved amniotic membrane transplant with conjunctival advancement for repair of late-onset glaucoma filtering bleb leaks. METHOD: A prospective, randomized clinical trial compared amniotic membrane transplant with conjunctival advancement in patients with leaking glaucoma filtering blebs. Intraocular pressure, number of glaucoma medications, and reoperation for glaucoma or persistent or recurrent bleb-leak were compared in the two groups. Patients were followed for a minimum of 1 year. RESULTS: Mean intraocular pressure was the same at 6 (amniotic membrane transplant, 15.4 +/- 4.4, conjunctival advancement 14.1 +/- 6.4, P = 0.6), 12 (amniotic membrane transplant, 15.0 +/- 6.3, conjunctival advancement, 13.2 +/- 6.6, P = 0.5), and 24 (amniotic membrane transplant, 17.2 +/- 7.1, conjunctival advancement, 15.0 +/- 6.3, P = 0.6) months. The mean number of glaucoma medications in use was the same in the two groups at all time intervals. After an average follow-up of 19 months, there were seven failures in the amniotic membrane transplant group (two with persistent leaks that were unresponsive to further suturing, two with late-onset leaks, and three who required repeat glaucoma surgery) and none in the conjunctival advancement group. The cumulative survival rate for amniotic membrane transplant was 81% at 6 months, 74% at 1 year, and 46% at 2 years. The cumulative survival rate was 100% for conjunctival advancement throughout follow-up. CONCLUSIONS: Amniotic membrane transplantation does not offer an effective alternative to conjunctival advancement for repair of leaking glaucoma filtering blebs.

Amnion↗

PubMed2000

Risk factors for development of post-trabeculectomy endophthalmitis.

BACKGROUND/AIMS: Although adjunctive use of antiproliferative agents improves the success rate of glaucoma filtration surgery it profoundly alters the morphology of the filtering bleb. In view of these structural changes, which have been suggested to predispose to bleb infection, the relative importance of potential risk factors in the development of post-trabeculectomy endophthalmitis was investigated. METHODS: A case-control study was performed on patients with post-trabeculectomy endophthalmitis presenting to a single academic centre over a 6 1/2 year period. Cases were diagnosed by the combination of vitreous and aqueous inflammation occurring 4 or more weeks postoperatively with control patients chosen by selecting the three patients undergoing trabeculectomy immediately following each index case. RESULTS: Analysis of these data, derived from 23 cases and 69 controls, demonstrated that an episode of blebitis and the presence of diabetes mellitus were statistically significantly associated with subsequent endophthalmitis (odds ratios (OR) 11.8, 95% CI: 2.21-88.31, p = 0.003 and OR 4.51, 95 % CI 1.02-20.29, p = 0.04 respectively). The data also suggest an association exists between antiproliferative use and endophthalmitis (OR 3.3, 95% CI 0.95-15.19, p = 0.07) as the time interval between filtration surgery and development of endophthalmitis was significantly shorter in patients treated with antiproliferative agents (p = 0.001). CONCLUSIONS: These results provide strong evidence of an increased risk of late endophthalmitis in patients who have diabetes mellitus or have had an episode of blebitis and suggest antiproliferative agents may also have an important role.

Aged↗

PubMed2000

The School Connection Scale: a factor analysis.

An individual's feeling of connection with a social system has been viewed by diverse traditions as an important predictor of social behavior. While some of these theoretical traditions have conceptualized and assessed a feeling of connection as a global phenomenon, more recent work has focused on the development of measures for separate contexts in which connection occurs. Using a diverse sample of 1,739 adolescents, this study examined an original scale designed specifically to assess youth's feeling of connection with school. Intercorrelations among scales were factor analyzed to examine the structural validity of elements developed from the literature and focus groups of students. The results yield for the School Connection Scale three subscales on which scores were reliable and valid and account for 49.5% of the variance.

Adolescent↗

PubMed1999

Mutation of K234 and K236 in the voltage-dependent anion channel 1 impairs its insertion into the mitochondrial outer membrane.

Previous in vitro studies indicated that mutation of both K234 and K236 to arginine, glutamine, or glutamic acid impaired the ability of the voltage-dependent anion channel (VDAC1) to insert into the outer membrane of the mitochondria (Smith et al. 1995). These same mutants were expressed in a strain of Saccharomyces cerevisiae with a disruption in the VDAC1 gene. The mutant VDAC1 forms were found in the mitochondria suggesting that they were correctly sorted to the outer membrane. However, only very small amounts of the mutants were inserted into the mitochondrial membranes. Mitochondria isolated from the strains expressing the mutants were capable of catalyzing the translocation of both wild-type VDAC1 and pre-alcohol dehydrogenase III indicating that the translocation apparatus was functional. These results confirm the previously drawn conclusion that K234 and K236 are part of a membrane insertion motif. The failure of the mutant VDAC1 forms to insert did not cause VDAC1 precursors to accumulate in the soluble cell cytoplasm or in the microsomal fraction. The apparent lack of a "precursor pool" suggested that a post-transcriptional control mechanism might limit the amounts of VDAC1 precursors in the cell. Such a control mechanism is consistent with the observation that the amount of VDAC1 was very similar after epichromosomal (gene in a 2u plasmid controlled by a Gal1 promoter) and chromosomal expression (endogenous gene controlled by the endogenous promoter).

Amino Acid Substitution↗

PubMed1999

Forced expression of the leukemia-associated gene EVI1 in ES cells: a model for myeloid leukemia with 3q26 rearrangements.

Chromosome band 3q26 is the locus of two genes, MDS1/EVI1 and EVI1. The proteins encoded by these genes are nuclear factors each containing two separate DNA-binding zinc finger domains. The proteins are identical, aside from the N-terminal extension of MDS1/EVI1, which is missing in EVI1. However, they have opposite functions as transcription factors. In contrast to MDS1/EVI1, EVI1 is often activated inappropriately by chromosomal rearrangements at 3q26 leading to inappropriate expression of the protein in hematopoietic cells and to myeloid leukemias, which are often characterized by abnormal megakaryopoiesis. We previously showed that the two proteins affect replication and differentiation of progenitor hematopoietic cell lines in opposite ways: whereas EVI1 inhibits the response of 32Dc13 cells to G-CSF and TGFbeta1, MDS1/EVI1 has no effect on the G-CSF-induced differentiation of the 32Dc13 cells, and it enhances the growth-inhibitory effect of TGFbeta1. In the present study, we analyzed the endogenous expression of the two genes during in vitro hematopoietic differentiation of murine embryonic stem (ES) cells and evaluated the effects of their forced expression on the ability of ES cells to produce differentiated hematopoietic colonies. We found that the expression of the two genes is independently and tightly controlled during differentiation. In addition, the forced expression of EVI1 led to a much higher rate of cell growth before and during differentiation, whereas the expression of MDS1/EVI1 repressed cell growth and strongly reduced the number of differentiated hematopoietic colonies. Finally, our study also found that the forced expression of EVI1 resulted in the differentiation of abnormally high numbers of megakaryocytic colonies, thus providing one of the first experimental models showing a clear correlation between inappropriate expression of EVI1 and abnormalities in megakaryopoiesis.

Animals↗

PubMed1998

Amniotic membrane transplantation with or without limbal allografts for corneal surface reconstruction in patients with limbal stem cell deficiency.

OBJECTIVE: To examine whether amniotic membrane transplantation (AMT), in preparing the perilimbal stroma, enhances the success of allograft limbal transplantation (ALT). METHODS: Thirty-one eyes of 26 consecutive patients had cytologically proven limbal deficiency resulting from chemical burns (14 eyes); Stevens-Johnson syndrome, toxic epidermal necrolysis, or pseudopemphigoid (5 eyes); contact lens-induced keratopathy (3 eyes); aniridia (3 eyes); multiple surgical procedures (2 eyes); atopy (2 eyes); or an unknown cause (2 eyes). Based on the severity of limbal deficiency, group A (mild), comprising 10 eyes, received AMT alone; group B (moderate), comprising 7 eyes, received AMT and ALT; and group C (severe), comprising 14 eyes, received AMT, ALT, and penetrating keratoplasty. All patients except those in group A received continuous oral cyclosporine. RESULTS: Except for the 2 eyes with atopy, all amniotic membrane-covered surfaces showed rapid epithelialization (in 2 to 4 weeks) and reduced inflammation, vascularization, and scarring, and the surfaces became smooth and wettable. For the mean follow-up period of 15.4 months, 25 (83%) of 30 eyes showed visual improvement, consisting of 6 or more lines (13 eyes), 4 to 5 lines (6 eyes), or 1 to 3 lines (6 eyes). Visual improvement decreased with the severity of limbal deficiency from 8 (100%) of 8 eyes in group A to 5 (71%) of 7 eyes in group B and 11 (79%) of 14 eyes in group C. In group C, corneal graft rejection occurred in 9 (64%) of 14 eyes, and reversible early limbal allograft rejection was noted in 3 (14%) of 21 eyes of groups B and C. CONCLUSIONS: For partial limbal deficiency with superficial involvement, AMT alone is sufficient and hence superior to ALT because there is no need to administer cyclosporine. For total limbal deficiency, additional ALT is needed, and AMT helps reconstruct the perilimbal stroma, with reduced inflammation and vascularization, which collectively may enhance the success of ALT.

Adult↗

PubMed1998

Cytokines and tear function in ocular surface disease.

In summary, tear EGF levels correlate most strongly with tear production in normals, and it is likely that some form of homeostatic mechanism exists to provide a constant supply to the ocular surface. Commercial ELISA kits appear to measure EGF in tears with good consistency and may be useful in the future to improve comparability of data from different studies. In addition, in ocular rosacea, which mimics keratoconjunctivitis sicca in a number of respects, there is a differential increase in the level of the inflammatory cytokine IL-1 alpha in the tear fluid. Much of this elevation appears to be the result of reduced tear turnover, which may form an important positive feedback mechanism encouraging tear stagnation and the perpetuation of ocular surface inflammation.

Adult↗

PubMed1998

Factors related to miles driven between drinking and arrest locations among convicted drunk drivers.

The objectives of the study were to estimate the distance driven between drinking and arrest locations among 3,107 offenders convicted of driving while impaired and to determined whether the drinking location, the driver's appearance (factors such as race, age, gender), or age of the vehicle account for any differences in the estimated distance driven. Statistical models were used to determine odds ratios for being arrested in the immediate vicinity of the drinking location, and for miles driven impaired. The independent sociodemographic and arrest variables included: age, gender, ethnicity/race, vehicle age, drinking location, whether the arrest followed a crash, time of arrest, blood alcohol concentration, and drinking in areas with varying levels of arrest intensity. The variables associated with arrest in the immediate vicinity of the drinking location (less than one half mile) were drinking in high or medium-high arrest intensity areas, Hispanic/Mexican ethnicity/nationality, Native American race, and drinking at home. Among those who were not arrested in the immediate vicinity, the number of miles driven ranged from 0.5 to 18.2, with a mean of 3.4 miles (median = 2.6). Analysis of covariance demonstrated that among those arrested outside the immediate vicinity of their drinking locations, persons who drank in a high or medium-high arrest intensity area, those with blood alcohol concentrations of > or = 200 mg/l, and those drinking at bars, restaurants, or private parties, drove fewer miles compared to other offenders. Our findings are mixed regarding ethnicity/race. Traits such as age, gender, and vehicle age are unrelated to how far drunk drivers travel before their arrests.

Adolescent↗

PubMed1998

The Ets-1 transcription factor is required for the development of natural killer cells in mice.

In this report we have investigated the role of the Ets-1 transcription factor in the differentiation of the NK cell lineage in mice. Splenic NK cells express high levels of Ets-1. Ets-1-deficient mice produced by gene targeting developed mature erythrocytes, monocytes, neutrophils, and T and B lymphocytes. However, spleens from the Ets-1-deficient mice contained significantly reduced numbers of natural killer (NK) cells, and splenocytes from these mice lacked detectable cytolytic activity against NK cell targets in vitro. Moreover, unlike wild-type animals, Ets-1-deficient mice developed tumors following subcutaneous injection of NK-susceptible RMA-S cells. These NK cell defects could not be correlated with defects in the expression of IL-12, IL-15, and IL-18 or the IL-2 or IL-15 receptors. Thus, Ets-1 defines a novel transcriptional pathway that is required for the development of the NK cell lineage in mice.

Animals↗

PubMed1998

The effect of covertly manipulating the energy density of mixed diets on ad libitum food intake in 'pseudo free-living' humans.

OBJECTIVE: This study examined the effects of covert alterations in the energy density (ED) of mixed, medium fat (MF) diets on ad libitum food and energy intake (EI), subjective hunger and body weight in humans. DESIGN: Randomised cross-over design. Subjects were each studied three times (factorial design), during 14d, throughout which they had ad libitum access to one of three covertly-manipulated MF diets. SUBJECTS: Six healthy men, mean age (s.e.m.) = 30.0 y (12.76 y), mean weight = 71.67 kg (19.80 kg); mean height = 1.79 m (0.22 m), body mass index (BMI) = 22.36 (2.60) kg/m2, were studied. The fat, carbohydrate (CHO) and protein in each diet (as a proportion of the total energy) and energy density (ED) were, low-ED (LED), 38:49:13%; 373 kJ/100 g; medium-ED (MED), 40:47:13%; 549 kJ/100 g; high-ED (HED), 39:48:13%; 737 kJ/100 g. Subjects could alter the amount but not the composition of foods eaten. They were resident in (but not confined to) a metabolic suite throughout the study. RESULTS: Solid food intake decreased as ED increased, giving mean values of 2.84, 2.51 and 2.31 kg/d, respectively. This was insufficient to defend energy balance, since energy intake increased with increasing ED (F(2,10) 16.08; P < 0.001) giving mean intakes of 10.12, 12.80 and 16.17 MJ/d, respectively. Rated pleasantness of food (measured on visual analogue scales) was not significantly different between diets nor was subjective hunger different between the LED, MED and HED diets, respectively. Diet significantly affected body weight (F(2,10) = 4.62; P = 0.038), producing changes of -1.20, 0.02 and 0.95 kg, respectively, by day 14. CONCLUSION: Dietary ED can influence EI and body weight, since changes in amount eaten alone are insufficient to defend energy balance, when subjects feed on unfamiliar diets and diet selection is precluded. Comparison with our previous studies suggest that there was compensation in solid food intake when ED was altered using mixed diets (as in this study) compared to previous studies which primarily used fat or CHO to alter dietary ED.

Adult↗

PubMed1997

Direction of temperature control in the thermal biofeedback treatment of vascular headache.

In order to test for the specific therapeutic effects of thermal biofeedback (TBF) for hand warming on vascular headache (HA), 70 patients with chronic vascular HA were randomly assigned to TBF for hand warming, TBF for hand cooling, TBF for stabilization of hand temperature, or biofeedback to suppress alpha in the EEG. Patients in each condition initially had high levels of expectation of therapeutic benefit and found the treatment rationales highly credible. Participants in each condition received 12 treatment sessions on a twice-per-week basis. Based on daily HA diary data gathered for 4 weeks prior to treatment and 4 weeks after treatment, HA Index was significantly (p = .003) reduced as was HA medication consumption. There were no differential reductions in HA Index or Medication Index among the four conditions. Global self-reports of improvement gathered at the end of the post-treatment monitoring period also did not differ among the four conditions. We were unable to demonstrate a specific effect of TBF for hand warming on vascular HA activity.

Adolescent↗

PubMed1997

Inflammatory cytokines in the tears of patients with ocular rosacea.

OBJECTIVE: The purpose of the study is to compare tear fluid concentrations of interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), and epidermal growth factor (EGF) in ocular rosacea with those in control subjects and to examine the relation between tear functions, such as production and clearance rate, and the concentrations of cytokines in tear fluid. PARTICIPANTS AND INTERVENTION: Fourteen patients with severe meibomian gland disease, facial rosacea, and symptoms of ocular irritation were examined for ocular surface disease, tear production, and tear clearance rate (TCR). Twelve control subjects, frequency-matched for age, and 15 ideal normal subjects with no ocular symptoms and normal tear function were assessed using the same parameters. Minimally stimulated tear samples (20 microl) were drawn from each subject and analyzed using a sandwich enzyme-linked immunosorbent assay to detect IL-1alpha, TNF-alpha, and EGF. RESULTS: Tear IL-1alpha concentration was significantly higher in patients with rosacea than in age-matched (P = 0.003) and ideal control subjects (P < 0.001). Tumor necrosis factor-alpha was not detected in patients or control subjects, indicating levels of less than 10 pg/ml. Epidermal growth factor was not significantly higher in patients with rosacea than in age-matched control subjects. Tear turnover LN(TCR) was lower in patients with rosacea than in both age-matched (P = 0.048) and ideal control subjects (P = 0.002). Schirmer I scores were statistically lower in patients with rosacea than in ideal control subjects (P = 0.013), but not age-matched control subjects. Interleukin-1alpha was correlated inversely with LN(TCR) (r= -0.58, P < 0.0001) and Schirmer I (r = -0.39, P = 0.012). CONCLUSIONS: Concentrations of IL-1alpha are present in normal tears but are elevated in ocular rosacea, whereas TNF-alpha is not present in either case. The reduced tear turnover, LN(TCR), its inverse correlation with IL-1alpha, and the absence of TNF-alpha in the tears of these patients suggest that the increased concentration of IL-1alpha observed may be largely because of clearance failure of cytokine normally produced at the ocular surface.

Adult↗