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Biomedical subjects

R E Smith

Publications and source records attributed to R E Smith.

At least 145 records · Page 8Linked to original sources
PubMed1994

Incidence and management of cataracts in Vogt-Koyanagi-Harada syndrome.

Of 65 consecutive patients (130 eyes) with Vogt-Koyanagi-Harada syndrome, 26 (40%) developed cataracts (49 eyes, 38%). Twenty-eight cataracts were posterior subcapsular, six nuclear, 14 combined nuclear and posterior subcapsular, and one anterior cortical. Risk factors for the development of cataracts included age (P = .003), long-standing recurrent anterior segment inflammation (P < .001), and systemic corticosteroid therapy for six months or more (P < .001). After at least three months of minimal to no intraocular inflammation, 19 eyes underwent cataract extraction, of which 11 also had posterior chamber intraocular lens implantation. Median visual acuity improved significantly from 20/400 to 20/40 (P < .01) after a median follow-up time of 13 months. Route of preoperative corticosteroids, pars plana vitrectomy, and glaucoma surgery did not markedly affect visual prognosis. If preoperative intraocular inflammation is rigorously controlled, cataract surgery can be performed safely and can result in significant visual improvement in patients with Vogt-Koyanagi-Harada syndrome.

Adult↗
PubMed1994

Keratitis as a complication of bilateral, simultaneous radial keratotomy.

During a one-month period, we examined four patients referred for evaluation of probable microbial keratitis after bilateral, simultaneous radial keratotomy. Each patient had midstromal infiltrates compatible with microbial keratitis that involved one or more of the radial incisions. In two patients the keratitis was bilateral. All patients had been treated empirically with antibiotic agents; superficial cultures with cotton-tipped applicators and corneal scraping by inserting a platinum spatula into the radial incisions were negative. Corneal biopsy of one patient disclosed gram-positive rods and culture of the biopsy specimen grew diphtheroids. The infiltrates gradually resolved over a period of several months with intensive antibiotic therapy. Sight-threatening infectious keratitis can occur after radial keratotomy, and we believe that simultaneous bilateral ocular surgery of any kind should be discouraged.

Adult↗
PubMed1994

New stroboscopic light source for intraoperative retinal fluorescein angiography.

We tested a new stroboscopic light source for intraoperative fluorescein angiography. A pulsed xenon light source and narrow-band interference filters are coupled to a 20-gauge endoilluminator and a 35-mm camera mounted on a surgical microscope. The system was tested with good success in a patient undergoing penetrating keratoplasty. An 18- to 22-microJ flash of 2 milliseconds' duration is achieved, which is well below the safety threshold level. This new stroboscopic light source provides a flash of sufficient light intensity to perform high-resolution, high-contrast fluorescein angiography during operations for the removal of opacified media.

Aged↗
PubMed1994

Cysteine proteinase inhibitors decrease articular cartilage and bone destruction in chronic inflammatory arthritis.

OBJECTIVE: To determine the effects of peptidyl fluoromethyl ketones on the in vitro activity of purified cathepsins B and L, on tissue cysteine proteinase activity, and on cartilage and bone destruction in experimental arthritis. METHODS: The effects of the fluoroketones on cathepsins B and L in vitro and the effects of oral administration of fluoroketones on ex vivo cysteine proteinase activity in tissue homogenates were determined by measuring the inhibition of fluorogenic substrate cleavage. To determine the effects on arthritis, animals were injected with adjuvant or type II collagen, treated orally with the fluoroketones, and the severity of arthritis was assessed by clinical, histologic, and radiologic methods. RESULTS: All of the fluoroketones tested were potent inhibitors of purified cathepsins B and L activity. Oral administration of the fluoroketones reduced tissue cysteine proteinase activity by up to 77%. In addition, fluoroketone treatment significantly reduced the severity of clinical joint disease and decreased the destruction of articular cartilage and bone. Quantitative analysis of radiographic images indicated that treatment significantly reduced soft tissue changes, periosteal proliferation, and bone erosion, but only partially reduced juxtaarticular osteoporosis. CONCLUSION: These studies suggest that cysteine proteinase inhibitors may limit tissue destruction in diseases such as rheumatoid arthritis.

Animals↗
PubMed1994

Prevalence of HPV 16 and 18 DNA sequences in CIN III lesions of adults and adolescents.

Adolescents may be more susceptible to cervical human papillomavirus (HPV) infections and may have more rapid progression of cervical intraepithelial neoplastic (CIN) lesions than adults. We evaluated Papanicolaou (Pap) smears and cervical tissue specimens from a consecutive series of 25 adolescent (age 15-20 yr) and 17 adult (age 35-40 yr) patients with a histologic diagnosis of CIN III. The study patients were all Detroit residents enrolled in a health maintenance organization (HMO) affiliated with Henry Ford Hospital. The cervical tissue specimens were evaluated for HPV 6b/11, HPV 16, and HPV 18 using agarose gel electrophoresis and Southern hybridization following polymerase chain reaction (PCR) DNA amplification. While the small sample size precluded testing for statistical significance, HPV 16 and/or HPV 18 DNA was detected in specimens from 21/25 (84%) adolescents compared to 12/17 (71%) adults (odds ratio [OR] = 2.2; 95% confidence interval [CI] = 0.49-9.74). The relationship between adolescence and HPV infections appears to be stronger for HPV 18 and mixed HPV 16/18 infections (OR = 5.6; 95% CI = 0.7-42.4) than for HPV 16 infections (OR = 1.93; 95% CI = 0.4-8.8). None of the cervical specimens contained HPV 6b/11 DNA. Oral contraceptive (OC) use was associated with HPV infection in patients with CIN III, but there was no association between cigarette smoking and HPV infection. The effect of OC use on the relationship of age and HPV could not be evaluated due to small sample size. The effects of previous sexually transmitted disease (STD) on the relationship of age and HPV were assessed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Isozymes of 11 beta-hydroxysteroid dehydrogenase: which enzyme endows mineralocorticoid specificity?

Intracellular enzymes which interconvert circulating hormones between active and inactive forms aid in regulating the biological activity of the ligand in a cell-specific manner. This is particularly important in mineralocorticoid target tissues where glucocorticoids and mineralocorticoids have equivalent affinity for the mineralocorticoid receptor. Inactivation of glucocorticoids at the 11-hydroxyl position by the action of 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) permits the occupation of the mineralocorticoid receptor by aldosterone in the presence of much higher levels of circulating cortisol. The suppression of dehydrogenase activity allows glucocorticoids to activate the mineralocorticoid receptor, leading to classical mineralocorticoid type effects such as sodium retention and potassium excretion. A number of 11 beta-OHSDs are currently candidate protectors of the mineralocorticoid receptor. This review examines the attributes of these 11 beta-hydroxysteroid dehydrogenase isozymes and suggests reasons why a high affinity, NAD-dependent enzyme appears to be the most likely candidate to endow specificity on the mineralocorticoid receptor.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Cloning and tissue distribution of the human 11 beta-hydroxysteroid dehydrogenase type 2 enzyme.

The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) is thought to protect the non-selective mineralocorticoid receptor from occupation by glucocorticoids, and to modulate access of glucocorticoids to glucocorticoid receptors resulting in protection of the fetus and gonads. A ubiquitous low affinity NADP+ dependent enzyme (11 beta HSD1) and a tissue specific, high affinity NAD+ dependent form (11 beta HSD2) of 11 beta HSD exist. We now report the isolation of a cDNA coding for human 11 beta HSD2. The new isoform is NAD+ dependent, exclusively dehydrogenase in directionality, inhibited by glycyrrhetinic acid and metabolizes the synthetic glucocorticoid dexamethasone; it displays Km values for corticosterone and cortisol of 5.1 nM and 47 nM, respectively. Sequence alignment shows that 11 beta HSD2 shares 35% identity with 17 beta HSD2, but is only 14% identical with 11 beta HSD1. The 11 beta HSD2 gene is highly expressed in kidney, colon, pancreas and placenta and the message is also present in the ovary, prostate and testis. These data suggest that 11 beta HSD2 plays an important role in modulating mineralocorticoid and glucocorticoid receptor occupancy by glucocorticoids.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Endogenous mediators and thrombophilia.

Platelet function is a balance between factors determined at thrombopoiesis and prothrombotic and antithrombotic mediators from the vascular wall. Nitric oxide is a crucial vasodilator and inhibitor of platelet activation synthesized constitutively by the vascular endothelium. In some pathological states this synthesis may be impaired leading to a prothrombotic state. In other situations, synthesis may be increased by a second inducible enzyme. Nitric oxide synergizes with other antithrombotic vasodilators such as prostacyclin and is opposed by prothrombotic vasoconstrictor mediators such as thromboxane. Platelets are anucleate and their reactivity is partly determined at thrombopoiesis by their progenitor cell, the megakaryocyte. In thrombotic states, such as myocardial infarction, larger, more reactive platelets from larger megakaryocytes are observed.

Animals↗
PubMed1994

Examination of the factorial validity of the Group Environment Questionnaire.

The purpose of this study was to test the hypothesized factor structure of the Group Environment Questionnaire (GEQ) with confirmatory factor analysis and to ascertain the degree of factorial invariance across gender and across type of sport (team, individual). Additionally, the underlying theoretical structure on which the GEQ was developed was examined by fitting the data to alternative hierarchical factor structures. These models were tested with GEQ data collected on 740 high school varsity athletes (426 males, 314 females). It was shown that the males and females had different factor structures and that neither group exhibited the hypothesized structure. Attempts to fit the data to a two-factor and a second-order hierarchical factor model were unsuccessful. Finally, exploratory factor analysis did not produce a satisfactory four-factor solution. It was concluded that the data from this sample do not support the hypothesized four-factor structure of the GEQ and that further examination of the factor structure of this instrument is required.

Adolescent↗
PubMed1994

Platelet glycoprotein IIb-IIIa and size are increased in acute myocardial infarction.

Platelet aggregation, which plays an important role in acute myocardial infarction (AMI), is mediated by fibrinogen binding to the platelet membrane glycoprotein (GP)IIb-IIIa (CD41). This study measured the relative number of GPIIb-IIIa complexes on platelets from patients immediately following AMI (n = 14) compared with those from controls (n = 14). Flow cytometry was used to demonstrate that there were, on average, 20% more GPIIb-IIIa complexes on platelets after AMI compared with controls. Platelet size was also 7% greater in AMI and it is known that larger platelets are more reactive. Since platelet size and protein content are determined at thrombopoiesis the majority of these platelets must have been circulating prior to AMI. Larger platelets, with more GPIIb-IIIa may, therefore, be causally related to AMI.

Aged↗
PubMed1994

Surgical diathermy is not suitable for vascular tissue welding.

The possibility of using radiofrequency energy (RFE) to produce a sutureless anastomosis is attractive both to the military surgeon and on the grounds of cost and simplicity. To investigate this, fresh rabbit aorta was divided lengthways into 4 mm strips and apposed, intima-to-itima. A Valleylab Force 30 Electrosurgery machine supplied RFE at 500 kHz. The energy was applied using standard bipolar forceps and 121 attempts were made to weld the tissue. Seventy seven welds resulted of which 36 were able to withstand a distraction force of greater than 0.1N: the strongest weld was disrupted at 0.35N. Intact tissue withstood a distraction force of greater than 2N, whilst sutured joints disrupted at 0.97 N. It is concluded therefore that radiofrequency energy at 500 kHz does not satisfactorily weld vascular tissue.

Anastomosis, Surgical↗
PubMed1994

The role of endoscopy in the evaluation of iron deficiency anemia in patients over the age of 50.

OBJECTIVE: To determine the prevalence of various etiologies of iron deficiency anemia in patients over the age of 50 yr in order to better define the role of endoscopy in the evaluation of these patients and to see whether historical features are predictive of subsequent diagnostic findings. METHODS: We retrospectively reviewed the records of all patients referred for endoscopic evaluation of anemia between 1986 and 1990. To be included in the study, patients had to meet the following criteria: they must be more than 50 yr old and must have anemia and documented iron deficiency. Data collected included historical features, endoscopic or radiological procedures performed, and diagnostic findings. RESULTS: Of a total of 375 patients referred, 170 patients (119 men, 51 women), with a mean age of 69 yr, met the inclusion criteria. A lower gastrointestinal source of iron deficiency was identified in only 30 patients (18%), with carcinoma of the colon (9%), colitis (4%), and arteriovenous malformations (3%) being most common. An upper gastrointestinal source of iron deficiency was identified in 70 patients (41%). Peptic ulcer disease (15%), erosive esophagitis (8%) or gastritis (7%), previous partial gastrectomy (6%), and sprue (3%) were found most often. The etiology of iron deficiency was not identified in 70 patients (41%). In addition, historical features, including gastrointestinal symptoms, fecal occult blood testing, or a history of smoking, excessive alcohol intake, or use of nonsteroidal anti-inflammatory drugs, were poor predictors of diagnostic findings. CONCLUSION: A minority of patients over 50 yr of age have a colonic etiology for iron deficiency. Upper gastrointestinal sources of iron deficiency are prevalent and are frequently asymptomatic, but often they can be identified by upper endoscopy. Therefore, esophagogastroduodenoscopy with small bowel biopsies should be included in the evaluation of iron deficiency anemia in older patients, especially when a colonic source has not been identified.

Aged↗
PubMed1994

Effectiveness of histocompatibility matching in high-risk corneal transplantation: a summary of results from the Collaborative Corneal Transplantation Studies.

The Collaborative Corneal Transplantation Studies (CCTS) were designed to evaluate the effect of donor-recipient histocompatibility matching and crossmatching on the survival of corneal transplants in high-risk patients. Corneas were allocated to the 419 patients in the double-masked Antigen Matching Study on the basis of HLA-A,-B and HLA-DR antigen match. ABO blood group compatibility was determined but not used for recipient selection. The 37 patients in the Crossmatch Study were randomly assigned to receive a cornea from either a positively or negatively crossmatched donor. All patients received topical steroid therapy according to a standard protocol. Matching for HLA-A,-B and HLA-DR antigens had no effect on overall graft survival, the incidence of irreversible rejection, or the incidence of rejection episodes. The positive group in the Crossmatch Study had fewer graft failures, rejection failures, and rejection episodes than the negative group; however, these differences were not statistically significant. The estimated proportion of eyes with failure from rejection by 3 years was 30% for the ABO-incompatible group and 16% for the ABO-compatible group (relative risk, 1.98; 95% confidence interval, 1.15 to 3.13). These studies demonstrate that, for high-risk patients who are immunosuppressed by topical steroid therapy: 1) neither HLA-A.-B nor HLA-DR antigen matching substantially reduced the likelihood of corneal graft failure; 2) a positive donor-recipient crossmatch did not increase the risk of corneal graft failure; and 3) ABO blood group matching may be effective in reducing the risk of graft failure from rejection.

ABO Blood-Group System↗
PubMed1994

Production of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 alpha by inflammatory granuloma fibroblasts.

The formation of hepatic granulomas around persistently deposited Schistosoma mansoni eggs leads to parenchymal damage, ongoing fibrosis, and ultimate loss of liver function. In this study, the production of macrophage inflammatory protein-1 alpha (MIP-1) and monocyte chemoattractant protein-1 (MCP-1) by granuloma fibroblasts was examined to establish the potential contribution of intragranuloma fibroblasts to the maintenance of the chronic inflammation. Isolated fibroblasts from dispersed acute infection hepatic granulomas were grown in tissue culture for 3 to 4 weeks and used on the third or fourth passage. We initially surveyed fibroblasts for production of MIP-1 and MCP-1 by reverse transcription-polymerase chain reaction (RT-PCR) after stimulation with interleukin (IL)-1, tumor necrosis factor, interferon (IFN)-gamma, IL-4, or IL-10: cytokines found within the granuloma. These studies demonstrated constitutive expression of MCP-1 and differential up-regulation of MIP-1 on cytokine stimulation. Protein expression was then verified by immunohistochemical localization of MIP-1 and MCP-1 in paraformaldehyde-fixed fibroblasts and by direct quantitation of MIP-1 and MCP-1 in culture supernatants by specific ELISAs. These studies demonstrated constitutive expression of MCP-1 in unstimulated and cytokine-stimulated granuloma fibroblasts. In contrast, IL-1 (0.1 to 2.5 ng/ml), IFN-gamma (10 micrograms/ml), and IL-10 (2.5 to 10 ng/ml) were able to induce the significant production of MIP-1 by the granuloma fibroblasts. Interestingly, normal noninflammatory fibroblasts from uninfected mice showed no significant production of MIP-1 or MCP-1 in response to these cytokines. These results suggest that granuloma fibroblasts may be phenotypically altered compared with normal fibroblasts and have a significant role in leukocyte recruitment, granuloma growth, and maintenance of the egg-induced lesion.

Animals↗
PubMed1994

Corneal endothelial modulation: bFGF as direct mediator and corneal endothelium modulation factor as inducer.

PURPOSE: Previously reported from this laboratory are two distinct factors responsible for corneal endothelium modulation: basic fibroblast growth factor (bFGF) and the corneal endothelium modulation factor (CEMF) that is released by inflammatory cells. The altered phenotypes mediated by these two distinct factors--marked increase in cell proliferation, cell shape changes, and synthesis of fibrillar collagens--are identical. The current study sought to determine if bFGF is the direct mediator for corneal endothelium modulation and if CEMF plays a role in inducing bFGF production. METHODS: bFGF synthesis mediated by CEMF was analyzed by immunoblot assay; cycloheximide was used to block protein synthesis. bFGF-Specific antisense oligonucleotide primer was used to inhibit CEMF-mediated bFGF synthesis and to block further the autocrine activity of bFGF. Cell proliferation was measured by cell counting. The steady-state levels of RNA were determined by Northern blot analysis. CEMF was further purified to homogeneity by sequential electrophoresis, elution, and renaturation of protein. RESULTS: The synergistic effect of CEMF and bFGF on corneal endothelial cells was measured by their growth-promoting activity on quiescent corneal endothelial cells. There was a dose-dependent cell proliferation mediated by bFGF at any given CEMF concentration. Thus, bFGF at 10 ng/ml with CEMF at 2.5 micrograms/ml demonstrated saturable synergistic activity on endothelial cell proliferation. When the steady-state levels of collagen RNA were measured under these conditions, the untreated cells showed the doublets of 5.6 and 5.0 kb of alpha 2(I) collagen RNA. The cells treated simultaneously with bFGF and CEMF contained mostly lower transcript, compared to the significant level of upper transcript in control cells. However, there was no significant change in the level of 6.9-kb type IV collagen RNA qualitatively or quantitatively; nonetheless, the level of alpha 2(IV) collagen RNA was lowest in cells treated with bFGF plus CEMF. Neither exogenous bFGF nor CEMF caused induction of bFGF messenger RNA in corneal endothelial cells, whereas simultaneous treatment with bFGF and CEMF selectively enhanced the 4.9-kb transcript. When protein synthesis was inhibited by cycloheximide, bFGF synthesis was blocked in the presence of CEMF, leading to inhibition of corneal endothelium modulation. The effect on endothelial cell growth of bFGF antisense primer was analyzed. Antisense primer blocked by 50% the enhanced growth potential mediated by bFGF induced with CEMF. Finally, CEMF was purified to homogeneity: the purified protein is approximately 17 kD and assumes the modulating activities. CONCLUSIONS: These findings suggest that de novo synthesis of bFGF induced by CEMF is required for corneal endothelium modulation.

Animals↗
PubMed1993

Subretinal neovascular membranes in Vogt-Koyanagi-Harada syndrome.

Subretinal neovascular membranes cause late visual loss and are important determinants of final visual acuity in patients with Vogt-Koyanagi-Harada syndrome. The purpose of this study was to determine the prevalence and risk factors associated with the development of subretinal neovascular membranes in Vogt-Koyanagi-Harada syndrome. We reviewed the charts of 58 patients (116 eyes) with Vogt-Koyanagi-Harada syndrome. We separated patients into two groups, one with and one without subretinal membranes. Demographic characteristics, namely age, gender, and race, initial and final visual acuities, duration and method of treatment, anterior chamber and vitreous cell, presence of fundus pigmentary disturbances, and phase of inflammation, were evaluated for each group. Overall, ten eyes (9%) of seven patients developed the subretinal neovascular membranes. Demographic characteristics among the two groups of patients were not markedly different (P > .10). Visual outcome of patients with subretinal membranes was significantly poorer than was that of patients without these membranes (P < .001). Eyes with subretinal membranes had a significantly greater degree of anterior chamber and vitreous inflammation (P < .02), greater incidence of fundus pigmentary disturbances (P < .02), and a greater frequency of chronic recurrent phase of inflammation, marked by recurrence of predominantly anterior chamber, and occasionally posterior segment, inflammation (P < .02). The membranes were located in the peripapillary (four eyes), subfoveal (three eyes), and macular extrafoveal (three eyes) regions.

Adult↗