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Biomedical subjects

C M Schmidt

Publications and source records attributed to C M Schmidt.

At least 55 records · Page 3Linked to original sources

Long term effect of apraclonidine.

AIMS: To evaluate the effect of the chronic use of apraclonidine 0.5% on the intraocular pressure (IOP) of patients with glaucoma; also, to study the side effect profile of this drug when used chronically. METHODS: All patients who had uncontrolled IOP, who were either already on glaucoma medications, or who were intolerant of other glaucoma medications were enrolled. A total of 185 patients were started on apraclonidine 0.5% two to three times a day in one eye. RESULTS: Follow up extended to 35 weeks. The mean difference in IOP between treated and control eyes was 2.1 (SD 5.0) mm Hg. A similar IOP lowering effect was obtained comparing IOP difference from baseline in the treated eye only. CONCLUSION: By the end of the follow up period, 46% of patients were still on the medication. The drug was stopped in 23% of patients because of side effects and in 31% of patients because of failure to lower IOP significantly.

Adolescent↗

Results of alloplastic tube shunt procedures before, during, or after penetrating keratoplasty.

The association of glaucoma and penetrating keratoplasty presents a difficult management problem, particularly when medical therapy and conventional glaucoma surgery have failed. We have found alloplastic tube shunt surgery to be an effective method for intraocular pressure control in glaucomatous eyes subjected to penetrating keratoplasty. We report 46 patients who underwent alloplastic tube shunt implantation before (13 patients, group A), in combination with (17 patients, group B), or after (16 patients, group C) penetrating keratoplasty. All groups had significantly lowered intraocular pressure postoperatively. The most common complication was graft failure, in 31% of patients in group A, 29% in group B, and 44% in group C. Other postoperative complications and results including visual outcome are reviewed. Because the management of advanced glaucoma in patients undergoing keratoplasty is difficult, alloplastic tube shunt implantation should be considered.

Adolescent↗

Trabeculectomy is associated with retrobulbar hemodynamic changes. A color Doppler analysis.

PURPOSE: To determine whether color Doppler hemodynamic changes occur in the retrobulbar circulation after trabeculectomy. METHODS: The authors prospectively enrolled 20 patients undergoing trabeculectomy and performed color Doppler imaging of both eyes before surgery and then at approximately 2-, 5-, and 14-week intervals after surgery. The systolic maximum velocity, mean velocity, end-diastolic velocity, and vascular resistance (resistance index) of the central retinal artery, nasal and temporal short posterior ciliary arteries, and ophthalmic arteries were determined. Statistical comparison of the preoperative and postoperative measures were performed on both the operative and nonoperative eye using the paired Student's t test. RESULTS: A statistically significant increase was observed in the mean and end-diastolic velocity and a significant decrease in the vascular resistance of the central retinal artery and both short posterior ciliary arteries at nearly all postoperative intervals (25 of 27 preoperative and postoperative comparisons; P < 0.05) The ophthalmic artery, while showing an increased velocity at all intervals, only attained a statistically significant increase in one of three postoperative intervals for mean velocity and two of three intervals for end-diastolic velocity (P < 0.05). There were no notable changes in resistance. The nonoperative eye did not show a statistically significant change in velocity or in resistance in the central retinal artery or either nasal or temporal short posterior ciliary artery at any interval (0 of 27 preoperative and postoperative comparisons for mean velocity, end-diastolic velocity, and resistance index.) CONCLUSION: Sustained increases in mean velocity and end-diastolic velocity and decreases in resistance index were observed in the central retinal artery and the short posterior arteries with clinically attainable reductions in intraocular pressure after trabeculectomy in patients with chronic glaucoma. These findings are consistent with, but not diagnostic of, increased blood flow through these vessels.

Adult↗

Cellular distribution of HLA-G mRNA in transgenic mouse placentas.

The human MHC class I gene, HLA-G, is unique among members of the class I gene family in that it is nonpolymorphic, and expression is primarily restricted to extraembryonic tissues. To examine regulatory elements that direct tissue- and cell lineage-specific expression of this gene, transgenic mice expressing HLA-G have been established. In this study, in situ hybridization was used to evaluate the cellular distribution of HLA-G mRNA in transgenic placentas. Extraembryonic tissues were obtained at gestation day 12.5 from embryos that had been microinjected with either 6.0 or 5.7 kb of HLA-G genomic DNA and had been transferred into pseudopregnant HLA-G transgenic mice or Swiss mice. The 6.0 kb transgene contained an additional 250 bp at the extreme 5'-end of the upstream region. Genotype of the recipient had no discernable effect on the cellular distribution of HLA-G mRNA. HLA-G mRNA was present in both trophoblast and mesenchymal cells in transgenic placentas carrying 6.0 kb of genomic HLA-G, a pattern strikingly similar to that of HLA-G message distribution in early gestation human placentas. By contrast, in placentas from embryos carrying 5.7 kb HLA-G DNA, specific mRNA was found primarily in mesenchymal cells at the base of the placenta. Thus, the 6.0 genomic fragment contains elements capable of directing HLA-G expression in placentas, and is particularly influential in the trophoblastic cell lineage.

Animals↗

Extraembryonic expression of the human MHC class I gene HLA-G in transgenic mice. Evidence for a positive regulatory region located 1 kilobase 5' to the start site of transcription.

Trophoblast, the only fetal tissue in direct contact with maternal cells, fails to express the polymorphic HLA class I molecules HLA-A and -B, but does express the nonpolymorphic class I molecule HLA-G. It is thought that HLA-G may provide some of the functions of a class I molecule without stimulating maternal immune rejection of the fetal semiallograft. As a first step in identifying the cis-acting DNA regulatory elements involved in the control of class I expression by extraembryonic tissue, several types of transgenic mice were produced. Two HLA-G genomic fragments were used, 5.7 and 6.0 kb in length. These included the entire HLA-G coding region, 1 kb of 3' flanking sequence, and 1.2 or 1.4 kb of 5' flanking sequence, respectively. A hybrid transgene, HLA-A2/G, was produced by replacing the 5' flanking sequence, first exon, and early first intron of HLA-G with the corresponding elements of HLA-A. Comparison of transgene mRNA expression patterns seen in HLA-A2/G and HLA-G transgenic mice suggests that 5' flanking sequences are largely responsible for the differing patterns of expression typical of the classical class I and HLA-G genes. Studies comparing the extraembryonic HLA-G expression levels of founder embryos transgenic for either the 5.7- or 6.0-kb HLA-G transgene showed that the 6.0-kb transgene directed HLA-G expression far more efficiently than did the 5.7-kb HLA-G transgene, producing extraembryonic HLA-G mRNA levels similar to those seen in human extraembryonic tissues. The results of these studies suggest that the 250-bp fragment present at the extreme 5' end of the 6.0-kb HLA-G transgene and absent from the 5.7-kb HLA-G transgene contains an important positive regulatory element. This 250-bp fragment lies further upstream than any of the previously documented class I regulatory regions and may function as a locus control region.

Animals↗

Glaucoma in the immediate postoperative period after penetrating keratoplasty.

In a prospective study 155 consecutive patients undergoing penetrating keratoplasty were examined for postoperative increase in intraocular pressure to determine the frequency and duration of intraocular pressure spikes, risk factors, and response to treatment. Patients were maintained on preoperative glaucoma medications except miotics. Additional medications to lower intraocular pressure perioperatively were not given. Intraocular pressure was measured two to five hours, one day, and one week postoperatively. An intraocular pressure of 30 mm Hg or greater was considered an increase in pressure and was treated according to a standardized protocol. The results were analyzed by procedure as well as by variables commonly perceived to be associated with intraocular pressure increase (history of glaucoma, use of hyaluronate, lysis of the synechiae, or vitrectomy at the time of the operation). Overall, intraocular pressure increases in the early postoperative period occurred in 18 of 155 patients (12%). Pressure increases occurred in ten of 48 patients (21%) with a history of glaucoma; five of 24 patients (21%) undergoing combined penetrating keratoplasty, extracapsular cataract extraction, and posterior chamber intraocular lens implantation; and ten of 43 patients (23%) undergoing vitrectomy at the time of penetrating keratoplasty.

Cataract Extraction↗

Effects of topical mitomycin C on primary trabeculectomies and combined procedures.

The charts were reviewed of all patients who underwent primary trabeculectomies (group 1) or combined procedures (phacoemulsification + intraocular lens implantation + trabeculectomy--group 2) and received intraoperative mitomycin C (0.4 mg/ml) between 1991 and 1992 at Wills Eye Hospital. A total of 54 eyes of 54 patients were included: 39 in group 1 and 15 in group 2. Intraocular pressure was controlled successfully in 97.4% of eyes in group 1 (mean follow up 6.7 months), and in 93.3% in group 2 (mean follow up 6.8 months). Main complications included choroidal detachment (n = 15), shallow anterior chamber (n = 9), cataract formation (n = 8), and hypotony maculopathy (n = 3). The use of mitomycin C in primary trabeculectomies and combined procedures is associated with high success rates. However, it may be associated with unacceptable risks of vision threatening complications related to excessive filtration.

Administration, Topical↗

Maternal/fetal interactions: the role of the MHC class I molecule HLA-G.

The unique pattern of class I major histocompatibility complex (MHC) antigen expression seen at the human maternal/fetal interface is thought to be vital for fetal well-being. The lack of polymorphic class I and II MHC antigens on trophoblasts, the only fetal tissue in direct contact with the mother, is likely to be at least a part of the explanation of fetal evasion of allograft rejection. The recent observation that the HLA-G-encoded class I MHC molecule is present on certain subpopulations of cytotrophoblasts suggests that this nonpolymorphic molecule may have a role in the maternal/fetal immune response. Although no experimental evidence exists to support a particular function for HLA-G, reasoned speculation about the possible roles of this nonpolymorphic class I molecule is possible. Data derived from sequence analysis, analysis of HLA-G expression patterns, analysis of the extraembryonic expression patterns of other genes, and analysis of decidual lymphocyte phenotype and function provide insight into the possible functions of HLA-G at the maternal/fetal interface and are considered here.

Base Sequence↗

The influence of primary open-angle glaucoma upon the retrobulbar circulation: baseline, postoperative and reproducibility analysis.

CDI is showing continued promise as a reliable, reproducible method to assess the hemodynamics of a variety of ophthalmic diseases in which vascular perfusion abnormalities are suspect. Moreover, some patients with advanced POAG appears to have abnormalities of the vasculature of the retrobulbar circulation that is corrected by trabeculectomy. Continued CDI clinical correlations with longitudinal studies are now required to elucidate the significance of this technology and these results for individual patients.

Adult↗

Hypotony maculopathy following the use of topical mitomycin C in glaucoma filtration surgery.

Intraoperative mitomycin C has been shown to be highly effective in increasing the success rate of glaucoma filtration surgery. Between October 1991 and June 1992, 169 eyes of 156 patients underwent filtration procedures with intraoperative mitomycin C. In the postoperative period, five eyes (2.9%) developed hypotony maculopathy, characterized by disc edema, vascular tortuosity, and chorioretinal folds in the macular area. Cryotherapy was applied to three eyes, and was effective in reversing the hypotony in two of them. However, the visual prognosis was poor: after a mean follow up of 5.3 months (range, 3.5 to 8 months), visual acuity returned to preoperative levels in one case. Hypotony maculopathy may develop after glaucoma filtration surgery with intraoperative mitomycin C. We suggest restricting the indication of its adjunctive use to eyes with poor surgical prognosis or those in which a very low intraocular pressure is desired. The use of extra sutures (which can be sectioned by laser) or releasable sutures to prevent excessive filtration in the postoperative period also is advisable.

Administration, Topical↗

Aqueous shunts. Molteno versus Schocket.

The authors conducted a multicenter, randomized, controlled trial to test whether the Schocket shunt with a larger shunt reservoir surface area would provide a lower final intraocular pressure than the double-plate Molteno implant. However, the Molteno implant produced a statistically lower intraocular pressure at 6 months compared with the Schocket shunt. Postoperative visual acuity, glaucoma medications, and complications were not statistically different.

Aqueous Humor↗

A physical linkage map of HLA-A, -G, -7.5p, and -F.

The class I region of the human leukocyte antigen (HLA) complex includes genes encoding the classical transplantation antigens (HLA-A, -B, -C), at least three nonclassical class I genes (HLA-E, -F, and -G), and many class I pseudogenes (including HLA-7.5p). We have used probes from DNA within or flanking the HLA -A, -F, -G, and -7.5p genes to construct a physical linkage map that places the HLA-F, -G, and -7.5p loci in order with respect to HLA-A. The map was constructed using clamped homogeneous electric field pulsed-field gel electrophoresis. DNA was isolated from LCL 721 (A1:B8, A2:B5), a human Epstein-Barr virus-transformed lymphoblastoid cell line (LCL), and from two gamma-irradiation-induced mutants of LCL 721 lacking complementary class I haplotypes. The physical linkage data place HLA-G closest to HLA-A and place HLA-7.5p between HLA-G and HLA-F. The map constructed supports a maximum distance of 490 kilobases between HLA-A and HLA-F.

Cell Line, Transformed↗

Methods in pathology. Immunophenotype of hairy cell leukemia in paraffin sections.

The immunophenotype of hairy cell leukemia (HCL) was investigated using 20 routinely fixed paraffin-embedded tissue sections (12 bone marrows, six spleens, one liver, one lymph node) from 12 patients known to have this disease. A panel of antibodies was used, including anti-leukocyte common antigen (anti-LCA), B-lineage antibodies (LN2, MB2, L26), T-lineage reagents (MT1, UCHL1), monocytic (anti-cathepsin B) and myelomonocytic (anti-lysosyme, Mac 387) antibodies, and other less lineage-specific markers (anti-S-100, anti-alpha-1-antichymotrypsin (anti-alpha 1-ACT), anti-alpha 1-antitrypsin (anti-alpha 1-AT), anti-vimentin). Anti-LCA stained hairy cells in seven of the 12 bone marrows and consistently recognized hairy cells in the spleen, liver, and lymph nodes. Hairy cells generally reacted with B-lineage antibodies and were not labeled by T-lineage markers. No reactivity was noted with myelomonocytic antibodies, anti-S-100, anti-alpha 1-ACT, or anti-alpha 1-AT. Vimentin was expressed in the majority of cases. Tartrate-resistant acid phosphatase reactivity was demonstrated in three of the 20 routinely processed tissue sections. These data suggest that immunohistochemical studies of hairy cell leukemia in routinely processed tissue may be useful in diagnostic hematopathology and surgical pathology.

Acid Phosphatase↗

The genetic risk screening, education, and referral program: a model program for training of health professionals.

This report describes a statewide program which trains family-planning personnel to provide genetic risk screening, to educate clients about potential genetic risks, and to make appropriate referrals to genetics centers. The program is unique in that training and service delivery are all done within the structure and agencies of the family-planning councils of Pennsylvania. Through the collaboration of the Pennsylvania Department of Health, the family-planning councils, and trainers from clinical genetics centers, a uniform and comprehensive program for training and service delivery has evolved. This program now provides genetic risk screening for nearly 100,000 women/year, many of whom are from groups typically underserved by genetics services.

Curriculum↗

Stem and stromal cell reconstitution of lethally irradiated mice following transplantation of hematopoietic tissue from donors of various ages.

If the limited life span of hematopoietic tissues in vitro is due to a finite proliferative capacity of individual stem cells, one might expect tissues of young donors to possess a greater proliferative capacity and to contain a larger population of primitive stem cells than those of older donors. To test this hypothesis, we used 12- and 8-day spleen colony formation (CFU-s) to assay more and less primitive stem cell subpopulations of three murine hematopoietic tissues: fetal liver (FL) and weanling (WBM) and adult (ABM) bone marrow. Subsequently, the same assays and a stromal cell assay were performed on the bone marrow from groups of lethally irradiated mice reconstituted with these tissues. Comparison of the CFU-s content of the donor tissues revealed that FL contained a significantly greater proportion of primitive stem cells as evidenced by a (Day 12):(Day 8) CFU-s ratio of 3.0 +/- 1.0 as compared to 0.9 +/- 0.1 for WBM and ABM. In addition, at 21 weeks post-transplantation the CFU-s/femur values of the FL reconstituted group were significantly greater than those of the ABM and WBM reconstituted groups. These results suggest that fetal hematopoietic tissue contains a greater proportion of primitive stem cells and has a greater proliferative potential than hematopoietic tissue from older donors. No differences were seen in stromal cell reconstitution of the three experimental groups. In all cases, assayable fibroblast colony forming cells (CFU-f) remained at 20-40% of control values, even at 21 weeks postreconstitution.

Aging↗

Encouraging patients to undergo prenatal genetic counseling before the day of amniocentesis. Its effect on the use of amniocentesis.

The purpose of this study was to determine if encouraging in-depth prenatal genetic counseling before the day of possible genetic amniocentesis affected the use of amniocentesis. Five hundred two patients were referred to our center for prenatal genetic services during a 15-month period. All patients were scheduled for genetic counseling before possible amniocentesis. During the initial three months (group I), patients were routinely scheduled for counseling on the same day of the procedure unless they requested earlier counseling. During the subsequent 12 months (group II), patients were encouraged to undergo counseling before the day of planned amniocentesis, and 48% agreed. When early counseling was encouraged, the use of amniocentesis decreased from 85% (group I) to 73% (group II) (P less than .025). Among patients with advanced maternal age as the only indication for testing (n = 375), utilization of amniocentesis decreased from 93% (group I) to 78% (group II) (P less than .005). A policy of encouraging early prenatal genetic counseling appears to be a significant factor in the use of genetic amniocentesis.

Amniocentesis↗