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Biomedical subjects

M Sherwood

Publications and source records attributed to M Sherwood.

18 recordsLinked to original sources

Six-month comparison of bimatoprost once-daily and twice-daily with timolol twice-daily in patients with elevated intraocular pressure.

The efficacy and safety of bimatoprost, a member of a new class of pharmacological agents called prostamides, were compared with the efficacy and safety of timolol in patients with glaucoma or ocular hypertension. Pooled 6-month results from two ongoing, multicenter, randomized, double-masked, clinical trials were analyzed. Patients were randomized in a 2:2:1 ratio to treatment with bimatoprost 0.03% once a day ([QD] n = 474), bimatoprost 0.03% twice a day ([BID] n = 483), or timolol 0.5% BID (n = 241). Scheduled visits were at prestudy, baseline, week 2, week 6, month 3, and month 6. The primary outcome measure was in diurnal intraocular pressure ([IOP] 8 AM, 10 AM, 4 PM, 8 PM). Bimatoprost QD provided significantly greater mean IOP reductions from baseline than timolol at every time of the day and at each study visit (p </=.05). BID dosing of bimatoprost also provided significantly greater mean IOP reductions than timolol at most timepoints, but was not as effective as QD dosing. The IOP lowering provided by bimatoprost QD was sustained for 6 months. At month 6, the mean IOP reduction from baseline at 10 AM was 8.1 mm Hg (33%) with bimatoprost QD, 6.3 mm Hg (26%) with bimatoprost BID, and 5.6 mm Hg (23%) with timolol. Low target pressures were achieved by a significantly higher percentage of patients in the bimatoprost QD group than in the timolol group. At 10 AM (peak timolol effect) at month 6, IOP </= 17 mm Hg was achieved by 63.9% of bimatoprost QD patients, compared with 37.3% of timolol patients (p <.001). Bimatoprost was safe and well-tolerated, with few discontinuations due to adverse events. The most frequent side effect was trace-to-mild conjunctival hyperemia. Changes in iris pigmentation were reported in 1.1% of bimatoprost patients. There were no other significant findings in slit lamp examinations, ophthalmoscopy, visual acuity, or visual fields, and systemic safety parameters were also unaffected. Together these results indicate that bimatoprost QD is statistically and clinically superior to timolol in lowering IOP, and is safe and well-tolerated in patients with glaucoma or ocular hypertension.

Adrenergic beta-Antagonists↗

The phototoxicity of photodynamic therapy may be suppressed or enhanced by modulation of the cutaneous vasculature.

In photodynamic therapy, the threshold for light induced toxicity depends on the drug concentration and the light dose. This study was aimed to show for vascular photosensitizers that the toxicity threshold on normal tissue may be predictably modified by modulation of the cutaneous vasculature. Albino rabbits were injected with 1.0 mg/kg of a vascular photosensitizer, benzoporphyrin derivative monoacid ring-A. The threshold light dose for toxicity to normal skin was determined at an absorption maximum of the drug (694 nm), 1 h after drug injection. The cutaneous vasculature was dilated by prior skin exposure to ultraviolet radiation or was constricted by iontophoretic application of epinephrine. Threshold toxicity was determined clinically and by assessing the effective concentration of hemoglobin in the skin by diffuse reflectance spectroscopy (DRS). Tissue samples that received threshold doses were investigated with light and electron microscopy. The toxicity threshold increased by 3.2+/-0.9 (mean+/-S.D.) following vasoconstriction and decreased by 3.6+/-0.8 following vasodilation, compared to control sites. Light and electron microscopy showed similar findings at threshold for both vasodilated and vasoconstricted sites. Therefore vascular modulation may be used to predictably enhance or suppress the level of phototoxicity of normal skin.

Animals↗

The Glaucoma Symptom Scale. A brief index of glaucoma-specific symptoms.

OBJECTIVE: To develop a brief symptom survey specific for persons with glaucoma, the Glaucoma Symptom Scale (GSS). DESIGN: Cross-sectional study of symptoms, functional impairment, and vision-targeted health-related quality of life among persons with glaucoma. PATIENTS: A sample of 147 persons with glaucoma among a broad range of treatment categories from 4 tertiary care glaucoma centers and 44 persons without eye disease enrolled from the same 4 centers. MAIN OUTCOME MEASURES: Participants completed a modified version of the Ocular Hypertension Treatment Study 10-item symptom checklist. Participants also completed 2 vision-specific measures, the National Eye Institute Visual Function Questionnaire and the VF-14. Participants underwent a clinical evaluation, including ocular and medical history, dilated ophthalmic examination, and Humphrey 24-2 automated visual field testing. RESULTS: The GSS has 2 underlying domains that demonstrate sufficient internal consistency reliability for between-group comparisons. The GSS discriminates well between persons with and without glaucoma. Additionally, tests of association with clinical markers of glaucoma severity support the clinical validity of the measure and tests of association with established vision-targeted measures provide evidence of construct validity. CONCLUSION: The simplicity, brevity, and psychometric properties of the GSS support its use in clinical practice and research to quantify symptoms in patients with glaucoma and to assist in investigations concerning the effect of glaucoma and treatments.

Cross-Sectional Studies↗

Latanoprost treatment for glaucoma: effects of treating for 1 year and of switching from timolol. United States Latanoprost Study Group.

PURPOSE: To determine the efficacy and safety of latanoprost treatment for 1 year in glaucoma patients, and to evaluate the effects of switching from timolol to latanoprost therapy. METHODS: Latanoprost 0.005% was topically applied once daily without masking for 6 months in 223 patients with elevated intraocular pressure after previous treatment with latanoprost once daily or 0.5% timolol twice daily for 6 months in a multicenter, randomized, double-masked, parallel group study. RESULTS: Compared with baseline values before treatment, a significant (P < .0001) diurnal reduction in intraocular pressure of 6 to 8 mm Hg was maintained with minimal fluctuation for the duration of treatment. When treatment was switched from timolol to latanoprost, intraocular pressure was reduced by 1.5 +/- 0.3 mm Hg (mean +/- SEM; 8% change in intraocular pressure; 31% of the intraocular pressure reduction produced by timolol; P < .001) compared with the change in intraocular pressure in patients remaining on latanoprost therapy. Of the patients initially enrolled, 95% successfully completed treatment. There was a slight overall increase in conjunctival hyperemia in patients who switched from timolol to latanoprost, but no change in those who continued latanoprost. The timolol-induced reduction of resting heart rate returned to baseline levels after switching to latanoprost. Of the 247 patients treated with latanoprost during the masked and/or open-label studies, 12 (5%) demonstrated a definite (n = 4) or possible (n = 8) increase in iris pigmentation. CONCLUSIONS: Latanoprost is a well-tolerated ocular hypotensive agent that appears to be more effective than timolol in reducing intraocular pressure. The increase in iris pigmentation appears to be harmless but requires further investigation.

Adult↗

t(1;18)(q32.1;q22.1) associated with genitourinary malformations.

We report a male infant who has impaired penile development, hypospadias, and mild developmental delay with a 46,XY,t(1;18)(q32.1;q22.1) karyotype. Fluorescent in situ hybridization (FISH) was performed to more precisely map the translocation breakpoint. The translocation breakpoint maps to a region that has been implicated in genitourinary malformations in the 18q- syndrome. This case report suggests that a gene involved in genitourinary development maps at or near the chromosome 18 translocation breakpoint.

Chromosomes, Human, Pair 1↗

The development of indications for the preoperative use of recombinant erythropoietin.

OBJECTIVE: To develop indications for the preoperative use of recombinant erythropoietin (rHuEPO) alone and in conjunction with preoperative autologous donation (PAD). DESIGN: A 2-round modified Delphi-consensus process. PARTICIPANTS: Nine physicians representing multiple clinical specialties, practice environments and geographic locations. METHOD: From evidence tables and a literature summary (MEDLINE database from January 1985 to August 1996) provided and using the RAND-UCLA appropriateness method, the physicians developed 264 indications for the preoperative use of rHuEPO by permuting 7 clinical factors (age, history of transfusion or antibody incompatibility, hemoglobin level, anemia of chronic disease, expected blood loss, presence of cardiovascular or cardiopulmonary disease and patient anxiety). These indications were rated on a 9-point appropriateness scale. Median scores and measures of agreement were determined. OUTCOME MEASURES: The significance of cost constraints or cost and blood supply constraints and the impact of each clinical factor on the ratings as judged by statistical analysis. RESULTS: Of the 264 indications, 54% were rated appropriate, 18% uncertain and 28% inappropriate. Expected blood loss had the greatest impact on the ratings (high expected blood loss had a 5.9 point more appropriate rating on the 9-point scale than low expected blood loss [p < 0.0001]). Preoperative hemoglobin level also significantly influenced the ratings (p < 0.0001). Compared with the clinical context, the ratings under the cost constraint were 1.0 less appropriate (p < 0.0001) for rHuEPO alone and 1.2 less appropriate for rHuEPO and PAD (p < 0.0001). The ratings for patients with moderate expected blood loss were significantly influenced by the cost constraint (less appropriate). CONCLUSIONS: Expected blood loss and preoperative hemoglobin level were the best indicators of rHuEPO appropriateness. Different contexts modify the appropriateness ratings of an expensive drug like rHuEPO.

Blood Loss, Surgical↗

Influence of glaucomatous visual field loss on health-related quality of life.

We examined the influence of glaucomatous visual field defects on vision-targeted and generic health-related quality of life. Vision-targeted and generic health status were assessed across 5 glaucoma treatment categories and a normal reference group from 5 tertiary care ophthalmology practices during regularly scheduled eye care visits. The sample consisted of 147 patients who were members of specific glaucoma treatment categories and 44 reference group patients. For patients with glaucoma, eligibility included a diagnosis of glaucoma at least 1 year prior to enrollment and no evidence of other eye disease. Participants completed 2 vision-targeted surveys, the National Eye Institute Visual Functioning Questionnaire and the VF-14, and a generic health-related quality of life measure, the Medical Outcomes Study 36-Item Short Form. Data from automated perimetry (Humphrey Field Analyzer 24-2, Humphrey Instruments, San Leandro, Calif) were used to generate Advanced Glaucoma Intervention Study scores for all participants. The Medical Outcomes Study 36-Item Short Form scores from glaucoma and reference group participants collected on a random half of the sample were similar. However, comparisons of the vision-targeted surveys demonstrated significant mean differences on 7 of 11 National Eye Institute Visual Functioning Questionnaire scales, and a trend toward significant differences for the VF-14 (P < .07 by linear regression). Greater visual field defects in the better eye were significantly associated with poorer National Eye Institute Visual Functioning Questionnaire scores (P < .05), as well as with worse VF-14 scores. These findings were most dramatic for patients with the most severe field loss in the better eye. Vision-targeted questionnaires were more sensitive than a generic health-related quality of life measure to differences between glaucoma and normal reference participants. Our findings indicate that self-reports of vision-targeted health-related quality of life are sensitive to visual field loss and may be useful in tandem with the clinical examination to fully understand outcomes of treatment for glaucoma.

Adult↗

The appropriateness of use of coronary artery bypass graft surgery in New York State.

OBJECTIVE: To determine the appropriateness of use of coronary artery bypass graft surgery in New York State. DESIGN: Retrospective randomized medical record review. SETTING: Fifteen randomly selected hospitals in New York State that provide coronary artery bypass graft surgery. PATIENTS: Random sample of 1338 patients undergoing isolated coronary artery bypass graft surgery in New York State in 1990. MAIN OUTCOME MEASURES: Percentage of patients who had bypass surgery for appropriate, inappropriate, or uncertain indications; operative (30-day) mortality; and complications. RESULTS: Nearly 91% of the bypass operations were rated appropriate; 7%, uncertain; and 2.4%, inappropriate. This low inappropriate rate differs substantially from the 14% rate found in a previous study of patients operated on in 1979, 1980, and 1982. The difference in rates was not due to more lenient criteria but to changes in practice, the most important being that the fraction of patients receiving coronary artery bypass grafts for one- and two-vessel disease fell from 51% to 24%. Individual hospital rates of inappropriateness (0% to 5%) did not vary significantly. Rates of appropriateness also did not vary by hospital location, volume, or teaching status. Operative mortality was 2.0%; 17% of patients suffered a complication. Complication rates varied significantly among hospitals (P < .01) and were higher in downstate hospitals. CONCLUSIONS: The rates of inappropriate and uncertain use of coronary artery bypass graft surgery in New York State were very low. Rates of inappropriate use did not vary significantly among hospitals, or according to region, volume of bypass operations performed, or teaching status.

Coronary Artery Bypass↗

DNA damage induced by 193-nm radiation in mammalian cells.

The contribution of DNA damage to the effects of 193-nm excimer laser radiation on mammalian cells in culture was studied in order to evaluate the mutagenic potential of this UV wavelength in vivo. Two approaches were taken: measurement of pyrimidine dimer-specific endonuclease-sensitive sites/megabase and comparison of the 193-nm radiation-induced cytotoxicity in normal versus DNA repair-deficient cells. The formation of pyrimidine dimer-specific endonuclease-sensitive sites/megabase was inversely related to the thickness of the cytoplasm overlying the nuclei of normal human fibroblasts (NHF) and Chinese hamster ovary cells. The results of these measurements and a calculation of the absorption coefficient of cytoplasm indicate that each 1 micron of cytoplasm attenuates the incident radiation by greater than 90% and, therefore, the nuclear DNA in tissue will be highly protected from 193-nm radiation by overlying cytoplasm. The reduction in colony-forming ability induced by 254-nm, 193-nm, and X-ray radiation was measured in NHF, xeroderma pigmentosum (group A) cells, and ataxia telangiectasia cells. Xeroderma pigmentosum (group A) cells were 16.5 times more sensitive to 254-nm radiation but only 3.5 times more sensitive to 193-nm radiation than NHF cells, indicating that cyclobutylpyrimidine dimers were not the major lethal lesion formed at 193 nm. AT cells were 3.4 times more sensitive to X-rays than NHF cells, but these cell types were almost equally sensitive to 193-nm radiation, indicating that 193 nm did not induce the same type of lethal lesions as X-rays.

Animals↗

Monoclonal antibodies distinguishing alpha and beta forms of calcitonin gene-related peptide.

A panel of 18 monoclonal antibodies was raised to the human calcitonin gene related peptide (CGRP). Of these mabs, seven were specific for alpha CGRP and five for beta CGRP, while the remainder reacted with both alpha and beta CGRP. Nine different epitopes on CGRP were defined with these mabs. In addition, the mabs were tested in various combinations to develop a series of two site assays specific for alpha or for beta CGRP as well as assays able to detect both.

Amino Acid Sequence↗

Longwave ultraviolet radiation (UVA, 320-400 nm)-induced tan protects human skin against further UVA injury.

The protective effect of a UVA (320-400 nm) induced tan against cutaneous injury by further UVA-irradiation was studied by evaluating the histopathologic changes in tanned and untanned normal human buttock skin 24 h after exposure to 2 and 4 minimal erythema doses of UVA. In each subject there were fewer polymorphonuclear leukocytes and less endothelial cell prominence and vessel wall necrosis in the UVA tanned skin than in the untanned UVA-irradiated skin. In the tanned control and tanned UVA-irradiated skin there was a prominent mononuclear cell inflammatory infiltrate that was much greater than in untanned skin. In immunoperoxidase stained tissue sections, the mononuclear cells were predominantly T cells, and in all of the specimens the number of phenotypic helper/inducer cells exceeded the phenotypic cytotoxic/suppressor cells. This demonstrates that a UVA tan provides photoprotection against acute UVA exposure. In addition, tanning, with or without further UVA-irradiation, was associated with a mononuclear cell inflammatory infiltrate.

Adult↗

Surgical treatment of progressive visual loss in traumatic optic neuropathy. Report of two cases.

In two patients with traumatic optic neuropathy progressive visual loss was reversed by surgical decompression of the optic nerve sheath. The first patient with hemorrhage beneath the optic nerve sheath had progressive loss of vision from counting fingers to no light perception within 24 hours after the injury. Surgical evacuation of the hematoma improved visual acuity to 8/30. The second patient had progressive visual loss from 20/20 to 20/400 within the 1st week after injury. Drainage of an arachnoid cyst of the optic nerve sheath improved visual acuity to 20/25. Computerized axial tomography disclosed the hemorrhage in the first case and enlargement of the optic nerve sheath in the second. While the management of traumatic optic neuropathy is controversial, surgical intervention for an arachnoid cyst and hematoma involving the optic nerve is clearly beneficial.

Adult↗

Extra structurally abnormal chromosomes (ESACs)--presentation of 10 new cases.

BACKGROUND: The goal of the presented studies as a retrospective reliability assessment of classical banding cytogenetic studies and of prognosing epicrises in a group of 14 cases, affected with additional marker chromosomes. MATERIAL AND METHODS: Having collected the study material from peripheral blood, by means of trophoblast biopsy or amniocentesis, cytogenetic preparations were obtained, allowing for pre- or postnatal evaluation of the karyotype. A panel of auxiliary cytogenetic techniques accompanied the routine CTG protocol. RESULTS: In a group of 6875 persons with recommendations to pre- or postnatal cytogenetic diagnostics, 14 (0.2%) cases of ESACs were diagnosed. In 5 cases of DA/DAPI(+) inv dup (15) as observed. A presence of polymorphic interstitial RHG(+) band was found within the marker chromosome. The measured size of that band allowed associating it with either the presence or the absence of pathological signs. In 9 cases of ESACs, DA/DAPI(-), the application of banding techniques (NOR and CBG) allowed to discover bisatellite heterochromatic ESACs in 6 cases (2 non-mosaic and 4 mosaic). In three other mosaic and non-satellite cases of ESACs, a 'genetic inactivity' of the marker chromosome was observed in one case, while a 'genetic activity' was ascertained in two cases. The 'activity' of marker chromosomes was studied by means of replication banding techniques. CONCLUSIONS: At the time of the outburst of molecular techniques, still up-to-date is the use of classical banding techniques and of the replication techniques, allowing DNA replication kinetics studies at the level of single band.

Adolescent↗