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Biomedical subjects

M R Fisher

Publications and source records attributed to M R Fisher.

At least 19 recordsLinked to original sources
PubMed2006

Addition of sildenafil to bosentan monotherapy in pulmonary arterial hypertension.

Combination therapy has been recommended for the treatment of pulmonary arterial hypertension (PAH). However, there is scant information on combination therapy after failure of monotherapy, particularly in patients with scleroderma-associated PAH (PAH-SSD). From a group of 82 consecutive patients with PAH who received initial bosentan monotherapy, a total of 13 idiopathic PAH (IPAH) and 12 PAH-SSD patients requiring additional therapy with sildenafil were studied. Sildenafil was added for clinical deterioration based upon symptoms, New York Heart Association (NYHA) classification or 6-min walk distance (6MWD). Clinical data and haemodynamics were collected at baseline. Assessments were made at 1-3-month intervals. At baseline, there were no differences in demographics, NYHA classification, haemodynamics or 6MWD between the two groups. After initiation of bosentan, both groups experienced clinical improvement but ultimately deteriorated (median time to monotherapy failure 792 versus 458 days for IPAH and PAH-SSD patients, respectively). After addition of sildenafil, more IPAH patients tended to improve in NYHA class (five out of 13 versus two out of 12) and walked further (mean difference in 6MWD 47+/-77 m versus -7+/-40 m) compared with PAH-SSD patients. In conclusion, addition of sildenafil after bosentan monotherapy failure improved New York Heart Association class and 6-min walk distance in idiopathic pulmonary arterial hypertension patients but failed to improve either parameter in scleroderma-associated pulmonary arterial hypertension patients. Additional studies are needed to assess the tolerability and efficacy of this combination in patients with scleroderma-associated pulmonary arterial hypertension.

Adult↗
PubMed1998

Risk factors for high-risk proliferative diabetic retinopathy and severe visual loss: Early Treatment Diabetic Retinopathy Study Report #18.

PURPOSE: To identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS). METHODS: Multivariable Cox models were constructed to evaluate the strength and statistical significance of baseline risk factors for development of high-risk PDR and of SVLV. RESULTS: The baseline characteristics identified as risk factors for high-risk PDR were increased severity of retinopathy, decreased visual acuity (or increased extent of macular edema), higher glycosylated hemoglobin, history of diabetic neuropathy, lower hematocrit, elevated triglycerides, lower serum albumin, and persons with mild to moderate nonproliferative retinopathy, younger age (or type 1 diabetes). The predominant risk factor for development of SVLV was the prior development of high-risk PDR. The only other clearly significant factor was decreased visual acuity at baseline. In the eyes that developed SVLV before high-risk proliferative retinopathy was observed, baseline risk factors were decreased visual acuity (or increased extent of macular edema), older age (or type 2 diabetes), and female gender. CONCLUSIONS: These analyses supported the view that the retinopathy-inhibiting effect of better glycemic control extends across all ages, both diabetes types, and all stages of retinopathy up to and including the severe nonproliferative and early proliferative stages and the possibility that reducing elevated blood lipids and treating anemia slow the progression of retinopathy.

Adolescent↗
PubMed1997

Histopathologic study of eyes after iodine I 125 episcleral plaque irradiation for uveal melanoma.

OBJECTIVES: To describe the histopathologic findings attributable to irradiation in eyes with uveal malignant melanoma treated with iodine I 125 brachytherapy and to compare these findings with those reviewed in a previous study that compared histopathologic findings in eyes enucleated after proton beam teletherapy with those seen in eyes in a nonirradiated control group. METHODS: The slides from 22 eyes with uveal melanoma that had undergone enucleation after the administration of 125I brachytherapy were studied. The histopathologic features of the tumor and the retina were graded. Results were compared with findings from a previously reported group of 47 proton beam-treated eyes and its control group. RESULTS: Patient age, time between irradiation and enucleation, and ciliary body involvement were similar for the 125I brachytherapy-treated group and the proton beam-treated group and its control group. This allows comparison of the histopathologic findings. Comparing the 125I brachytherapy- and proton beam-treated groups, most histopathologic features were similar with nominally statistically significant differences only for cell type, number of mitotic figures, and fibrous metaplasia of the retinal pigment epithelium adjacent to the tumor. CONCLUSIONS: Irradiation of uveal melanoma induces changes in the tumor and in the surrounding retina. Brachytherapy and charged particle therapy are the 2 principal methods of irradiation. This study demonstrates that similar changes are produced by 125I plaque irradiation and proton beam irradiation.

Adult↗
PubMed1997

The development of an isokinetic squat device: reliability and relationship to functional performance.

This study was performed to determine the reliability and validity of a new isokinetic squat device in comparison to knee-extension tests performed using a Cybex. Athletic male subjects (n = 29) performed a series of isokinetic squat tests at 0.4 m.s-1, knee-extension tests at 1.05, 2.09 and 3.14 rad.s-1, and a 6-s stationary cycle test which was used as the measure of functional performance. The squat tests included a purely concentric squat without pre-load, a test with pre-load and a stretch-shorten cycle test. Two trials of each test were performed on one testing occasion. Intraclass correlation co-efficients (r = 0.89-0.96) and co-efficients of variation (3.1-8.7%) were determined between trials, and these indicated that all of the tests were highly reliable. The velocity characteristics of the newly developed system demonstrated that it was an effective isokinetic device, with the mean velocity of 0.41 m.s-1 varying within narrow limits, a relatively small velocity overshoot and an isokinetic portion of movement of approximately 80%. The squat tests demonstrated a higher relationship to cycling performance (r = 0.57-0.65) as compared to the knee-extension tests (r = 0.45-0.51). This difference was amplified when a more homogeneous group of subjects was examined. Further, the squat tests were superior to the knee-extension tests in discriminating between differing levels of cycling performance ability. These differences were believed to be due to the greater specificity of the squat movement, in comparison to the knee extension, to the performance of interest.

Adolescent↗
PubMed1997

Feasibility of angle independent Doppler color imaging for in vivo application: preliminary study on carotid arteries.

An experimental system has been used to acquire Doppler color images using a linear transducer from an ultrasound scanner to reconstruct angle independent Doppler color (AIDC) images in normal carotid arteries in 21 volunteers. Images were first taken from relatively straight segments in the common carotid artery, and comparisons were made in a small area at the center stream. At peak systole, the correlation coefficient of the velocity amplitudes between AIDC imaging (AIDCI) and duplex scanning was 0.94; the correlation coefficient between the flow angles measured from AIDCI and the angles of the vessel wall was 0.99. Periodic variations of the flow angle over the cardiac cycle were always observed by AIDCI, whereas the changes in the geometric angle of the vessel itself were insignificant. This observation suggests that the AIDCI technique is sensitive to alterations of flow direction. On the other hand, the deviation of the flow angle from a fixed correction angle in duplex scanning may cause a certain degree of error in velocity determination. AIDC images were also obtained at the carotid bifurcation. The results show that the AIDCI technique is able to depict major flow features, such as velocity skewing, flow separation, flow reversal and vortical flow, in a complex flow field.

Carotid Arteries↗
PubMed1996

Melanocytes and iris color. Light microscopic findings.

OBJECTIVE: To systematically evaluate morphologic differences in iris stroma that contribute to clinically perceptible differences in iris color, using immunohistochemical identification of stromal melanocytes and fluorescence microscopy. METHODS: Paraffin-embedded sections from 51 human irides were stained with S100a and fluorescein isothiocyanate. Cells were counted and scored as melanocytes or other. Melanocyte number, proportion, and density were determined for light-colored (blue), medium-colored (hazel) and dark-colored (brown) irides and compared. RESULTS: No statistically significant difference was observed for mean total cellularity or mean melanocyte number among the three color groups. Mean total stromal cell count was 1177 +/- 259 (mean +/- SEM), and mean melanocyte number was 778 +/- 196 per 5-micrometer section. In human irides, 65.9% of the iris stroma is composed of melanocytes. Melanocyte density (number of cells per square millimeter) is not related to iris color. CONCLUSION: The number of melanocytes, the proportion of melanocytes, and iris stromal cellularity are not major contributors to iris color.

Aged↗
PubMed1996

Aging effects on accommodation and outflow facility responses to pilocarpine in humans.

OBJECTIVE: To determine the relationships among age, outflow facility, and refractive and facility responses to pilocarpine in humans. METHODS: Refraction, intraocular pressure, and outflow facility were determined in 30 normal volunteers aged 20 to 75 years, by coincidence refractometry, applanation tonometry, and Schiøtz tonography, respectively, before and 1 hour after a 30-microL drop of 2% or 6% pilocarpine. Simple regression of baseline facility, postpilocarpine facility, and facility change, on age and refractive change singly and jointly, was performed. Stepwise regression models and graphic conditioning plots were used to determine, for each facility variable, its relationship to age or refractive change specifically. RESULTS: Baseline outflow facility and maximum pilocarpine-induced refractive change (ie, accommodation) declined with age, but the decrease in intraocular pressure and the facility response to pilocarpine did not. After adjusting for age, for baseline facility, there was no further relationship to 6% pilocarpine-induced accommodation, and a slight residual relationship to 2% pilocarpine-induced accommodation. After adjusting for both 2% or 6% pilocarpine-induced accommodation, the relationship to age was still significant. The facility increase after 2% or 6% pilocarpine did not depend on age and/or accommodative amplitude. CONCLUSIONS: In humans, as previously described in rhesus monkeys, an age-related loss of ciliary muscle mobility may compromise the basal function of the trabecular meshwork. However, unlike monkeys, humans exhibit no loss of the intraocular pressure or outflow facility response to pilocarpine with age.

Accommodation, Ocular↗
PubMed1995

Decreased splanchnic perfusion measured by duplex ultrasound in humans undergoing small volume hemorrhage.

OBJECTIVES: To quantitate duplex Doppler measurements of splanchnic perfusion to determine if these measurements are reproducible in euvolemic humans and if such measurements are sensitive to mild degrees of systemic hypovolemia. DESIGN: Prospective, nonrandomized, controlled trial. SETTING: Clinical research center. PARTICIPANTS: Seven fasting, healthy male and female volunteers, ranging in age from 25 to 37 yrs and weighing 60 to 90 kg. INTERVENTIONS: Pulse, blood pressure, hematocrit, and duplex Doppler measurements of the peak systolic velocity and time averaged velocity of the subdiaphragmatic aorta, celiac artery, and superior mesenteric artery were obtained at four time points. Time points I and II were on separate days before hemorrhage and consisted of routine blood donation of 450 mL. Time point III was immediately after blood donation. Time point IV was 24 hrs after donation. Estimated blood flow was calculated from time averaged velocity (estimated blood flow = 60[vessel cross-sectional area][time averaged velocity]). MEASUREMENTS AND MAIN RESULTS: Vital signs and hematocrit remained without significant change at all time points. Peak systolic velocity, time averaged velocity, and estimated blood flow were also unchanged between measurements at time points I and II. However, after a mean reduction of 9.1% of total blood volume, duplex ultrasound detected significant decreases of 14.5% in celiac artery and superior mesenteric artery peak systolic velocity, as well as 15.1%, 17.3%, and 20.2% decreases in aorta, celiac artery and superior mesenteric artery time averaged velocity and estimated blood flow, respectively (all values p < .05 vs. baseline, Duncan's multiple range test). All measured variables returned to baseline 24 hrs after hemorrhage. CONCLUSIONS: Noninvasive duplex Doppler measurements of splanchnic peak systolic velocity, time averaged velocity, and estimated blood flow are reproducible and sensitive to small changes in intravascular volume. These data suggest a potential clinical role for duplex imaging in the treatment of critically ill patients to guide therapy to optimize splanchnic perfusion.

Adult↗
PubMed1993

Factors influencing response to strabismus surgery.

Based on analyses in a series of 116 patients, we found that the response to strabismus surgery (degrees of change of ocular alignment per millimeter of rectus recession) correlated significantly with the preoperative deviation for esotropic and exotropic patients. The prediction of response to strabismus surgery was not improved significantly with the inclusion of axial length, age, and/or preoperative refractive error beyond the prediction provided with use of only the preoperative deviation, even though we have previously suggested that the response to strabismus surgery should be related to axial length. We believed that larger eyes should have a smaller response for the same number of millimeters of surgery than smaller eyes. We now believe that although the response to strabismus surgery does correlate significantly and inversely with axial length, this correlation may not be clinically important given the much stronger influence of preoperative deviation.

Adolescent↗
PubMed1993

A diet history questionnaire ranks nutrient intakes in middle-aged and older men and women similarly to multiple food records.

We evaluated the reproducibility of a modified version of the National Cancer Institute diet history questionnaire and also studied comparability of nutrient estimates from this questionnaire to those from four 2-d food records. Subjects (n = 211) were from a population-based sample of middle-aged and older adults participating in the Beaver Dam Eye Study in south-central Wisconsin. Median age-specific correlation coefficients between the questionnaire, administered twice at a 3-mo interval, were 0.8 in men and 0.7 in women (range = 0.5 to 0.9). Questionnaire estimates of protein, cholesterol, thiamin, niacin, iron and zinc were consistently lower than food record estimates whereas estimates of fat were higher. Correlation coefficients between estimates from the questionnaire and records were generally > 0.5, indicating overall good agreement in ranking. However, the range in correlation coefficients was wide [ranging from 0.06 for iron (without supplements) in middle-aged women to 0.8 for alcohol in middle-aged men and women]. Questionnaire estimates similarly classified persons into the lowest two food record quintiles of intake 50 to 93% of the time depending on nutrient. These results suggest that the questionnaire produces nutrient estimates that rank individuals on the basis of intake of most nutrients similarly to estimates from multiple food records.

Adult↗
PubMed1993

Gamma Knife thalamotomy and pallidotomy in patients with movement disorders: preliminary results.

The Leksell Gamma Knife is a useful and safe method to perform thalamotomy and pallidotomy in selected older patients with Parkinson's disease and related movement disorders. In this preliminary report, 2 of 3 patients with severe intention tremor were relieved of their symptoms by thalamotomy, as were 4 of 7 patients with Parkinson's tremor. Four of 8 patients had significant improvement of contralateral rigidity following pallidotomy.

Aged↗
PubMed1993

Leksell Gamma Knife treatment of tic douloureux.

Stereotactic radiosurgery under local anesthesia with the Leksell Gamma Knife can effectively treat some patients with recurrent tic douloureux after unsuccessful medical/surgical procedures. Seven of 12 patients have shown complete relief or improvement of their trigeminal neuralgia. No complications have been observed.

Adult↗
PubMed1993

Systemic hypertension produces pericyte changes in retinal capillaries.

PURPOSE: The purpose of this study was to examine retinal capillaries and their pericytes that previous research suggests to be contractile. A contractile role regulating capillary blood flow may be more apparent when the vasculature is subjected to the stress of systemic hypertension. METHODS: Using ultrastructural morphometry and the myosin subfragment-1 technique, retinal capillaries of normal and hypertensive rats were measured at three different time points, early, intermediate, and late (24, 44, and 68 wk). RESULTS: Hypertensive capillaries seemed to dilate at the early time point (P = 0.002), were constricted at the intermediate time point (P < 0.001), and did not redilate later. Wall thickness was enlarged at all times, pericyte coverage (the ratio of plasma membrane length in contact with the vascular circumference to the outer circumference of the endothelial tube) was greater at early and intermediate time points, and the total area of viable cytoplasm relative to the vessel wall area was increased at the intermediate time (all P < 0.001). Also, at the intermediate time, the circumferential coverage of the endothelial tube by actin filament bundles within pericytes and the actin area relative to the vessel wall area had increased (P < 0.001). CONCLUSIONS: These data indicate that the effects of systemic hypertension extend into the retinal capillary bed, causing pericyte change with actin increase and capillary constriction. They represent the first in vivo indirect evidence by morphologic criteria for pericyte contractility in retinal vascular disease.

Actins↗
PubMed1991

MRI of hepatic iron deposition in patients with renal transplant.

Excess hepatic iron deposition was found in five of 15 (33%) renal transplant patients undergoing magnetic resonance (MR) screening for avascular necrosis of the femoral heads. Only one of these patients had overt liver disease. The number of prior blood transfusions was a significant factor for this deposition, whereas the age and sex of the patients, number and type of transplants, histocompatibility alleles (HLA), and years of hemodialysis and of chronic renal failure were not significant etiological factors. Liver/fat intensity ratios of less than 0.29 on T1-weighted images and ratios of less than 0.21 on T2-weighted images and a calculated T2 value of less than 35 ms were the best indicators of iron overload. Renal transplant patients are at great risk for excess hepatic iron deposition and MR imaging is a promising tool for the diagnosis of iron overload in this patient population.

Adult↗
PubMed1991

MRI of cardiac pseudoaneurysm and other complications of myocardial infarction.

The purpose of this paper is to review the spectrum of pathology revealed by cardiac magnetic resonance (MR) in the evaluation of myocardial infarction. In addition, the paper is intended to provide a concise introduction to the capabilities and limitations of MR in the evaluation of myocardial infarction and its complications. To provide this introductory guide, three cases of infarction are reviewed in detail, including one unusual case of infarction with both true and false ventricular aneurysm formation. A selected review of the literature is included to demonstrate the current role of MR in the work-up and follow-up of acute infarction.

Aged↗
PubMed1990

Relationship between rate of patient enrollment and quality of clinical center performance in two multicenter trials in ophthalmology.

Those responsible for managing and overseeing multicenter clinical trials often express concern that differential rates of patients enrollment among participating clinical centers may be reflected in poorer compliance with study protocols or poorer patient care in the centers enrolling fewer patients. The purposes of the present investigation were (1) to determine whether rate of patient enrollment was related to other measures of clinical center performance in two multicenter clinical trials in ophthalmology, the Macular Photocoagulation Study (MPS) and the Early Treatment Diabetic Retinopathy Study (ETDRS), and (2) to compare findings from these two studies with findings reported from cooperative oncology groups. Percent of major data forms ever failing computerized edit was the only measure of performance examined that demonstrated a strong positive relationship to rate of patient enrollment in both studies under both analytic approaches employed (F test for linear trend in means and Spearman's rank correlation). In the MPS, but not in the ETDRS, percent of patients who had missed all visits scheduled during the past 12 months (inactive patients) also was related to rate of patient enrollment. However, the major finding from this investigation has been that it is not possible to predict overall performance of an individual clinical center based on rate of patient enrollment. Clinical centers enrolling fewer patients in these multicenter clinical trials performed in some areas as well as or better than centers enrolling larger numbers of patients.

Diabetic Retinopathy↗
PubMed1989

Magnetic resonance for evaluation of the thorax.

Evaluation of diseases in the chest by MR is continually evolving. Early studies showed the potential of the technique for imaging the mediastinal and hilar structures and for demonstrating the normal anatomy of the thorax on sagittal, coronal, and transverse MR images. As more data have been compiled, investigators have compared MR to computed tomography for its ability to assess mediastinal and hilar adenopathy and masses, bronchogenic carcinoma and other pulmonary parenchyma lesions, and for assessment of the pulmonary vascularity. MR has been shown in these situations generally to provide equivalent information to that provided by computed tomography. MR, compared to computed tomography, is still in its infancy in regard to the length of time of its availability and in relation to the MR technology for obtaining images. MR is a technique that has wide variation as to type of image quality obtained depending upon the MR system utilized and the pulse sequence utilized. Because of the diverse nature of potential variables for imaging, many times the images are not equal in quality. As a consequence of this significant variability, the data in the literature are divergent on the precise utility of MR. Although the recommended use of MR may change rapidly, the current feeling is that MR should be used as a procedure complementary to computed tomography in those patients with allergy to iodinated contrast material and to aid in defining equivocal lesions as seen on computed tomography, such as small central hilar bronchogenic carcinomas.

Humans↗