Search PubMed⌕ Search

Biomedical subjects

R M Hill

Publications and source records attributed to R M Hill.

At least 37 records · Page 2Linked to original sources

Lymphoblastic lymphoma following prenatal exposure to phenytoin.

PURPOSE: Oncogenesis has been associated with prenatal exposure to phenytoin, concomitant with or independent of the fetal hydantoin syndrome. The majority of reported cases have been embryonal tumors of neural crest origin and have occurred in the first 3 years of life. PATIENTS AND METHODS: We report a boy who was exposed to phenytoin throughout gestation and later developed T-lymphocyte lymphoblastic lymphoma, a previously unreported malignancy associated with in utero phenytoin exposure. Previously reported cases of neoplasia occurring after such exposure are tabulated. CONCLUSION: The actual transplacental oncogenic potential of phenytoin and the epidemiology of this association are poorly understood. Phenytoin-induced alterations in lymphocyte-mediated immunosurveillance or oxidative metabolic clearance may be etiologic. Inquiry into prenatal phenytoin exposure should be done in any child who develops cancer, especially those who develop a rare tumor or present with a more common tumor at an unusually young age. Continued documentation of such cases will advance the understanding of phenytoin-associated transplacental oncogenesis.

Anticonvulsants↗

The influence of center of gravity and lens mass on rigid lens dynamics.

PURPOSE: Center of gravity and lens mass have both been shown to influence rigid lens centration and stability. The purpose of this study was to investigate the relative contributions of these two factors to rigid lens dynamics. METHODS: Eight subjects (four with high-riding lenses and four with low-riding lenses) participated in the study. Each subject was fit with 12 lenses-six designs in each of two materials. Center of gravity and lens mass were recorded in every case. For each lens, four lens dynamics variables were assessed over a five-blink cycle for both the vertical and the horizontal meridians: 1) initial lens position; 2) settled lens position; 3) amount of lens movement; and 4) rate of lens movement. RESULTS: Multiple regression and correlation analysis showed that center of gravity influences initial and settled lens position, in both the horizontal and the vertical meridians. Mass alone was found not to be a significant predictor of rigid lens dynamics. The effect of center of gravity on settled vertical lens position was only apparent when high rider and low rider subgroups were analyzed separately, with a posterior movement of the center of gravity being associated with a lowering of the settled lens position for high rider subjects, and a raising of the settled lens position for low rider subjects. The results suggest that a rigid lens will become more stable as the center of gravity is shifted further behind the lens vertex, but this effect is reduced as lens mass is increased. CONCLUSIONS: The location of the center of gravity of a rigid lens influences its on-eye centration and stability more so than does lens mass.

Contact Lenses↗

Evaluation of twin growth status at birth using individualized growth assessment: comparison with conventional methods.

OBJECTIVE: We sought to evaluate the growth status of twins at birth using individualized growth assessment methods and to compare this assessment with that obtained with conventional methods. STUDY DESIGN: Twenty twin pregnancies were studied longitudinally with ultrasound. Measurements of the head and abdominal cubes (A,B), head circumference (HC), abdominal circumference (AC), thigh circumference (ThC), and femur diaphysis length (FDL) made in the 2nd trimester were used to specify Rossavik growth models for each parameter in each fetus. These models were used to predict weight (WT), HC, AC, ThC, and crown-head length (CHL) at birth. Actual birth measurements made within 24 hours of delivery were compared to predicted values, the latter corrected using singleton [corrects for both technical problems (TP)] or twin [corrects for both technical problems (TP) and decreased soft-tissue deposition (DSTD)] correction factors where appropriate. Two sets of growth potential realization index (GPRI) values and their corresponding neonatal growth assessment scores (NGAS) were calculated and compared to previously established normal values. Birth measurements were compared with appropriate population age-specific size curves. These data were used to characterize and classify the growth status of each twin neonate. RESULTS: Individualized growth assessment identified five primary types of growth outcomes: normal (Group I, 45%); primarily DSTD (Group II, 22.5%); IUGR (Group III, 15%); above average soft-tissue deposition (Group IV, 5%); and growth acceleration (Group V, 7.5%). Within Group I was a subgroup with evidence of DSTD (Group Ib, 33.3% of Group I). Group II could be divided into two subgroups, one with only DSTD (Group IIa, 44.4% of Group II) and one with both DSTD and other growth abnormalities (Group IIb, 55.6% of Group II). Group III had multiple growth abnormalities which were more severe than those seen in Group II. All normal neonates were AGA and had virtually all anatomic parameters within their respective normal ranges. Of the neonates with definite evidence of IUGR (Groups IIb and III), only 4 of 11 (36.4%) were SGA and only 6 of 11 (54.5%) had any of the five anatomic parameters below their respective normal ranges. Only 1 of 3 (33.3%) of neonates with growth acceleration was LGA and none (0%) of the five anatomic parameters were above their respective normal ranges. CONCLUSIONS: Individualized growth assessment methods provide a more comprehensive assessment of growth outcome in twins and detect a decrease in soft-tissue deposition not identifiable with conventional growth assessment procedures. The latter procedures are also less sensitive in the detection of both IUGR and growth acceleration.

Adolescent↗

Comparison of the molecular forms of the Kex2/subtilisin-like serine proteases SPC2, SPC3, and furin in neuroendocrine secretory vesicles reveals differences in carboxyl-terminus truncation and membrane association.

The molecular forms and membrane association of SPC2, SPC3, and furin were investigated in neuroendocrine secretory vesicles from the anterior, intermediate, and neural lobes of bovine pituitary and bovine adrenal medulla. The major immunoreactive form of SPC2 was the full-length enzyme with a molecular mass of 64 kDa. The major immunoreactive form of SPC3 was truncated at the carboxyl terminus and had a molecular mass of 64 kDa. Full-length 86-kDa SPC3 with an intact carboxyl terminus was found only in bovine chromaffin granules. Immunoreactive furin was also detected in secretory vesicles. The molecular masses of 80 and 76 kDa were consistent with carboxyl-terminal truncation of furin to remove the transmembrane domain. All three enzymes were distributed between the soluble and membrane fractions of secretory vesicles although the degree of membrane association was tissue specific and, in the case of SPC3, dependent on the molecular form of the enzyme. Significant amounts of membrane-associated and soluble forms of SPC2, SPC3, and furin were found in pituitary secretory vesicles, whereas the majority of the immunoreactivity in chromaffin granules was membrane associated. More detailed analyses of chromaffin granule membranes revealed that 86-kDa SPC3 was more tightly associated with the membrane fraction than the carboxyl terminus-truncated 64-kDa form.

Adrenal Medulla↗

Dynamic scaling in the dielectric response of excised EMT-6 tumours undergoing hyperthermia.

A constant-phase-angle response (CPA) has been identified in the dielectric spectrum of EMT-6 tissues undergoing hyperthermia. A dynamic scaling relationship between the static permittivity and conductivity using the CPA frequency exponent n has been shown to occur during the destructive phase of hyperthermia. This behaviour has been attributed to the self-similar structure of the internal membrane compartments of the cells and described by means of a hierarchical circuit model. In this way the CPA exponent has been related to the convolution of internal membrane surfaces lying in between the mitochondria and the outer cell wall. The dynamic scaling is assigned to the progressive destruction of cell membranes in sequence from the outside inwards.

Animals↗

Prediction of neonatal crown-heel length in normal singletons, twins, and triplets using individualized growth assessment.

In groups of normally growing singletons (20), twins (20), and triplets (13), predicted femur diaphysis length (FDL) values at birth were obtained using Rossavik growth models specified from second-trimester ultrasound studies of fetal growth. Six previously published functions were utilized to obtain predicted crown-heel length (CHL) values from predicted FDL values. These values were compared to the actual CHL values and the percent differences calculated. Based on their systematic (mean percent difference) and random (standard deviation of percent difference) prediction errors, the functions of Vintzileos (singletons), Hadlock (twins), and Brown (triplets) were found to give optimal results (no systematic error; random error: +/- 6%). Using predicted CHL values obtained with these optimal functions, growth potential realization index values for CHL (GPRICHL) were determined for singletons, twins, and triplets. In all three groups, the mean GPRICHL value was 100% with a range of approximately 95% to 105%. These results indicate that the CHL can be predicted from second-trimester growth patterns and evaluated using individualized growth assessment methods.

Embryonic and Fetal Development↗

Evaluation of triplet growth status at birth using individualized growth assessment: comparison with conventional methods and development of a new classification system.

A new growth classification system for triplets based on individual growth curve standards provides new information on the growth status of triplets at birth. OBJECTIVES. The objectives of this study were to characterize growth outcome at birth in triplet pregnancies using Individualized Growth Assessment methods, and to compare these results to conventional methods of growth outcome evaluation. STUDY DESIGN. Rossavik growth models derived from second-trimester ultrasound measurements were used to predict the birth characteristics of 21 triplet neonates. Actual measurements of weight, head, abdominal, and thigh circumferences at birth were compared to population standards and to predicted values, the latter by calculation of Growth Potential Realization Index (GPRI) values. GPRI values were calculated using singleton (measurement procedure correction) and triplet (measurement procedure correction+decreased soft tissue deposition) correction factors (SCF, TCF). Neonatal Growth Assessment Scores (NGAS) were calculated using both sets of GPRI values. RESULTS. Three types of triplet neonates were identified. Group I (33.3%) were normal with both types of NGAS values, had very few abnormal GPRI values or anatomic measurements, and were all appropriate for gestational age. Group III (14.3%) were abnormal with both types of NGAS values, most GPRI values were abnormal, and all were small for gestational age. Group II (52.4%) had abnormal NGAS values when calculated from GPRI values determined with SCF and normal NGAS values when calculated from GPRI values determined with TCF. All but one was AGA. Almost all GPRIWT and GPRIThC values were abnormal using SCF and normal using TCF. CONCLUSION. Although growth outcome in triplet neonates can be normal (Group I) or intrauterine growth retarded (Group III), the majority are in an intermediate group (Group II) characterized by a decrease in soft tissue mass, which may or may not be pathological.

Adult↗

Influence of lens design on the tear pump efficiency associated with plus-power rigid contact lenses: a comparison of single cut, lenticular, and minus-carrier designs.

In order to determine the tear pump efficiencies associated with three plus-power rigid contact lens designs (single cut, lenticular, and minus-carrier), we measured corneal oxygen uptake rates on the right eyes of six human subjects under three conditions: (1) normal open eye, (2) after 5 min of static (without blinking) wear of the contact lens, and (3) after 5 min of dynamic (with blinking once every 5 s) wear of the same lens. The differences among the corneal oxygen uptake rates measured under static and dynamic conditions, relative to those measured for the normal open eye, served as an index of tear pump efficiency. Under both static and dynamic conditions, no significant differences were found among the corneal oxygen uptake rates associated with the three plus-power lens designs. In addition, no significant differences were found in the differences among the static and dynamic condition data, an indication of tear pump efficiency, associated with the three plus-power lens designs. This was true for both the population data and for the data from each subject. Nevertheless, there were significant differences among subjects in the static condition, dynamic condition, and difference data.

Adult↗

Rigid contact lens design equivalencies of overall diameter and axial edge lift: individual variations.

We compared the effects on rigid contact lens tear pump efficiency of changes in lens overall and optic zone diameter and of changes in lens axial edge lift by measuring corneal oxygen uptake on the right eyes of six human subjects after 5 min of both static and dynamic contact lens wear. Two sets of five lenses were worn by each subject. In set 1, overall diameter varied from 8.2 to 9.4 mm in 0.3-mm steps, with the optic zone diameter being 1.4 mm smaller and a 0.09 mm axial edge lift. In set 2, axial edge lift varied from 0.05 to 0.13 mm in 0.02-mm steps; overall diameter was 8.8 mm, and optic zone diameter was 7.4 mm. For the pooled data, a 0.3-mm decrease in overall diameter was approximately equivalent to a 0.03-mm increase in axial edge lift as a means of enhancing tear pump efficiency. However, considerable intersubject differences were exhibited, with the following increases in axial edge lift being equivalent to the 0.3-mm reduction in overall diameter: 0.01, 0.01, 0.04, 0.06, 0.09, and > 0.20 mm. This illustrates that subject factors (i.e., palpebral aperture size, lid-to-cornea geometry, corneal toricity, peripheral corneal topography, lid tension) influence lens positioning, movement, and tear pump efficiency.

Adult↗

Using corneal oxygen demand to optimize rigid contact lens design.

To evaluate the effects of base curve radius, overall diameter, and axial edge lift on rigid contact lens tear pump efficiency, corneal oxygen uptake rates were measured on six eyes under three conditions: normal open eye, after 5 min of static (without blinking) wear, and after 5 min of dynamic (with blinking once every 5 s) wear. The three parameters were varied one at a time from a standard lens design. Differences in corneal oxygen demands between the static and dynamic rates provided quantitative measures of the tear pump efficiency for each lens design. Tear exchange was found to be most sensitively related to changes in base curve radius, followed by overall diameter changes (66.9% as effective) and axial edge lift changes (64.6% as effective). Design equivalencies (to produce identical tear exchange to a 0.05-mm flattening of base curve toward alignment) were 0.07-mm steepening of the base curve toward alignment, 0.35-mm decrease in overall diameter, or 0.037-mm increase in axial edge lift.

Adult↗

Human basic tear fluid osmolality. I. Importance of sample collection strategy.

Osmolalities of 200 human tear prism fluid samples collected from two subjects were determined from their melting-point temperatures with the Clifton Nanoliter Osmometer by calibration with 200 standard solution samples (290 mOsm/kg). Comparisons were made between tear fluid osmolalities obtained using a single-sample simultaneous-recalibration method: 1) for tear samples collected using finely-drawn microcapillaries without biomicroscopy, vs secondly with biomicroscopic observation by illumination of only the sampling area on the inferior tear prism, the two collections separated by an interval of 10 min; and 2) for samples collected without biomicroscopy before, vs after a 10-min interval. Tear fluid collection using a biomicroscope resulted in values that were significantly lower than those collected without (overall mean = 299.5 and 306.6 mOsm/kg, respectively; p < 0.0001). The difference (7.1 mOsm/kg) may have resulted from mechanical, photic, and/or psychogenic reflex stimulation due to biomicroscopy, as the 10-min interval had no osmotic effect on samples collected without biomicroscopy. Based on these results from two subjects, we suggest that relatively rapid, repetitive collections of human tear prism fluid can be made without significantly disturbing the osmotic outcome. However, physiological representation of basic human tear fluid is more accurate by avoidance of reflex-inducing collection methods that were formerly considered unobtrusive. Basic human tear prism fluid is more hypertonic, by at least 7 mOsm/kg, than generally realized.

Humans↗

Human basic tear fluid osmolality. II. Importance of processing strategy.

Osmolalities of 100 human inferior tear prism fluid samples collected from two subjects and 100 standard solution samples (290 mOsm/Kg) were determined from their melting-point temperatures with the Clifton Nanoliter Osmometer. Accuracy and reliability comparisons were made for endpoints obtained using a single-sample simultaneous-recalibration (SS/SR) strategy, vs a lowest-of-six periodic-recalibration (LS/PR) strategy. Tear fluid osmolality values based on the LS/PR strategy were significantly lower (hypotonic) than for the SS/SR strategy (overall mean = 302.4 and 307.8 mOsm/Kg, respectively; p < 0.0012). The mean difference (5.4 mOsm/Kg) resulted from the combined effects of machine drift and reduced reliability of endpoint determination for tear fluid in comparison to that of a homogenous standard solution. LS/PR osmolality was linearly correlated to SS/SR osmolality with a slope of 0.433 and the two endpoint strategies resulted in equivalent values at 298.4 mOsm/Kg. Eighty-four percent (84%) of individual osmolality readings were greater than 298.4 mOsm/kg, and an 'averaging-type' effect caused LS/PR osmolalities to be increasingly less than SS/SR values above this value. These outcomes from two subjects were approximated by a parallel statistical model. We suggest that physiological representation of basic human tear fluid is more accurate using the single-sample simultaneous-recalibration strategy. Basic human tear prism fluid is more hypertonic and has a greater within-subject range in normal (non-dry eye) humans than previously realized.

Humans↗

Influence of rigid contact lens base curve radius on tear pump efficiency.

The effects of rigid contact lens base curve radius changes on tear pump efficiency were determined by measuring oxygen uptake on six with-the-rule corneas (with toricities between 0.37 and 1.00 D) under three conditions: (1) normal open eye, (2) after 5 min of static (without blinking) wear of polymethyl methacrylate (non-gas permeable) contact lenses, and (3) after 5 min of dynamic (with blinking once every 5 s) wear of the same lenses. The difference between the oxygen uptake rates measured under static and dynamic conditions provides an index of tear pump efficiency. Each subject wore a series of five lenses: fitted on K and 0.05 or 0.10 mm steeper and flatter than the flattest corneal meridian. The overall diameter of all lenses was 8.8 mm, the optic zone was 7.4 mm, the axial edge lift was 0.09 mm, and all other parameters were constant. The contact lens fitted on K was associated with the greatest central corneal oxygen debt under static conditions, whereas the same lens also provided for the best tear exchange with the blink. In addition, better tear exchange was found to be associated with larger palpebral aperture sizes.

Adult↗

Influence of power changes in single cut rigid contact lenses on tear pump efficiency.

Differences between corneal oxygen uptake rates measured after 5 min of static (without blinking) and 5 min of dynamic (with blinking once every 5 s) non-gas permeable (polymethyl methacrylate) contact lens wear, referenced to the oxygen uptake rates of the normal open eye, were used as indications of tear pump efficiencies associated with each of seven contact lens back vertex powers (-9.00 to +9.00 D, in 3.00 D steps). Measurements were made in vivo on six human corneas showing with-the-rule (0.25 to 0.87 D) toricity. Lens overall diameter was 8.8 mm, optic zone diameter was 7.4 mm, and base curve radius was fitted "on K." Lens center thickness was 0.14 mm for all minus-powered lenses, and 0.19, 0.26, 0.34, and 0.41 mm for the plano, +3.00, +6.00, and +9.00 D lenses, respectively, maintaining an edge thickness of 0.11 mm. Under both static and dynamic wearing conditions, no significant differences were found among the corneal oxygen uptake rates associated with the various contact lens back vertex powers; however, the difference between the static and dynamic condition data, an indication of tear pump efficiency, was greatest for the -3.00 D lens. The difference values associated with the +9.00 and +6.00 D lenses were significantly lower than those associated with the minus power lenses.

Adult↗

Corneal epithelial healing under contact lenses. Quantitative analysis in the rabbit.

The rate of corneal epithelial healing was determined as a function of the oxygen level present at the tear-cornea interface. Oxygen levels of 1.77, 2.3, 5.3, 8.55, 10.12, and 16.45% were created over the rabbit cornea with tarsorrhaphy and various contact lenses. Full depth epithelial defects of 4.5 mm diameter were created in 6 animals for each test condition with the fellow eye serving as a control and healing in air (21.09% oxygen). The defect (radius) was measured at 24-h intervals until healing occurred. Statistically significant (p less than 0.05, paired Student t-test) delays in healing were found with oxygen levels of 8.55% and below. These delays were most profound over the initial 24 h. The healing rate with tarsorrhaphy, at the 1.77% oxygen level, over the first 24 h was 5.2 microns/h radius, only 15.2% of the paired control, 34.0 microns/h radius, healing in air (21.09% oxygen). Healing rates over the initial 24 h under contact lenses allowing 2.3, 5.3, 8.55, 10.12, and 16.45% oxygen were 6.1, 23.5, 26.5, 43.0, and 45.0 microns/h in radius, respectively.

Animals↗

Responses to oxygen deprivation: variations among human corneas.

The cornea's interface with the atmosphere makes it uniquely accessible among avascular tissue for the study of local oxygen demand and proximal reservoir dynamics. Corneal oxygen-uptake rates obtained under normoxic vs hypoxic conditions are not predictive of each other. Proximal tissue reservoirs appear to play a role in moderating oxygen demands following periods of hypoxic stress: as the ratio of epithelia/stromal thickness rises, so does oxygen demand (r = +0.932, P = 0.01). The thickness of the stroma was most closely related to the oxygen uptake rates associated with the normal, open eye (r = +0.773, P = 0.07), whereas the thickness of the epithelium was more closely related to rates obtained after the cornea had been deprived of oxygen (r = +0.783, P = 0.07).

Adult↗

Rigid contact lens design: effects of overall diameter changes on tear pump efficiency.

The effects of rigid contact lens overall diameter changes on tear pump efficiency were studied for lenses of 7 overall diameters (8.2 to 10.0 mm in 0.3-mm steps) while maintaining all other parameters (including a 7.4-mm optic zone diameter) constant. Oxygen uptake rates were measured in the normal, open eye and after static (without blinking) and dynamic (with blinking once every 5 s) wear of oxygen-impermeable (polymethyl methacrylate) contact lenses. Differences between uptake rates obtained under static vs. dynamic conditions served as an index of tear pump efficiency for each lens. Tear pump efficiency increased with the use of progressively smaller lens diameters and subjects with large palpebral aperture sizes were also found to have better tear exchange (r = 0.934, p = 0.006 for the 9.1-mm overall diameter reference lens).

Adult↗

Rigid lens tear pump efficiency: effects of overall diameter/base curve combinations.

The effect of changes in rigid contact lens overall and optic zone diameters on tear pump efficiency were studied using a polarographic technique. Six overall diameters ranged from 7.6 to 10.6 mm in 0.6-mm steps, with the optic zone diameter always being 1.4 mm smaller. Base curve radii were made flatter as lens overall/optic zone diameters increased in order to maintain a constant tear layer thickness. All other parameters were held constant. Oxygen uptake rates were measured for the normal, open eye, as well as after 5 min of static (without blinking) and dynamic (with blinking once every 5 s) wear of each lens design. Under both static and dynamic conditions, oxygen uptake rates increased with increase in lens overall/optic zone diameter. The differences between the static and dynamic condition data served as an index of tear pump efficiency for each lens. These differences decreased with increase in lens overall/optic zone diameter.

Analysis of Variance↗