Biomedical subjects

R M Hansen

Publications and source records attributed to R M Hansen.

At least 19 recordsLinked to original sources

PubMed2001

Cycloplegic refractions in healthy children aged 1 through 48 months.

OBJECTIVES: To provide a description of refractive errors in healthy, term-born children, aged 1 through 48 months, and to test the hypotheses that spherical equivalent becomes significantly less hyperopic and less variable with increasing age. METHODS: Following a prospective, cross-sectional design, cycloplegic retinoscopy was used to measure the refractive error in both eyes of 514 healthy, term-born children in 12 age groups. Three hundred were aged 12 months or younger. Spherical equivalent and cylindrical power and axis were analyzed as a function of age. Prediction limits for spherical equivalent were calculated. RESULTS: Spherical equivalents of right and left eyes did not differ at any age. Hyperopia declined significantly with increasing age. The variability in spherical equivalent also decreased significantly with age. Cylindrical error of 1 diopter or more was found in 25% of the children; the proportion with astigmatism was highest in infancy and then waned. Myopia and anisometropia were rare, occurring in 3% and 1% of the sample, respectively. CONCLUSIONS: Significant declines in hyperopia and variability of spherical equivalent appear to be features of emmetropization. The normal prediction limits provide guidelines against which data from individual patients can be compared.

Age Distribution↗

PubMed2001

The rod photoreceptors in retinopathy of prematurity: an electroretinographic study.

OBJECTIVE: To test the hypothesis that the more severe the acute phase retinopathy of prematurity (ROP) was in the preterm weeks, the more severely compromised is rod photoreceptor function after the ROP has resolved. METHODS: Electroretinographic (ERG) responses were recorded from 25 dark-adapted children (ages 2.5 months' postterm to 14 years) categorized by maximum, acute phase ROP (None to Very Severe). From the ERG a-wave "S," a sensitivity parameter for the rod photoreceptor response, and R(mp3), the saturated amplitude of the rod photoreceptor response were calculated using a model of the activation of rod phototransduction. The patients' results were compared with those of healthy controls (n = 71). RESULTS: Among those in the None, Mild, Moderate, and Severe categories, both S and R(mp3) varied significantly with severity of acute phase ROP. In the Very Severe category, ERG responses were too attenuated to calculate S and R(mp3). CONCLUSIONS: The rod photoreceptors must be involved in ROP. The more severe the acute phase ROP, the more severe is the compromise of the processes involved in the activation of phototransduction in the rods.

Acute Disease↗

PubMed2000

Background adaptation in children with a history of mild retinopathy of prematurity.

PURPOSE: In children with a history of mild retinopathy of prematurity (ROP), test the hypothesis that elevation of the parafoveal over peripheral dark-adapted threshold is due to photoreceptor rather than postreceptor dysfunction. METHODS: A forced choice procedure was used to measure thresholds, for detection of 2 degrees diameter, 50 msec, blue stimuli presented 10 degrees (parafoveal) or 30 degrees (peripheral) eccentric in the dark and in the presence of steady red backgrounds (-4 to +2 log scot td). Four ROP and four control subjects were tested at both eccentricities. A model of the increment threshold function was fit to the data to calculate the eigengrau and dark-adapted threshold. RESULTS: Both ROP subjects with elevated parafoveal thresholds also have elevated parafoveal eigengraus. On the other hand, parafoveal and peripheral eigengraus are equal in ROP subjects without parafoveal threshold elevation. Nevertheless, the dark-adapted thresholds of all ROP subjects are higher than those of any control subject at both sites. CONCLUSIONS: The parafoveal threshold elevation is due to rod dysfunction. There is also evidence of peripheral rod photoreceptor involvement in the subjects with ROP.

Adolescent↗

PubMed2000

The development of scotopic sensitivity.

UNLABELLED: PURPOSE. Test the hypothesis that the developmental increases in rod photoreceptor sensitivity and rod-mediated visual sensitivity at 10 degrees, 20 degrees , and 30 degrees eccentric are concurrent. It is known that maturation of the parafoveal (10 degrees eccentric) rod outer segments and visual sensitivity is delayed compared to that at 30 degrees eccentric. METHODS: Rod isolated electroretinographic (ERG) responses to full-field stimuli were obtained from dark-adapted subjects (n = 71), ranging in age from early infancy through middle age. Rod photoreceptor sensitivity was calculated by fitting a model of the activation of phototransduction to the a-wave response. Rod driven b-wave sensitivity was calculated from stimulus-response functions. A logistic growth model was used to summarize the developmental increases in sensitivity of the rod photoreceptors and the b-wave. Previously reported dark-adapted, rod-mediated visual sensitivities at 10 degrees , 20 degrees, and 30 degrees eccentric, obtained using preferential looking procedures, were reanalyzed using the logistic growth model. RESULTS: The logistic growth model accounted for 57% to 85% of the variance of each sensitivity parameter with age in normal subjects. The shape of the growth curve and the age at which sensitivity reaches 50% of the adult value is similar (10.0-13.5 weeks) for the rods, the b-wave, and peripheral visual sensitivity, but is significantly older, 19.5 weeks, for rod-mediated parafoveal visual sensitivity. CONCLUSIONS: Rod photoreceptor sensitivity and peripheral, rod-mediated visual sensitivity develop concurrently. A parsimonious explanation is that rod photoreceptor sensitivity determines dark-adapted, rod-mediated visual sensitivity during development.

Adolescent↗

PubMed2000

Rod-mediated increment threshold functions in infants.

PURPOSE: To obtain and analyze scotopic increment threshold functions to test the hypothesis that rod photoreceptor immaturity accounts for the elevation of infants' over controls' dark-adapted thresholds and elevation of parafoveal over peripheral thresholds in infants. METHODS: Using a preferential looking method, thresholds for detection of 2(o), 50 msec, blue stimuli presented 10(o) (parafoveal) or 30(o) (peripheral) eccentric were measured in the dark and in the presence of steady red backgrounds. Ten 10-week-old infants and four control subjects (8-35 years) were tested. To evaluate pre- and postadaptation site determinants of threshold, a model of the increment threshold function was fit to the data, and the dark-adapted threshold (T(D)) and eigengrau (A(O)) were calculated. The values of T(D) and A(O) were compared between infants and controls and between parafoveal and peripheral eccentricities. RESULTS: At both parafoveal and peripheral eccentricities, infants' values of T(D) and A(O) were significantly higher than those of controls. The locus of the coordinates (A(O), T(D)) differed significantly between parafoveal and peripheral eccentricities. In every infant, the parafoveal value of T(D) was higher (by 0.3-0.6 log unit) and A(O) lower (by 0.2-0.5 log unit) than the peripheral value, whereas controls had no difference in T(D) and A(O) at the two eccentricities. CONCLUSIONS: The results indicate that both receptoral and postreceptoral immaturities have a role in the elevation of infants' over controls' thresholds. In infants, rod photoreceptor immaturity before the site of adaptation accounts for elevation of parafoveal over peripheral thresholds.

Adolescent↗

PubMed1999

Rod photoreceptor maturation does not vary with retinal eccentricity in mammalian retina.

PURPOSE: Test the hypothesis that the development of mammalian rod outer segments (ROS) varies with retinal eccentricity. METHODS: During the period of photoreceptor cell development, ROS lengths, opsin mRNA and (rhod)opsin were measured in central and peripheral retina of cows and pigmented rats. Published ROS length and/or rhodopsin data from albino rats, cows and monkeys were re-analyzed. Logistic growth curves were fitted to the newly obtained and published data. Within a species, growth in central and peripheral regions was compared. RESULTS: The logistic growth curves fit all the data well and provide an excellent view of the developmental increases in ROS length, opsin mRNA and (rhod)opsin in each retinal region. Within a species, the growth curves for ROS length, opsin mRNA and (rhod)opsin concentration are superimposable. The age at which ROS length reaches 50% of its adult value is invariant with eccentricity. An exception to this pattern is the simian parafoveal ROS, which appears to have a delayed course of development. CONCLUSIONS: The hypothesis is disproved. Unlike rod photoreceptor cell genesis, ROS development is invariant with retinal eccentricity. Primate parafoveal ROS appear to have a different pattern of development.

Aging↗

PubMed1999

The rhodopsin content of human eyes.

PURPOSE: To measure the total amount of rhodopsin in human eyes across the life span and to test the hypothesis that the rhodopsin content of infants' and the elderly's eyes is lower than at other ages. METHODS: Rhodopsin was extracted from retinal and pigment epithelial fractions of 196 eyes of 102 donors, ages 27 weeks' gestation through 94 years, using quantitative procedures. To recover photopigment bleached by unavoidable light exposure, the fractions from 78 eyes were incubated with 9-cis retinal. The total photopigment (retinal plus pigment epithelial fractions) per eye was examined for significant changes with age, using the higher value from pairs of eyes. RESULTS: The median rhodopsin content of the higher eye of adults is 6.45 nmoles (range, 3.33-10.84 nmoles) with 8 nmoles or more recovered from 28% of all adult eyes. The rhodopsin content of infants' eyes (< 12 months post-term) is significantly lower than that of older individuals and increases with age. After infancy, no change with age is found. For both infants and adults, 9-cis retinal significantly increases the amount of photopigment recovered without reducing the variance in the amount of photopigment recovered. The rhodopsin content is estimated to be 50% of the median adult amount early in infancy, approximately 5 weeks postterm (95% confidence interval, 0-10 weeks postterm). CONCLUSIONS: A developmental increase in rhodopsin content occurs during infancy. Thereafter rhodopsin content remains constant. The amount of rhodopsin recovered from human eyes is quite variable. Bleaching alone cannot explain the variability.

Adolescent↗

PubMed1999

The course of maturation of rod-mediated visual thresholds in infants.

PURPOSE: To measure the developmental course of infants' rod-mediated thresholds. METHODS: Thresholds for detecting stimuli (2 degrees diameter, 50 msec duration) presented at 10 degrees (parafoveal site) or 30 degrees (peripheral site) from a central fixation target were estimated using a preferential-looking method. Nine infants were tested at both stimulus positions at ages 10, 18, and 26 weeks. RESULTS: At 10 weeks, infants' thresholds at both sites were significantly higher than those of adults. The infants' average threshold at 10 degrees was 0.5 log unit higher than the infants' average threshold at 30 degrees. Adults' thresholds at the two sites were equal. Thresholds of all infants decreased with age until by age 26 weeks the parafoveal and peripheral thresholds were equal and were the same as those of adults. The rate of change of parafoveal thresholds was significantly faster than the rate of change of peripheral thresholds. CONCLUSIONS: Although postreceptoral factors cannot be ruled out, the results suggest that developmental increases in rod outer segment length and rhodopsin density account for most of the threshold changes during infancy.

Adult↗

PubMed1999

Rod photoreceptors in infant rats with a history of oxygen exposure.

PURPOSE: To study in an infant rat model of retinopathy of prematurity, the rod photoreceptors, which are known to have attenuated photoresponses. METHODS: Rhodopsin was extracted from whole retinas, the thickness of the rod outer segment (ROS) layer was measured, large phagosomes were counted, and the ROS ultrastructure was examined in the retinas of oxygen-exposed and control rats, ages 13 and 18 days. Rhodopsin absorbances in the ROS were measured by microspectrophotometry at age 20 days. RESULTS: The rhodopsin content did not differ significantly between the oxygen-exposed and control rats at either 13 or 18 days. The thickness of the ROS layer was equal in 13-day-old oxygen-exposed and control rats; however, at 18 days, the ROS layer was significantly thinner in the oxygen-exposed rats than in the control rats. The number of phagosomes did not vary significantly among the oxygen-exposed and control groups. Opsin immunoreactivity was seen only in the ROS layer in oxygen-exposed and control rats. The ROS were disorganized in oxygen-exposed rats. The rhodopsin absorbances of the oxygen-exposed ROS were significantly more variable and higher than in the control rats. CONCLUSIONS: Attenuation of the rod photoresponse parameters does not result simply from shortening of the outer segments and consequent low rhodopsin content. Rather, the structure of the outer segments is altered. A fault in the synthesis of the outer segments, rather than disposal of outer segment discs, is suspected.

Animals↗

PubMed1997

Dark-adapted thresholds in children with histories of mild retinopathy of prematurity.

PURPOSE: To test the hypothesis that rod-mediated visual thresholds at 10 degrees eccentricity are elevated in children with histories of mild retinopathy of prematurity (ROP). METHODS: Dark-adapted thresholds for detection of 50 msec, 2 degrees diameter spots at a 10 degrees eccentric site, and at a peripheral reference site, 30 degrees eccentric, were measured in 20 children with a history of mild ROP and known courses of refractive development. Ten myopic control subjects also were tested. The thresholds of the ROP and control subjects were compared. RESULTS: Six of the subjects with ROP had elevated thresholds at the 10 degrees site. High myopia had been present since age 18 months or younger in each of the six. The thresholds of all other subjects with ROP, whose courses of refractive development had been toward emmetropia, and the control subjects with myopia were normal. In subjects with ROP, the association of early, persistent high myopia and an elevated threshold at 10 degrees was significant (chi 2 = 20; P < 0.01). Among the subjects with ROP, refractive error and axial length were correlated. CONCLUSIONS: ROP or factors causing ROP appear to alter rod-mediated retinal function. The association of abnormal rod-mediated sensitivity and refractive development suggests that rod-mediated retinal function is involved in the regulation of eye growth in children with a history of mild ROP.

Adolescent↗

PubMed1996

Phase III study of bolus versus infusion fluorouracil with or without cisplatin in advanced colorectal cancer.

BACKGROUND: Phase II studies of fluorouracil (5-FU) administered by protracted intravenous infusion have suggested an improved response rate and decreased toxicity profile when compared with 5-FU given by bolus injection in patients with metastatic colorectal cancer. Additional studies have suggested further enhancement of infusion 5-FU activity when it is combined with low-dose weekly cisplatin administration. PURPOSE: This phase III study in adults with metastatic colorectal cancer was planned as a comparison of objective response rates, toxicity, and survival in patients receiving bolus versus protracted-infusion 5-FU with or without cisplatin. METHODS: Four hundred ninety-seven previously untreated patients with advanced, measurable metastatic colorectal cancer were randomly assigned to receive treatment A (bolus 5-FU at 500 mg/m2 for 5 days followed in 2 weeks by weekly bolus 5-FU at 600 mg/m2), treatment B (bolus 5-FU at 500 mg/m2 for 5 days followed in 2 weeks by weekly bolus 5-FU at 600 mg/m2, plus weekly cisplatin at 20 mg/m2), treatment C (5-FU at 300 mg/m2 per day by continuous infusion), or treatment D (5-FU at 300 mg/m2 per day by continuous infusion plus weekly cisplatin at 20 mg/m2). All drugs were administered intravenously. Enrollment in the trial occurred from August 1987 through December 1990, and follow-up was through September 1995. The Kaplan-Meier method was used to estimate overall and disease-free survival, and Cox regression models were used to assess the effects of patient characteristics on survival. All P values resulted from two-sided tests. RESULTS: Objective tumor response was observed in 28 (18%) of 153 patients receiving treatment A, in 45 (28%) of 159 patients receiving treatment C (C versus A; P = .045), and in 47 (31%) of 153 patients receiving treatment D (D versus A; P = .016). Because of excessive toxicity, treatment B was discontinued after only 12 patients had begun treatment. Median time to disease progression was 5.1 months for patients in arm A compared with 6.2 and 6.5 months for patients in arms C and D, respectively (C versus A, P = .007; D versus A, P = .017). Patterns of toxic effects differed substantially among the treatment arms. Forty-five percent of the patients receiving bolus 5-FU alone (A) experienced grade 3-4 leukopenia, with two sepsis-related deaths. Hand-foot syndrome and mucositis were the major treatment-limiting toxic effects for patients in the two treatment arms involving infusion. Despite the improvement in response rates and time to disease progression with infusion 5-FU with or without cisplatin (C and D, respectively) (P = .003), the overall survival for the three groups (A, C, and D) was similar (P = .307). This may have been due in part to a longer median survival time of 10.4 months for patients in arm A, compared with an anticipated survival of 7 months. CONCLUSION: 5-FU given as a continuous infusion produced a higher objective response rate, a modest prolongation in time to disease progression, and less life-threatening myelosuppression in patients than bolus 5-FU. Concomitant treatment with low-dose cisplatin caused added toxicity and complexity of treatment and did not provide a major clinical benefit. No statistically significant survival differences were observed among the three treatment groups.

Antimetabolites, Antineoplastic↗

PubMed1996

Vision in Leber congenital amaurosis.

OBJECTIVE: To determine if vision changed with age in infants and children with Leber congenital amaurosis. PATIENTS: Grating acuity and dark-adapted visual thresholds were tested in 36 patients with Leber congenital amaurosis. Longitudinal assessments were obtained for 24 patients and analyzed for significant changes over time. Visual acuity and threshold and the courses of visual acuity and threshold were examined for significant associations with hyperopia, fundus appearance, and complicated vs uncomplicated status. RESULTS: Measurable grating acuities ranged from 0.16 to 6 cycles per degree (median, 1.27 cycles per degree or about 20/500), and dark-adapted visual thresholds were elevated 1.0 to 5.6 log units (median, 2.33 log units). Eighteen patients never had demonstrable grating acuity, and 12 had no light perception. Among those with serial tests, visual acuity improved or remained stable in 10 patients and declined in 4. Dark-adapted visual thresholds were stable in those with improving or stable visual acuities but worsened in 5 patients, including the 4 whose visual acuity worsened. No significant associations of visual acuity, dark-adapted visual threshold, the course of visual acuity, or the course of dark-adapted visual threshold with hyperopia, fundus appearance, or complicated vs uncomplicated status were found. CONCLUSIONS: Visual capabilities varied widely. Vision was stable in the majority by longitudinal measures but increased in a few and deteriorated in others. Neither ocular characteristics nor complicated vs uncomplicated status predicted visual function. Thus, if vision and its course are to be known in a patient with Leber congenital amaurosis, it must be tested.

Aging↗

PubMed1996

Photoreceptor function in infants and children with a history of mild retinopathy of prematurity.

Five infants and children with a history of mild retinopathy of prematurity (ROP) were tested for postulated alterations in rod photoreceptor function. The photoreceptor responses were derived from the electroretinographic alpha waves. Postreceptoral components, the beta wave and the oscillatory potentials, were also examined. The saturated amplitude and sensitivity of the rod photoreceptor responses were low, except for the sensitivity in one patient. The beta-wave sensitivity was low, but saturated amplitudes were within the 95% prediction interval for normal. The amplitudes of the oscillatory-potential responses were also attenuated. The results indicate that retinal dysfunction may be present in patients with a history of mild ROP long after the ROP has completely resolved. Additionally, the data suggest that the photoreceptors are the primary site of retinal dysfunction in mild ROP.

Adult↗

PubMed1996

Rhodopsin in immature rod outer segments.

PURPOSE: To test the hypothesis that rhodopsin concentration is low in immature rat rod outer segments (ROS). METHODS: Microspectrophotometry (MSP) was used to assess rhodopsin absorbances in localized regions of isolated ROS from dark-adapted 13-, 19-, and 34-day-old and adult rats. Photopigment was extracted from the retinas of paired eyes in dark-adapted and light-adapted rats. One retina of each pair was treated with 9-cis retinal before extraction of photopigment. Rhodopsin with native 11-cis retinal was extracted from the fellow retina. RESULTS: By MSP, rhodopsin absorbance was low in the short ROS of 13-day-old rats. In 19-day-old rats with ROS lengths approximately equal to those of adults, absorbance was low at the tip, but at the base, it was equal to the high absorbance at both the tip and the base in adults. The 9-cis retinal did not add absorbance to the photopigment extracts of dark-adapted retinas at any age, but it did add absorbance to extracts of the light-adapted retinas at every age. CONCLUSIONS: The MSP results show that the accumulation of rhodopsin in developing rat rods depends on increasing concentrations in localized regions. No evidence of apo-opsin is found in immature rat rods. Thus, in immature ROS regions, the low rhodopsin absorbances suggest that the amount of opsin is also low. Greater disk-to-disk spacing in immature ROS regions than in mature regions could account for these findings.

Aging↗

PubMed1995

The course of myopia in children with mild retinopathy of prematurity.

The courses of spherical equivalent in patients (n = 62) who had mild, non-cicatricial retinopathy of prematurity (ROP), and in those without a history of ROP (n = 25) were modeled as a linear function of age; an exponential model was also considered. A few (n = 5) without ROP have abnormal courses characterized by hyperopia in early infancy; none have poor acuity. Although the majority of patients with ROP have courses indistinguishable from those of term born controls, 27 (43.5%) have abnormal courses, most of which are toward myopia. Optotype acuities were significantly poorer among the ROP patients with abnormal than normal refractive courses. Thus abnormal refractive development and acuity deficits are associated in eyes that have had mild ROP.

Adolescent↗

PubMed1995

Effect of prior oxygen exposure on the electroretinographic responses of infant rats.

PURPOSE: To study electroretinographic responses of infant rats with a history of exposure to high-ambient oxygen. METHODS: Electroretinographic responses to a range of full-field stimuli were recorded from 13-day-old (n = 8) and 18-day-old (n = 10) rats with a history of intermittent exposure to 80% oxygen and age-matched controls. The a-waves were fitted with a model of rod cell sensitivity and saturated response amplitude. The amplitudes and implicit times of the b-wave and oscillatory wavelets were examined as a function of stimulus energy. Response parameters in oxygen-exposed rats were compared to those in controls. RESULTS: The amplitude of the saturated rod response was reduced in oxygen-exposed 13-day-old but not 18-day-old rats. The sensitivity of the rod response was reduced in both 13- and 18-day-old oxygen-exposed rats. The saturated amplitude and sensitivity of the b-wave did not differ significantly between oxygen-exposed and control rats age 13 days, but both amplitude and sensitivity were significantly decreased in 18-day-old oxygen-exposed rats. Oscillatory potentials, which could be investigated only in 18-day-old rats, showed significant attenuation of OP3 but not OP4 amplitudes in the oxygen-exposed rats. The sensitivity of OP2 did not differ significantly between oxygen-exposed and control rats. The avascular area in the oxygen-exposed rats was not correlated with any of the rod cell, b-wave, or oscillatory potential response parameters. CONCLUSION: The function of the rod photoreceptors, as well as the inner retina, is altered in infant rats with a history of oxygen exposure.

Aerobiosis↗

PubMed1995

The effects of acetazolamide on the electroretinographic responses in rats.

PURPOSE: To study the mechanisms and sites of action of the carbonic anhydrase inhibitor, acetazolamide (AZM), on the rod- and cone-mediated electroretinogram (ERG) of the dark-adapted rat. METHODS: After a within-subjects design, ERG responses to brief, full-field flashes were recorded from adult (60 to 90 days old) albino rats, with and without AZM (5 mg/100 g, intraperitoneally). Flickering stimuli (6 and 26 Hz) were used to study rod- and cone-mediated responses. Aspartate-isolated responses of the isolated retina were recorded with and without AZM in the superfusate. The a-wave and PIII responses were fitted with a model of the rod's response by estimating the maximum response (Rmp3), sensitivity (S), and delay td. The b-wave response amplitude and implicit time were examined as a function of stimulus energy. The parameters obtained in the AZM-treated and untreated conditions were compared. RESULTS: Acetazolamide causes a significant decrease in saturated rod response, b-wave amplitude, aspartate-isolated PIII, and the rod- and cone-mediated responses to flickering light. The estimated sensitivity of the rod response (S), b-wave sensitivity, and b-wave implicit time are not altered significantly by AZM. CONCLUSION: Acetazolamide, probably through mechanisms that acidify the retina, attenuates the amplitudes of the retinal responses without significant effect on sensitivity.

Acetazolamide↗

PubMed1995

The development of the rod photoresponse from dark-adapted rats.

PURPOSE: To study electroretinographic a- and b-wave responses of rats at the ages during which rod outer segment length (ROS) and rhodopsin content increase. METHODS: Electroretinographic responses to brief, full-field stimuli were recorded from dark-adapted young (ages 12 to 30 days) and adult rats. The amplitude of the a-wave and the amplitude and implicit time of the b-wave were examined as a function of stimulus intensity. Sensitivity (S), saturated amplitude (RmP3), and delay (td) of the rod cell responses were calculated from the a-waves. RESULTS: The developmental increase in saturated a-wave amplitude parallels, but lags behind, growth of outer segment length, whereas the saturated b-wave amplitude increases with about the same course as rhodopsin content of the retina. The sensitivity, S, depends on rhodopsin content, and the developmental decrease in the flash energy required to produce a half-maximum b-wave amplitude is inversely proportional to the developmental increase in rhodopsin content. No significant age-dependent variation in td can be detected. CONCLUSION: During development, ROS length and rhodopsin content of the retina are significant determinants of a- and b-wave response parameters.

Aging↗