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Biomedical subjects

R Michael

Publications and source records attributed to R Michael.

At least 37 records · Page 2Linked to original sources

Change in muscle mass and muscle strength after a hip fracture: relationship to mobility recovery.

BACKGROUND: Hip fracture in elderly persons has a serious impact on long-term physical function. This study determines the change in muscle strength and muscle mass after a hip fracture, and the associations between these changes and mobility recovery. METHODS: Ninety community-dwelling women aged 65 years and older who had recently experienced a fracture of the proximal femur were included in the study. At 2 to 10 days after hospital admission, the women's grip strength, ankle dorsiflexion strength, and regional muscle mass (by dual-energy x-ray absorptiometry) were measured, and the prefracture level of independence for five mobility function items was assessed. All measurements were repeated at 12 months. RESULTS: At follow-up, only 17.8% of the women had returned to their prefracture level of mobility function for all five items. Mobility function recovery was not related to change in skeletal muscle mass of the nonfractured leg or the arms. However, women who lost grip strength (mean loss of -28.7%, SD = 16.9%), or who lost ankle strength of the nonfractured leg (mean loss of -21.5%, SD = 14.7%), had a worse mobility recovery compared with those who gained strength (p = .04 and p = .09, respectively). In addition, chronic disease (p = .03), days hospitalized (p = .04), and self-reported hip pain (p = .07) were independent predictors of decline in mobility function. CONCLUSIONS: The results suggest that loss of muscle strength, but not loss of muscle mass, is an independent predictor of poorer mobility recovery 12 months after a hip fracture. When confirmed by other studies, these findings may have implications for rehabilitation strategies after a hip fracture.

Aged↗

Repair in the rat lens after threshold ultraviolet radiation injury.

PURPOSE: To investigate the development and recovery of lens damage after in vivo close-to-threshold exposure to ultraviolet B radiation. METHODS: One eye of young, female Sprague-Dawley rats was exposed to 5 kJ/m2 narrowband ultraviolet radiation (UVR) (lambda(max) = 302 nm) for 15 minutes. Groups of rats were killed 1, 7, and 56 days after exposure. The structure of the exposed and nonexposed lenses was examined with light microscopy, scanning electron microscopy, transmission electron microscopy, freeze-fracture, fluorescent membrane staining, and Fourier transform analysis. RESULTS: One day after UVR exposure the lens surface had flakelike opacities. Seven days after exposure, the lens surface appeared opaque and corrugated, and the equatorial cortex had small opacities. At 56 days postexposure, the surface and equator appeared clear, but the cortex had a subtle shell-shaped opacity. At 1 day postexposure, apoptotic cell death occurred in the lens epithelium, but the cortical fibers were normal. At 7 days postexposure, the epithelium and the fibers between the 10th and 40th growth shell below the capsule contained extracellular spaces of different sizes. After 56 days, the epithelial layer appeared normal, and the extracellular spaces had disappeared; but abnormal fibers were found between the 60th and 100th growth shell below the capsule. Fibers above and below the damaged growth shells appeared fully normal. CONCLUSIONS: A close-to-threshold dose of UVR causes cataract, which is largely reversible. The UVR exposure leads to apoptosis in the lens epithelium, and after a latency period of several days, lens fibers are abnormal. Extracellular spaces develop in the epithelium and fibers. Within several weeks after exposure, the epithelium fully recovers and new fibers develop normally. The originally affected fibers are repaired. However, this repair is incomplete, leaving a small zone of enhanced light scattering in the equatorial cortex.

Animals↗

Development and repair of cataract induced by ultraviolet radiation.

BACKGROUND: Several epidemiological investigations show a correlation between cataract development and the dose of ultraviolet radiation (UVR) received. It is experimentally well established that exposure of animal eyes to UVR induces cataract. Most cataracts develop as a gradual increase in lens opacity. Despite this, current estimations of toxicity for cataract are based on the concept that cataract is a binary event. Moreover, current exposure limits for UVR are based on subjective inspections with slit lamp microscopy. PURPOSE: The first purpose of the present study was to determine a statistically defined maximum acceptable dose for ultraviolet radiation-induced cataract based on quantitative data of forward light scattering in lenses. The second purpose was to find possible explanations for light scattering by investigating the morphology and the refractive index distribution in the lens. The third purpose was to describe the development of cataract after UVR on the cellular level. METHODS: Six-week-old, female Sprague-Dawley rats received UVR unilaterally in vivo. The radiation from a high pressure mercury lamp was collimated, passed through a water filter and an interference filter or a monochromator (lambdaMAX = 300 nm), and projected onto the cornea. The exposure time was 15 min. The exposure dose ranged between 0.1 and 20 kJ/m2 and the animals were kept between 6 hours and 32 weeks after exposure. The extracted lenses were photographed and forward light scattering was measured. Other methods included light microscopy, fluorescence microscopy, transmission and scanning electron microscopy, freeze-fracture and microradiography. RESULTS AND CONCLUSIONS: From a long-term experiment, it was concluded that UVR-exposed lenses scatter light more than their contralaterals and that a higher dose induces more light scattering. After exposure to 5 kJ/m2, the mean forward light scattering remains unchanged between 1 and 32 weeks. Earlier observations, taken together with the current findings, indicate that the optimal time to detect low dose UVR-induced cataract is one week after exposure in rats. The intensity of forward light scattering increases exponentially with increased UVR dose between 0.1 and 14 kJ/m2. Based on this continuous dose-response, a method to determine a maximum acceptable dose to avoid UVR-induced cataract was developed. The statistically defined lower limit of pathologic light scattering is projected on the dose-response function. The dose corresponding to that point can be estimated and was suggested to be called the Maximum Acceptable Dose (MAD). Two low dose UVR exposures with 0 or 6 h intervals between the exposures produce the same degree of lens opacification. When the second exposure follows 24 or 48 h after the termination of the first, lenticular damage increases. Repair processes between 24 and 48 h after exposure appear to be sensitive to UVR, and an additional exposure during this time may aggravate cataract development. Lenses exposed to UVR grow more slowly than their non-exposed contralaterals. This decrease in lens growth was more pronounced with increasing dose. Low doses led to decreased water content in the lens whereas high doses led to swelling. At 6 months after low dose UVR exposure, no global change of the refractive index was found. However, local variations of the refractive index induce a subtle cortical light scattering. In vivo low dose UVR induces programmed cell death which peaks 24 h post-exposure and involves the entire lens epithelium. Dead cells are removed from the epithelium by phagocytosis. This leads to disintegration of the lens epithelium, associated with flake-like opacities at the lens surface. After one week, the epithelium and the equatorial parts of superficial lens fibers contain extracellular spaces. The extracellular spaces together with locally disarranged fibers produce a corrugated opaque lens surface and equatorial opacities. Within several weeks after ex

Animals↗

An action spectrum for UV-B radiation and the rat lens.

PURPOSE: To determine an action spectrum for UV-B radiation and the rat lens and to show the effect of the atmosphere and the cornea on the action spectrum. METHODS: One eye of young female rats was exposed to 5-nm bandwidths of UV-B radiation (290, 295, 300, 305, 310, and 315 nm). Light scattering of exposed and nonexposed lenses was measured 1 week after irradiation. A quadratic polynomial was fit to the dose-response curve for each wave band. The dose at each wave band that produced a level of light scattering greater than 95% of the nonexposed lenses was defined as the maximum acceptable dose (MAD). Transmittance of the rat cornea was measured with a fiberoptic spectrophotometer. The times to be exposed to the MAD in Stockholm (59.3 degrees N) and La Palma (28 degrees N) were compared. RESULTS: Significant light scattering was detected after UV-B at 295, 300, 305, 310, and 315 nm. The lens was most sensitive to UV-B at 300 nm. Correcting for corneal transmittance showed that the rat lens is at least as sensitive to UV radiation at 295 nm as at 300 nm. The times to be exposed to the MAD at each wave band were greater in Stockholm than in La Palma, and in both locations the theoretical time to be exposed to the MAD was least at 305 nm. CONCLUSIONS: After correcting for corneal transmittance, the biological sensitivity of the rat lens to UV-B is at least as great at 295 nm as at 300 nm. After correcting for transmittance by the atmosphere, UV-B at 305 nm is the most likely wave band to injure the rat lens in both Stockholm and La Palma.

Animals↗

Influence of exposure time for UV radiation-induced cataract.

PURPOSE: It is believed that for a certain ultraviolet radiation (UVR) exposure, the biologic effect depends on the product of irradiance and exposure time (the reciprocity Bunsen-Roscoe law). The purpose of this study was to investigate the validity of the reciprocity law for UVR-induced cataract. METHODS: Two experiments were conducted. In the first one, 100 Sprague-Dawley rats were exposed to UVR divided into five groups according to exposure time: 7.5, 15, 30, 60, and 120 minutes. In the second experiment, 80 Sprague-Dawley rats were exposed to UVR divided into four groups according to exposure time: 5, 7.5, 11, and 15 minutes. All the animals were unilaterally exposed to the same dose of UVR (8 kJ/m(2)) in the 300-nm wavelength region. One week after exposure both lenses were removed to measure the intensity of forward light scattering and for microphotography. Groups were compared by evaluating the difference between exposed and nonexposed eyes. RESULTS: The group exposed to UVR for 5 minutes had the lowest intensity of forward light scattering. The highest intensity of forward light scattering was found in the group that was exposed for 15 minutes. With longer exposure intervals, the intensity of forward light scattering decreased as the exposure time increased. No difference in intensity of forward light scattering was found between the groups exposed for 60 and 120 minutes. CONCLUSIONS; Exposure time strongly influenced cataract formation after low-dose UVR. In this model of UVR-induced cataract, the photochemical reciprocity law was modulated by a biologic response.

Animals↗

Effect of follicular cells on calcitonin gene expression in thyroid parafollicular cells in cell culture.

Expression of calcitonin (CT) gene in thyroid parafollicular cells involves alternate formation of CT mRNA or CGRP mRNA. High amounts of CT mRNA are formed only in thyroid gland and formation of CGRP mRNA dominates in the remaining organs. Apart from paracrine and endocrine factors, mRNA formation on the CT gene seems to be affected also by direct contacts with other cells present in the thyroid gland, in which parafollicular cells are located next to follicular cells. The present study aimed at examining whether thyroid follicular cells affect formation of mRNAs for CT and CGRP in parafollicular cells. The studies were performed in cell cultures. A parafollicular cell line (TT cells) and a follicular cell line (F6BTY cells) served as the experimental model. For comparison, co-cultures with fibroblasts, 3T3 cells, and malignant melanoma, MM cells, were also examined. CT gene expression was examined at the level of mRNAs (in situ hybridization and morphometric studies) and at the level of hormones (immunocytochemistry, morphometric studies and radioimmunological estimation of hormone levels in the medium). The immunocytochemical and hybridocytochemical studies, in line with morphometry studies, demonstrated that F6BTY and 3T3 cells were capable of affecting mRNA production for CT and CGRP and that they changed the ratio of CGRP/CT secretion by TT cells, as a sequel of contact between the two cell types and due to mediation of secreted substances. On the other hand, the malignant melanoma MM cells showed no effect on the secretion ratio. Our study seems to indicate that control of mRNA formation from CT gene may involve not only humoral factors but also direct contacts with other cells, which may explain differences in expression of the gene between cells localized in different organs.

Calcitonin↗

Lens opacities after repeated exposure to ultraviolet radiation.

PURPOSE: To investigate the effect of the interval between two, near-threshold exposures to ultraviolet radiation (UVR) on cataract development. METHODS: One eye of Sprague-Dawley rats was exposed twice to 4 kJ/m2 narrow band UVR (lambdaMAX=300 nm) for 15 min each. The interval between exposures was 0, 6, 24 or 48 h. One week after the first exposure both lenses were removed for photography and measurement of the intensity of forward light scattering to quantify lens opacities. RESULTS: All exposed lenses developed cataract. Forward light scattering was the same after double exposure with no interval or a 6 h interval. Forward light scattering after a 24 or 48 h interval was nearly twofold greater than that following no interval or a 6 h interval. The exposed lenses in all groups had mild anterior surface opacities and intense equatorial opacities as judged with a stereomicroscope. CONCLUSION: Two, near-threshold UVR exposures at 0 or a 6 h interval produce the same degree of lens opacification. When the second exposure follows 24 or 48 h after the first, lenticular damage increases. Repair processes between 24 and 48 h after exposure appear to be sensitive to UVR, and an additional exposure during this time may aggravate cataract development.

Animals↗

Outpatient costing and classification: are we any closer toa national standard for ambulatory classification systems?

The Outpatient Costing and Classification Study was commissioned by the Department of Health and Family Services to evaluate the suitability of the Developmental Ambulatory Classification System (DACS). Data on the full range of ambulatory services (outpatient clinics, emergency departments and allied health services) were collected prospectively from a stratified sample of 28 public hospitals. Patient encounters captured in the study represent 1% of the total ambulatory encounters in Australia in one year. Costing per encounter included time spent with the patient, cost of procedures, indirect costs (salaries and consumables), overhead costs and diagnostic costs. The most significant variable explaining cost variation was hospital type, followed by outpatient clinic type. Visit type and presence or absence of a procedure--major splits for the proposed DACS--did not produce splits that were consistent across all hospital strata. The study found that DACS is not an appropriate classification for hospital ambulatory services. A clinic-based structure for outpatients and allied health departments is recommended for classifying and funding ambulatory services in Australia.

Ambulatory Care↗

Dose-response function for lens forward light scattering after in vivo exposure to ultraviolet radiation.

BACKGROUND: It is known that different types of radiation, as well as aging and metabolic disorders, can cause cataract. Several epidemiological investigations show a correlation between cataract development and the dose of ultraviolet radiation (UVR) received. It is well established experimentally that exposure of animal eyes to UVR induces cataract. The purpose of the present study was to determine the dose-response function for UVR-induced opacities in the rat lens after in vivo exposure. METHODS: Sprague-Dawley rats received 0.1, 0.4, 1.3, 3, 5, 8 or 14 kJ/m2 UVR (lambda MAX = 300 nm, lambda 0.5 = 10 nm) unilaterally for 15 min. At 1 week after exposure both lenses were removed, photographs were taken and the intensity of forward-scattered light was measured. RESULTS: One week after UVR exposure, opacities occurred on the lens surface, as observed with a microscope. With increased UVR dose the opacities became more intense and occurred also in the equatorial area of the lens, but not in the nucleus. The intensity of forward light scattering increased with increased UVR dose between 3 and 14 kJ/m2. No significant change in intensity of forward light scattering was observed for lower UVR doses. CONCLUSION: The intensity of forward light scattering in the rat lens increase exponentially with increased UVR dose between 0.1 and 14 kJ/m2.

Animals↗

Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity.

Plasma leptin shows a nocturnal rise and a pulsatile pattern. This work was undertaken to determine the effects of gender and obesity on this pattern. Twenty-four-hour leptin profiles were evaluated in 31 subjects [17 male, 14 female; age: 36 +/- 2 yr (mean +/- SEM); body mass index: 27.5 +/- 1.0 kg/m2]. Plasma leptin profiles were higher in obese (body mass index > 27 kg/m2) than in lean subjects and higher in women than in men, regardless of fat mass. Leptin showed diurnal rhythmicity with peaks between 2200-0300 (median: 0120) and nadirs between 0800 and 1740 (median: 1033). Spectral analysis revealed 2 components (periodicities: 24 and 12 h) with higher relative amplitudes in lean than in obese subjects. The relative diurnal amplitude also was higher in men than in women, controlling for adiposity. Insulinemia, female sex, and age were negative determinants of diurnal rhythm relative amplitude. Pulse analysis revealed 3.6 +/- 0.3 pulses/24 h, occurring mostly 2-3 h after meals. Pulse frequency correlated negatively with fat mass and insulinemia (Spearman's r = -0.54 and -0.37, respectively; P < 0.05 for each). Thus, obesity is associated not only with higher leptin levels but also with blunted diurnal excursions and dampened pulsatility. This abnormal rhythmicity may contribute to leptin resistance in obesity. The significance of the sexual dimorphism in the diurnal amplitude is unclear, but it may be related to leptin's putative role as a metabolic signal to the reproductive axis.

Adipose Tissue↗

Physiological insulinemia acutely modulates plasma leptin.

Whether insulin acutely regulates plasma leptin in humans is controversial. We examined the dosage-response and time-course characteristics of the effect of insulin on leptin in 10 men (age 42+/-2 years [mean+/-SE]; BMI 29.3+/-2.0 kg/m2). Each individual underwent four 9-h euglycemic clamps (insulin at 20, 40, 80, and 400 mU x m[-2] x min[-1) and a control saline infusion. Although plasma glucose and insulin levels remained constant, leptin diminished from 9.1+/-3.0 to 5.9+/-2.1 ng/ml (P < 0.001) by the end of the control experiment. Conversely, plasma leptin showed a dosage-dependent increase during the insulin infusions that was evident within 30-60 min. The insulin-induced increase in leptin was proportionately lower in obese insulin-resistant men. Free fatty acids (FFAs) decreased during insulin and did not change during saline infusions. ED50 (the dose producing half-maximal effect) for insulin's effect on leptin and FFA was similar (138+/-36 vs. 102+/-24 pmol/l, respectively; P=0.11). To further define the role of physiological insulinemia, we compared the effect of a very low dosage insulin infusion (10 mU x m[-2] x min[-1]) with that of a control saline infusion in another group of 10 men (mean age 39+/-3 years; BMI 27.1+/-1.0 kg/m2). Plasma leptin remained stable during that insulin infusion, but fell by 37+/-2% in the control experiment. Thus physiological insulinemia can acutely regulate plasma leptin. Insulin could mediate the effect of caloric intake on leptin and could be a determinant of its plasma concentration. Inadequate insulin-induced leptin production in obese and insulin-resistant subjects may contribute to the development or worsening of obesity.

Adult↗

Apoptosis in the rat lens after in vivo threshold dose ultraviolet irradiation.

PURPOSE: To investigate DNA damage in the rat lens after in vivo close-to-threshold exposure to ultraviolet radiation (UVR). METHODS: Sprague-Dawley rats received 5 kJ/m2 UVR (lambdaMAX = 300 nm, lambda0.5 = 10 nm) unilaterally for 15 minutes. Animals were killed at 1, 6, and 24 hours and at 1 week after exposure. DNA-strand breaks were investigated in sagittal paraffin sections using the TdT-dUTP terminal nick-end labeling (TUNEL) technique and propidium iodide for counterstaining. Other lenses were prepared for transmission electron microscopy (TEM). RESULTS: TUNEL-positive nuclei were found at only 24 hours after UVR exposure. About one tenth of the epithelial cell nuclei were TUNEL positive, and affected cells were scattered over the entire epithelium. No TUNEL-positive cells were found at 1 or 6 hours or at 1 week after UVR exposure or in the nonexposed lenses. TEM verified the occurrence of programmed cell death and showed the breakdown of the apoptotic cells by adjacent cells. No signs of necrosis were found. CONCLUSIONS: Threshold-dose UVR induces programmed cell death that peaks 24 hours after exposure and involves the entire epithelium. Dead cells are removed from the epithelium by phagocytosis.

Animals↗

Bronchiolitis obliterans in a man who used his wood-burning stove to burn synthetic construction materials.

Many people heat their homes with wood-burning stoves. However, toxic fire effluent can escape from old or improperly operated stoves. The authors describe a case in which bronchiolitis obliterans developed in a man within hours after he burned synthetic construction materials in his wood-burning stove. Certain factors, such as careless or improper use of the stove, the size of the room, the lack of open-air ventilation and the composition of the materials burned, strongly point to inhalation of the fire effluent as the cause.

Adult↗

Correlation of genetic and serologic approaches to HIV-1 subtyping in Thailand.

The aim of this study was to compare the performance of differential polymerase chain reaction (PCR) typing and peptide enzyme-linked immunosorbent assay (V3-EIA) for human immunodeficiency virus type 1 (HIV-1) subtyping in Thailand using heteroduplex mobility assay (HMA) as the reference standard. Paired peripheral blood mononuclear cells (PBMC) and sera were collected from 38 HIV-1 seropositive persons in Thailand. HMA was done by standard methods; differential PCR employs primer pairs that differentially amplify either subtype E or B. V3-EIA used peptides specific for subtypes E or B. Thirty-two cases (84%) were found by HMA to be infected with subtype E: and six with (16%) subtype B. The results obtained with differential PCR were 100% concordant with those of HMA; V3 EIA correctly predicted the subtype in 95% (36 of 38). Six samples that molecularly subtyped as E were repeatedly dual reactive by screening V3-EIA, but these resolved to subtype E using an antigen-limiting EIA. Two samples were serologically nontypeable because of overall low levels of V3 antibody. Using HMA as the standard, differential PCR was shown to subtype HIV-1 reliably from patient PBMC samples. V3-EIA correctly predicted HIV-1 subtype in most (95%) of our cases. Because of the less rigorous sampling requirements, specimen processing, and logistical and technical requirements of serotyping compared with molecular techniques, it appears to be practical for screening purposes in a field environment. Samples that cannot be definitively subtyped serologically should undergo differential PCR and antigen-limiting V3 EIA. These approaches to HIV-1 subtyping should be used in complementary fashion in Thailand, where subtypes B and E are currently known to cocirculate.

Adult↗

Long-term development of lens opacities after exposure to ultraviolet radiation at 300 nm.

The long-term development of lens opacities after short-term exposure to ultraviolet radiation (UVR) was determined. Altogether, 200 Sprague-Dawley rats received unilaterally 5 or 20 kJ/m2 UVR (lambda MAX = 300 nm, lambda 0.5 = 10 nm) in vivo, during 15 min. At 1, 4, 8, 16 and 32 weeks after exposure subgroups of 20 rats from each dose group were sacrificed. Both lenses were removed for measurement of intensity of forward scattered light. It was found that exposed lenses scatter light more than their contralaterals and that a higher dose induces more light scattering. After exposure to 5 kJ/m2, the mean difference in scattering remained unchanged between 1 and 32 weeks' latency, but the distribution of the individual differences in scattering became skew. For several animals, lens opacities induced by 5 kJ/m2 seemed to decrease during the observation period. Earlier observations in complement to current findings implicate that it is optimal to detect close-to-threshold UVR-induced cataract at 1 week after exposure.

Animals↗

Casemix--what is it and what does it mean to ophthalmology?

The Australian government is committed to the establishment of a prospective payment system based on casemix information for acute hospital care in the near future, because these systems are demonstrably socially equitable and more efficient than present 'historical' systems. Since ophthalmology is an outpatient-based specialty, the establishment of a good ambulatory casemix system is essential to this specialty. Considerable input from clinicians will be required to establish a satisfactory system, and to maintain it in years to come.

Ambulatory Care↗