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Biomedical subjects

M L Katz

Publications and source records attributed to M L Katz.

At least 55 records · Page 3Linked to original sources

The piezoelectric pulse sensor device: a prospective evaluation.

The goal of this prospective study of the piezoelectric pulse sensor device was to determine its technical applications and its ability to detect lower extremity occlusive arterial disease. Ten extremities (five volunteers) were evaluated to assess the ability to place the sensor in the correct anatomic position on a foot without a palpable pulse during cuff occlusion so that pulsatile flow would be detected following cuff deflation; its sensitivity as an end-point detector for pulsatile perfusion; and whether there is a linear qualitative pulse wave response with increasing perfusion pressures. Forty extremities (20 patients) with suspected occlusive arterial disease were studied to evaluate its capability of detecting perfusion as compared with the presence of a palpable pulse, an audible Doppler signal, and a foot volume waveform. The placement of the sensor on 10 normal limbs with temporary arterial occlusion resulted in a recordable waveform following cuff deflation in 100% of the dorsalis pedis arteries and in 10% of the posterior tibial arteries. The piezoelectric pulse sensor was as sensitive for detecting pulsatile perfusion as an audible Doppler signal and demonstrated a linear change in the waveform's amplitude and shape with incremental changes in perfusion pressure. In the 40 extremities with ankle/brachial indices ranging from 0.00 to 1.35, there was uniform agreement between pulse volume and Pulse Check waveforms. The piezoelectric pulse sensor is a sensitive method for monitoring lower extremity arterial perfusion when supplied by the dorsalis pedis artery; however, it is inadequate for the posterior tibial artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Arterial Occlusive Diseases↗

Variability of venous-hemodynamics with daily activity.

PURPOSE: This study was designed to evaluate changes in venous hemodynamics that occur in normal, symptom-free male and female volunteers, as a consequence of daily activity. METHODS: Each leg of 25 symptom-free volunteers was prospectively studied twice in the early morning and twice in the late afternoon on 2 days. Air plethysmography was used to evaluate venous volumes, venous valvular function, calf muscle pump function, and the noninvasive equivalent of ambulatory venous pressure. RESULTS: There was significant change in venous valvular function (venous filling index) indicating progressive insufficiency in the late afternoon compared with the results of the morning studies (p = 0.039). This was demonstrated by a shortened venous filling time (p = 0.033) but not a change in venous volume (p = 0.794). Calf muscle pump function and ambulatory venous pressures remained constant. Although there were significant leg volume and ejection volume differences at baseline in male volunteers compared with female volunteers, no gender differences were evident as a result of daily activity. Five of 25 (20%) volunteers and seven of 50 (14%) extremities had normal venous refill times and venous function index in the morning, which became abnormal in the afternoon, indicating deterioration of venous valve function. CONCLUSIONS: Venous hemodynamic changes occur normally as a consequence of daily activity and seem to result from valvular dysfunction. This occurs in men and women and can alter diagnostic conclusions in 20% of otherwise normal patients. These findings have important implications for venous testing and accurate patient evaluation. However, extrapolation of these data to patients with established venous disease should not be made.

Activities of Daily Living↗

Iron-induced fluorescence in the retina: dependence on vitamin A.

PURPOSE: Intravitreal iron injection induces fluorophore formation in the photoreceptor outer segments, followed by an accumulation of inclusions with lipofuscin-like fluorescence in the retinal pigment epithelium (RPE). The accumulation of RPE lipofuscin during aging is dependent on vitamin A availability. Experiments were conducted to determine whether iron-induced fluorophore formation in the outer segments and in RPE is also dependent on vitamin A, and thus whether oxidation promotes the participation of vitamin A in lipofuscin formation. METHODS: For 23 weeks, beginning at weaning, albino Fischer rats were fed diets containing vitamin A either in the form of retinyl palmitate (+A), which can be metabolically converted into the retinoids involved in vision, or retinoic acid (-A), which does not support visual function. After 23 weeks, when rhodopsin levels had decreased more than 90% in the -A rats, some animals in this group were given an intramuscular injection of all-trans retinol and were allowed to recover from retinoid deficiency for 7 days (-A+A). Animals in all three treatment groups were then given an intravitreal injection of ferrous sulfate. Both 1 day and 7 days after the iron injections, the retinas and RPEs were examined for fluorophores with excitation and emission properties similar to those of RPE lipofuscin fluorophores. RESULTS: In retina sections examined with fluorescence microscopy 24 hours after the ferrous sulfate treatment, the photoreceptor outer segments of rats in all of the treatment groups displayed a fluorescence with a blue emission maximum. This outer-segment fluorescence was not present in untreated eyes. The in situ outer-segment fluorescence was correlated with the appearance of blue-emitting fluorophores in organic solvent extracts of the retinas. One week after the iron injections, the RPE cells of the +A animals became filled with inclusions that displayed a golden-yellow fluorescence emission when excited by blue light. Very little of this lipofuscin-like fluorescence was observed in the RPE of the -A rats 1 week after iron treatment. However, in the -A rats that had been repleted with vitamin A, the ability of iron to induce the RPE fluorescence was restored. Several orange-emitting fluorophores were present in organic solvent extracts of the RPE-choroids of the +A rats. The amounts of these fluorophores were not appreciably affected by the iron treatment. These orange-emitting compounds were not observed in extracts of any eyes in the -A or -A+A groups. CONCLUSIONS: The results of this study suggest that oxidation of the photoreceptor outer-segment lipids generates blue-emitting fluorophores that are not directly involved in RPE lipofuscin fluorophore formation. The findings also indicate that retinoids are direct precursors of RPE lipofuscin fluorophores, and that oxidative stress to the retina promotes participation of vitamin A in the formation of some of the compounds responsible for RPE lipofuscin fluorescence.

Animals↗

Photoreceptor recovery in retinoid-deprived rats after vitamin A replenishment.

Dietary deficiency in the retinoid precursors of the visual pigment chromophore 11-cis retinal results in the synthesis of photoreceptor outer segments containing opsin in excess of the vitamin A available for rhodopsin regeneration. This suggests that vitamin A-free opsin may be incorporated into newly synthesized outer segment disc membranes. If this opsin is functionally intact, it should be possible convert it to rhodopsin in vivo by providing the appropriate retinoids, and the resulting rhodopsin should should be able to mediate visual transduction. Experiments were conducted to evaluate this possibility and to identify the rate-limiting steps in photoreceptor recovery from retinoid depletion. Rates were maintained on diets either containing or lacking retinoid precursors of 11-cis retinal for 23 weeks, at which time outer segment opsin content greatly exceeded the availability of visual cycle retinoids in the retina. The retinoid-deprived animals were then each given a single intramuscular injection of all-trans retinol. At various time intervals after retinol administration, electroretinograms (ERGs) were recorded on some rats, and retinal rhodopsin contents were determined in others. At similar time intervals, blood and retinal pigment epithelial (RPE) retinoid levels and photoreceptor outer segment size were also determined. No significant increase in retinal rhodopsin content was observed up to 8 hr after injection, despite the fact that by 3 hr, blood retinol levels had recovered to more than 30% of normal. By 1 day after injection, however, rhodopsin levels had recovered to 30% of normal and ERG responses showed increases in visual sensitivity commensurate with the recovery of rhodopsin. The lag in rhodopsin recovery was apparently due to delayed uptake of retinol from the blood by the RPE. Photoreceptor outer segment size was reduced by over 50% in the retinoid- deprived rats and did not begin to recover by 1 day. By 1 week, however, outer segment size had returned to an average of 65% of normal. Commensurate with this regrowth of the outer segments, both rhodopsin levels and visual sensitivity increased between 1 and 7 days after vitamin A administration. Because the rates of recovery in rhodopsin levels and visual sensitivity greatly exceeded the normal rate of new opsin synthesis at short time intervals after vitamin A repletion, it appears that the opsin incorporated into the disc membranes of retinoid-deprived rats is able to form functional rhodopsin in vivo when the chromophore is supplied. Regrowth of the outer segments back to their normal size is required for full recovery of visual sensitivity.

Animals↗

Regulation of the interphotoreceptor retinoid-binding protein content of the retina by vitamin A.

A retinoid-binding protein has been identified in the extracellular space that separates the photoreceptor cells and the retinal pigment epithelium (RPE) of the mammalian retina. This protein (interphotoreceptor retinoid-binding protein, IRBP) appears to be involved in the transport of visual cycle retinoids between the photoreceptors and the RPE. Experiments were conducted to evaluate the possibility that the amount of IRBP in the retina is regulated by the availability of retinoids in the retina. Rats were fed diets containing vitamin A either in the form of retinyl palmitate (+A), which can be metabolically converted into the retinoids involved in vision, or retinoic acid (-A), which does not support visual function. After 23 weeks, when rhodopsin levels had declined by over 90% in the -A rats, some animals in the latter group were given a single intramuscular injection of all-trans retinol. Both 1 day and 1 week later, the IRBP immunoreactivities in the retinas from the treated rats were determined with quantitative immunocytochemistry. IRBP immunolabeling densities were also determined in the +A and -A groups. Retinas of animals that had consumed the -A diet for 23 weeks bound an average of 50% less anti-IRBP antibody in the retina than rats that had been fed the +A diet for the same period. One day after retinol administration, the mean IRBP immunolabeling density had returned to that observed in the +A rats. The restored level of IRBP immunoreactivity was maintained 1 week after injection. The immunocytochemical findings were confirmed by immunoblot analysis of eyecup homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Popliteal venous aneurysm: report of two cases and review of the world literature.

Two new cases of popliteal venous aneurysm are reported and added to the 22 other cases of popliteal venous aneurysm available for review. Both patients were first seen with acute pulmonary embolism and were treated with thrombolytic therapy followed by anticoagulation. Each had recurrent venous thromboembolism before discovery of the popliteal venous aneurysm. One popliteal venous aneurysm was diagnosed with phlebography and the second with venous duplex imaging, confirmed with phlebography. Both were surgically corrected with tangential aneurysmectomy and lateral venorrhaphy. Twenty-four cases of popliteal venous aneurysm are now available for review. Seventy-one percent (17 of 24) presented with pulmonary embolism, 88% (21 of 24) were saccular, and 96% (23 of 24) were located in the proximal popliteal vein. All but two were diagnosed by ascending phlebography. Three patients received no treatment: in two of these the outcome was not documented and the third had occasional pain. Two patients received anticoagulation without subsequent operative repair and both died of recurrent pulmonary emboli. Operative correction resulted in a 75% patency rate with 21% complications, most of which were related to postoperative anticoagulation. No patient who was operated on had subsequent pulmonary embolism, and there were no operative deaths. We suggest that all patients who have pulmonary embolism have lower-extremity venous duplex imaging. All popliteal venous aneurysms should be surgically repaired, inasmuch as nonoperative therapy results in recurrent thromboembolism and an unacceptably high mortality rate. Tangential aneurysmectomy with lateral venorrhaphy is the recommended procedure.

Adult↗

Venous duplex imaging for the diagnosis of acute deep venous thrombosis.

Acute deep venous thrombosis (DVT) continues to be a common clinical problem requiring objective evaluation. Hemodynamic testing for acute DVT has been popular, but is inadequate for evaluating asymptomatic patients and symptomatic patients with isolated calf vein thrombi. Venous duplex imaging (VDI) has rapidly gained in popularity, and is generally accepted to be the noninvasive technique of choice for the evaluation of patients with acute DVT. Twenty-five reports evaluate gray-scale venous duplex imaging versus ascending phlebography in 2,781 symptomatic patients. The sensitivity for proximal DVT and calf DVT is 96 and 80%, respectively. Seven reports review the use of VDI for surveillance in 857 asymptomatic patients, with an overall sensitivity of 76% for proximal DVT and of 11% for isolated calf vein thrombosis. The results of color-flow duplex appear to be somewhat better; however, the numbers are considerably smaller. The results for identification of calf vein thrombosis in asymptomatic surveillance patients continue to be poor. VDI appears to be the best noninvasive diagnostic test for acute DVT, and may challenge ascending phlebography as the best diagnostic test for proximal DVT in symptomatic patients, although it will miss 20% of isolated calf DVT. VDI appears to be the best noninvasive screening technique for high-risk asymptomatic patients under surveillance; however, additional correlative studies with ascending phlebography are required. The addition of color Doppler images appears to have improved results, although these higher sensitivities may be the consequence of improved experience as much as the addition of color to the image.

Acute Disease↗

Dietary restriction slows age pigment accumulation in the retinal pigment epithelium.

PURPOSE: The accumulation of age pigment, or lipofuscin, in postmitotic cells appears to be a universal feature of the aging process in animals. In mammals, the lipofuscin content of the retinal pigment epithelium (RPE) increases progressively during senescence. Dietary restriction has been shown to slow the rate at which many biologic parameters change during aging. Experiments were conducted to determine if dietary restriction alters the rate of age pigment accumulation in the RPE. METHODS: Male Wistar rats were placed on one of three dietary regimens starting at weaning. One group was fed a nutritionally complete diet ad libitum. Another group was fed the same diet but was only allowed to consume 60% as much food daily as the ad libitum group ate. The final group was fed ad libitum a nutritionally complete diet that had a lower caloric density per gram than the diets fed to the other animals primarily because of the replacement of carbohydrate with oat fiber. Ultrastructural morphometric analysis was used to determine the RPE age pigment content in the first group at 6 months of age, and in all of the groups at 18 months of age. RESULTS: Dietary restriction, achieved either by reducing total food intake or by reducing the caloric content of the diet, resulted in significant decreases in RPE lipofuscin accumulation. CONCLUSIONS: Dietary restriction provides a relatively simple means by which RPE age pigment content can be modulated. This should prove useful in assessing the role of RPE lipofuscin accumulation in age-related retinal disorders. That the oat fiber diet fed ad libitum was almost as effective as restriction of total food intake in slowing RPE age pigment accumulation indicates that the effect of restricted caloric intake is not mediated by almost constant hunger.

Aging↗

Iron-induced accumulation of lipofuscin-like fluorescent pigment in the retinal pigment epithelium.

PURPOSE: One of the most prominent changes that occurs in the retinal pigment epithelium during senescence is the progressive accumulation of the autofluorescent pigment lipofuscin. Experiments were conducted to evaluate the role of nonenzymatic oxidation of photoreceptor outer segments in retinal pigment epithelium lipofuscin formation. METHODS: Albino Fischer rats were given intravitreal injections of ferrous sulfate, a catalyst that promotes nonenzymatic lipid oxidation. At 2 hours, 24 hours, and 7 days after ferrous sulfate administration, the retinas were examined with fluorescence microscopy to assess the formation of fluorescent products. At these same time intervals, organic solvent extracts of the retinas and retinal pigment epithelium-choroid complexes were prepared. The extracts were analyzed with thin layer chromatography to assay for the presence of soluble fluorophores. The ultrastructural appearances of the retinas were examined at the same time points. RESULTS: At both 2 hours and 24 hours after the ferrous sulfate treatment, the photoreceptor outer segments displayed a yellow-green fluorescence emission that was not present in untreated eyes. Associated with this in situ fluorescence were a number of blue-green emitting fluorophores in organic solvent extracts that did not correspond to any of the fluorophores extracted from the retinal pigment epithelium of old animals. One week after the ferrous sulfate treatment, the photoreceptor cells had degenerated and the retinal pigment epithelium contained large amounts of an autofluorescent pigment with a golden-yellow emission typical of lipofuscin. The iron-induced fluorophores could not be extracted from this pigment into either chloroform or dichloromethane. CONCLUSIONS: The initial fluorophores that were formed as a result of nonenzymatic oxidation of outer segment components did not appear to be the same as those responsible for retinal pigment epithelium lipofuscin fluorescence. However, after the oxidized outer segments were phagocytosed by the retinal pigment epithelium, the latter cells became filled with a yellow-emitting fluorescent pigment that was similar in its fluorescence properties to lipofuscin. These observations suggest that lipofuscin fluorophores are not direct products of nonenzymatic lipid oxidation. However, some of these oxidation products may be modified after uptake by the retinal pigment epithelium to form insoluble lipofuscin fluorophores.

Animals↗

Bright environmental light accelerates rhodopsin depletion in retinoid-deprived rats.

PURPOSE: Dietary deficiency in the retinoid precursors of the visual pigment chromophore 11-cis retinal eventually results in selective degeneration of the photoreceptor cells of the vertebrate retina. An early effect of retinoid deficiency is depletion of chromophore from the photoreceptor outer segments. Experiments were conducted to determine whether the rate of chromophore depletion was affected by the intensity of environmental light. METHODS: Rats were maintained on diets either containing or lacking retinoid precursors of 11-cis retinal for up to 30 weeks. Animals in both dietary groups were exposed to either bright (90 lux) or dim (5 lux) cyclic light for the duration of the experiment. At various time intervals retinal rhodopsin content and photoreceptor densities were determined in animals from each treatment group. RESULTS: Bright light greatly accelerated the depletion of rhodopsin from the retina. Rhodopsin was almost completely depleted from the retinas of the retinoid-deficient animals raised under bright light for 25 weeks, whereas the dim-light-reared animals fed the retinoid-deficient diet still had significant amounts of retinal rhodopsin even after 30 weeks. Bright light alone moderately depressed retinal rhodopsin levels in animals fed the diet containing a vitamin A precursor of 11-cis retinal. Among rats fed the latter diet, retinal rhodopsin content in the animals kept in bright cyclic light was maintained throughout the experiment at about 70% of the amount of rhodopsin in rats housed in dim cyclic light. The light-related rhodopsin depletion in the retinoid-deprived rats was accompanied by photoreceptor cell death. After 30 weeks of treatment, photoreceptor cell densities remained similar in all treatment groups except the retinoid-deprived group housed under bright cyclic light. In the latter group, photoreceptor cell densities in the central retinas were reduced by an average of more than 50% after 30 weeks. Retinoid deficiency and bright light exposure alone each resulted in a reduction in rod outer segment size. An even greater reduction in outer segment size was observed in vitamin A-deprived animals housed under bright cyclic light. CONCLUSION: These findings indicate that light accelerates the depletion of retinoids from the retina and the accompanying photoreceptor cell degeneration.

Animals↗

Methylated lysine in storage body protein of sheep with hereditary ceroid-lipofuscinosis.

Juvenile ceroid-lipofuscinosis (Batten disease) is a hereditary storage disease with an autosomal-recessive mode of transmission. This disorder has been identified in humans, dogs and sheep. It is characterized by massive accumulations of autofluorescent storage bodies in many tissues. This storage body accumulation is accompanied by functional decline and degeneration of the affected tissues, and ultimately results in premature death. The primary defect responsible for juvenile ceroid-lipofuscinosis has not been identified. Previous studies have indicated that the storage material is primarily protein. Why this protein accumulates in storage bodies remains to he determined. In affected humans, the storage body protein appears to be abnormally rich in a methylated derivative of lysine (epsilon-N-trimethyllysine). Studies were undertaken to determine whether the storage bodies from sheep with hereditary ceroid-lipofuscinosis were also characterized by the presence of this modified amino acid. Chromatographic and mass spectral analyses of hydrolysates of the storage body protein indicated a significant fraction of the lysine residues in this protein were present as the epsilon-N-trimethyl derivative. This modified amino acid was not detected in hydrolysates of protein from normal sheep tissues or from tissues of sheep with GM1 gangliosidosis, nor did it appear to be present in the storage body protein from a human subject with the late infantile form of ceroid-lipofuscinosis. Thus, it is apparently specific to the storage body protein that accumulates in the juvenile type of this disease. The abnormal presence of epsilon-N-trimethyllysine in proteins could interfere with their sorting or degradation within cells and thus cause them to accumulate in the storage bodies characteristic of the human juvenile and ovine ceroid-lipofuscinoses.

Amino Acids↗

The hemodynamics of venous ulceration.

Venous ulceration is the result of progressive chronic venous insufficiency, the pathophysiology of which is complex and incompletely understood. Ambulatory venous hypertension in this disease has been well-documented; however, relatively little attention has been directed toward other parameters of venous function. This study evaluates a spectrum of hemodynamic variables and the degree to which they are altered in patients with venous ulceration, and correlates ambulatory venous pressure (AVP) with the noninvasive estimate of this parameter. Air-plethysmography was used to evaluate 36 ulcerated extremities from 30 patients with chronic venous disease and 80 asymptomatic extremities from 54 patients. This technique measures the functional venous volume (VV), assesses valvular function [Venous Filling Index (VFI)], evaluates the efficiency of the calf muscle-pump [Ejection Fraction (EF)], and provides an estimation of ambulatory venous pressure [Residual Volume Fraction (RVF)]. In addition, AVP's were recorded in 13 asymptomatic extremities from 10 patients and 16 ulcerated extremities from 14 patients with chronic venous disease. Significant differences existed between the two groups for all of the hemodynamic parameters. Ulcerated extremities had greater venous volumes, displayed marked deterioration in valvular competence and calf muscle-pump function, and showed significant ambulatory venous hypertension compared to the asymptomatic group. Additionally, the relationship between RVF and AVP appeared linear, with a correlation coefficient of 0.87. Air-plethysmography currently provides the most complete evaluation of venous hemodynamics and should improve our understanding of the pathophysiology of chronic-venous disease.

Adult↗

Why does prophylaxis with external pneumatic compression for deep vein thrombosis fail?

External pneumatic compression (EPC) devices are increasing in popularity for deep vein thrombosis (DVT) prophylaxis. Patients who have these devices applied postoperatively are assumed to have effective prophylaxis, although a number of extensive postoperative DVT complications have been observed. This study evaluates the proper application of EPC devices in patients in intensive care units and regular nursing floor units and assesses whether dedicated in-service instruction can improve proper use. In a prospective study of 138 patients with 2 or more risk factors for postoperative DVT, it was found that patients on routine nursing units had properly functioning EPC devices during 48% (306 of 636) of the visits compared with 78% (312 of 398) of the visits in the intensive care unit (ICU) (p less than 0.0001). Follow-up of patients transferred from an ICU to a regular nursing unit showed that functional application decreased from 82% (129 of 157) to 33% (40 of 122) (p less than 0.005). The compression sleeves were not applied in 84% of the nonfunctional devices and were properly in place but the pump nonfunctional in 16%. Unfortunately, dedicated in-service instruction did not improve the proper use of EPC. Although proper application of EPC is better in the ICU compared with regular nursing units, improper use is frequent and failure of DVT prophylaxis with EPC devices may be due to improper use, rather than failure of the method itself.

Adult↗

Influence of dietary vitamin A on autofluorescence of leupeptin-induced inclusions in the retinal pigment epithelium.

Substantial evidence indicates that the major precursors for retinal pigment epithelial (RPE) lipofuscin are molecular components of the photoreceptor outer segments. Previous experiments have demonstrated that the retinoids required for transduction by the photoreceptors promote RPE lipofuscin fluorophore formation. Animals deficient in these retinoids accumulate lipofuscin in the RPE at greatly reduced rates. The protein components of the photoreceptor outer segments also appear to be involved in the formation of RPE lipofuscin fluorophores. When degradation of phagocytosed photoreceptor outer segment proteins by the RPE is blocked, this tissue rapidly becomes engorged with phagosome-derived inclusions that have fluorescence properties similar to lipofuscin. Experiments were conducted to determine whether the development of lipofuscin-like fluorescence in these inclusions was dependent on the availability of retinoids. Rats were fed diets containing vitamin A either in the form of retinyl palmitate (+A), which can be metabolically converted into the retinoids involved in vision, or retinoic acid (-A), which does not support visual function. After the retinas of the -A animals had been depleted of retinoids involved in vision, animals from both groups were given intraocular injections of the protease inhibitor leupeptin. Two days later, the amounts of lipofuscin-like autofluorescence from the RPEs of rats in each group were determined. Leupeptin treatment produced an increase in this fluorescence in RPEs of the +A animals, but not in the RPEs of the rats fed the -A diet, despite the fact that phagosome-like inclusions accumulated in the RPE in both dietary groups. This finding suggests that retinoids involved in the visual process are probably directly involved in RPE lipofuscin fluorophore formation.

Animals↗

Hemodynamic deterioration in chronic venous disease.

Clinical deterioration of patients with chronic venous disease (CVD) has been well described and a standardized classification has been proposed. The progressive hemodynamic deterioration producing these clinical findings is less well appreciated. This study examines and correlates venous hemodynamics with clinical severity in patients with CVD. Two hundred seventy-four extremities from 149 patients with varying degrees of CVD and 56 extremities from 28 symptom-free volunteers were evaluated clinically and hemodynamically. Each limb was assessed for functional venous volume, degree of valvular insufficiency, efficiency of the calf muscle pump, and noninvasive estimate of ambulatory venous pressure. In addition, exercise venous pressures were recorded in 56 extremities from 36 patients and 9 extremities from 6 volunteers. As CVD progresses from class 0 to class 2, venous volume expands, valvular function deteriorates, the calf muscle pump becomes inefficient, and ambulatory venous hypertension develops. However, once extremities develop brawny edema or hyperpigmentation, further deterioration of limb hemodynamics does not occur. Patients with deep venous obstruction have more severe valvular insufficiency, calf muscle pump dysfunction, and ambulatory venous hypertension than have patients without evidence of obstruction. Residual volume fraction offers a reliable noninvasive estimate of ambulatory venous pressure (r = 0.76), although its correlation was significantly better for patients without venous obstruction (r = 0.86) than for those with obstruction (r = 0.40; p < 0.05). Deterioration in venous hemodynamics parallels clinical severity through class 2. Once brawny edema and hyperpigmentation occur, ulceration develops without additional deterioration of venous hemodynamics.

Adult↗

Reduced phagosomal content of the retinal pigment epithelium in response to retinoid deprivation.

Previous investigations have shown that lipofuscin accumulation in the retinal pigment epithelium (RPE) is reduced greatly as a consequence of vitamin A deprivation. The mechanism by which vitamin A regulates RPE lipofuscin deposition remains to be determined. It is possible that retinoids are direct precursors of this substance. Alternatively, vitamin A deficiency may reduce the uptake and processing of other potential precursors. In retinas lacking photoreceptor cells, RPE lipofuscin accumulation is decreased substantially. This finding suggested that components of phagocytosed photoreceptor outer segments may be precursors for RPE lipofuscin. The effect of vitamin A deprivation on RPE lipofuscin content therefore could be the result of reduced outer segment phagocytosis by the RPE of vitamin A-deprived animals. To evaluate this possibility, experiments were conducted to determine whether vitamin A deprivation altered the phagosomal content of the RPE. Rats were fed diets containing or lacking retinoid precursors of 11-cis retinal. Retinoic acid was included in the diets of the vitamin A-deprived animals. After both 10 and 26 weeks, the RPE phagosomal contents were determined in animals from each dietary group. Photoreceptor cell densities also were measured in these rats. At both time points, the RPE phagosomal content was lower significantly in the retinoid-deprived animals than in those fed a vitamin A precursor of the visual pigment chromophore. This reduction was not the result of photoreceptor cell death; the density of these cells was not affected significantly by dietary vitamin A. Thus, it appears that retinoid deprivation reduces the rate of photoreceptor outer segment turnover and, consequently, outer segment phagocytosis by the RPE.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗