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Biomedical subjects

R Juster

Publications and source records attributed to R Juster.

14 recordsLinked to original sources

The proportional decrease in prostate specific antigen level best predicts the duration of survival after hormonal therapy in patients with metastatic carcinoma of the prostate.

OBJECTIVE: To examine the usefulness of a test for prostate specific antigen (PSA) to predict survival in hormonally treated patients with metastatic prostate cancer. PATIENTS AND METHODS: The study comprised 49 patients (mean age 72 years, SD 6) who underwent orchidectomy for metastatic prostate cancer. PSA was measured before orchidectomy and after 6 months, and the absolute, differential and proportional decreases calculated. A Cox proportional hazards regression model, which controlled for patient age, tumour (Gleason) grade and the number of skeletal metastases, was then used to evaluate these estimates of PSA as predictors of survival. RESULTS: The 6-month proportional decrease in PSA from the pre-operative level was the most accurate predictor of patient survival (P = 0.006) after hormonal therapy for metastatic prostate cancer. CONCLUSION: This information may help to direct appropriate patients to new and experimental therapies for metastatic disease.

Aged

Delayed implantation of demineralized bone powder after local irradiation in rats.

Previous studies have shown that osteoinduction is inhibited when demineralized bone powder (DBP) is implanted within 48 hours of local irradiation (i.e., when the acute effects of radiation injury are present). This study sought to determine whether normal osteoinduction can proceed if the implantation of DBP is delayed until 21 days postirradiation. At 21 days, the acute effects of radiation injury are likely to have subsided, but the long-term effects have not yet appeared. Twenty-eight-day-old rats were administered a radiation dose of either 7 or 20 Gy over a localized area of one thigh. The contralateral, nonirradiated thigh served as a control. Demineralized bone powder was subcutaneously implanted 21 days later. Subcutaneous pellets were retrieved at various intervals thereafter (up to Day 45) and were histologically graded for evidence of osteoinduction. No difference in osteoinduction was detected at any time interval in pellets from the 7-Gy-treated sites, compared with controls. Pellets from the 20-Gy-treated sites, however, demonstrated significantly a lower osteoinductive response at each interval. These latter pellets showed small scattered areas of osteoinduction and reduced formation of marrow elements. Thus, although osteoinduction proceeds normally when the implantation of DBP is delayed for 21 days after irradiation with 7 Gy, this is not the case when 20 Gy are administered. Given the absence of gross impairment of tissue vascularity in irradiated sites, it is possible that inhibition of osteoinduction after higher doses of radiation results from permanent damage to mesenchymal precursor cells.

Animals

Contrast-enhanced magnetic resonance imaging of tumor-bearing mice treated with human recombinant tumor necrosis factor alpha.

Pharmacological effects of recombinant human tumor necrosis factor alpha (TNF) were studied in a mouse fibrosarcoma model using magnetic resonance imaging enhanced with a macromolecular contrast agent, albumin(gadolinium-diethylenetriamine pentaacetic acid)35. TNF was administered i.v. in a dose of 150 micrograms/kg, 60 to 80 min prior to imaging. Contrast-enhanced and nonenhanced magnetic resonance images of TNF-treated (n = 10) and untreated (n = 8) Meth A fibrosarcomas were obtained at 2.0 Tesla using T1-weighted spin-echo pulse sequences. Serial images spanning an interval of 60 to 120 min after TNF administration showed that the TNF-treated tumors enhanced significantly more overall than did untreated tumors (43% versus 31%). The most marked differential tumor enhancement was observed in the tumor rim (59% versus 40%). Nontumorous tissue, including muscle and brain, revealed no significant enhancement differences between TNF-treated animals and controls. The observed tumor enhancement corresponded strongly with Evans blue staining; the TNF-treated tumors stained deep blue, while untreated tumors and normal tissues observed did not stain. The different enhancement and Evans blue staining patterns between TNF-treated tumors and untreated tumors are attributed to TNF-induced changes in tumor capillary integrity. The data indicate that TNF effects on tumors include an increased capillary permeability for macromolecules at early times after administration. The ability to detect changes in capillary permeability in vivo using contrast-enhanced magnetic resonance imaging may prove to be clinically useful to monitor tumor response to TNF.

Animals

Clonal heterogeneity in populations of Leishmania major.

Forty clones of Leishmania major were derived by direct plating from lesions and from cultures of recent isolates, followed by plating as well as by additional limit dilution in some. The parental strains originated from and represented three geographical areas in each of which a distinct electrophoretic type of the enzyme 6-phosphogluconate dehydrogenase (6PGD) is found. Each clone was characterized in terms of its virulence in Sabra mice, morphology, serotype, enzyme electrophoretic profile based on 11 enzymes, and kinetoplast DNA endonuclease restriction pattern. All the clones showed a similar virulence in the mice and similar polymorphism in fresh drops of living cultures and in Giemsa-stained preparations. Ten clones from the Jordan Valley were all serotype A1, 15 clones from the Arava were all A1Bz--confirming the mixed serological nature of parasites from this region, 11 of the 20 clones from the western Negev-eastern Sinai included a new A subserotype, and 9 were A1. Generally, the geographical separation of the 6PGD variants was upheld. Two of the Jordan Valley clones were similar to those of the western Negev. On two occasions, different enzyme types were isolated from the same individual, in one case from the same lesion. All clones from the western Negev were alike and similar to the type previously found in that region. The situation in the Arava was more complicated, since clones representative of all three regional types were found. In cases where the first two types were found, the clones and their parental strains were similar. However, one parental culture yielded three clones that resembled the reference strain for the Jordan Valley and two which resembled that of the western Negev. In one of these cases, two dissimilar clones originated from the same lesion. One aberrant clone from the western Negev was variant for nucleoside hydrolase. The kinetoplast DNA of each clone was distinct but relatively complicated, which made differentiation of these regional types difficult. However, clones from the same area displayed more similarity to each other than to those of other regions, implying a closer genetic relationship.

Animals

Limbal disease in trachoma and other ocular chlamydial infections: risk factors for corneal vascularisation.

Ocular infection with Chlamydia trachomatis, whether of genital or endemic trachoma origin, usually produces diffuse infiltration and swelling of the scleral limbus, grey infiltrates of the corneal limbus, and superficial extension of vessels onto the corneal limbus. In genitally transmitted C. trachomatis infections, subepithelial infiltrates have been reported as well. In classic endemic trachoma, limbal changes also include limbal follicles which resolve, leaving Herbert's peripheral pits, and an extensive vascular pannus. To evaluate the limbal changes in trachoma, follow-up studies were done in 1986-1987 in a group of 213 children originally seen between 1969-1972. Pannus formation occurred at a much earlier age than conjunctival scar formation and was an excellent predictor of later severe conjunctival scarring. The evidence from this study suggests that the mechanisms for corneal pannus formation from the limbus are quite different from those for scarring of the conjunctiva.

Adolescent

Trabecular meshwork cells grown on filters. Conductivity and cytochalasin effects.

A system was developed to measure the hydraulic conductivity of cultured monolayers of human trabecular meshwork (HTM) cells. By optimizing the cell growth conditions and evaluating a number of filter supports, confluent HTM cells in single layers were obtained for measurement of hydraulic conductivity. The HTM monolayers had hydraulic conductivities of 0.3-2.0 microliters/min/mm Hg/cm2 measured at near-physiological flow rates. Evaluations of cytochalasin B (CB) effects on the hydraulic conductivity of our HTM monolayers revealed that CB (10(-6) to 10(-5) M) caused a dramatic dose-related increase in conductivity within 10 to 30 min, which parallels CB effects on outflow facility in vivo. Morphologic observations show that the increase in hydraulic conductivity was accompanied by a retraction of the trabecular cells and widening of the intercellular spaces. Our findings suggest that growth of HTM cells on filter supports can provide a useful in vitro system to study the regulation of aqueous outflow.

Adult

Correlation of visual field, treatment fields, and dose in helium ion irradiation of uveal melanoma.

We correlated predicted radiation distributions in 29 patients with uveal melanoma (treated with 5,000 to 8,000 rads of helium ion therapy) with fundus photography and visual field deficits. The tumor was entirely within the treatment region in all patients. The fraction of the predicted high-dose and low-dose regions corresponding with an absolute scotoma was fitted by a linear regression model (r2 = .721) with three independent variables: dose region, initial condition, and time since therapy. The defect in the maximum-dose region increased at an average rate of 0.270/year. This differed (P = .002) from the rate in the penumbra region: (0.104/year). The rate in the penumbra differed (P = .01) from that in the predicted low-dose region, where scotoma did not increase with time. The pattern and time course of visual field loss in the different radiation dose regions tended to support the conclusion that isodose calculations are accurate. The data were consistent with the hypothesis that visual loss secondary to irradiation results primarily from radiation vasculopathy and not from direct damage to photoreceptors or ganglion cells. Development of an absolute scotoma may require a dose in excess of 5,000 rads.

Helium

Trabecular meshwork cellularity in primary open-angle glaucoma and nonglaucomatous normals.

The trabecular meshwork cellularity (cells/unit tissue area) was compared in patients with primary open-angle glaucoma (POAG) with that of nonglaucomatous (NG) individuals. The NG specimens (n = 69) include specimens from the prenatal period (n = 14) as well as the postnatal period to age 98 years (n = 55). The glaucoma specimens (n = 49) covered a wide-range of ages (23-80 years) and were obtained at trabeculectomy (n = 31) or at autopsy (n = 18). Our results show that the trabecular cellularity in NG specimens decreases most rapidly and in a nonlinear manner in the late fetal period and for the first few years of postnatal life. This rapid decline in cellularity then slows down to proceed in a nearly linear manner for the remainder of the 98 years of life studied. The meshworks from patients with POAG have a lower cellularity than normals over the wide range of ages examined, but both types of specimens undergo similar declines in cellularity with age. Thus, the age-cellularity curves for both the NG and POAG specimens are parallel to each other. The loss of cells occurs in a gradient-like manner with the inner tissues being most affected and the outermost tissues least affected. A variety of statistical tests show that these changes in cellularity are highly significant and specific. These findings are compared to the loss of endothelial cells in the cornea and they are discussed in relation to the important clinical characteristics of POAG.

Adolescent

Prenatal and postnatal growth of the human Descemet's membrane.

The origin, growth in thickness, and differentiation of Descemet's membrane was studied by light, electron microscopic, morphometric, and statistical methods in 67 specimens from 12 weeks of gestation to 98 years. Descemet's membrane is formed by three major processes: growth in thickness during the prenatal period, prenatal differentiation into a striated basement membrane, and growth in thickness during the postnatal period. The initial step is the synthesis of an ordinary basement membrane, which is very thin and quite different in appearance from the adult Descemet's membrane. Growth of the prenatal Descemet's membrane then proceeds by deposition of a series of similar "membrane units," which are stacked to form a lamellar structure consisting of at least 30 layers by the end of gestation. Second, during prenatal life, differentiation of the membrane leads to the formation of a striated structure through the gradual addition of short and thin cross-linking bridges separated by 110-nm intervals that are disposed in a plane perpendicular to the lamellae. The third process occurs in postnatal life when the membrane continues to grow in thickness by deposition of a nonstriated, nonlamellar material posterior to the striated prenatal layer. Regression analysis suggests that prenatal growth proceeds at a rapid but variable rate best described by a "sigmoid-like" function of age. Postnatal growth, in contrast, proceeds in a predominantly exponential manner but at a slower pace than in the prenatal period. The low variability and large size of our set of measurements make these data especially useful for comparisons with pathologic specimens.

Adolescent

Prenatal and postnatal cellularity of the human corneal endothelium. A quantitative histologic study.

The authors studied the cellularity of the normal corneal endothelium by histologic methods in 56 specimens from 16 weeks of gestation to 98 years of age. Ten step-serial sections were taken from each specimen through the central 6 mm of the cornea, in an area measuring 1.8 mm. The number of nuclei were counted on each section and a ratio of the number of nuclei per 100 micron of endothelial length was determined. This ratio provides a measure of cell density that they call cellularity. There is a decrease in cellularity that proceeds in a nonlinear manner and at a very rapid rate during the prenatal period and for the first few years of life. Cell death or necrosis, which might have contributed to this apparent loss of cells, was not observed. Instead, this rapid change in cellularity is correlated with a concomitant change in corneal size. The authors' calculations show that cell division may play a minor role in the formation of the endothelium after the second trimester of fetal life as most of the cells present by birth already exist by this time. After the first few years of life, the rate of change in endothelial cellularity decreases to proceed in a linear manner for the rest of the near 100 years of life examined. This latter age-related decline in cellularity is probably due to the loss of 0.56% cells per year from the endothelial layer, since the cornea does not appear to change in size during this time. Statistical analysis of the authors' data shows that these results are highly significant.

Adult

Immediate intraocular pressure response to argon laser trabeculoplasty.

We conducted a randomized, double-masked study of 40 patients with open-angle glaucoma to ascertain the immediate intraocular pressure response after treatment of either one half (180 degrees) or the entire (360 degrees) trabecular meshwork by argon laser trabeculoplasty. We found a statistically significant difference in the magnitude of intraocular pressure changes between the two groups (P less than .02), with those patients receiving fewer burns having a smaller increase. Substantial increases in intraocular pressure were observed in five of the 20 patients in whom the entire trabecular meshwork was treated. One of these patients had marked loss of visual field within 24 hours.

Adult

Influence of the number of laser burns administered on the early results of argon laser trabeculoplasty.

We conducted a prospective, randomized, double-masked study to examine the influence of the number of burns administered on intraocular pressure after argon laser trabeculoplasty. Each of 40 patients with open-angle glaucoma had 50 burns placed over one half the trabecular meshwork (Group 1, 20 patients) or 100 burns placed over the entire trabecular meshwork (Group 2, 20 patients). There was no significant difference between the mean intraocular pressure decreases in Group 1 (-9.20 +/- 6.43 mm Hg) and Group 2 (-6.95 +/- 5.74 mm Hg) after two months (P less than .25). In each group, the intraocular pressure was lowest after two months in those patients in whom it was not increased during the immediate postoperative period (Group 1, P less than .006; Group 2, P less than .07). Because the changes in intraocular pressure were statistically similar in the two groups and because patients receiving only 50 burns may have fewer complications, administering 50 laser burns to one half the trabecular meshwork appears to be the better choice for an initial procedure.

Double-Blind Method

Age-related changes in the basement membrane of the human corneal epithelium.

An ultrastructural evaluation and morphometric analysis of the basement membrane of the normal human corneal epithelium in 45 specimens from subjects ranging in age from 17 weeks of gestation to 93 years was conducted. It was found that thickening of the corneal epithelial basement membrane takes place by two main processes: continued membrane deposition (forming unilaminar membranes) and membrane reduplication (forming multilaminar membranes). During the fetal period and for the first two decades of postnatal life, membrane thickening occurs exclusively by continued membrane deposition so that these unilaminar membranes increase in thickness by 3 nm each year. Membrane reduplication in focal areas after the age of 20 and with increasing frequency and greater involvement of the membrane thereafter was observed. Since anchoring fibrils and hemidesmosomes are important in the adhesion of the epithelium to Bowman's layer, we paid particular attention to these structures. We could find no relation between hemidesmosome content and the formation of reduplicated or multilaminar membranes. However, the anchoring fibrils become disrupted with increasing age, and the membrane thickness exceeds fibril length in some specimens. It is proposed that this phenomenon effectively blocks linkage between the anchoring fibrils and Bowman's layer. The evidence for cell injury and death as a promoter of membrane reduplication was compared to the evidence for a primary deterioration of the basement membrane.

Aging

Age-related changes in trabecular meshwork cellularity.

To investigate whether alterations in the cellular component of the trabecular meshwork occur with age, we evaluated trabecular meshwork cellularity and absolute cell number, using specimens obtained from patients ranging in age from newborn to 81 years. We obtained reproducible, quantitative measurements of these parameters, using montages of 1 micrometer meridional sections. A progressive decrease in cellularity (58%) and absolute cell number (47%) in the trabecular meshwork occurred over the 81-year period studied. Regression analysis suggested that the decrease in cellularity and cell number is linear function of age, resulting from a loss of approximately 0.58% of all cells per year. This change in cellularity parallels that seen in the corneal endothelium. implying that trabecular cells, like corneal endothelial cells, may have a limited reparative capacity.

Adolescent