[A comment to a comment. Depleted uranium].
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Biomedical subjects
Publications and source records attributed to E B Olsen.
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AIMS: To examine a possible effect of 7-methylxanthine, theobromine, acetazolamide, or L-ornithine on the ultrastructure and biochemical composition of rabbit sclera. METHODS: Groups of pigmented rabbits, six in each group, were dosed during 10 weeks with one of the substances under investigation, and one untreated group was the control. Samples of anterior and posterior sclera were taken for determination of hydroxyproline, hydroxylysine, proline, proteoglycans, uronic acids and dermatan sulphate, chondroitin sulphate, and hyaluronic acid. Sections were examined with electron microscopy, and the diameter of the individual collagen fibrils was measured. RESULTS: Treatment with theobromine produced a significant increase in the contents of hydroxylysine, hydroxyproline, and proline in both anterior and posterior sclera, while 7-methylxanthine increased the contents of hydroxyproline and proline selectively in posterior sclera. Acetazolamide, on the other hand, significantly decreased the contents of hydroxyproline and proline in samples from anterior sclera. Uronic acids in both anterior and posterior sclera were significantly reduced by treatment with 7-methylxanthine, and L-ornithine significantly reduced uronic acids in posterior sclera. An inverse correlation between contents of hydroxyproline and uronic acids was found. The mean diameter of collagen fibrils was significantly higher in the posterior sclera from rabbits treated with 7-methylxanthine or theobromine, and significantly lower in rabbits treated with acetazolamide or L-ornithine compared with controls. In the anterior sclera, fibril diameter was significantly reduced in all treatment groups compared with controls. A positive, significant correlation between fibril diameter and content of hydroxyproline and proline was found in posterior sclera. CONCLUSION: 7-Methylxanthine, a metabolite of caffeine, increases collagen concentration and the diameter of collagen fibrils in the posterior sclera, and may be useful for treatment or prevention of conditions associated with low level and/or inferior quality of scleral collagen, such as axial myopia, chronic open angle glaucoma, and possibly neovascular age related macular degeneration. The apparent loss of collagen induced by chronic treatment with acetazolamide should be taken into consideration as a potentially harmful side effect. These results may indicate that scleral biochemistry and ultrastructure are influenced by the retinal pigment epithelium. One possible explanation is that the scleral fibroblasts which produce the collagen are sensitive to changes in the physiological electric field created by the retinal pigment epithelium.
The control of ventilatory responses to mild or moderate dynamic exercise has been the subject of considerable debate for over a century. The prevailing view has been that the ventilatory response to exercise is stereotypical and rather unmalleable. However, paradigms involving novel associations of stimulus inputs have been shown to modulate breathing in short and longer time scales. The scope of this review includes examples of modified ventilatory responses to exercise which have been investigated in terms of neural mechanisms. An attempt to synthesise the available data into a model of neuromodulation is presented.
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We observed 55 inpatients with "do-not-resuscitate" (DNR) orders to determine what happened to their DNR status after hospital discharge. All were admitted to the medical service of a Department of Veterans Affairs hospital. Of the 55 patients, 16 died in the hospital, 10 were discharged to inpatient hospice units, and 1 was transferred to an acute care hospital. An additional 19 patients were discharged to nursing homes. The other 9 patients (16% of the total) survived their hospital stays; 6 successful contacts were made with patients' spouses. In 1 case the spouse thought a DNR order was no longer desirable. In the other 5 cases the spouse said the DNR status was "probably" or "definitely" still warranted, but only 1 spouse had a written DNR order at home. We contacted 9 of the 14 house officers who had cared for the patients in hospital. Only 2 had ever written a DNR order after hospital discharge. Two house officers said they routinely discussed with family members a patient's expected dying process at home. Unwanted resuscitation is as undesirable at home as in the hospital. Physicians should discuss future resuscitation procedures with patients who have DNR orders at the time of hospital discharge. Physicians, paramedic service directors, and policymakers also should develop protocols and standardized home DNR orders so that paramedics can honor the wishes of patients in the prehospital setting.
In the normal adult eye the content of uronic acid, hydroxyproline, hydroxylysine and proline from different parts of sclera was examined. Scleral samples from the posterior eyeball showed a higher content of uronic acid than the scleral samples from papilla, equator and limbus. Apart from a lower concentration of hydroxyproline in sclera from equator, no major differences in concentration of hydroxyproline, hydroxylysine or proline was found in sclera samples.
The long-term effect of destruction of the pigment epithelium by sodium iodate on the biochemistry of rabbit sclera was studied in one group with intravenous injection of sodium iodate, and in a second group with injection of sodium iodate into the right eye. Intravenous treatment produced a non-significant increase in the uronic acid concentration. In the second group the untreated fellow eye was microscopically intact, but was shown (as the treated eye) to alter the concentration of uronic acid in different parts of the sclera. All eyes from treated animals exhibited changes in the relative content of the various glycosaminoglycans and in the content of hydroxyproline, hydroxylysine and proline. This work indicates that the pigment epithelium may play a key role in the control mechanism of the scleral connective tissue, and this again has major implications in terms of a possible medical treatment of axial myopia.
L-Malate transport in Lactobacillus plantarum was inducible, and the pH optimum was 4.5. Malate uptake could be driven by an artificial proton gradient (delta pH) or an electroneutral lactate efflux. Because L-lactate efflux was unable to drive L-malate transport in the absence of a delta pH, it did not appear that the carrier was a malate-lactate exchanger. The kinetics of malate transport were, however, biphasic, suggesting that the external malate concentration was also serving as a driving force for low-affinity malate uptake. Because the electrical potential (delta psi, inside negative) inhibited malate transport, it appeared that the malate transport-lactate efflux couple was electrogenic (net negative) at high concentrations of malate. De-energized cells that were provided with malate only generated a large proton motive force (greater than 100 mV) when the malate concentration was greater than 5 mM, and malate only caused an increase in cell yield (glucose-limited chemostats) when malate accumulated in the culture vessel. The use of the malate gradient to drive malate transport (facilitated diffusion) explains how L. plantarum derives energy from malolactic fermentation, a process which does not involve substrate-level phosphorylation.
Out of 30 adult rabbits, 20 had one knee immobilized with a plaster of Paris cast for 6 or 12 weeks, and 10 rabbits were used as untreated controls. Prior to immobilization, 10 knees were injected with high-molecular weight hyaluronic acid. The articular cartilage of the femoral condyles was studied by light microscopy, whereas that of the patella and tibia was analyzed biochemically. Degenerative changes of the articular cartilage similar to those seen in arthrosis were observed after 6 weeks. The intraarticular injection of hyaluronic acid did not prevent these changes; instead, the reparative processes seemed inhibited.
Human sclera from different parts of the normal adult eye was analyzed for content of uronic acid and the distribution of specific glycosaminoglycan types. Uronic acid is widely determined as representative of glycosaminoglycans in biological substances and variations of about 2-fold were found. Differences of up to 50% were detected in the relative abundance of hyaluronic acid and of dermatan sulphate, depending on the site on the globe from which the sample was taken. Sclera from around the papilla was found to be rich in content of dermatan sulphate. Sclera from the posterior eyeball showed a higher percentage of chondroitin sulphate as compared with sclera from equator and limbus. Equatorial sclera was richer in hyaluronic acid than posterior sclera. Sclera from the posterior eyeball showed a higher content of uronic acid as compared with sclera from equator and limbus. This work is an addition to the understanding of the scleral biochemistry and this finding may have some relevance in connection with ocular disease, as the proteoglycans and their content of glycosaminoglycans play a key role in the regulation of collagen fibril assembly and in the biomechanical strength of collagen fibrils.
We obtained samples of patellar cartilage at the time of surgery from 20 patients: 11 with normal and 9 with macroscopic cartilaginous degeneration. The glycosaminoglycans were separated by cellulose acetate electrophoresis, and the relative content of major glycosaminoglycans was measured by optic scanning. The total content of glycosaminoglycans was estimated by uronic acid analysis. We found that degenerated cartilage contained an increase in dermatan sulfate and hyaluronic acid and a decrease in chondroitin 6-sulfate and total uronic acid concentration, with only slight changes in chondroitin 4-sulfate and keratan sulfate compared with normal cartilage.
Abnormal concentrations of glycosaminoglycans (GAG) have been reported for various types of tumors, suggesting that they may play a role in neoplasia. The correlation between the content of individual GAGs was studied in breast tumor tissues. The total content of GAG was estimated by uronic acid analysis. The relative distributions of dermatan sulphate, heparan sulphate, hyaluronic acid and chondroitin sulphate were measured after cellulose acetate electrophoresis. Mammary tissue samples were obtained at the time of surgery from 11 women, 6 with fibroadenomata and 5 with carcinoma. From each patient, biopsies were obtained centrally in the tumor and perilesional areas adjacent to the tumor, and also from clinically uninvolved tissue in the same region. In the central areas, it was found that carcinoma had a significant increase in chondroitin sulphate and uronic acid content, and a significant decrease in dermatan sulphate content, as compared with fibroadenoma. The chondroitin sulphate content in perilesional carcinomatous tissue was significantly greater than in clinically uninvolved tissue.
This study was conducted to describe the distributions of the initial decidual PRL content (D-PRL) and the decidual PRL secretion (D-PRL-s) in vitro at term and to ascertain whether the clinical data might influence these decidual PRL measures and their correlation with the amniotic fluid PRL concentration (A-PRL). Decidual tissue was obtained after 134 normal pregnancies at term. D-PRL and D-PRL-s into the medium after an 8 h incubation were determined. The distributions of D-PRL and D-PRL-s were skewed to the right. A logarithmic transformation generated symmetric distributions. Eight women who were delivered by vacuum extraction due to intra-uterine asphyxia had D-PRL values similar those in normal vaginal parturition, whereas D-PRL-s values were significantly reduced (p less than 0.02). No significant difference (p greater than 0.05) was found in the decidual PRL measures in the vaginal deliveries between those receiving labor stimulating medication and those without, or between women who gave birth vaginally and women undergoing elective cesarean section. Stepwise multiple regression analyses of data obtained from 30 women who gave birth after uncomplicated or various pathological pregnancies showed logarithmically transformed A-PRL to be closely correlated with D-PRL, and these correlations were improved by including the week of gestation as a second step (p less than 0.00001). After normal pregnancy, D-PRL-s was significantly correlated with D-PRL (p less than 0.01), and D-PRL was correlated with the week of gestation (p less than 0.05). None of the remaining clinical data improved the correlations.(ABSTRACT TRUNCATED AT 250 WORDS)
Human decidual explants were incubated in vitro in media containing 10(-5) mol/l ouabain or 10(-4) mol/l ouabain or 0.5 X 10(-4) mol/l bumetanide to change the intracellular ionic concentrations. In isosmotic incubations (osmolality 315 mmol/kg), no significant effect of either 10(-5) mol/l ouabain or 0.5 X 10(-4) mol/l bumetanide was found on the decidual prolactin secretion (D-PRL-s). 10(-4) mol/l ouabain significantly decreased both decidual prolactin production and D-PRL-s (P less than 0.05) and was therefore not used for the following cross-over experiments. Hyperosmotic media (387 mmol/kg) were produced by changing the concentration of either sodium chloride, potassium chloride, or mannitol. All increased D-PRL-s compared with the isosmotic media (315 mmol/kg). 10(-5) mol/l ouabain significantly diminished the increase otherwise elicited by the sodium chloride and the mannitol hyperosmotic media. However, in the hyperosmotic potassium chloride medium with 10(-5) mol/l ouabain, the D-PRL-s remained increased. The hyperosmotic medium (252 mmol/kg) reduced D-PRL-s compared with the isosmotic media (315 mmol/kg) and no significant effect of ouabain was found. Bumetanide did not change the D-PRL-s into any of the hypo- or hyperosmotic media compared with the secretion at 315 mmol/kg. Based on experience from other cell types, the results further indicate that the intracellular ionic concentrations could be of importance to the secretion of decidual prolactin in vitro.
Human decidual tissue from uncomplicated term pregnancies was incubated in vitro using a cross-over design of incubation lasting for 72 h. The decidual issue of each membrane was added sequentially to media with the osmolalities 252, 315 and 387 mmol/kg, and the different osmolalities were in 33 experiments induced by changing the concentration either of sodium chloride, potassium chloride, mannitol, sucrose, or choline chloride. At 387 mmol/kg all substances elicited a significant increase in Prl secretion compared with the 315 mmol/kg media (14-27%) or the 252 mmol/kg media (26-46%). When the sodium chloride, potassium chloride, sucrose, and choline chloride media at 387 mmol/kg were compared in another 7 experiments, potassium chloride increased Prl secretion more effectively than the others (10%, P less than 0.05). The incubation cross-over design did not permit determination of the decidual Prl content after incubation in each of the various media, but in 28 experiments the mean decidual Prl content was 12.7 mIU per 100 mg dry tissue (range 4-30) before and 8.7 mIU per 100 mg dry tissue (1-17) after the experiments. The mean amount of Prl secreted during the successive incubations was 152.2 mIU per 100 mg dry tissue (19-672) which showed the secretion to be a result of continued Prl production. The effect of osmolality was independent of the basal production rate. These results indicate that the intracellular ionic concentrations, probably of potassium ion or of chloride ion, are of importance in the regulation of the synthesis and secretion of decidual Prl in vitro.
This study evaluated in pregnant women with diabetes mellitus (DM) the prolactin (PRL) concentration in amniotic fluid (A-PRL), the initial decidual PRL content (D-PRL), and the decidual PRL secretion (D-PRL-s) in vitro into isosmotic (315 mmol/kg), hyperosmotic (426 mmol/kg) and hyposmotic (252 mmol/kg) media. Decidual tissue was collected at term from 18 normal pregnancies and from 23 women with DM (White's classification: 7 of class A (without insulin treatment) and 16 of the classes B-F. Twelve of the women with DM had signs of hydramnion. Amniotic fluid specimens were collected from 52 normal pregnancies and 17 of the women with DM. No significant difference was found between normals and diabetics when D-PRL, D-PRL-s into isosmotic medium and A-PRL were compared. No trends could be detected when the insulin treated women were grouped according to White's classification. The increment of D-PRL-s into hyperosmotic medium was 15% in normals (p less than 0.001 compared with isosmotic medium), in the DM group 23% for the non-insulin-treated women (p less than 0.05 when compared with normals) and 25% for the insulin treated women (p less than 0.01). In normals the hyposmotic medium reduced D-PRL-s by secretion 19% (p less than 0.001 compared with isosmotic medium) but no significant difference was observed between normals and diabetic groups (p greater than 0.10). In the group of diabetics no significant difference was found in any of the PRL quantities investigated between those with and without hydramnion.(ABSTRACT TRUNCATED AT 250 WORDS)