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Biomedical subjects

B Ross

Publications and source records attributed to B Ross.

At least 127 records · Page 7Linked to original sources

Pharmacokinetics of percutaneous estradiol: a crossover study using a gel and a transdermal system in comparison with oral micronized estradiol.

The pharmacokinetics of three transdermal estradiol (E2) replacement regimens were studied following establishment of steady-state dynamics. Oestrogel 3.0 mg, Oestrogel 1.5 mg, and Estraderm transdermal delivery system 4 mg (0.05 mg/day) were administered for 14 days each to 15 postmenopausal volunteers, with a 14-day washout period between each regimen. The percutaneous E2 pharmacokinetics were compared with an oral micronized E2 preparation. Venous samples were obtained at 0, 1, 2, 4, 8, 12, and 24 hours on 3 sequential days 11 days after initial application of the Oestrogel and the transdermal delivery system, and at the same times after oral E2 ingestion. All three percutaneous regimens provided nearly constant serum E2 and estrone (E1) levels throughout their use. The mean serum E2 levels were 102.9 +/- 39.9, 68.1 +/- 27.4, and 41.1 +/- 13.5 pg/mL for Oestrogel 3.0 mg, Oestrogel 1.5 mg, and Estraderm, respectively. Oral E2 resulted in a mean serum E2 level of 114.0 +/- 65.2 pg/mL with marked peak and nadir values. The E1/E2 ratio was comparable with all three percutaneous regimens (1.08-1.33) and was significantly lower than that found with oral Estrace (5.05).

Administration, Cutaneous↗

Lithotripsy.

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Humans↗

Lymphocyte metabolism and cytotoxic activity monitored with 31P magnetic resonance spectroscopy.

Continuous metabolic monitoring of human lymphocytes and a tumor cell line was achieved by means of nuclear magnetic resonance (NMR) applied to cells suspended in alginate gels. Human peripheral blood lymphocytes cultured in vitro were examined with 31P magnetic resonance spectroscopy (MRS) before and after activation with phytohemagglutinin and interleukin-2 (IL-2). Following the addition of these biological response modifiers, increases in [ATP], phosphomonoesters (PME), and phosphodiesters occurred. These appear to be markers of lymphocyte stimulation. Lymphocyte pH was unchanged. A target tumor cell line (K562) showed 31P NMR spectra that differed significantly from that of lymphocytes. When lymphocytes were mixed with tumor cells (to induce tumor cell death), and monitored by 31P MRS, levels of inorganic phosphate (Pi) increased, [PME] levels fell, and release of H+ was inhibited. 31P MRS may therefore provide a noninvasive assay of lymphocyte-mediated tumor cell killing that will have application in monitoring treatment in patients undergoing this type of therapy.

Adenosine Triphosphate↗

Amplification or obfuscation: is localization improving our clinical understanding of phosphorus metabolism?

Localization techniques are considered an indispensable part of the clinical spectroscopy examination. The results are often a marked improvement in diagnostic information (amplification), but because of the introduction of new artifacts and the more prolonged examination time, some of the undoubted advantage is lost (obfuscation). There is thus an argument for continued development of more rapid methods of clinical spectroscopy and, if necessary, sacrificing some spatial information.

Brain Neoplasms↗

Short-term effects of extracorporeal shock wave lithotripsy on the human gallbladder.

Extracorporeal shock wave lithotripsy (ESWL), whereby shock wave energy is focused upon gallstones causing their disintegration into fragments sufficiently small to be passed via the biliary system, offers a promising non-invasive alternative to surgery for gallstone disease. The tissue effects in humans of ESWL are poorly characterized and no systematic study of the tissue effects of ESWL by piezoelectrically generated shock waves has been published. Sixteen patients for elective cholecystectomy were therefore subjected to ESWL before surgery and detailed histology of the gall-bladders (including scanning electron microscopy of the mucosa) was compared with that from 20 age/sex-matched control cases. The gall-bladders treated by ESWL, in addition to showing the histological changes associated with chronic cholecystitis, showed serosal vasodilatation, mural oedema, and serosal and mucosal petechial haemorrhages focally over the entire surface. Between 10 and 90 per cent epithelial denudation was observed, but all cases showed surviving columnar epithelial cells in the crypts. No case showed vascular thrombosis, tissue necrosis, or acute inflammation. These tissue effects are likely to be reversible and unlikely to present a risk of perforation, although the long-term clinicopathological effects await investigation.

Adult↗

Interleukin-1 mediated signal transduction associated with synovial cell activation.

The early biochemical events that link interleukin-1 (IL-1) receptor occupancy to neutral proteinase production in synovial cells were studied. Addition of human r-IL-1 to human synovial cells in culture stimulated phospholipase A2 (PLA2) activity, inositol triphosphate production and plasminogen activator (PA) activity in a dose dependent manner with similar EC50 values (0.1-0.5 nM). These results, coupled with time courses and other studies, suggest that the IL-1 modulation of PA involves both products of PLA2 and phospholipase C (PLC) activation. On the other hand, the IL-1 induction of collagenase may primarily involve PLC and protein kinase C activation.

Arthritis, Rheumatoid↗

Effects of clomiphene citrate on episodic luteinizing hormone secretion throughout the menstrual cycle.

Pituitary luteinizing hormone secretory dynamics (pulse frequency and amplitude) were evaluated in eight normal women administered clomiphene citrate or placebo. After 5 days of treatment clomiphene citrate was found to increase mean luteinizing hormone secretion by increasing the amount of pituitary luteinizing hormone released per pulse. No change in pituitary luteinizing hormone interpulse interval was found in the follicular phase of the cycle, although a faster pulse frequency in the luteal phase was found after clomiphene citrate when compared with placebo. No differences were found in the luteal phase (pulse frequency, amplitude, and mean luteinizing hormone level) after clomiphene citrate versus placebo in the volunteers. These data suggest that the principal mechanism of action of clomiphene citrate is an increase in the concentration of hypothalamic gonadotropin releasing hormone into the hypothalamic-pituitary portal circulation, with a resultant increase in pituitary luteinizing hormone secretion.

Adult↗

Software manipulations to speed up a real-valued fast Fourier transform algorithm.

It is described how a real-valued fast Fourier transform (RFFT) algorithm can be converted quite easily into a computer program in which loops, evaluation of subscripts, exchange of data, and logical operations are completely avoided. The resulting program runs considerably faster than the original algorithm. The actual saving of execution time depends upon both the computer system and the length of the RFFT. In the majority of the investigated cases the execution time was reduced by a factor between 1.8 and 5. The described technique can be recommended especially for critical real-time tasks and for applications requiring a huge amount of RFFT evaluations. Other algorithms as for example the complex-valued FFT, the inverse RFFT or correlation algorithms can be treated in a similar way.

Algorithms↗

Differentiation between renal cortex and medulla in the response to hypotension using localized 31P magnetic resonance spectroscopy.

Experiments were designed to test the hypothesis that renal medulla is more sensitive to hypoxia than is the cortex. Using the one-dimensional phase encoding technique to perform 31phosphorus magnetic resonance spectroscopy in a perfused porcine kidney preparation, cortex and medulla were differentiated on the basis of the unique resonance at 3 ppm found only in medulla. Hypotension-induced hypoxia reduced total renal oxygen consumption by 60%, and urine flow by 44%. Nonlocalized 31P MRS spectra showed that [ATP]/[Pi] ratio fell by 40%, and intrarenal pH by 0.1 unit. Virtually all of these changes could be accounted for by changes in the renal cortex, where initial [ATP]/[Pi] was higher than in medulla (1.16 vs. 0.68). In medulla [ATP]/[Pi] fell only 29% (n.s. versus control) and pH remained unchanged during hypotension. Thus the cortex appears to be more sensitive to hypoxia in this preparation, and observations fail to support the proposed hypothesis. They are consistent, however, with the greater capacity of medulla for anaerobic glycolysis. Localized 31P MRS provides improved noninvasive metabolic assessment of cold-preserved kidneys.

Adenosine Triphosphate↗

Microbial burdens in disposable and nondisposable ventilator circuits used for 24 and 48 h in intensive care units.

One hospital sought to study the differences in using resterilizable permanent versus disposable ventilator circuits and changing the circuits on a 24-h versus a 48-h basis. Over a period of 13 months 656 condensate samples from 92 permanent and 72 disposable circuits were collected and plated by a loop dilution technique. Two samples were collected from the inspiratory limb (humidifier; tubing or nebulizer), and two were collected from the expiratory limb (tubing and trap) of each circuit. Contamination rates were higher for disposable circuits than for permanent circuits and for 48-h changes than for 24-h changes. Results of chi 2 testing by site indicated there was more contamination on the inspiratory and expiratory limbs each with use of disposable circuits than with the use of permanent circuits. The total results (chi 2 analysis) showed significantly greater microbial growth with the use of disposable circuits (permanent versus disposable, P less than 0.001) and extension of time to 48-h changes (24 h versus 48 h, P less than 0.05). In the experience of this hospital permanent circuits proved more advantageous from the standpoint of contamination risk and cost.

Adolescent↗

Glomerular and tubular handling of differently charged human immunoglobulin light chains by the rat kidney.

1. To examine the effect of charge and molecular size on the renal handling of immunoglobulin light chain, three different human light chains were purified, iodinated and characterized with regard to molecular weight and isoelectric point. The molecular weights were similar, whereas the isoelectric points ranged from markedly cationic to markedly anionic. 2. Renal handling of the light chains was determined in vivo in the Munich-Wistar rat and in vitro in the isolated perfused rat kidney. 3. Significant restriction to the transglomerular passage of all three light chains was evident in the intact kidney, with the most anionic light chain being restricted most while the cationic light chain was restricted least. The charge dependence of filtration of these naturally occurring proteins was, however, much less pronounced than has previously been reported for the synthetic dextrans. 4. Tubular reabsorption of the three light chains was quite variable in the intact kidney and did not appear to be related to molecular charge. In the isolated perfused kidney, once account had been taken of the abnormally high rate of filtration of these proteins, the reabsorption of the three light chains was strikingly similar to that seen in vivo. 5. With these three purified human light chains no marked influence of charge (pI) has been demonstrated in vivo or in vitro, for glomerular restriction or renal tubular reabsorption. Some other properties of human myeloma light chains may determine their renal handling and nephrotoxicity.

Absorption↗

Osteosarcoma and other neoplasms of bone. Magnetic resonance spectroscopy to monitor therapy.

Fourteen patients with malignant tumors of bone (ten osteogenic sarcomas, one Ewing's tumor, one giant-cell tumor, two non-Hodgkin's lymphomas), plus one patient with a synovial cell sarcoma, who had been treated by standard extremity-conserving chemotherapy regimens, were examined before treatment by means of localized phosphorus 31 magnetic resonance spectroscopy. Thirteen (86%) of 15 examinations were successful, and 100% of successful examinations showed metabolic abnormality in the tumor. Tumors contained excess adenosine triphosphate and inorganic phosphate, an unusual peak of phosphomonoester, consistent with excessive glycolysis in tumors. The intratumor pH was normal in the 12 bone tumors, but acidic in the single soft-tissue sarcoma (pH 6.8). Metabolic response was observed in all seven patients monitored during chemotherapy, with the earliest examinations being performed two days after first treatment. An increase in the inorganic phosphate level, loss of adenosine triphosphate, and loss of phosphomonoester indicated tumor response; loss of all abnormal metabolites (two of seven patients) indicated regression of the tumor. Tumor relapse was accompanied by reappearance of abnormalities in the magnetic resonance spectrum. Phosphorus 31 magnetic resonance spectroscopy offers a unique means of determining the early response of these malignant tumors to therapy as well as predicting their relapse.

Adenosine Triphosphate↗

Maturational changes in the pharmacological characteristics and actomyosin content of canine arterial and venous tissue.

The purpose of this study was to compare the pharmacological characteristics and actomyosin content of arterial and venous tissue at different times during development. Rings of arteries (femoral, renal, carotid, pulmonary) and veins (saphenous, pulmonary, jugular) were obtained from 1 wk, 1 month, and adult dogs, mounted at their optimal length for force development and the contractile response to potassium chloride and phenylephrine determined. The strain at optimal length was less at all ages in pulmonary artery and pulmonary and jugular veins than in other vessels. All vessels exhibited an increase in maximum contractile response with development but the increase was greater for phenylephrine. In general, the magnitude of the maximum response of the jugular and pulmonary veins and pulmonary artery was less than other vessels at all ages. The sensitivity (half maximum response) either increased or was unchanged in arteries with development, while in the veins it either decreased or was unchanged. The relaxant effects of verapamil and isoproterenol were determined on potassium chloride contracted vessels. Arterial tissue was minimally responsive to isoproterenol at all ages while venous tissue either increased its responsiveness (saphenous, pulmonary) with development or remained highly responsive (jugular). Verapamil, unlike isoproterenol, was an effective relaxant of all vessels. The actomyosin content (mg/mm) of femoral and renal arteries and saphenous and jugular veins increased with development but this increase was accompanied by a parallel increase in total protein so that the ratio (actomyosin/total protein) was unchanged. In jugular veins from adult dogs this ratio was smaller than in arterial tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Actomyosin↗