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Biomedical subjects

D L Walters

Publications and source records attributed to D L Walters.

At least 19 recordsLinked to original sources

Platelet-monocyte aggregates predict troponin rise after percutaneous coronary intervention and are inhibited by Abciximab.

BACKGROUND: Platelet-monocyte aggregates and other markers of platelet activation were investigated before and after percutaneous coronary intervention (PCI) with abciximab therapy. The study sought to assess the relationship between the level of platelet-monocyte aggregation and increases in cardiac troponin I post coronary intervention. METHODS: Blood samples were collected from 40 patients before PCI and 10 min after abciximab administration. These were tested for platelet activation markers by flow cytometry. Cardiac troponin I levels were assayed at baseline and at 24 h post PCI. RESULTS: Compared to healthy controls, patients with coronary artery disease had elevated markers of platelet activation including platelet-monocyte aggregates, P-selectin and PAC-1 (a marker specific for activated glycoprotein IIb/IIIa) prior to PCI. Increased levels of platelet-monocyte aggregates before PCI were associated with increased expression of P-selectin on the platelet surface. Abciximab therapy reduced platelet-monocyte aggregate levels but had no effect on P-selectin expression. The high levels of expression of activated glycoprotein IIb/IIIa (PAC-1) on platelets prior to PCI was reduced with abciximab therapy. Patients with higher levels of platelet-monocyte aggregates prior to PCI were more likely to develop an elevation of cardiac troponin I during the 24 h after PCI. CONCLUSIONS: Increased levels of platelet-monocyte aggregates may predict patients at risk for troponin elevation following PCI and identify those most likely to benefit from abciximab.

Abciximab↗

Adjunctive pharmacotherapy for coronary stenting.

The use of coronary stents improves the outcomes of percutaneous coronary intervention (PCI). This has led to a rapid increase in their use. Coronary stenting is not without problems and is complicated by both early ischemic events and late restenosis. The combination of anticoagulation with unfractionated heparin (UFH) and the use of antiplatelet agents including aspirin, thienopyridines, and glycoprotein IIb/IIIa inhibitors has led to a major reduction in early ischemic events after stenting. Low molecular weight heparin (LMWH) and direct thrombin inhibitors have a number of theoretical advantages over UFH. Their role as an adjunct to coronary stenting is still under investigation. Trials of systemic pharmacotherapy aimed at reducing in-stent restenosis have been consistently disappointing. Preliminary results of stents coated with agents that inhibit neointimal proliferation are extremely promising. The results of ongoing phase III trials of these coated stents are eagerly awaited.

Coronary Disease↗

The use of mechanical devices as adjuncts to intracoronary stenting.

A number of mechanical adjuncts to intracoronary stenting are now available to the interventional cardiologist. These devices have assisted in the development of a safer and more effective stenting practice. Intravascular ultrasound-guided stenting has been shown to reduce the rate of subacute thrombosis and subsequent restenosis. It allows a greater appreciation of lesion structure and severity so that an appropriate intervention strategy can be devised. Debulking techniques may allow the optimal deployment of stents so that restenosis is reduced; however, the results of large randomized studies are still awaited. The use of thrombectomy and distal embolization protection devices is emerging as a safer alternate to stenting alone in difficult patient subsets, such as those with thrombus-laden lesions and degenerated vein grafts. Doppler and pressure wires may be useful in determining optimal stent deployment and predict subsequent patient outcomes. An understanding of the indications and limitations of these devices is of increasing importance to the interventional cardiologist as the coming decade threatens to yield an impressive array of high-tech innovations.

Cardiac Surgical Procedures↗

Analysis of various nucleosides in plasma using solid phase extraction and high-performance liquid chromatography with UV detection.

The National Cancer Institute (NCI) has screened many nucleosides for antiviral activity to the HIV-1 virus. Drugs demonstrating antiviral activity are tested in animal models to evaluate their toxicity and pharmacokinetic characteristics. These drugs are subsequently evaluated for efficacy in human clinical trials. Sensitive analytical methodology is needed to quantify nucleosides in plasma and other biological matrices in support of these studies. Battelle has modified and validated a reversed phase high-performance liquid chromatography (HPLC) method for several of these nucleosides that could be easily adapted for similar compounds. Methods have been validated for 6-chloro-2',3'-dideoxyguanosine (6ClddG), 6-chloro-2',3'-dideoxyinosine (6ClddI) and their primary metabolites 2',3'-dideoxyguanosine (ddG) and 2',3'-dideoxyinosine (ddI) in both rat and dog plasma containing EDTA. The method has also been validated for 2'-fluoro-2',3'-dideoxyara-adenosine (betaFlddA) and its primary metabolite 2'-beta-fluorodideoxyinosine (betaFddI) in rat plasma containing heparin. Calibration plasma standards were prepared over ranges of 0.1-10 microg ml(-1) for betaFlddA and betaFddI, 0.1-50 microg ml(-1) for 6ClddG and ddG, and 0.25-50 microg ml(-1) for 6ClddI and ddI in plasma containing 4 microg ml(-1) pentostatin. The addition of pentostatin to the plasma samples inhibits in-vitro deamination of the drug after collection. Quality control (QC) standards were prepared containing the appropriate anticoagulant and 4 microg ml(-1) pentostatin at concentrations within each of the bracketed calibration ranges in plasma. These methods have been successfully applied to plasma samples generated during various animal studies.

Animals↗

Development and validation of a gradient reversed-phase high-performance liquid chromatographic assay for S(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0923) from a transdermal delivery system.

A gradient reversed-phase HPLC method for potency determination of N-0923 (10 mg) from a transdermal delivery system (TDS), was developed and validated with single point calibration using internal standard quantitation. N-0923 and the internal standard, N-0434, are eluted from a reversed-phase C18 column using a gradient which contains 0.1 M triethylamine-0.04 M citrate buffer, pH 5.9, water, and acetonitrile with UV detection at 272 nm. N-0923 is isolated from the transdermal delivery system by extraction with n-heptane followed by extraction of the resulting organic phase with 0.1 M citric acid containing the internal standard. The method was free from matrix interferences in both untreated and forced degraded placebo delivery systems. Acceptable linearity and quantitative recovery from spiked placebo delivery systems over the range 50-150% of nominal label claim were demonstrated. Within-day assay precision from individual samples of active transdermal delivery systems (n = 10) was 5.6% R.S.D. The detection limit was at least 0.1 microgram/ml which is equivalent to 0.05% of the working standard concentration. Replicate injection precision at this level was 0.08% R.S.D. (n = 4). Analysis of thermally stressed active and placebo delivery systems with this HPLC method and photodiode-array detection showed that the chromatography was stability-indicating as demonstrated by the absence of measurable interferences from principal degradation products of either the n-0923 or the delivery system excipients.

Administration, Cutaneous↗

Pharmacokinetic study of zeolite A, sodium aluminosilicate, magnesium silicate, and aluminum hydroxide in dogs.

Zeolite A is a synthetic zeolite which may have therapeutic utility in osteoporotic individuals because of its ability to stimulate bone formation. A study of Zeolite A (30 mg/kg), sodium aluminosilicate (16 mg/kg), magnesium trisilicate (20 mg/kg), and aluminum hydroxide (675 mg) was designed in beagle dogs. The purpose of this study was to compare the oral bioavailability of silicon and aluminum from Zeolite A, sodium aluminosilicate, magnesium trisilicate, and aluminum hydroxide in dogs. Twelve female dogs received each compound as a single dose separated by one week in a randomized, 4-way, crossover design. Plasma samples were drawn at time 0 and for 24 hours after dosing. The concentrations of silicon and aluminum were determined by graphite furnace atomic absorption. The mean plasma silicon AUC values (+/- S.D.) were 9.5 +/- 4.5, 7.7 +/- 1.6, 8.8 +/- 3.0, 6.1 +/- 1.9 mg.hr/L and the mean plasma silicon Cmax values (+/- S.D.) were 1.07 +/- 1.06, 0.67 +/- 0.27, 0.75 +/- 0.31, 0.44 +/- 0.17 mg/L for Zeolite A, sodium aluminosilicate, magnesium trisilicate, and aluminum hydroxide respectively. Although mean silicon AUC and Cmax values were elevated when compared to baseline after administration of the silicon containing compounds, only the AUC from Zeolite A reached statistical significance (p = 0.041). The mean plasma silicon Tmax values (+/- S.D.) were 7.9 +/- 6.4, 5.8 +/- 4.6, 6.9 +/- 6.3 and 8.5 +/- 3.4 hrs for Zeolite A, sodium aluminosilicate, magnesium trisilicate and aluminum Hydroxide respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗

Team approach to home health care delivery: optometry as the primary vision care provider.

The purpose of this report is to describe a vision care program, utilizing optometry as the primary vision care provider, for patients unable to obtain care in traditional ways. The impact of this program upon the community, its impact upon an educational curriculum, and the program itself are discussed. The program provides a model for delivery of health care to patients who would otherwise go without care.

Age Factors↗

Preovulatory biosynthesis and granulosa cell secretion of immunoreactive oxytocin by goat ovaries.

Oestrous cycles of goats were synchronized hormonally. Immunoreactive oxytocin was undetectable (less than 0.1 ng/mg protein) in media from granulosa cells isolated before the LH surge for small (1-2 mm), medium (3-5 mm) and large (greater than 5 mm diameter) follicles when cultured for 24 h without or with added hormones. Granulosa cells from large and medium, but not small, follicles isolated 6-12 h after spontaneous preovulatory LH surges secreted high concentrations of oxytocin (4-12 ng/mg protein). Addition of PGE-2 (1 microgram/ml) caused a further significant (P less than 0.05) increase in oxytocin secretion by cultured granulosa cells, whereas PGF-2 alpha, FSH and LH were ineffective when added to culture media. Ovarian venous blood and granulosa cells were collected at 0, 6, 12 or 18 h after GnRH injection in hormonally synchronized goats. Peripheral serum LH values were increased significantly in all but 2 of 22 goats within 2 h of GnRH injection. At the earliest sampling time after GnRH (6 h), ovarian venous levels of oxytocin were increased significantly from basal levels of 0.4 pg/ml to 2.4 pg/ml. Oxytocin concentrations in follicular fluid increased from a basal value of 67 pg/ml to 155 pg/ml by 6 h and to 372 pg/ml by 18 h after GnRH injection. Oxytocin secretion by cultured granulosa cells was not increased significantly by 6 h (0.1 ng/mg protein) but rose to 1.4 and 3.5 ng/mg protein at 12 and 18 h, respectively. Approximately parallel increases occurred in progesterone in ovarian venous blood and granulosa cell culture media over the same time period. (ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Gonadotrophins and ovarian steroids in cattle. I. Pulsatile changes of concentrations in the jugular vein throughout the oestrous cycle.

Short-term secretion patterns of LH, FSH, progesterone and oestradiol-17 beta were evaluated throughout complete oestrous cycles of 6 heifers. Frequent blood samples (in 20-min intervals for 12 continuous h) were taken every 3-5 days from indwelling jugular catheters. There was a high incidence of concomitant LH and FSH pulses ranging from 72% at luteolysis to 83-100% during the luteal phase. Almost the same total number of LH and FSH pulses occurred during the early luteal phase (7.0 vs 7.4/12 h, respectively), however, there was an average of one additional FSH pulse in between the synchronous LH/FSH ones during the mid- and late luteal phase (6.9 FSH vs 3.4 LH pulses/12 h). Basal LH and FSH concentrations remained unchanged from the early until the late luteal period. During and after luteolysis frequency of LH and FSH release (14.5 vs 10.5 pulses/12 h) increased considerably as well as basal concentrations and magnitude of LH pulses. Secretion of both gonadotrophins persisted very frequently (13.3 LH and 10.7 FSH pulses/12 h) during pro-oestrus and oestrus when basal FSH concentrations and FSH pulse maxima approached a nadir. During the mid-luteal phase 45% of pulsatile progesterone occurred concomitantly with each coinciding LH/FSH pulse and 44% of pulsatile progesterone happened after additional single FSH pulses. Distinct short-term changes of oestradiol concentrations were not observed in the jugular vein but concentrations fluctuated randomly ranging from 2-6 pg/ml throughout the luteal period. Prior to and during heat mean concentrations of oestradiol were approximately 2-fold higher (P less than 0.05) than during the other periods of the cycle. It is concluded that the frequency of pulsatile LH release is modulated to a much greater extent than FSH by negative feedback of ovarian steroids. Some pulsatile progesterone secretion resulting from the stimulation of FSH (and LH) is still detectable in the jugular vein whereas of oestradiol-17 beta is not. The additional frequent monitoring of FSH might be more appropriate reflecting pituitary and hypothalamic function than only measuring LH.

Animals↗

Gonadotrophins and ovarian steroids in cattle. II. Pulsatile changes of concentrations in the jugular vein throughout pregnancy.

Short-term secretion patterns (derived from samples collected from jugular vein cannulae every 20 min for 12 h) of LH, FSH, progesterone, oestradiol-17 beta, oestrone and prolactin were studied every 30 days during gestation in heifers. LH pulse frequency and amplitude was greater during the early (months 1-3) and end (months 8-9) than during mid-gestation when pulsatile LH secretion was almost abolished. The frequency of pulsatile FSH release, which was already twice as fast than of LH during early pregnancy, did not change throughout the whole gestation period. Mean, basal and maximal progesterone concentrations were highest during the first 3 months of gestation, were slightly reduced during mid-gestation and decreased further during the last 2 months preceding parturition. Pulses of progesterone occurred concomitantly with the parallel LH/FSH as well as the separate FSH pulses. Average oestradiol-17 beta concentrations during the first months of gestation were slightly higher than during the mid-luteal phase of the cycle and exceeded during mid-gestation concentrations measured at oestrus. Free oestrone could be detected as early as day 60 of pregnancy. Frequency and amplitude of short-term changes of oestrone increased after the 5th month. Discontinuous secretion of oestrone as well as oestradiol-17 beta was only arbitrarily but never consistently correlated with either each other or with pulsatile gonadotrophin release. Apart form an occasional coincidence with pulsatile release of other hormones prolactin concentrations seemed to depend rather on the season of the year and time of the day than on the individual pregnancy stage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of exogenous steroids, nutrition and calf removal on reproductive performance of anestrous beef cows.

Methods for inducing a fertile estrus in anestrous beef cows suckling calves were explored in three studies. Trial 1 . Eighty-two primiparous and pluriparous Brahman-Hereford crossbred and Angus cows suckling calves were divided into four groups: 1) good body condition, high level of nutrition (GH); 2) good body condition, low level of nutrition (GL); 3) poor body condition, high level of nutrition (PH); 4) poor body condition, low level of nutrition (PL). All cows received the Shang Treatment (S). Following treatment, more cows (P<0.05) ovulated in the GH group (95%) than either the GL (61%), PH (58%), or PL (53%) group. Pregnancy rates were low and were not different between groups following the insemination taking place 54 hours after implant removal or after cows had been bred for 21 days. Trial 2 . One hundred fourteen two-year-old Santa Gertrudis-Hereford crossbred cows in poor body condition were divided into four groups. Forty-nine cows received S treatment and 65 cows served as controls (C) with approximately half of each group fed a high (H) or a medium (M) level of nutrition (SH, SM, CH, CM). One cow in the SH group ovulated and was pregnant 21 days after breeding. The remaining cows failed to exhibit estrus, ovulate or become pregnant. Trial 3 . Cows used in this trial were those from Trial 2 which did not exhibit estrus nor had a palpable corpus luteum present 21 days after implant removal. Cows were divided into 1) control (C), 2) wean (W), 3) wean + Syncro-Mate-B (W+SMB) and 4) Syncro-Mate-B + wean (SMB+W). The percentage of cows ovulating by 2 and 40 days after the start of breeding was similar (P>0.05) in the W, W+SMB, and SMB+W groups but all were greater (P<0.05) than the percentage of cows ovulating in the C groups. Pregnancy rates of cows in the W+SMB and SMB+W groups were higher (P<0.05) than pregnancy rates of cows in the W and C groups by two days after the start of breeding. Pregnancy rates 40 days after the start of breeding were higher (P<0.05) for cows in the W, W+SMB) and SMB+W groups than for cows in the C group.

Journal Article↗

Pulsatile secretion of gonadotrophins, ovarian steroids and ovarian oxytocin during the luteal phase of the oestrous cycle in the cow.

All hormones were determined in blood samples collected simultaneously from the caudal vena cava and jugular vein at 20-min intervals for 12 h during the early (Day 4) and mid- (approximately Day 11) luteal phases of the oestrous cycle in 7 cows. Mean concentrations of oestradiol, progesterone and oxytocin were greater (P less than 0.01) in the vena cava than in the jugular vein. Pulses of these hormones were also more easily identifiable in the vena cava. The frequency of LH pulses was higher (P less than 0.01) during the early luteal than during the mid-luteal phase (8.0 versus 3.6 pulses/12 h). During both phases, 90-96% of all LH pulses were followed within 60 min by a pulse of oestradiol. Basal concentration and amplitude of oestradiol pulses were greater (P less than 0.05) during the early than during the mid-luteal phase. The frequency of FSH pulses was similar to that of LH during the early luteal phase (8.5 and 8.0 pulses/12 h) but was greater (P less than 0.01) than that of LH during the mid-luteal phase (6.3 versus 3.6 pulses/12 h). Thus, 41% more (P less than 0.01) FSH pulses than LH pulses were observed during the mid-luteal phase. However, the separate FSH pulses were associated with low-amplitude short-duration pulses of LH as clarified by an additional study (in 3 cows) using 5-min sampling intervals: 90-100% of all LH/FSH pulses and separate FSH pulses were secreted either concomitantly with or followed by a pulse of progesterone. However, no separate FSH pulses were associated with a pulse of oestradiol. Basal concentration and amplitude of progesterone were greater (P less than 0.01) during the mid-luteal than during the early luteal phase. The frequency of oxytocin pulses was similar to that of progesterone during the mid-luteal but not during the early luteal phase. During the mid-luteal phase 97% of all oxytocin pulses were associated with a pulse of progesterone. It is concluded that (1) separate FSH pulses are secreted in addition to parallel LH and FSH pulses during the mid-luteal phase; therefore, the frequency of secretion of LH may be modulated to a greater extent by ovarian steroids than is FSH pulse frequency; (2) pulses of progesterone are probably a result of stimulation by pulses of FSH and/or LH whereas pulses of oestradiol are caused by LH pulses; (3) ovarian oxytocin and progesterone are secreted concomitantly during the mid-luteal phase of the oestrous cycle.

Animals↗

Pulsatile secretion of gonadotrophins, ovarian steroids and ovarian oxytocin during prostaglandin-induced regression of the corpus luteum in the cow.

A luteolytic dose (500 micrograms) of cloprostenol was given on Day 12 of the oestrous cycle to 5 heifers. Blood samples were collected simultaneously from the caudal vena cava and jugular vein at 5-20-min intervals from -6 to 0 (control period), 0 to 12 and 24 to 36 h after PG injection. Pulses of LH were secreted concomitantly with pulses of FSH during all sampling periods. However, during the control period separate FSH pulses were detected resulting in a shorter (P less than 0.01) interpulse interval for FSH than LH (93 versus 248 min). LH and FSH pulse frequencies increased (P less than 0.01) beginning 1-3 h after PG to interpulse intervals of 59 and 63 min, respectively, and continued to be maintained 24-36 h after PG. Concomitantly there was a 2-3-fold increase (P less than 0.01) in basal concentrations and pulse amplitude for LH (but not FSH). FSH basal concentrations and pulse amplitudes decreased (P less than 0.05) in 3 heifers 24-36 h after PG. Pulsatile secretion of oestradiol was observed at frequencies similar to LH during the periods 4-12 h (3 heifers) and 24-36 h (2 heifers) after PG, respectively, resulting in higher (P less than 0.05) mean oestradiol concentrations. Progesterone concentrations in the vena cava increased (P less than 0.01) 5-10 min after PG but decreased (P less than 0.01) 67% by 20 min after PG. This decrease was followed by a rise (P less than 0.05) beginning 2-3 h after PG and lasting for an average of 3.3 h.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Pulsatile secretion of gonadotrophins, ovarian steroids and ovarian oxytocin during the periovulatory phase of the oestrous cycle in the cow.

An injection of 500 micrograms prostaglandin (PG) analogue was given on Day 12 (mid-luteal phase) of the oestrous cycle to 8 cows. An LH surge occurred 59 +/- 2 h later. LH, FSH, prolactin, oestradiol-17 beta, progesterone and oxytocin concentrations were determined in blood samples collected from the caudal vena cava and/or the jugular vein at 20-min (5 cows) or 5-min (3 cows; only LH and FSH concentrations were determined) intervals for 24 h, beginning 48 h after the PG injection. Oxytocin concentrations were low and similar in the vena cava and the jugular vein. In blood samples collected every 5 min the interpulse interval for LH and FSH during the period before the LH surge was 38-40 min. In the 20-min samples the interpulse interval for oestradiol was similar to that for LH and FSH, but pulse amplitude and basal concentrations steadily increased to reach maximum concentrations 6-8 h before and again during the LH surge. A decrease in oestradiol concentrations, lasting at least 60 min, occurred just before the start of the LH surge. Progesterone concentrations also increased at the same time as the LH surge. The magnitude of the LH surges varied from 7 to 32 ng/ml, but all cows ovulated and had oestrous cycles of normal length. Distinct pulses of LH and FSH were observed throughout the LH and FSH surges. Pulsatile secretion of LH was not detected for a period of up to 6-12 h following the LH surge, but then low-amplitude pulses occurred. In contrast, the pulsatile secretion of FSH remained at a frequency similar to that observed during the descending phase of the FSH surge. Furthermore, a second increase in FSH concentrations occurred, beginning 4-12 h after the LH-surge. It is concluded that: (1) the frequent, high-amplitude pulses of oestradiol that occur before and during the LH surge are probably due to stimulation by pulses of LH; (2) the LH surge is the result of an increase in frequency and amplitude of the LH pulses; (3) the second increase in FSH that follows the LH and FSH surges appears to be the result of an increase in the amplitude (not frequency) of the FSH pulses; and (4) very little, if any, oxytocin is secreted from the ovary during the periovulatory phase of the oestrous cycle.

Animals↗

Pituitary and ovarian function in postpartum beef cows. I. Effect of suckling on serum and follicular fluid hormones and follicular gonadotropin receptors.

The effect of suckling on serum and follicular fluid hormones and on follicular gonadotropin receptors was studied. Sixteen anestrous postpartum cows were assigned to 1 of 2 groups: suckled (S) or weaned (W). All calves were allowed to suckle ad libitum from parturition to 21 days postpartum when calves from W cows were weaned. All cows were ovariectomized on Day 25 postpartum. W cows had more (P less than 0.01) pulses of LH during the 96-h period from weaning until ovariectomy than S cows (6.3 vs. 1.3 pulses). Serum concentrations of prolactin (Prl), estrone (E1), estradiol-17 beta (E2) and progesterone (P) were not different (P greater than 0.10) between groups. Furthermore, there were n differences (P greater than 0.10) in follicular in contents of luteinizing hormone (LH), E1, E2 and P between the treatment groups. However, follicular fluid content of Prl was greater (P less than 0.05) in the W cows than in the S cows (123 vs. 65.1 ng/cow). The number of follicular LH receptors was greater (P less than 0.05) in the W cows than in the S cows (71.1 vs. 48.3 fmoles/mg protein) although the number of follicular follicle-stimulating hormone (FSH) receptors was not different (P greater than 0.10) between W cows and S cows (1531 vs. 1862 fmoles/mg protein). There were no correlation between serum hormone concentrations and follicular fluid hormone content; however, the numbers of follicular LH receptors and follicular fluid Prl content were highly correlated in the W cows (r = 0.85; P less than 0.05). It is concluded that removal of the suckling stimulus increases pulsatile LH release and the accumulation of Prl in the follicular fluid. These factors, either together or separately, may at least in part be responsible for the increase in follicular LH receptor concentrations that were observed in the W cows.

Animals↗