PubMed Health⌕ Search

Biomedical subjects

R Waite

Publications and source records attributed to R Waite.

At least 19 recordsLinked to original sources
PubMed2003

Preliminary investigations into possible resistance to oxytetracycline in Melissococcus plutonius, a pathogen of honeybee larvae.

AIMS: To investigate the occurrence of oxytetracycline (OTC) resistance in Melissococcus plutonius, which causes European foulbrood in honeybee colonies. METHODS AND RESULTS: Strains of M. plutonius were isolated from diseased colonies in England and Wales and tested for resistance to OTC. The minimum inhibitory concentration (MIC) of OTC was also determined for selected isolates. No resistance to the antibiotic was found in any isolate and the average MIC was found to be 3.9 microg ml-1. Melissococcus plutonius was found to be susceptible to both chlortetracycline and tetracycline. CONCLUSIONS: No resistance to OTC was found in M. plutonius. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that OTC can continue to be used to treat European foulbrood and that resistance may not explain why some treatments fail.

Animals↗
PubMed2001

Potassium channels regulate tone in rat pulmonary veins.

Intrapulmonary veins (PVs) contribute to pulmonary vascular resistance, but the mechanisms controlling PV tone are poorly understood. Although smooth muscle cell (SMC) K(+) channels regulate tone in most vascular beds, their role in PV tone is unknown. We show that voltage-gated (K(V)) and inward rectifier (K(ir)) K(+) channels control resting PV tone in the rat. PVs have a coaxial structure, with layers of cardiomyocytes (CMs) arrayed externally around a subendothelial layer of typical SMCs, thus forming spinchterlike structures. PVCMs have both an inward current, inhibited by low-dose Ba(2+), and an outward current, inhibited by 4-aminopyridine. In contrast, PVSMCs lack inward currents, and their outward current is inhibited by tetraethylammonium (5 mM) and 4-aminopyridine. Several K(V), K(ir), and large-conductance Ca(2+)-sensitive K(+) channels are present in PVs. Immunohistochemistry showed that K(ir) channels are present in PVCMs and PV endothelial cells but not in PVSMCs. We conclude that K(+) channels are present and functionally important in rat PVs. PVCMs form sphincters rich in K(ir) channels, which may modulate venous return both physiologically and in disease states including pulmonary edema.

4-Aminopyridine↗
PubMed1999

O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase.

The rapid response to hypoxia in the pulmonary artery (PA), carotid body, and ductus arteriosus is partially mediated by O2-responsive K+ channels. K+ channels in PA smooth muscle cells (SMCs) are inhibited by hypoxia, causing membrane depolarization, increased cytosolic calcium, and hypoxic pulmonary vasoconstriction. We hypothesize that the K+ channels are not themselves "O2 sensors" but rather respond to the reduced redox state created by hypoxic inhibition of candidate O2 sensors (NADPH oxidase or the mitochondrial electron transport chain). Both pathways shuttle electrons from donors, down a redox gradient, to O2. Hypoxia inhibits these pathways, decreasing radical production and causing cytosolic accumulation of unused, reduced, freely diffusible electron donors. PASMC K+ channels are redox responsive, opening when oxidized and closing when reduced. Inhibitors of NADPH oxidase (diphenyleneiodonium) and mitochondrial complex 1 (rotenone) both inhibit PASMC whole-cell K+ current but lack the specificity to identify the O2-sensor pathway. We used mice lacking the gp91 subunit of NADPH oxidase [chronic granulomatous disease (CGD) mice] to assess the hypothesis that NADPH oxidase is a PA O2-sensor. In wild-type lungs, gp91 phox and p22 phox subunits are present (relative expression: macrophages > airways and veins > PASMCs). Deletion of gp91 phox did not alter p22 phox expression but severely inhibited activated O2 species production. Nonetheless, hypoxia caused identical inhibition of whole-cell K+ current (in PASMCs) and hypoxic pulmonary vasoconstriction (in isolated lungs) from CGD vs. wild-type mice. Rotenone vasoconstriction was preserved in CGD mice, consistent with a role for the mitochondrial electron transport chain in O2 sensing. NADPH oxidase, though a major source of lung radical production, is not the pulmonary vascular O2 sensor in mice.

Animals↗
PubMed1995

Long-term efficacy with fluvastatin as monotherapy and combined with cholestyramine (a 156-week multicenter study). French-Dutch Fluvastatin Study Group.

Fluvastatin monotherapy up to 40 mg/day over 52 weeks in patients with primary hypercholesterolemia decreased plasma low density lipoprotein cholesterol (LDL-C) by 28%, with varying decreases in plasma triglycerides and increases in high density lipoprotein cholesterol (HDL-C). Patients completing the 52-week study participated in a further trial to assess whether the efficacy of fluvastatin (20-40 mg/day), either as monotherapy or in combination with cholestyramine (CME; 4-16 g/day), taken at least 4 hours prior to fluvastatin, is sustained for up to 3 years. Patients were assessed every 12 weeks on average for safety and efficacy, the latter being calculated as a percent change from baseline of lipids or lipoproteins. During the second year (endpoint up to week 104), 147 patients received monotherapy (estimated mean dose, 30.2 mg/day) and 127 received additional CME (38.1 mg/day fluvastatin plus 10.1 g/day CME). During the third year (endpoint up to week 156), 140 patients received monotherapy (32.5 mg/day) and 67 received additional CME (39.3 mg/day fluvastatin plus 10.3 mg/day CME). Statistically significant reductions in mean total cholesterol and LDL-C and increases in mean HDL-C were achieved in both treatment groups and maintained throughout the study. A significant reduction in triglyceride levels was only observed at the second year endpoint in patients receiving monotherapy (-10.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗
PubMed1994

Placebo-controlled comparison of spirapril at 6, 12 and 24 mg/day in mild to severe essential hypertension.

In a double-blind, parallel-group study, 260 patients with mild to severe essential hypertension were randomized to treatment with placebo or spirapril at 6, 12 or 24 mg once daily for 6 weeks. When blood pressures were measured at the end of the dosing interval (trough), all spirapril regimens had produced similar reductions in sitting systolic and diastolic blood pressures (siSBP/siDBP) which were significantly greater than those observed in placebo-treated patients. There were no relevant changes in resting heart rate in any of the study groups. At the study endpoint, the mean reductions in siSBP/siDBP were 14.9/11.5 mmHg with spirapril at 6 mg, 15.4/12.0 mmHg with spirapril at 12 mg and 17.8/12.4 mmHg with spirapril at 24 mg/day vs. 3.1/3.6 mmHg with placebo. In a subgroup of 122 patients, blood pressure was recorded at the end of the dosing interval and during the 8 hours immediately postdose to monitor the peak effects on blood pressure. All spirapril dosages produced similar reductions at peak with a mean decrease of siDBP of approximately 20 mmHg in comparison to baseline values vs 6-7 mmHg with placebo. The trough:peak ratios for 6, 12 and 24 mg all lay between 60% and 90% for siSBP and siDBP, indicating that most of the peak effect was maintained at trough. Spirapril was well tolerated; the adverse event profile was not different from that with placebo, and no dose-related adverse events were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Hormone specific regulation of natural killer cells by cortisol. Direct inactivation of the cytotoxic function of cloned human NK cells without an effect on cellular proliferation.

Corticosteroids have previously been reported to partially inhibit the natural cytotoxic activity of peripheral blood lymphocytes. However, since only a few percent of peripheral lymphocytes are natural killer (NK) cells, it has not been possible to determine whether corticosteroids directly inhibit NK cells or mediate this effect via other cell types. This report documents direct functional inactivation, but unimpeded proliferation, of cloned human NK cells by subphysiologic levels of cortisol. In contrast, high concentrations of testosterone, progesterone or estradiol had no significant effect on proliferation or cytotoxic activity of the cloned NK cells. The kinetics of inhibition of NK function by cortisol are consistent with a transcription-dependent mechanism.

Cell Division↗
PubMed1991

Quantification of effector/target conjugation involving natural killer (NK) or lymphokine activated killer (LAK) cells by two-color flow cytometry.

Precise estimates of the frequency of NK- and LAK-target conjugates were obtained by two-color flow cytometry using hydroethidine and calcein as intracellular labels for target cells and effector cells, respectively. These two dyes can easily be used with a standard single-laser flow cytometer with excellent signal separation and dye retention. Hydroethidine labeling did not alter target susceptibility, and calcein labeling did not significantly alter NK function. Excellent agreement was obtained between this flow cytometric method and visual estimation of the frequency of fresh or IL-2-activated human lymphocytes that form conjugates with K-562 target cells. The percentage of cloned NK or LAK cells that form conjugates with K-562 target cells was dependent on the E:T ratio, with extrapolated maximum conjugate frequencies (alpha max) of 40-50%. However, the frequency of lymphocytes forming conjugates with K-562 cells did not closely correlate with the cytolytic activity of a given lymphocyte population. This two color flow cytometric method employing a pair of fluorochromes that do not modify cell membranes or alter cell function in cytotoxicity assays should facilitate further studies of mechanisms involved in the initial stages of target cell recognition by NK and LAK cells.

Cell Survival↗
PubMed1991

Characterization of effector-target conjugates for cloned human natural killer and human lymphokine activated killer cells by flow cytometry.

The present studies demonstrate that the intracellular fluorochromes calcein and hydroethidine can be used for quantification of effector-target conjugates involving cloned human natural killer (NK) or interleukin-2 (IL-2) activated human lymphokine activated killer (LAK) cells by dual color flow cytometry without potential artifacts that might result from extensive modification of effector and/or target cell membranes. Cloned NK cells and LAK cells form conjugates with cultured cell lines regardless of susceptibility to lysis. The strength of the interactions in these conjugates was investigated using a variable speed vortexer. Even relatively gentle vortexing disrupted most conjugates involving fresh human peripheral blood lymphocytes (PBL) but only about one-fourth of conjugates between K-562 cells and human PBL that had been cultured with or without IL-2 by this treatment. The rate of conjugate formation for LAK cells was determined to be about 3 times faster than for cloned NK cells, and both rates are considerably faster than the reported rate of formation of cytotoxic T lymphocyte (CTL) target conjugates. The differences in the rate of conjugate formation are apparently not related to target cell specificity, since LAK cells form conjugates with susceptible and resistant cell lines at comparable rates. When effector-target conjugates are incubated at 37 degrees C in the absence of calcium--thereby precluding lysis--the percentage of conjugated LAK or cloned NK cells decreases logarithmically with time. These results suggest that an initial equilibrium between free and conjugated lymphocytes gradually shifts in favor of unconjugated cells.

Cell Communication↗
PubMed1989

A multicenter evaluation of the safety, tolerability, and efficacy of isradipine in the treatment of essential hypertension.

Six hundred outpatients aged between 22 and 84 years with essential hypertension (diastolic blood pressure of at least 95 mm Hg) entered a multinational, multicenter, single-blind trial with dose titration to assess the safety, tolerability, and efficacy of isradipine in doses of 1.25, 2.5, and 5.0 mg twice daily over 12 weeks, following a two-week placebo run-in period. Isradipine alone was taken by 321 patients, the remainder receiving, in addition, other antihypertensive drugs. In valid patients receiving monotherapy, the mean final isradipine dose was 3.4 mg (median, 2.5 mg) twice daily, which normalized supine diastolic blood pressure in 85 percent and 64 percent of patients two to four hours and 10 to 14 hours post-dose, respectively. Overall, 242 patients (40 percent) reported adverse events, 39 (7 percent) of whom withdrew from the study for this reason. The most common side effects were flushing (11 percent), headache (10 percent), and localized edema (4 percent). None of the pathologic changes in hematologic or biochemical values was attributable to isradipine. It is concluded that a slow titration of isradipine by increments at three-week intervals results in an effective and well-tolerated treatment for essential hypertension, both in mono- and combination therapy.

Adult↗
PubMed1989

The value of non-contrast-enhanced CT in blunt abdominal trauma.

The usefulness of non-contrast CT, limited to the upper abdomen, in conjunction with conventional IV contrast-enhanced scanning was studied prospectively in 190 patients who had sustained blunt abdominal trauma. In 78, visceral injuries were confirmed at surgery or at follow-up CT. Of the patients with injuries, 14 (18%) had hyperdense hematomas on the non-contrast studies that became isodense after IV administration of contrast material. These hematomas generally were small and posed an immediate threat to life in only one patient (0.5% of all subjects). In 13% of patients with injury (5% of the total), the additional information did influence treatment planning (surgery in two and intensive conservative treatment in eight). Compared with conventional contrast scanning, the combined non-contrast-contrast technique increased the scanning time only by about 5 1/2 min, but it improved the sensitivity and accuracy of CT in detecting visceral injuries from 74% and 84% to 92% and 91%, respectively (p less than or equal to .003 and p less than or equal to .04). Although contrast-enhanced scanning alone accurately depicts visceral injuries requiring surgical treatment, the incorporation of a non-contrast sequence can detect a subgroup of patients who require intensive conservative management with bed rest and close observation. This additional information can be obtained expeditiously, with minimal additional effort or intervention. The use of non-contrast scanning alone is not recommended.

Abdominal Injuries↗
PubMed1985

Analysis of the cardiovascular effects of co-derocrine (Hydergine).

The antihypertensive effect of co-dergocrine (Hydergine) has previously been thought to be due to alpha-adrenoceptor blockade and/or an action exerted in the CNS. The present experiments do not support this view. The doses necessary to inhibit vasoconstrictor responses to phenylephrine and noradrenaline by 50% in anaesthetized cats and dogs are 10-50 times that which lowers blood pressure in these species by 30 mmHg. Despite the fact that co-dergocrine is a potent alpha-adrenoceptor antagonist in isolated tissues (pA2: 8.4-9.4), its activity in vivo is too weak to contribute significantly to its effect on blood pressure. Slow intravertebral artery infusion of 10 micrograms/kg co-dergocrine produces a smaller blood pressure fall in the dog than intravenous infusion of the same dose. The reverse is true for the centrally-acting alpha 2-adrenoceptor stimulant, guanfacine. In addition, efferent splanchnic nerve activity in the cat is not affected by doses up to 100 micrograms/kg i.v. The dose of co-dergocrine depressing nerve activity by 50% is approximately 900 micrograms/kg; the dose of clonidine producing comparable inhibition is 3.4 micrograms/kg i.v. Since falls in blood pressure and heart rate can be obtained with co-dergocrine at a dose of only 10 micrograms/kg i.v., a central action cannot be considered to play a role in the cardiovascular effects of the drug in response to acute administration. Heart rate increases evoked by stimulating the accelerans nerve of ganglion-blocked cats are inhibited dose-dependently by co-dergocrine from a dose of 1 microgram/kg i.v. The drug also depresses pressor responses to stimulation of the lumbar sympathetic outflow in pithed rats. Both effects are prevented by pretreatment with the dopamine receptor antagonist, sulpiride (300 micrograms/kg). Intravenous administration of 10 micrograms/kg co-dergocrine depresses pressor responses to a psychological stimulus or raising the forequarters in conscious dogs, and produces marked falls in blood pressure and heart rate in anaesthetized, baroreceptor-denervated dogs. These effects are also abolished by sulpiride. It is concluded that the cardiovascular responses to acute administration of low doses of co-dergocrine are due to stimulation of prejunctional dopamine receptors.

Adrenergic alpha-Antagonists↗
PubMed1982

Haemodynamic differences in untreated hypertension and hypertension treated with various beta-adrenoceptor antagonists.

1 As a rule, hypertension progresses from an early stage with a high cardiac output (CO) and an inappropriately normal total peripheral resistance (TPR) to later stages with a normal or decreased CO and a high TPR. 2 Low CO and high TPR can be considered detrimental to the blood perfusion in the tissues and organs and thus to their functional and structural integrity. 3 Among beta-adrenoceptor antagonists, some lower blood pressure by reducing CO, thus bringing about a reactive increase in TPR. The result is that, even though blood pressure is reduced, the haemodynamic conditions commanding regional blood flow are qualitatively similar to those in untreated hypertension. To what extent these circumstances may curtail the benefit expected from blood-pressure reduction deserves careful investigation. 4 Pindolol, a beta-adrenoceptor antagonist with an appropriate degree of intrinsic sympathomimetic activity (ISA), lowers blood pressure while lowering TPR and not unduly reducing cardiac performance. These features should on theoretical grounds lead to a greater improvement in the prognosis of hypertension.

Adrenergic beta-Antagonists↗
PubMed1981

A study of beta-adrenoceptors in the guinea pig.

The interaction of isoprenaline with propranolol and pindolol at beta-adrenoceptors in isolated guinea pig atria, trachea and fat cells has been investigated. The affinity constants obtained revealed that in all three preparations both drugs acted as simple competitive antagonists. Although pindolol showed a somewhat greater affinity for atrial receptors than for those in the trachea neither of the antagonists showed any marked selectivity for adrenoceptors in either of these two preparations. In contrast, the affinity of fat cell receptors for either antagonist were markedly and consistently lower than those of the atrial or tracheal adrenoceptors. The theoretical implications of these results are discussed.

Animals↗