A single-center, open-label, three-way crossover study was conducted in 24 healthy subjects to assess (1) the bioequivalence of a combined lamivudine 150 mg/zidovudine 300 mg tablet relative to the separate brand-name components administered concurrently and (2) the effect of food on the bioavailability of the drugs from the combination tablet. The subjects were randomly assigned to receive each of the following three treatments, separated by a 5- to 7-day washout period: one lamivudine/zidovudine combination tablet after an overnight fast, one lamivudine 150 mg tablet and one zidovudine 300 mg tablet simultaneously after an overnight fast, or one lamivudine/zidovudine combination tablet 5 minutes after completing a standardized high-fat breakfast (67 g fat, 58 g carbohydrate, and 33 g protein). Serial blood samples were collected up to 24 hours postdose for the determination of lamivudine and zidovudine plasma concentrations. Standard pharmacokinetic parameters were estimated. Treatments were considered bioequivalent if 90% confidence intervals for the ratio of least squares (LS) means for the lamivudine and zidovudine area under the plasma concentration-time curve (AUC infinity) and maximum observed plasma concentration (Cmax) fell entirely within 0.80 to 1.25 for log-transformed parameters. The combined lamivudine/zidovudine tablet was bioequivalent in the extent (AUC infinity) and rate of absorption (Cmax and time of Cmax [tmax]) to the individual brand-name drug components administered concurrently under fasted conditions. Geometric LS mean ratios and 90% confidence intervals for AUC infinity and Cmax were 0.97 (0.92, 1.03) and 0.94 (0.84, 1.06), respectively, for lamivudine and 0.99 (0.91, 1.07) and 0.97 (0.82, 1.15), respectively, for zidovudine. The extent of absorption of lamivudine and zidovudine from the combination tablet was not altered by administration with meals, indicating that this formulation may be administered with or without food. However, food slowed the rate of absorption, delayed the tmax, and reduced the Cmax of lamivudine and zidovudine. These changes were not considered clinically important. All formulations were well tolerated under fasted and fed conditions.

Absorption↗

PubMed1999

Providing quality care in childhood cancer survivorship: learning from the past, looking to the future.

As we move into the 21st century, we are faced with an increasing number of childhood cancer survivors who are living into their middle adult years and beyond. Providing appropriate, comprehensive follow-up care is a challenge for health care providers and one that can be met by developing quality follow-up programs for all childhood cancer survivors. The focus of these programs should be to educate these survivors on strategies to maximize their health and well being. This article discusses the evolution of survivor clinics, strategies for developing a quality program, and the role of nursing in the care of childhood cancer survivors.

Child↗

PubMed1999

Endothelial dysfunction in acute renal failure: role of circulating and tissue endothelin-1.

The kidney is an important target and source of the potent vasoconstrictor and mitogen endothelin-1 (ET-1). However, its exact role in acute renal failure (ARF) remains to be determined. ARF was induced in male Wistar-Kyoto rats (n = 7) in a 2-kidney, 2-clip model of 30-min clamping. Twenty-four hours after clamp release, contractions to angiotensin I (Angl) and II, ET-1, and big ET-1 were studied in isolated aortic and renal artery rings. Endothelium-dependent and -independent relaxations were assessed by acetylcholine and sodium nitroprusside. ET-1 clearance, tissue uptake, plasma levels, and vascular and kidney content were investigated. In addition, ET(A) and Et(B) receptor mRNA expression was determined. Sham-operated animals served as controls (n = 7). In ARF, ET-1 plasma levels and tissue content of the renal artery, the aorta, and the kidney markedly increased (P<0.01). Plasma half-life of radiolabeled 125I-ET-1 was markedly prolonged, whereas 125I-ET-1 tissue uptake decreased in the kidney in ARF. Contractions to AngI and AngII were blunted (P<0.05) and those to KCl were unchanged, whereas vascular responses to big ET-1 and ET-1 were enhanced in the renal artery and also in the aorta in ARF (P<0.05 to 0.001). Correspondingly, ET(A) and Et(B) receptor mRNA expression significantly increased in both vascular beds. In addition, endothelium-dependent relaxation to acetylcholine was diminished and inversely correlated with vascular ET-1 protein levels in the renal artery (r = -0.827, P<0.001) and the aorta (r = -0.812, P<0.001). In conclusion, the present study demonstrates that increase of circulating and tissue ET-1 protein levels and ET(A) and Et(B) receptor gene expression occurs, which induces endothelial dysfunction and enhanced vasoconstriction in different vascular beds in ARF.

Acute Kidney Injury↗

PubMed1999

Allergic contact dermatitis to acrylates in disposable blue diathermy pads.

We report 2 cases of elicitation of allergic contact dermatitis to acrylates from disposable blue diathermy pads used on patients who underwent routine surgery. Their reactions were severe, and took approximately 5 weeks to resolve. Both patients gave a prior history of finger tip dermatitis following the use of artificial sculptured acrylic nails, which is a common, but poorly reported, cause of acrylate allergy. Patch testing subsequently confirmed allergies to multiple acrylates present in both the conducting gel of disposable blue diathermy pads, and artificial sculptured acrylic nails. We advocate careful history taking prior to surgery to avoid unnecessary exposure to acrylates in patients already sensitized.

Acrylates↗

PubMed1999

The advantages of cardiac rehabilitation.

Cardiac rehabilitation is a significant element in recovery from myocardial infarction. An effective programme may reverse arterial damage without the aid of lipid-lowering medication. Benefits can occur for patients three to four years after undertaking a programme.

Follow-Up Studies↗

PubMed1998

Endothelin ETA receptor blockade restores NO-mediated endothelial function and inhibits atherosclerosis in apolipoprotein E-deficient mice.

This study investigated whether endothelin-1 (ET-1), a potent vasoconstrictor, which also stimulates cell proliferation, contributes to endothelial dysfunction and atherosclerosis. Apolipoprotein E (apoE)-deficient mice and C57BL/6 control mice were treated with a Western-type diet to accelerate atherosclerosis with or without ETA receptor antagonist LU135252 (50 mg/kg/d) for 30 wk. Systolic blood pressure, plasma lipid profile, and plasma nitrate levels were determined. In the aorta, NO-mediated endothelium-dependent relaxation, atheroma formation, ET receptor-binding capacity, and vascular ET-1 protein content were assessed. In apoE-deficient but not C57BL/6 mice, severe atherosclerosis developed within 30 wk. Aortic ET-1 protein content (P < 0.0001) and binding capacity for ETA receptors was increased as compared with C57BL/6 mice. In contrast, NO-mediated, endothelium-dependent relaxation to acetylcholine (56 +/- 3 vs. 99 +/- 2%, P < 0.0001) and plasma nitrate were reduced (57.9 +/- 4 vs. 93 +/- 10 micromol/liter, P < 0.01). Treatment with the ETA receptor antagonist LU135252 for 30 wk had no effect on the lipid profile or systolic blood pressure in apoE-deficient mice, but increased NO-mediated endothelium-dependent relaxation (from 56 +/- 3 to 93 +/- 2%, P < 0.0001 vs. untreated) as well as circulating nitrate levels (from 57.9 +/- 4 to 80 +/- 8.3 micromol/liter, P < 0.05). Chronic ETA receptor blockade reduced elevated tissue ET-1 levels comparable with those found in C57BL/6 mice and inhibited atherosclerosis in the aorta by 31% without affecting plaque morphology or ET receptor-binding capacity. Thus, chronic ETA receptor blockade normalizes NO-mediated endothelial dysfunction and reduces atheroma formation independent of plasma cholesterol and blood pressure in a mouse model of human atherosclerosis. ETA receptor blockade may have therapeutic potential in patients with atherosclerosis.

Acetylcholine↗

PubMed1998

Hemodynamic and coronary effects of the endothelin antagonist bosentan in patients with coronary artery disease.

BACKGROUND: Endothelin is a potent endothelium-derived vasoconstrictor peptide with proliferative properties. Elevated levels of the peptide occur in coronary artery disease; however, its pathophysiological role as a regulator of coronary tone and structure is uncertain. Endothelin-receptor antagonists are specific tools to clarify this issue and might be useful in the treatment of coronary artery disease. METHODS AND RESULTS: In a double-blind, placebo-controlled randomized study, we investigated the effects of the ETA/ETB endothelin-receptor antagonist bosentan or placebo on systemic and coronary hemodynamics in 28 patients with angiographically documented stable coronary artery disease by quantitative coronary angiography and an intracoronary Doppler guidewire. Bosentan 200 mg IV decreased systolic blood pressure (P<0. 05), whereas heart rate increased slightly (P<0.05). Coronary diameter increased, particularly in vessels with no or mild angiographic changes (P<0.01). Glycerol trinitrate did not further dilate these segments, whereas coronary diameter increased significantly after nitrate in the placebo group. The increase in coronary diameter after bosentan correlated inversely with plasma LDL-cholesterol levels (P<0.01) in both stenotic and angiographically normal coronary segments. Coronary flow velocity did not change. Bosentan was well tolerated. CONCLUSIONS: Endogenous endothelin exerts a vasoconstrictor tone in epicardial coronary arteries of patients with coronary artery disease, as evidenced by the vasodilation exerted by the combined ETA/ETB endothelin-receptor antagonist bosentan under acute conditions. Bosentan can safely be given to these patients. Hence, further long-term studies are necessary to determine the therapeutic potential of endothelin-receptor antagonists in patients with coronary artery disease.

Antihypertensive Agents↗

PubMed1998

Evidence for linkage to psychosis and cerebral asymmetry (relative hand skill) on the X chromosome.

The hypothesis that psychosis arises as a part of the genetic diversity associated with the evolution of language generates the prediction that illness will be linked to a gene determining cerebral asymmetry, which, from the evidence of sex chromosome aneuploidies, is present in homologous form on the X and Y chromosomes. We investigated evidence of linkage to markers on the X chromosome in 1) 178 families multiply affected with schizophrenia or schizoaffective disorder with a series of 16 markers spanning the centromere (study 1), and 2) 180 pairs of left-handed brothers with 14 markers spanning the whole chromosome (study 2). In study 1, excess allele-sharing was observed in brother-brother pairs (but not brother-sister or a small sample of sister-sister pairs) over a region of approximately 20 cM, with a maximum LOD score of 1.5 at DXS991. In study 2, an association between allele-sharing and degree of left-handedness was observed extending over approximately 60 cM, with a maximum lod score of 2.8 at DXS990 (approximately 20 cM from DXS991). Within the overlap of allele-sharing is located a block in Xq21 that transposed to the Y chromosome in recent hominid evolution and is now represented as two segments on Yp. In one of two XX males with psychosis we found that the breakpoint on the Y is located within the distal region of homology to the block in Xq21. These findings are consistent with the hypothesis that an X-Y homologous determinant of cerebral asymmetry carries the variation that contributes to the predisposition to psychotic illness.

Female↗

PubMed1998

The health care market.

Explore the source record for details and available documents.

Insurance Coverage↗

PubMed1998

The plasminogen activator system in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the plasminogen activator system in women with polycystic ovary syndrome (PCOS). DESIGN: Case-control study. SETTING: A district general hospital in the United Kingdom. PATIENT(S): Eleven women with PCOS and 12 controls. INTERVENTION(S): Venipunctures for assays of the plasminogen activator system. MAIN OUTCOME MEASURE(S): Euglobulin clot lysis times, plasminogen activator inhibitor 1 (PAI-1) activity, fibrinogen, plasminogen, and alpha-2 antiplasmin concentrations in plasma. RESULT(S): Women with PCOS may had a significantly longer euglobulin clot lysis time (mean +/- SD, 389 +/- 164 minutes vs. 220 +/- 110 minutes), a higher PAI-1 activity (mean +/- SD, 19.7 +/- 12 arbitrary units (AU) per mL vs. 10.9 +/- 7.9 AU/mL), and a higher fibrinogen level (mean +/- SD, 4.02 +/- 0.64 g/L vs. 3.15 +/- 0.6 g/L) compared to controls. CONCLUSION(S): Women with the PCOS may have an imbalance in the plasminogen activator system that is tilted toward a reduced production of the proteolytic enzyme plasmin. Systemically, this may increase their risk of cardiovascular disease, but at cellular level in the ovaries, it may result in impaired follicular rupture and anovulation.

Adult↗

PubMed1998

High-resolution video and digital-enhanced differential interference contrast light microscopy of cell division in budding yeast.

Explore the source record for details and available documents.

Cell Cycle↗

PubMed1998

Stimulation of monocyte interleukin-8 by lipid peroxidation products: a mechanism for alcohol-induced liver injury.

Interleukin-8 (IL-8), an inflammatory cytokine that promotes neutrophil accumulation, has been implicated in the pathogenesis of alcoholic liver disease but the mechanism of its production is unknown. The ability of lipid peroxidation products, also implicated in alcoholic liver disease, to stimulate IL-8 production was studied because of their alleged role in alcoholic liver disease. Peroxidized fatty acids (arachidonic and linolenic) as well as microsomal membranes stimulated IL-8 production by peripheral blood monocytes whereas ethanol and acetaldehyde did not. Hydrocortisone (5 microg/ml) prevented the IL-8 stimulation by peroxidized fatty acids. Ethanol-induced lipid peroxidation may secondarily further alcohol-induced liver injury through IL-8 chemotaxis of neutrophils.

Acetaldehyde↗

PubMed1998

Endothelial vasoconstrictor prostanoids, vascular reactivity, and acute renal failure.

The interaction of endothelium-derived vasoconstrictor prostaglandins, the angiotensins (Ang), and the sympathetic nervous system in acute renal failure still remains to be determined. In this study, acute renal failure (ARF) was induced in male Wistar Kyoto rats (N = 7) in a 2K/2C model of 30-minute clamping. Contractions to Ang I and II and norepinephrine (NE) were studied in isolated aortic and renal artery rings 24 hours after clamp release. Sham-operated animals served as controls (N = 7). In ARF, contractions to NE were increased in the aorta and even further enhanced in the renal artery (P < 0.05 to 0.001), whereas contractions to Ang I and II were blunted (P < 0.05). Contractions were inhibited by SQ 30741, a thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist. We conclude that ARF is characterized by abnormal vascular reactivity both in the renal as well as the systemic vasculature that is in part mediated by endothelium-derived vasoconstrictor prostaglandins.

Acute Kidney Injury↗