Biomedical subjects

P Mulder

Publications and source records attributed to P Mulder.

At least 19 recordsLinked to original sources

PubMed2002

Endovascular photodynamic therapy with aminolaevulinic acid prevents balloon induced intimal hyperplasia and constrictive remodelling.

BACKGROUND AND OBJECTIVE: intimal hyperplasia (IH) and constrictive remodelling are important causes of restenosis following endovascular interventions, such as percutaneous transluminal angioplasty. Photodynamic therapy (PDT) with 5-aminolaevulinic (ALA) may prevent restenosis by cellular depletion and the elimination of cholinergic innervation. STUDY DESIGN/MATERIALS AND METHODS: rats (n=90) were subdivided into 4 main groups. In the experimental group (n=36: 3 replications x 4 doses x 3 examination time-points), ALA was administered (200mg/kg i.v.) 2-3h before balloon injury (BI) of the common iliac artery followed by endovascular illumination with 633nm at either 12.5, 25, 50 or 100J/cm diffuser length (dl BI+PDT group). As control groups served the BI+Light only (LO) group (n=36) that received no ALA, the BI only group (n=9) (BI), and a group (n=9) that received a Sham procedure (Sham group). RESULTS: planimetric analysis showed IH of 0.28+/-0.12mm(2) (BI), 0.27+/-0.12mm(2) (BI+LO at 100J/cmdl) in contrast to 0.02+/-0.02mm(2) after BI+PDT at 100J/cmdl at 16 weeks (p<0.05). In the BI+PDT groups, a light-dose increase of a factor 2 led to an IH decrease of 17% (p<0.05). In the BI and BI+LO groups constrictive remodelling was found, in contrast to BI+PDT treated groups at 16 weeks. The staining of cholinergic innervation of the tunic media of the blood vessel wall in BI+PDT showed no damage at the highest fluence. CONCLUSION: endovascular ALA-PDT prevents IH and constrictive remodelling after BI without damage of cholinergic innervation of the tunica media. The effective light fluence rate in the rat is 50-100J/cmdl.

Aminolevulinic Acid↗

PubMed2002

Emerging concepts of neurohumoral modulation in the treatment of congestive heart failure.

The angiotensin converting enzyme (ACE), endothelin (ET) converting enzyme (ECE) and neutral endopeptidase (NEP) are all zinc-metallopeptidases expressed in almost all the organs, such as heart, vessels and kidneys. While ACE and ECE are respectively involved in the transformation of angiotensin I and Big-ET into angiotensin II and ET-1 respectively, which possess vasoconstrictor and mitogenic properties, NEP is involved in the degradation of atrial natriuric factor (ANF), which possesses vasorelaxant, diuretic/natriuretic and antihypertrophic properties. These three systems are activated in heart failure and modulate the progression of heart failure. This article will discuss preliminary date concerning simultaneous inhibition of ACE, ECE and/or NEP and their therapeutic potential interest in the treatment of heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2001

Thermal reduction of 7H-benz[d,e]anthracen-7-one and related ketones under hydrogen-transfer conditions.

In the presence of hydrogen donor solvents and at elevated temperatures, aromatic ketones can be selectively deoxygenated to the corresponding hydroaromatic compounds. The kinetics for reduction of 7H-benz[d,e]anthracen-7-one (benzanthrone, 6) into 7H-benz[d,e]anthracene (benzanthrene, 1) in 9,10-dihydroanthracene (3) solvent has been investigated in detail. The relatively slow hydrogenation of 6 is due to reversibility of the initial hydrogen-transfer step according to a reverse radical disproportionation (RRD). The dynamics could well be rationalized using the energetics of species computed by density functional theory (DFT). The application of hydrogen donors such as 1 as a hydrogen-transfer agent, although favorable in terms of a low benzylic carbon-hydrogen bond dissociation enthalpy, is limited due to the slow self-hydrogenation, which in case of 1 gives 5,6-dihydro-4H-benz[d,e]anthracene (7).

Journal Article↗

PubMed2001

Oxygen-carbon bond dissociation enthalpies of benzyl phenyl ethers and anisoles. An example of temperature dependent substituent effects.

For some time it has been assumed that the direction and magnitude of the effects of Y-substituents on the Z-X bond dissociation enthalpies (BDE's) in compounds of the general formula 4-YC(6)H(4)Z-X could be correlated with the polarity of the Z-X bond undergoing homolysis. Recently we have shown by DFT calculations on 4-YC(6)H(4)CH(2)-X (X = H, F, Cl, Br) that the effects of Y on CH(2)-X BDE's are small and roughly equal for each X, despite large changes in C-X bond polarity. We then proposed that when Y have significant effects on Z-X BDE's it is due to their stabilization or destabilization of the radical. This proposal has been examined by studying 4-YC(6)H(4)O-X BDE's for X = H, CH(3), and CH(2)C(6)H(5) both by theory and experiment. The magnitudes of the effects of Y on O-X BDE's were quantified by Hammett type plots of DeltaBDE's vs sigma(+) (Y). Calculations reveal that changes in O-X BDE's induced by changing Y are large and essentially identical (rho(+) = 6.7-6.9 kcal mol(-)(1)) for these three classes of compounds. The calculated rho(+) values are close to those obtained experimentally for X = H at ca. 300 K and for X = CH(2)C(6)H(5) at ca. 550 K. However, early literature reports of the effects of Y on O-X BDE's for X = CH(3) with measurements made at ca. 1000 K gave rho(+) approximately 3 kcal mol(-)(1). We have confirmed some of these earlier, high-temperature O-CH(3) BDE's and propose that at 1000 K, conjugating groups such as -OCH(3) are essentially free rotors, and no longer lie mainly in the plane of the aromatic ring. As a consequence, the 298 K DFT-calculated DeltaBDE for 4-OCH(3)-anisole of -6.1 kcal mol(-)(1) decreases to -3.8 kcal mol(-)(1) for free rotation, in agreement with the ca. 1000 K experimental value. In contrast, high-temperature O-CH(3) DeltaBDE's for three anisoles with strongly hindered substituent rotation are essentially identical to those that would be observed at ambient temperatures. We conclude that substituent effects measured at elevated temperatures may differ substantially from those appropriate for 298 K.

Journal Article↗

PubMed2001

Pulmonary endothelinergic system in experimental congestive heart failure.

OBJECTIVES: Endothelin-1 (ET-1), plays an important role in the pathophysiology of CHF and the pulmonary endothelium is an early hemodynamic target in diastolic left ventricular dysfunction. Therefore we hypothesized that the lung is a main source of humoral endothelin in CHF and that its secretion is proportional to the degree of heart failure. METHODS AND RESULTS: We used rats with coronary artery ligation as an experimental model of either compensated or decompensated heart failure, depending on infarct size. Reverse transcriptase polymerase chain reaction (RT-PCR) revealed that in the lung, the expression of preproET-1 mRNA was higher in decompensated HF than in control and compensated HF rats (P<0.001). Run-on assay demonstrated that ET-1 overexpression is regulated at a transcriptional level (P<0.01). In contrast, there was no change in ET-1 mRNA expression in aortae, left ventricular myocardium and skeletal muscle. The expression of endothelin-converting enzyme (ECE)-1 mRNA was not modified and the expression of ET(B) receptor mRNA in the congestive lung was significantly lower than in control and compensated HF rats (P<0.0001), while the expression of ET(A) receptor mRNA did not differ between groups. The lung and plasma ET-1 peptide levels were respectively 4.2 and 9 fold higher in the rats with decompensated HF than in control rats (P<0.05; P<0.0001). Organoculture experiments showed that the lung ET-1 peptide secretion level in rats with decompensated HF was higher than that in control rats (P<0.01). In contrast, there was no change in ET-1 peptide secretion by the left ventricular myocardium and skeletal muscle. In plasma of rats with decompensated HF, the rate of bigET-1 conversion to ET-1 was 22%. ET-1 peptide was also present in the pleural effusion of decompensated heart failure. Plasma ET-1 concentration was significantly correlated with upstream markers of left ventricular diastolic dysfunction, with the expression of preproET-1 mRNA in the lung, with lung and pleural ET-1 concentration and with the expression ratio of ET-1/ET(B) receptor mRNA. CONCLUSION: Taken together, these data suggest that overexpression of ET-1 and down-regulation of ET(B) receptors in the lung are determinants of circulating endothelin in CHF. As a corollary, increased plasma endothelin may provide evidence of pulmonary endothelial dysfunction in CHF.

Analysis of Variance↗

PubMed2001

Randomized clinical trial of cryotherapy versus laser photocoagulation for retinopexy in conventional retinal detachment surgery.

PURPOSE: To investigate whether the method of retinopexy influences the visual recovery rate and the breakdown of the blood-ocular barrier after conventional retinal detachment surgery. METHODS: Forty-eight patients (48 eyes) with primary rhegmatogenous retinal detachment entered into the study. All eyes were phakic, had an attached macula, and were scheduled for conventional scleral buckling surgery. Patients were randomly assigned to have either laser or cryotherapy for retinopexy. All visual acuity and flare measurements were performed by a masked observer. The interventional procedure was cryopexy at the time of scleral buckling surgery or postoperative (4 weeks) laser photocoagulation. Visual acuity testing with ETDRS chart and aqueous flare measurement with laser flare photometry were performed by a masked observer at standard intervals: preoperatively and 1 day, 7 days, 4 weeks, and 10 weeks postoperatively. Analysis of covariance by multiple linear regression was used for statistical evaluation. RESULTS: Postoperative flare values from patients receiving cryotherapy were significantly higher at each measurement point in time (P < or =.001). The visual recovery was slower in the patients receiving cryotherapy (1 week, P =.003; 4 weeks, P =.03; 10 weeks, P =.081). CONCLUSION: Laser flare photometry proved sufficiently sensitive to quantify an increase in aqueous flare after limited external retinal cryotherapy. Postoperative flare, as a measure of blood-ocular barrier breakdown, was significantly higher and visual recovery slower in the cryotherapy group. Visual acuity after 10 weeks was not significantly different between both groups.

Blood-Retinal Barrier↗

PubMed2001

Endothelin antagonism in experimental ischemic heart failure: hemodynamic, structural and neurohumoral effects.

Heart failure is characterized both by an activation of the endothelin system and an increased vasoconstrictor contractile response to the peptide. Given its pharmacological profile, it is likely that endothelin (ET-1) plays a deleterious role in the development of heart failure, and that blockers of the endothelin system are beneficial in this disease. Indeed, in rats with heart failure, ET(A) and dual ET(A)-ET(B) receptor antagonists reduce arterial pressure as well as left ventricular end diastolic pressure. The same antagonists also prevent the degradation of left ventricular function, as evidenced by the increased left ventricular fractional shortening and wall thickening. ET(A) and ET(A)-ET(B) antagonists also reduce LV dilatation and LV fibrosis, but do not affect LV hypertrophy. Moreover, comparison between selective ET(A) and combined ET(A)-ET(B) antagonists reveal no differences in terms of their effects on blood pressure, LV hemodynamics or remodeling. However, only combined ET(A)-ET(B) antagonists significantly decreased heart rate. ET(B) antagonists alone do not affect blood pressure or LV hemodynamics, but reduce LV fibrosis. With regard to survival, we have shown that long term treatment with the dual ET(A)-ET(B) antagonist bosentan increased survival to the same extent as an angiotensin converting enzyme inhibitor. However, the effect of selective ET(A) antagonists on survival is more controversial, since we found that the non-peptide ET(A) antagonists LU 135252 did not affect survival of rats with myocardial infarction, while others have shown that the peptide ET(A) antagonist BQ-123 increased survival in the same model. These conflicting data regarding the efficacy of selective ET(A) vs dual ET(A)-ET(B) blockade points out the need for controlled long term studies comparing the effects of theses two pharmacological approaches on survival.

Animals↗

PubMed2001

Carbohydrate metabolism during long-term growth hormone treatment in children with short stature born small for gestational age.

OBJECTIVE: To assess possible side-effects of long-term continuous growth hormone (GH) treatment on carbohydrate (CH) metabolism in children with short stature born small for gestational age. DESIGN: In a prospective, randomised double-blind, dose-response multicentre trial, the effect of GH treatment on CH metabolism was evaluated, comparing two GH dosages [3 vs. 6 IU/(m(2) body surface.day)]. PATIENTS: Seventy-eight children with short stature (height SD-score < - 1.88) born small for gestational age (birth length SD-score < - 1.88) being all prepubertal with a mean (SD) chronological age of 7.3 (2.2) years before start of treatment. MEASUREMENTS: Glucose and insulin concentrations during oral glucose tolerance tests (OGTTs) and glycosylated haemoglobin (HbA(1c)) were measured before and during 6 years of GH treatment. RESULTS: Before treatment, the glucose response to oral glucose after 120 min was in six of the 78 children (8%) above 7.8 mmol/l but below 11.1 mmol/l, indicating impaired glucose tolerance (IGT), whereas after 6 years of GH treatment, IGT was found in 4% of the children. None of the children developed diabetes mellitus. Mean fasting glucose levels had increased significantly by 0.5 mmol/l after 1 year of GH treatment, without a further increase thereafter. The 2-h area under the curve adjusted for fasting levels (AUCab) for glucose and the HbA(1c) levels were lower after 6 years of GH treatment compared to baseline. During GH treatment, all HbA(1c) levels were in the normal range. In contrast to the effects on glucose levels, GH treatment induced considerably higher fasting insulin levels and glucose-stimulated insulin levels. The increase in AUCab for insulin occurred particularly during the first year of treatment, whereas the fasting insulin levels showed a further increase from one to six years. As a result, the 30- and 120-min ratios of insulin to glucose were higher during GH treatment compared to the start of treatment. The children who remained prepubertal during the entire study period showed similar patterns in glucose and insulin levels compared to the children who entered puberty. None of the observed changes were different between the GH dosage groups. CONCLUSIONS: Continuous GH treatment during 6 years in children with short stature born small for gestational age has no adverse effects on glucose levels, even with dosages up to 6 IU/(m(2) d). However, as has been reported in other patient groups, GH treatment induces higher fasting insulin levels and glucose-stimulated insulin levels, indicating relative insulin resistance. Since the consequences of long-term hyperinsulinism during childhood are unknown, careful follow-up of these GH-treated children born small for gestational age is required.

Area Under Curve↗

PubMed2001

Fluticasone propionate aqueous nasal spray reduces inflammatory cells in unchallenged allergic nasal mucosa: effects of single allergen challenge.

BACKGROUND: Topical corticosteroid therapy reduces symptoms and nasal mucosal inflammatory cells in patients with allergic rhinitis. Usually patients are advised to start their medication (1 week) before the beginning of the pollen season. The effect of pretreatment with a topical corticosteroid on unchallenged nasal mucosa is not well documented. OBJECTIVES: The purpose of this study was to investigate, in a double-blind, placebo-controlled study, the effect of 6 weeks' pretreatment with 200 microg twice daily fluticasone propionate on nasal symptoms and inflammatory cell numbers after nasal allergen provocation in patients with seasonal allergic rhinitis. METHODS: Nineteen patients with grass pollen-induced allergic rhinitis were treated for a 6-week period out of the grass pollen season. After completing the treatment period, patients were challenged with grass pollen. Nasal mucosal biopsy specimens were taken 5 times in every patient. In nasal mucosa changes in numbers of T cells, B cells, mast cells, eosinophils, macrophages, and Langerhans' cells were investigated. RESULTS: After 4 weeks of treatment but before allergen provocation, significantly fewer epithelial Langerhans' cells, macrophages, mast cells, T cells, and eosinophils were found in the fluticasone propionate group compared with those found in the placebo group. In the lamina propria significantly fewer Langerhans' cells and eosinophils were found in the fluticasone propionate group. Cell influx in nasal mucosa after allergen provocation was significantly inhibited in the fluticasone propionate group compared with that in the placebo group for epithelial Langerhans' cells, mast cells, macrophages, and T cells and for lamina propria eosinophils, mast cells, Langerhans' cells, macrophages, and T cells. CONCLUSIONS: Fluticasone propionate is effective in reducing early- and late-phase nasal symptoms. Topical corticosteroid treatment reduces inflammatory cells in unchallenged nasal mucosa.

Administration, Intranasal↗

PubMed2001

Effects of combination of low doses of angiotensin-converting enzyme inhibitor and diuretics on renal function in spontaneously hypertensive rats: comparison between acute and chronic treatment.

The goal of this study was to assess the effect of acute or chronic treatment with S5590, a combination of the angiotensin-converting enzyme inhibitor perindopril (0.76 mg/kg/day) and the diuretic indapamide (0.24 mg/kg/day) on renal function in spontaneously hypertensive rats with moderate renal injury. Renal function was evaluated in conscious rats by clearance methods using labelled inulin and PAH, after catheterisation of the carotid artery, jugular vein and bladder. Both acute and chronic treatment normalised renal vascular resistance, although the effect on blood pressure was more marked after chronic than after acute treatment. Although acute treatment with S5590 increased glomerular filtration rate and renal blood flow, chronic treatment did not affect these parameters. Diuresis and natriuresis were only slightly modified and the results suggest a marked renal vasodilatation. In conclusion, the maintenance of renal function after chronic treatment, in a setting of normalisation of arterial pressure, suggest that such a combined treatment may exert marked renal functional protective effects in hypertension.

Animals↗

PubMed2000

Selective endothelin-A versus combined endothelin-A/endothelin-B receptor blockade in rat chronic heart failure.

BACKGROUND: The relative efficacy of endothelin-A (ET(A)) receptor blockade versus combined ET(A)-ET(B) receptor blockade in chronic heart failure (CHF) is still largely unknown. METHODS AND RESULTS: We compared, in a rat model of CHF (coronary ligation), the hemodynamic and structural effects of 1 month of treatment with the ET(A) antagonist ABT-627 (5 mg x kg(-1) x d(-1)), the ET(B) antagonist A-192621 (30 mg x kg(-1) x d(-1)) or a combination of the 2 drugs. Doses were chosen for their capacity to block the pressor response to ET-1 (for ET(A) blockade) or the depressor responses to sarafotoxin S6c or ET-1 (for ET(B) blockade). ET(A) and combined ET(A)-ET(B) blockade reduced systolic blood pressure to the same extent, whereas ET(B) blockade had no effect. In contrast, only combined ET(A)-ET(B) blockade significantly reduced heart rate. Both ET(A) and combined ET(A)-ET(B) blockade, but not ET(B) blockade alone, increased left ventricular (LV) fractional shortening and wall thickening and reduced LV end-diastolic pressure, as well as LV end-diastolic and end-systolic volumes. However, all treatments (including ET(B) blockade) decreased LV collagen accumulation. CONCLUSIONS: The chronic blockade of both ET(A) and ET(B) receptors improved systemic hemodynamics, as well as LV function and remodeling, to the same extent as ET(A) receptor blockade alone. However, only combined ET(A)-ET(B) receptor blockade decreased heart rate. Whether this differential effect on heart rate affects the long-term outcome after treatment with ET(A) or mixed ET(A)-ET(B) antagonists in CHF remains to be determined.

Animals↗

PubMed2000

Improvement of endothelial function by chronic angiotensin-converting enzyme inhibition in heart failure : role of nitric oxide, prostanoids, oxidant stress, and bradykinin.

BACKGROUND-Chronic heart failure (CHF) impairs the endothelium-dependent, flow-mediated dilation (FMD) of small arteries. However, whether chronic angiotensin-converting enzyme (ACE) inhibition affects the impairment of FMD in CHF is unknown. We investigated the effects of long-term ACE inhibition on the FMD of peripheral arteries in rats with CHF and the mechanism(s) involved. METHODS AND RESULTS-FMD was assessed in isolated, perfused gracilis muscle arteries from sham-operated, and untreated or ACE inhibitor-treated (perindopril 2 mg. kg(-1). day(-1) for 10 weeks) rats with CHF (coronary artery ligation). The role of nitric oxide (NO), prostaglandins, and free radicals was assessed by pretreating the vessels with the NO synthase inhibitor N(W)-nitro-L-arginine, the cyclooxygenase inhibitor diclofenac, or the free radical scavenger N-2-mercaptopropionyl-glycine (MPG). Endothelial NO synthase mRNA expression was determined by reverse transcriptase polymerase chain reaction. In animals with hemodynamic and echographic signs of CHF, FMD was converted into vasoconstriction, and this was prevented by ACE inhibition. FMD of arteries from sham-operated or ACE inhibitor-treated CHF rats was abolished by N(W)-nitro-L-arginine. In untreated CHF rats, FMD was increased by diclofenac and MPG. In contrast, in arteries from ACE inhibitor-treated rats, neither diclofenac nor MPG affected FMD. In parallel, ACE inhibition prevented the reduction of endothelial NO synthase mRNA by CHF. CONCLUSIONS-In CHF, ACE inhibition normalized NO-dependent dilatation and suppressed the production of vasoconstrictor prostanoid(s), resulting in improved FMD. The improvement of FMD might contribute to the beneficial effects of ACE inhibition during CHF.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Long-term effects of growth hormone treatment on growth and puberty in patients with chronic renal insufficiency.

Several prospective trials have shown that recombinant human growth hormone (GH) accelerates growth significantly during the first years of therapy, but the effects of long-term GH therapy with regard to long-term growth response and safety have not yet been established. Forty-five Dutch prepubertal children [28 boys, 17 girls, mean (SD) age 7.8 (3.4) years] with chronic renal insufficiency (CRI) and severe growth retardation started GH therapy between 1988 and 1991 within one of the randomized Dutch trials. Long-term GH therapy, in this study a maximum of 8 years, resulted in a sustained and significant improvement of height standard deviation score (SDS) compared with baseline values (P<0.001). The mean height SDS reached the lower end (-2 SDS) of the normal growth chart after 3 years of GH therapy. During the following years the mean height SDS gradually increased, thereby approaching the mean target height SDS after 6 years of GH therapy. Three factors were significantly associated with the height SDS after 4 years of GH therapy: height SDS at the start (+) of therapy, age at the start of therapy (-), and the duration of dialysis treatment (-). Bone maturation did not accelerate during long-term GH therapy. Children on a conservative regimen at the start of GH therapy had no accelerated deterioration of renal function during 6 years of GH therapy. The average daily GH dose administered over the years had no significant influence on the glomerular filtration rate after 4 years. GH therapy had no adverse effects or significant effect on parathyroid hormone concentration, nor were there any radiological signs of renal osteodystrophy. Puberty started at a median age, within the normal range, of 12.4 years in boys and 12.0 years in girls, respectively. Long-term GH therapy leads to a sustained improvement in height SDS in children with growth retardation secondary to CRI, resulting in a normalization of height in accordance with their target height SDS, without evidence of deleterious effects on renal function or bone maturation. A GH dosage of 4 IU/m2 per day appears efficient and safe. Our long-term data show that final height will be within the normal target height range when GH therapy is continued for many years.

Child↗

PubMed2000

Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency.

To assess the effects of long-term continuous GH treatment on body composition, blood pressure (BP), and lipid metabolism in children with short stature born small for gestational age (SGA), body mass index (BMI), skinfold thickness measurements, systemic BP measurements, and levels of blood lipids were evaluated in 79 children with a baseline age of 3-11 yr with short stature (height SD-score, < -1.88) born SGA (birth length SD-score, < -1.88). Twenty-two of the 79 children were GH deficient (GHD). All children participated in a randomized, double-blind, dose-response multicenter GH trial. Four- and 6-yr data were compared between two GH dosage groups (3 vs. 6 IU/m2 body surface/day). Untreated children with short stature born SGA are lean (mean BMI SD-score, -1.3; mean SD-score skinfolds, -0.8), have a higher systolic BP (SD-score, 0.7) but normal diastolic BP (SD-score, -0.1), and normal lipids (total cholesterol, 4.7 mmol/L; low-density lipoprotein, 2.9 mmol/L; high-density lipoprotein, 1.3 mmol/L) compared with healthy peers. During long-term continuous GH treatment, the BMI normalized without overall changes in sc fat compared with age-matched references, whereas the BP SD-score and the atherogenic index decreased significantly. Although the mean 6-yr increase in height SD-score was significantly higher in the children receiving GH treatment with 6 IU/m2 x day (2.7) than in those receiving treatment with 3 IU/m2 day (2.2), no differences in the changes in BMI, skinfold measurements, BP, and lipids were found between the GH dosage groups. The pretreatment SD-scores for BMI, skinfold, and BP, as well as the lipid levels, were not significantly different between GHD and non-GHD children, but after 6 yr of GH treatment the skinfold SD-score and BP SD-score had decreased significantly more in the GHD than in the non-GHD children. Our data indicate that GH treatment has at least up to 6 yr positive instead of negative effects on body composition, BP, and lipid metabolism. In view of the reported higher risk of cardiovascular diseases in later life in children born SGA, further research into adulthood remains warranted.

Blood Pressure↗

PubMed1999

Exercise improves flow-mediated vasodilatation of skeletal muscle arteries in rats with chronic heart failure. Role of nitric oxide, prostanoids, and oxidant stress.

BACKGROUND: Flow-mediated dilatation (FMD) of the peripheral arteries may be impaired in chronic heart failure (CHF), and this could contribute to the increased peripheral resistance and exercise intolerance that occur with this disease. Physical exercise improves the FMD of large conduit arteries in CHF, but whether a similar impairment also occurs in smaller arteries is unknown. The mechanisms of the changes in FMD after CHF or exercise are also unknown. METHODS AND RESULTS: FMD was assessed in isolated, perfused, and preconstricted gracilis muscle arteries from sham-operated rats or CHF rats (coronary artery ligation) who were either sedentary or exercised (30-minute swimming period twice a day for 10 weeks, starting 7 days after ligation). In animals with hemodynamic and echographic signs of CHF, FMD was abolished and converted into vasoconstriction (percent change in diameter after 370 microL/min flow: sham, 42+/-5%; CHF, -4+/-3%; P<0.05). Exercise partially restored FMD (18+/-3%; P<0.05 versus CHF). In sham rats, FMD was abolished by the nitric oxide-synthase inhibitor Nomega-nitro-L-arginine (L-NA) but unaffected by the cyclooxygenase inhibitor diclofenac or the free radical scavenger N-(2-mercaptopropionyl)-glycine (MPG). In arteries from sedentary CHF rats, FMD was not modified by L-NA, but it was partially restored by diclofenac or MPG. In exercised CHF rats, FMD was abolished by L-NA and only moderately improved by diclofenac or MPG. Likewise, endothelial nitric oxide synthase mRNA expression (determined by reverse transcription polymerase chain reaction at the level of the gracilis muscle) was reduced by CHF, and this was prevented by exercise. CONCLUSIONS: CHF abolishes the FMD of small arteries by impairing the nitric oxide pathway, increasing oxidant stress, and releasing a prostanoid-contracting factor. Exercise partially restores FMD by increasing expression of endothelial nitric oxide synthase and preventing the production of vasoconstrictor prostanoids and free radicals. Such restoration of FMD might contribute to the increase in exercise capacity after physical exercise in CHF.

Animals↗

PubMed1999

Follow-up of functionally lost eyes after vitrectomy and silicone oil tamponade for tractional retinal detachment.

BACKGROUND: Is there any association between, on the one hand, retention or removal of silicone oil or any specific ocular finding in patients with functionally lost eyes after vitrectomy and silicone oil tamponade for tractional retinal detachment and, on the other, a greater chance of preservation of the eye? This information is important in deciding whether to remove silicone oil, as well as in counseling patients about their individual chances of preserving their eye. METHODS: Seventy-three consecutive patients with a functionally lost eye with a minimum follow-up of 3 years were retrospectively studied. The relation between the variables at study entry or the removal of silicone oil during the follow-up period and a subsequent intervention (enucleation, evisceration or conjunctival cover with a scleral shell) were tested for statistical significance with Cox proportional hazards analysis. RESULTS: The absence or removal of silicone oil was not associated with a greater chance of finally preserving the eye. Nor could we identify other factors which predicted better chances of preservation. CONCLUSION: The notion that functionally lost eyes after treatment with vitrectomy and silicone oil tamponade for complicated tractional retinal detachment have better chances of preservation of the eye without silicone oil is not supported by our study.

Blindness↗

PubMed1999

Topographic anatomy of the eyelids, and the effects of sex and age.

AIMS: To describe the effects of sex and age on eyeball, eyelid, and eyebrow position. METHODS: A cross sectional cohort study was performed in which both eyes of 320 normal subjects aged between 10 and 89 years were included. Of each 10 year age cohort, there were 20 men and 20 women. Frontal, as well as lateral, slides were taken of both eyes. On projected slides, a reference line through the medial canthi and vertical lines through the pupil centre and the lateral canthus were constructed. Using these lines, we measured the size of the horizontal eyelid fissure, the distance from the reference line to the pupil centre and to the lateral canthus, the distance between the pupil centre and the upper and lower eyelid margin, and the distance between the upper eyelid margin and the skin fold and eyebrow. On lateral slides, the distance between the lateral canthus and the anterior corneal surface was measured. RESULTS: Between the ages of approximately 12 and 25 years, the horizontal eyelid fissure lengthened 3 mm, while the position of other eyelid structures remained virtually unchanged. Between the average ages of 35 and 85 years, the horizontal eyelid fissure gradually shortened again by about 2.5 mm. Meanwhile, the distance between the lateral canthal angle and the anterior corneal surface decreased almost 1.5 mm. Aging caused an increase of the distance between the pupil centre and the lower eyelid of about 1 mm in men, and 0.5 mm in women. Aging also caused a higher skin crease and raised eyebrows in men and women, but it did not affect the position of the pupil centre and the lateral canthus. Men showed an 0.7 mm larger horizontal eyelid fissure than women. In women, however, the eyebrows were situated about 2.5 mm higher than in men. CONCLUSION: Aging mainly affects the size of the horizontal eyelid fissure, which lengthens by about 10% between the ages of 12 and 25, and shortens by almost the same amount between middle age and old age. Aging causes sagging of the lower eyelid, especially in men, and a higher skin fold and eyebrow position in both sexes. Aging does not affect the position of the eyeball proper, or of the lateral canthus.

Adolescent↗

PubMed1999

Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial.

The growth-promoting effect of continuous GH treatment was evaluated over 5 yr in 79 children with short stature (height SD score, less than -1.88) born small for gestational age (SGA; birth length SD score, less than -1.88). Patients were randomly and blindly assigned to 1 of 2 GH dosage groups (3 vs. 6 IU/m2 body surface-day). GH deficiency was not an exclusion criterium. After 5 yr of GH treatment almost every child had reached a height well within the normal range for healthy Dutch children and in the range of their target height SD score. Only in children who remained prepubertal during the study period was the 5-yr increase in height SD score (HSDS) for chronological age significantly higher in the study group receiving 6 compared to 3 IU GH/m2 x day. Remarkably, the 5-yr increment in HSDS for chronological age was not related to spontaneous GH secretion, maximum GH levels after provocation, or baseline insulin-like growth factor I levels. GH treatment was associated with an acceleration of bone maturation regardless of the GH dose given. The HSDS for bone age and predicted adult height increased significantly. GH treatment was well tolerated. In conclusion, our 5-yr data show that long term continuous GH treatment at a dose of 3 or 6 IU/m2 x day in short children born SGA results in a normalization of height during childhood followed by growth along the target height percentile.

Aging↗