PubMed Health⌕ Search

Biomedical subjects

J M Ritter

Publications and source records attributed to J M Ritter.

At least 73 records · Page 4Linked to original sources
PubMed1994

Effect of intracardiac repair on biosynthesis of thromboxane A2 and prostacyclin in children with a left to right shunt.

OBJECTIVE: To investigate the effect of intracardiac repair on the abnormal biosynthesis of prostacyclin (PGI2) and thromboxane A2 (TXA2) in children with congenital heart disease and increased pulmonary blood flow. DESIGN: A prospective study with immunoaffinity chromatography and gas chromatography-mass spectrometry to measure the urinary excretion products of PGI2 (2,3-dinor-6-oxo-prostaglandin (PG) F1 alpha (2,3-dinor-6-oxo-PGF1 alpha)) and TXA2 (2,3-dinor-TXB2) before operation, in the first 12-24 h after operation, and at discharge from hospital. SETTING: A supraregional referral centre for patients with congenital heart disease. PATIENTS: 15 patients aged 2 to 60 months (median 7 months) with a left to right shunt who underwent intracardiac repair. RESULTS: The preoperative 2,3-dinor-TXB2 excretion rate was greater than that found previously in a control group of 16 healthy children with a median (range) age of 24 (6-36) months (1159(201) v 592(122) ng/g creatinine in controls, P = 0.006). The excretion rate rose after operation to 9600(3832) ng/g creatinine (P = 0.01) and decreased before discharge to 1071(191) ng/g creatinine (NS), but remained greater than that of the control group (P = 0.014). Before operation 2,3-dinor-6-oxo-PGF1 alpha excretion rates were similar to those of the healthy children (482(68) v 589(95) ng/g creatinine in controls) but increased after operation to 19,668(11,162) ng/creatinine (P = 0.002) and fell at discharge to 1621(245) ng/g creatinine although this was higher than both preoperative and control rates (P = 0.005 and P = 0.0002 respectively). The preoperative ratio of 2,3-dinor-TXB2 to 2,3-dinor-6-oxo-PGF1 alpha excretion was greater than that of the control group (3.2(0.8) v 1.3(0.22) in controls, (P = 0.005)), decreased significantly after operation to 0.9(0.13) (P = 0.016), and changed little, to 0.7(0.12), before discharge. The last two ratios were similar to those in normal children and significantly lower than those before operation (P = 0.004). CONCLUSION: In children with a left to right shunt the ratio of the excretion rates of the metabolites of TXA2 and PGI2 was abnormal before operation, which favoured vasoconstriction and platelet aggregation, but had decreased at discharge from hospital. The increase in excretion of PGI2 metabolites over TXA2 metabolite after intracardiac repair augurs well for pulmonary vascular recovery.

Child, Preschool↗
PubMed1993

Inhibition of nitric oxide synthesis in forearm vasculature of insulin-dependent diabetic patients: blunted vasoconstriction in patients with microalbuminuria.

1. Microalbuminuria is a risk factor for cardiovascular disease in patients with insulin-dependent diabetes mellitus, and may be a marker of microvascular dysfunction including endothelial damage. The purpose of this study was to determine whether vasoconstrictor responses to NG-monomethyl-L-arginine, an inhibitor of endothelium-derived relaxing factor/nitric oxide biosynthesis, differ between healthy subjects and insulin-dependent patients with or without microalbuminuria. 2. Twenty-eight insulin-dependent diabetic patients (14 with normal albumin excretion, 14 with microalbuminuria) were studied under euglycaemic conditions, together with 14 healthy control subjects. Forearm vascular responses to brachial artery infusions of NG-monomethyl-L-arginine, sodium nitroprusside (an endothelium-independent nitrovasodilator) and carbachol (an endothelium-dependent vasodilator) were determined by strain gauge plethysmography. 3. Basal blood flow and vasodilator responses were similar in each group. NG-Monomethyl-L-arginine reduced blood flow by 41.3 +/- 2.3% (mean +/- SEM) in healthy control subjects, 34.0 +/- 3.4% in diabetic patients without microalbuminuria and 29.2 +/- 2.0% in diabetic patients with microalbuminuria. Diabetic patients differed from healthy subjects (P = 0.005), due to a difference between control subjects and microalbuminuric diabetic patients (P < 0.001). NG-Monomethyl-L-arginine did not influence nitroprusside responses but reduced carbachol responses in control subjects and normoalbuminuric diabetic patients but not in microalbuminuric diabetic patients. 4. These results provide evidence of abnormal endothelium-derived relaxing factor/nitric oxide biosynthesis in insulin-dependent diabetic patients with microalbuminuria.

Adult↗
PubMed1993

Inhibition by nitroprusside of platelet calcium mobilization: evidence for reduced sensitivity to nitric oxide in essential hypertension.

OBJECTIVE: Although platelets from patients with moderate hypertension are abnormally sensitive to agonist-induced aggregation, their sensitivity to antagonists is not known. Nitric oxide (NO) is an endogenous antagonist of platelet function. The objective of this study was to determine whether platelet sensitivity to the inhibitory activity of sodium nitroprusside, a donor of NO, is abnormal in hypertension. DESIGN AND METHODS: Untreated patients with uncomplicated essential hypertension (mean arterial pressure > 120 mmHg) were studied. The rise in cytosolic calcium in response to 9,11-deoxy-11 alpha, 9 alpha-epoxymethanoprostaglandin F2 alpha (U46619, a thromboxane mimetic) was measured in fura-2-loaded platelets from 20 patients and 15 normotensive healthy subjects. Inhibition by sodium nitroprusside was measured in a further group of 14 patients and 20 normotensive subjects. RESULTS: Basal cytosolic calcium concentration and the rise in this parameter induced by U46619 were significantly greater in platelets from hypertensive patients than in those from normotensive controls. The mean half-maximal inhibitory concentration of nitroprusside to calcium mobilization induced by 3 mumol/l U46619 was 3.1-fold greater in platelets from hypertensive patients than in those from controls (95% confidence interval 1.6-6.0). CONCLUSION: The sensitivity of platelets to nitroprusside is reduced in essential hypertension. This reduced sensitivity to NO might influence the risk of arterial thrombosis in hypertensives.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Comparison of angiotensin-converting enzyme inhibition with angiotensin II receptor antagonism in the human forearm.

The object of this study was to differentiate losartan, an AT1-selective angiotensin II (ANG II) receptor antagonist, from enalapril, an angiotensin-converting enzyme (ACE) inhibitor, by measuring forearm vascular responses to AI, AII, and bradykinin. Eight healthy men were studied in a randomised, 4-period crossover study in which placebo, enalapril (10 mg), losartan (20 mg) and losartan (100 mg) were given double-blind on separate occasions. Forearm blood flow was measured by venous occlusion plethysmography during sequential infusions of ANG I, ANG II, and bradykinin into the brachial artery 4-6 h after dosing. Analysis of variance for repeated measures indicated that losartan inhibited constriction to ANG I and ANG II (both p < 0.02) in a dose-dependent manner without significantly influencing vasodilator responses to bradykinin. Enalapril (10 mg) inhibited AI similarly to losartan 100 mg without significantly influencing responses to angiotensin II, and augmented vasodilator responses to bradykinin (p < 0.0001). In human forearm vasculature, oral losartan (20-100 mg) inhibits vasoconstriction to ANG I and ANG II without significantly influencing bradykinin-induced vasodilation, whereas enalapril selectively inhibits ANG I-induced vasoconstriction while potentiating the vasodilator effect of bradykinin.

Adult↗
PubMed1993

Lack of effect of enalaprilat on the action of vasoactive intestinal polypeptide in the human forearm.

It has been proposed that angiotensin converting enzyme (ACE) may play a role in the metabolism of the vasodilator peptide vasoactive intestinal polypeptide (VIP). Reduced metabolism following treatment with ACE inhibitors may cause accumulation of VIP which in turn may mediate some of the beneficial haemodynamic effects of ACE inhibition observed in patients with heart failure. This study has shown that inhibition of local vascular ACE does not interfere with the vascular effects of VIP on forearm resistance vessels when this peptide is infused into the brachial artery of normal volunteers. These results suggest that endothelial ACE plays little part in the metabolism of intravascular VIP.

Adult↗
PubMed1993

Differential inhibition by NG-monomethyl-L-arginine of vasodilator effects of acetylcholine and methacholine in human forearm vasculature.

1. We compared the effects of NG-monomethyl-L-arginine (L-NMMA), an NO synthase inhibitor, on vasodilatation produced by acetylcholine and methacholine in human forearm vasculature. 2. Acetylcholine (83 nmol min-1) infused into the brachial artery of 8 healthy volunteers caused a submaximal increase in forearm blood flow, measured by venous occlusion plethysmography, from 3.3 +/- 0.5 (mean +/- s.e. mean) to 13.3 +/- 1.7 ml min-1 100 ml-1. 3. Co-infusion of L-NMMA (4 mumol min-1) with acetylcholine (83 nmol min-1) over 6 min resulted in a 58% +/- 12% fall in the response to acetylcholine whereas during co-infusion of saline over the same time period in the same subjects (n = 8) on a different day the response to acetylcholine fell by only 9% +/- 17% (P < 0.01). 4. Methacholine (1.5 and 15 nmol min-1) increased forearm blood flow from 2.5 +/- 0.4 to 5.9 +/- 0.9 and from 3.2 +/- 0.4 to 17.0 +/- 1.9 ml min-1 100 ml-1 respectively. 5. Co-infusion of L-NMMA (4 mumol min-1) had no significant effect on the response to methacholine (1.5 or 15 nmol min-1) when compared with saline control (n = 8). Co-infusion of a higher dose of L-NMMA (8 mumol min-1) with methacholine (1.5 nmol min-1) did not significantly inhibit the vasodilator response (n = 7). 6. These results suggest that, in human forearm vasculature, methacholine acts predominantly through mechanisms other than the L-arginine/nitric oxide pathway.

Acetylcholine↗
PubMed1993

Abnormalities in the biosynthesis of thromboxane A2 and prostacyclin in children with cyanotic congenital heart disease.

BACKGROUND: Children with cyanotic congenital heart disease and pulmonary outflow tract obstruction have shortened platelet survival times and are susceptible to thrombosis and organ infarction. Thromboxane A2 and prostacyclin have opposing actions on platelet aggregability and an imbalance in their biosynthesis might contribute to the pathophysiology of these complications. METHODS: Biosynthesis of thromboxane A2 and prostacyclin was investigated in 16 children (4-32 months, median 18 months) with cyanotic congenital heart disease and pulmonary outflow tract obstruction and compared with 16 healthy children of a similar age (6-34 months, median 24 months). Urinary excretion of 2,3-dinor-thromboxane B2 (a metabolite of thromboxane A2) and of 2,3-dinor-6-oxo-prostaglandin F1 alpha (a metabolite of prostacyclin) was measured. RESULTS: The children with cyanotic congenital heart disease and pulmonary outflow tract obstruction excreted more 2,3-dinor-thromboxane B2 than the healthy children: 916(163) compared with 592(122) ng/g creatinine (mean(SEM); 2p = 0.014). The ratio of excretion of 2,3-dinor-thromboxane B2 to 2,3-dinor-prostaglandin F1 alpha was greater in the patients than in the healthy control group (2.38(0.28) v 1.3(0.22)) (2p = 0.002). CONCLUSION: The balance between biosynthesis of prostacyclin and of thromboxane A2 is abnormal in children with cyanotic congenital heart disease and pulmonary outflow tract obstruction and favours platelet aggregation and vasoconstriction.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Blind drunk: alcoholic pancreatitis and loss of vision.

Acute loss of vision and alcoholic intoxication suggests the possibility of methanol poisoning. In this report we describe an alcoholic patient who complained of blindness after recovering from alcoholic pancreatitis and delirium tremens. Visual acuity was severely impaired and fundoscopy revealed florid bilateral cotton wool spots and a cherry red spot at the right macula. Such appearances have previously been reported in cases of post-traumatic visual loss, and may share a common aetiology of fat embolization. The association between alcoholic pancreatitis and visual loss is rare, and fundal examination should be performed on all patients with pancreatitis, especially those who complain of visual disturbance.

Acute Disease↗
PubMed1993

Thromboxane A2 and prostacyclin biosynthesis in children and adolescents with pulmonary vascular disease.

BACKGROUND: The pathogenesis of pulmonary vascular disease in children with congenital heart disease is incompletely understood. Thromboxane (TX) A2 and prostacyclin (PGI2) have opposing effects on platelet aggregation and pulmonary vascular smooth muscle. An imbalance in their biosynthesis could contribute to the progressive increase in pulmonary vascular resistance seen in older untreated patients with pulmonary hypertensive congenital heart disease and the thrombotic complications they may develop. METHODS AND RESULTS: We investigated TXA2 and PGI2 biosynthesis in 15 young children (0.2 to 2.25 years old) with congenital heart disease with increased pulmonary blood flow and potentially reversible pulmonary vascular disease by measuring urinary excretion of 2,3-dinor-TXB2 and 2,3-dinor-6-oxoprostaglandin (PG) F1 alpha and compared the findings with those in 16 healthy children (0.5 to 2.8 years old). 2,3-Dinor-TXB2 excretion was greater in the patients than in control subjects (1253 +/- 161 versus 592 +/- 122 ng/g creatinine; P < .001). Excretion of 2,3-dinor-6-oxo-PGF1 alpha was 452 +/- 54 compared with 589 +/- 95 ng/g creatinine in control subjects. In 5 patients who underwent successful cardiac surgery > or = 1 year later excretion of 2,3-dinor-TXB2 decreased from 1100 +/- 298 to 609 +/- 131 ng/g creatinine (P < .05), a value comparable to those in 5 healthy children of similar age (749 +/- 226 ng/g creatinine). We also compared 15 patients (11 to 23 years old) with advanced irreversible pulmonary vascular disease with 19 healthy control subjects (10 to 23 years old). The ratio of TX to PGI2 metabolite excretion was greater in the patients than in control subjects (3.5 +/- 0.6 versus 2.0 +/- 0.3; P < .05). CONCLUSIONS: There is increased 2,3-dinor-TXB2 excretion in children with congenital heart disease and a high pulmonary blood flow that may reflect an imbalance in biosynthesis of TXA2 and PGI2 in the pulmonary vascular bed. The imbalance may contribute to the progressive development of increased pulmonary vascular resistance and persists in older patients whose heart defects are uncorrected.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Thromboxane A2 receptor antagonism and synthase inhibition in essential hypertension.

Short-term effects of ridogrel, a combined thromboxane synthase inhibitor and receptor antagonist, were investigated in 16 patients with uncomplicated essential hypertension. After a 2-week placebo period without antihypertensive medication, patients were admitted to the hospital overnight on two occasions 3 weeks apart. On each occasion, they received two doses of either placebo or ridogrel (300 mg) 12 hours apart according to a double-blind crossover protocol. Renal and systemic thromboxane A2 and prostacyclin biosynthesis were investigated by measuring urinary excretion of thromboxane B2, 6-oxo-prostaglandin F1 alpha, and their respective 2,3-dinor metabolites using gas chromatography/mass spectrometry. Responses of platelets to a thromboxane A2 mimetic and to adenosine diphosphate were studied turbidometrically. Blood pressure was measured automatically at 20-minute intervals. Ridogrel reduced excretion of 2,3-dinor-thromboxane B2 and thromboxane B2 compared with placebo (21 +/- 6 versus 279 +/- 28 and 14 +/- 4 versus 39 +/- 9 ng/g creatinine, respectively; P < .0001 and P < .05). Excretion of 2,3-dinor-6-oxoprostaglandin F1 alpha and 6-oxoprostaglandin F1 alpha was increased by ridogrel compared with placebo (184 +/- 20 versus 146 +/- 11 and 86 +/- 9 versus 58 +/- 6 ng/g creatinine, respectively; P < .05). Ridogrel selectively antagonized platelet aggregation to the thromboxane mimetic (P < .0001). Blood pressure did not differ significantly between ridogrel and placebo treatment periods. Thus, in patients with essential hypertension, acute administration of ridogrel reduces renal and extrarenal thromboxane A2 biosynthesis, increases renal and extrarenal prostacyclin biosynthesis, inhibits thromboxane receptor-activated platelet aggregation, but has no effect on systemic arterial pressure.

Adult↗
PubMed1993

Clinical pharmacology of angiotensin and bradykinin in human forearm vasculature.

HYPOTHESIS: Losartan inhibits the renin-angiotensin system by blockade of angiotensin II receptors, whereas enalapril blocks the renin-angiotensin system by inhibiting the conversion of angiotensin I to angiotensin II by the angiotensin converting enzyme (ACE). Since ACE inactivates bradykinin in addition to its action on angiotensin I we hypothesized that losartan and enalapril have different effects on the response to angiotensin and bradykinin. METHODS: We studied healthy volunteers dosed with placebo, enalapril and losartan 4-6 h before measurement of forearm blood flow by venous occlusion plethysmography. Saline, angiotensin I, angiotensin II and bradykinin were infused into the left brachial artery. RESULTS: Losartan produced a similar inhibition of the vasoconstriction induced by angiotensin I and angiotensin II without significantly influencing the bradykinin-induced vasodilation, whereas enalapril potentiated the vasodilator effect of bradykinin and selectively inhibited the vasoconstriction induced by angiotensin I without altering the response to angiotensin II. CONCLUSION: These pharmacological differences suggest that angiotensin II receptor antagonists and ACE inhibitors may not be therapeutically equivalent.

Angiotensin II↗
PubMed1993

Effect of selective inhibition of thromboxane synthesis on renal function in diabetic nephropathy.

Studies of nondiabetic renal disease suggest that thromboxane may be an important mediator of abnormal renal function. The role of thromboxane in diabetic nephropathy is not fully understood. We measured in a double-blind, randomized, placebo-controlled crossover study the effect of a thromboxane synthase inhibitor (FCE 22178, 400 mg two or three times per day) on urinary excretion of thromboxane B2 and 6-keto-prostaglandin F1 alpha, glomerular filtration rate (measured as clearance of polyfructosan), effective renal plasma flow (clearance of para-aminohippuric acid), fractional clearances of albumin and immunoglobin G and the reabsorption rate of beta 2-microglobulin in 15 patients with type 1 (insulin-dependent) diabetic nephropathy. In seven additional patients, the effect of the thromboxane synthase inhibitor given as 400 mg twice per day was compared with that of the thromboxane synthase inhibitor given as 400 mg three times per day. FCE 22178 administration caused a significant inhibition in the excretion of urinary thromboxane B2 and 2,3-dinor-thromboxane B2 compared with placebo (12.3 +/- 2.1 vs 24.6 +/- 5.1 ng/gm creatinine, p = 0.006, and 78.5 +/- 20.3 vs 335.5 +/- 84.1 ng/gm creatinine, p = 0.004, respectively) without any compensatory increase of 6-keto- prostaglandin F1 alpha or 2,3-dinor-6-keto-prostaglandin F1 alpha that reflect prostacyclin I2 biosynthesis. Glomerular filtration rate, effective renal plasma flow, renal vascular resistance, and filtration fraction were not significantly different after placebo or thromboxane synthase inhibitor treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolaemia.

Endothelium-dependent vasodilation in response to acetylcholine is impaired in the coronary microvasculature of hypercholesterolaemic subjects. Outside the coronary circulation, however, it has been suggested that hypercholesterolaemia results in a functional abnormality of vascular smooth muscle rather than in endothelial dysfunction. We examined vasodilator responses to acetylcholine, methacholine, and the endothelium-independent vasodilator sodium nitroprusside in the forearm resistance vessels of 12 men with primary hypercholesterolaemia and 12 normocholesterolaemic male controls. Endothelium-dependent vasodilation in response to acetylcholine was impaired in hypercholesterolaemic patients compared with controls: at the highest dose of drug (15 micrograms per min) mean blood flow in the forearms of the hypercholesterolaemic group was only 52% (95% Cl 31-88%) of that in the control group. Responses to sodium nitroprusside and to methacholine in the two study groups were not significantly different. These results indicate that endothelial dysfunction in hypercholesterolaemic subjects is generalised and extends to vascular beds outside the coronary circulation. Selective impairment to acetylcholine suggests that, at a molecular level, the defect is limited to a specific pathway.

Acetylcholine↗
PubMed1992

Hallucinations as a presenting feature in malignant hypertension.

A 68-year-old man with malignant hypertension of renovascular origin presented with visual impairment and complex visual hallucinations. Four weeks after the hypertension had been controlled by drugs, the hallucinations ceased and electroencephalographic evidence of encephalopathy resolved.

Aged↗
PubMed1991

Effects of a monoclonal antibody to glycoprotein IIb/IIIa (P256) and of enzymically derived fragments of P256 on human platelets.

The anti-platelet monoclonal antibody P256 is currently undergoing development for in vivo detection of thrombus. We have examined the actions of P256 and two fragments on human platelet function. P256, and its divalent fragment, caused aggregation at concentrations of 10(-9)-3 x 10(-8) M. A monovalent fragment of P256 did not cause aggregation at concentrations up to 10(-7) M. P256-induced platelet aggregation was dependent upon extracellular calcium ions as assessed by quin2 fluorescence. Indomethacin partially inhibited platelet aggregation and completely inhibited intracellular calcium mobilisation. Apyrase caused partial inhibition of aggregation. Aggregation induced by the divalent fragment was dependent upon fibrinogen and was inhibited by prostacyclin. Aggregation induced by the whole antibody was only partially dependent upon fibrinogen, but was also inhibited by prostacyclin. P256 whole antibody was shown, by flow cytometry, to induce fibrinogen binding to indomethacin treated platelets. Monovalent P256 was shown to be a specific antagonist for aggregation induced by the divalent forms. In-111-labelled monovalent fragment bound to gel-filtered platelets in a saturable and displaceable manner. Monovalent P256 represents a safer form for in vivo applications.

Adult↗