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Biomedical subjects

J G Brook

Publications and source records attributed to J G Brook.

At least 91 records · Page 5Linked to original sources

Accumulation of lipoprotein remnants in patients with chronic renal failure.

The composition and concentration of remnant lipoprotein particles accumulating in the plasma of patients with chronic renal failure (CRF) was determined. Ten patients on chronic hemodialysis were compared with 8 controls. The patients' very low density lipoproteins (VLDL) were abnormal and contained more of the dense VLDL subfraction (VLDL3). The concentration of intermediate density lipoproteins (IDL) was increased 3-fold in CRF plasma, whereas the amount of low density lipoprotein (LDL) was decreased by 25%. On electrophoresis of plasma lipoproteins the beta-band from the patients' samples demonstrated increased anodal mobility, indicating an abnormality in composition of the patients' LDL. These abnormalities were present regardless of whether patients were hyperlipidemic or not. These findings suggest defective conversion of VLDL to LDL in CRF, allowing for the accumulation of lipoprotein particles usually absent from plasma. The latter may account for the accelerated atherosclerosis reported in patients with CRF.

Adult↗

Platelet interaction with high and low density lipoproteins.

Gel-filtered platelets (GFP) from normal human subjects bound both low density lipoproteins (LDL) and high density lipoproteins (HDL). This binding was saturable and 125I-labelled lipoprotein uptake was inhibited by plasma. Platelets are also able to degrade lipoproteins but only to a limited extent. LDL appeared to compete with 125I-labelled HDL for platelet uptake, whereas the ability of HDL to displace 125I-LDL was limited. Cyclohexanedione-treated LDL (CHD-LDL), unlike CHD-HDL, did not compete with [125I]LDL for platelet accumulation, suggesting that arginine residues are necessary for LDL but not HDL binding. Addition of HDL or LDL to GFP did not alter platelet aggregation. However, in the presence of thrombin (0.5 U/ml), 1 mg/ml LDL incubated for 1 h at 23 degrees C enhanced platelet aggregation (215% increase) whereas HDL under similar conditions decreased aggregation by 53%. LDL also shortened the time of maximal aggregation whereas HDL had the opposite effect.

Blood Platelets↗

Increased platelet adhesion and aggregation in hypertensive patients: effect of atenolol.

Fourteen patients with established hypertension followed a double-blind crossover-styled trial to study the effects of 100 mg/day atenolol compared to placebo. Atenolol was found to be an effective antihypertensive agent, reducing both systolic and diastolic blood pressure. Hypertensive patients appear to have increased in vitro platelet adhesion and aggregation. Atenolol significantly reduced platelet adhesion, but had little effect on aggregation. This may be important in contributing towards the now-recognised cardio-protective effect of the beta-adrenoceptor blocking agents. Blood chemistry and haematological parameters were unchanged; but whereas plasma cholesterol and plasma triglyceride levels remained normal, there was a significant fall in plasma high-density lipoprotein cholesterol levels. Side effects were very few.

Adult↗

Fibrinogen "Haifa" - a new fibrinogen variant. A case report.

A 30-year-old female presenting with arterial occlusions of the lower limbs was discovered to have a markedly abnormal thrombin time and reptilase time. Further investigations revealed the presence of a qualitatively abnormal fibrinogen. Two other family members who were completely asymptomatic had similar defects. The abnormal fibrinogen has been characterized and found to be a new variant and as such designated fibrinogen 'Haifa'.

Adult↗

Characterization of the effect of plasma lipoproteins on platelet function in vitro.

Thrombin-induced platelet activation is enhanced by very low and low density lipoproteins but decreased by high density lipoprotein. Plasma lipoproteins maximally affect platelet aggregation and 14C-serotonin release in a gel-filtered platelet preparation within 10 min of incubation at 37 degrees C. This effect is saturable and physiologic concentrations of lipoproteins are required in order to attain this saturation. When no aggregating agent is added to the incubation medium, the lipoproteins alone did not alter platelet aggregation. However, 14C-serotonin release is increased by very-low- and low-density lipoproteins alone more than by high density lipoprotein. On removal of the lipoproteins after incubation with the platelets, and subsequent testing of platelet function, minimal influence of these lipoproteins on the platelet function remains. Arachidonic acid causes similar results to thrombin when added to the platelet suspension after incubation with the lipoprotein. Our results further emphasize the 'opposing effects' of very low and low density lipoproteins as compared to high density lipoproteins on platelets and/or platelet-thrombin interaction.

Arachidonic Acid↗

The effect of blood constituents on platelet function: role of blood cells and plasma lipoproteins.

Platelet aggregation as well as [14C] serotonin release were increased in platelet-rich plasma in comparison to gel-filtered platelet preparation. The addition of red blood cells to platelet-rich plasma enhanced thrombin-induced [14C] serotonin release by 7%, whereas in a gel-filtered platelet preparation free of any plasma constituents a 47% increment was noted. In the presence of white blood cells, no effect could be shown. Purified lipoproteins were incubated (in their normal plasma concentration) with gel-filtered platelets for 30 minutes at 37 degrees C, and the effect on in vitro platelet function was studied. Very low density lipoprotein and low density lipoprotein increased thrombin-induced platelet aggregation and [14C] serotonin release induced by epinephrine, ADP, and thrombin. In contrast, high density lipoprotein inhibited these platelet functions. Lipoprotein-deficient plasma increased platelet aggregation and release reaction. It appears that plasma lipoproteins have a profound effect on in vitro platelet function. Since both platelets and lipoproteins are of importance in atherosclerosis, the platelet-lipoprotein interaction might be of major significance in this process.

Adolescent↗

The effect of oestrogen implants on high density lipoproteins and its subfractions in women in their pre-mature menopause.

Oestrogen is recognized as having profound effects on lipid and lipoprotein levels. It is also considered as the agent protecting the pre-menopausal woman from arteriosclerotic cardiovascular disease. High density lipoprotein (HDL) has also been ascribed a protective role against the development of arteriosclerosis. The effect of natural oestrogen (17 beta-oestradiol) administered in the form of a subcutaneous pellet on concentrations of lipids and lipoproteins, particularly high density lipoproteins and its subfractions were determined in three young women with premature menopause. Plasma cholesterol, low density lipoprotein and very low density lipoprotein and very low density lipoprotein levels decreased following oestrogen implantation. High density lipoproteins and in particular subfraction 2 (density cut 1.063-1.125 gm/ml) and subfraction 3 (density cut 1.125-1.21 gm/ml) increased profoundly but there was a slight fall in the HDL 2/HDL 3 cholesterol ratio. The HDL/LDL cholesterol ratio increased from 0.21 to 0.46. A decrease in the urinary FSH levels paralleled these changes in the lipoprotein concentrations. Oestrogen administered in this form, unlike other oestrogen or mixed oestrogen--progestogen compounds is a definite modifier of arteriosclerotic risk, and as such could be given therapeutically in menopausal hypercholesterolemic females.

Adult↗

Lipid and lipoprotein pattern in thyroid dysfunction and the effect of therapy.

Lipid and lipoprotein concentrations were studied in 12 hypothyroid and 11 hyperthyroid female subjects, both before and after therapy, and in 27 age matched female controls. Recognized clinical and laboratory criteria established the diagnosis. Lipoproteins, including the sub-fractions of the high density lipoproteins (HDL), were isolated by preparative ultracentrifugation, and the cholesterol (c) and protein (p) contents of each were determined. Total cholesterol, and in particular HDL-c, were elevated in the hypothyroid patients. The low density lipoprotein (LDL) -c/HDL-c ratio was 1.9 in this group, compared to 2.2 in the control group and 1.35 in the hyperthyroid patients. The HDL-2/HDL-3 ratio in the hypothyroid group was 3.75, as compared to 1.75 in the controls and 4.2 in the hyperthyroid group. Plasma triglycerides were moderately elevated in the hypothyroid patients and were significantly reduced in the hyperthyroid group. Total cholesterol was significantly lower in the hyperthyroid group as compared to the control group. Very low density (VLDL) cholesterol and protein were significantly increased and LDL and HDL cholesterol were reduced in the hyperthyroid patients. On rendering the patients euthyroid, most of these changes were reversed. Thyroid function profoundly affects lipoprotein concentration and composition. The change in the plasma HDL concentrations of the hypothyroid group questions the relationship of this group to arteriosclerosis. Therapy partially corrects the abnormalities, but complete correction may be related to duration of therapy.

Adolescent↗

High-density lipoprotein subfractions in normolipidemic patients with coronary atherosclerosis.

High-density lipoprotein (HDL) levels were studied in 10 male patients with severe coronary atherosclerosis and in 10 well-matched controls. All subjects were normolipidemic, and the presence of a disease or other factor influencing HDL levels were excluded. Very low density lipoprotein and low-density lipoprotein levels were similar in both groups, but HDL concentration was significantly lower in the patient group. Analysis of HDL subfractions revealed that both HDL2 and HDL3 concentrations were significantly lower in the patient group. The composition of both HDL subfractions was also altered in the patient group: an increased cholesterol-to-protein ratio was found. These data strengthen the evidence in support of an important and independent role for HDL in the pathogenesis of coronary atherosclerosis. It appears that both HDL2 and HDL3 are implicated and that both the concentration and composition of HDL are important.

Adult↗

Splenic abscess diagnosed with the aid of abdominal computerized tomography: report of 2 cases.

Two patients with splenic abscess successfully diagnosed and treated are described. The first case, a diabetic, developed a pyogenic abscess caused by klebsiella, while the other suffered a splenic infarct complicated by splenic abscess. although relatively easy to treat, solitary abscess of the spleen is a potentially lethal condition due to diagnostic difficulties. In both present instances the final diagnosis was easily achieved before surgery by the aid of computerized tomography (CT). This investigation seems to be more accurate than 99Tcm-sulphur colloid scan and ultrasound scan, which failed in both cases to diagnose splenic abscess clearly. The use of this investigation is suggested in every suspected case and will, no doubt, confirm the diagnosis at an early stage of the disease. Splenectomy with antibiotic cover will usually result in cure.

Abscess↗

High density lipoprotein and arteriosclerosis. Different patterns in primary hypothyroidism and type IIa hyperlipoproteinemia.

Concentrations of high density lipoprotein (HDL) and its subfractions were contrasted in two groups of patients with hypercholesterolemia and a control group of normocholesterolemic subjects. HDL-cholesterol and HDL-protein were low in patients with Type IIa hyperlipoproteinemia, but elevated in patients with primary hypothyroidism. HDL-3 levels were low whereas those of HDL-2 remained unchanged in patients with Type IIa hyperlipoproteinemia. In contrast, in the hypothyroid patients, HDL-3 remained unchanged, while HDL-2 levels were high. The role of HDL in the development of arteriosclerosis in patients with primary hypothyroidism is therefore questioned. Our findings also suggest that measurement of HDL-cholesterol alone cannot be regarded as an accurate indicator of changes in total HDL concentration in different clinical situations.

Arteriosclerosis↗

The concentration of high density lipoprotein in patients with type IV hyperlipoproteinemia and the effect of clofibrate.

Lipid and lipoprotein concentrations, including high density lipoproteins (HDL) and its subfractions, were contrasted in subjects with Type IV hyperlipoproteinemia, before and after therapy with clofibrate. Very low density lipoprotein (VLDL) levels were raised, whereas both low density lipoprotein (LDL) and HDL values were reduced in the patient group. Clofibrate reversed this trend and VLDL cholesterol and protein levels fell to approximate control values. LDL and HDL cholesterol increased but remained significantly lower than in normal controls. However, LDL and HDL protein did approach control values. Of the HDL subfractions, HDL-3 was significantly reduced in the group with Type IV hyperlipoproteinemia. Clofibrate resulted in a significant increase in the HDL-2: HDL-3 cholesterol ratio, but had only a modest effect on HDL-3 concentrations. HDL-3 may be the critical HDL subfraction responsible for the inverse correlation between levels of HDL and the development of ischemic heart disease.

Adult↗