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Biomedical subjects

R S Lees

Publications and source records attributed to R S Lees.

At least 91 records · Page 5Linked to original sources
PubMed1978

Activation of the kallikrein system in hyperbetalipoproteinemia.

In 30 patients with hyperlipoproteinemia (19 type II and 11 type IV), the role of the intrinsic coagulation pathway was evaluated by assays of preK, Kl's, and Hageman factor (factor XII). Analysis of the plasma of type II patients suggested activation of the intrinsic pathway characterized by a 40% decrease in preK (p less than 0.01) and a 50% decrease Kl (p less than 0.01); in contrast, analysis of the plasma of type IV patients showed no activation of the intrinsic pathway. In type II patients C-1INH was present in normal concentrations as measured by immunochemical techniques. The findings of normal levels of C-1INH by immunoassay, in association with altered electrophoretic mobility, are suggestive of formation of a kallikrein-C-1INH complex in vivo.

Blood Coagulation↗
PubMed1977

Tangier disease (alpha-lipoprotein deficiency).

A patient with asymptomatic hypocholesterolemia, mild hyperbilirubinemia, and splenomegaly was found, on lipoprotein analysis, to have Tangier disease (alpha-lipoprotein deficiency). He represents the first patient with the disease in the northeastern Unit States. Although free of clinical evidence of atherosclerosis at age 38 years, the patient has widespread tissue cholesterol ester deposition and a stron family history of atherosclerosis. Tangier disease may be much underdiagnosed; it should be suspected in every patient with hypocholesterolemia.

Adult↗
PubMed1977

Failure of complete bile diversion and oral bile acid therapy in the treatment of homozygous familial hypercholesterolemia.

Two patients with nomozygous familial hypercholesterolemia, refractory to medical therapy, underwent complete bile diversion by common-duct ligation and cholecystostomy, in an attempt to arrest the progression of their xanthomatosis and atherosclerosis by depletion of body cholesterol. Clofibrate was given after operation to one patient, and cholic acid to both, in an effort to enhance further the negative sterol balance. Bile diversion produced an increase of six to eight times in gastrointestinal sterol output, which was not increased further by either clofibrate or cholic acid therapy. Despite a calculated sterol loss of 560 g over 14 months in one patient and 400 g over 10 months in the other, neither plasma cholesterol nor xanthoma size decreased. Continuity of the biliary tree was therefore restored. The data suggest that patients with homozygous familial hypercholesterolemia respond to even massive gastrointestinal sterol depletion with equal increases in sterol synthesis.

Administration, Oral↗
PubMed1977

Coagulation abnormalities in women taking oral contraceptives.

Thirteen asymptomatic women taking oral contraceptives (OCs) were compared with normal subjects. Platelet aggregation and serotonin (tagged with carbon 14) release with adenosine diphosphate, epinephrine, and collagen did not differ from controls. Activation of the intrinsic coagulation pathway was evaluated by measurements of factor XII, prekallikrein, and kallikrein inhibitors. Women taking OCs had normal factor XII levels, moderately elevated prekallikrein levels, and decreased kallikrein inhibitor levels, a pattern not consistent with activation of the intrinsic pathway. The concentration of heavy molecular weight fibrinogen derivatives (HMWFD) was significantly elevated (P less than .001). In contrast, fibrin and fibrinogen degradation products in serum were lower than normal (P less than .05). The increased HMWFD concentration may reflect activation of the coagulation system not mediated by factor XII activation nor potentiated by decreased antithrombin III. Thus, plasma coagulation abnormalities rather than platelet changes may be the factor that predisposes women taking OCs to thromboembolic disorders.

Adult↗
PubMed1977

Echocardiographic spectrum of posterior systolic motion of the mitral valve in the general population.

The prevalence of mitral valve prolapse has been established in selected groups of patients but not in the general population. The present study was designed to define the echocardiographic spectrum of mitral valve motion in a population of young individuals without clinical evidence of significant cardiac disease or hypertension. Echocardiograms were performed on 136 normal volunteers. Six subjects (4.4 per cent) had mitral valve prolapse. Eighteen subjects (13.2 per cent) had a lesser degree of posterior systolic motion of the mitral valve leaflets which was suggestive but not diagnostic of prolapse. Minor degrees of posterior systolic mitral valve motion may represent a variant of normal. Caution should be exercised in making the echocardiographic diagnosis of mitral prolapse until this question is settled.

Adolescent↗
PubMed1977

Plant sterols as cholesterol-lowering agents: clinical trials in patients with hypercholesterolemia and studies of sterol balance.

We have evaluated the efficacy of plant sterol preparations from two different sources and in two different physical forms in lowering the plasma cholesterol of a total of 46 patients with type II hyperlipoproteinemia when given in addition to appropriate diet therapy. In addition, the mechanisms of the hypocholesterolemic effect were investigated in 7 patients by a sterol balance technique. The maximal mean cholesterol lowering in response to any preparation was 12 percent, although it was much greater in some individual patients. Sterol balance data showed that plant sterols inhibit cholesterol absorption with maximal negative cholesterol balance in adults at a dose of 3 g/day of a tall oil sterol suspension. Interestingly, maximal plasma cholesterol reduction in the adult outpatients on this preparation was seen at the same dose level. Since the tall oil sterol suspension is relatively palatable and is poorly absorbed, it has potential value as an adjunct to dietary therapy in patients with mild hypercholesterolemia for whom long-term drug therapy is deemed advisable.

Cholesterol↗
PubMed1977

Effect of clofibrate on intravascular coagulation in hyperlipoproteinemia.

Intravascular coagulation (IVC) was evaluated in 19 patients with type II and 11 with type IV hyperlipoproteinemia before and after clofibrate therapy by measurements of soluble fibrin complexes (SFC) in plasma; fibrinolysis was estimated by quantitation of fibrin (ogen) degradation products in serum. Untreated type II and type IV patients had increased SFC (P less than 0.01). The former also had activation of the intrinsic coagulation pathway as evidenced by decreased plasma prekallikrein (P less than 0.001), kallikrein inhibitors (P less than 0.001), and factor XII (P less than 0.02). Although clofibrate treatment of the type II patients did not change plasma lipids, it decreased intravascular coagulation, apparently via decreased factor XII activation and stimulation of fibrinolysis. In contrast, treated type IV patients had unchanged SFC and FDP levels, despite decreased plasma triglycerides (P less than 0.01). Clofibrate-induced changes in blood coagulation are independent of lipid-lowering. Clofibrate therapy decreases intravascular coagulation in type II patients and may help to prevent thromboembolic sequelae.

Antithrombins↗
PubMed1977

The distribution of labeled albumin across the rabbit thoracic aorta in vivo.

125I-albumin was injected intravenously into normal conscious rabbits. The rabbits were killed after 10 minutes to 24 hours, and the descending thoracic aorta was excises immediately, opened longitudinally, rinsed, and frozen. Samples of frozen aorta were sectioned paralled to the intimal surface and washed with trichloroacetic acid (TCA) prior to counting. TCA-soluble tissue radioactivity slowly increased with time, suggesting that 125I was cleaved gradually from the labeled albumin within the aortic wall. At up to 4 hours, transmural concentration profiles of TCA-precipitable radioactivity had steep gradients near the intimal surface, moderate gradients near the medial-advential border, and were relatively falt in the middle of the media. After 24 hours, the steep intimal gradient had disappeared. Concentrations were otherwise comparable to those at 4 hours. The rate of accumulation of TCA-precipitable radioactivity was rapid initially (measurable concentrations were found throughout the media after only 10 minutes) and decreased with time. The results are consistent with entry of 125I-albumin into the media from both the luminal and adventitial sides. Approximate calculations indicate that the albumin mass transfer resistance associated with the intimal endothelium is about 1 order of magnitude greater than that associated with the media.

Animals↗
PubMed1977

The storage lipids in Tangier disease. A physical chemical study.

The physical states and phase behavior of the lipids of the spleen, liver, and splenic artery from a 38-yr-old man with Tangier disease were studied. Many intracellular lipid droplets in the smectic liquid crystalline state were identified by polarizing microscopy in macrophages in both the spleen and liver, but not in the splenic artery. The droplets within individual cells melted sharply over a narrow temperature range, indicating a uniform lipid composition of the droplets of each cell. However different cells melted over a wide range, 20-53 degrees C indicating heterogeneity of lipid droplet composition between cells. Furthermore, most of the cells (81%) had droplets in the liquid crystalline state at 37 degrees C. X-ray diffraction studies of splenic tissue at 37 degrees C revealed a diffraction pattern typical of cholesterol esters in the smectic liquid crystalline state. Differential scanning calorimetry of spleen showed a broad reversible transition from 29-52 degrees C, with a maximum mean transition temperature at 42 degrees C, correlating closely with the polarizing microscopy observations. The enthalpy of the transition, 0.86+/-0.07 cal/g of cholesterol ester, was quantitatively similar to that of the liquid crystalline to liquid transition of pure cholesterol esters indicating that nearly all of the cholesterol esters in the tissue were free to undergo the smectic-isotropic phase transition. Lipid compositions of spleen and liver were determined, and when plotted on the cholesterol-phospholipid-cholesterol ester phase diagram, fell within the two phase zone. The two phases, cholesterol ester droplets and phospholipid bilayers were isolated by ultracentrifugation of tissue homogenates. Lipid compositions of the separated phases approximated those predicted by the phase diagram. Extracted lipids from the spleen, when dispersed in water and ultracentrifuged, underwent phase separation in a similar way. Thus (a) most of the storage lipids in the liver and spleen of this patient were in the liquid crystalline state at body temperature, (b) the phase behavior of the storage lipids conformed to that predicted by lipid model systems indicating lipid-lipid interactions predominate in affected cells, (c) lipid droplets within individual cells have similar compositions, whereas droplet composition varies from cell to cell, and (d) cholesterol ester does not accumulate in the splenic artery. Since Tangier patients lack high density lipoprotein, we conclude that high density lipoprotein-mediated cholesterol removal from cells is essential only for those cells which have an obligate intake of cholesterol (macrophages).

Adult↗
PubMed1976

[Coronary lesions in type II and IV hyperlipoproteinemias. Coronarographic study].

Coronary arteriography was performed in 24 patients with type-II and in 22 patients with type-IV hyperlipoproteinemia. The findings of the present study allow definition of several angiographic characteristics which seem to be linked to the type of hyperlipoproteinemia. Patients with type II generally have more widespread disease in the coronary tree at younger ages than do those with type IV. Type-II patients usually have proximal and distal disease, whereas type-IV patients have more often proximal disease only. Significant stenosis of the main left coronary artery is frequent in type-II but very rare in type-IV patients. Extensive calcification of the ascending aorta, sometimes associated with narrowing of the proximal aortic root, is present in 25% of type-II but in none of type-IV patients.

Angiography↗
PubMed1976

Coronary arteriographic findings in type-II and type-IV hyperlipoproteinaemia.

Coronary arteriography was performed in 46 patients with type-II and type-IV hyperlipoproteinaemia. Type-II patients had a high prevalence of main left coronary disease and of distal coronary atherosclerosis, while type-IV patients usually had disease localised to the proximal coronary tree. These differences may be related to the differing plasma-lipoprotein patterns in these two syndromes.

Adolescent↗
PubMed1976

Therapy of the hyperlipidemias.

Although the diagnosis of hyperlipidemia is somewhat arbitrary, in that the upper limits of normal are not universally agreed upon, it is clear that the risk of atherosclerosis increases with plasma cholesterol concentration; it may also increase in hyperglyceridemia. We take 220 mg/100 ml as the upper limit of normal for plasma cholesterol and 140 mg/100 ml as the upper limit for triglycerides. Treatment of hyperlipidemia is aimed at reducing the risk of atherosclerosis or arresting its course. Alteration of diet is the first step. If maximal diet therapy does not lower plasma lipids to acceptable levels, drug therapy is added. The decision to treat hyperlipidemia with drugs should be based on a careful weighing of risk vs. benefit for each patient. Because of the rapid change in our knowledge of both the risks and the benefits of therapy, that decision must be reviewed and updated at regular intervals.

Anticoagulants↗
PubMed1975

Evaluation of carotid stenosis by phonoangiography.

Quantitative spectral (frequency) analyses were performed on 60 carotid bruits in 48 patients with suspected carotid stenosis. The technic was totally noninvasive. Bruits were recorded at the skin surface, analyzed by a minicomputer, and the degree of arterial stenosis estimated using a recently derived theory of sound production by turbulent blood flow. This method has been named phonoangiography. Fifty of the 60 bruits (83 per cent) had spectrums characteristic of turbulent blood flow, and a residual lumen diameter could be calculated. Results from the noninvasvie technic compared well with data obtained from radiographic carotid arteriograms in the 50 bruits with internal carotid artery stenosis. The residual lumen diameter estimated from phonoangiography differed from the radiographic value by less than 1 mm in 83 per cent and less than 1.5 mm in 92 per cent of the studies. Phonoangiography appears to be a useful method for assessment of carotid artery stenosis.

Arteriosclerosis↗
PubMed1975

Homozygous familial hypercholesterolemia. A possible biochemical explanation of clinical heterogeneity.

Patients with homozygous familial hypercholesterolemia fall into two groups: one responds to diet and drug therapy; the other does not. Fibroblasts from patients in each group were compared for low-density lipoprotein suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and low-density lipoprotein binding. In fibroblasts from four therapy-responsive patients, low-density lipoprotein (100 mug per milliliter) suppressed 3-hydroxy-3-methylglutaryl coenzyme A reductase activity to 41 +/- 12 per cent of control (without low-density lipoprotein) whereas fibroblast enzyme activity from two therapy-unresponsive patients was not suppressed (P less than 0.001). Low-density lipoprotein binding to fibroblasts from both groups was defective as compared to normal controls. Fibroblasts from two therapy-responsive patients had specific binding of low-density lipoprotein of 27 +/- 4 per cent of normal -- greater than the 12 +/- 2 per cent (P less than 0.005) binding to fibroblasts from one therapy-unresponsive patient. These biochemical differences may help explain the variable response to therapy in homozygous familial hypercholesterolemia.

Adolescent↗
PubMed1975

Thermal transitions in human plasma low density lipoproteins.

Thermal analysis of human plasma low density lipoproteins reveals a broad reversible transition encompassing body temperature. The calorimetric and x-ray scattering data identify this transition as a cooperation, liquid-crystalline to liquid phase change involving the cholesterol esters in the lipoprotein. This behavior requires the presence of a region rich in cholesterol ester within the lipoprotein.

Chemical Phenomena↗