PubMed Health⌕ Search

Biomedical subjects

S Bacon

Publications and source records attributed to S Bacon.

At least 19 recordsLinked to original sources
PubMed1993

Hypocholesterolemic effects of cholestyramine and colestipol in patients with familial defective apolipoprotein B-100.

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which substitution of the amino acid glutamine for arginine at position 3500 in the apoprotein B molecule results in LDL particles which bind poorly to the LDL receptor. To date, patients with FDB have been heterozygous for this disorder and their plasma contains both normal and defective-binding LDL particles, with a predominance of the latter. In the present report, we have compared the hypocholesterolemic effects of bile acid sequestrant therapy (cholestyramine or colestipol) in eight patients with FDB, to the response seen in sixteen patients with heterozygous familial hypercholesterolemia (FH), treated with the same drugs. Concentrations of LDL cholesterol fell by 32.0% in the patients with FDB and by 21.6% in the patients with FH. The results indicate that the hypercholesterolemia of both FDB and FH responds to treatment with bile acid sequestrants.

Adult↗
PubMed1993

Hypolipidemic effects of nicotinic acid in patients with familial defective apolipoprotein B-100.

Familial defective apolipoprotein B-100 (FDB) is a dominantly inherited disorder associated with hypercholesterolemia, in which an amino acid substitution in apolipoprotein B-100 results in low-density lipoprotein (LDL) particles that bind poorly to the LDL receptor and accumulate in plasma. Patients with FDB described to date have been heterozygous for this disorder, and their plasma contains both normal and defective-binding LDL particles. We have evaluated the hypocholesterolemic effects of nicotinic acid (3 g/d) in four patients with FDB, and compared the response to that of nine patients with heterozygous familial hypercholesterolemia (FH). Concentrations of LDL decreased by 24% in patients with FDB and by 14% in patients with FH. These results support the view that drugs which reduce LDL synthesis may be particularly effective in the treatment of patients with FDB.

Adult↗
PubMed1992

Comparative hypolipidemic effects of lovastatin and simvastatin in patients with heterozygous familial hypercholesterolemia.

We have compared the effects of lovastatin and simvastatin on plasma lipoproteins, fibrinogen and urinary mevalonic acid excretion in twenty-three patients with heterozygous familial hypercholesterolemia. After a baseline period patients were randomly assigned to receive lovastatin or simvastatin at doses of 10, 20 and 40 mg twice daily, for a period of 2 months each, and then, after a 4-week wash-out period, all patients received the alternate drug for a similar period of therapy. Both drugs were well-tolerated and no patients were withdrawn due to side effects. Lipid values returned to baseline after discontinuation of therapy and no carry-over effect was observed. Treatment with lovastatin resulted in decreases in LDL cholesterol concentrations from 274 mg/dl at baseline to 211, 192 and 178 mg/dl, respectively, on doses of 20, 40 and 80 mg/day. Treatment with simvastatin reduced concentrations of LDL cholesterol to 194, 168 and 156 mg/dl, respectively, on doses of 20, 40 and 80 mg/day. Concentrations of HDL cholesterol increased on both drugs, but no dose response relationship was apparent. Both drugs reduced the 24-h urinary excretion of mevalonic acid, an intermediate in cholesterol biosynthesis, but the magnitude of decrease was similar with lovastatin and simvastatin. Small, but statistically non-significant decreases in fibrinogen occurred with both drugs. Patients who showed the greatest hypolipidemic effect during treatment with lovastatin also showed an excellent therapeutic response to simvastatin and vice versa. We conclude that, on a milligram per milligram basis, simvastatin is twice as potent as lovastatin in the treatment of familial hypercholesterolemia and that with both drugs, reductions in LDL cholesterol concentrations are accompanied by decreases in the urinary excretion of mevalonic acid.

Adult↗
PubMed1991

Temporal replacement of donor erythrocytes and leukocytes in nonanemic W44J/W44J and severely anemic W/Wv mice.

The dominant white spotting, W, locus in the mouse encodes Kit, a receptor molecule with cytosolic tyrosine kinase activity. Mutations in Kit deplete hematopoietic cells by an as yet unknown mechanism, but one that presumably affects the early progenitors of all cell lineages. To examine cell lineage-specific changes caused by different W mutations, we injected genetically marked normal marrow cells into mutant mice and monitored repopulation kinetics. In the present report, we compare repopulation of the various peripheral blood cells in nonanemic W44J/W44J and severely anemic W/Wv mice administered increasing increments of donor cells. At all doses of cells tested, donor erythrocyte repopulation precedes leukocyte repopulation regardless of the recipient phenotype. There is, in fact, little difference in the rate or extent of nonerythroid repopulation in W44J/W44J mice injected with between 6 x 10(6) and 2 x 10(7) donor cells. The fact that donor cells rapidly replace erythrocytes, even in the nonanemic W44J/W44J host, while other cell lineages become donor type more slowly provides further evidence that mutations at the W locus are especially damaging to erythrocyte progenitors. We suggest that host nonerythroid hematopoietic cells compete with normal cells, probably at the level of early progenitors rather than at the level of the totipotent hematopoietic stem cell. The fact that successively higher doses of donor cells do not markedly alter nonerythroid repopulation kinetics implies that it may be possible to maximize autologous therapeutic marrow transplantation.

Anemia, Macrocytic↗
PubMed1989

Reduction in plasma low-density lipoprotein cholesterol and urinary mevalonic acid by lovastatin in patients with heterozygous familial hypercholesterolemia.

The effects of lovastatin, an inhibitor of 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG CoA reductase), on 24-hour urinary excretion rates of mevalonic acid (an intermediate in cholesterol biosynthesis) and plasma low-density lipoprotein (LDL) cholesterol concentrations were evaluated in patients with heterozygous familial hypercholesterolemia (FH). The mean rates of urinary mevalonate excretion of 28 FH patients were initially higher (2.95 +/- 0.29 (+/- SEM) mumols/d) than in 17 control subjects (1.82 +/- 0.12 mumols/d). Patients with FH were treated with sequentially increasing doses of lovastatin (10, 20, 40, and 80 mg daily, taken as a twice daily dosage) for a period of 6 weeks on each dose. When compared to baseline, LDL cholesterol levels fell by 22%, 26%, 30%, and 35% respectively, on these different doses. The mean daily urinary mevalonate excretion decreased from baseline by 19% after 4 weeks on 10 mg daily of lovastatin, 35% on 20 mg, and 31% on 40 mg and 80 mg daily. Similar decreases in urinary mevalonate excretions were observed when patients with FH were treated directly with 40 mg (20 mg twice daily) or 80 mg (40 mg twice daily) mg of lovastatin daily. The magnitude of decrease in LDL cholesterol did not show any significant correlation with the changes in urinary excretion of mevalonic acid. Lovastatin therapy decreases rates of urinary mevalonate excretion (which has previously been shown to reflect rates of cholesterol synthesis) by up to 35% at doses of 20 to 80 mg/d; such a decrease seems unlikely to compromise other important cellular requirements for mevalonate.

Adult↗
PubMed1989

Influence of lovastatin plus gemfibrozil on plasma lipids and lipoproteins in patients with heterozygous familial hypercholesterolemia.

We investigated the hypocholesterolemic effects of lovastatin alone and in combination with gemfibrozil on plasma lipids and lipoproteins in 12 adult patients with well-characterized heterozygous familial hypercholesterolemia. Plasma concentrations of low density lipoprotein (LDL) cholesterol decreased from 321 +/- 14 mg/dl on diet only to 207 +/- 8 mg/dl (-35.5%) on single-drug therapy with lovastatin at a dose of 40 mg twice daily, whereas triglyceride concentrations fell by 27.6% (from 145 +/- 20 to 105 +/- 20 mg/dl). Subsequent addition of gemfibrozil at a dose of 600 mg twice daily resulted in a nonsignificant further reduction in LDL cholesterol to 194 +/- 7 mg/dl (-39.6% change from baseline), whereas triglycerides decreased to 80 mg/dl (-44.8%, p less than 0.05 vs. single-drug therapy with lovastatin). Plasma concentrations of high density lipoprotein (HDL) increased slightly during lovastatin and combined drug therapy (from 45 +/- 4 mg/dl at baseline to 46 +/- 4 mg/dl on lovastatin to 48 +/- 4 mg/dl on lovastatin plus gemfibrozil). The response to combination drug therapy in individual patients was heterogeneous and clinically significant decreases in LDL cholesterol concentrations were noted in two of the 12 patients, whereas in three patients LDL cholesterol concentrations increased on the combined drug regimen. One patient developed an asymptomatic increase in creatine kinase on monotherapy with lovastatin and a more pronounced and symptomatic increase during combination drug therapy with lovastatin plus gemfibrozil.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Hypolipidemic effects of HMG-CoA reductase inhibitors in patients with hypercholesterolemia.

Hypercholesterolemia with increased plasma concentrations of low density lipoproteins (LDL) is a major risk factor for the premature development of coronary atherosclerosis in humans and is best exemplified by patients with familial hypercholesterolemia. The recent development of several specific competitive inhibitors of the rate-limiting enzyme in cholesterol biosynthesis (3-hydroxy-3-methylglutaryl-coenzyme A reductase, HMG CoA reductase) has opened up an important new avenue of therapy for patients with hypercholesterolemia who are not responsive to dietary treatment alone. Three drugs, lovastatin (mevinolin), simvastatin (synvinolin) and pravastatin (CS 514), are currently undergoing clinical trials in North America and Europe; the former has recently been approved for general use. Experience with lovastatin and simvastatin in the treatment of patients with primary and secondary causes of hypercholesterolemia is reviewed. The relative potency of simvastatin appears to be greater than that of lovastatin and pravastatin but, with each drug, decreases in the plasma concentrations of LDL cholesterol of 30% to 50% can be achieved. The hypocholesterolemic effects of HMG CoA reductase inhibitors can be potentiated by combination therapy with other approved lipid-lowering medications including the bile acid sequestrants and nicotinic acid. If long-term safety can be satisfactorily established, specific inhibitors of HMG CoA reductase represent a major advance in the therapy of hypercholesterolemia and afford the potential to reduce substantially the high incidence of premature atherosclerosis that occurs in patients with persistent hypercholesterolemia.

Anticholesteremic Agents↗
PubMed1982

The effects of age, body wight and family relationships on plasma lipoproteins and lipids in men, women and children of randomly selected families.

Two hundred thirty-three families were randomly selected from a designated population base. Data from 619 persons ages 6--65 years had distributions of lipid and anthropometric values typical for the U.S. population. The typical rise in plasma cholesterol and triglyceride with age was also demonstrated. The plasma cholesterol and low-density lipoprotein (LDL) correlated more strongly with age than body weight, whereas the plasma triglyceride was more related to body weight than to age. High-density lipoprotein (HDL) was inversely correlated with weight and plasma triglyceride. Family membership accounted for approximately 20% of the variability in cholesterol, LDL, HDL and weight. Related family members (father-child, mother-child and siblings) had strong correlations for plasma cholesterol, LDL and HDL. These measurements did not correlate in the spouse pairs. The plasma triglyceride did not correlate for the family as a whole nor for the individual family members. This study indicates the importance of both chronic environmental factors and genetic family relationships on plasma lipids and lipoproteins.

Adolescent↗
PubMed1981

Clinical usefulness of urinary 3-methylhistidine excretion in indicating muscle protein breakdown.

Urinary excretion of the post-translationally modified amino-acid 3-methylhistidine, derived from the contractile proteins actin and myosin, was measured in patients with conditions associated with nitrogen loss. The ratio of 3-methylhistidine:creatinine excretion, a measure of the fractional catabolic rate of myofibrillar protein was increased in severe injury, thyrotoxicosis, neoplastic disease, prednisolone administration, and sometimes Duchenne muscular dystrophy. In myxoedema, osteomalacia, and hypothermia the ratio was decreased; and starvation, elective operations, and rheumatoid arthritis had little effect. Provided that the diet is meat free, measurement of urinary 3-methylhistidine may provide useful information on the cause of protein loss.

Adolescent↗
PubMed1981

Group therapy in the management of manic-depressive illness.

Because patients with bipolar affective illness have generally been viewed as poor candidates for psychotherapy, many clinicians have relied on lithium prophylaxis as the major treatment modality. However, even with lithium prophylaxis many patients still relapse, often in settings providing little support for maintenance treatment. This report presents the results of a long-term therapy group composed exclusively of bipolar manic-depressive patients, many of whom had histories of poor adherence ot lithium maintenance. The group met weekly and was conducted with an interpersonal, interactional "here and now" format. Patients attended an average of 47 sessions. Members were initially somewhat aloof and remote and minimized their problems. Over the course of their participation, members became more open and began to discuss their concerns about their illness and lithium maintenance treatment; during this time they functioned much as members in any long-term psychotherapy group. In the two-year period prior to entering the group, patients averaged 16.8 weeks of hospitalization; in the subsequent two-year period they averaged 3.6 weeks of hospitalization. Groups of this kind may offer a simple, cost-effective adjunct to lithium maintenance treatment and may provide the advantages and opportunities of psychotherapy to a group of patients generally seen as resistant to such approaches.

Adolescent↗
PubMed1980

Relationship between the basal blood alanine concentration and the removal of an alanine load in various clinical states in man.

1. Blood alanine was measured in six patients undergoing total hip replacement and in four normal subjects starved for 4 days. Hypoalaninaemia occurred in both groups and persisted in the surgical patients despite an adequate diet. The blood alanine was also low in four insulin-dependent diabetic patients and in four patients with muscular dystrophy; it was normal in four patients with cirrhotic liver disease. 2. The removal of an intravenous L-alanine load (12 g; 133 mmol) was significantly increased after surgery and in the diabetic patients, unaltered by starvation, and decreased in the cirrhotic patients. 3. Increases in blood glucose were observed when alanine infusion was performed 6 h after surgery and after 3 days' starvation. Increases in blood lactate and pyruvate always occurred after alanine infusion but were most marked 6 h after surgery. 4. These results show that the metabolic response to an alanine load and the ability of the body to remove it alter with change in physiological state, and that the hypoalaninaemia after surgery and in diabetes is related to an increased removal of intravenous alanine, whereas that during starvation is not.

Adolescent↗
PubMed1980

The effect of 3-methylhistidine in food on its urinary excretion in man.

1. To establish whether 3-methylhistidine in food is quantitatively excreted in the urine, five normal adults on a vegetarian diet were given known amounts of 3-methylhistidine in meat or fish. The mean cumulative 5-day increment in 3-methylhistidine excretion in non-hydrolysed urine accounted for an average of 90% of the 3-methylhistidine given during the first 3 days of this period. 2. To define the variation in urinary 3-methylhistidine on a constant mixed intake, the daily 3-methylhistidine excretion was measured for 6 days in four patients on a metabolic "balance" diet. The mean daily variation was less than 10%. 3. The results show that under the conditions of this study the increase in urinary 3-methylhistidine above basal levels can be quantitatively accounted for by the 3-methylhistidine content of additional food; in subjects on a constant diet it should be possible to detect relatively small changes in 3-methylhistidine excretion.

Adult↗
PubMed1980

Diabetic diets: high carbohydrate combined with high fiber.

The ideal level of carbohydrate intake for diabetics placed on high-fiber diets is unknown. Nineteen diabetics, therefore, took part in a total of twenty-four 5-day studies of fiber supplementation (guar) with carbohydrate intakes ranging from 22 to 61% of total calories. Where carbohydrate formed more than 40% of the calorie intake, there was a mean 64% reduction in glycosuria over the last 2 days on guar (P < 0.001, 14 studies, 11 patients). No significant reduction in glycosuria was seen in the 10 studies on lower carbohydrate intakes. This suggests that dietary fiber supplements in diabetes should be given against a background of higher rather than lower carbohydrate intake.

Adult↗