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Biomedical subjects

E M Berry

Publications and source records attributed to E M Berry.

At least 19 recordsLinked to original sources

Significant weight reduction in obese subjects enhances carbamazepine elimination.

Single-dose (200 mg) carbamazepine pharmacokinetics was evaluated in six obese, otherwise healthy subjects, before and after a mean +/- SEM weight reduction of 30.0 +/- 5.0 kg over 11.3 +/- 1.2 months. After weight loss the mean +/- SEM plasma elimination half-life (t1/2) of carbamazepine was significantly shortened (60.3 +/- 3.1 versus 30.8 +/- 3.3 hours, p less than 0.01) and the total plasma clearance (CL) increased (20.4 +/- 1.8 versus 31.6 +/- 5.0 ml/min, p less than 0.05). The apparent volume of distribution (Varea) decreased (106.2 +/- 9.9 versus 77.7 +/- 4.5 L, p less than 0.01); however, no difference was evident when carbamazepine Varea was corrected for body weight. In addition, weight loss coincided in all participants with a complete sonographic disappearance of the initial fatty liver infiltration noted on enrollment. In conclusion, obesity associated with fatty liver presents an enlarged carbamazepine Varea, prolonged carbamazepine t1/2, and reduced carbamazepine CL. Whenever carbamazepine is initiated in obese subjects, steady-state concentrations should be expected only after twice the time required to achieve steady state in lean subjects. Thus carbamazepine maintenance dose should be reduced, dose interval prolonged, and monitoring of carbamazepine plasma levels provided.

Administration, Oral

Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins--the Jerusalem Nutrition Study. II. Monounsaturated fatty acids vs carbohydrates.

Seventeen male Yeshiva students were randomly allocated to a crossover study with two 12-wk dietary periods of monounsaturated fatty acids (MUFAs) vs a carbohydrate (CHO)-rich diet while concentrations of saturated (SFAs) and polyunsaturated (PUFAs) fatty acids were kept similar. Total plasma cholesterol (TC) decreased significantly by approximately 7.7% and low-density-lipoprotein cholesterol (LDL-C) by 14.4% on the MUFA diet, whereas on the CHO diet no significant change in cholesterol concentrations occurred, in contrast to that predicted by the equations of Keys and Hegsted. Concentrations of high-density-lipoprotein cholesterol (HDL-C) did not change significantly on either diet. On the MUFA diet there was a significantly lower proneness to peroxidation of plasma and LDL lipids and less extensive metabolism of conditioned LDL by peritoneal macrophages. We conclude that dietary MUFAs lower TC and LDL-C concentrations, independently of other dietary fatty acids and in addition may reduce the susceptibility of LDL to oxidative stress.

Adult

Fish oil ingestion in smokers and nonsmokers enhances peroxidation of plasma lipoproteins.

The effect of fish oil ingestion (10 g MaxEPA/day) on the susceptibility of plasma lipoproteins to peroxidation was examined in 20 smokers (study A and B) and 22 nonsmokers (study C). The subjects were examined at the onset of each study (baseline values), divided into control and experimental groups and reexamined 4 weeks later. Smokers were examined 40 h after abstention from smoking (0 time) and 90 min after acute smoking (4-6 cigarettes). The parameters studied were TBARS, which provide an indication of peroxidative injury, and metabolism of conditioned LDL by macrophages as a biological indicator. These parameters were significantly higher (P less than 0.05-0.001) when the 90 min values of smokers were compared to time 0. After 4 weeks of fish oil ingestion, a significant rise above baseline values (33-50%) in plasma and LDL TBARS was found in smokers examined at time 0 and after acute smoking. Peroxidative modification of LDL isolated from smokers fed fish oil resulted in significantly higher TBARS (34-41%) and its metabolism by macrophages was higher (65-139%) compared to baseline values. In nonsmokers, the baseline values of the above parameters were lower than in smokers. Ingestion of fish oil resulted in a significant rise in TBARS in plasma (33%), LDL (137%), conditioned LDL (36-40%) and metabolism of conditioned LDL (70%) by macrophages. In 6 nonsmokers and 4 smokers, 400 mg of vitamin E/day were given with the fish oil. In the nonsmokers, vitamin E counteracted the effect of fish oil more effectively than in the smokers. In the light of the present results, indiscriminate recommendation of fish oil supplementation to the population at large should be cautioned.

Animals

Polymyxin B reduces cecal flora, TNF production and hepatic steatosis during total parenteral nutrition in the rat.

Hepatic complications are common in patients receiving total parental nutrition (TPN) and who have no underlying liver disease. In the present study we examined the hypothesis that endotoxin (LPS) or possibly TNF derived from the overgrowth of intestinal gram-negative bacteria is responsible for TPN-associated hepatic steatosis, and that bowel decontamination and specific anti-LPS activity of polymyxin B will reduce fatty infiltration of the liver during TPN. Forty-five male Sabra rats underwent jugular vein cannulation, were placed in metabolic cages, and were randomized into five groups. Group I was continuously infused with normal saline and allowed food ad lib, while group II-V were continuously infused with a TPN formula containing 4.25% amino acids and 25% dextrose for a total of 36 calories and 3.0 g protein per 100 g body weight/day. In addition, groups III-IV were also treated by oral polymyxin B while Groups IV and V received a combination of neomycin, metronidazole, and vancomycin (NMV). Thus, Group III received polymyxin B, Group IV received both polymyxin B and NMV, while Group V received NMV only. On Days 7-8 of the study, all animals were sacrificed and spontaneous production of TNF by peritoneal macrophages, bacterial translocation to mesenteric lymph nodes, culture of the cecum, and fat, triglyceride, and cholesterol contents of the liver were determined. All groups infused with TPN exhibited higher levels of total fat, triglycerides, and cholesterol compared to the free feeding control group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue

Effects of diets rich in monounsaturated fatty acids on plasma lipoproteins--the Jerusalem Nutrition Study: high MUFAs vs high PUFAs.

Twenty-six Yeshiva students were randomly assigned to a 24-wk crossover study of monounsaturated fatty acid (MUFA) vs polyunsaturated fatty acid (PUFA) diets (50% carbohydrate, 32% fat, 18% protein) fed alternately during two 12-wk periods. Total plasma cholesterol (TC) decreased significantly by approximately 10% and approximately 16% on the MUFA and PUFA diets, respectively. Plasma triglyceride response was variable. Low-density-lipoprotein cholesterol (LDL-C) decreased in both groups with an additional significant effect between periods. Concentrations of high-density-lipoprotein cholesterol did not change significantly. LDL-receptor status in fresh monocytes, affinity of LDL towards the LDL receptor in cultured fibroblasts, zonal-centrifugation profiles, and lipoprotein composition were not significantly different between the diets. There was a significantly higher tendency toward lipid peroxidation on the PUFA diet, as ascertained by more thiobarbituric acid-reactive-substances formation on that diet. Dietary PUFA results in somewhat lower TC and LDL-C concentrations whereas with MUFA the susceptibility of LDL to oxidative stress is lower.

Binding, Competitive

Metabolic and hemodynamic responses to endogenous and exogenous catecholamines in formerly obese subjects.

Formerly or reduced-obese (RO) subjects exhibit diminished systemic energy requirements for weight maintenance. Based on studies in animals and humans, there is reason to believe that the autonomic nervous system (ANS) plays an important role in coordinate regulation of energy metabolism and may be altered in the RO state. We have, therefore, investigated aspects of autonomic physiology in obese (OB), RO, and never obese (NO) subjects subjected to insulin-mediated hypoglycemia and incremental intravenous infusions of epinephrine. Total catecholamine secretion during insulin-induced hypoglycemia was significantly lower in the RO. The RO showed increased sensitivity to in vivo lipolytic and cardiovascular effects of endogenous and infused catecholamines. In these studies, OB subjects responded more like the NO subjects than did the RO. The RO display characteristic changes in autonomic status that may play a role in their enhanced energy efficiency.

Adult

A balanced carbohydrate: protein diet in the management of Parkinson's disease.

Although restricting dietary protein is a proposed adjunct to treating Parkinson's disease (PD), the effect of carbohydrate consumption is unknown. We measured plasma levodopa and large neutral amino acid (LNAA) levels in nine PD patients treated with carbidopa/levodopa and different isocaloric meals containing high protein-low carbohydrate, low protein-high carbohydrate, and balanced 5:1 carbohydrate:protein mixtures. We found that levodopa levels increased significantly regardless of the type of diet, but that plasma LNAA levels varied less and motor performance was superior after the balanced diet than after the other two meals. We conclude that PD patients can consume nutritionally adequate meals and still maintain a stable plasma levodopa:LNAA ratio.

Amino Acids

Smoking depresses adipose lipoprotein lipase response to oral glucose.

Adipose tissue lipoprotein lipase was studied in smokers (n = 17) aged 18-47 years and compared with enzyme activity in non-smokers of comparable age (n = 8) and a second time in some of the subjects 5-9 weeks after cessation of smoking (n = 7). Serum cotinine levels served to validate the smoking status of the subjects. Fasting enzyme activity was similar in smokers and non-smokers, when expressed per 10(6) cells, but was significantly increased when normalized for cell size. When lipoprotein lipase was determined in the same individual 4 h after an oral glucose load, a significant decrease (P less than 0.002) occurred in the smokers, while enzyme activity rose in the nonsmokers (P less than 0.02). A tendency for enzyme activity to rise after oral glucose was seen in ex-smokers, which did not reach statistical significance. Even though the mean serum insulin and glucose levels did not differ in the three groups of subjects, the per cent decrease in lipoprotein lipase after oral glucose in smokers was negatively correlated with insulin release into serum in the same subject, i.e., the greater the insulin release, the less the decrease in lipoprotein lipase activity. We would like to propose that the lower body weight in smokers is related to the paradoxical response of adipose tissue lipoprotein lipase to carbohydrate and that the reversal of this behaviour contributes to the weight gain often observed after cessation of smoking.

Adipose Tissue

Modification of cellular fatty acid composition of Hep-G2 cells: effect of antioxidants on cholesterol esterification and secretion.

Modification of fatty acid composition of Hep-G2 cells was achieved by 7-9 days of supplementation of culture medium with palmitic, oleic or linoleic acid. Cholesterol release into serum-free culture medium during 24 h of incubation was significantly lower in cells supplemented with linoleic acid, when compared to those supplemented with palmitic, oleic or no additional fatty acid. In cells cultured in the presence of linoleic acid, less [3H]cholesterol was esterified to cholesteryl ester and the mass of cholesteryl ester was significantly lower than in cells cultured with palmitic acid or with no additional fatty acid. The reduction in [3H]cholesterol secretion and the impairment in cholesterol esterification in linoleic acid-treated cells was prevented by addition of butylated hydroxytoluene or probucol concurrently with the fatty acid. The antioxidants also increased esterification and [3H]cholesterol release in cells supplemented with the other fatty acids. It is suggested that cholesterol secretion and esterification are sensitive to peroxidation.

Antioxidants

Diagnosis deferred--the clinical spectrum of diagnostic uncertainty.

This study attempts to define the term "Diagnosis Deferred" (DD) and determine its natural history and outcome. It is suggested that such a "non-diagnosis" should be used when the clinical and laboratory picture cannot be explained by any known disease entity after a minimum of 5 days hospitalization. During a 9 year period (1972-1980) 250 patients (1.8%) were identified as warranting the term DD from a total of 14,098 admissions to a department of Internal Medicine. Their average stay in hospital was 11.5 days. There was no sex difference between the patients, whose average age was 42.8 +/- 17.6 years (mean +/- SD; range 14-93). Three complaints predominated: joint pains (21.6%), abdominal pain (20.4%) and chest pain (16.8%). In 103 of the patients, there was follow-up information until the diagnosis was made or for at least 24 months (average 53.0 +/- 40.0 months, range 2-186). These patients were representative of the original cohort in both age, sex and classification of symptoms. Forty-three patients (42%) were subsequently diagnosed. 58% of these patients were diagnosed as a result of a change in or appearance of a clinical symptom during the follow-up period. "The survival of diagnostic uncertainty" in 50% of the patients was 84.5 months (7 years) with a range of 2-13 years. This time was significantly shorter for chest pain than for abdominal pain (33 months vs 87 months) (p = 0.003). In patients with "Diagnosis Deferred", a diagnosis was reached in 42%; in 22% the symptoms disappeared leaving 36% undiagnosed, and a continuing clinical challenge.

Abdomen, Acute

Preferential metabolism by macrophages of conditioned rabbit hypercholesterolemic remnant lipoproteins.

Rabbits were fed a diet containing 1% cholesterol, and lipoproteins were isolated from their plasma by sequential ultracentrifugation. Lipoprotein remnants (d = 1.019-1.063) were conditioned by incubation with bovine aortic smooth muscle cells for 24 h and then incubated for 4 h with J774 cells or mouse peritoneal macrophages. Conditioning of remnants and low-density lipoproteins resulted in enhancement of their uptake and metabolism by the macrophages in culture. The macrophages metabolized conditioned remnant lipoproteins more extensively than controls at all concentrations tested. Addition of 10% safflower oil or 10% butter to the 1% cholesterol diet resulted in a molar ratio of linoleic/oleic acid of 1.62 and 0.62 in plasma neutral lipids and of 5.7 and 2.5 in plasma phospholipids. Conditioned remnants, derived after safflower oil feeding, were metabolized more extensively by macrophages than those obtained after butter feeding. This was also true for control remnants (preincubated without cells). Thiobarbituric acid-reactive substances were higher in remnants from safflower oil-fed than butter-fed rabbit plasma prior to and after conditioning. Mouse peritoneal macrophages metabolized remnant lipoproteins more extensively than low-density lipoproteins. The present results indicate that modification of remnant lipoproteins, the major atherogenic fraction of cholesterol-fed rabbit plasma, results in their enhanced metabolism by macrophages, and that an increase in the linoleic/oleic acid ratio in these lipoproteins might enhance their susceptibility to peroxidative modification.

Animals

The relationship between dietary fat, adipose tissue composition, and neoplasms of the breast.

Dietary fat has been implicated in the development of carcinoma of the breast. Because of the difficulties in obtaining accurate dietary histories, we analyzed subcutaneous adipose fatty acids to compare the quality of fat intake in three groups of patients undergoing investigations for breast masses. These included carcinoma (n = 37, avg. age 54 yrs.), fibroadenoma (n = 27, age 31 yrs.), and other types (n = 21, age 50 yrs.). Subjects in the carcinoma group were heavier, although they were not obese. A one-way analysis of variance of nine adipose fatty acids and their derived ratios [polysaturates:saturates (P:S)] did not show any systematic differences in the three groups. The quality of dietary fat does not appear to be associated with the development of neoplasia of the breast in this population, which consumes a diet of a high P:S ratio.

Adenofibroma

Familial aggregation of body mass index in ethnically diverse families in Jerusalem. The Jerusalem Lipid Research Clinic.

Familial aggregation of body mass index in different ethnic populations was studied in a sample of nearly 4000 families resident in Jerusalem. Covariate adjustments were applied to body mass index (BMI) to adjust for variation in means and variances with sex, age and origin and for the effect of education, socioeconomic status and seasonality. The analyses were done separately in each of the origin groups categorized according to the parents' country of birth (Europe, Asia, North Africa, Israel/mixed origin), in order to account for the heterogeneity among the groups. Parent-child correlations were generally homogeneous across the origin groups. Sibling correlations for BMI differed to a greater extent among the groups. The highest correlation was observed in the Asian group (r = 0.49) and the lowest in the North African group (r = 0.16). Pooled correlations among biological relatives across the origin groups were highly significant. Spouse correlation, although significant was smaller, suggesting a stronger influence of genes than shared environment in the determination of the trait. Father-child correlation was significantly higher (r = 0.25) than mother-child value (r = 0.19), suggesting a possible paternal influence on BMI. There was also asymmetry in parent-offspring correlations by the sex of the offspring. Sibling correlation was higher (r = 0.33) than parent-offspring correlation (r = 0.22), suggesting that shared environment within generations tended to have some importance.

Adolescent

Fat-free diet and myocardial excitability, refractoriness and ventricular fibrillation.

The lipid composition of the sarcolemma influences its function. The purpose of this study is to investigate the electrophysiological alterations induced in the rat's heart by dietary manipulation of cardiac fatty-acid composition. Strength-duration and strength-interval relationships were used to study excitability and refractoriness respectively. Ventricular fibrillation threshold measured by short bursts of rapid stimulation was used to indicate ventricular vulnerability. Gas liquid chromatography was used to analyse cardiac fatty-acid-composition. We used two-week-old rats fed with fat-free diet and 5% and 10% soya bean oil-supplemented diets for 6-9 weeks. Fat-free diet only was associated with increased eicosatrienoic acid content, a marker of essential fatty-acid deficiency. A decrease in poly-unsaturated to saturated (P:S) fatty-acid ratio was also observed. Five percent oil supplementation was associated with a delay and attenuation of this effect. Fat-free diet was associated with increased excitability, decreased refractoriness and reduced ventricular fibrillation threshold. Ten percent oil supplementation prevented these effects while 5% oil supplementation had only a temporary protective effect. We conclude that manipulation of dietary fat content can affect cardiac fatty-acid composition and electrophysiology.

Animals

Does dietary linolenic acid influence blood pressure?

Short-term intervention studies have shown that diets rich in polyunsaturated fats have hypotensive properties. We have studied the long-term effects of dietary fat on blood pressure (BP) using adipose-tissue, fatty acid composition analysis in 399 free-living male subjects (average age, 47 yr). Stepwise-regression analysis showed that adipose linoleic acid (18:2 n-6) was not associated with BP, whereas an absolute 1% increase in linolenic acid (18:3 n-3) was associated with a decrease of 5 mm Hg in the systolic, diastolic, and composite mean arterial BP. Linolenic acid (18:3) comprised only one-eighth the amount of linoleic acid (18:2)--the major polyunsaturate in adipose tissue and hence in the diet (2% vs 16%)--and yet it had a disproportionate association with BP. This may be related to its role as a precursor for the production of prostaglandins and/or other vasoregulators. Dietary manipulation with n-3 fatty acids may be helpful in the treatment and prevention of hypertension.

Adipose Tissue

The role of dietary fat in human obesity.

Both the amount and quality of dietary fat have been implicated in the pathogenesis of obesity. Adipose tissue fatty and composition, which is known to reflect dietary intake, was sampled in 413 free-living, healthy American males appearing for a routine medical examination. The average age was 46.8 +/- 11.4 years (mean +/- s.d.) and body mass index (BMI)--weight/height--was 25.2 +/- 3.4. The BMI was correlated (P less than 0.01) with known risk factors for cardiovascular disease as follows: total cholesterol (TC) r = 0.18, triglycerides (TG) r = 0.32, low-density lipoprotein cholesterol (LDL-C) r = 0.18, high-density lipoprotein cholesterol (HDL-C) r = -0.24, systolic and diastolic blood pressure (BP) r = 0.30. Underlying patterns which might be related to diet were sought in the distribution of the seven major fatty acids in adipose tissue. Statistical analysis permitted delineation of three factors which were hypothetically related to animals fat intake (F1--monounsaturates), carbohydrate intake (F2--saturates) and vegetable oil intake (F3--polyunsaturates). F1 and F3 together accounted for 12 percent of the variance in BMI while F2 had no influence. Our conclusions are that the variance in BMI is related much more to non-dietary factors than to adipose tissue fatty acid composition and that the nature of dietary fat was not a major distinguishing factor in obesity in this population. There was also no evidence for a high dietary carbohydrate (low fat) intake in the obese.

Adipose Tissue

Dietary fat, adipose tissue composition, and the development of carcinoma of the colon.

Dietary fat and plasma lipids have been implicated in the development of carcinoma of the colon. Because of the difficulties in obtaining accurate dietary histories, subcutaneous adipose tissue fatty acids were analyzed to compare fat intake in 3 groups of patients undergoing colonoscopy: patients with carcinoma of the colon (n = 53; average age, 64 yr; 47% male), patients with neoplastic polyps (n = 34; age 63 yr; 71% male), and patients with normal findings (controls; n = 68; age 58 yr; 40% male). The groups were similar with regard to body mass index and coffee and egg consumption. One-way analysis of variance of the plasma total cholesterol, triglycerides, high-density lipoprotein cholesterol, 9 adipose fatty acids, groups of polyunsaturated fatty acids (vegetable origin), saturated fatty acids (animal origin), or the ratio of polyunsaturated to saturated fatty acids did not show any significant differences across the 3 groups. The quality of dietary fat does not appear to be associated with the development of carcinoma of the colon or of neoplastic polyps in this population.

Adipose Tissue