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Injectable silicone and the foot: a 41-year clinical and histologic history.

BACKGROUND: Since 1964, the author has investigated injectable liquid silicone as a soft tissue substitute for the loss of plantar fat. This form of fatty tissue depletion over the sole is closely linked to a common painful weight-bearing foot disorder, metatarsalgia, and to painless diabetic foot ulcers. OBJECTIVES: To present the history of injectable silicone, corporate interest, individuals who helped pursue approval, its misuses, and events that have delayed its availability. MATERIALS AND METHODS: Dow Corning Corporation's 360 Medical Fluid of 350 centistoke was injected beneath corns and calluses in 1585 patients. Diabetic neuropathic foot ulcers were injected after healing in an effort to prevent their recurrence. Surgical and postmortem specimens were gathered for histologic analysis. RESULTS: There was no evidence of significant adverse response in long-term clinical follow-up. Silicone specimens studied by two departments of pathology found no inflammation, infection, allergy, or granulomas. CONCLUSIONS: Medical Fluid silicone appears to be safe, effective, and stable biomaterial for treating weight-bearing loss of plantar fat. Trademarked PodiSil (Richard-James Inc., Peabody, MA, USA), a 350-centistoke injectable silicone has been approved for marketing in Europe for the prevention of diabetic foot ulcers.

Callosities↗

Diabetes and plasma lipoproteins in Native Americans. Studies of the Pima Indians.

OBJECTIVE--To determine the effects of diabetes on plasma lipoproteins in Pima Indians, to identify metabolic determinants of these differences, and to examine the effects of various modes of diabetes therapy. RESEARCH DESIGN AND METHODS--A series of studies was performed including a population survey of lipoprotein concentrations, kinetic studies of VLDL and LDL metabolism, and studies of the effects of weight loss, sulfonylureas, and high carbohydrate diets. RESULTS--Population data established that diabetes was consistently associated with elevations in total and VLDL TGs and decreases in HDL cholesterol. Metabolic studies indicated multiple alterations in VLDL metabolism induced by NIDDM, including overproduction of VLDL TG, impaired clearance of VLDL TG and apoB, and decreases in adipose tissue lipoprotein lipase. Although changes in LDL concentrations accompanying NIDDM were minimal, the clearance of LDL appeared to be impaired and a higher proportion of VLDL was metabolized without conversion to LDL. There were significant changes in the flux of particles to the LDL compartment. Total and VLDL TG concentrations were found to be inversely related to rates of insulin-mediated glucose disposal, and HDL cholesterol concentrations were positively related to glucose disposal. These relationships between lipoproteins and insulin action were independent of adiposity and insulin, suggesting that insulin resistance may be involved with diabetes-induced changes in VLDL and HDL. Weight loss was associated with decreases in total and VLDL TG, decreases in total and LDL cholesterol, and improvements in the ratio of HDL to LDL cholesterol. Sulfonylurea therapy was associated with lower total and VLDL TGs and lower LDL cholesterol, but little change in HDL. Substitution of complex carbohydrates for saturated fat in the diet showed consistent and significant decreases in total and LDL cholesterol, no decreases in HDL cholesterol, or elevation of total or VLDL TG. CONCLUSIONS--Studies suggest that there are multiple changes in plasma lipoproteins accompanying NIDDM in Pima Indians, but that many of these may be reversed by current modes of hypoglycemic therapy.

Adolescent↗

Effect of a high concentration perfluorocarbon emulsion on platelet function.

Perfluorocarbon (PFC) and lipid emulsions (eg. Fluosol, Intralipid,) containing phospholipid have been reported to modify platelet function after intravenous infusion. Platelet activation might be responsible for the generation of mediators responsible for PFC-induced side effects. In view of this, we investigated the effect of a highly concentrated perfluorocarbon emulsion containing 90% (w/v) perfluorooctylbromide (perflubron; PFOB), on porcine and human platelet activation and function. We measured both: a) stimulated ex-vivo porcine platelet aggregation pre and post infusion of either perflubron or control (vehicle only) emulsions, and b) stimulated in vitro human platelet calcium flux in the presence of perflubron emulsion or control emulsions. Platelet aggregation stimulated by collagen, ADP or arachidonic acid (AA) was inhibited in ex-vivo porcine platelets following infusion of perflubron emulsion at a dose of 3 ml/kg (0.2 ml/kg/min). Inhibition was dose dependent and was decreased when the dose of perflubron emulsion was reduced to 1.0 or 0.3 ml/kg. Infusion of saline or "vehicle" emulsions had little or no effect on stimulated ex-vivo pig platelet aggregation. Fluosol, infusion was associated with inconsistent inhibition of platelet aggregation. A23187- or AA-stimulated calcium flux of human platelets in vitro was inhibited in the presence of 1% (v/v) perflubron emulsion. Similar effects were seen with Fluosol, or Intralipid. This inhibition was agonist dose-dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Alternative therapies: Part II. Congestive heart failure and hypercholesterolemia.

Natural supplements are widely used by the American public but, while claims of their therapeutic effects abound, medical research does not always support their effectiveness. Clinical trials using Q10 for the management of congestive heart failure have had conflicting results; hawthorn is prescribed in Germany for the treatment of this condition, but no trials have been conducted in the United States. Although initial research about the use of garlic in the management of hypercholesterolemia was encouraging, follow-up studies have failed to verify these results. Substituting soy protein for high-fat animal protein diets, however, does have a beneficial effect on serum lipid levels. So far, cholestin (a natural product containing several statins) has proved to be a cost-saving lipid-lowering medication, and fenugreek may offer modest improvement as well. Gugulipid is also promising but requires further research.

Clinical Trials as Topic↗

[Effect of hormone replacement therapy on the cardiovascular system].

OBJECTIVE: Analysis of contemporary knowledge of influences of hormone replacement therapy on cardiovascular system. DESIGN: Literary review. SETTING: Department of Gynecology and Obstetrics, 1st Faculty of Medicine, Charles University, Prague. METHOD: Informations were collected from full-texts which were chosen in database Medline and Ovid. CONCLUSION: Hormone replacement therapy (HRT) has positive influence on some risk factors of cardiovascular disease. Changes in the lipoprotein spectrum are well known. Oral estrogens cause a decrease of low density lipoprotein cholesterol (LDL-C) and, especially an increase of high density lipoprotein cholesterol (HDL-C) levels, which both have potentially favourable effects; they also cause a triglyceride level increase, which probably has no clinical relevance except in cases with basal hypertriglyceridemia. Transdermal estradiol causes generally a minor decrease in LDL-C and minor increase HDL-C levels, with no increase or even decrease in triglyceride levels. The addition of androgenic progestins at conventionally used doses, while not interfering with LDL-C variations, causes a HDL-C decrease, which contrasts he effect of oral estrogens and completely reverses the effect of transdermal estradiol. On the contrary, the addition of a non-adrogenic progestin does not interfere with any of the estrogen induced lipid profile modifications. Transdermal estradiol does not cause change of insulinoresistance. Estrogen substitution protects gynoid distribution of body fat that is connected with lower risk of ischemic heart disease. Estrogens have possibility to dilate vessels. Decreasing of levels of cytoadhesive molecules was verify during HRT so as lowering of homocysteine level to premenopausal levels. Newly uncovered changes like the significant increase of CRP connected with oral estrogen therapy could explain increasing of cardiovascular risk on the beginning of HRT especially in group of women with history of ischemic heart disease.

Cardiovascular Diseases↗

Food intake of very obese persons: quantitative and qualitative aspects.

To document the caloric intake of very obese persons and investigate the food choices and dietary composition that maintain severe obesity, we studied the self-selected food intake required to maintain stable weight in two groups of very obese subjects: 11 inpatients with a mean weight 181% above desirable body weight and 35 outpatients with a mean weight 125% above desirable body weight. Qualitative and quantitative food intake were evaluated using records obtained on the hospital metabolic ward for the inpatients and using self-recorded food records for the outpatients. Absolute caloric intake in both groups was greater in proportion to the degree of obesity (deviation from desirable body weight); caloric intake per unit of lean body mass (kilocalories per gram urinary creatinine) was constant regardless of the degree of obesity and was essentially the same as that of normal nonobese persons. Food records indicated that the obese subjects maintained their high caloric intake by consuming mostly foods of high caloric density, with occasional binge eating. They largely avoided foods of low intrinsic energy density and modified-calorie foods, ie, foods with decreased fat, nonnutritive sweeteners, or fillers. By substituting foods of lower caloric density for usual food choices from the same food group, obese persons could decrease caloric intake by 20% and increase potential for notable weight loss.

Adult↗

[Detoxification by the rat of compounds formed during thermal polymerization of linseed oil. II. Effects of discontinuous administration of the heated oil on the urinary excretion of glucuronides, liver weight and the tissue content of cyclic monomers].

During four successive periods of 9 days each, adult rats were fed alternatively fresh or hermopolymerized linseed oil in their diet. As compared to the control animals, the rats fed with the thermopolymerized oil showed increased urinary glucuronide excretion and higher liver weight, as well as a rise in the cyclic monomer content in that organ and, to a lesser degree, in the fat tissue. When fresh oil was substituted for heated oil in the diet, these animals recovered the levels of urinary glucuronides and liver monomers observed in the control rats. On the contrary, the rise in liver weight still observed can be considered as an indication of diet toxicity.

Animals↗

[Surgical treatment of chronic calcifying pancreatitis].

A total of 58 patients with chronic pancreatitis had undergone partial duodenopancreatectomy. They were subdivided by histological differentiation according to the presence or absence of calcification and it was found that pancreatic function was far more severely reduced in patients with organ calcification. Exocrine insufficiency was also more marked in these patients, as shown by the weight and fat content of their stool. Enzyme substitution therapy usually has no complications. Endocrine function was also affected, as seen in the preoperative presence of diabetes in 36% of patients with pancreatic stones, three times that of those with sclerosing pancreatitis. Resection of the pancreatic head led to an increase of 12%, i.e. 48%. This indicates that non-resecting operations are preferable in calcifying pancreatitis. Recommendations are made as to the choice of partial duodenopancreatectomy or pancreaticojejunostomy, depending on radiological classification, the course of the disease and the symptoms in each individual case.

Calcinosis↗

Effects of legume consumption on serum cholesterol, biliary lipids, and sterol metabolism in humans.

Legume consumption appears to lower serum cholesterol and to increase cholesterol saturation of bile, but the mechanisms of these effects have not been established. We studied nine human subjects on a metabolic ward during two randomly ordered 6-7 week periods: one during consumption of a control diet and the other during consumption of the same diet with 120 gm mixed legumes substituted for foods having equivalent calories, fat, protein, and carbohydrate. Mean serum LDL cholesterol was significantly lower during legume consumption (126 vs. 138 mg/dl, P = 0.039). Legume consumption significantly increased mean cholesterol saturation index of gallbladder bile from 1.07 to 1.26 (P = 0.016), largely because of an increase in hepatic secretion of cholesterol from a mean of 90.2 mumol/h to 100.8 mumol/h (P = 0.042). Fecal neutral sterol output was unaffected by legumes, but fecal acidic sterols increased from a mean of 861 to 1202 mumol/day (P = 0.002) during legume consumption. Mean sterol balance became significantly more negative during legume consumption (-2140 vs. -2700 mumol/day, P = 0.037) indicating an increase in cholesterol synthesis. Mean fractional absorption of bile acid was lower during legume consumption than (0.947 vs. 0.960, P = 0.003). These data suggest that legume consumption lower LDL cholesterol by partially interrupting the enterohepatic circulation of bile acids and increases cholesterol saturation of bile by increasing hepatic secretion of cholesterol.

Adult↗

[Postoperative treatment of patients after pancreatectomy. Closely meshed monitoring of blood sugar (author's transl)].

A report is presented on the postoperative treatment of 4 patients who had undergone duodeno-pancreatectomy because of chronic pancreatitis. When the patients co-operate well satisfactory metabolic compensation can be achieved with small doses of insulin. Replacement of the pancreatic enzymes with the appropriate preparations can be particularly well monitored by means of the fat content of the faeces. The substitution of vitamins A, D, K, and B12 parenterally at intervals of several weeks is also advisable as a safety measure. A method is described for the closely meshed monitoring of the blood sugar. This method is suitable in co-operative patients who are capable of collecting capillary blood for achieving a particularly good control of the metabolic state.

Adult↗

Codon 54 polymorphism of the fatty acid binding protein 2 gene is associated with increased fat oxidation and hyperinsulinemia, but not with intestinal fatty acid absorption in Korean men.

The alanine to threonine substitution at codon 54 (Ala54Thr) of the fatty acid binding protein 2 (FABP2) gene has been reported to be associated with increased fat oxidation and insulin resistance in several populations. It has been hypothesized that Ala54Thr substitution results in enhanced intestinal uptake of fatty acids and thereby an impairment of insulin action, but this hypothesis has not been proven in vivo. We studied the association between the Ala54Thr polymorphism of the FABP2 gene and intestinal (3)H-oleic acid absorption, as well as basal insulin level, basal metabolic rate, and fat oxidation rate in 96 healthy young Korean men. Among our subjects, the allele frequency of the Ala54Thr substitution was 0.34. Subjects with Thr54-encoding allele were found to have a higher mean fasting plasma insulin concentration and a higher basal fat oxidation rate compared with the subjects who were homozygous for the Ala54-encoding allele. However, there was no significant difference in basal metabolic rate or (3)H-oleic acid absorption according to the FABP2 gene polymorphism. These results suggest that the Ala54Thr substitution in the FABP2 gene is associated with increased fat oxidation and hyperinsulinemia in normal Korean men, but these effects are not mediated by an increase in the intestinal fatty acid absorption.

Animals↗

Effects of dietary carbohydrates on metabolism of calcium and other minerals in normal subjects and patients with noninsulin-dependent diabetes mellitus.

Transient hypercalciuria has been noted after high carbohydrate meals which is independent of dietary calcium and is probably due to impaired renal calcium reabsorption mediated by an increase in plasma insulin levels. Based on these observations, some investigators believe that long term intake of high carbohydrate diets may increase the risk of nephrolithiasis and possibly osteoporosis. Using a randomized cross-over design, we compared high carbohydrate diets (60% carbohydrate and 25% fat) with high fat diets (50% fat and 35% carbohydrate) for effects on metabolism of calcium and other minerals in eight normal subjects and eight euglycemic patients with noninsulin-dependent diabetes mellitus. All other dietary constituents, such as protein, fiber, fluid, minerals (including Ca, Mg, Na, K, and P), and caffeine intake, were kept constant. Despite higher daylong levels of plasma insulin on the high carbohydrate diets compared to the high fat diet in both normal and noninsulin-dependent diabetic subjects, no changes in daily urinary excretion of calcium or other constituents, associated with renal stone risk, were observed. Furthermore, there was no change in fractional intestinal 47Ca absorption. Although hypercalciuria may ensue transiently after high carbohydrate meals, we conclude that substitution of simple or complex carbohydrates for fats in an isocaloric manner for a longer duration does not result in significant urinary calcium loss, and therefore, high intakes of digestible carbohydrates may not increase the risk of nephrolithiasis or osteoporosis via this mechanism.

Adult↗

Characterization of the DGAT1 gene in the New Zealand dairy population.

Recently, DGAT1 was identified as the gene that underlies the QTL for bovine milk production on chromosome 14. This study investigated the effect of the reported polymorphism in three dairy breeds in New Zealand. Statistically significant results were identified for milk fat, milk protein, and volume for Jersey and Holstein-Friesian breeds, and only milk volume for Ayrshires. The average allele substitution effects were 2 to 3 kg of protein and 120 to 130 l milk for both the Jersey and Holstein-Friesian breeds. For milk fat, the average allele substitution effect was 6 kg for Holstein-Friesians and 3 kg for Jerseys. In all breeds, where the polymorphism increased milk fat yield, it decreased milk protein yield and milk volume.

Acyltransferases↗

Composition and variability of the branched-chain fatty acid fraction in the milk of goats and cows.

Branched-chain fatty acids of the milk fat of goats were analyzed by high resolution gas chromatography-mass spectrometry. Iso-and anteiso-acids predominated, but a range of other monomethyl-branched components, mostly with methyl-substitution on carbons 4 and 6, was present. Analysis of the milk fat of cows revealed the presence of iso-and anteiso-fatty acid; other monomethyl-substituted fatty acids, as found in the milk fat of the goat, were virtually absent. Only a trace amount of 6-methylhexadecanoate was detected. The difference between goats and cows in the effectiveness with which these animals metabolize propionyl-CoA and methylmalonyl-CoA is discussed.

Acyl Coenzyme A↗

Milk-substitutes comparable to rat's milk; their preparation, composition and impact on development and metabolism in the artificially reared rat.

1. Procedures are described to prepare nutritionally adequate rat milk-substitutes by modifying commercially available processed cow's milk, rich in carbohydrate and low in protein and fat compared with rat's milk. 2. Premilk formulas, prepared as intermediates in the preparation of rat milk-substitutes, are rich in protein but low in their concentration of fat, carbohydrate, and minerals when compared with rat's milk. 3. Premilks were supplemented with lactose, vitamins, minerals, fat as oil mixtures, certain amino acids and other constituents to yield rat milk-substitutes which resemble the known composition of rat's milk in their properties and composition. 4. Detailed analyses of the milk-substitutes show them to be comparable to rat's milk in energy content, pH, osmolarity, the concentration of the macronutrients, fat, protein and carbohydrate, and the major minerals. 5. Rat pups were artificially reared from postnatal day 4 or 5 until days 16-18 by fitting them with gastric cannulas through which the milk-substitutes could be infused automatically. 6. The nutritional impact of the milk-substitutes was assessed by a comparison of growth and metabolic characteristics for artificially reared rats with age-matched sucking rats reared by their mother. 7. Indices which were taken to be appropriate included (a) body-weight gain; (b) the concentration in blood of protein, amino acids, ketone bodies, carnitine, glucose, galactose, lactate, insulin, and the electrolytes calcium, sodium, potassium and chloride; (c) the turnover of glucose and 3-hydroxybutyrate; (d) the concentration in brain of protein, cholesterol, cerebroside sulphate and the activities of the enzymes pyruvate dehydrogenase (EC 1.2.4.1), 3-oxo-acid-CoA transferase (EC 2.8.3.5) and acetoacetyl-CoA ligase (EC 6.2.1.16). 8. The studies suggest that milk-substitutes approximating to rat's milk in composition promote acceptable metabolism in the artificially reared rat pup.

Amino Acids↗

Concentrations of polychlorinated dibenzo-p-dioxins, dibenzofurans and non-ortho substituted biphenyls in polar bear milk from Svalbard (Norway).

Polychlorinated dibenzo-p-dioxins (PCDD), dibenzofurans (PCDF) and non-ortho substituted biphenyls (PCB, CB) were determined in 6 polar bear milk samples from Svalbard (Norway). For these compounds, no data for polar bears have been reported before from this region. Most of the PCDD/PCDF congeners were found at detectable levels. Concentrations expressed as 2,3,7,8-TCDD equivalents (Nordic model) were in the order of 1-3 pg/g(-1) fat (0.2-1.6 pg ml(-1) milk) which is comparable with ringed and harp seal blubber from the same region. On whole milk basis, concentrations were similar to those found in human milk. An estimation of the daily uptake via milk showed that the intake is lower for polar bears compared to humans. As in human milk, relatively high levels of OCDD were found in some polar bear milk samples. The PCDD/PCDF congener pattern in the milk was different to that found in polar bear fat from the Canadian Arctic. Non-ortho substituted PCB levels in polar bear milk were similar to those found in polar bear fat from the Canadian North. However, CB 77 or 169 dominated in the milk while CB 126 was the most abundant congener in fat. PCDD/PCDF levels expressed as 2,3,7,8-TE were highly correlated with the fat content of the milk. No correlation between CB and PCDD/PCDF concentrations was found. Some data indicate that PCDD/PCDF concentrations in polar bear milk decrease with increasing time after delivery.

Journal Article↗

Dietary protein source determines the degree of hypertension and renal disease in the Dahl salt-sensitive rat.

Previous studies demonstrated that a whole-grain diet attenuated sodium-dependent hypertension and renal disease in Dahl salt-sensitive rats from the colony at the Medical College of Wisconsin (Dahl SS/Mcw rats) compared with rats maintained on a purified AIN-76A diet. The present experiments determined which component(s) of the grain diet prevented renal and cardiovascular disease. Male SS/Mcw rats were maintained on isocaloric diets identical to AIN-76A, except the source of protein (wheat gluten for casein), carbohydrate (wheat flour for sucrose), or fat (soybean oil for corn oil) was substituted in separate diets. Rats were maintained on the different diets from weaning and studied after 3 weeks on a high-salt (4.0% NaCl) diet. Substitution of the carbohydrate in the diet did not affect body weight, arterial pressure, or renal disease. Replacement of casein with wheat gluten significantly reduced body weight (258+/-7 versus 353+/-3 grams), mean arterial pressure (133+/-2 versus 153+/-2 mm Hg), and albumin excretion (9+/-1 versus 50+/-7 mg/d) to levels of rats fed the whole-grain diet (n=7 to 16/group). Replacement of the fat in the diet increased arterial pressure without affecting body weight or albumin excretion. The results of the present study indicate that dietary components other than sodium play an important role in the development of hypertension and renal disease in the Dahl SS/Mcw rat.

Albuminuria↗

Exposure of neonatal male rats to estrogen induces abnormal morphology of the penis and loss of fertility.

The research objectives are to determine whether estrogen-induced infertility is associated with abnormal morphology of the penis and if morphological alterations can be reversed by testosterone (T). Male pups received diethylstilbestrol (DES) on alternate days from postnatal days 2 to 12. They received T or empty implants at 180 days, were tested for fertility at 188 days, and terminated at 200 days. While 5/7 control males sired pups, only 1/6 did in the DES group, and 0/8 in the DES plus T group. In addition to reductions in penile length and weight, the novel structural change induced by DES, and not reversed by T, was a replacement of cavernous spaces by fat cells in the penis body. Hence, T substitution for 8 days at adulthood did not reverse infertility in rats treated neonatally with DES and provided evidence that infertility probably resulted from absence of cavernous spaces and/or accumulation of fat cells in the penis body.

Age Factors↗