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Biomedical subjects

I Grosskopf

Publications and source records attributed to I Grosskopf.

At least 19 recordsLinked to original sources
PubMed1998

Fluctuations of lipid and lipoprotein levels in hyperlipidemic postmenopausal women receiving hormone replacement therapy.

BACKGROUND: Fluctuations in lipid and lipoprotein levels are encountered quite often in hyperlipidemic patients. We examined the possibility that lipid and lipoprotein levels fluctuate due to the different effects of estrogen and progestogen in postmenopausal hyperlipidemic women receiving combined hormonal replacement therapy. METHODS: In an open-label study conducted during 3 consecutive hormonal cycles (3 months), levels of fasting total cholesterol, triglycerides, and low (LDLC)- and high-density lipoprotein cholesterol (HDLC) were determined in 36 postmenopausal hyperlipidemic women on day 13 of conjugated equine estrogen (1.25 mg/d) therapy and on day 25 after 12 days of receiving estrogen plus medroxyprogesterone acetate (5 mg/d). RESULTS: While receiving estrogen and combined therapies, means +/- SD total cholesterol levels increased from 6.50 +/- 0.97 mmol/L (251 +/- 37 mg/dL) to 6.88 +/- 1.42 mmol/L (266 +/- 54 mg/dL) (P<.001); LDLC levels, from 4.05 +/- 1.14 mmol/L (156 +/- 44 mg/dL) to 4.62 +/- 1.36 mmol/L (178 +/- 52 mg/dL) (P<.001). Mean +/- SD HDLC cholesterol levels decreased from 1.44 +/- 0.32 mmol/L (55 +/- 12 mg/dL) to 1.29 +/- 0.28 mmol/L (50 +/- 10 mg/dL) (P<.001); triglyceride levels, from 2.23 +/- 1.03 mmol/L (197 +/- 91 mg/dL) to 2.06 +/- 1.04 mmol/L (182 +/- 92 mg/dL) (P<.001). CONCLUSIONS: Hyperlipidemic postmenopausal women receiving combined sequential estrogen and progestogen replacement therapy demonstrate very significant fluctuations in their lipid and lipoprotein levels. These fluctuations depend on the hormonal phase, ie, estrogen alone or combined with progestogen.

Estrogen Replacement Therapy↗
PubMed1998

Effects of fibric acid derivatives and metformin on postprandial lipemia.

It was suggested that postprandial lipoproteins (PPLp) may play an important role in atherogenesis. We studied PPLp metabolism and its response to drugs in seven hypertriglyceridemic subjects, 23 men with isolated low HDL-C levels, and nine non-diabetic glucose intolerant subjects. Results were compared with those found in a group of 19 healthy normolipidemic individuals. We used the vitamin A-fat loading test which specifically labels PPLp with retinyl palmitate (RP). In the hypertriglyceridemics the areas under RP curves of the chylomicrons were 6.3-fold and those of non-chylomicrons 2.9-fold higher than in normals (P < 0.01). Gemfibrozil 1200 mg/day caused a dramatic decrease in chylomicrons 73% and nonchylomicrons 31%. In subjects with isolated low HDL-C, RP chylomicron curves were significantly higher than in normals (17.733+/-6.821 vs 13939+/-6217 microg/l per h, P < 0.005). Bezafibrate 400 mg/day reduced RP chylomicrons and nonchylomicron levels by 35% (P < 0.0001) in 15 responders with an increase in fasting HDL-C 35+/-3 to 40+/-22 mg/dl (P < 0.0001). No response was found in eight subjects. In the nine glucose intolerant subjects, metformin reduced postprandial insulin area under the curve from 389 to 245 mU/ml (P <0.01) chylomicron and nonchylomicron RP areas were 3.6- and 3-fold higher than in normals and were reduced by 56 and 32%, respectively. In conclusion gemfibrozil, bezafibrate and metformin were shown to be beneficial in the clearance of PPLp in hypertriglyceridemic patients, subjects with isolated low HDL-C levels and nondiabetic glucose intolerant subjects, respectively.

Bezafibrate↗
PubMed1998

Low nitric oxide production in patients with chronic renal failure.

BACKGROUND: Rats with chronic renal failure have a low nitric oxide (NO) production and a diminished NO excretion. The supplementation of L-arginine has an inhibitory effect on the progression of renal insufficiency. METHODS: The present study was designed to determine whether chronic renal failure patients have a low NO production. Plasma and urine nitrate (NO3) and nitrite (NO2), stable metabolites of NO, were measured in 83 consecutive patients with chronic renal failure. The 83 chronic renal failure patients were divided into three groups: group 1, mild renal failure (creatinine clearance >60 ml/min/1.73 m2); group 2, moderate renal failure (creatinine clearance >30 <60 ml/min/1.73 m2), and group 3, severe renal failure (creatinine clearance <30 ml/min/1.73 m2). Thirty-three healthy volunteers served as controls. RESULTS: The daily urinary NO excretion was significantly lower in patients with moderate and severe renal failure as compared with those with mild renal failure and normal controls. The lowest values were found in the severe renal failure group. When the 24-hour urinary NO excretion or NO per milligram creatinine and the NO clearance were correlated with the renal function in all patients as a group, these parameters were directly correlated with the creatinine clearance and inversely correlated with the serum creatinine level. The plasma NO concentration was not different between the three chronic renal failure groups, but higher than in the controls. Plasma NO in renal failure patients was not correlated with the creatinine clearance or serum creatinine levels. CONCLUSIONS: Chronic renal failure is a state of NO deficiency. Treatment strategies to increase NO production (L-arginine supplementation or other NO compounds) may prove to be useful in maintaining the renal function and slow the progression of renal disease.

Aged↗
PubMed1998

Decreased fecal bile acid output in patients with coronary atherosclerosis.

In most patients with atherosclerosis, the underlying metabolic derangement remains undefined. Animal experiments have suggested that the ability to produce and excrete large amounts of bile acids may be an adaptation mechanism to cholesterol overload protecting against the atherogenic effects of cholesterol. However, there are very few data on bile acid excretion in human atherosclerosis. In the present study, we have investigated fecal bile acid secretion in subjects with and without coronary artery disease. The target group consisted of 30 patients with proven coronary artery disease and the control group consisted of 27 matched subjects without clinical or laboratory evidence of coronary atherosclerosis. Fecal bile acids were measured by gas-liquid chromatography from 24-hr stool collections under a controlled diet. The patients excreted significantly less bile acids than the controls (325+/-135 vs. 592+/-223 mg/day, respectively, p < 0.0001). The difference was primarily due to a reduced excretion of secondary bile acids. Less than 50% of deoxycholate was excreted by patients (180+/-81 mg/day) as compared to controls (367+/-168 mg/day, p < 0.0002), while lithocholic acid excretion was 111+/-62 mg/day in patients vs. 190 +/-70 mg/day in controls (p < 0.005). The fecal output of the two primary bile acids, cholic and chenodeoxycholic acid, did not differ significantly between patients and controls. The fecal output of total bile acids correlated with that of both secondary bile acids in patients as well as in controls. These findings suggest that patients with coronary heart disease are unable to excrete adequate amounts of bile acids to rid themselves of excess cholesterol, even if they are able to maintain a plasma cholesterol level comparable to that of healthy controls.

Aged↗
PubMed1997

Disturbances in dietary fat metabolism and their role in the development of atherosclerosis.

It was suggested that postprandial lipoproteins (PPLp) may play an important role in atherogenesis. To examine this hypothesis, we studied PPLp metabolism in normolipidemic individuals and hyperlipoproteinemic (HLP) patients on various diets, physical activity programs and hypolipidemic drugs as well as in patients with coronary artery disease (CAD). We used the vitamin A-fat loading test, which labels intestinally derived lipoproteins with retinyl palmitate. Type IV HLP patients demonstrated a severe defect in chylomicron clearance. Type III HLP patients showed severely disordered clearance of chylomicron remnants. Compared to the saturated fatty acid enriched diet, the omega 6 polyunsaturated acid enriched diet reduced chylomicrons and their remnant levels by 56% and 38%, respectively. The diet enriched in omega 3 polyunsaturated acid decreased chylomicrons and their remnant levels by 67% and 53%, respectively. Physical conditioning reduced chylomicron levels by 37%. Gemfibrozil decreased chylomicron levels in type IV HLP patients. Cholestyramine increased chylomicron levels by 88%. Bezafibrate reduced chylomicrons and their remnants levels and increased fasting HDL-C in patients with isolated low HDL-C levels. Continuous prolonged intravenous heparin administration inhibited chylomicron clearance. Normolipidemic patients with CAD had significantly higher plasma levels of chylomicron remnants than matched controls with normal coronary arteries. The studies reported here demonstrate that both chylomicrons and their remnants are present in the plasma of normolipidemic people and more so for hyper- or dyslipidemic patients for a prolonged period of time after fat ingestion. The duration and magnitude of this postprandial lipemia can be regulated or altered by such interventions as diet, physical activity, and drugs. Our case control studies strongly support the hypothesis that PPLp may play a crucial part in atherogenesis, and therefore justify measuring their levels in high risk patients. We believe that in selected patient groups the use of one or more of the interventions mentioned here is warranted.

Arteriosclerosis↗
PubMed1997

The influence of Vicia faba (broad bean) seedlings on urinary sodium excretion.

Dopamine (DA) is known to increase diuresis and natriuresis through its action on renal dopaminergic receptors. Augmentation of intra-renal DA concentration by enhancement of its in situ production is greatly dependent on the availability of its precursor L-DOPA to the sites of its renal decarboxylation. Vicia faba (Vf) is a ubiquitous plant rich in easily absorbable L-DOPA. Following ingestion of 40 g freshly chopped Vf containing 120-130 mg of L-DOPA, plasma L-DOPA and urinary sodium and DA excretion increased significantly. The DA/Cre ratio reached a maximum level (280 +/- 58 micrograms/g) 60 minutes after Vf ingestion. This was significantly higher than the DA/Cre ratio after a control meal (1.8 +/- 0.2 micrograms/g; P < 0.0005). The Na/Cre ratio reached the maximal level (2.85 +/- 0.42 mmol/g) 90 minutes after Vf ingestion. This was significantly higher than the Na/ Cre ratio after the control meal (1.4 +/- 0.24 mmol/g; P < 0.005). We suggest that Vf might be of value in treating conditions such as hypertension, heart failure, renal failure, and liver cirrhosis in which natriuresis and diuresis are medically beneficial.

Adult↗
PubMed1997

Metformin enhances clearance of chylomicrons and chylomicron remnants in nondiabetic mildly overweight glucose-intolerant subjects.

OBJECTIVE: To assess the effect of metformin on the metabolism of intestinally derived lipoproteins in nondiabetic individuals who were mildly overweight and glucose intolerant. RESEARCH DESIGN AND METHODS: A total of nine subjects with a BMI > or = 25 kg/m(2) and fasting serum glucose < or = 6.1 mmol/l and who were glucose intolerant were studied. The subjects underwent a vitamin A fat-loading test before and after a 3-month treatment with 850 mg metformin twice a day. The metabolic behavior of the postprandial lipoproteins was compared with that found in a group of 19 healthy normolipidemic individuals who participated in a previous study. RESULTS: Mean total plasma, chylomicron fraction, and nonchylomicron fraction retinyl palmitate (RP) pretreatment levels were 3.4-fold, 3.59-fold, and 3-fold higher, respectively, in the study group than in the normolipidemic group and were reduced by 50, 56, and 32%, respectively, after 3 months of metformin treatment. The decrease of chylomicron levels after treatment was positively correlated to the fasting triglyceride values before treatment (r = 0.73, P = 0.039) and to the serum insulin level at 120 min of standard glucose loading before treatment (r = 0.91, P = 0.002). CONCLUSIONS: Metformin was shown to be beneficial in the clearance of postprandial lipoproteins in nondiabetic individuals who were mildly overweight and glucose intolerant.

Cholesterol↗
PubMed1996

Clearance of chylomicron remnants in normolipidaemic patients with coronary artery disease: case control study over three years.

OBJECTIVE: To test the hypothesis that subjects who clear chylomicron remnants slowly from plasma may be at higher risk of coronary artery disease than indicated by their fasting plasma lipid concentrations. DESIGN: Case control study over three years. SETTING: An 800 bed general municipal hospital. SUBJECTS: 85 normolipidaemic patients with coronary artery disease selected prospectively and matched with 85 normolipidaemic subjects with normal coronary arteries on angiography. INTERVENTIONS: All subjects were given a vitamin A fat loading test which specifically labels intestinal lipoproteins with retinyl palmitate. MAIN OUTCOME MEASURE: Postprandial lipoprotein metabolism. RESULTS: The area below the chylomicron remnant retinyl palmitate curve was significantly increased in the coronary artery disease group as compared with the controls (mean 23.4 (SD 15.0) v 15.3 (8.9) mumol/l.h; 95% confidence interval of difference 4.37 to 11.82). CONCLUSION: Normolipidaemic patients with coronary artery disease had significantly higher concentrations of chylomicron remnants in plasma than normolipidaemic subjects with normal coronary vessels. This may explain the mechanism underlying the susceptibility to atherosclerosis of coronary artery disease patients with normal fasting lipid values. As diet and drugs can ameliorate the accumulation of postprandial lipoproteins in plasma, the concentration of chylomicron remnants should be measured in patients at high risk of coronary artery disease.

Adult↗
PubMed1995

Bezafibrate therapy in patients with isolated low high-density lipoprotein cholesterol levels may have a beneficial effect in prevention of atherosclerosis.

Although a low plasma high-density lipoprotein cholesterol (HDL-C) level is a well-accepted risk factor for coronary artery disease (CAD), it is unclear whether pharmacologic agents can effectively increase HDL-C levels and/or reduce the incidence of CAD in patients with isolated low HDL-C levels. An important determinant of HDL levels is the efficiency of postprandial lipoprotein catabolism. The purpose of the present study was to evaluate the efficacy of bezafibrate therapy in increasing HDL-C levels in these patients and to examine its effect on postprandial lipoprotein levels. Fasting and postprandial lipid and lipoprotein levels were studied in 23 patients with isolated low HDL-C levels before and during 3 and 6 months of bezafibrate treatment. Postprandial lipoprotein levels were evaluated using the vitamin A-fat loading test, in which these intestinally derived lipoproteins are specifically labeled with retinyl palmitate (RP). Patients with isolated low HDL had significantly higher levels of chylomicron RP than a control group of 19 normolipidemic subjects. The area below the chylomicron RP curve was 17,773 +/- 6,821 versus 13,936 +/- 6,217 micrograms/L.h, respectively (P < .005). No differences were found in chylomicron remnant levels between the groups. Bezafibrate therapy reduced the chylomicron RP area by 27%, from 17,773 +/- 6,821 to 12,895 +/- 2,576, and the nonchylomicron RP area by 25%, from 6,059 +/- 3,310 to 4,430 +/- 1,963 (P < .0001). It increased fasting HDL-C levels from 35 +/- 3 to 38 +/- 1.4 mg/dL after 3 months (P < .001) and to 40 +/- 2.2 mg/dL after 6 months (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Postprandial intestinal-derived chylomicron and chylomicron remnants in essential hypertensive patients before and after prolonged captopril therapy.

The metabolism of the postprandial intestinal-derived lipoproteins, chylomicron and chylomicron remnants, is not known in patients with essential hypertension. After a fat meal, using the vitamin A test as a marker, retinyl palmitate was measured in the total plasma, chylomicron, and chylomicron remnant fractions in 14 untreated nondiabetic essential hypertensive patients with normal fasting lipids and lipoproteins. The vitamin A fat loading test was repeated in eight hypertensive patients after 3 months of captopril therapy. Fifteen matched normotensive subjects were used as controls. The untreated essential hypertensive patients had significantly higher chylomicron fraction concentration curves (AUC 17,469 +/- 2553 micrograms/L/h) P < .001 compared with the control group (AUC 13,208 +/- 1245 micrograms/L/h), by two-way analysis of variance with repeated measurements. After 3 months of captopril therapy, the chylomicron fraction (AUC 9701 +/- 1566 micrograms/L/h), and chylomicron remnants fraction (AUC 3487 +/- 580 micrograms/L/h) were much lower (P < .001) than before captopril therapy. Oral glucose tolerance tests were borderline in five of the eight hypertensives before captopril treatment but returned to normal after 3 months of therapy. In summary, postprandial intestinal-derived lipoprotein metabolism is altered in essential hypertensive patients. Captopril therapy caused significant improvement in the postprandial chylomicron metabolism.

Captopril↗
PubMed1994

Role of nitric oxide (EDRF) in radiocontrast acute renal failure in rats.

This study was undertaken to examine the possible role of endothelium-derived relaxing factor (EDRF), identified as nitric oxide (NO), in the pathogenesis of radiocontrast-induced acute renal failure in rats. Normal and salt-depleted rats were monitored for 60 min or 24 h after radiocontrast administration. The administration of L-arginine to normal rats abolished the immediate decrease in p-aminohippurate clearance (CPAH) and attenuated the decrease in inulin clearance (CIn). The administration of NO synthase inhibitor to the salt-depleted animals resulted in a significantly more pronounced decrease in CPAH compared with both the control and the L-arginine-treated animals. The recovery of CIn 24 h after radiocontrast administration to the salt-depleted rats was significantly better in the L-arginine-treated rats than in either the control or inhibitor-treated groups. The administration of radiocontrast material resulted in a significant decrease in urinary guanosine 3',5'-cyclic monophosphate as well as NO2 + NO3 excretion. This decrease was significantly attenuated by L-arginine. Our results 1) suggest that NO plays a major role in the pathogenesis of radiocontrast-induced acute renal failure and 2) suggest a novel therapeutic approach, i.e., the use of L-arginine in this form of acute renal failure.

Acute Kidney Injury↗
PubMed1994

Continuous intravenous heparin administration in humans causes a decrease in serum lipolytic activity and accumulation of chylomicrons in circulation.

Heparin is a well-known, widely used anticoagulant drug. In addition to its anticoagulant properties, however, it also has a marked influence on fat metabolism. Postprandial lipoproteins may contribute significantly to the development of coronary heart disease. Therefore, it is important to evaluate the effects of heparin on these lipoproteins. The effect of continuous heparin administration on postprandial lipoprotein metabolism was studied in 11 patients with thromboembolic disease. Results were compared with those in a group of six patients given no heparin. Two vitamin A-fat loading tests were done: the first, 5 days before heparin was started and the second, on the fourth day of continuous heparin drip of 1000 U/h, maintaining PTT levels at twice the baseline. To study the effect of acute heparin, an additional fat loading test was done in five patients on the first day of heparin treatment. Vitamin A, specifically labels intestinally derived lipoproteins with retinyl palmitate (RP). The concentrations of chylomicron (Sf > 1000)- and nonchylomicron (Sf < 100)-retinyl palmitate were measured for 10 h postprandially. Four days of continuous intravenous heparin administration increased the area below the chylomicron RP curve from 11091 +/- 4393 to 17684 +/- 5949 micrograms/l.h (P < 0.003). When measured on the first day of heparin treatment in five patients, the area of the chylomicron fraction was reduced from 16678 +/- 6895 to 10474 +/- 3893 micrograms/l.h (P < 0.05). Postheparin lipoprotein lipase activity was significantly lower on the fourth day of heparin, administration than before treatment: 1.8 +/- 1.1 vs. 4.1 +/- 1.3 mumol/FFA per ml per h, respectively (P < 0.0005). In the six control patients with thromboembolic disease in whom heparin therapy was not indicated, no changes in postprandial lipoprotein levels or in lipolytic activity during hospitalization were found. The study demonstrates that 4 days of heparin administration causes an accumulation of chylomicrons in the circulation, most probably as a result of a marked decrease in serum lipolytic activity.

Adult↗
PubMed1994

Bone and joint tuberculosis--a 10-year review.

The incidence of bone and joint tuberculosis has declined ever since the advent of medical antituberculous therapy. To evaluate the evolving presentation, we undertook a 10-year review of this form of extrapulmonary tuberculosis in 7 general hospitals in Israel. Thirty-eight patients were identified on the basis of strict criteria. Median age of 63 years in this series was higher than foreseen in this relatively underdeveloped region. Spinal involvement was remarkably low. Involvement of the extremities had a trend towards right side predominance. Overt clinical manifestations were encountered rarely in cases of deep-seated infection. However, unsuspecting doctors and incomplete workup frequently contributed to a further delay in diagnosis. A significant fraction of aberrant management was also found with undue surgical intervention in many cases.

Adolescent↗
PubMed1991

Hyperphosphataemia and hypocalcaemia induced by hypertonic phosphate enema--an experimental study and review of the literature.

1. The study objective was to determine the hyperphosphataemic and hypocalcaemic effect of hypertonic phosphate enema. The study was conducted in a department of Internal Medicine at a University Medical Center. 2. Fourteen patients were studied. Patients' mean age (+/- s.d.) was 78.5 +/- 9 years. The creatinine clearance was 48.2 +/- 17.4 ml min-1 (mean +/- s.d.). 3. 500 ml (approx. 7 ml kg-1) of Fleet enema (FE - Na2HPO4.7H2O 224 mmol l-1 and NaH2PO4.H2O 1160 mmol l-1) were administered to each patient. Blood was drawn before FE administration and 1/2, 1, 3, 5, 12 and 24 h thereafter. Serum was analysed for levels of inorganic phosphorus and for calcium. 4. The serum inorganic phosphorus level rose from 1.01 +/- 0.3 mmol l-1 to 1.4 +/- 0.5 mmol l-1 (P = 0.001) 1 h after FE was administered. Serum calcium decreased from 2.32 +/- 0.12 mmol l-1 to 2.12 +/- 0.1 mmol l-1 (P less than 0.001) 12 h after FE was administered. 5. We conclude that FE carries a potential risk for acutely ill elderly patients. To avoid untoward effects due to hyperphosphataemia and hypocalcaemia, the phosphate load must be adjusted to the patient's renal function, i.e. enema volume is to be lowered when phosphate concentration is high, so that if renal function is compromised the amount of phosphate absorbed does not exceed renal excretion capacity.

Adolescent↗
PubMed1988

Recurrent erythema nodosum, arthritis and IgA nephropathy.

Erythema nodosum and IgA nephropathy are nosologic entities with an immunologic background. IgA nephropathy is a specific disease of the kidneys, while erythema nodosum may be associated with other illnesses. We report a unique case in which intermittent hematuria due to IgA nephropathy was superimposed on recurrent attacks of erythema nodosum and arthritis. A common pathophysiology is suggested.

Adult↗