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Biomedical subjects

T Hayek

Publications and source records attributed to T Hayek.

65 records · Page 4Linked to original sources

Accumulation of human apolipoprotein E in the plasma of transgenic mice.

Three separate lines of transgenic mice were created with integrated copies of an 11.1-kilobase pair human DNA fragment containing the apolipoprotein (apo) E gene. The endogenous mouse apoE gene is primarily expressed in the liver with varying levels of expression in other tissues. However, in all three transgenic lines high levels of human apoE mRNA were detected only in the kidney, with lower levels found in the liver and other tissues; despite this profile of human apoE mRNA, human apoE was found in the plasma of the transgenic mice at levels comparable to those found in human plasma. All of the human apoE in the plasma of the transgenic mice was associated with lipoproteins. These results suggest that the domain responsible for the high level of apoE expression in liver lies outside of the microinjected DNA fragment and that an ectopic site of expression of an introduced gene may be permissive for the accumulation of its protein in plasma.

Animals↗

Intralipid infusion in patients with familial hypercholesterolemia. Effect of serum and plasma lipoproteins on platelet aggregation and on macrophage cholesterol metabolism.

Intralipid infusion into normal volunteers was recently shown to possess anti-atherogenic properties. We studied the effect of intralipid infusion in patients with severe Familial Hypercholesterolemia (FH) refractory to conventional therapy. FH patients and normal subjects, who served as controls, were given an intravenous infusion of intralipid for 6 h. Serum samples taken from both groups before, during and after intralipid infusion were studied for their ability to inhibit cellular cholesterol accumulation by macrophages. A significantly lower rate of cellular cholesterol esterification (of 46%, P less than 0.005 and 44%, P less than 0.005 in patients and normals, respectively) was demonstrated in macrophages incubated with serum obtained during intralipid infusion compared to those incubated with preinfusion serum. The maximal effect was demonstrated with serum samples taken at the end of the infusion, but the inhibitory effect persisted even at 24 h post-infusion. It was found that chylomicron like particles could induce the above-mentioned effects on macrophage cholesterol esterification. A significant decrement of 50% (P less than 0.005) in aggregation of platelets isolated from plasma samples taken during and after intralipid infusion from both groups was demonstrated, when compared to platelets isolated in the preinfusion state. This effect persisted 18 h subsequent to infusion. We conclude that intralipid infusion abolishes serum ability to stimulate cholesterol esterification in cultured macrophages, and exhibits inhibitory effects upon platelet aggregation. If similar events occur in the arterial wall, intralipid might inhibit foam cell formation.

Adolescent↗

[Nontropical pyomyositis].

Pyomyositis of the pectoralis major was diagnosed in a 79-year-old man and Staphylococcus aureus was grown from pus drained from the infected muscle. Bacteremia and overwhelming sepsis accompanied the infection, and the patient died despite early diagnosis, combined chemotherapy and surgical drainage. The incidence of pyomyositis has been increasing lately in temperate climates. To our knowledge, this is the first report of nontropical pyomyositis in Israel.

Aged↗

[Intralipid infusion in familial hypercholesterolemia].

Intralipid, used for intravenous alimentation and containing triglyceride emulsion particles and phospholipid liposomes, has been shown to induce regression of atherosclerosis in experimental animals. Intravenous infusions of Intralipid were given to 2 patients with severe familial hypercholesterolemia refractory to conventional therapy, and to control subjects. Intracellular cholesterol esterification was inhibited in macrophages incubated with serum taken during infusions as compared to the preinfusion state, with maximal effect after 6 h of infusion. A significant decrease in platelet aggregation was also demonstrated in both groups, which persisted for 18 h after infusion. We conclude that infusion of Intralipid may have anti-atherogenic effects and plan to use it in patients with severe atherosclerosis.

Cholesterol↗

Recurrent spontaneous bacterial peritonitis in a patient with polycythemia vera.

Spontaneous bacterial peritonitis (SBP) is an infectious process that usually occurs in patients with cirrhosis. There are few reports of SBP in patients with other pathologies such as nephrotic syndrome, acute and chronic hepatitis, cardiac ascites, and ascites secondary to neoplastic disease. We report a patient with polycythemia vera in whom recurrent episodes of SBP occurred 8 months following a portacaval shunt operation for Budd-Chiari syndrome. Conceivably, the polycythemia vera (PV) complicated by hepatic vein thrombosis and portacaval shunt resulted in significant loss of hepatic reticuloendothelial system function and predisposed the patient to bacterial peritonitis.

Budd-Chiari Syndrome↗

Preoperative diagnosis of Mirizzi syndrome.

Mirizzi syndrome is defined as an obstruction of the common hepatic duct by a stone present in the cystic duct or neck of the gallbladder. This entity rarely has been reported, and in only a few cases was the diagnosis made preoperatively. The preoperative diagnosis is of great importance since intraoperative findings may be similar to carcinoma of the extrahepatic biliary system, which requires a different technical approach. Furthermore, unrecognized cholecystobiliary or cholecystoenteric fistula resulting from stone penetration lead to serious postoperative complications, which can be avoided if the condition is properly recognized.

Cholelithiasis↗

Bacterial meningitis in infants two to six weeks old.

We reviewed our experience with bacterial meningitis in older neonates (2 to 6 weeks of age) during a five-year period. Seventeen patients with bacterial meningitis were diagnosed and treated. Bacteria recovered from the cerebral spinal fluid (CSF) included pneumococci (29%), E. coli and meningococci (23% each), group B streptococci (12%), Enterobacter and H. influenzae (6% each). There were no cases of Listeria monocytogenes. The mean duration of symptoms before admission was 3.1 days. The mortality rate was high (30%), and 36% of the patients had significant neurologic residua. Our study shows that this specific age group is different from newborns or older infants. Therefore, the initial selection of antibiotics for the treatment of meningitis in this age group should include antibiotics that are effective across this spectrum of potential pathogens.

Age Factors↗

24,25(OH)2D3 enhances the calcemic effect of 1,25(OH)2D3.

The effect of 24,25(OH)2D3 on 1,25(OH)2D3-induced hypercalcemia was studied in normal rats. Serum (S) levels and urinary excretion of Ca2+ (UCaV) were measured in (a) control rats, (b) rats receiving a daily sc injection of 54 ng 1,25(OH)2D3, (c) rats receiving 24,25(OH)2D3 in the same dose and same manner, and (d) rats receiving 1,25(OH)2D3 + 24,25(OH)2D3. The animals were housed in metabolic cages and 24-hr urine specimens were collected. After 24 hr SCa2+ increased similarly with 1,25(OH)2D3 and with 1,25(OH)2D3 + 24,25(OH)2D3, while 24,25(OH)2D3 alone did not change SCa2+. UCaV after 24 hr increased significantly less (P less than 0.025) with 1,25(OH)2D3 + 24,25(OH)2D3 than with 1,25(OH)2D3 alone. After 5 days of 1,25(OH)2D3, SCa2+ rose from 5.1 +/- 0.15 to 6.29 +/- 0.08 whereas 1,25(OH)2D3 + 24,25(OH)2D3 effected a greater increase in SCa2+ up to 6.63 +/- 0.09 (P less than 0.01). 24,25(OH)2D3 alone did not change SCa2+. UCaV after 5 days of treatment rose similarly with 1,25(OH)2D3 and with 1,25(OH)2D3 + 24,25(OH)2D3. After 10 days of 1,25(OH)2D3 SCa2+ was 6.17 +/- 0.15 meq/liter while with the combination SCa2+ rose to 6.74 +/- 0.2 (P less than 0.025). 24,25(OH)2D3 alone did not change SCa2+. These results show that (a) 24,25(OH)2D3 alone does not alter SCa2+ in normal rats, (b) combined administration of 1,25(OH)2D3 + 24,25(OH)2D3 enhances the hypercalcemic response to 1,25(OH)2D3 without a parallel increase in UCaV, and (c) it is suggested that the effect of 24,25(OH)2D3 on serum Ca2+ level, at least partly, may result from its hypocalciuric effect.

24,25-Dihydroxyvitamin D 3↗

Probucol decreases apolipoprotein A-I transport rate and increases high density lipoprotein cholesteryl ester fractional catabolic rate in control and human apolipoprotein A-I transgenic mice.

Probucol effects on lipoprotein metabolism were determined in control and human apolipoprotein A-I transgenic (HuAITg) mice. In control mice, probucol reduced total cholesterol from 67 +/- 2 to 25 +/- 2 mg/dl by reducing high density lipoprotein (HDL) cholesterol from 46 +/- 20 to 14 +/- 1 mg/dl and low density lipoprotein (LDL) cholesterol from 11 +/- 1 to 5 +/- 1 mg/dl. Apolipoprotein (apo) A-I levels were reduced from 122 +/- 8 to 56 +/- 5 mg/dl. In HuAITg mice, probucol reduced total cholesterol from 121 +/- 5 to 77 +/- 3 mg/dl by reducing HDL cholesterol from 84 +/- 4 to 56 +/- 3 mg/dl and LDL cholesterol from 19 +/- 2 to 11 +/- 2 mg/dl. Human apo A-I levels were reduced from 267 +/- 13 to 144 +/- 12 mg/dl and mouse apo A-I levels from 18 +/- 2 to 9 +/- 2 mg/dl. Control animals have primarily a monodisperse HDL with a particle diameter of 10 nm. Probucol did not appear to change the particle size distribution in the control animals. The HuAITg mice have a polydisperse HDL with particle diameters of 10.1 and 8.5 nm. Probucol treatment of these animals resulted in HDL with particle diameters of 9.4 and 8.5 nm, apparently reducing the size of the larger particles. In vivo turnover studies revealed that the reduction in apo A-I was primarily due to a decrease in transport rate, whereas the reduction in HDL cholesterol was primarily due to an increase in HDL cholesteryl ester fractional catabolic rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗