The effect of a low fat diet on estrogen metabolism

Women who consume a diet low in fat are at lower risk for breast cancer than women whose diet is relatively high in fat. To investigate the effects of a low fat diet on estrogen metabolism, six normal young women were studied while eating a Western-style high fat diet and again after 2 months of consuming a defined low fat diet. Both studies involved the simultaneous administration of [3H]estradiol [( 3H]E2) orally and [14C]E2 iv and the subsequent collection of multiple blood samples and urine for 96 h. The blood samples were analyzed for radioactivity as estrone (E1), E2, their glucuronides, and E1 sulfate. An aliquot of the pooled 96-h urine was analyzed for radioactivity as the glucuronides and sulfates of E1, E2, estriol, 16 alpha-hydroxyestrone (16 alpha-OHE1), and the catechol estrogens, i.e. 2-hydroxy and 2-methoxy metabolites of E1 and E2. The low fat diet resulted in a consistent and significant (P less than 0.05) decrease in urinary excretion of both 16-hydroxylated metabolites, estriol and 16 alpha-OHE1, expressed as a percentage of administered dose of [3H]E2 and [14C]E2, and an increase in the excretion of the catechol estrogens. These changes in metabolite excretion were not, however, mirrored by changes in the MCRs or conversion ratios of either [3H]E2 or [14C]E2. Thus, while neither the clearance of E2 from the blood nor its absorption from the intestinal tract was altered by a relatively short term decrease in dietary fat, there was a shift in the pattern of urinary metabolites away from the purported carcinogenic estrogen (16 alpha-OHE1) and toward the less active catechol estrogens. This may represent an important mechanism whereby low fat diets decrease the risk of breast cancer.     

Studies on the effect of vanadate on endocytosis and shape changes in human red blood cells and ghosts

When amphipathic cationic drugs are added to intact human RBCs, the RBCs first undergo a stomatocytic shape change and then, if relatively large amounts of drug are added and if the metabolic state of the RBC is appropriate, endocytic vacuoles form. Vanadate has a structural similarity to the transition state of phosphate, which presumably accounts for its ability to inhibit phosphohydrolases, although other actions of vanadate have been described. Vanadate inhibited three forms of drug-induced endocytosis in intact RBCs despite the fact that the three drugs chosen (primaquine, chlorpromazine, and vinblastine) are known to have differing requirements for RBC ATP. Vanadate also inhibited the stomatocytic shape change produced by primaquine, chlorpromazine, and vinblastine, but not the stomatocytosis produced by low pH. Vanadate had no effect on RBC echinocytosis produced by lysophosphatidylcholine. In studying endocytosis in hypotonic, leaky, "white" ghosts, we discovered that vanadate inhibited only the endocytosis produced by Mg-ATP and not the endocytosis produced by manipulations that directly attack the cytoskeletal proteins. These findings suggest that ATP hydrolysis has a role in some forms of amphipathic cation-induced stomatocytosis and endocytosis in intact RBCs. In addition, studies in ghosts support the idea that Mg-ATP does indeed produce "energized" endocytosis dependent on utilization or hydrolysis of ATP.     

Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA

Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state.     

Childhood cardiac function after twin-to-twin transfusion syndrome – a 10-year follow up

Aim:  To perform a 10-year follow up of cardiac structure and function after twin-to-twin transfusion syndrome (TTTS) – a severe foetal circulatory complication associated with myocardial hypertrophy in the recipient twin.
Methods:  Cardiac dimensions, systolic and diastolic function as assessed by echocardiography including flow and tissue Doppler velocimetry in 22 healthy survivors of TTTS with a mean age of 9.6 (7.2–11.8) years.
Results:  The donor and recipient twin did not show any differences in end-diastolic ventricular size, interventricular septum thickness, diameter of right ventricular outflow tract, cardiac valves, coronary arteries or in systolic blood flow velocities. However, compared with the donors, the recipients had significantly lower E/A ratios because of lower E-waves in both mitral (−0.15 ± 0.10, p < 0.01) and tricuspid (−0.09 ± 0.07, p < 0.01) valves, indicating reduced early diastolic ventricular fillings compared with donors.
Conclusion:  At school age, twins surviving TTTS had a cardiac structure and function within normal range. There were no differences in heart structure or systolic ventricular function between twins but, compared with the donor twin, we found a reduced early diastolic function in the recipient.     

Effect of Computer-Assisted Interviewing on Self-Reported Sexual Behavior Data in a Microbicide Clinical Trial

In a microbicide safety and effectiveness trial (HPTN 035) in Malawi, 585 women completed the same questionnaire through a face-to-face interview (FTFI) and an audio computer-assisted self-interview (ACASI). Concordance between FTFI and ACASI responses ranged from 72.0 % for frequency of sex in the past week to 95.2 % for anal intercourse (AI) in the past 3 months. Reported gel and condom use at last sex act were marginally lower with ACASI than FTFI (73.5 % vs. 77.2 %, p = 0.11 and 60.9 % vs. 65.5 %, p = 0.05, respectively). More women reported AI with ACASI than FTFI (5.0 % vs. 0.2 %, p < 0.001). Analyses of consistency of responses within ACASI revealed that 15.0 % of participants in the condom-only arm and 28.7 % in the gel arm provided at least one discrepant answer regarding total sex acts and sex acts where condom and gel were used (19.2 % reported one inconsistent answer, 8.1 % reported two inconsistent answers, and 1.4 % reported three inconsistent answers). While ACASI may provide more accurate assessments of sensitive behaviors in HIV prevention trials, it also results in a high level of internally inconsistent responses.     

Magnetic resonance angiography findings in the early post-carotid endarterectomy period

This preliminary study was designed to investigate the ability of multiple axial volume three-dimensional fourier transform (3DFT) time-of-flight (TOF) magnetic resonance angiography (MRA) to depict the carotid bifurcation in the early post-carotid endarterectomy period. Five patients underwent intra-operative digital subtraction angiography (DSA) and carotid MRA within 5 days of carotid endarterectomy. An axial volume fast imaging in steady-state precession (FISP) gradient-echo 3DFT TOF carotid MRA technique in this limited series appeared to display accurately the surgically significant abnormalities at the carotid bifurcation after endarterectomy. However, in normal or near-normal intra-operative DSA studies, overestimation of internal carotid artery stenoses was encountered. Postoperative MRA demonstrates potential as a useful non-invasive investigation after carotid endarterectomy but should be interpreted with caution until larger studies become available.