Imaging of primary Ewing sarcoma with 13N-L-glutamate

Eleven patients with untreated primary Ewing sarcoma were studied with intravenously administered 13N-labeled L-glutamate. Seven were repeatedly scanned during chemotherapy using this agent and 99mTc-methylene diphosphonate (99mTc-MDP). The untreated primary tumor was distinctly visualized with 13N-L-glutamate in all cases; the distribution of 13N label in the tumor sometimes differed from that of 99mTc. A kinetic study showed rapid uptake of 13N by tumor tissue. Repeat scans following therapy indicated that 13N-L-glutamate and 99mTc-MDP uptake showed changes consistent with histological findings following subsequent surgery. 13N uptake often decreased more markedly than 99mTc uptake during chemotherapy, but metastatic lesions were not visualized with 13N-L-glutamate. Tumor imaging with this labeled amino acid may be of value in assessing the response of primary Ewing sarcoma to chemotherapy.     

INDEPENDENCE OF H-2K AND H-2D ANTIGENIC DETERMINANTS ON THE SURFACE OF MOUSE LYMPHOCYTES

At 37°C, fluorescein-conjugated anti-H-2 alloantibodies specifically induce, at the surface of living mouse lymphocytes, the redistribution of the corresponding H-2 antigens, which cluster as patches and sometimes single caps at one pole of the cell. This aggregation is inhibited at 0°C and the H-2 antigens, stained by fluorescent antibodies in the cold, appear evenly spread over the cell surface. This phenomenon was used to define the relationships between the membrane structures bearing the antigens coded by the H-2K and the H-2D genes of the H-2 region. Monospecific anti-H-2 antibodies coupled to either tetramethyl rhodamine isothiocyanate or fluorescein isothiocyanate were used to induce the redistribution of H-2D and H-2K antigens of the H-2^b and H-2^k haplotype at the surface of lymph node cells from homozygous and F₁ hybrid mice. It was observed that the diffuse distribution of H-2K antigens labeled at 0°C was not affected by the prior antibody-induced aggregation of H-2D antigens and vice versa. The results were the same for H-2 antigens governed by genes located either in cis or in trans position. These data indicate that the H-2K and H-2D antigens migrate independently at the cell surface, and suggest that the gene products from the D and the K end of the H-2 region are expressed on independent molecules or structures at the cell membrane.     

Lung function decline in bronchial asthma

STUDY OBJECTIVE: We evaluated the longitudinal changes in lung function and the factors associated with FEV(1) changes over time in a sample of asthmatic subjects. SETTING: FEV(1) measures were recorded every 3 months over a 5-year follow-up period. To compare all subjects independently of body size, FEV(1) values were normalized for the subject's height at the third power. We evaluated the possible effect of age, baseline FEV(1), disease duration, and FEV(1) variability on the rate of change of FEV(1). PATIENTS: We studied 142 subjects with asthma diagnosed on the basis of validated clinical and functional criteria. RESULTS: FEV(1) showed a linear decay with aging in each subject. For a subject 1.65 m in height, the median overall FEV(1) decay was 40.9 mL/yr. FEV(1) decay slopes were significantly influenced by age and sex, being steeper in younger male subjects. A significant interaction was found between age and baseline FEV(1): the FEV(1) decay was significantly higher among younger asthmatics with a poorer baseline functional condition. A longer disease duration was associated with a lower FEV(1) slope. FEV(1) variability was strongly associated with an increased rate of FEV(1) decline. CONCLUSIONS: FEV(1) decline in patients with bronchial asthma is significantly influenced by baseline FEV(1), disease duration, and FEV(1) variability. Moreover, the rate of FEV(1) decline seems to increase in younger subjects only when the baseline function is poorer.     

Are optical aberrations during accommodation a significant problem for refractive surgery?

PURPOSE: To study the limits to a perfect ideal customized wavefront correction due to the change of aberrations during accommodation. METHODS. We measured the dynamic changes of ocular aberrations during accommodation in normal eyes with a real-time Hartmann-Shack wavefront sensor. Those results were used in computer simulations to predict the benefit of a perfect customized correction. RESULTS: Due to the continuous changes of the aberrations over time, an ideal perfect static correction will not provide stable aberration-free optics. For example, when the eye accommodates to near objects, due to the changing aberrations, the eye will become aberrated again. An alternative correction using the aberration pattern for a slightly accommodated condition could provide a better-correction in a larger accommodative range, although at the cost of non-perfect correction for far vision. CONCLUSIONS: Due to the dynamic nature of ocular optics, a static perfect correction, for instance performed in customized refractive surgery, would not remain perfect for every condition occurring during normal accommodation.     

Transvaginal ultrasonography and hysteroscopy in postmenopausal bleeding: a prospective study

OBJECTIVE: To determine the diagnostic value of transvaginal ultrasonography and hysteroscopy in patients with postmenopausal bleeding. MATERIAL AND METHODS: Between January 1, 1998 and June 30, 1999, 88 outpatient women with postmenopausal bleeding were enrolled in a prospective study. They underwent transvaginal ultrasonography and hysteroscopy, and were submitted to directed biopsy during hysteroscopy. Findings were classified as normal endometrium, suggestive of atrophy, focal abnormality (benign or suspicious), and diffuse thickness (benign or suspicious). Data was compared with the final diagnosis, established by histological examination, as atrophy, benign pathology, atypical hyperplasia and endometrial carcinoma. RESULTS: Among 88 women enrolled, 15 were excluded because hysteroscopy was impossible, and four had abandoned the study. The histological findings were scanty material in 12 (17.4%), atrophy in 24 (34.8%), cystic atrophy in one (1.4%), normal endometrium in five (7.2%), tuberculous endometritis in one (1.4%), polyps in 12 (17.4%), leiomyoma in one (1.4%), non-atypical hyperplasia in three (4.3%), atypical hyperplasia in one (1.4%) and endometrial carcinoma in nine cases (13.0%). For the assessment of endometrial carcinoma, ultrasonography revealed sensitivity 77.8%, specificity 93.3%, positive predictive value 63.6%, negative predictive value 96.6%; and hysteroscopy revealed sensitivity of 88.9%, specificity 98.3%, positive predictive value 88.9%, negative predictive value 98.3%. The combined use of both methods revealed sensitivity 100%, specificity 91.7%, positive predictive value 64.3%, negative predictive value 100%. CONCLUSIONS: Both imagiological methods were found to be useful screening tests for endometrial carcinoma. Hysteroscopy was a superior diagnostic procedure.     

Acyl coenzyme A:cholesterol acyltransferase inhibitors as hypolipidemic and antiatherosclerotic drugs

Acyl coenzyme A:cholesterol acyltransferase (ACAT) is the enzyme that catalyzes the conversion of intracellular cholesterol into cholesteryl esters. Two ACAT isoforms, termed ACAT1 and ACAT2, have been described. ACAT1 is ubiquitously found, with high expression levels in macrophages, adrenals, sebaceous glands and foam cells from human atherosclerotic lesions. In contrast, ACAT2 expression is restricted to the intestine and the liver of mice and non-human primates. The reaction catalyzed by ACAT is essential for intestinal cholesterol absorption, synthesis and secretion of apolipoprotein B (apoB)-containing lipoproteins, and intracellular storage of cholesterol. Therefore, ACAT inhibitors would theoretically reduce plasma cholesterol levels by blocking cholesterol absorption from the diet and by reducing hepatic VLDL synthesis. Moreover, ACAT inhibition could limit the accumulation of cholesteryl esters in the cytoplasm of macrophages, thus reducing the formation of foam cells. In view of these attractive possibilities, a great deal of molecules with ACAT inhibitory properties have been synthesized in the last 20 years. However, only a few of them have reached clinical studies, mainly due to unexpected side effects. On the other hand, most of the compounds assayed in humans have not shown substantial hypolipidemic efficacy. The present article focuses on the current knowledge of the pharmacology of ACAT inhibitors, and, specifically, on the different pharmacological approaches used to evaluate these compounds as hypolipidemic and antiatherosclerotic agents.     

Comparison of energy-restricted very low-carbohydrate and low-fat diets on weight loss and body composition in overweight men and women

OBJECTIVE: To compare the effects of isocaloric, energy-restricted very low-carbohydrate ketogenic (VLCK) and low-fat (LF) diets on weight loss, body composition, trunk fat mass, and resting energy expenditure (REE) in overweight/obese men and women. DESIGN: Randomized, balanced, two diet period clinical intervention study. Subjects were prescribed two energy-restricted (-500 kcal/day) diets: a VLCK diet with a goal to decrease carbohydrate levels below 10% of energy and induce ketosis and a LF diet with a goal similar to national recommendations (%carbohydrate:fat:protein = ~60:25:15%). SUBJECTS: 15 healthy, overweight/obese men (mean +/- s.e.m.: age 33.2 +/- 2.9 y, body mass 109.1 +/- 4.6 kg, body mass index 34.1 +/- 1.1 kg/m2) and 13 premenopausal women (age 34.0 +/- 2.4 y, body mass 76.3 +/- 3.6 kg, body mass index 29.6 +/- 1.1 kg/m2). MEASUREMENTS: Weight loss, body composition, trunk fat (by dual-energy X-ray absorptiometry), and resting energy expenditure (REE) were determined at baseline and after each diet intervention. Data were analyzed for between group differences considering the first diet phase only and within group differences considering the response to both diets within each person. RESULTS: Actual nutrient intakes from food records during the VLCK (%carbohydrate:fat:protein = ~9:63:28%) and the LF (~58:22:20%) were significantly different. Dietary energy was restricted, but was slightly higher during the VLCK (1855 kcal/day) compared to the LF (1562 kcal/day) diet for men. Both between and within group comparisons revealed a distinct advantage of a VLCK over a LF diet for weight loss, total fat loss, and trunk fat loss for men (despite significantly greater energy intake). The majority of women also responded more favorably to the VLCK diet, especially in terms of trunk fat loss. The greater reduction in trunk fat was not merely due to the greater total fat loss, because the ratio of trunk fat/total fat was also significantly reduced during the VLCK diet in men and women. Absolute REE (kcal/day) was decreased with both diets as expected, but REE expressed relative to body mass (kcal/kg), was better maintained on the VLCK diet for men only. Individual responses clearly show the majority of men and women experience greater weight and fat loss on a VLCK than a LF diet. CONCLUSION: This study shows a clear benefit of a VLCK over LF diet for short-term body weight and fat loss, especially in men. A preferential loss of fat in the trunk region with a VLCK diet is novel and potentially clinically significant but requires further validation. These data provide additional support for the concept of metabolic advantage with diets representing extremes in macronutrient distribution.