Although quantification of the lesion burden from serial MR examinations of patients with multiple sclerosis (MS) is a common technique to assess disease activity in clinical trials, pathologic change may occur within a lesion without a corresponding change in volume. Therefore, measures of lesion volume and composition may improve the sensitivity of detecting disease activity. A new technique has been developed that provides information about the intensity composition of MS lesions in standard spin-echo MR examinations. The new technique is based on the multispectral "feature space" intensity distributions of the lesions and normal tissues. Analysis of MR examinations of materials with known T1 and T2 times showed that feature space position from spin-echo examinations is largely determined from proton density (rho), T2, and the interecho delay. Information about intensity composition was obtained by reducing the multidimensional intensity distribution to one dimension while minimizing the loss of information. This technique was used to analyze eight lesions in standard spin-echo MR examinations of three patients with MS. Lesion distributions were compared between examinations by first calibrating the examinations based on the intensity distributions of cerebrospinal fluid (CSF), an internal reference tissue. Many of the lesion distributions had a distinctive peak at low intensity, corresponding to normal-appearing white matter (WM). Within the lesion distributions, increases in high intensity peaks generally were accompanied by reductions in the WM peak. Serial analysis of the lesion distributions revealed some dramatic fluctuations, even when lesion volume remained constant.

Calibration↗

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Hemodynamic abnormalities in fetuses with congenital heart disease.

The purpose of this investigation was to assess left and right ventricular function, volume ejection fraction, combined stroke volume, and combined ventricular output in the human fetus with congenital heart disease compared to the normal healthy fetus. Seventy-two fetuses with a variety of in utero diagnosed congenital cardiac defects were compared with a control group of fetuses with structurally normal hearts matched for race, maternal age, and gestational age. We demonstrated significant hemodynamic changes in the fetus with congenital heart disease. There was a significant (p < 0.0001) decrease in the volume ejection fractions, biventricular stroke volume, and cardiac output in the congenital heart disease group compared to matched controls. Our findings suggest that hemodynamic abnormalities in the fetus with congenital heart disease are present before birth and we speculate that myocardial reserve may not be adequate to respond to hemodynamic stressors such as birth or heart surgery.

Adult↗

PubMedDate not supplied

The effect of treatment for colorectal cancer on long-term health-related quality of life.

BACKGROUND: Little information is available on the impact that therapies used in the treatment of colorectal cancer (CRC) have on long-term, health-related quality of life (HRQL). Knowledge of how HRQL is affected by these therapies is essential in properly selecting patients for treatment. The purpose of this study was to determine the long-term impact that surgical and adjuvant therapy for resectable CRC has on patient-reported HRQL in a male veteran population through a case-control design. METHODS: All participating patients had completed therapy at least 6 months before enrollment. One hundred fifty-eight patients were accrued over a 3-year period (January 1, 1997 to December 31, 1999) at a single institution. The impact of CRC surgery on HRQL was measured by comparing a cohort of 61 patients undergoing surgery alone for the treatment of CRC (CRC-S group) with 44 patients undergoing surgery for benign colonic disease (BCD group). To study the effect of adjuvant therapy for CRC on HRQL, a third cohort of 53 patients undergoing both surgical and adjuvant treatment (CRC-S/A group) was compared with the CRC-S group. For each group, health status was measured by a health survey questionnaire, SHORT FORM 36 (SF36). For patients treated for CRC, an additional disease-specific supplemental questionnaire also was used. RESULTS: Self-reported health status, as measured by mean SF36 score, was significantly reduced for the BCD group compared with CRC-S patients on general health perception (41.9 +/- 3.9 vs. 52.2 +/- 3.0, P = .04) and the standardized physical component score (31.2 +/- 1.7 vs. 37.5 +/- 1.5, P < .005). Despite an increased number of distally located tumors, later stage cancers, and an increased number of recurrences in the CRC-S/A group compared with the CRC-S cohort, no significant differences were identified between these groups on any of the subscales or standardized scores of SF36. Using the supplemental questions, no differences were identified between the CRC groups with respect to appetite, weight, or gastrointestinal or urinary functioning. CONCLUSIONS: Surgical therapy for CRC probably has minimal impact on long-term HRQL when compared with surgery for benign colonic processes. Similarly, there does not appear to be a measurable, lasting impact of CRC adjuvant therapy on HRQL when compared with surgery alone. Although overall impact of therapies for CRC on HRQL appears to be limited, measurement of therapeutic influence on an individual level and identification of selection criteria based on estimated impact on HRQL for these therapies requires prospective validation.

Adult↗

PubMedDate not supplied

Characterization of angiotensin II receptors in the rat fetus.

The presence of AII receptors during early and late embryonic development was studied by binding of 125I[Sar1, Ile8] AII to whole mouse blastocysts and membrane-rich fractions from rat conceptuses, 7 to 21 days in gestation. In early mouse embryos there was no detectable binding under a variety of experimental conditions. However, in late gestation rat fetuses, specific and high affinity binding was observed, with a concentration of sites similar in membranes from whole and eviscerated fetuses. Using less than 100 micrograms of membrane protein, binding was time and temperature dependent, maintaining equilibrium from 30 to 120 min at 23 degrees C and it was enhanced by addition of Mg+2 up to 5 mM, EGTA 2 mM and dithiothreitol up to 2.5 mM. Scatchard analysis of the binding data indicated Kd values ranging between 0.7 and 0.9 nM. Binding was first detectable at day 10 (14.3 +/- 2.3 fmol/mg), increasing to 104 +/- 16, 2,625 +/- 168, 5,993 +/- 152 and 5,902 +/- 92 by days 12, 15, 18, and 21 of gestational age, respectively. Since the functional significance of these binding sites depends on the availability of the agonist ligand, acid extracts from eviscerated 10-day-old fetuses were analyzed for the presence of AII. Measurement of AII by radioimmunoassay revealed immunoreactive AII-like material (845 pg/g of tissue), with an elution pattern identical to that of AII standard in a Sephadex G-50 column. This material was bioactive, as demonstrated by its ability to displace 125I[Sar1, Ile8]AII from adrenal glomerulosa membranes, an effect which was abolished by pretreatment of the extract with AII antibody.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMedDate not supplied

Recognition of food in weanling rats exposed to alcohol prenatally.

Offspring of rats fed a liquid diet containing ethanol during their pregnancies were compared to controls on a caloric discrimination test beginning at 22 days of age. All pups received simultaneous choice between a palatable, noncaloric diet and a similar diet containing starch. Each diet contained a distinctive flavor. To test for flavor preference learning, pups then received an extinction test: a simultaneous choice between two noncaloric diets, identical except for flavor. Prenatal alcohol exposure had no substantial effect on the caloric discrimination, and all groups preferentially ingested the starch diet on all test days. However, during the extinction test, alcohol-exposed pups showed a significantly weaker flavor preference than control pups. These data extend the effects of prenatal alcohol exposure on learning and ingestive behavior to include solid food discriminations at the time of weaning.

Analysis of Variance↗

PubMedDate not supplied

Characterization of cell-cycle arrest by fumonisin B1 in CV-1 cells.

Fusarium moniliforme is a widespread fungal pathogen which primarily infects corn, but can also infect rice or wheat. Fusarium moniliforme produce several mycotoxins, the most prominent of which is called fumonisin B1 (FB1). Epidemiological studies have indicated that ingestion of fumonisins correlates with a higher incidence of oesophageal cancer in Africa and China. Fumonisins also cause a neurodegenerative disease in horses, induce hepatic cancer in rats, are nephrotoxic in rats, or cause pulmonary oedema in swine. Structurally, fumonisins resemble sphingolipids and can alter sphingolipid biosynthesis. suggesting that sphingolipid alterations play a role in disease and carcinogenesis. Previous studies determined that FB1 blocked cell-cycle progression in CV-1 cells but not COS-7 cells. Herein, we have examined the effects that FB1 treatment has on cell-cycle regulatory proteins. Our studies established that FB1 treatment of CV-1 cells, but not COS-7 cells, leads to dephosphorylation of the retinoblastoma (Rb) protein. Cyclin dependent kinase 2 (CDK2) activity was repressed five- to 10-fold and cyclin E protein levels were lower in CV-1 cells after fumonisin treatment. Two CDK inhibitors, Kip1 and Kip2, were induced within 3 hours after fumonisin treatment of CV-1 cells, suggesting these two proteins mediate cell-cycle arrest induced by FB1. This mycotoxin caused large increases in sphinganine within 3 hours after addition of FB1. As sphingoid bases are known to induce Rb phosphorylation, this increase in sphinganinie might be the stimulus for the suppression of cyclin dependent kinase activities via Kip1 and Kip2. The ability of FB1 to accumulate sphingosine or sphinganine and arrest the cell cycle in some cells but not others may play an important role in carcinogenesis or disease.

Animals↗