1H magnetic resonance spectroscopy evidence that aberrant crypt foci are preneoplastic lesions in the colon.

BACKGROUND: Histopathological and genetic studies support the hypothesis that aberrant crypt foci (ACF) represent one of the earliest events in colon carcinogenesis. The purpose of this study is to make use of 1H MRS in conjunction with multivariate methods of analysis to ascertain the validity of the above mentioned hypothesis. MATERIALS AND METHODS: ACF, colonic mucosa and tumor samples taken from thirty-two carcinogen (azoxymethane)-treated Sprague Dawley rats, and of colon mucosa taken from ten healthy animals, were investigated ex vivo by 1H MRS and analyzed using multivariate methods of analysis. RESULTS: The 1H magnetic resonance peak intensities and areas of ACF lie between those from normal and carcinogen- treated mucosa samples and tumors. Multivariate analysis classification of the spectra suggests that the ACF exhibit biochemical characteristics intermediate between the control and AOM-mucosa samples and the tumor groups. CONCLUSION: The use of sophisticated methods of data classification has enabled us to support the hypothesis that ACF represent preneoplastic lesions of the colon.

Nuclear magnetic resonance spectroscopy study of muscle growth, mdx dystrophy and glucocorticoid treatments: correlation with repair.

Proton nuclear magnetic resonance spectroscopy (1H NMR) can be used to study skeletal muscle metabolism. The mdx mouse is a unique animal for studies of muscle regeneration, and models the disease of Duchenne muscular dystrophy (DMD). The goals of this study were to determine the potential of 1H NMR spectroscopy as an alternative to conventional histology in monitoring: (1) normal growth in control muscle and the progression of dystrophy in mdx muscle, and (2) beneficial treatments (glucocorticoids) on mdx dystrophy. Ex vivo 1H NMR spectra of limb and diaphragm muscles were obtained from different ages of control and mdx mice, and from mice which were treated with prednisone or deflazacort. Peaks with contributions from creatine, taurine and lipids were examined. Lower levels of taurine and creatine characterized predystrophy and active dystrophy intervals in mdx muscle compared to control. Levels of taurine increased with stabilization of the disease by repair. A measure of accumulated muscle repair, fiber centronucleation and many spectral peaks were highly and significantly correlated. Greater amounts of lipids were found in the diaphragm compared to limb spectra. Treatment of dystrophy, which improved muscle phenotype, resulted in greater levels of taurine and creatine, especially in the limb muscle. Therefore, 1H NMR differentially discriminates: (1) control and mdx muscle; (2) the progression of mdx dystrophy and developmental stages in normal growth; (3) mild and severe dystrophic phenotypes (diaphragm vs limb); and (4) changes associated with improved muscle phenotype and regeneration (due to treatment or injury). The results focus on monitoring muscle repair, not degeneration. We conclude that 1H NMR is a reliable tool in the objective investigation of muscle repair status during muscular dystrophy.

Classification of 1H MR spectra of human brain neoplasms: the influence of preprocessing and computerized consensus diagnosis on classification accuracy.

We study how classification accuracy can be improved when both different data preprocessing methods and computerized consensus diagnosis (CCD) are applied to 1H magnetic resonance (MR) spectra of astrocytomas, meningiomas, and epileptic brain tissue. The MR spectra (360 MHz, 37 degrees C) of tissue specimens (biopsies) from subjects with meningiomas (95; 26 cases), astrocytomas (74; 26 cases), and epilepsy (37; 8 cases) were preprocessed by several methods. Each data set was partitioned into training and validation sets. Robust classification was carried out via linear discriminant analysis (LDA), artificial neural nets (NN), and CCD, and the results were compared with histopathological diagnosis of the MR specimens. Normalization of the relevant spectral regions affects classification accuracy significantly. The spectra-based average three-class classification accuracies of LDA and NN increased from 81.7% (unnormalized data sets) to 89.9% (normalized). CCD increased the classification accuracy of the normalized sets to an average of 91.8%. CCD invariably decreases the fraction of unclassifiable spectra. The same trends prevail, with improved results, for case-based classification. Preprocessing the 1H MR spectra is essential for accurate and reliable classification of astrocytomas, meningiomas, and nontumorous epileptic brain tissue. CCD improves classification accuracy, with an attendant decrease in the fraction of unclassifiable spectra or cases.

Mobile lipid accumulation in necrotic tissue of high grade astrocytomas.

Multiple samples from 42 astrocytomas were investigated ex vivo by 1H MR spectroscopy followed by histological assessment. MR visible lipids were detected in 27 of 32 grade 4 astrocytomas. These lipids were heterogeneously distributed within the tumours. Their amount correlated positively with the amount of histologically detected necrosis. Mobile lipids were also observed in grade 4 astrocytoma samples without necrosis, as well as in one of three grade 3, two of three grade 2 and two of four grade 1 astrocytomas. The clinical significance of MR visible lipids, their cellular location, and their possible biological bases are discussed.

Diagnostic potential for cancer via 1H magnetic resonance spectroscopy of colon tissue.

Specimens of colon tissue were examined by 1H MRS (360 MHz) in order to determine the usefulness of rat colon (n = 44) as a model for human colon (n = 60), particularly for the characterization of preneoplastic lesions. Human tissue was characterized by 1H MRS as a precursor to in vivo studies. For both tissues, resonances from mobile lipids were not characteristic of pure mucosa, but correlated with the presence of submucosa. The mean intensities of the resonances at 3.2 and 3.4 ppm (assigned mainly to choline-containing compounds and taurine, respectively) of rat mucosa compared to those of human mucosa, and of rat tumours compared to human tumours, were not significantly different, while both resonances were significantly more intense in rat tumours compared to rat mucosa. The spectra of premalignant lesions in rat colon have features between those due to tumours and normal tissue. We conclude that rat colon is a useful model for human colon in 1H MR spectroscopic studies. MR spectra from human colon control tissue and tumours were classified with 100% accuracy using multivariate analysis.

The integrity of cisplatin in aqueous and plasma ultrafiltrate media studied by 195Pt and 15N nuclear magnetic resonance.

195Pt and 15N nuclear magnetic resonance (NMR) was used to study the chemical equilibria of cisplatin in water and plasma ultrafiltrate (PUF). Cisplatin was found to be stable for at least 2, but no longer than 5 months in a reconstituted clinical formulation, as determined by 195Pt NMR. In aqueous solution, the cis-PtCl2(NH3)2 195Pt and 15N NMR signal intensities decreased with time and the formation of [PtCl(H2O)(NH3)2]+ at PH values of 3.0, 6.5, 7.5 and 9.5 was observed within 24 h of sample preparation. In addition, [Pt(H2O)2(NH3)2]++ was observed at pH 3.0, and [PtCl(OH)(NH3)2] and [Pt(OH)2(NH3)2] were observed at pHs 7.5 and 9.5. During incubation of PUF with cisplatin for 35 h, 15N NMR signals for at least eight cisplatin derivatives appeared at different times, whereas only four were observed by 195Pt NMR. With our NMR protocols, the detection limit for quantifiable cisplatin derivatives is estimated at 500 microM using 195Pt NMR and < or = 200 microM using 15N NMR. In addition to providing useful information about the chemical stability of cisplatin and derivatives formed in aqueous solution, these magnetic resonance techniques, particularly 15N NMR, can provide useful information about the metabolism of cisplatin in biological regimes.

1H MR visible lipids in colon tissue from normal and carcinogen-treated rats.

Metabolic characteristics of colon mucosa, submucosa, muscularis and tumour specimens from four control (n = 105) and nine carcinogen (azoxymethane)-treated (n = 91) Sprague-Dawley rats were investigated by ex vivo 1H MRS. Ninety-seven per cent of pure mucosa samples (n = 59) yielded spectra with narrow lipid resonances (chemical shift delta of -(CH2)n-, 1.3 ppm; linewidth at half-height v1/2, 30-50 Hz). Eighty-two per cent of control mucosa samples with histologically proven submucosa contamination (n = 11) and 46% of control cross-sections (containing mucosa, submucosa and muscularis; n = 57) yielded spectra with broad lipid resonances (delta-(CH2)n-, 1.5 ppm; v1/2, 80-100 Hz) identical to those of adipose tissue surrounding rat colon. Thirty per cent of tumour samples (n = 10) yielded spectra with narrow lipid resonances while 70% contained no significant amount of MR visible lipids. We conclude that (i) lipids giving rise to broad resonances are in the heterogeneously distributed adipocytes of submucosa, (ii) lipids giving rise to narrow resonances are within the mucosa in an unknown structural environment, and (iii) the type and distribution of lipids in human and rat colon are similar. Tumours contained significantly more taurine than pure control mucosa (n = 15; p < 0.004) and pure mucosa containing aberrant crypt foci (putative preneoplasm, n = 36; p < 0.002). Our results suggest that the rat colon is a good model for 1H MR investigations of human colon carcinogenesis.

Impaired recovery of strength in older patients after major abdominal surgery.

OBJECTIVE: This study compared changes in muscle strength after major elective abdominal surgery in young and old patients, and related these changes to body composition and nitrogen balance. SUMMARY BACKGROUND DATA: The breakdown of muscle protein, erosion of lean tissue, and negative nitrogen balance are characteristic metabolic responses to surgical illness. With a substantial loss of muscle mass typical of advancing age, the authors postulated that older patients would be weaker during acute surgical illness and less able to maintain muscle function and meet metabolic demands. METHODS: Active, community-dwelling individuals undergoing major abdominal procedures who were 70 years of age or older or 50 years of age or younger were studied. Total body water (TBW) was determined preoperatively by deuterium oxide dilution. Maximal voluntary handgrip, respiratory muscle strength, and visual analog pain scores were measured preoperatively and on postoperative days 2, 4, and 6. All urine was collected postoperatively for 7 days for determination of total nitrogen, creatinine, and cortisol. RESULTS: The young (age, 36 +/- 9 years [mean +/- standard deviation]; n = 20) and old groups (age, 77 +/- 5 years; n = 20) were similar regarding weight, sex distribution, nutritional status, surgical procedures and anesthesia, and postoperative urine cortisol values. Age group, time after operation, and interaction effects were significant for each strength variable (all p < 0.005 by analysis of variance). Older patients had lower preoperative strength (29% to 41%) and mean 24-hour urine creatinine (27%). Postoperative strength was decreased most markedly on postoperative day 2, with similar proportional changes in the two age groups but lower absolute levels in the older patients. The rate of recovery of strength was substantially less rapid and complete in older patients. Older patients had less postoperative pain and received much less parenteral narcotic than younger patients. Postoperative urine nitrogen was similar in each group. Recovery of strength was not related to malignancy, preoperative strength, muscle mass (urine creatinine), lean body mass (TBW), sex, malignancy, pain, or narcotic administration. CONCLUSIONS: Older patients are weaker preoperatively than younger patients; their strength falls to lower levels after surgery and their postoperative recovery of strength is impaired. The lesser preoperative strength of older patients is due in large part but not totally to diminished muscle mass. Their impaired postoperative recovery appears to be related to more acute factors, such as muscle energetics or substrate availability.

Glycosphingolipid backbone conformation and behavior in cholesterol-containing phospholipid bilayers.

2H NMR spectroscopy was used to consider correspondence between existing single-crystal X-ray data for glycosphingolipids and their ceramide backbone conformation in fluid phospholipid membranes. A monoglycosylated sphingolipid, glucosylceramide (GlcCer), which represents the core structure of many important glycosphingolipids, was derived by partial synthesis through replacement of all native fatty acids with the 18-carbon species, stearic acid, deuterated at C2. N-[2,2-2H2]stearoyl-GlcCer was used to probe glycosphingolipid orientation and motion at low concentration in "fluid" phospholipid bilayers composed of dimyristoylphosphatidylcholine (DMPC), with and without physiological amounts of cholesterol. Spectral analysis, aided by stereoselective monodeuteration of the GlcCer fatty acid at C2, demonstrated that glycosphingolipid average acyl chain backbone conformation in fluid phospholipid membranes, with or without cholesterol, is likely closely related to that predicted from single crystal X-ray studies [Pascher, I. (1976) Biochim. Biophys. Acta 455, 433-451; Pascher, I., & Sundell, S. (1977) Chem. Phys. Lipids 20, 175-191]. To test the generality of this observation, specific comparisons were made involving galactosylceramide (GalCer) and globoside. GalCer provided a glycolipid differing only in monosaccharide stereochemistry (galactose vs glucose). Globoside permitted isolation of the effect of headgroup size, since it is derived from GlcCer via extension of the carbohydrate portion by the oligosaccharide, GalNAc beta 1-->3Gal alpha 1-->4Gal attached in beta 1-->4 linkage to the Glc residue.(ABSTRACT TRUNCATED AT 250 WORDS)