Bone and soft-tissue lesions: diagnosis with combined H-1 MR imaging and P-31 MR spectroscopy

The feasibility of combined magnetic resonance (MR) imaging and surface coil phosphorus-31 MR spectroscopy at 1.5 T was examined in a clinical study of 34 patients before biopsy of bone or soft-tissue lesions of the extremity and trunk. The results confirmed the inability of MR imaging alone to distinguish most benign lesions from malignant ones. Malignant lesions were distinguished from benign lesions on the basis of significantly higher mean peak ratios of phosphomonoester (PME) to beta-nucleoside triphosphate (NTP) and of phosphodiester to NTP, a significantly lower mean peak area ratio of phosphocreatine to NTP, and a higher mean pH. The diagnostic performance of the PME/NTP peak area ratio is characterized by a sensitivity (true-positive fraction) of 1.00 and a specificity (true-negative fraction) of 0.93. This study provided preliminary evidence that P-31 MR spectroscopy may be used to improve diagnostic specificity in bone and soft-tissue lesions.     

A Study of Neuropathy in HIV Infection

A prospective study of possible aetiological factors for neuropathyassociated with HIV infection was performed in 80 patients and28 homosexual controls. At entry to the study twelve patients(15 per cent) had evidence of a generalized neuropathy not dueto any other cause and a further three patients developed symptomaticneuropathy during a mean (SD) follow-up of 20 (7.5) months.All but two of these neuropathies were of the distal symmetricalsensory type. Electrophysiology was consistent with an axonalpathology and nerve biopsy confirmed this as the major pathologicalchange. Warming threshold was the diagnostic test most frequentlyabnormal, sometimes in the absence of other electrophysiologicalabnormalities. No association was seen with opportunistic infection(cytomegalovirus, herpes simplex, Pneumocystis pneumonia, toxoplasmosis,Cryptococcus infection or tuberculosis). HIV proviral DNA couldnot be detected in paraffin sections of peripheral nerve insix patients with neuropathy. The presence of the neuropathydid not show significant correlation with depression of thenumber of CD4⁺T cells in the blood, impaired T cell functiontests, or IgG, IgM, or IgA levels. Immune complexes containingC1q,but not those containing IgG, IgM, IgA or C3c, were significantlymore common among neuropathic patients (     

Techniques in the Angiographic Analysis of Coronary Flow: Past, Present, and Future

The current method of analyzing coronary flow data is the TIMI flow grade method. This method is convenient and easy to apply, but there are limitations to this categorical method of analyzing coronary artery flow. We have developed a new method of analyzing coronary blood flow called the "TIMI frame count." Using the TIMI frame counting method, we have shown that the flow in the coronary arteries is in fact distributed as a continuous variable and that there are nondiscrete categories of slow and fast flow. This article discusses the statistical basis for the development of this new, simple, and continuous index of coronary flow and provides a "how-to manual" describing the practical implementation of the new TIMI frame count method. We also describe simple new techniques for measuring the distance to the landmark used for TIMI frame counting. Knowing the distance and the time from the TIMI frame count, velocity can easily be calculated. Tables are provided that can be used for these calculations on-line in the cardiac catheterization laboratory. If the diameter is known, flow can also be calculated from these tables. We also describe new applications of marker wires to measure distance and velocity .     

Heat-stable antigen may be an early marker of extrathymic murine intestinal intraepithelial lymphocytes

Using a system of bone marrow (BM) hematopoietic repopulation of irradiated euthymic and athymic mice, we have examined the early stages of extrathymic T-cell development within the murine small intestine epithelium. During a period of active extrathymic T-cell development, two distinct populations of intraepithelial lymphocytes (IEL) were present. One consisted of CD3+ lymphocytes with phenotypic properties of mature IEL. The other population consisted of a transient IEL subset that increased in abundance between days 5 and 14 post-BM transfer, and then declined. The majority of transient IEL in both types of mice expressed the heat-stable antigen, of which some cells coexpressed CD3 but were void of other markers common to mature T cells. Studies using freshly extracted IEL from normal nonirradiated mice found that approximately 3% to 5% of the IEL had phenotypic properties similar to the transient IEL observed during repopulation of radiation chimeras, indicating that such IEL are present within the gut epithelium of normal, nonirradiated mice. Identification of this IEL subset should greatly facilitate studies of extrathymic IEL development.     

Functional analysis in Saccharomyces cerevisiae of naturally occurring amino acid substitutions in human dihydrolipoamide dehydrogenase

Dihydrolipoamide dehydrogenase is a common component of mammalian multienzyme complexes that decarboxylate alpha-ketoacids and catabolize glycine. The common function is to reoxidize a reduced lipoate component of each complex, thereby preparing that lipoate for another round of catalysis. Regions within dihydrolipoamide dehydrogenase involved in association with other proteins of the complexes are poorly defined, and despite high amino acid sequence conservation through evolution, it is unknown if dihydrolipoamide dehydrogenases are functionally equivalent across species. To address this issue, we asked whether the human enzyme could restore function to the alpha-ketoacid dehydrogenase complexes in a yeast strain deficient in endogenous dihydrolipoamide dehydrogenase. This dihydrolipoamide dehydrogenase null mutant will not grow on non-fermentable carbon sources. The human enzyme expressed from a CEN plasmid complemented the growth phenotype and restored full activity to the pyruvate and alpha-ketoglutarate dehydrogenase complexes. Human dihydrolipoamide dehydrogenases with selected amino acid substitutions were then tested in the null strain for their ability to restore function. Substitutions tested represented naturally occurring candidate mutations identified in an individual with inactive dihydrolipoamide dehydrogenase. A K37E change had full function while a P453L change resulted in reduced dihydrolipoamide dehydrogenase abundance in the mitochondria and no detectable catalytic activity.      

Vitamin D metabolites and growth hormone therapy in uraemic rats: the short-term effect on growth failure and hyperparathyroidism

Summary: The aim of our study was to evaluate the effect of 1,25 dihydroxyvitamin D3 (D), 22-oxacalcitriol (O) or recombinant human growth hormone (GH) on growth failure and hyperparathyroidism in 5/6 nephrectomized uraemic (Ur) rats. Seven groups of rats were studied: (i) sham controls (SC; n =6); (ii) Ur controls (UrC; n =8); (iii) Ur treated either with D (UrD; n =7); (iv) O (UrO, n =8); (v) GH (UrGH; n =7); (vi) D+GH (UrDGH; n =9); or (vii) O+GH (UrOGH; n =7). For 14 days, D and O were administered intraperitoneally daily at 30 ng/kg per day and GH subcutaneously daily at 1.3 i.u./day. Four weeks after 5/6 nephrectomy, plasma creatinine (Cr), plasma and urine calcium (Ca), plasma phosphate (P), ratio of urine Ca/urine Cr, amino-terminal parathyroid hormone (PTH; pg/mL) and Ca/dry bone weight in the left femur (mg/g) were measured. Uraemic controls, UrD, UrO and UrDGH rats were lower in weight gain than SC rats over the study period, but linear growth was not retarded in any uraemic group. Plasma Cr was greatly increased in any Ur group as compared with SC group. Plasma Ca and P concentrations did not differ among each group. the ratio of urine Ca/urine Cr in UrD and UrDGH groups was higher than SC, UrCand UrGH groups. the use of Dor D+GH suppressed PTH, returning the level in these rats to the normal level of the SC rats, while the PTH concentrations in the UrO and UrOGH rats were less decreased. Bone Ca content was enhanced by D+GH and O+GH administration in comparison with UrC rats, but there was no difference in the bone Ca content between UrD and UrDGH rats, and between UrO and UrOGH rats. In conclusion, growth failure in weight was shown in uraemia, but linear growth was not retarded in any uraemic group. 1.25 dihydroxyvitamin D3 and D plus GH successfully suppressed secondary hyperparathyroidism. Further studies are needed in order to elucidate the interactions on bone between vitamin D rnctabolites and GH.