Quantification of myocardial blood flow and extracellular volumes using a bolus injection of Gd-DTPA: kinetic modeling in canine ischemic disease.

In order to clarify the relationship between coronary artery disease (including myocardial infarction) and image contrast in gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-enhanced MRI it was decided to model the myocardial tissue distribution and clearance of Gd-DTPA using the modified Kety equation. Using a canine model, myocardial tissue Gd-DTPA concentrations ([Gd-DTPA]m) were measured 1 or 5 min after a bolus injection of Gd-DTPA or immediately after the end of a constant infusion of Gd-DTPA in a total of 35 dogs. It was found that within 5 min of a bolus injection [Gd-DTPA]m is determined primarily by myocardial blood flow (MBF) and after about 10 min primarily by myocardial extracellular volumes (MECV). This study suggests that repeat, rapid (every 2-4 s) measurements of myocardial T1 relaxation rates following the bolus injection of Gd-DTPA are required to calculate MBF (i.e., myocardial tissue perfusion) and MECV.     

Popliteal artery entrapment syndrome

Three cases of popliteal artery entrapment syndrome, one of them bilateral, are presented with a review of the literature, with special reference to the embryological development of the popliteal space and the diagnostic and therapeutic problems presented by this syndrome.     

Reduced incidence and severity of accelerated graft atherosclerosis in cardiac transplant recipients treated with prophylactic antilymphocyte globulin.

Allograft coronary artery disease (ACAD) is the major factor limiting long-term survival of cardiac transplant recipients (CTRs). Although cyclosporine based triple drug immunosuppression has not decreased the occurrence of ACAD, some preliminary data suggests that prophylactic antilymphocyte preparations may reduce the incidence of this problem. All CTRs at Henry Ford Hospital have uniformly received prophylactic Minnesota Antilymphocyte Globulin (ALG), thereby providing a unique opportunity to investigate this hypothesis. One hundred three CTRs were followed for a median duration of 34 months with annual angiograms begun one year after transplant. Patients who died without an angiogram were considered to have ACAD based on autopsy results or if their death was clinically suspicious. Ninety-two patients underwent at least one angiogram. Fourteen patients had abnormal angiograms. Nine patients were identified as having ACAD by non-angiographic criteria. Five had autopsy proven disease, 3 died suspiciously, and 1 underwent successful re-transplantation for ACAD. By Kaplan-Meier analysis, the risk of developing ACAD was 12% in 1 year, 16% in 2 years, 22% in 3 years, 26% in 4 years, and 29% in 5 years. Risk of ACAD increased with older recipient's age, higher triglyceride levels, and diabetes, but was not affected by active CMV infection, number of acute rejection episodes, and HLA mismatching. These results suggest that prophylactic ALG reduces the occurrence of ACAD.     

Mapping corpus callosum deficits in autism: an index of aberrant cortical connectivity.

BACKGROUND: Volumetric studies have reported reductions in the size of the corpus callosum (CC) in autism, but the callosal regions contributing to this deficit have differed among studies. In this study, a computational method was used to detect and map the spatial pattern of CC abnormalities in male patients with autism. METHODS: Twenty-four boys with autism (aged 10.0 +/- 3.3 years) and 26 control boys (aged 11.0 +/- 2.5 years) underwent a magnetic resonance imaging (MRI) scan at 3 Tesla. Total and regional areas of the CC were determined using traditional morphometric methods. Three-dimensional (3D) surface models of the CC were also created from the MRI scans. Statistical maps were created to visualize morphologic variability of the CC and to localize regions of callosal thinning in autism. RESULTS: Traditional morphometric methods detected a significant reduction in the total callosal area and in the anterior third of the CC in patients with autism; however, 3D maps revealed significant reductions in both the splenium and genu of the CC in patients. CONCLUSIONS: Statistical maps of the CC revealed callosal deficits in autism with greater precision than traditional morphometric methods. These abnormalities suggest aberrant connections between cortical regions, which is consistent with the hypothesis of abnormal cortical connectivity in autism.     

The use of a priori knowledge to quantify short echo in vivo 1h mr spectra

In vivo ¹H MR spectra of the prefrontal cortex acquired with the stimulated echo acquisition mode (STEAM) TE = 20 ms sequence were quantified to determine relative levels of cerebral metabolites. A priori knowledge of spectra from individual metabolites in aqueous solution was incorporated into a frequency domain quantification technique. The accuracy and precision of modeling these metabolites were investigated with simulated spectra of varying signal-to-noise ratios (SNRs) and relative metabolite levels. The efficacy of modeling in vivo data was tested by quantifying 10 repeated measures of two consecutively acquired in vivo spectra (an 8?cm³ volume of interest (VOI) and a 4?cm³ VOI positioned within the 8?cm³ VOI) on the same normal subject. The differences in levels of glutamate (Glu), phosphocreatine plus creatine (PCr+Cr) and choline-containing compounds (Cho₁ between spectra from the 8? and 4?cm³ VOIs corresponded with the expected differences observed in the proportions of gray matter within the VOIs (estimated from ¹H images). Correcting for the T₁ and T₂ relaxation, the estimated concentrations of N-acetylaspartate, PCr+Cr, Cho₁, Glu, and glutamine were consistent with previous in vivo and in vitro reports.     

Factor IX mutations in South Africans and African Americans are compatible with primarily endogenous influences upon recent germline mutations

Similar patterns of germline mutations in the factor IX gene (F9) have been observed in certain geographically and racially diverse populations. Germline mutation data have not been available from any region of Africa or from the Black race. Analysis of mutation data for Blacks is of interest, since this race has a high frequency of polymorphism compared to other races. This high frequency has been interpreted as evidence for the "out of Africa" hypothesis for the origin of humans, but it is possible that Blacks have a higher mutation rate due to genetic differences or environmental exposures. We report 26 independent mutations that were detected in patients of mixed races with hemophilia B from South Africa. The pattern of mutation in patients from this African country was similar to that of U.S. Caucasians. In addition, 22 independent mutation were detected in African American patients. The patterns of independent germline mutation in 22 African Americans (and in a combination 34 North American and African Blacks) is similar to that of U.S. Caucasians. Neither genetic differences between the Black and Caucasian races nor environmental and cultural differences between South Africa and the U.S. alter the germline pattern of mutation observed in F9. Hum Mutat 16:372, 2000.     

Expression and carbonylation of creatine kinase in the quadriceps femoris muscles of patients with chronic obstructive pulmonary disease

Oxidative protein modification involving carbonylation has recently been identified as an important factor in skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD). However, the exact identity of modified proteins inside limb muscles of patients with COPD remains unknown. We used 2D electrophoresis, immunoblotting, and mass spectrometry to identify carbonylated proteins in the vastus lateralis muscle of 12 patients with COPD and 6 control subjects. Both creatine kinase (CK) and carbonic anhydrase III (CAIII) were identified as being strongly carbonylated in this muscle in both groups of subjects. Total CK activity, CK protein expression, and the intensity of CK carbonylation were significantly greater in the muscles of patients with COPD as compared with control subjects, whereas CAIII protein expression and intensity of carbonylation were similar in the two groups. In patients with COPD, CK activity and protein expression correlated positively with FEV(1) and V O(2)max, whereas the intensity of CK carbonylation correlated negatively with the same parameters. These results indicate that oxygen radicals selectively target CK and CAIII inside limb muscles of humans. The observation that the intensity of CK carbonylation correlates negatively with CK activity in limb muscles of patients with COPD suggests that carbonylation may have a deleterious effect on CK activity, and may contribute to impaired CK function in the limb muscles of these patients.     

The human factor IX gene as germline mutagen test: samples from Mainland China have the putatively endogenous pattern of mutation

Germline mutations are the major source of genetic variation that allows a species to evolve over time but at the cost of Mendelian disease and genetic predisposition to multifactorial diseases. Previous analyses have revealed that the pattern of germline mutations in the factor IX gene (F9) is similar among a variety of ethnically and geographically diverse populations and compatible with the ancient pattern that has shaped the mammalian genome. Here, we compare the pattern of germline mutation in a population of hemophilia B patients from Mainland China (n=66) to that in U.S. Caucasians, Blacks, and Mexican Hispanics and stratify by disease severity and ethnicity. The similar pattern of germline mutation in all ethnic groups studied to date provides additional data compatible with the inference that endogenous processes predominate in germline mutations.     

Cruzipain induces autoantibodies against cardiac muscarinic acetylcholine receptors. Functional and pathological implications

The goal of this study was to investigate whether cruzipain, a Trypanosoma cruzi immunodominant antigen, was able to induce antibodies reactive to the cardiac M(2) muscarinic acetylcholine receptor (M(2) mAChR). Immunization with cruzipain that was devoid of enzyme activity triggered IgG antibodies against cardiac M(2) mAChR. By radioligand competition assay we proved that the anti-cruzipain IgG fraction, purified from serum, inhibited binding of the specific M(2) mAChR radioligand [(3)H]quinuclidinyl benzilate. We also demonstrated that anti-cruzipain IgG reacted against the second extracellular loop of the M(2) mAChR. The corresponding affinity-purified serum anti-M(2)e2 IgG (reacting against a synthetic peptide corresponding to this loop in humans) displayed agonist-like activity associated with specific M(2) mAChR activation - increase of cGMP, inositol phosphate accumulation and nitric oxide synthase activity - triggering a decrease in myocardial contractility. Moreover, the same IgG fraction decreased heart frequency, related to inhibition of adenylate cyclase activity. These results imply that cruzipain plays a role in the production of antibodies against M(2) mAChR, which have been related to the pathogenesis of dysautonomic syndrome described in Chagas' disease.