Radionuclide ventriculography (equilibrium gated blood pool scanning) —its present clinical position and recent development

Myocardial scanning (MS) and radionuclide ventriculography (RNV) are the foundation of nuclear cardiology. These procedures aim in two completely different directions: RNV tries to image heart motion, that is, mechanical (pump) function, and therefore belongs to the group of first-order functional imaging (FI, imaging mechanical function), whereas MS is based on myocardial metabolism, and therefore can be attributed to third-order functional imaging (metabolism). This statement is relevant for the assessment of the clinical position of RNV: Third-order (metabolism) functional imaging is the domain of nuclear medicine (NM), whereas first-order FI has to face the competition of alternative noninvasive procedures such as ultrasound (US), digital subtraction angiography (DSA), computer tomography (CT), and nuclear magnetic resonance (NMR). The domain of RNV includes stages two (acute infarction) and three (postinfarction period) of coronary arterial disease (CAD). The advantageous combination of quantitative data on global, left ventricular (LV) function and imaging of regional motion ensures the superiority of RNV over US. However, RNV is inferior to MS in physical examinations in the preinfarction stage of CAD, whereas US is clearly inferior to both NM procedures. Recent progress could be attained by gated SPECT (GASPECT). A proposal is presented for simplification of this time-consuming procedure. Technetium-labeled isonitriles offer the chance for the combination of perfusion-motion imaging of the myocardium. However, even standard RNV offers new possibilities. The multitude of parameters produced by quantitation has not yet been exploited completely. This can be done by discriminant analysis. The computer finds out an optimal subset from the whole set of parameters for the solution of a significant clinical problem. The software learns to find the label of a special pathognomonic entity. This computer work is supported by a relational data bank (Oracle) and an optical disk. Two examples for the effectiveness of the computer in problem solving are presented. It is concluded that RNV, even in the very competitive class of first-order functional imaging, enjoys a preferred position. The future indeed seems brighter because labeled isonitriles offer the chance for the combination of perfusion-motion imaging of the myocardium.Dedicated to Prof. Heinz Hundeshagen on the occasion of his 60th birthday     

Functional analysis of human MLH1 and MSH2 missense variants and hybrid human-yeast MLH1 proteins in Saccharomyces cerevisiae

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant inherited disease caused by defects in the process of DNA mismatch repair (MMR), and mutations in the hMLH1 or hMSH2 genes are responsible for the majority of HNPCC. In addition to clear loss-of-function mutations conferred by nonsense or frameshift alterations in the coding sequence or by splice variants, genetic screening has revealed a large number of missense codons with less obvious functional consequences. The ability to discriminate between a loss-of-function mutation and a silent polymorphism is important for genetic testing for inherited diseases like HNPCC where the opportunity exists for early diagnosis and preventive intervention. In this study, quantitative in vivo DNA MMR assays in the yeast Saccharomyces cerevisiae were performed to determine the functional significance of amino acid replacements observed in the human population. Missense codons previously observed in human genes were introduced at the homologous residue in the yeast MLH1 or MSH2 genes. This study also demonstrated feasibility of constructing genes that encode functional hybrid human-yeast MLH1 proteins. Three classes of missense codons were found: (i) complete loss of function, i.e. mutations; (ii) variants indistinguishable from wild-type protein, i.e. silent polymorphisms; and (iii) functional variants which support MMR at reduced efficiency, i.e. efficiency polymorphisms. There was a good correlation between the functional results in yeast and available human clinical data regarding penetrance of the missense codon. The results reported here raise the intriguing possibility that differences in the efficiency of DNA MMR exist between individuals in the human population due to common polymorphisms.     

Positron emission tomography in combination with sentinel node biopsy reduces the rate of elective neck dissections in the treatment of oral and oropharyngeal cancer.

PURPOSE: To assess the impact of a diagnostic ladder including [(18)F]fluorodeoxyglucose positron emission tomography (PET) and lymphoscintigraphy guided sentinel node biopsy (LS/SNB) on neck treatment in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). PATIENTS AND METHODS: Prospectively, 62 patients with resectable T1-3 OOSCC underwent computed tomography (CT) and PET. Patients without neck uptake in PET were defined as cN0 and were accrued for LS/SNB. Results were correlated with histopathology. The traditional guidelines according to CT findings were compared to the actual regimen and the outcome. RESULTS: Sensitivity, specificity, validity, and positive and negative predictive value of PET versus CT were 72% v 89%, 82% v 77%, 79% v 80.5%, 62% v 61.5%, and 88% v 94.5% (not significant). Thirty-eight PET negative patients underwent LS/SNB. Sentinel lymph nodes were found in all 38 patients. Five patients had positive nodes (PET false-negatives) and underwent neck dissection (ND). Fifty-one neck sides in 36 patients who were CT-negative would have been treated with selective ND according to the guidelines, and at least 45 neck sides would have had to undergo extensive ND because of positive CT findings (96 of 124 neck sides). In contrast, PET in combination with LS/SNB spared 59 neck sides, and 41 of 124 neck sides actually underwent ND as a result of PET staging, LS/SNB, and intraoperative decision. After a median follow-up of 35 months, two patients (both cN+ve and pN+ve) suffered from neck relapses. CONCLUSION: Diagnostics using PET in combination with LS/SNB considerably reduced the number of extensive ND in OOSCC as compared to CT without locoregional hazard.     

Randomized Controlled Clinical Trial on Proximal Caries Infiltration: Three-Year Follow-Up

We report the 3-year efficacy of resin infiltration (Icon, pre-product; DMG, Hamburg) to arrest progression of proximal non-cavitated caries lesions as compared with placebo treatment. In 22 young adults, 29 lesion pairs with radiographic extensions into the inner half of enamel up to the outer third of dentin were included (split-mouth design). All subjects received risk-related instructions for diet, flossing and fluoridation. No unwanted effects could be observed. Radiographically 1/26 test lesions (4%) and 11/26 control lesions (42%) had progressed (p = 0.002, McNemar). After 3-year follow-up, infiltration of proximal caries lesions can be said to be efficacious to reduce lesion progression.     

Effects of molsidomine on global and regional left ventricular function at rest and during exercise in patients with angina pectoris

Although the antianginal properties of molsidomine are well-established, little is known about its effects on global and regional left ventricular dysfunction secondary to myocardial ischemia. In the present study, left ventricular performance was assessed by radionuclide ventriculography at rest and during exercise in 15 patients with coronary artery disease (CAD) and angina pectoris before and after the administration of 2 mg molsidomine sublingually. Gated blood pool studies were performed for evaluation of left ventricular ejection fraction (LVEF) and regional wall motion by analyzing amplitudes and phases of the first Fourier coefficient of regional time–activity curves. In contrast to normal subjects, during the control study period LVEF in patients with CAD decreased from 50.9% at rest to 42.7% during exercise (p<0.01). After molsidomine the resting values of LVEF increased slightly from 50.9% to 55.7% (p<0.05). Exercise values of LVEF increased from 42.7% to 51.3% (p<0.01). This is usually associated with amelioration of anginal pain and ischemic ST depression in the precordial ECG (0.15 mV vs. 0.09 mV; p<0.01). Before molsidomine, regional wall motion deteriorated from rest to exercise in 11 of 15 patients. These wall motion abnormalities usually expressed themselves as newly developed regions of left ventricular dysfunction (8 patients) or as accentuation of pre-existing contraction disturbances (3 patients). After molsidomine, regional wall motion did not show consistent changes at rest. Comparison during exercise showed enhanced regional function in 10 of the 15 patients after administration of the drug. At rest a slight but significant increase in heart rate was measured following molsidomine, whereas exercise heart rate remained unchanged. Only minor changes in systolic blood pressure occurred after molsidomine (rest, 143 mmHg vs. 134 mmHg; p<0.05; exercise, 177 mmHg vs. 174 mmHg; p>0.10). In conclusion, assessment of left ventricular performance at rest and during exercise in patients with CAD revealed significant improvement of global and regional left ventricular function, indicating reduction of myocardial ischemia. These effects may result primarily from reduction of left ventricular wall tension.