Characterization of normal and infarcted rat myocardium using a combination of small-animal PET and clinical MRI.

The combination of small-animal PET and MRI data provides quantitative in vivo insights into cardiac pathophysiology, integrating information on biology and morphology. We sought to determine the feasibility of PET and MRI for the quantification of ischemic injury in the rat model. METHODS: Fourteen healthy male Wistar rats were studied with 18F-FDG PET and cine MRI. Myocardial viability was determined in a transmural myocardial infarction model in 12 additional rats, using 18F-FDG PET and delayed-enhancement MRI with gadolinium-diethylenetriaminepentaacetic acid. All PET was acquired with a dedicated small-animal PET system. MRI was performed on a 1.5-T clinical tomograph with a dedicated small-animal electrocardiographic triggering device and a small surface coil. RESULTS: In normal rats, 18F-FDG uptake was homogeneous throughout the left ventricle. The lowest mean uptake of the 18F-FDG was found in the apical regions (79% +/- 6.0% of maximum) and the highest uptake was in the anterior wall (93% +/- 4.3 % of maximum). Myocardial infarct size as determined by histology correlated well with defects of glucose metabolism obtained with 18F-FDG PET (r = 0.89) and also with delayed-enhancement MRI (r = 0.91). Left ventricular ejection fraction in normal rats measured by cine MRI was 57% +/- 5.4% and decreased to 38% +/- 12.9% (P < 0.001) in the myocardial infarction model. CONCLUSION: Integrating information from small-animal PET and clinical MRI instrumentation allows for the quantitative assessment of cardiac function and infarct size in the rat model. The MRI measurements of scar can be complemented by metabolic imaging, addressing the extent and severity of ischemic injury and providing endpoints for therapeutic interventions.     

Homozygous microdeletion of chromosome 4q11-q12 causes severe limb-girdle muscular dystrophy type 2E with joint hyperlaxity and contractures

Microdeletion syndromes are commonly transmitted as dominant traits and are frequently associated with variably expressed pleiotropic phenotypes. Nonlethal homozygous microdeletions, on the other hand, are very rare. Here, we delineate the fifth and so far largest homozygous microdeletion in nonmalignancies of approximately 400 kb on chromosome 4q11-q12 in a large consanguineous East-Anatolian family with six affected patients. The deleted region contains the beta-sarcoglycan gene (SGCB), the predicted gene SPATA18 (spermatogenesis associated 18 homolog) and several expressed sequence tags. Patients presented with a severe and progressive Duchenne-like muscular dystrophy phenotype, a combination of hyperlaxity and joint contractures, chest pain, palpitations, and dyspnea.     

Surface-Attached Polymer Networks Made from Cationic Poly(diitaconates): Synthesis,Surface Characterization,and Bioactivity

Facially amphiphilic polymers carrying cationic and hydrophobic groups on the same repeat unit have shown promising antimicrobial activity and biocompatibility, yet they are prone to suffer from protein adhesion which may induce biofilm formation. To overcome this problem, poly(diitaconate)-based copolymers with cationic/hydrophobic and protein-repellent/charge-neutral repeat units are synthesized. The bioactivity profile of surface-attached polymer networks made from these copolymers depends on the ratio of the cationic and charge-neutral repeat units. In all cases, the protein adhesion is substantially reduced compared to purely cationic polymers. At a 50:50 ratio, the polymer coatings are partially protein-repellent and antimicrobial, yet slightly cell toxic. At an intermediate composition of 30:70, they are still antimicrobial and the cell compatibility is substantially improved. The long-term stability of these materials still has to be determined to judge their suitability for medical applications.     

A patient's guide to protease inhibitors

Dosage guidelines and side effects of three currently available protease inhibitors (saquinavir, ritonavir, indinavir) reveal very different patterns. Dosage regimens are as follows: saquinavir, 3 capsules every 8 hours with food; ritonavir, 6 capsules every 12 hours with food; and indinavir, 2 capsules every 8 hours on an empty stomach. Ritonavir has the severest side effects, including nausea, diarrhea, and initially, tingling feeling of the mouth, arms, or legs. The drugs work best when taken with well-studied medicines such as AZT, d4T, and ddI.     

Impact of advanced maternal age on neonatal survival of twin small-for-gestational-age subtypes

AIM: We examined the impact of advanced maternal age (>40 years old) on the survival of twin small-for-gestational-age (SGA) infants, that is, infants who were smaller in size than was expected for the baby's sex, genetic heritage, and gestational age. METHODS: The present study was a retrospective cohort study on twin live births in the USA from 1995 to 1998 inclusive. Two categories of SGA babies were defined: discordant (when only one of a twin pair was SGA) and concordant (when both were SGA). Otherwise, the twin pair was appropriate-for-gestational-age (AGA) concordant. RESULTS: 192,195 twin pairs were analyzed. The incidence of SGA discordance and concordance was 11.8% and 3.9%, respectively. The occurrence of both SGA subtypes tended to decrease with increasing maternal age. The unadjusted risk for neonatal mortality increased when both twins were affected (15.8: 22.8 and 56.6 per 1000 among AGA concordant, SGA discordant and SGA concordant twins; P-value for trend < 0.0001). Using maternal-age-specific AGA babies as reference, the adjusted risk for neonatal mortality climbed progressively with advancing maternal age in a dose-dependent pattern, being lowest among teenagers and highest in mothers aged > or =40 years. CONCLUSIONS: SGA discordance and concordance declined with advancing maternal age. In contrast, neonatal mortality of both SGA subtypes worsened with the increase in maternal age compared with that of the age-specific AGA infants. These findings are potentially useful to care providers in counseling older women, a group that is progressively increasing in size and is most susceptible to twining.     

A Positron Emission Tomograph based on LSO-APD modules with a sampling ADC read-out system for a students’ advanced laboratory course

A one-day laboratory course on positron emission tomography (PET) for the education of physics students and PhD students in medical physics has been set up. In the course, the physical background and the principles of a PET scanner are introduced. Course attendees set the system in operation, calibrate it using a ²²Na point source and reconstruct different source geometries filled with ¹⁸F. The PET scanner features an individual channel read-out of 96 lutetium oxyorthosilicate (LSO) scintillator crystals coupled to avalanche photodiodes (APD). The analog data of each APD are digitized by fast sampling analog to digital converters (SADC) and processed within field programmable gate arrays (FPGA) to extract amplitudes and time stamps. All SADCs are continuously sampling with a precise rate of 80 MHz, which is synchronous for the whole system. The data is transmitted via USB to a Linux PC, where further processing and the image reconstruction are performed. The course attendees get an insight into detector techniques, modern read-out electronics, data acquisition and PET image reconstruction. In addition, a short introduction to some common software applications used in particle and high energy physics is part of the course.     

Carnosine as a protective factor in diabetic nephropathy: association with a leucine repeat of the carnosinase gene CNDP1

The risk of diabetic nephropathy is partially genetically determined. Diabetic nephropathy is linked to a gene locus on chromosome 18q22.3-q23. We aimed to identify the causative gene on chromosome 18 and to study the mechanism by which the product of this gene could be involved in the development of diabetic nephropathy. DNA polymorphisms were determined in 135 case (diabetic nephropathy) and 107 control (diabetes without nephropathy) subjects. The effect of carnosine on the production of extracellular matrix components and transforming growth factor-beta (TGF-beta) after exposure to 5 and 25 mmol/l d-glucose was studied in cultured human podocytes and mesangial cells, respectively. A trinucleotide repeat in exon 2 of the CNDP1 gene, coding for a leucine repeat in the leader peptide of the carnosinase-1 precursor, was associated with nephropathy. The shortest allelic form (CNDP1 Mannheim) was more common in the absence of nephropathy (P = 0.0028, odds ratio 2.56 [95% CI 1.36-4.84]) and was associated with lower serum carnosinase levels. Carnosine inhibited the increased production of fibronectin and collagen type VI in podocytes and the increased production of TGF-beta in mesangial cells induced by 25 mmol/l glucose. Diabetic patients with the CNDP1 Mannheim variant are less susceptible for nephropathy. Carnosine protects against the adverse effects of high glucose levels on renal cells.