Evaluation of a modular all-in-one high-resolution PET detector and readout electronics setup.

Objective. The all-in-one solution and modularity of the C13500 series TOF-PET detector modules (Hamamatsu Photonics K.K., Hamamatsu, Japan) make them a highly attractive candidate for the development of positron emission tomography (PET) systems. However, the commercially available portfolio targets clinical whole-body PET systems with a scintillation crystal cross area of 3.1 × 3.1 mm2. To extend the modules for high resolution (preclinical or organ specific) systems, the support for smaller scintillation crystals is required.Approach.In this work, a PET detector was developed based on the TOF-PET modules using a light sharing approach, 16 × 16 lutetium oxyorthosilicate (LSO) scintillation crystals with a size of 1.51 × 1.51 × 10.00 mm3readout with 8 × 8 photosensor channels of size 3.0 × 3.0 mm2. In addition to hardware and software development, the optimized parameter settings for the adapted configuration were evaluated.Main Results.A factor of two in amplification of the analog signal compared to the minimum gain setting was necessary for an accurate crystal identification (peak-to-valley ratio 14.9 ± 5.9). A further increase to a factor of three was not determined as optimum as the time over threshold duration, thus pile-up probability, increased from 1032.1 ± 109.5 to 1789.5 ± 218.5 ns (photopeak position). With this amplification a full width at half maximum (FWHM) energy resolution of 14.1 ± 2.0% and a high linearity of the energy detection was obtained. A FWHM coincidence resolving time (CRT) of 313 ps was achieved by using a low timing threshold, increasing the bandwidth of the front-end circuit and using a narrow ± 1σenergy window. To approximately double the sensitivity and reduce the power consumption, the timing parameters were adjusted resulting in a FWHM CRT of 354 ps (±2σ).Significance.Based on the results obtained with the proof-of-concept detector setup, we confirm the modularity and flexibility of the all-in-one TOF-PET detector modules for the future development of application-specific high-resolution PET systems.

The ultrastructure of the nasal polyps in patients with and without cystic fibrosis.

Nasal polyps are commonly associated with cystic fibrosis (CF) and also with idiopathic allergies, asthma, and aspirin intolerance. The pathogenesis of nasal polyp formation is controversial. The present study investigates the ultrastructure of thirteen nasal polyps surgically removed from seven CF patients and six non-CF (NCF) patients with allergic diseases, asthma, and aspirin intolerance. All nasal polyps showed focal edema, hyperplasia, atrophy, or squamous metaplasia of the epithelium. The lamina propria was moderately populated with small blood vessels and mucous glands and showed focal accumulation of inflammatory cells. The CF nasal polyps, however, revealed several specific characteristics: 1) minimal damage to the surface epithelium, 2) presence of a mucus blanket lining the apical epithelium, 3) occasional intracytoplasmic lumens, 4) continuous and fenestrated type capillaries, 5) numerous degranulated mast cells, 6) many plasma cells, often with atypical morphology and intracisternal Russell bodies, and 7) a smaller number of eosinophils as compared to the NCF nasal polyps. The results indicate significant differences between CF and NCF nasal polyps and support the multifactorial pathways theory of nasal polyp formation.

Growth hormone improves weight velocity and height velocity in prepubertal children with cystic fibrosis.

We undertook this study to determine if growth hormone treatment of prepubertal children with cystic fibrosis could improve their height and weight. Nine prepubertal children with cystic fibrosis were treated with human recombinant growth hormone for one year. Results obtained during this year were compared to similar measurements made for each patient for the one year prior to the treatment year. Anthropometric data including: height, height velocity, weight, weight velocity and skin fold thickness were measured at three month intervals. Pulmonary function and skeletal muscle strength were measured at three month intervals. Glucose tolerance was evaluated by HbAlc and by fasting blood glucose and insulin levels every three months. Our results demonstrate that growth hormone treatment resulted in significant improvement in height velocity and height Z scores. Weight increased in all subjects, with a significant increase in weight velocity (year prior to treatment = 1.7+/-1.0 kg/yr, treatment year = 3.8+/-1.6 kg/yr; p=0.03). Measurements of skin fold thickness suggests that lean body mass improved with growth hormone treatment. Pulmonary function improved in all but two patients, whose pulmonary function remained the same and muscle strength improved in all subjects. These results suggest that growth hormone used in prepubertal children with cystic fibrosis can improve height and weight and may improve lean body mass.

Cystic fibrosis in the southern Midwest United States: molecular characterization of the common mutations.

The identification of different mutations that cause cystic fibrosis in the people of Kansas and Oklahoma has been performed by examining 124 independent cystic fibrosis genes for the 14 most commonly mutated loci. The delta F508 3bp deletion represented 79% of the alleles, and 7% of the remaining alleles were found to harbor the mutations of R553X, G542X, or G551D. None of the remaining 10 common mutations were identified. This pattern of results contrasts with the patterns found in major cities of the United States. The ethnic diversity in these cities is much greater than in the southern Midwest region, and the remaining mutations, therefore, may represent specific ethnic contributions absent in the Midwest population studies. These results directly affect the counseling given to the Midwest patient and impact on any strategies for screening.

Psychosocial factors related to perceived compliance with cystic fibrosis treatment.

The present research was designed to investigate the adjustment of patients with cystic fibrosis (CF) and their families as well as the relationship between adjustment and physician perceptions of compliance with CF treatment. Patient and family adjustment was assessed by means of the Personality Inventory for Children as well as measures of marital adjustment, depression, and social isolation completed by mothers of CF patients. Results indicated no characteristic pattern of psychopathology or adjustment problems. However, higher levels of perceived compliance with CF treatment were found to be associated with less satisfactory marital relationships and with less frequent maternal social contacts. These findings are discussed in terms of achieving a balance between compliance and psychological adjustment.

ATP-dependent unwinding of messenger RNA structure by eukaryotic initiation factors.

Interaction of protein synthesis initiation factors with mRNA has been studied in order to characterize early events in the eukaryotic translation pathway. Individual reovirus mRNAs labeled with 32P in the alpha position relative to the m7G cap and eukaryotic initiation factor (eIF)-4A, -4B, and -4F purified from rabbit reticulocytes were employed. It was found that eIF-4A causes a structural change in mRNA, as evidenced by a nuclease sensitivity test: addition of high concentrations of eIF-4A greatly increase the nuclease sensitivity of the mRNA, suggesting that this factor can melt or "unwind" mRNA structure. ATP is required for this reaction. At low concentrations of eIF-4A, addition of eIF-4B is required for maximal unwinding activity. Thus eIF-4B enhances eIF-4A activity. Addition of eIF-4F also makes the mRNA sensitive to nuclease indicating a similar unwinding role to that of eIF-4A. Stoichiometric comparisons indicate that eIF-4F is more than 20-fold more efficient than eIF-4A in catalyzing this reaction. The unwinding activity of eIF-4F is inhibited by m7GDP, while that of eIF-4A is not. This suggests that eIF-4A functions independent of the 5' cap structure. Our results also suggest that the unwinding activity of eIF-4F is located in the 46,000-dalton polypeptide of this complex, which has shown by others to be similar or identical to eIF-4A.

Methadone maintenance for opiate dependence.

The use of the synthetic opiate methadone on a continuing maintenance scheduled is unquestionably the most successful and most widely applicable treatment for the control of opiate dependence. Though the medical aspects of the treatment are simple, the nature of the medication and the nature of the problems of opiate dependence are such that administration of a program requires careful attention. Because the problem is so serious both to society and the addict, it is urgent that we develop and adequate number of well run methadone programs throughout the state and the nation.