Cumulative input function method for linear compartmental models and spectral analysis in PET

Compartmental modeling and spectral analysis are often used for tracer kinetic modeling in positron emission tomography (PET). The concentrations in kinetic equations are usually considered to be instantaneous, whereas PET data are inherently integrated over time, which leads to uncertainties in the results. A new formalism for kinetic analysis that uses cumulative tracer concentrations and avoids approximating the image-derived input function and PET measurements with midframe instantanous values was developed. We assessed the improvements of the new formalism over the midframe approximation methods for three commonly used radiopharmaceuticals: [¹¹C]raclopride, 2′-deoxy-2′-[¹⁸F]fluoro--glucose (FDG), and 3′-deoxy-3′-[¹⁸F]fluoro-thymidine (FLT). We found that improvements are case dependent and often not negligible. Improvements for determination of binding potential for [¹¹C]raclopride ranged from 5% to 25%. Improvements in estimation accuracy of FDG and FLT microparameters ranged up to 25%. On the other hand, estimation of macroparameter K_i=K₁k₃/(k₂+k₃) for FDG or FLT did not show significant benefit with the new method; only modest improvement up to 2% was observed. Assessment of the benefits of using new method is far from being exhaustive, but possibly significant improvement was demonstrated. Therefore, we consider the proposed algorithm a necessary component of any kinetic analysis software.     

The T-cell protein tyrosine phosphatase

In recent years, the T-cell protein tyrosine phosphatase (TC-PTP) has become an important member of the protein-tyrosine phosphatase (PTP) family in two aspects. Firstly, TC-PTP has been reported to act on downstream signalling events initiated by the epidermal growth receptor, suggesting that it may act as an important modulator of receptor tyrosine kinases and mitogenic signalling. Secondly, the finding of immune deficiency and lethality observed in TC-PTP null mice emphasizes the importance of this small PTP in the hematopoietic system. In this review, we provide a summary of the recent literature published on the TC-PTP and its various orthologs. Although much remains to be uncovered, some recent findings on the function of this small PTP suggest that it plays a critical role in regulating mammalian cell signalling.     

Kashin Beck Disease: more than just osteoarthrosis

The purpose of this study was to investigate the influence of body function, activities and pain on the level of activity in adults with Kashin Beck Disease (KBD). Seventy-five KBD patients with a mean age of 54.8 years (SD 11.3) participated. Anthropometrics, range of joint motion (ROM) and muscle strength were measured as well as the time-up-and-go test and functional tests for the lower and upper extremities. Activity was assessed with the participation scale and the WHO DAS II. In the shoulder, elbow, hip and knee joints, a severe decrease in ROM and bilateral pain was noted. A decrease in muscle strength was observed in almost all muscles. The timed-up-and-go test scores decreased. No or mild restriction in activity was found in 35%, and 33% experienced a moderate restriction whereas 32% had severe to extreme restriction. Activities in the lower extremities were mildly to moderately correlated to ROM and muscle strength, whereas in the upper extremities activities were correlated to range of joint motion. Activity was significantly associated with ROM after correction for muscle strength, gender and age. Participation was borderline significantly associated with ROM after correction for muscle strength, gender, age and the activity time-up-and-go. In KBD adults, a severe decrease in activity is primarily caused by decrease in ROM. These findings have strong influence on rehabilitation and surgical intervention.     

Mediastinal teratoma with hydrops fetalis in a newborn and development of chronic respiratory insufficiency

Background

Mediastinal fetal teratoma can be detected as a mass in the chest during a routine prenatal ultra-sound screening. Because of the pressure on mediastinal structures it can be the cause of non-immune hydrops fetalis and polyhydramnion. The development of hydrops fetalis leads to fetal death or premature delivery in most reported cases. Early surgical removal is important, but, the result of treatment depends on the stage of development of mediastinal organs and complications in the postoperative period.

Case report.

A 31-year-old gravida carrying twins, with spontaneous membrane rupture at 32 weeks gestation underwent urgent caesarean section after antenatal ultrasound revealed severe polyhydramnion and hydrops fetalis in geminus A. The child was intubated immediately after birth due to severe respiratory distress. Ultrasound and X-ray revealed a tumour mass in the right hemithorax. Tumour resection was performed at the age of 7 days. Histology examination revealed an encapsulated immature teratoma. The postoperative course was complicated with respiratory insufficiency which turned into chronic at the age of eight months.

Conclusion

This is the fifth reported child with fetal mediastinal teratoma and severe hydrops fetalis that survived the neonatal period. Additional diagnostic search revealed abnormal course of both pulmonary arteries, which was probably one of the main causes of respiratory insufficiency.     

Use of microcalorimetry in determination of stability of enalapril maleate and enalapril maleate tablet formulations

The stability properties of enalapril maleate (EM) and of different tablet formulations including EM were studied by isothermal microcalorimetry and by high performance liquid chromatography (HPLC). It was shown that water content of the sample and elevated temperature have a high impact on stability properties of the substance itself and of the formulations including this substance. The degradation is more extensive at higher water content and at elevated temperature. The type of the tablet formulation (5 or 20mg EM tablet formulation) also has an impact: the 5 EM tablet formulation is the less stable one. The heat output of individual tablet formulations was used to evaluate the enthalpy changes and to calculate the difference in the amount of degraded EM between various samples. These results agreed satisfactorily with those obtained by HPLC. Isothermal microcalorimetry proved to be a fast and predictive method that could be used in preformulation studies to accelerate the pharmaceutical development and shorten the time before launching the product to the market.