Bremsstrahlung parameters of praseodymium-142 in different human tissues: a dosimetric perspective for 142Pr radionuclide therapy

Objective

Praseodymium-142 [T _1/2?=?19.12?h, $ E_{\beta^{-}}$ ?=?2.162?MeV (96.3%), E???=?1575?keV (3.7%)] is one of the ¹⁴¹Pr radioisotopes. Many studies have been attempted to assess the significance of usage ¹⁴²Pr in radionuclide therapy. In many studies, the dosimetric parameters of ¹⁴²Pr sources were calculated by modeling ¹⁴²Pr sources in the water phantom and scoring the energy deposited around it. However, the medical dosimetry calculations in water phantom consider Bremsstrahlung production, raising the question: ??How important is to simulate human tissues instead of using water phantom??? This study answers these questions by estimation of ¹⁴²Pr Bremsstrahlung parameters.

Methods

The Bremsstrahlung parameters of ¹⁴²Pr as therapeutic beta nuclides in different human tissues (adipose, blood, brain, breast, cell nucleus, eye lens, gastrointestinal tract, heart, kidney, liver, lung deflated, lymph, muscle, ovary, pancreas, cartilage, red marrow, spongiosa, yellow marrow, skin, spleen, testis, thyroid and different skeleton bones) were calculated by extending the national council for radiation protection model. The specific Bremsstrahlung constant (?? _Br), probability of energy loss by beta during Bremsstrahlung emission (P _Br) and Bremsstrahlung activity (A _release)_Br were estimated. It should be mentioned that Monte Carlo simulation was used for estimation of ¹⁴²Pr Bremsstrahlung activity based on the element compositions of different human tissues and the calculated exposures from the anthropomorphic phantoms.

Results

?? _Br for yellow marrow was smallest amount (1.1962?×?10^?3 C/kg-cm²/MBq-h) compared to the other tissues and highest for cortical bone (2.4764?×?10^?3 C/kg-cm²/MBq-h), and, overall, ?? _Br for skeletal tissues were greater than other tissues. In addition, ?? _Br breast was 1.8261?×?10^?3 C/kg-cm²/MBq-h which was greater than sacrum and spongiosa bones. Moreover, according to (A _release)_Br of ¹⁴²Pr, the patients receiving ¹⁴²Pr do not have to be hospitalized for radiation precautions and the Bremsstrahlung production does not prevent the therapy for outpatients.

Conclusion

However, modeling ¹⁴²Pr source in water phantom for simulation of ¹⁴²Pr source in soft tissues could be acceptable due to similarity of ?? _Br in water and soft tissues; this approximation is a gross computation in the mediums encompassing high atomic numbers. These data may be practical in the investigation of Bremsstrahlung absorbed dose where ¹⁴²Pr is involved in radionuclide therapy.     

Effects of multiple daily injection therapy with Humalog mixtures versus separately injected insulin lispro and NPH insulin in adults with type I diabetes mellitus

BACKGROUND: Injection of insulin lispro (LP) before meals provides a more physiologic insulin activity profile than regular human insulin, but the relatively short duration of action of LP may allow the blood glucose (BG) level to increase during the late postprandial period (4-7 hours after meals) unless basal insulin is optimally replaced. One approach to basal insulin optimization has been to combine small doses of NPH with LP before meals. When used in a similar fashion, premixed, fixed-ratio insulin preparations containing LP and NPL (an LP-based intermediate-acting insulin) may provide the basis for an optimized basal-bolus insulin regimen. OBJECTIVE: This study assessed mean late postprandial glycemic control during treatment with a premixed formulation consisting of a high proportion of LP (75% LP/25% NPL; H) and a premixed formulation consisting of a medium proportion of LP (50% LP/50% NPL; M). The H/M formulation was given before meals and was compared with treatment with preprandial LP + NPH (LP + N) in patients with type 1 diabetes mellitus (DM). METHODS: This multicenter, randomized, open-label, 2-period crossover study was conducted at 4 centers in Italy and 1 center in France. Patients eligible for the study had type 1 DM, were > or = 18 years of age, and had a glycosylated hemoglobin (HbA(1c)) <150% of the upper limit of normal. Patients were randomly assigned to 1 of 2 treatment sequences: LP self-mixed with NPH before meals plus NPH alone at bedtime for 8 weeks (LP + N) followed by preprandial H or M, plus NPH alone at bedtime for 8 weeks (H/M), or the opposite sequence. Assessments included 8-point self-monitored BG profiles, HbA(1c), and hypoglycemia (any sign or symptom of hypoglycemia or BG < 3.0 mmol/L [<54.0 mg/dL]). The primary outcome measure was the late postprandial BG value, calculated as the mean of the combined prelunch (late postbreakfast), predinner (late postlunch), and bedtime (late postdinner) values. RESULTS: A total of 89 patients with type 1 DM were enrolled (44 men, 45 women; mean [SD] age, 38.3 [12.8] years; mean [SD] body weight, 70.8 [11.6] kg; mean [SD] body mass index, 24.6 [3.0] kg/m(2); mean [SD] duration of diabetes, 17.8 [10.5] years; mean HbA(1c), 7.9% [0.88%]). The mean (SD) late postprandial BG values were similar between treatments (8.9 [2.1] mmol/L [160.3 (37.8) mg/dL] for H/M vs 9.0 [1.8] mmol/L [162.1 (32.4) mg/dL] for LP + N), as were the end point HbA(1c) values (7.8% [0.9%] for H/M vs 7.9% [0.8%] for LP + N). The rate of hypoglycemia was significantly higher during treatment with H/M, primarily because of episodes occurring between 12 PM and 6 PM, but was relatively low in both groups (mean/median rate per patient per 30 days: 2.87/2.14 for H/M and 2.11/1.07 for LP + N; P < 0.05). CONCLUSIONS: In this population of patients with type 1 DM, preprandial H/M provided an effective alternative regimen for prandial and basal insulin replacement. Late postprandial BG control, an indicator of basal insulin sufficiency, was similar to that achieved with an intensified regimen of LP + N injected separately before meals, and the end point HbA(1c) was similar between the 2 treatments.     

Jaundice and the sepsis syndrome: a neglected link

The relationship between the sepsis syndrome and the development of jaundice is intriguing, with jaundice having been described as the presenting sign of septicaemia in very few cases. We describe a patient who developed a deep jaundice with conjugated hyperbilirubinaemia caused by Staphylococcus aureus during the early course of septicaemia, when no other sign of the sepsis syndrome could be recognised. It is generally accepted that a mild jaundice may complicate the course of the sepsis syndrome, but it is most unusual to observe such a protracted phase of jaundice before the emergence of other specific clinical signs and laboratory abnormalities. Clinicians should be aware of this presentation of the sepsis syndrome in order to avoid a potentially harmful delay in diagnosis and treatment.     

Centronuclear myopathies: genotype–phenotype correlation and frequency of defined genetic forms in an Italian cohort

Centronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. To date, mutation in 7 different genes has been reported to cause CNMs but 30 % of cases still remain genetically undefined. Genetic investigations are often expensive and time consuming. Clinical and morphological clues are needed to facilitate genetic tests and to choose the best approach for genetic screening. We aimed to describe genotype–phenotype correlation in an Italian cohort of patients affected by CNMs, to define the relative frequencies of its defined genetic forms and to draw a diagnostic algorithm to address genetic investigations. We recruited patients with CNMs from all the Italian tertiary neuromuscular centers following clinical and histological criteria. All selected patients were screened for the four ‘canonical’ genes related to CNMs: MTM1, DNM2, RYR1 and BIN1. Pathogenetic mutations were found in 38 of the 54 screened patients (70 %), mostly in patients with congenital onset (25 of 30 patients, 83 %): 15 in MTM1, 6 in DNM2, 3 in RYR1 and one in TTN. Among the 13 patients with a childhood–adolescence onset, mutations were found in 6 patients (46 %), all in DNM2. In the group of the 11 patients with adult onset, mutations were identified in 7 patients (63 %), again in DNM2, confirming that variants in this gene are relatively more common in late-onset phenotypes. The present study provides the relative molecular frequency of centronuclear myopathy and of its genetically defined forms in Italy and also proposes a diagnostic algorithm to be used in clinical practice to address genetic investigations.     

Identification of a geographic area characterized by extreme longevity in the Sardinia island: the AKEA study

High prevalence and low female/male ratio for validated centenarians are observed in Sardinia and these findings appear to be thus far unique to this island. Moreover a specific region on the island is characterized by exceptional male longevity. We calculated the extreme longevity index (ELI), defined as the percentage of persons born in Sardinia between 1880 and 1900, who became centenarians. A gaussian smoothing method was used in order to identify the so-called 'Blue Zone', where longevity is concentrated in the central-eastern part of the island and covers all the mountainous areas of central Sardinia. The estimated life expectancy in the 'Blue Zone' is longer than in the remaining territory of the island especially for men and the male to female ratio among centenarians born in this area is 1.35 compared to 2.43 in the rest of Sardinia. The specific mechanism by which persons living in this territory were more likely to reach extreme longevity remains unknown but it is interesting to note that most of the 'longevity hot spots' identified in various regions of the world over the years have been located in mountainous geographical areas even if none of these longevity regions have been fully validated. An alternative and interesting hypothesis is that the high rate of inbreeding determined by frequent marriages between consanguineous individuals and low immigration rates have progressively decreased the variability of the genetic pool and facilitated the emergence of genetic characteristics that protect individuals from diseases that are major causes of mortality particularly in older individuals. Given the exceptionally high prevalence of male centenarians in the 'Blue Zone', it is reasonable to assume that either the environmental characteristics or the genetic factors, or both, exert their favorable effect more strongly in men than in women. Thus, the mechanism involved may be modulated by the hormonal milieu, or may be associated with genes located in the sex chromosomes.