Pulmonary hypertension before first and second lung transplantation

Tonelli AR, Timofte I, Minai OA, Baz M, Akindipe O. Pulmonary hypertension before first and second lung transplantation. Abstract: Background: Pulmonary hypertension (PH) is frequently encountered in patients with advanced lung disease before the first and second lung transplantation. We sought to determine whether there is any relationship between pulmonary hemodynamics obtained before first and second lung transplantation. We also assessed whether PH has prognostic implications in lung transplant patients going for second transplantation. Methods: We included consecutive adult (16‐yr‐old or older) patients who underwent lung re‐transplantation, between 1997 and 2009, and had right heart catheterization before their first and second lung transplantation. Results: Eighteen patients were included in the study. Age at first transplantation was 50.4 (SD 10.4) yr, and bronchiolitis obliterans syndrome (BOS) in the transplanted lung was the only indication for re‐transplantation. PH was observed in 39% of the patients before the first lung transplant and in 56% of the subjects before re‐transplantation (p = 0.91). Pre‐capillary PH was present in 28% (n = 5) and 33% (n = 6) of the patients before first and second lung transplantation, respectively. None of the hemodynamic variables obtained before the first transplant predicted the development of PH before re‐transplantation. PH before re‐transplantation did not predict survival or development of BOS after re‐transplantation. Conclusions: PH before initial lung transplantation did not predict the development of PH before the second transplantation. In our cohort, PH before second lung transplantation did not predict outcomes after re‐transplantation.     

Molecular Imaging of Neuroblastoma Progression in TH-MYCN Transgenic Mice

Purpose

TH-MYCN transgenic mice represent a valuable preclinical model of neuroblastoma. Current methods to study tumor progression in these mice are inaccurate or invasive, limiting the potential of this murine model. The aim of our study was to assess the potential of small animal positron emission tomography (SA-PET) to study neuroblastoma progression in TH-MYCN mice.

Procedure

Serial SA-PET scans using the tracer 2-deoxy-2-[¹⁸F]fluoro-d-glucose (¹⁸F-FDG) have been performed in TH-MYCN mice. Image analysis of tumor progression has been compared with ex vivo evaluation of tumor volumes and histological features.

Results

[¹⁸F]FDG-SA-PET allowed to detect early staged tumors in almost 100 % of TH-MYCN mice positive for disease. Image analysis of tumor evolution reflected the modifications of the tumor volume, histological features, and malignancy during disease progression. Image analysis of TH-MYCN mice undergoing chemotherapy treatment against neuroblastoma provided information on drug-induced alterations in tumor metabolic activity.

Conclusions

These data show for the first time that [¹⁸F]FDG-SA-PET is a useful tool to study neuroblastoma presence and progression in TH-MYCN transgenic mice.     

Paretic neurosyphilis and cerebral gumma. Case report

A rare case of neurosyphilis presenting with dementia paralytica and radiological appearance of cerebral gumma is reported. In accordance with previous comparable reports Authors noticed that diagnosis of this disease actually is still based on serological tests and clinical examination. CT, NMR and Cerebral angiography were not able to provide diagnostic findings, although NMR confirmed its ability to detect lesions not discovered by CT scan. Also findings from stereotactic biopsy only revealed an old not active infection.     

Pharmacokinetic comparison of leucovorin and levoleucovorin

Summary The pharmacokinetic values of d,l-leucovorin and l-leucovorin were compared in eight healthy volunteers following oral administration of 25 mg d,l-leucovorin and 12.5 mg l-leucovorin. Serum levels of l-5-for-myltetrahydrofolate, l-5-methyltetrahydrofolate, and total reduced folates were measured by an established microbiological method. Pharmacokinetic data for both preparations were consistent with those previously reported for d,l-leucovorin, with essentially complete first pass metabolism to l-5-methyltetrahydrofolate, the active metabolite. No differences were found between the two preparations in serum concentrations of active folate fractions, AUC, or C_max, or in clearance and volume of distribution estimates. These data suggest that after administration of 25 mg of d,l-leucovorin, the d-diastereoisomer has no significant effect on the standard pharmacokinetic measurements of the active l-folates.     

Sodium depletion induces Fos immunoreactivity in circumventricular organs of the lamina terminalis

Acute sodium depletion by peritoneal dialysis (PD) induces c-fos expression in the subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT), in conscious rats. Fos immunoreactive (Fos-ir) neurons detected by immunohistochemistry first appeared in these nuclei 60 min after PD, increased gradually in the next 4 h and remained high for 27 h following PD. Fos-ir cells were distributed throughout the body of SFO, being the core of the posterior sections preferentially activated, whereas Fos-ir neurons occurred around the periphery of OVLT (annular disposition). When rats were allowed to drink sodium salt (1.8% NaCl) 24 h after PD, there was a marked reversion of the c-fos expression in the OVLT and a comparatively smaller effect in the SFO. Intracerebroventricular infusion of hypertonic CSF (170 mM NaCl) from 30 min before and during 4 h after PD, significantly inhibited the c-fos expression in both nuclei.These results demonstrate that an acute body sodium deficit induces c-fos activity in SFO and OVLT neurons, indicating the special role of these structures in sodium balance regulation. They also show that the sodium-depletion-induced production of Fos in neurons of the lamina terminalis can be modulated by central or systemic reposition of sodium.     

Indexed effective orifice area after mechanical aortic valve replacement does not affect left ventricular mass regression in elderly.

OBJECTIVE: After aortic valve replacement, the effects of a small functional prosthesis on the extent and pattern of regression of left ventricular hypertrophy and on clinical outcomes may be less significant in older patients with low cardiac output requirements. The objective of this study was therefore to determine whether patient-prosthesis mismatch affects left ventricular mass regression in the elderly. METHODS: The population studied was made up of 88 patients over 65 years of age with pure aortic stenosis who underwent mechanical aortic valve replacement. The effective orifice area index was calculated for each patient on the basis of the projected prosthesis in vivo effective orifice area. It was considered a continuous variable and influence of its entire range of values on the extent of left ventricular mass regression was analyzed in a multivariate prediction model. RESULTS: Even though, in the group with prosthesis-patient mismatch there was a trend for lower postoperative left ventricular mass index (115+/-24 g/m(2) vs 102+/-27 g/m(2), p=0.24) and postoperative peak trans-prosthetic gradients (32+/-9.8 mmHg vs 28.9+/-7.79 mmHg, p=0.35) these differences were not statistically significant. The prevalence of residual left ventricular hypertrophy at follow-up was 50% in the group with patient-prosthesis mismatch and 50% in the group without patient-prosthesis mismatch (p=0.83). In multivariate analysis the only factors associated with indexed left ventricular mass were the follow-up time (p=0.015, r(2)=0.22) and preoperative indexed left ventricular mass (p=0.0012, r(2)=0.11). CONCLUSIONS: The major finding of our study is that patient-prosthesis mismatch does not affect left ventricular mass regression in patients older than 65 with pure aortic stenosis who underwent mechanical aortic valve replacement. In older patients with low cardiac output requirements, even a small change in the valve effective orifice area after aortic valve replacement with modern efficient mechanical prosthesis, will result in a marked reduction of pressure gradient and this will be associated with a significant regression of left ventricular mass.