Study of the microcirculation in hDAF transgenic rat livers xenoperfused with human blood

Abstract: Background: The microcirculation was assessed in the livers of human decay accelerating factors (hDAF) and wild‐type transgenic rats by fluorescent intravital microscopy, histology and histomorphology to determine the benefits of hDAF expression for the microcirculation of a rat liver xenograft perfused with human blood. Methods: Male hDAF transgenic rats (group A; n = 20) and wild‐type Sprague–Dawley rats (group B; n = 20) were xenoperfused with human blood, while other male wild‐type Sprague–Dawley rats (group C; n = 10) were perfused with allogeneic blood. Following plasma and leukocyte staining with fluorescein sodium, and platelet staining with rhodamine, the right lobe of the liver was assessed by intravital microscopy, counting the numbers of perfused sinusoids and leukocytes adhering to the endothelium per mm², and calculating the acinar perfusion index (Pi). The liver underwent histological assessment at the end of each experiment. Mean ± SEM values were calculated and the Mann–Whitney U‐test was used for statistical analysis. Results: The number of perfused sinusoids was higher in the group of hDAF rat livers (group A) and controls (group C) than in the group of non‐transgenic rat livers perfused with human blood (group B) (P < 0.05), although only group C still had a significantly more perfused sinusoids than the other groups after 90 min of perfusion (P < 0.05). The acinar perfusion index was higher in groups A and C than in group B (P < 0.05); here again, only group C still had a significantly higher Pi than group B after 90 min of perfusion (P < 0.05). There was a massive accumulation of leukocytes that peaked after 5 min and persisted throughout the perfusion in all three groups. Histology showed portal and subendothelial hepatic vein hemorrhage, necrosis and inflammatory reaction, which were particularly evident in group B. Conclusion: In our study, rat livers transgenic for hDAF were better protected against early tissue damage by perfusion with human blood, but this did not result in a longer xenograft survival.     

How many parkinsonian patients are suitable candidates for deep brain stimulation of subthalamic nucleus? Results of a questionnaire

We used a CAPSIT-based questionnaire to estimate the percentage of parkinsonian patients suitable for subthalamic nucleus (STN) deep brain stimulation (DBS) in a movement disorders clinic. We found that out of 641 consecutive PD patients only 1.6% fulfilled strict STN-DBS criteria. When we applied more flexible criteria, the percentage of eligibility increased to 4.5%. Most patients (60%) were ineligible because they did not satisfy multiple questionnaire items. Items related to disease severity were responsible for the largest number of exclusions. This knowledge will help make decisions on resource allocation in centres wishing to start DBS surgery.     

Pressor responses to hyperventilation in elderly subjects differentiate essential from secondary hypertension

We evaluated pressor responses to the hyperventilation test in elderly normotensive (n=43, mean age 82 ± 5 years) and elderly hypertensive subjects (n=45 with essential hypertension, mean age 82 ± 2 years, and n=49 with secondary hypertension, mean age 82 ± 3 years). Hyperventilation did not change blood pressure (BP) in normotensive and secondary hypertensive subjects, whereas it decreased BP in essential hypertensives. Hierarchical cluster analysis based on BP responses to hyperventilation disclosed three groups of subjects in each population: group 1 exhibited a reduction in BP (essential hypertensives: 76%), group 2 no change (normotensives: 70%, secondary hypertensives: 76%), and group 3 an increase (normotensives: 19%, essential hypertensives: 13%, secondary hypertensives: 14%). Ambulatory BP monitoring found significant differences in pressor daytime profiles of hypertensive patients according to pressor responses to hyperventilation showing wide fluctuations in group 1 and 3 patients. Interestingly, the peak ambulatory SBP values correlated to the pre-hyperventilation SBP values in group 1, and to the hyperventilation peak SBP values in group 3. In conclusion: 1) Aging decreases reactivity to respiratory alkalosis in elderly normotensives; 2) hyperventilation induces significant pressor changes frequently in essential hypertension, but rarely in secondary hypertension; 3) the significant pressor responses to hyperventilation reflect the daytime pressor profiles predicting the highest daily fluctuations of BP values.     

Peg-filgrastim versus filgrastim after autologous stem cell tranplantation: case-control study in patients with multiple myeloma and review of the literature

We investigated the effects of a single s.c. injection of peg-filgrastim in 32 patients with multiple myeloma who underwent autologous stem cell transplantation (AuSCT) as first line treatment. For comparison, 32 myeloma patients with similar characteristics and receiving standard daily administration of filgrastim were matched. Overall, there were no statistically significant differences between peg-filgrastim and filgrastim in terms of tolerability, marrow recovery, severity of neutropenia, incidence and duration of febrile neutropenia, documented infections and transfusions. However, some favourable trends or effects in favour of peg-filgrastim were observed. This was confirmed by a review of the published papers about this topic.     

Optimizing therapy in primary biliary cholangitis: Alkaline phosphatase at six months identifies one-year non-responders and predicts survival

Background and Aims

Patients with primary biliary cholangitis (PBC) and insufficient response to ursodeoxycholic acid (UDCA), currently assessed after 1 year, are candidates for second-line therapy. The aims of this study are to assess biochemical response pattern and determine the utility of alkaline phosphatase (ALP) at six months as a predictor of insufficient response.

Methods

UDCA-treated patients in the GLOBAL PBC database with available liver biochemistries at one year were included. POISE criteria were used to assess response to treatment, defined as ALP <1.67 × upper limit of normal (ULN) and normal total bilirubin at one year. Various thresholds of ALP at six months were evaluated to predict insufficient response based on negative predictive value (NPV) and that with nearest to 90% NPV was selected.

Results

For the study, 1362 patients were included, 1232 (90.5%) female, mean age of 54 years. The POISE criteria were met by 56.4% (n = 768) of patients at one year. The median ALP (IQR) of those who met POISE criteria compared to those who did not was 1.05 × ULN (0.82–1.33) vs. 2.37 × ULN (1.72–3.69) at six months (p < .001). Of 235 patients with serum ALP >1.9 × ULN at six months, 89% did not achieve POISE criteria (NPV) after one year of UDCA. Of those with insufficient response by POISE criteria at one year, 210 (67%) had an ALP >1.9 × ULN at six months and thus would have been identified early.

Conclusions

We can identify patients for second-line therapy at six months using an ALP threshold of 1.9 × ULN, given that approximately 90% of these patients are non-responders according to POISE criteria.     

Cardiac infections: focus on molecular diagnosis

The role of different types of infections in heart diseases is more important than commonly thought, with new and re-emerging infections (i.e., Mycobacterium tuberculosis).This review addresses the pathology of infective pericarditis, myocarditis, and endocarditis, mainly focusing on the significance of molecular techniques in the detection of infective agents. Molecular investigations represent important ancillary diagnostic tools and combined with other conventional approaches provide a more precise final diagnosis. A close collaboration and communication among cardiologists, cardiac surgeons, pathologists, and microbiologists is essential to ensure optimal diagnoses and management as well as a favorable impact on patient outcome.     

Changes in presynaptic proteins, SNAP-25 and synaptophysin, in the hippocampal CA1 area in ischemic gerbils

A general consensus exists that the presynaptic terminals in the hippocampal CA1 area are resistant to ischemic stress in spite of the loss of their target cells (CA1 pyramidal neurons). We have verified this by immunostaining and Western immunoblotting using the antibodies for presynaptic proteins, synaptosomal-associated protein of 25 kDa (SNAP-25) and synaptophysin in gerbils after bilateral carotid artery ligature. In the immunohistochemical analysis, decreases in SNAP-25 and synaptophysin immunoreactivities in the strata radiatum and oriens, especially around the apical dendrite of CA1 neurons, and disappearance of SNAP-25 immunoreactivity in the alveus were observed on day 2 after ischemia. On days 7 and 14, SNAP-25-positive granular materials were expressed in the CA1 area, and intense synaptophysin immunoreactivity around surviving CA1 neurons was observed. Western immunoblot analysis revealed significant decreases of SNAP-25 and synaptophysin (about 60% of control levels) on day 2, and then increase of their proteins (130–140% of control levels) on day 14. These results indicate that presynaptic degeneration occurs in the hippocampal CA1 area after ischemia, and it precedes the delayed neuronal death of CA1 neurons. The presynaptic terminal damage may be responsible for some pathological changes in ischemic brains.     

Exploring the efficacy of behavioral skills training to teach basic behavior analytic techniques to oral care providers

Performing oral care procedures with children with autism who exhibit noncompliance can be challenging for oral care professionals. Previous research has elucidated a number of effective behavior analytic procedures for increasing compliance, but some procedures are likely to be too time consuming and expensive for community-based oral care providers to adopt. The purpose of this study was to use Behavioral Skills Training to teach dental hygiene students and staff to implement basic function-based behavior analytic strategies to reduce noncompliance and increase their success in performing oral care exams and cleanings in vivo. All participants rapidly acquired the techniques and used them effectively during exams and cleanings following BST, and skills generalized to their completion of an X-ray procedure with several children with autism. The number of steps attempted in all procedures increased relative to baseline for all participants.