Distribution of PK11195 binding sites in porcine brain studied by autoradiography in vitro and by positron emission tomography

The cerebral distribution of peripheral-type benzodiazepine binding sites (PBBS) in human brain has been investigated by positron emission tomography (PET) with the specific radioligand [11C]PK11195 in diverse neuropathological conditions. However, little is known about the pattern of PK11195 binding sites in healthy brain. Therefore, we used quantitative autoradiography to measure the saturation binding parameters for [3H]PK11195 in cryostat sections from young Landrace pigs. Specific binding was lowest in the cerebellar white matter (85 fmol mg(-1)) and highest in the caudate nucleus (370 fmol mg(-1)), superior colliculus (400 fmol mg(-1)), and anterior thalamic nucleus (588 fmol mg(-1)). The apparent affinity was in the range of 2-6 nM in vitro, predicting high specific binding in PET studies of living brain. However, the distribution volume (V(d), ml g(-1)) of high specific activity [11C]PK11195 was nearly homogeneous (3 ml g(-1)) throughout brain of healthy Landrace pigs, and was nearly identical in studies with lower specific activity, suggesting that factors in vivo disfavor the detection of PBBS in Landrace pigs with this radioligand. In young, adult G?ttingen minipig brain, the magnitude of V(d) for [11C]PK11195 was in the range 5-10 ml g(-1), and had a heterogeneous distribution resembling the in vitro findings in Landrace pigs. There was a trend toward globally increased V(d) in a group of minipigs with acute MPTP-induced parkinsonism, but no increase in V(d) was evident in the same pigs rescanned at 2 weeks after grafting of fetal mesencephalon to the partially denervated striatum. Thus, [11C]PK11195 binding was not highly sensitive to constituitively expressed PBBS in brain of young Landrace pigs, and did not clearly demonstrate the expected microglial activation in the MPTP/xenograft model of minipigs.     

Acute Respiratory Distress Syndrome as a presenting manifestation in young patients infected with H1N1 influenza virus

Introduction

The new strain of influenza A (H1N1) 2009, often referred to colloquially as “swine flu”, which was first detected in April 2009, raised to a pandemic of which the impact was not completely predictable. As reported, numerous cases with severe respiratory failure were also seen among young previously healthy people.

Patients

In the present study, we report eight cases of influenza A (H1N1) 2009 admitted to our medical intensive care with severe respiratory failure between November and December 2009 and in January 2011. All patients were older than 30 but younger than 50 years, had clinical and radiological evidence of an Acute Respiratory Distress Syndrome (ARDS) and needed invasive ventilatory support.

Results

Six of the eight patients had no relevant underlying disease; one had a pre-existing idiopathic lung fibrosis and another had a chronic obstructive pulmonary disease (COPD), an abuse of alcohol and an adiposities grade 3. Four patients needed an extracorporeal membrane oxygenation (ECMO) due to severe respiratory failure with global respiratory insufficiency that could not be treated by conservative ventilatory support. The one patient with a pre-existing lung fibrosis died shortly after lung transplantation despite use of an extracorporeal membrane oxygenation. One other patient died due to a subarachnoidal bleeding under the anticoagulatory regime during ECMO therapy. The adipose COPD-patient died due to septic shock with multiple organ failure without possibility for ECMO support.

Conclusions

The clinical course of severe cases of influenza A (H1N1) 2009-infection is markedly different from the disease pattern seen during epidemics of seasonal influenza. Most of the patients admitted to our intensive care unit due to influenza A (H1N1) 2009 associated ARDS were previously healthy young people.     

Prolongation of allograft survival in ccr7-deficient mice

BACKGROUND: Lymphocyte homing to secondary lymphoid organs is thought to be required for initiation of the alloreactive immune response. Because CCR7 is the essential chemokine receptor responsible for lymphocyte and dendritic cell homing to secondary lymphoid organs, allograft survival was analyzed in CCR7-deficient (CCR7) mice. METHODS: Heterotopic heart and skin allotransplantation was performed in CCR7 and wild-type (WT) recipients. Graft survival was monitored daily. Grafts and draining lymph nodes were analyzed by immunohistology and flow cytometry at different time points. Groups of mice were splenectomized at the day of allotransplantation. RESULTS: A significant though modest prolongation of allograft survival in CCR7 recipients was observed for heart grafts (WT, 7.3 +/- 0.5 days; CCR7, 10.7 +/- 2.8 days) and skin grafts (WT, 8.9 +/- 0.9 days; CCR7, 12.3 +/- 0.9 days). This was accompanied by a delay in the cellular infiltration of allografts. T-cell accumulation and expansion in the draining lymph nodes in CCR7 recipients was severely impaired. Splenectomy had only a moderate prolongation effect on allograft survival in CCR7 mice. CONCLUSIONS: These results suggest that CCR7-dependent processes support allograft rejection yet are dispensable for the rejection response.     

Five‐grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents

Halken S, Agertoft L, Seidenberg J, Bauer C‐P, Payot F, Martin‐Muñoz MF, Bartkowiak‐Emeryk M, Vereda A, Jean‐Alphonse S, Melac M, Le Gall M, Wahn U. Five‐grass pollen 300IR SLIT tablets: efficacy and safety in children and adolescents.
Pediatr Allergy Immunol 2010: 21: 970–976.
© 2010 John Wiley & Sons A/S The efficacy and safety of five‐grass pollen 300IR sublingual immunotherapy (SLIT) tablets (Stallergènes SA, France) have previously been demonstrated in paediatric patients. This report presents additional data concerning efficacy at pollen peak, efficacy and safety according to age, nasal and ocular symptoms, use of rescue medication, satisfaction with treatment and compliance. Children (5–11 yr) and adolescents (12–17 yr) with grass pollen–allergic rhinoconjunctivitis were included in a multinational, randomized, double‐blind, placebo‐controlled study and received either a 300IR five‐grass pollen tablet or placebo daily in a pre‐ (4 months) and co‐seasonal protocol. The severity of six symptoms (sneezing, rhinorrhoea, nasal congestion, nasal and ocular pruritis, and tearing) was scored, and rescue medication use was recorded daily during the pollen season. Patient satisfaction was recorded at the season end. A total of 161 children and 117 adolescents were evaluated (n = 267). 300IR SLIT was effective over the whole season (p = 0.0010) and at the pollen peak (p = 0.0009). The adjusted mean difference between 300IR and placebo groups was significant for both nasal (p = 0.0183) and ocular (p < 0.0001) symptoms. Rescue medication use was statistically lower in the SLIT group during the pollen season and at the pollen peak (both p < 0.05). More patients in the SLIT group were satisfied with their treatment compared to placebo (83.2% vs. 68.1%, p = 0.0030), and compliance was high (SLIT 93.9% of patients were compliant, placebo 94.8% of patients were compliant). SLIT was well tolerated by children and adolescents. 300IR five‐grass pollen tablets are effective and safe during the pollen season and at the pollen peak in children and adolescents with grass pollen rhinoconjunctivitis.     

Significant loss of primordial follicles after prolonged gonadotropin stimulation in xenografts of cryopreserved human ovarian tissue in severe combined immunodeficient mice

This study evaluated the effect of gonadotropin stimulation on the primordial follicle reserve of cryopreserved human ovarian tissue after transplantation in severe combined immunodeficient mice. We found that prolonged gonadotropin stimulation significantly reduces primordial follicles.     

Triaging HPV-positive women with p16/Ki-67 dual-stained cytology: Results from a sub-study nested into the ATHENA trial

Objectives

In addition to genotyping for HPV16/18, dual-immunostaining for p16/Ki-67 has shown promise as a triage of HPV-positive women. We assessed the performance of p16/Ki-67 dual-stained cytology for triaging HPV-positive women undergoing primary HPV screening.

Häufigkeit und kleinräumige Variabilität von Operationen

On the basis of the claims data of the statutory health insurance funds, surgery rates and small-area variations within the catchment area of the AOK Magdeburg were examined for the year 1997. Substantial variation can be constantly seen. The extremal quotient at the 30 most frequent ICPM groups ranged from 2 to 5. Generally, the extent of the variation was larger with elective procedures than with acute. Correlation analyses do not show clear associations with hospital bed supply and physician density in primary sectors. The extent of the small-area variation requires further research to evaluate possible determinants of surgery rates. Criteria for hospital admission and indications for surgery should be made explicit.