Pick’s disease with Pick bodies combined with progressive supranuclear palsy without tuft‐shaped astrocytes: A clinical,neuroradiologic and pathological study of an autopsied case

We report clinical, neuroradiologic features, and neuropathologic findings of a 76‐year‐old man with coexistent Pick’s disease and progressive supranuclear palsy. The patient presented with loss of recent memory, abnormal behavior and change in personality at the age of 60. The symptoms were progressive. Three years later, repetitive or compulsive behavior became prominent. About 9 years after onset, he had difficulty moving and became bed‐ridden because of a fracture of his left leg. His condition gradually deteriorated and he developed mutism and became vegetative. The patient died from pneumonia 16 years after the onset of symptoms. Serial MRI scans showed progressive cortex atrophy, especially in the bilateral frontal and temporal lobes. Macroscopic inspection showed severe atrophy of the whole brain, including cerebrum, brainstem and cerebellum. Microscopic observations showed extensive superficial spongiosis and severe neuronal loss with gliosis in the second and third cortical layers in the frontal, temporal and parietal cortex. There were Pick cells and argyrophilic Pick bodies, which were tau‐ and ubiquitin‐positive in neurons of layers II–III of the above‐mentioned cortex. Numerous argyrophilic Pick bodies were observed in the hippocampus, especially in the dentate fascia. In addition, moderate to severe loss of neurons was found with gliosis and a lot of Gallyas/tau‐positive globus neurofibrillary tangles in the caudate nucleus, globus pallidus, thalamus, substantia nigra, locus coeruleus and dentate nucleus. Numerous thorned‐astrocytes and coiled bodies but no‐tuft shaped astrocytes were noted in the basal ganglion, brainstem and cerebellar white matter. In conclusion, these histopathological features were compatible with classical Pick’s disease and coexistence with progressive supranuclear palsy without tuft‐shaped astrocytes.     

Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.     

Nodular lymphocyte-predominant Hodgkin’s lymphoma

Lymphocyte-predominant Hodgkin’s lymphoma (LPHL) differs in histologic and clinical presentation from classical Hodgkin’s lymphoma (cHL). Treatment of LPHL patients using standard Hodgkin’s lymphoma protocols leads to complete remission in more than 95% of patients. Survival and freedom from treatment failure are substantially worse in advanced-stage patients than for early-stage patients. Thus, patients in advanced stages and those in early stages with unfavorable risk factors should be treated similar to those with cHL. In contrast, patients with early-stage LPHL without risk factors might be sufficiently treated with reduced-intensity programs having less severe adverse effects. As a result, treatment of early LPHL is rather heterogeneous, including radiotherapy using extended-fleld technique, involved-fleld radiotherapy (IF-RT), combined-modality treatment, and, more recently, monoclonal antibodies. Watch-and-wait strategy plays an important role in pediatric oncology, to avoid adverse effects associated with therapy. IF-RT seems to be emerging as a treatment of choice for patients with stage IA LPHL; most larger study groups, such as the German Hodgkin Study Group and the European Organisation for Research and Treatment of Cancer, have adopted IF-RT as the treatment of choice for these patients.     

Pharmacokinetics of Moxifloxacin in Rabbits After Intravenous,Subcutaneous and a Long‐acting Poloxamer 407 Gel Formulation Administration

The pharmacokinetics (PK) of moxifloxacin in healthy white New Zealand rabbits was studied following intravenous (IV) and subcutaneous (SC) administration routes as well as a SC long‐acting poloxamer 407 gel formulation (SC‐P407). Moxifloxacin concentrations were determined by high‐performance liquid chromatography assay with fluorescence detection. Mean half‐life for IV, SC and SC‐P407 routes was 2.15, 5.41 and 11.09 h. Clearance value after IV dosing was 0.78 l/kg/h. After SC administration, the mean absolute bioavailability was 117% and the C_max was 1.61 ± 0.49 mg/l. After SC‐P407 administration, the bioavailability was 44% and the C_max 1.83 was ±0.62 mg/l. No adverse effects were observed in any of the rabbits following IV, SC and SC‐P407 administration of moxifloxacin. Minimal inhibitory concentrations of moxifloxacin against different strains of Staphylococcus aureus from different european countries were used to compute the main pharmacodynamic (PD) surrogate markers of efficacy. The high tolerability of this SC‐P407 formulation and the favourable PK behaviour such as the long half‐life, acceptable bioavailability and excellent PK–PD ratios achieved indicate that it is likely to be effective in rabbits.     

Anxiety in medically III patients

Anxiety disorders and anxiety symptoms are highly prevalent in the general population and more so in the medically ill. They have a number of negative consequences for these patients and may worsen the outcome of the medical illness and increase health care utilization. In the evaluation of these patients, it is of paramount importance to identify the etiology of the anxiety and, in particular, to differentiate primary from secondary anxiety. Management includes medications (especially benzodiazepines and selective serotonin reuptake inhibitors) and psychotherapy (particularly cognitive-behavioral therapy).