Poly(ɛ-caprolactone) (PCL)-polymeric micelle hybrid sheets for the incorporation and release of hydrophilic proteins.

Sheets have several advantages over conventional gel- or particle-type drug carriers. Sheets have several notable attributes: sheets' size and shape are easily adjustable, sheets are highly accessible in surgery, and sheets have a large contact area relative to drug-targeting sites. However, it is difficult to incorporate hydrophilic proteins into hydrophobic sheets and to release the proteins over the long term in a sustained manner. In the present study, we show that "poly(ɛ-caprolactone) (PCL)-polymeric micelle hybrid sheets" can be used for the incorporation and release of hydrophilic proteins. Polymeric micelles (i.e., spaces that can incorporate hydrophilic compounds) are, in this study, uniformly dispersed in hydrophobic and biocompatible biomaterial sheet. We have clarified that the composition of block copolymer, methoxy-terminated poly(ethylene glycol)-block-poly(ɛ-caprolactone) (CH3O-PEG-b-PCL), can affect two variables: the stability of w/o emulsion and the release properties of the resulting sheets, by means of visual qualitative observations, newly developed quantitative analyses (advanced fractal analysis, advanced FD) based on deviation of the fractal dimension (FD), and release experiments. We clarified that the release behavior of BSA was affected by the composition of the block copolymers and the resulting emulsion. The results obtained in this paper show that the hydrophobic sheets in which polymeric micelles providing hydrophilic spaces were dispersed could be an effective platform for incorporating and releasing hydrophilic proteins.

[A patient with Creutzfeldt-Jakob disease supported by home medical care from the stage of disease progression to death through hospital-clinic cooperation and medical-welfare cooperation].

The patient was a 63-year-old woman who presented with slowness of speech after cerebral infarction. Diffusion-weighted MR images and investigations of cerebrospinal fluid showed abnormal values, and the patient was diagnosed as having sporadic Creutzfeldt-Jakob disease(CJD). This is an intractable disease and affects one in one million people; it progresses relatively rapidly, eventually resulting in death. For procedures such as intravenous fluid replacement and the treatment of pressure sores, we require thorough hand washing, eye protection, and disposal of gloves and dressings by incineration. It is desirable for patients to spend the limited amount of time available to them peacefully at home with their family. Visiting physicians and nurses need to take the initiative in sharing information obtained from the CJD infection control guidelines and core hospitals with welfare personnel such as caregivers, in order to provide correct information on all aspects of patient care and the management of this disease in the home environment. Excellent supportive care was provided for the patient at home, and she passed away with her family by her side.

A free-standing, sheet-shaped, "hydrophobic" biomaterial containing polymeric micelles formed from poly(ethylene glycol)-poly(lactic acid) block copolymer for possible incorporation/release of "hydrophilic" compounds.

Sheet-shaped materials with a large contact area relative to the drug targeting site lead to advantages over conventional particle-shaped drug carriers and have several advantages for their biomedical applications. The present study proposes a methodology for preparing a novel sheet-shaped "hydrophobic" and biocompatible biomaterial in which polymeric micelles are uniformly dispersed for the incorporation of "hydrophilic" compounds into the sheet. The methoxy-terminated poly(ethylene glycol)-block-poly(lactic acid) block copolymer (CH(3)O-PEG-b-PLA) was successfully synthesized by means of the anionic ring-opening polymerization of both ethylene oxide and dl-lactide. CH(3)O-PEG-b-PLA was self-assembled and formed stable micelle-like w/o emulsion with a hydrophilic inner core in organic solvents. A sheet-shaped material containing a hydrophilic inner space for incorporating hydrophilic compounds was obtained by spin-coating both the micelle solution and a sheet-forming polymer. Fluorescent images of the sheet proved that polymeric micelles providing hydrophilic spaces were uniformly dispersed in the hydrophobic sheet. The facile technique presented in this paper can be a tool for fabricating sheet-shaped biomaterials that have a hydrophilic inner core and, consequently, that are suitable for the sustained release of hydrophilic compounds.

Clinical study of childhood acute disseminated encephalomyelitis, multiple sclerosis, and acute transverse myelitis in Fukuoka Prefecture, Japan.

Acute disseminated encephalomyelitis (ADEM) has recently been studied in several countries owing to the development and wide spread use of imaging technology, but few epidemiological studies of childhood ADEM have been undertaken in Asian countries. To perform a comprehensive survey of ADEM and related diseases in Japanese children, we conducted a multicenter, population-based study on childhood ADEM, multiple sclerosis, and acute isolated transverse myelitis in Fukuoka Prefecture, Japan. We identified 26 children with ADEM, 8 with multiple sclerosis, and 4 with acute transverse myelitis during 5 years between September 1998 and August 2003. The incidence of childhood ADEM under the age of 15 years was 0.64 per 100,000 person-years, mean age at onset was 5.7 years, and male-female ratio was 2.3:1. The prevalence of childhood multiple sclerosis was 1.3 per 100,000 persons. The mean age at onset of multiple sclerosis, 9.3 years, was significantly higher than that of ADEM. Nineteen (73%) and four (15%) patients with ADEM experienced antecedent infectious illnesses and vaccinations, respectively, within 1 month before the onset. Clinical and radiological findings of ADEM revealed that the frequency of seizures, mean white blood cell counts in cerebrospinal fluid, and the frequency of subcortical lesions in Fukuoka study, seemed to be higher than those in previous non-Asian studies. These findings suggest that there are ethnic or geographical differences in the incidence and clinical features of ADEM, and that there might be potent genetic or environmental risk factors for ADEM distinct from those for multiple sclerosis.

First case of feline systemic Cryptococcus albidus infection.

This paper, as best as the authors can determine, is the first to describe a documented case of systemic infection caused by Cryptococcus albidus in a cat. The patient had a history of paralysis of the hind legs and had been treated with prednisone for 1 month. Microscopic examination of a fine needle biopsy specimen from a right popliteal lymph node showed granulomatous inflammation with many encapsulated yeast cells. Moreover, microscopic examination of Indian ink preparations of the cerebrospinal fluid revealed encapsulated ovoid yeast cells. Thus this case was diagnosed to be cryptococcosis. However, the cat died after treatment for three days with voriconazole. Isolates recovered from samples of the cerebrospinal fluid, liver and spleen were identified as C. albidus by molecular analysis, as well as through morphologic and biochemical studies. Therefore, this case indicates that C. albidus should be considered as a potential feline pathogen.

[Temporal bone histopathology in a patient suspected of inner ear extension of otitis media].

We report the histopathological findings in the temporal bone of a 30-year-old female who died of cervical esophageal carcinoma. The temporal bone sections revealed severe bilateral suppurative labyrinthitis and otitis media that presumably occurred immediately before her death. Many inflammatory cells were present in the middle ear, particularly around the stapes and the round window niche. They had also infiltrated the inner ear via the annular ligament of the stapes and the round window membrane. Inflammatory cell accumulation was also observed in the peri- and endolymphatic spaces, and it was most severe in the basal turn. Most of the inner and outer hair cells were preserved, but some had degenerated or were missing. Numerous round cells were observed in the modiolus, and some of the spiral ganglion cells had degenerated. On the basis of these findings, we concluded that bacterial otitis media had extended in to the inner ear via the oval window and round window membrane and had resulted in suppurative labyrinthitis. These findings are consistent with those of stage II suppurative labyrinthitis according to the classification of Schuknecht.

[Temporal bone histopathology exhibiting cochleosaccular degeneration in a patient with profound deafness].

We herein report the histopathological findings of the temporal bone taken from a patient with unilateral profound deafness since early childhood. The patient was a 72-year-old male who died of lung cancer and extensive metastases including the tongue. The patient had a history of profound hearing loss in his left ear since childhood. The histopathological finding of the left temporal bone revealed a severe atrophy of the organ of Corti, a detached and rolled-up tectorial membrane, a moderate loss of the stria vascularis, and a severe loss of spiral ganglion cells. In addition, the macula of the saccule was severely degenerated. The marked degeneration in the inner ear indicated a cochleosaccular disorder, which is a typical temporal bone finding in cases of viral labyrinthitis and hereditary hearing impairment. The present patient was suspected to have suffered cochleosaccular degeneration as a result of an inner ear viral infection during childhood because the number of spiral ganglion cells was significantly reduced because of secondary neural degeneration.