[Successful Experience of Negative Pressure Wound Therapy with Instillation and Dwelling(NPW Ti-d)for Patient with Wound Dehiscence Developed by Infection after Right-Hemicolectomy for Ascending Colon Cancer].

We report a case of infected and incised wound cured by negative pressure wound therapy with instillation and dwelling (NPWTi-d)after right hemicolectomy for ascending colon cancer. The patient was a 72-year-old male. An ascending colon cancer with abdominal wall invasion and enterocutaneous fistula was found. We performed the right hemicolectomy and debridement of abdominal wall for the patients. However, the leakage of ileum-transverse colon anastomosis was found on postoperative day 3. We performed the resection of anastomosis and ileostomy. Nevertheless, 2 days after second operation, the abdominal wall of debridement became open by infection, and the small intestine was exposed. As the surgical treatment and NPWT was thought to be difficult because of infection, we started NPWTi-d on day 4 after second operation. 25 day after starting NPWTi-d, benign granulation covered the small intestine. NPWTi-d may be useful for wound dehiscence after surgery in infectious conditions.

[A Case of Neuroendocrine Carcinoma Originating from the Papilla of Vater].

A woman in her late 70s with fatigue, nausea, and epigastric discomfort was found to have a tumor at the papilla of Vater through endoscopy. We performed subtotal stomach-preserving pancreaticoduodenectomy with regional lymph node dissection. The immunohistological analysis showed positive staining for chromogranin A, synaptophysin, and CD56. The definitive diagnosis was neuroendocrine carcinoma of the papilla of Vater. Although the patient declined adjuvant chemotherapy, she had to start chemotherapy with carboplatin and etoposide because multiple liver metastases, lymph node metastasis, and peritoneal dissemination occurred 6 months after surgery. We performed 6 courses of chemotherapy. However, progressive disease(PD)was assessed, and she died of cancer 13 months after the surgery. The prognosis of the disease is poor when surgery alone is performed. Adjuvant chemotherapy, in addition to surgery, may be necessary.

Phenotypic variability of Niemann-Pick disease type C including a case with clinically pure schizophrenia: a case report.

BACKGROUND: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder with severe prognosis. Disease-specific therapy is crucial to prevent disease progression; however, diagnosing NPC is quite difficult because of remarkably variable clinical presentations. The NPC Suspicion Index (NPC-SI) was developed to overcome this problem. Identifying preclinical cases is important for prevention and therapy. Here, we report three newly diagnosed NPC cases, one typical juvenile-onset case and the cases of two sisters with symptoms neurologically/psychiatrically indistinguishable from dystonia and schizophrenia, respectively. CASE PRESENTATION: In Case 1, a 25-year-old man presented with a 14-year history of intellectual disability, clumsiness, spastic ataxia, dysphagia, and frequent falls. Neurological examination revealed vertical supranuclear gaze palsy and involuntary movements. Ultrasonography revealed mild splenomegaly, and filipin staining of skin fibroblasts was positive with a variant staining pattern. NPC1 gene analysis showed compound heterozygous mutations, including c.1421C > T (p.P474L), a known causative mutation, and c.3722 T > C (p.L1241S), a new mutation. In Case 2, a 28-year-old woman, the proband, who had marked splenomegaly in her childhood, survived well, contrary to the expected severe prognosis of infantile NPC. She had minor neuropsychiatric symptoms including auditory hallucinations, nocturnal urination, and sleep paralysis. At the age of 28 years, she presented with a 1-year history of orofacial and oromandibular painful dystonia. The patient's 35-year-old sister (Case 3) was diagnosed with schizophrenia. In both cases, filipin staining of skin fibroblasts was positive with variant staining patterns, as well as elevated levels of urinary bile acids. NPC1 gene analysis showed compound heterozygous mutations including c.3011C > T (p.S1004 L), a known causative mutation, and c.160_161insG (p.D54GfsX4), a new mutation. Their mother, who was under therapy with modafinil for narcolepsy, shared the latter mutation. CONCLUSIONS: Marked clinical variability was observed in our three cases. NPC could masquerade as a pure neuropsychiatric disorder such as dystonia or schizophrenia. Abdominal ultrasonography, history evaluation, and neurological examination were quite important in the diagnostic process.

Differential effects of fingolimod on B-cell populations in multiple sclerosis.

BACKGROUND: Fingolimod is an oral drug approved for multiple sclerosis (MS) with an ability to trap central memory T cells in secondary lymphoid tissues; however, its variable effectiveness in individual patients indicates the need to evaluate its effects on other lymphoid cells. OBJECTIVE: To clarify the effects of fingolimod on B-cell populations in patients with MS. METHODS: We analysed blood samples from 9 fingolimod-treated and 19 control patients with MS by flow cytometry, to determine the frequencies and activation states of naive B cells, memory B cells, and plasmablasts. RESULTS: The frequencies of each B-cell population in peripheral blood mononuclear cells (PBMC) were greatly reduced 2 weeks after starting fingolimod treatment. Detailed analysis revealed a significant reduction in activated memory B cells (CD38(int-high)), particularly those expressing Ki-67, a marker of cell proliferation. Also, we noted an increased proportion of activated plasmablasts (CD138(+)) among whole plasmablasts, in the patients treated with fingolimod. CONCLUSIONS: The marked reduction of Ki-67(+) memory B cells may be directly linked with the effectiveness of fingolimod in treating MS. In contrast, the relative resistance of CD138(+) plasmablasts to fingolimod may be of relevance for understanding the differential effectiveness of fingolimod in individual patients.

CCR2(+)CCR5(+) T cells produce matrix metalloproteinase-9 and osteopontin in the pathogenesis of multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the CNS that is presumably mediated by CD4(+) autoimmune T cells. Although both Th1 and Th17 cells have the potential to cause inflammatory CNS pathology in rodents, the identity of pathogenic T cells remains unclear in human MS. Given that each Th cell subset preferentially expresses specific chemokine receptors, we were interested to know whether T cells defined by a particular chemokine receptor profile play an active role in the pathogenesis of MS. In this article, we report that CCR2(+)CCR5(+) T cells constitute a unique population selectively enriched in the cerebrospinal fluid of MS patients during relapse but not in patients with other neurologic diseases. After polyclonal stimulation, the CCR2(+)CCR5(+) T cells exhibited a distinct ability to produce matrix metalloproteinase-9 and osteopontin, which are involved in the CNS pathology of MS. Furthermore, after TCR stimulation, the CCR2(+)CCR5(+) T cells showed a higher invasive potential across an in vitro blood-brain barrier model compared with other T cells. Of note, the CCR2(+)CCR5(+) T cells from MS patients in relapse are reactive to myelin basic protein, as assessed by production of IFN-γ. We also demonstrated that the CCR6(-), but not the CCR6(+), population within CCR2(+)CCR5(+) T cells was highly enriched in the cerebrospinal fluid during MS relapse (p < 0.0005) and expressed higher levels of IFN-γ and matrix metalloproteinase-9. Taken together, we propose that autoimmune CCR2(+)CCR5(+)CCR6(-) Th1 cells play a crucial role in the pathogenesis of MS.

Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica.

Neuromyelitis optica (NMO) is an inflammatory disease affecting the optic nerve and spinal cord, in which autoantibodies against aquaporin 4 (AQP4) water channel protein probably play a pathogenic role. Here we show that a B-cell subpopulation, exhibiting the CD19(int)CD27(high)CD38(high)CD180(-) phenotype, is selectively increased in the peripheral blood of NMO patients and that anti-AQP4 antibodies (AQP4-Abs) are mainly produced by these cells in the blood of these patients. These B cells showed the morphological as well as the phenotypical characteristics of plasmablasts (PB) and were further expanded during NMO relapse. We also demonstrate that interleukin 6 (IL-6), shown to be increased in NMO, enhanced the survival of PB as well as their AQP4-Ab secretion, whereas the blockade of IL-6 receptor (IL-6R) signaling by anti-IL-6R antibody reduced the survival of PB in vitro. These results indicate that the IL-6-dependent B-cell subpopulation is involved in the pathogenesis of NMO, thereby providing a therapeutic strategy for targeting IL-6R signaling.

Testing immediate dosage compensation in Drosophila miranda via irradiation with heavy-ion beams.

Many organisms with heteromorphic sex chromosomes possess a mechanism of dosage compensation (DC) in which X-linked genes are upregulated in males to mitigate the dosage imbalance between sexes and between chromosomes. However, how quickly the DC is established during evolution remains unknown. In this study, by irradiating Drosophila miranda male flies, which carry young sex chromosomes (the so-called neo-sex chromosomes), with heavy-ion beams, we induced deletions in the neo-Y chromosome to mimic the condition of Y-chromosome degeneration, in which functional neo-Y-linked genes are nonfunctionalized; furthermore, we tested whether their neo-X-linked gametologs were immediately upregulated. Because the males that received 2-Gy iron-ion beam irradiation exhibited lower fertility, we sequenced the genomes and transcriptomes of six F1 males derived from these males. Our pipeline identified 82 neo-Y-linked genes in which deletions were predicted in the F1 males. Only three of them showed a one-to-one gametologous relationship with the neo-X-linked genes. The candidate deletions in these three genes occurred in UTRs and did not seriously affect their expression levels. These observations indirectly suggest that DC was unlikely to have operated on the neo-X-linked genes immediately after the pseudogenization of their neo-Y-linked gametologs in D. miranda. Therefore, the dosage imbalance caused by deletions in the neo-Y-linked genes without paralogs may not have effectively been compensated, and individuals with such deletions could have exhibited lethality. Future studies on sex chromosomes at different ages will further reveal the relationship between the age of sex chromosomes and the stringency of DC.

Medullary ischemia due to vertebral arteritis associated with Behçet syndrome: a case report.

Here we report an extremely rare case of Behçet syndrome (BS) that showed acute onset of Wallenberg syndrome and was treated successfully by corticosteroids. A 51-year-old woman with BS had a sudden onset of Wallenberg syndrome. Three days after the onset, she was transferred to our institute. In the magnetic resonance imaging (MRI) study on admission, T2-weighted and fluid-attenuated inversion recovery images showed a high intensity area in the left paramedian region of the medulla oblongata. Contrast-enhanced T1-weighted images showed enhancement in the vessel wall of the left vertebral artery. We diagnosed her as having Wallenberg syndrome due to the acute vertebral arteritis associated with BS. After initiation of high-dose steroid therapy, her symptoms gradually improved. Two months after admission, she was discharged from our institute with mild hemihypesthesia. We hypothesized that vertebral arteritis due to BS had caused hypoperfusion of the medullary perforators causing Wallenberg syndrome in our patient.

[A case of long survival after resection and treatment with imatinib mesylate against metachronous liver metastases and a lung metastasis of a small intestine gastrointestinal stromal tumor].

A 68-year-old man was admitted to our hospital because of an abdominal tumor. Computed tomography(CT)showed a 6 cm tumor in the abdominal cavity. Surgery was performed. Upon laparotomy, a 6 cm tumor was found at the small intestine (210 cm)on the anal side from the Treitz ligament. A partial resection of the small intestine was performed. Immunohistochemistry showed positive staining for c-kit, and the diagnosis of gastrointestinal stromal tumor was confirmed. Multiple liver metastases and a lung metastasis were observed over the next 2 years. We started chemotherapy with imatinib mesylate at a dose of 400mg/day. The size of the tumors was unchanged, and no new lesion was observed. The patient has been alive and well as of 6 years after the initial operation.

Intrathecal baclofen therapy for Lesch-Nyhan disease: illustrative case.

BACKGROUND: Lesch-Nyhan disease (LND) is a very rare metabolic disorder involving the purine salvage pathway. LND manifests hyperuricemia, self-mutilation, cognitive impairment, and movement disorders such as spasticity and dystonia, whose control is difficult pharmaceutically. OBSERVATIONS: Intrathecal baclofen (ITB) therapy was received by a 22-year-old male for generalized dystonia. His paroxysmal abnormal dystonic posturing reduced after surgery, making the task of caregivers easier despite the unchanged assignment on the dystonia scale during a follow-up period of 4 years. LESSONS: ITB may be a safe and feasible option for dystonic symptoms and difficulty with nursing care in patients with LND.

Premorbid instrumental activities of daily living predicts discharge home following stroke.

BACKGROUND AND PURPOSE: Stroke survivors who remain dependent require multiple healthcare resources, including rehabilitation and nursing care. The effect of premorbid instrumental ADL (IADL) on the discharge destination, which has not been studied previously in detail, is analyzed. MATERIALS AND METHODS: Between April and September 2015, 40 stroke patients admitted to hospital were enrolled prospectively in the present study. The ADL (Barthel index) and IADL (Frenchay activities index: FAI) scores in their premorbid status were recorded. Baseline demographic data, stroke severity (NIHSS) and type of stroke, and whether they lived with family were also recorded. Simple univariate regression was performed between the two discharge destination groups (Home or Not Home). Significant factors were then included in multivariate logistic regression in order to determine the adjusted odds ratio for the discharge destination. A P value <.05 was taken as significant. RESULTS: 25 patients (64.1%) returned home. According to univariate analysis, NIHSS on admission and premorbid FAI were significantly associated with the discharge destination. Multivariate analysis found that NIHSS (OR, 0.71; 95% CI0.56-0.92; p = .008) and premorbid FAI (OR, 1.17; 95% CI1.03-1.33; p = .01) were independent predictors of the discharge destination. CONCLUSIONS: Severity of stroke upon admission and premorbid IADL are associated with discharge destination following stroke.

[Nasal flaring during hypoxemia in myotonic dystrophy and duchenne muscular dystrophy].

We investigated the relationship between nasal flaring and SpO2 in 19 patients with Duchenne muscular dystrophy (DMD) and 26 patients with myotonic dystrophy (DM1). In DMD patients, nasal flaring was observed when SpO2 was lower than 96%, while it was not seen even at 82% of SpO2 in DM1. None of the DM1 patients could perform voluntary nasal flaring. Nasal flaring is a useful indicator of hypoxemia in DMD but not in DM1. It remains to be elucidated whether the lack of nasal flaring in DM1 patients is due to abnormal respiratory central mechanism or nasal muscle weakness.

[Severe kyphosis and esophagus hiatal hernia affected in the levodopa absorption of a patient with Parkinson's disease].

An 82 year-old woman with Parkinson's disease complained of a tendency to fall. She has had an extensive kyphosis since she was 66 years old. Over the last 6 months, she has repeatedly fallen. Even though she took anti-parkisonian drugs, she had also developed camptocormia. Her plasma levodopa concentration was analyzed for 4 hrs after administrating an oral dose of levodopa (200 mg) plus carbidopa (20 mg) at the time of fasting. The change in the plasma levodopa concentration showed bimodal peaks. The physical symptoms depended on the plasma concentration and improved twice. Esophageal tortuosity and esophageal hiatal hernia were detected by esophagography and upper gastric endoscopy. Such physical symptoms were speculated to have been caused by the transit disturbance of the drug in the gastrointestinal duct. During a second analysis of the plasma levodopa concentration, the patient was instructed to keep extending her back after consuming the same dose of drugs but with a greater amount of water than in the first analysis. A single and a higher peak were observed for the plasma levodopa concentration, and the physical symptoms, including camptocormia and parkinsonism, were improved. Hunched posture could influence the absorption of antiparkinsonian drugs.

[Local Contributions and Regional Alliances by Pharmaceutical Wholesalers].

Recently, we considered the term 'integrated community care system' and aimed to play a role in the process by joining various healthcare occupations as part of this new integrated system. Given our company's ties with people involved in a range of occupations, we are poised to play a liaison role. We called a "face-to-face meeting" with local healthcare practitioners to begin exploring this cooperation. We believe that as meetings such as these become more widespread across the Kinki Region, they can serve as part of an integrated community care system. Through the formation of a number of alliances by this means, we hope to facilitate the transition to an integrated community care system. The meetings will provide opportunities for a range of healthcare and long-term care professionals, such as physicians, pharmacists, care managers, social workers, and home-visit nurses, to engage in discussions centered on the interests and needs of patients. Another important topic is whether we can derive from these conversations efforts that would assist in the development of "health support pharmacies". In that regard, we have set up some support tools for pharmacies that have held health fairs for local inhabitants. We consider these meetings beneficial in finding a solution to the situation of "polypharmacy"-a recent medical problem. We hope that our meetings will create an opportunity to work cooperatively toward a vision for the future of healthcare and long-term care within a community, through communicating and sharing our proposals for pharmacists based on these experiences.

Plaque-type deposition of prion protein in the damaged white matter of sporadic Creutzfeldt-Jakob disease MM1 patients.

Plaque-type deposition of prion protein (PrP) in the brain has been extremely rare in sporadic Creutzfeldt-Jakob disease patients with methionine homozygosity at polymorphic codon 129 of the PrP gene and type 1 abnormal isoform of PrP (sCJD-MM1). Here we report three sCJD-MM1 patients who showed prominent PrP-positive amyloid plaques in the cerebral and cerebellar white matter. All three patients showed clinical courses of long duration (2 years < or =), particularly at the end-stage. The white matter of these patients was severely damaged because of the prolonged disease duration. Furthermore, Alzheimer's amyloid precursor protein, which accumulates within the axonal swellings under pathological conditions, co-accumulated with the PrP-amyloid plaques. These findings suggest that the axonal damage reflecting the prolonged disease duration causes the deposition of PrP-amyloid plaques in the white matter. The present study shows that PrP-amyloid plaques can occur in the white matter of sCJD-MM1 cases.

[Case of suspected multiple sclerosis with transcallosal lesions involving the upper surface of the corpus callosum].

A 26-year-old woman noticed gradually progressive, right lower leg weakness over a 1.5-month period. Neurological examination revealed right hemiparesis with slightly increased deep tendon reflexes, Babinski's sign on the right side, loss of position sense in the right leg, and slight loss of superficial sensation in the right toes. MR FLAIR images showed a high intensity area measuring 5 x 2 x 3 cm in the left frontal lobe, extending to the outer surface of the body of the corpus callosum and the adjacent right cingulate gyrus. Gadolinium enhancement was seen along the cortex and the outer surface of the body of the corpus callosum. CSF findings showed no pleocytosis, a protein content of 32 mg/dl, a sugar level of 85 mg/dl, and an IgG index of 0.46. The biopsy specimen obtained from the superior frontal gyrus showed perivascular cuffing of T-lymphocytes and some B-lymphocytes, as well as multiple small foci of demyelination. Starting on the second day of admission, the patient was treated with methylprednisolone pulse therapy (1,000 mg/day for 3 days); she was then switched to oral prednisolone (20 mg/day). Thereafter, the patient had two clinical relapses: one was due to a lesion in the dorsal part of the medulla oblongata associated with a disturbance of deep sensation in both hands, and the other was due to a lesion involving the right internal capsule, the globus pallidus, and the caudate nucleus associated with left facial nerve palsy. Visual evoked potentials suggested a demyelinating lesion in the right optic nerve. We suspected a diagnosis of multiple sclerosis based on the presence of more than two clinical episodes of neurological deficits with identifiable lesions on MRI. Multiple sclerosis should be considered in the differential diagnosis of lesions located in the outer part of the corpus callosum and transcallosal bilateral hemispheres on MRI, even though inner callosal lesions are common in multiple sclerosis.

[Immunohistochemical distribution of single-stranded DNA in the brain in medico-legal autopsy cases of carbon monoxide intoxication].

To evaluate apoptotic neuronal damage by carbon monoxide (CO) in medico-legal autopsy cases, we investigated the immunohistochemical distribution of single-stranded DNA (ssDNA) as a marker of apoptosis and programmed cell death in the brain. Formalin-fixed paraffin-embedded brain tissue specimens, including cerebral cortex of frontal lobe, substantia nigra of the midbrain and pallidum, from medico-legal autopsy cases of fire fatality (n=63), including cases with blood carboxyhemoglobin (COHb) of a lower (<60%) and a higher (>60%) level (n = 39 and 24, respectively), and CO intoxication without burns (n = 6) were examined, in comparison with acute ischemic heart disease (IHD, n = 29) and asphyxiation due to strangulation (AS, n= 14). In the pallidum, neuronal immunopositivity for ssDNA was significantly higher in fire fatality with a higher COHb level than in IHD (p<0.0001), and CO intoxication cases showed significantly higher positivity than other groups excluding fire fatality with a higher COHb level (p< 0.05). In cases without cardiopulmonary resuscitation, ssDNA-positivity in the pallidum mildly correlated to COHb concentrations (r = 0.31, p<0.05), and the positivity was significantly higher in higher COHb (>60%) cases than in lower COHb (<30%) cases. In the cerebral cortex and substantia nigra of the midbrain, neuronal ssDNA-positivity showed no significant findings with regard to the cause of death and COHb concentration. These findings suggest that CO causes selective neuronal damage in the pallidum.

[Videofluorographic evaluation of dysphagia in a patient with myasthenia gravis].

A 64-year-old woman with myasthenia gravis (MG) presented with isolated bulbar symptoms. Two years earlier, she had developed neck weakness, diplopia, and ptosis and was diagnosed with MG. Extensive thymectomy was performed, and she was treated with predonisolone (PSL). The neck weakness, diplopia, and ptosis improved over a 2-year period. However, dysphagia developed, and her voice took on a nasal tone that did not improve subjectively even after administration of 10 mg of edrophonium chloride (EC). We then performed videofluorography (VF). After consumption of 10 ml of liquid barium and 8 g of corned beef hash, she attempted to swallow, but the residue remained in the valleculae and the piriform fossa. After the EC injection, her dysphagia on ingestion of corned beef hash improved; however, there was slight subjective improvement in swallowing. Drinking of liquid barium resulted in some residue with slight improvement of dysphagia. After treatment with 70 mg of PSL for 4 weeks, VF showed improvement of dysphagia. Thus, VF, particularly during consumption of solid food, with EC administration is helpful in evaluating bulbar symptoms in patients with MG.

[Influence of inhaling carbon monoxide-containing gas in fire fatalities--an investigation of forensic autopsy cases].

To investigate the influence of inhaling carbon monoxide (CO)-containing gases in fires, forensic autopsy cases of fire victims (n=193) were examined in comparison with control cases involving other causes of fatal CO intoxication (n=6 :COHb, 69.5-83.0%). Fire victims with blood carboxyhemoglobin (COHb) levels over 60% (n=76) showed a larger arterio-venous difference in blood COHb level compared with other fire victims and other fatal CO intoxication. However, biochemical findings for myocardial, cerebral damage or respiratory distress were milder in most cases, independent of blood cyanide levels, being similar to those in fatality due to inhalation of blast furnace gas with an extremely high concentration of CO (ca. 40%). These observations suggest that an acutely fatal factor in fires involves inhalation of gases containing high amounts of CO, which may induce peracute circulatory collapse before causing marked myocardial and cerebral damage or respiratory distress.