Mandibular reconstruction with free fibula flaps in the elderly: a retrospective evaluation.

The purpose of this study was to evaluate surgical outcomes in elderly patients who had undergone free fibula flap transfer for malignant head and neck tumours. A retrospective chart review was performed to identify patients who had undergone free fibula flap transfer for mandibular reconstruction after malignant tumour resection at Jichi Medical University Hospital between May 2009 and April 2015. Enrolled patients were divided into an elderly group (≥80years old) and a younger group (<80years old). Seventeen patients met the inclusion criteria and were included in the elderly group. Age at surgery ranged from 80 to 92years. Thirteen patients (76.5%) experienced postoperative complications. Surgical site complications occurred in seven patients. The success rate of free fibula flap transfer was 100%. Systemic complications occurred in nine patients, most commonly delirium (n=6). No perioperative mortality was encountered. The overall 1-year survival rate was 94.1% (16/17). No patient reported gait disturbance as a donor site complication or any other major complication. The incidence of postoperative complications did not differ significantly between the elderly and younger groups. Almost no difference in postoperative course was seen between the groups. Elderly patients appear to tolerate free fibula flap reconstruction just as well as younger patients.

Efficacy of sucroferric oxyhydroxide treatment in Japanese hemodialysis patients and its effect on gastrointestinal symptoms.

Sucroferric oxyhydroxide (SFOH) is a non-calcium, iron-based phosphate binder indicated for the treatment of hyperphosphatemia in adult dialysis patients. Studies in Japan about the side effects of SFOH treatment indicate that the incidence of diarrhea (25%) is greater while that of constipation (2.9%) is lesser in comparison to that observed upon treatment with an existing phosphate binder. In the present study, the effect of treatment with a combination of the existing phosphate binders and SFOH on the serum phosphorus level and digestive symptoms was observed in hemodialysis patients with hyperphosphatemia, which is untreatable using only the existing phosphate binders. We evaluated the serum phosphorus levels and gastrointestinal symptoms (using the gastrointestinal symptom rating scale) of 6 patients (2 men, 4 women) before and 2, 4, 6, and 8 weeks after continuous administration. The serum phosphorus levels before and 2, 4, 6, and 8 weeks after combination treatment were 7.4±1.0 mg/dL, 5.9±1.3 mg/dL, 5.8±1.5 mg/dL, 5.8±1.4 mg/dL, and 5.8±1.3 mg/dL, respectively, with significant reduction in the levels being observed 2 weeks after administration (p<0.05) and persisting even 8 weeks after continuous administration. The constipation scores before and 2, 4, and 8 weeks after drug administration were 2.39±0.85, 2.34±1.93, 2.56±1.44, and 3.28±2.19, respectively, with no changes observed during the investigation period. The diarrhea scores before and 2, 4, and 8 weeks after drug administration were 2.22±0.91, 2.06±1.16, 1.28±0.39, and 1.06±0.13 respectively. The scores improved significantly, 4 weeks after drug administration (p<0.05), and the improvement persisted, even 8 weeks after continuous administration. Thus, by using a combination of the existing phosphate binders and SFOH, we were able to reduce the serum phosphorus level in patients with hyperphosphatemia, which is untreatable using the existing phosphate binder alone, with no sign of exacerbation of the gastrointestinal symptoms despite a few contradictory case reports.

Cancer emerging from the recurrence of sessile serrated adenoma/polyp resected endoscopically 5 years ago.

Since the serrated neoplastic pathway has been regarded as an important pathway of colorectal carcinogenesis, few reports have been published on clinical cases of cancer derived from sessile serrated adenoma/polyp, especially on recurrence after resected sessile serrated adenoma/polyp. An elderly woman underwent endoscopic mucosal resection of a flat elevated lesion, 30 mm in diameter, in the ascending colon; the histopathological diagnosis at that time was a hyperplastic polyp, now known as sessile serrated adenoma/polyp. Five years later, cancer due to the malignant transformation of the sessile serrated adenoma/polyp was detected at the same site. The endoscopic diagnosis was a deep invasive carcinoma with a remnant sessile serrated adenoma/polyp component. The carcinoma was surgically removed, and the pathological diagnosis was an adenocarcinoma with sessile serrated adenoma/polyp, which invaded the muscularis propria. The surgically removed lesion did not have a B-RAF mutation in either the sessile serrated adenoma/polyp or the carcinoma; moreover, the initial endoscopically resected lesion also did not have a B-RAF mutation. Immunohistochemistry confirmed negative MLH1 protein expression in only the cancer cells. Lynch syndrome was not detected on genomic examination. The lesion was considered to be a cancer derived from sessile serrated adenoma/polyp recurrence after endoscopic resection, because both the surgically and endoscopically resected lesions were detected at the same location and had similar pathological characteristics, with a serrated structure and low-grade atypia. Furthermore, both lesions had a rare diagnosis of a sessile serrated adenoma/polyp without B-RAF mutation. This report highlights the need for the follow-up colonoscopy after endoscopic resection and rethinking our resection procedures to improve treatment.

Gastrointestinal symptoms after the substitution of sevelamer hydrochloride with lanthanum carbonate in Japanese patients undergoing hemodialysis.

Lanthanum carbonate has the same phosphorus depressant effect as the other phosphorus adsorbents, and is expected to decrease digestive symptom onset such as constipation in Japanese patients undergoing hemodialysis compared to sevelamar hydrochloride. In this study, we investigated the short- and long-term changes in digestive symptoms in these patients after substituting sevelamar hydrochloride with lanthanum carbonate. We studied 16 patients (4 men, 12 women) and evaluated their gastrointestinal symptoms before administration, at the time of administration, and 2, 4, 8, and 12 weeks after administration, using the Gastrointestinal Symptom Rating Scale. In addition, we conducted repeat evaluations 52 weeks after administration for the patients in whom lanthanum carbonate was administered continuously for 52 weeks. Fourteen (87.5%) out of the 16 patients could tolerate continuous administration for 12 weeks. The constipation score was 3.21 ± 1.74 before administration, 2.07 ± 0.83 2 weeks after administration, 1.76 ± 0.83 4 weeks after administration, 1.57 ± 0.56 8 weeks after administration, and 11.41 ± 0.48 12 weeks after administration. The scores improved significantly 4 weeks after administration (p < 0.05) and even 12 weeks after continuous administration. Among the 16 study patients, 9 patients (1 men, 8 women) were received lanthanum carbonate continuously for 52 weeks. The constipation score was 3.74 ± 1.92 at the start of administration, 1.37 ± 0.56 12 weeks after administration, and 1.85 ± 0.63 52 weeks after administration, with significant improvement even 52 weeks after administration (p < 0.05). This study shows that substituting sevelamar hydrochloride with lanthanum carbonate improves constipation symptoms in hemodialysis patients from an early stage, which indicates its usefulness in improving constipation symptoms caused by sevelamar hydrochloride.

Influence of cerebral fluid drainage on the pharmacokinetics of vancomycin in neurosurgical patients.

The objective of this study was to retrospectively investigate the influence of cerebral fluid drainage on the serum concentrations and pharmacokinetic parameters of vancomycin (VCM). We analyzed 55 patients with normal renal function who had been hospitalized in the neurosurgical ward and received intravenous infusions of VCM. We compared the daily doses of VCM, serum VCM concentrations, serum concentration/dose ratio (C/D ratio), and pharmacokinetic parameters calculated using the Sawchuk-Zaske method between patients who underwent cerebral fluid drainage (drainage group) and controls (non-drainage group). The patients in the drainage group showed a significantly lower trough concentration of VCM (5.8 ± 3.3 µg/mL) than that shown by the non-drainage group (9.9 ± 5.4 µg/mL, p = 0.017). Further, the patients in the drainage group showed a significantly lower trough C/D ratio (0.32 ± 0.17) than that shown by the non-drainage group (0.50 ± 0.31, p = 0.047). In conclusion, cerebral fluid drainage may influence VCM pharmacokinetics. Our findings strongly suggest that a high dose of VCM is required to maintain optimal serum concentrations of VCM in patients managed with cerebral fluid drainage.

The association between risk factors and time of onset for thrombocytopenia in Japanese patients receiving linezolid therapy: a retrospective analysis.

WHAT IS KNOWN AND OBJECTIVE: Linezolid (LZD) is an oxazolidinone antibiotic that is active against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. The major adverse effect related to its use in humans is reversible myelosuppression, which mostly manifests as thrombocytopenia. This retrospective study was conducted to identify risk factors that might contribute towards the development of thrombocytopenia due to intravenous administration of LZD. METHOD: Patients who were administered LZD between January 2008 and March 2013 were included. Thrombocytopenia was defined as a decrease in platelet count of ≥10 × 10(4) cell/µL from baseline or of ≥30%. RESULTS: A total of 47 patients were included in this study. These patients were divided into two groups: 22 patients (46·8%) were assigned to a non-thrombocytopenia group and 25 patients (53·2%) to a thrombocytopenia group. Multivariate logistic regression analysis revealed significant intergroup differences in duration of LZD treatment [odds ratio (OR) = 1·278; 95% confidence interval (CI) = 1·068-1·529; P = 0·007] and white blood cell (WBC) count (>12000 cells/µL; OR = 10·399; 95% CI = 1·667-64·882; P = 0·012). WHAT IS NEW AND CONCLUSIONS: This finding suggests that duration of LZD treatment and WBC count (>12000 cells/µL) are risk factors associated with thrombocytopenia resulting from LZD administration.

Evaluation of the potassium adsorption capacity of a potassium adsorption filter during rapid blood transfusion.

The concentration of extracellular potassium in red blood cell concentrates (RCCs) increases during storage, leading to risk of hyperkalemia. A potassium adsorption filter (PAF) can eliminate the potassium at normal blood transfusion. This study aimed to investigate the potassium adsorption capacity of a PAF during rapid blood transfusion. We tested several different potassium concentrations under a rapid transfusion condition using a pressure bag. The adsorption rates of the 70-mEq/l model were 76·8%. The PAF showed good potassium adsorption capacity, suggesting that this filter may provide a convenient method to prevent hyperkalemia during rapid blood transfusion.

TLR1-induced chemokine production is critical for mucosal immunity against Yersinia enterocolitica.

Our gastrointestinal tract is a portal of entry for a number of bacteria and viruses. Thus, this tissue must develop ways to induce antigen-specific T cell and antibody responses quickly. Intestinal epithelial cells are a central player in barrier function and also in communicating signals from invading pathogens to the underlying immune tissue. Here we demonstrate that activation of Toll-like receptor 1 (TLR1) in the epithelium leads to the upregulation of the chemokine CCL20 during oral infection with Yersinia enterocolitica. Further, both neutralization of CCL20 using polyclonal antibody treatment and deletion of TLR1 resulted in a defect in CCR6+ dendritic cells (DCs), which produce innate cytokines that help to induce anti-Yersinia-specific T helper 17 (TH17) cells and IgA production. These data demonstrate a novel role for TLR1 signaling in the intestinal epithelium and demonstrate that together TLR1 and CCL20 are critical mediators of TH17 immunity through the activation and recruitment of DCs.

Immunosuppressive effect of prolactin-induced protein.

Prolactin-induced protein (PIP) has been shown to bind to CD4 and is speculated to block CD4-HLA-DR interaction. However, the immunomodulatory effect of PIP on chronic allergic contact dermatitis (ACD) remains to be elucidated. The aim of this work was to define the role of PIP during the immunoresponse. Using an oxazolone-induced mouse chronic ACD model, expression of PIP was immunohistologically examined. Furthermore, effects of continued exposure of a peptide mimicking the major binding site of PIP (amino acids 106-132) for CD4 was examined in a mouse chronic ACD model. We clarified that keratinocytes and dermal infiltrating cells are positively stained with anti-PIP antibody. The PIP peptide significantly downregulated oxazolone-induced mouse ACD compared to the controls. We also found that inflammation of PIP-non-applied control ear was also suppressed in a synchronized manner in the late phase of the PIP peptide applied mouse. These findings suggest that PIP might have an immunosuppressive effect in mouse chronic ACD.

Nerve growth factor and associated nerve sprouting contribute to local mechanical hyperalgesia in a rat model of bone injury.

To clarify the mechanism of tenderness after bone injury, we investigated changes in the withdrawal threshold to mechanical stimuli, nerve distribution and nerve growth factor (NGF)-expression in a rat model of bone injury without immobilization for bone injury healing. Rats were divided into three groups as follows: (1) rats incised in the skin and periosteum, followed by drilling a hole in the tibia [bone lesion group (BLG)]; (2) those incised in the skin and periosteum without bone drilling [periosteum lesion group (PLG)]; and (3) those incised in the skin [skin lesion group (SLG)]. Mechanical hyperalgesia continued for 28 days at a lesion in the BLG, 21 days in PLG and 5 days in SLG after treatments, respectively. Endochondral ossification was observed on days 5-28 in BLG and on days 5-21 in PLG. Nerve growth appeared in deep connective tissue (DCT) at day 28 in BLG. Nerve fibres increased in both cutaneous tissue and DCT at day 7 in PLG, but they were not found at day 28. Mechanical hyperalgesia accompanied with endochondral ossification and nerve fibres increasing at the lesion in both BLG and PLG. NGF was expressed in bone-regenerating cells during the bone injury healing. Anti-NGF and trk inhibitor K252a inhibited hyperalgesia in the different time course. This study shows that localized tenderness coincides with the bone healing and involves NGF expression and nerve sprouting after bone injury. The findings present underlying mechanisms and provide pathophysiological relevance of local tenderness to determination of bone fracture and its healing.

Intrapartum care at a tertiary hospital in Cambodia: a survey using the Bologna Score.

BACKGROUND: developing countries strive to reduce maternal- and child mortality, partly through establishing health centres/hospitals with skilled birth attendants. The aim of this study was to describe childbirth care, by the use of the Bologna Score at a tertiary hospital in Cambodia with approximately 8,500 births per year. METHODS: a prospective cross-sectional study. The Bologna Score instrument, which reflects the adaption of evidence-based care and attitudes of caregivers, was used for data collection and three study specific questions. The midwives collected data from 177 consecutive childbirths. RESULTS: all women were assisted by a skilled birth attendant, the majority by a midwife (63%) and the remaining women by a physician (35%) or midwife student under supervision. A spontaneous vaginal birth was planned for 82% of the women. All women seeking care at the hospital survived the childbirth. A full 5-point Bologna Score, suggesting evidence-based management for women with spontaneous vaginal birth, was not achieved for any of the women. The use of supine position and lack of an accompanying person in the birth room, were items responsible for loss of points. Partogram and skin-to-skin contact between baby and mother were items noted for three quarters of the planned vaginal births, and the item 'Absence of labour augmentation', was affirmed to a great extent. Little more than half of the women had an episiotomy and almost 16% of the children had an Apgar score <7 at 5 mins. CONCLUSION: the Bologna Score was easy to use and pointed at items that could be improved. It was satisfying that all women survived, but alarming that 16% of the children had a low Apgar score. The findings suggest that childbirth care can be improved at the hospital.

Hydroxylated and non-hydroxylated sulfatide are distinctly distributed in the human cerebral cortex.

Sulfatide (ST) is a sphingolipid with an important role in the central nervous system as a major component of the myelin sheath. ST contains a structurally variable ceramide moiety, with a fatty acid substituent of varying carbon-chain length and double-bond number. Hydroxylation at the α-2 carbon position of the fatty acid is found in half the population of ST molecules. Recent genetic studies of fatty acid 2-hydroxylase (FA2H) indicate that these hydroxylated sphingolipids influence myelin sheath stability. However, their distribution is unknown. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables the analysis of distinct distributions of individual ST molecular species in tissue section. We examined human cerebral cortex tissue sections with MALDI-IMS, identifying and characterizing the distributions of 14 ST species. The distribution analysis reveals that the composition ratios of non-hydroxylated/hydroxylated STs are clearly reversed at the border between white and gray matter; the hydroxylated group is the dominant ST species in the gray matter. These results suggest that hydroxylated STs are highly expressed in oligodendrocytes in gray matter and might form stable myelin sheaths. As a clinical application, we analyzed a brain with Alzheimer's disease (AD) as a representative neurodegenerative disease. Although previous studies of AD pathology have reported that the amount of total ST is decreased in the cerebral cortex, as far as the compositional distributions of STs are concerned, AD brains were similar to those in control brains. In conclusion, we suggest that MALDI-IMS is a useful tool for analysis of the distributions of various STs and this application might provide novel insight in the clinical study of demyelinating diseases.

Imaging mass spectrometry revealed the production of lyso-phosphatidylcholine in the injured ischemic rat brain.

To develop an effective neuroprotective strategy against ischemic injury, it is important to identify the key molecules involved in the progression of injury. Direct molecular analysis of tissue using mass spectrometry (MS) is a subject of much interest in the field of metabolomics. Most notably, imaging mass spectrometry (IMS) allows visualization of molecular distributions on the tissue surface. To understand lipid dynamics during ischemic injury, we performed IMS analysis on rat brain tissue sections with focal cerebral ischemia. Sprague-Dawley rats were sacrificed at 24 h after middle cerebral artery occlusion, and brain sections were prepared. IMS analyses were conducted using matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) in positive ion mode. To determine the molecular structures, the detected ions were subjected to tandem MS. The intensity counts of the ion signals of m/z 798.5 and m/z 760.5 that are revealed to be a phosphatidylcholine, PC (16:0/18:1) are reduced in the area of focal cerebral ischemia as compared to the normal cerebral area. In contrast, the signal of m/z 496.3, identified as a lyso-phosphatidylcholine, LPC (16:0), was clearly increased in the area of focal cerebral ischemia. In IMS analyses, changes of PC (16:0/18:1) and LPC (16:0) are observed beyond the border of the injured area. Together with previous reports--that PCs are hydrolyzed by phospholipase A(2) (PLA(2)) and produce LPCs,--our present results suggest that LPC (16:0) is generated during the injury process after cerebral ischemia, presumably via PLA(2) activation, and that PC (16:0/18:1) is one of its precursor molecules.

Immunosuppressive effect of prolactin-induced protein: a new insight into its local and systemic role in chronic allergic contact dermatitis.

BACKGROUND: Prolactin-induced protein (PIP) has been shown to bind to CD4 and is speculated to block CD4-HLA-DR interaction. However, the immunomodulatory effect of PIP on chronic allergic contact dermatitis (ACD) remains to be elucidated. OBJECTIVES: To define the role of PIP during the immunoresponse. METHODS: Using a low-dose oxazolone-induced mouse chronic ACD model, expression of PIP was examined immunohistologically. Furthermore, effects of continued exposure to a peptide mimicking the major binding site of PIP (amino acids 106-132) for CD4 was examined in a mouse chronic ACD model. RESULTS: We clarified that keratinocytes, dermal infiltrating cells and spleen infiltrating mononuclear cells are positively stained with anti-PIP antibody. The PIP peptide significantly downregulated oxazolone-induced mouse ACD compared with controls. We also found that inflammation of the control ear, to which the PIP peptide had not been applied, was also suppressed in a synchronized manner in the late phase of ACD. CONCLUSIONS: These findings suggest that PIP might have a local and systemic immunosuppressive effect in mouse chronic ACD.

Immunohistolocalization and gene expression of the carbonic anhydrase isoenzymes (CA-II and CA-VI) in glands associated with the canine lacrimal apparatus.

Cytosolic and secretory carbonic anhydrase isoenzymes (CA-II and CA-VI, respectively) were detected by immunohistolocalization using specific canine CA-II and CA-VI antisera. CA-II and CA-VI were identified in glands associated with the canine lacrimal apparatus, such as lacrimal gland, superficial gland of the third eyelid (third eyelid gland) and tarsal gland. CA-II and CA-VI mRNA signals were also detected by reverse-transcriptase polymerase chain reaction in the same tissues. Some serous acinar cells and duct segments in the lacrimal gland and serous acinar cells in the third eyelid gland were immunopositive for anti-CA-II and CA-VI antisera. In particular, some immunopositive acini to CA-II and CA-VI on the edge of the third eyelid gland are histologically similar to sebaceous gland cells. Sebaceous gland cells in the tarsal and ciliary glands also showed immunopositivity to both CA antisera. CA-II and CA-VI gene transcripts were detected in the same regions. These results suggest that secreted CA-VI may form together with cytosolic CA-II, a high-activity isozyme mostly considered as a bicarbonate producer, in a mutually complementary system for the maintenance of bicarbonate levels to regulate pH in tear fluid and protect the corneal epithelia against injuries. In sebaceous gland cells in the lacrimal apparatus, CA-VI may be related to lipogenesis in an unknown function.

[Tonsillar metastais from primary lung large cell neuroendocrine carcinoma in the early stage; report of a case].

We experienced an extremely rare case of large cell neuroendocrine carcinoma (LCNEC) of the lung metastasizing to the tonsil. A 66-year-old woman who had been undergone radical hysterectomy and radiated on whole pelvis in June, 2006, was pointed out 2 cm diameter abnormal shadow at the right S8 of the lung by computed tomography (CT) in May, 2007. In June, 2007, the right lower lobectomy with lymphandenectomy was done by video-assisted thoracic surgery (VATS). The pathological diagnosis was stage IA LCNEC of the lung. In April, 2008, multiple metastases to the brain appeared, and the patient unederwent gamma knife treatment. In addition, metastases to the liver, lymphnode of abdomen, left adrenal and bone followed in 1 month. Although we considered a chemotherapy, her general condition deteriorated rapidly with development of right tonsil metastasis and died as lasly as 3 months later.

A case of bilateral parietal cortical laminar necrosis with a loss of vertiginous sensation.

BACKGROUND: Animal experiments demonstrated that there are vestibular cortical areas at the parietal cortex. Moreover, in humans, recent functional neuroimaging studies revealed that caloric stimulation activated the parietoinsular vestibular cortex and optokinetic stimulation activated the parieto-occipital cortex. These activations indicate that the parietal vestibular areas play some role in nystagmus generation or in spatial information processing in the eye movement tasks. AIMS OF THE STUDY: The aim of this communication was to present a patient giving some information about parietal cortical function in nystagmus production and vertigo. CASE: We report a 51-year-old, heavy alcoholic man with Bálint syndrome, constructional disability, limb-kinetic apraxia and ideo-motor apraxia. Brain magnetic resonance imaging demonstrated bilateral parietal cortical laminar necrosis anterior to the parieto-occipital sulci without any involvement of the primary sensory and parietoinsular cortices. Optokinetic nystagmus (OKN) was not elicited whereas cold caloric stimulation fully evoked nystagmus toward the opposite side with oscillopsia when eyes opened. However, he did not feel vertiginous sensation when the eyes were closed. CONCLUSIONS: These findings suggest that the parietal cortices are indispensable for OKN production and vertiginous sensation.

Ribosomal P protein P0 as a candidate for the target antigen of anti-endothelial cell antibodies in mixed connective tissue disease.

OBJECTIVE: To evaluate the presence of anti-endothelial cell antibodies (AECA) in patients with mixed connective tissue disease (MCTD) compared to those with systemic sclerosis (SSc) and to determine the candidates for the endothelial auto-antigen that reacts with AECA in patients with MCTD using a molecular cloning strategy. METHODS: AECA were measured by a cellular enzyme-linked immunosorbent assay (ELISA) using fixed human umbilical vein endothelial cells (HUVEC) in 47 MCTD patients, 68 SSc patients, and 52 normal controls. A HUVEC cDNA expression library was immunoscreened with pooled sera from 6 patients with high AECA levels determined by cellular ELISA to explore the endothelial autoantigens in MCTD. An ELISA assay for anti-ribosomal protein P0 antibodies was used to assess the correlation with AECA levels. RESULTS: The candidate target proteins recognized by AECA in MCTD included: (i) ribosomal protein P0; (ii) a putative oncogene derived from dek mRNA; (iii) SS-B/La protein; (iv) U1 RNA-associated 70K protein; and (v) DNA-binding protein B. A significant correlation between the levels of AECA and anti-ribosomal protein P0 antibodies was demon-strated in MCTD, but not in systemic sclerosis. The sera containing high levels of AECA from patients with MCTD frequently cross-reacted with ribosomal protein P0. On the other hand, sera without AECA activity from patients with MCTD never reacted with ribosomal protein P0. CONCLUSION: AECA were more frequently seen in patients with MCTD than in patients with SSc. Ribosomal protein P0 may be one of the major target antigens of AECA in patients with MCTD.