A clinical investigation of the association between perioperative oral management and prognostic nutritional index in patients with digestive and urinary cancers.

Background: The prognostic nutritional index (pni) is a simple metric calculated using serum albumin and the peripheral lymphocyte count. It was reported that a low pni score is significantly associated with major postoperative complications and poor prognosis. The purpose of the present study was to investigate the effects of perioperative oral management (pom) on the perioperative pni profiles of patients with digestive system or urinary cancers. Study Design: The medical records of 181 patients with cancer who underwent surgery and for whom a pni could be calculated were retrospectively reviewed. Results: The intervention rate with pom was 34.8%. The median preoperative pni score was 48.25 in all patients with a pom intervention [25% to 75% interquartile range (iqr): 44.38-54.13] and 47.25 in those without an intervention (iqr: 42.0-53.5). Compared with patients not receiving pom, those who received pom had significantly higher pni scores from the early postoperative period (p < 0.05). Notably, of patients who could resume oral intake within 3 days after surgery, those who received pom intervention, compared with those who did not, had significantly higher pni scores from the early postoperative period (p < 0.05). Conclusions: Perioperative oral management interventions might have positive effects on the postoperative pni scores of patients with cancer.

[Delayed augmentation effect of cytokine production after hyperthermia stimuli].

Heatstroke is considered an important condition that may contribute to endothelial cell damage. The aim of this study was to assess temporal profiles of the cytokine (IL-6 and IL-8) and mRNA production when endothelial cells undergo higher temperature stimuli. In the first group, human umbilical vascular endothelial cells (HUVECs)were cultured at 4 different temperatures (37, 38, 39 or 40 degrees C) for 1, 3 and 5 h. In the second group, HUVECs were cultured at 37 degrees C for 4 h or 23 h, after stimulation by heating for one hour at the same culture temperatures used in the first group (37 degrees C to 40 degrees C). After culturing, IL-6 and IL-8 mRNA and protein levels were measured. It has been found the cytokine mRNA levels being significantly higher (p < 0.001) in all cells incubated at higher temperatures than those in the control (cultivation at 37 degrees C). At the same time, the productionof IL-6 and 8 at a higher temperature (39, 40 degrees C) was significantly lower (p < 0.001) than at 37 degrees C (control), and the decrease was temperature dependent. However, IL-6 and IL-8 levels were significantly greater in the cells at 23 h after transient hyperthermic (40 degrees C, 1 h) stimulation than in control ones (p < 0.001).After a transient hyperthermia, the production of the cytokines in HUVECs is initially inhibited and then augmented. The results indicated that tissue injury might continue to develop after a hyperthermic event. There might be a potent risk for underestimation of cytokine induced tissue injury in the acute phase of a heatstroke.

Exercise effects on methylation of ASC gene.

Chronic moderate exercise has been reported to reduce pro-inflammatory cytokines. To analyze the molecular mechanisms by which training exerts these effects, the epigenetic influences of age and exercise on the ASC gene, which is responsible for IL-1beta and IL-18 secretion, were investigated by ASC gene methylation. Further, the relationship between carcinogenesis and exercise, and methylation of the P15 tumor suppressive gene was also analyzed. High-intensity interval walking exercise, consisting of 3 min low-intensity walking at 40% of peak aerobic capacity followed by a 3 min high-intensity walking period above 70% of peak aerobic capacity, was continued for 6 months. Peripheral blood DNA extracts from young control (n=34), older control (n=153), and older exercise (n=230) groups were then analyzed by pyrosequencing for DNA methylation. Methylation of ASC decreased significantly with age (young control vs. older control, p<0.01), which is indicative of an age-dependent increase in ASC expression. Compared to the older control group, the degree of ASC methylation was higher in the older exercise group (older control vs. older exercise: p<0.01), and presumably lower ASC expression. Neither exercise nor age affected the methylation of the P15. In summary, chronic moderate exercise appears to attenuate the age-dependent decrease in ASC methylation, implying suppression of excess pro-inflammatory cytokines through reduction of ASC expression.

Correlation of axillary osmidrosis to a SNP in the ABCC11 gene determined by the Smart Amplification Process (SmartAmp) method.

Axillary osmidrosis (AO) is caused by apocrine glands secretions that are converted to odouriferous compounds by bacteria. A potential link between AO and wet earwax type has been implicated by phenotype-based analysis. Recently, a non-synonymous single nucleotide polymorphism (SNP) 538G> A (Gly180Arg) in the human adenosine triphosphate (ATP)-binding cassette (ABC) transporter ABCC11 gene was found to determine the type of earwax. In this context, we examined a relationship between the degree of AO and the ABCC11 genotype. We have genotyped the SNP 538G> A in a total of 82 Japanese individuals (68 volunteers and 14 AO patients) by both DNA sequencing and the recently developed Smart Amplification Process (SmartAmp). The degree of AO in Japanese subjects was associated with the genotype of the ABCC11 gene as well as wet earwax type. In most AO patients investigated in this study, the G/G and G/A genotypes well correlated with the degree of AO, whereas A/A did not. The specific SmartAmp assays developed for this study provided genotypes within 30 min directly from blood samples. In East Asian countries, AO is rather infrequent. Although the judgement of the degree of AO prevalence is subjective, the SNP 538G> A in ABCC11 is a good genetic biomarker for screening for AO. The SmartAmp method-based genotyping of the ABCC11 gene would provide an accurate and practical tool for guidance of appropriate treatment and psychological management for patients.

Rewarming following accidental hypothermia in patients with acute subdural hematoma: case report.

A 57-year-old man was admitted to the Emergency and Critical Care Department with accidental hypothermia (31.5 degrees C) after resuscitation from cardiopulmonary arrest (CPA). Brain CT revealed an acute subdural hematoma. Active core rewarming to 33 degrees C was performed using an intravenous infusion of warm crystalloid. The patient underwent craniotomy soon after admission, with bladder temperature maintained at 33 to 34 degrees C throughout the surgery. Therapeutic hypothermia (34 degrees C) was continued for 2 days, followed by gradual rewarming. After rehabilitation, the patient was able to continue daily life with assistance. Traumatic brain injury (TBI) following CPA is associated with extremely unfavorable outcomes. Very few patients with acute subdural hematomas presenting with accidental hypothermia and CPA have been reported to recover. No suitable strategies have been clearly established for the rewarming performed following accidental hypothermia in patients with TBI. Our experience with this patient suggests that therapeutic hypothermia might improve the outcome in some patients with severe brain injury. It also appears that the method used for rewarming might play an important role in the therapy for TBI with accidental hypothermia.

Therapeutic importance of transplantation of a vascularised free flap for an oromandibular injury with infection and severe scar contracture.

We report three patients who had transplantation of vascularised free flaps, peroneal osteocutaneous flap in two patients and radial forearm flap in one patient, for the treatment of oromandibular injuries that had not healed as a result of infection after initial treatment.

Cyclophilin A-independent replication of a human immunodeficiency virus type 1 isolate carrying a small portion of the simian immunodeficiency virus SIV(MAC) gag capsid region.

Hybrid viruses between human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus strain mac (SIV(MAC)) are invaluable to various fields of HIV-1 research. To date, however, no replication-competent HIV-1 strain containing the gag capsid (CA) region of SIV(MAC) has been reported. To obtain the viable gag gene chimeric virus in an HIV-1 background, seven HIV-1 strains carrying a part of SIV(MAC) CA or a small deletion in the CA region were constructed and examined for their biological and biochemical characteristics. While all the recombinants and mutants were found to express Gag and to produce progeny virions on transfection, only one chimeric virus, which has 18 bp of SIV gag CA sequence in place of the region encoding the HIV-1 CA cyclophilin A (CyPA)-binding loop, was infectious for human cell lines. Although this chimeric virus was unable to grow in monkey lymphocytic cells like wild-type (wt) HIV-1 did, it grew much better than wt virus in the presence of cyclosporin A in a human cell line which supports HIV-1 replication in a CyPA-dependent manner. These results indicate that the transfer of a small portion of the SIV(MAC) CA region to HIV-1 could confer the CyPA-independent replication potential of SIV(MAC) on the virus.

Expression of multidrug resistance protein and messenger RNA correlate with (99m)Tc-MIBI imaging in patients with lung cancer.

UNLABELLED: In vitro studies have shown that (99m)Tc-sestamibi (MIBI) is a transport substrate for the P-glycoprotein (Pgp) pump and the multidrug resistance-associated protein (MRP) pump. However, whether MRP and lung resistance protein (LRP) affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer is not known. In this study, we explored whether Pgp and the other pumps, MRP and LRP, affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer. METHODS: Thirty-four lung cancer patients who underwent surgery were examined. Before surgery, (99m)Tc-MIBI SPECT was performed 15 min and 180 min after injection, and early uptake, delayed uptake (L/Nd), and washout rate (L/Nwr) of (99m)Tc-MIBI were obtained. Pgp, MRP, and LRP expression were investigated by immunohistochemistry. The messenger RNA (mRNA) level of Pgp, MRP, and LRP was determined by real-time reverse-transcription polymerase chain reaction. The lung cancer (99m)Tc-MIBI images were correlated with protein and mRNA expression. RESULTS: The mean L/Nd of the Pgp (-) group was significantly higher than that of the Pgp (++) group (P = 0.0324). The Pgp (++) group had a higher L/Nwr than did the Pgp (-) group (P = 0.0269). The mean L/Nd of the Pgp mRNA low-expression group was significantly higher than that of the Pgp mRNA high-expression group (P = 0.0127). The Pgp mRNA high-expression group had a higher L/Nwr than did the Pgp mRNA low-expression group (P = 0.0825). No appreciable correlation was found between the lung cancer (99m)Tc-MIBI images and the expression of MRP or LRP on the level of protein or mRNA. CONCLUSION: These data suggest that an increased level of Pgp expression correlates with a low accumulation on delayed scans and a high L/Nwr of (99m)Tc-MIBI in lung cancer. Neither MRP nor LRP expression on the level of either protein or mRNA correlated significantly with tumor accumulation or efflux of (99m)Tc-MIBI in lung cancer.

A case of familial isolated hyperparathyroidism with ectopic parathyroid cancer.

We report the kindred with familial isolated hyperparathyroidism with parathyroid cancer. The proband was diagnosed as having primary hyperparathyroidism at age 43. The same disorder was also found in his daughter who had low bone mass. His son was found to have primary hyperparathyroidism by family screening. The pathological diagnosis of the resected parathyroid in both father and daughter was parathyroid cancer, and that in son was parathyroid adenoma. The right lower gland of the proband and the left lower gland of the son were present in thymus. No mutations were found in the sequences of MEN1 gene, hence gene(s) other than MEN1 gene may have contributed to the malignant potency in our cases.

Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1: comparison with sporadic parathyroid adenomas.

A prospective study on the natural course of primary hyperparathyroidism has recently been reported. Since hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN 1) is genetically distinct from most forms of sporadic hyperparathyroidism, it is important to know the natural course of hyperparathyroidism in MEN 1 for better clinical management. For this purpose, we retrospectively reviewed clinical parameters of patients with MEN 1 when they were diagnosed as having hyperparathyroidism, and compared them with those of patients with sporadic primary hyperparathyroidism. In patients with MEN 1: 1) levels of intact PTH (i-PTH) gradually increased with age, which accelerated over 40 years; 2) compared to the steep rise in i-PTH levels in aged patients, increase in serum calcium or decrease of serum inorganic phosphate concentration was relatively mild, and 3) the high concentrations of i-PTH in aged patients were not due to renal insufficiency. These features were not observed in patients with sporadic primary parathyroid adenomas. Clinical features of untreated hyperparathyroidism in MEN 1 may be significantly affected by the age of the patient. The effect, if any, of age-dependent deterioration on recurrence rate after subtotal or total parathyroidectomy requires further elucidation.

Skeletal analysis of craniofacial deformities in brachycephaly: comparison with craniofacial deformities in plagiocephaly.

The deformities of craniofacial bones in brachycephaly (n = 2) and plagiocephaly (n = 2) were compared using three-dimensional skull replicas. In brachycephaly the bilateral deformities of the cranial base were similar to the unilateral deformities on the affected side in plagiocephaly. Shortening of the anterior-middle cranial fossas and expansion of the middle cranial fossas suggest downward and anterior displacement of both temporomandibular (TM) joints resulting in the underdevelopment of the middle-inferior facial bones, though this is less conspicuous in brachycephaly for three reasons. The most important one is that the patients have an imposing facial morphology characterised by high, protruding facial bones, as found on the affected side in plagiocephaly. Secondly, the frontal bones are flattened and positioned posteriorly in the anteroposterior direction, which also helps to mask the underdevelopment of the middle-inferior facial bones. Finally, as bony deformities are symmetrical in brachycephaly, they are not as obvious as they would be if they were unilateral.

Pathological study of the diffuse myelin pallor in the anterolateral columns of the spinal cord in amyotrophic lateral sclerosis.

An immunohistochemical study using a monoclonal antibody against macrophage (Ki-M1p) was performed to examine which fiber tracts are affected in the spinal cords and brainstems of ALS patients. In 21 out of 30 ALS patients, various degrees of macrophage infiltration were observed diffusely in the anterolateral columns beyond the corticospinal tracts. On the other hand, a few macrophages were scattered in 20 non-ALS patients in the anterolateral columns outside the corticospinal tracts. In ALS brainstems, the macrophages were mainly localized in the corticospinal tracts. The result suggests that the diffuse myelin pallor in the anterolateral columns beyond the corticospinal tracts may be derived from intrinsic spinal cord lesions. Quantitative investigation using a monoclonal antibody against phosphorylated neurofilaments (SMI-31) revealed that the decrease in the numbers of small fibers would induce the diffuse myelin pallor in anterolateral columns of ALS patients. From these findings, we propose that the propriospinal bundles are candidates for the degenerating fibers in the anterolateral columns of ALS.

Insulin and somatostatin releasing islet cell tumor caused hypoglycemia.

We report a hypoglycemic case with normal insulin levels, which was caused by an islet cell tumor that was releasing insulin and somatostatin. A fasting test suggested the over secretion of insulin. Moreover, this hypoglycemia was enhanced by the inhibitory effect of somatostatin on the secretion of insulin counter-regulatory hormones, such as glucagon, in addition to the autonomous secretion of insulin from the tumor. In cases of hypoglycemia with apparently normal insulin levels, the measurement of somatostatin and various provocative tests are recommended. Arterial stimulation venous sampling (ASVS) was useful to detect the location of this functioning islet cell tumor.

Optimized 3-D CT scan protocol for longitudinal morphological estimation in craniofacial surgery.

Frequent three-dimensional computed tomography scanning may cause deterioration of the lenses of the eye, which are susceptible to x-rays. The authors performed an experimental study using a phantom head to establish an optimized three-dimensional computed tomography scan protocol for longitudinal morphological estimation in craniofacial surgery. Volume computed tomography scans were performed using a Hi-Speed Advantage SG CT scanner (GE Medical Systems, Milwaukee, WI) in the axial plane with a combination of scan parameters of varied values. The radiation doses induced by each scanning were measured using thermoluminescent dosimeter chips attached to the position of the lenses in the phantom. Two-dimensional images in the coronal plane and three-dimensional images of the osseous surface were generated from each accumulated data set. For each scan parameter, the images generated from data accumulated using different values were compared. The study showed that lens radiation dose increased with tube potential and was almost directly proportional to tube current and 1/pitch. The slice thickness did not affect lens radiation doses significantly. Images with good contrast resolution and low artifact level sufficient for estimating morphological changes were obtained using a low tube potential of 100 kVp and a tube current of 100 mA. In regard to z-axis spatial resolution, a slice thickness of less than 3 mm was required for precisely pointing out bony edges in the two-dimensional reformation images. These results led us to conclude that volume computed tomography for longitudinal examination in craniofacial surgery should be kept to a minimum frequency and performed using a low-dose technique, small slice thickness, and large pitch.

Duodenal somatostatinoma and erythrocytosis in a patient with von Hippel-Lindau disease type 2A.

A female with von Hippel-Lindau (VHL) disease type 2A first presented with erythrocytosis at the age of 9 years. This patient revealed multiple paragangliomas at age 22. After the removal of tumors, a retinal hemangioblastoma developed. Our diagnosis of VHL disease type 2A was confirmed. Moreover, systemic examination showed a duodenal somatostatinoma. Frequent and long-term monitoring is important for patients with pheochromocytomas or paragangliomas, and a screening for VHL disease and other hereditary cancer syndromes is recommended. Recognition of neuroendocrine tumors as a manifestation of VHL disease permits earlier diagnosis and improves prognosis.

Cell-dependent gag mutants of HIV-1 are crucially defective at the stage of uncoating/reverse transcription in non-permissive cells.

We have previously shown that some of the human immunodeficiency virus type 1 (HIV-1) gag matrix (MA), capsid (CA), and nucleocapsid (NC) mutants display host-cell-dependent replication potential, and that they are defective at the early phase of the virus replication cycle in non-permissive cells. To determine the defective replication stage of the cell-dependent mutants precisely, the processes of virus entry into cells and virus DNA synthesis were monitored by the highly sensitive enzyme-linked immunosorbent assay and polymerase chain reaction amplification analysis. The results obtained indicated that all the cell-dependent MA, CA and NC mutants are defective at the stage of uncoating/reverse transcription, and that a cellular factor(s) is involved in this process.

FDG PET in the evaluation of the aggressiveness of pulmonary adenocarcinoma: correlation with histopathological features.

2-[Fluorine-18]fluoro-2-deoxy-d-glucose (FDG) uptake within the primary lesion correlates with survival on positron emission tomography (PET) studies of patients with non-small cell lung cancer. The more metabolically active the tumour, the worse the outcome. The aim of this study was to determine whether a correlation exists between aggressiveness as determined by pathology and the findings of FDG PET in pulmonary adenocarcinoma. Thirty-five patients with 38 adenocarcinomas of the lung were studied. All patients underwent thoracotomy within 4 weeks of the FDG PET study. For semiquantitative analysis, standardized uptake values (SUVs) were calculated. Patients were classified into high SUV (> or = 4.0) and low SUV (<4.0) groups. The degree of FDG uptake (SUVs) in primary lung lesions was correlated with the histopathological features of aggressiveness (pleural involvement, vascular invasion or lymphatic permeation). The mean SUV of aggressive adenocarcinomas (4.36+/-1.94, n = 22) was higher than that of non-aggressive ones (1.53+/-0.88, n = 16) (P < 0.0001). Tumours with a high FDG uptake have a significantly higher likelihood of aggressiveness than those with a low FDG uptake (P = 0.0004). Analysis by the Kaplan-Meier methods revealed that the groups had different prognoses (log-rank test, P = 0.0099). The high SUV group had a significantly worse prognosis. In conclusion, a correlation was seen between aggressiveness as determined by pathology and glucose metabolism as measured by FDG PET in adenocarcinoma of the lung. FDG PET may be used as a non-invasive diagnostic technique in measuring aggressiveness and prognosis in patients with pulmonary adenocarcinoma.