Co-feeding transmission facilitates strain coexistence in Borrelia burgdorferi, the Lyme disease agent.

Coexistence of multiple tick-borne pathogens or strains is common in natural hosts and can be facilitated by resource partitioning of the host species, within-host localization, or by different transmission pathways. Most vector-borne pathogens are transmitted horizontally via systemic host infection, but transmission may occur in the absence of systemic infection between two vectors feeding in close proximity, enabling pathogens to minimize competition and escape the host immune response. In a laboratory study, we demonstrated that co-feeding transmission can occur for a rapidly-cleared strain of Borrelia burgdorferi, the Lyme disease agent, between two stages of the tick vector Ixodes scapularis while feeding on their dominant host, Peromyscus leucopus. In contrast, infections rapidly became systemic for the persistently infecting strain. In a field study, we assessed opportunities for co-feeding transmission by measuring co-occurrence of two tick stages on ears of small mammals over two years at multiple sites. Finally, in a modeling study, we assessed the importance of co-feeding on R0, the basic reproductive number. The model indicated that co-feeding increases the fitness of rapidly-cleared strains in regions with synchronous immature tick feeding. Our results are consistent with increased diversity of B. burgdorferi in areas of higher synchrony in immature feeding - such as the midwestern United States. A higher relative proportion of rapidly-cleared strains, which are less human pathogenic, would also explain lower Lyme disease incidence in this region. Finally, if co-feeding transmission also occurs on refractory hosts, it may facilitate the emergence and persistence of new pathogens with a more limited host range.

Incorporation of log odds of positive lymph nodes into the AJCC TNM classification improves prediction of survival in oral cancer.

OBJECTIVES: To assess the prognostic performance of a new N classification that incorporates the log odds of positive lymph nodes (LODDS) into the routinely used pathological N classification for oral squamous cell carcinoma (OSCC) patients. DESIGN: Retrospective cohort study utilising LODDS into pN category was performed, and the AJCC TNM stage and T-New N-M stage were compared with respect to 5-year disease-specific survival (DSS) rates. The discriminability was evaluated from the linear trend chi-square test, Akaike information criterion (AIC) and Harrell's c-statistic. SETTING: Medical centrer in Taiwan. PARTICIPANTS: A total of 463 patients received primary surgery and neck dissection between 2004 and 2013 for OSCC. MAIN OUTCOME MEASURES: The discriminability for 5-year DSS rates. RESULTS: The median follow-up period was 54 months, the mean patient age was 54 ± 11 years and 428 patients (92.4%) were male. The patients with higher LODDS had worse 5-year DSS rates. Incorporation of LODDS into the prognostic model based on the seventh edition of the TNM classification significantly improved discriminative performance for 5-year DSS with a lower AIC (1883 versus 1897), and higher prediction accuracy (Harrell's c-statistic: 0.768 versus 0.764). CONCLUSIONS: By utilising a merger of the LODDS and pN classifications to create a new N classification has better discriminatory and predictive ability than pathological TNM staging and could help identify high-risk patients for intense adjuvant therapy.

A new automatic algorithm to extract craniofacial measurements from fetal three-dimensional volumes.

OBJECTIVES: Three-dimensional (3D) ultrasound is useful in the prenatal evaluation of fetal craniofacial structures, particularly as it provides a multiplanar view. However, an expert must designate the area of interest and the appropriate view, making measurement of fetal structures using 3D ultrasound both time-consuming and subjective. In this study we propose an image analysis system that measures automatically and precisely the fetal craniofacial structures and evaluate its performance in the second trimester of pregnancy using a new 3D volume analysis algorithm. METHODS: A universal facial surface template model containing the geometric shape information of a fetal craniofacial structure was constructed from a fetal phantom. Using the proposed image analysis system we fitted this stored template model using a model deformation approach to individual fetal 3D facial volumes from 11 mid-trimester fetuses, and extracted automatically the following standard measurements: biparietal diameter (BPD), occipitofrontal diameter (OFD), interorbital diameter (IOD), bilateral orbital diameter (BOD) and distance between vertex and nasion (VN). The same five parameters were measured manually by an expert and the results compared. RESULTS: Comparison of the algorithm-based automatic measurements with manual measurements made by an expert gave correlation coefficients of 0.99 for BPD, 0.98 for OFD, 0.80 for BOD, 0.83 for IOD and 0.99 for VN. There were no significant differences between automatic and manual measurements. CONCLUSION: Our proposed system measures precisely the fetal craniofacial structures using 3D ultrasound, making it potentially useful for clinical service. This system could also be applied to other clinical fields in future testing.

Expression of the triggering receptor expressed on myeloid cells-1 mRNA in a heterogeneous infected population.

This study is to investigate the clinical utility of detection of peripheral blood triggering receptor expressed on myeloid cells (TREM)-1 mRNA as an early indicator of sepsis among critically ill patients and to compare the results of TREM-1 with those of C-reactive protein (CRP). A prospective, non-interventional study of 127 patients with at least two criteria of the systemic inflammatory response (SIRS) was performed. TREM-1 was assessed by real-time quantitative reverse transcription-polymerase chain reaction. The diagnosis of SIRS only was made in 41 patients (32%), and the diagnosis of sepsis was made in other 86 patients (68%). TREM-1 mRNA expression had the comparably discriminative value to differentiate the presence from the absence of infection, with an area under the receiver-operating characteristic curve (AUC) of 0.75 [95% confidence interval (95% CI), 0.67-0.84] than CRP [AUC, 0.72 (95% CI, 0.62-0.81)]. As an indicator of sepsis, a TREM-1 mRNA expression ratio cutoff value of 58.8 had a sensitivity of 72%, a specificity of 71%, a positive likelihood ratio of 2.5 and a negative likelihood ratio of 0.39. Furthermore, TREM-1 mRNA expression was selectively higher in septic patients caused by extracellular bacteria or fungi [112.4 (19.3-680.1)], than in those caused by intracellular bacteria or viruses [18.8 (7.6-53.0), p < 0.001]. There was no difference in plasma CRP levels between both septic groups (p = 0.782). TREM-1 and CRP are similar diagnostic markers of sepsis. The different ability of extracellular and intracellular pathogens to induce TREM-1 expression may provide a potential marker for differential diagnosis.

HLA class I antibodies in patients awaiting kidney transplantation and the association with renal graft survival.

The presence of alloantibodies against human leukocyte antigens (HLA) in the circulation of a transplant recipient shows a significant negative impact on the outcome of solid-organ transplantations. The aim of this study was to examine the impact on renal graft survival of various patterns of alloantibodies detected among patients awaiting kidney transplantation. Among more than 2000 patients awaiting kidney transplantations between July 1992 and March 2006, were 683 patients who displayed anti-HLA alloantibodies, 318 of whom were enrolled in this study. Each patient was followed for at least 9 months; the presence of HLA alloantibodies was checked every 3 months by an enzyme-linked immunosorbent assay. Among these 318 patients, 55 patients underwent kidney transplantations. Their median follow-up time was 69 (range, 9-129) months, including 267 (84%) who displayed persistent class I HLA alloantibodies. The intermittent presence of class I HLA alloantibodies was seen in 20 (6.3%) patients. Serum class I HLA antibodies which was positive at first then became undetectable in 4 (1.3%) patients. Three (0.9%) patients were unsensitized at first and then developed class I HLA alloantibodies later; & 24 (7.5%) patients had class I HLA alloantibodies only once during the follow-up period. Among these patients, 55 patients received renal transplantations. The median survival time was shortest in the patients with persistent class I HLA alloantibodies (59.9 months) and longest among patients who were positive at first and then became negative thereafter or in whom class I HLA alloantibodies was detected only once (132 months). There was a significant difference in graft survival times between patients who had persistent HLA alloantibodies and those in whom to have class I HLA alloantibodies were detected only once (P < .05). In this study, the persistent presence of class I HLA alloantibodies among pretransplantation patients was associated with poorer renal graft outcomes. Surveys of various patterns of sensitization to class I HLA antigen may help us to perform risk stratification. High-risk patients may need more aggressive approaches to deplete antibody or complement levels.

Percutaneous transhepatic gall bladder drainage: a better initial therapeutic choice for patients with gall bladder perforation in the emergency department.

OBJECTIVES: To investigate clinical features and outcomes in patients with acute cholecystitis with gall bladder perforation receiving open cholecystectomy or percutaneous transhepatic gall bladder drainage in the emergency department. METHODS: From 1996 through 2005, 33 patients with non-traumatic gall bladder perforation, among 585 patients with acute cholecystitis, were enrolled. Patients were divided into two groups: open cholecystectomy in 16 patients and percutaneous transhepatic gall bladder drainage in 17 patients. Medical records, including demographic data, past history of systemic diseases or gallbladder stones, initial clinical presentations, laboratory data, physical status, therapeutic interventions, and outcomes, were analysed. RESULTS: Mean patient age was 72.6 years (range 54-92 years). 28 patients (84.8%) were male. Median time of symptom onset before emergency department diagnosis was 5 days (range 0.5-30 days). Estimated incidence of gall bladder perforation was 5.6% (33/585). 27 patients (81.8%) had gallstones operatively or in image studies. All patients had either right upper quadrant pain/tenderness or epigastric pain/tenderness. Only 9 (27.3%) patients had positive Murphy's sign. Six patients in the percutaneous transhepatic gall bladder drainage group received further open cholecystectomy. Overall mortality was 24.2% (8/33). The direct cause of death was disease related sepsis in all patients. Patients receiving percutaneous transhepatic gall bladder drainage had a higher survival rate than those receiving open cholecystectomy (100% vs 50%, p<0.001). No differences in complications and length of hospital stay of survivors were observed between groups. CONCLUSIONS: In this study, we delineated clinical features of patients with gall bladder perforation. Better clinical outcome is observed for percutaneous transhepatic gall bladder drainage, and this is suggested as an initial therapeutic choice, especially in high risk patients who are likely to need surgery.

Coenzyme q10 confers cardiovascular protection against acute mevinphos intoxication by ameliorating bioenergetic failure and hypoxia in the rostral ventrolateral medulla of the rat.

Coenzyme Q10 (CoQ10, ubiquinone) is a highly mobile electron carrier in the mitochondrial respiratory chain that also acts as an antioxidant. We evaluated the cardiovascular protective efficacy of CoQ10 at the rostral ventrolateral medulla (RVLM), a medullary site where sympathetic vasomotor tone originates and where the organophosphate poison mevinphos (Mev) acts to elicit cardiovascular intoxication. Experiments were carried out in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Microinjection bilaterally of Mev (10 nmol) into the RVLM induced progressive hypotension and minor bradycardia, alongside significant depression of the activity of NADH cytochrome c reductase (enzyme marker for Complexes I and III) or cytochrome c oxidase (enzyme marker for Complex IV) in the mitochondrial respiratory chain, reduction in ATP concentration, or tissue hypoxia in the RVLM. On the other hand, the activity of succinate cytochrome c reductase (enzyme marker for Complexes II and III) remained unaltered. The Mev-induced hypotension, bioenergetic failure, or hypoxia was significantly reversed when CoQ10 (4 microg) was coadministered bilaterally into the RVLM with the organophosphate poison. We conclude that CoQ10 confers cardiovascular protection against acute Mev intoxication by acting on the RVLM, whose neuronal activity is intimately related to the "life-and-death" process. We also showed that amelioration of the selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain, the reduced ATP level, and the induced tissue hypoxia in the RVLM are among some of the underlying mechanisms for the elicited protection.

Depression of mitochondrial respiratory enzyme activity in rostral ventrolateral medulla during acute mevinphos intoxication in the rat.

We investigated possible changes in bioenergetics at the rostral ventrolateral medulla (RVLM), a medullary site where sympathetic vasomotor tone originates and where the organophosphate poison mevinphos (Mev) acts to elicit cardiovascular intoxication. In Sprague-Dawley rats maintained under propofol anesthesia, microinjection bilaterally of Mev (10 nmol) into the RVLM induced progressive hypotension that was accompanied by an early augmentation (80-100 min post-Mev; Phase I), followed by a decrease (>100 min post-Mev; Phase II) in the power density of the vasomotor components (0-0.8 Hz) in systemic arterial pressure (SAP) signals. Enzyme assay revealed that local application of Mev into the RVLM also significantly and progressively depressed the activity of NADH cytochrome c reductase (marker for Complexes I and III) and cytochrome c oxidase (marker for Complex IV) in the mitochondrial respiratory chain of the RVLM, but not the heart. On the other hand, the activity of succinate cytochrome c reductase (marker for Complexes II and III) remained unaltered. Both the cardiovascular consequences and depression of mitochondrial respiratory chain enzymes elicited by Mev were significantly antagonized on comicroinjection of atropine (3.5 or 7 nmol) bilaterally into the RVLM. We conclude that Mev adversely effects cardiovascular control by acting as a cholinesterase inhibitor in the RVLM, whose neuronal activity is intimately related to the death process. The resulting accumulation of acetylcholine and prolonged activation of muscarinic receptors in the RVLM is manifested by a selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain that underlies cardiovascular toxicity associated with organophosphate poisons such as Mev.

A metastatic pituitary carcinoid tumor successfully treated with gamma knife radiosurgery.

Intracranial metastasis occurs in a certain number of patients with carcinoid tumor. However, carcinoid tumor with metastasis to the pituitary gland is extremely rare. Up to the present, no effective treatment for either a metastatic intracranial carcinoid tumor or a metastatic pituitary lesion of any origin has been documented. We have treated a case of metastatic carcinoid tumor of the pituitary gland with transsphenoidal tumor resection followed by gamma knife radiosurgery. A 59-year-old man presented with headache and left oculomotor palsy. He was treated at the same hospital for bronchial atypical carcinoid tumor one and a half years ago. Magnetic resonance image of the brain showed a pituitary tumor. There were no signs of recurrent or metastatic lesion elsewhere despite thorough investigation. Transsphenoidal approach for removal of tumor was done and the pathology turned out to be a metastatic carcinoid tumor. Subsequent gamma knife radiosurgery was given for residual tumor. The oculomotor palsy improved after radiosurgery. No neurological deficit occurred. Follow-up CT scan of the brain showed complete resolution of the tumor. We concluded that gamma knife radiosurgery could be used to treat a metastatic intracranial carcinoid tumor. It can also be used to treat a metastatic lesion of the pituitary gland without causing neurological deficit.

Effect of methanol-containing additive on the emission of carbonyl compounds from a heavy-duty diesel engine.

This study was aimed at determining the effect of methanol-containing additive (MCA) on the emission of carbonyl compounds (CBCs) generated from the diesel engine. For this experiment, a heavy-duty diesel engine was connected with a full flow critical flow ventri (CFV) type dilution tunnel, a Schenck GS-350 DC dynamometer, and a DC-IV control system in series. The operating conditions of the heavy-duty diesel engine for both cold-start and hot-start Transient Cycle tests and for both low-load and high-load steady-state tests were ascertained. The exhaust of CBCs collected from a 2,4-dinitrophenylhydrazine (2,4-DNPH)-coated cartridge were first converted to corresponding hydrazone derivatives, which were then solvent-eluted and analyzed by a High Performance Liquid Chromatograph (HPLC) with an ultraviolet-visible (UV) detector. When either 10% or 15% MCA was used, the emission factors of the CBCs acrolein and isovaleraldehyde increased by at least 91%. Accordingly, future studies must be done to cut down the emission of CBCs when MCA and methanol alternative fuels are used.

p16 protein expression is associated with a poor prognosis in squamous cell carcinoma of the lung.

An immunohistochemical analysis for p16 protein was performed in 171 patients with non-small-cell lung cancer (NSCLC). Sixty-two carcinomas (36.3%) were classified as p16-negative. p16-negative tumours in squamous cell carcinomas (SCCs) were significantly more than those in adenocarcinomas (P = 0.039). There was no significant difference in survival according to tumour p16 status in patients with NSCLCs or in patients with adenocarcinomas. In contrast, of patients with SCCs, the 5-year survival rate of patients with p16-negative tumours was significantly lower than those with p16-positive tumours (P = 0.001). Especially, the survival of patients with p16-negative tumours was significantly worse than that of patients with p16-positive tumours in the early stage of the SCC, e.g. stage I (P = 0.005). Multivariate analysis showed that p16 status and nodal status were significant prognostic factors for the survival of patients with SCCs of the lung (P = 0.024 and P = 0.008 respectively). In conclusion, our study showed that alteration of p16 was one of the significant factors of a poor prognosis in SCCs of the lung, and that p16 might play an important role in some SCCs of the lung due to its high prevalence and prognostic value.

Emission characteristics of VOCs from athletic tracks.

Dynamic and flow-through flux chambers are convenient tools for field measurements of gas or VOC emission flux from solid surfaces in the field. This study was undertaken to collect on site and quantify the emissions of volatile organic compounds (VOCs) released from athletic running tracks. Three typical types of tracks, one synthetic rubber and two tracks (types I and II) consisting mainly of polyurethane, were studied. They were all installed with adhesives and backings, both of which contributed significant amount of VOCs. VOCs released from the track surface were collected with a flux chamber and subsequently analyzed by a gas chromatograph/mass spectrometer (GC/MS). Also, for each track and at each selected time the emission flux and mass emission were measured on site under outdoor conditions over a period of 40 min. GC/MS analyses show that the VOCs emitted include 2-methyl furan, butanal, methyl ethyl ketone, benzene, heptane, methyl isobutyl ketone, toluene+octane, hexanal, nonane+ethylbenzene, xylenes+styrene, propyl benzene, decane, 1,3,5-trimethyl benzene, 1,2,4-trimethyl benzene, 1,2, 3-trimethyl benzene and undecane. Of these, hexanal was the common and principal compound for all three types of tracks. 2-Methyl furan and methyl isobutyl ketone were the characteristic compounds for the synthetic rubber and the type II of polyurethane tracks, respectively. In the field studies, no unique compounds were found in the type I of polyurethane tracks. For each of these three types of tracks the total-VOCs emission flux was correlated to the track age and track surface temperature. The results of multiple regression analysis showed good correlation. The type II polyurethane track had the highest decay rate, while the synthetic rubber track had the lowest decay rate. Two years after the track installation, the VOC concentrations measured at 1.5 m above the track, the breathing height of school children, were not significantly higher than the background levels.

Detection of mammosomatotrophs in paraffin-embedded specimens of various pituitary adenomas.

BACKGROUND: There are various classification systems for pituitary adenomas based on whether mammosomatotroph cells, which simultaneously express both prolactin (PRL) and growth hormone (GH), can be found. Until the present, the identification of such cells required special techniques and could not be performed in paraffin-embedded specimens. This hindered large-scale studies for detection of mammosomatotrophs in various pituitary adenomas and, as a result, such classification has remained controversial. To establish a methodology for the detection of mammosomatotrophs in paraffin-embedded specimens and to propose a more logical classification for pituitary adenomas, the authors conducted this retrospective study. METHODS: We performed double immunofluorescence staining of PRL and GH in paraffin-embedded specimens of various pituitary adenomas with subsequent observation with a confocal laser-scanning microscope. RESULTS: Mammosomatotrophs were found in four of the 10 GH-secreting adenomas and one of the 10 clinically nonfunctioning adenomas. However, mammosomatotrophs were not identified in all 10 cases of prolactinoma. CONCLUSIONS: This is the first report in the literature that successfully demonstrates the presence of mammosomatotrophs in routine paraffin-embedded pituitary adenomas. The new methodology is important for future study of the function and role of these cells. A large-scale study for mammosomatotrophs in various pituitary adenomas with this method and a more logical classification of pituitary adenomas are proposed.

Anterior cervical stabilization with the synthes cervical spine locking plate system.

BACKGROUND: The Synthes cervical spine locking plate (CSLP) was originally designed by Mörscher and colleagues, who refined it to prevent the migration and loosening of a locking screw by using a cross-split screw head that could be locked into the plate. This eliminated the requirement of the posterior cortex purchase and thereby decreased the risk of spinal cord injury. The purpose of this report is to review our experience using the cervical spine locking plate system and to evaluate its ability to stabilize the cervical spine. METHODS: Twenty patients with cervical trauma, cervical spondylosis of failed anterior interbody fusion underwent anterior cervical fusion with the Synthes CSLP system between August, 1993, and April, 1996. All patients were evaluated preoperatively and postoperatively by plain radiography and magnetic resonance imaging (MRI). RESULTS: All 20 patients achieved solid bone fusion and 19 of them had neurologic improvement, by a mean follow-up period of 36 months. No patients suffered from neurologic injury as a result of the locking device. No patient demonstrated radiologic evidence of implant failure. The postoperative MRI examination disclosed minimal implant artifacts and adequate spinal cord decompression. CONCLUSIONS: The Synthes CSLP system for anterior stabilization provides efficacy, safety and ease of use. It also caused less distortion and minimal artifacts on postoperative MRI.

Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients.

MRP-1/CD9, KAI1/CD82, and ME491/CD63, have been reported to be associated with the metastatic potential of solid tumors. The aim of this study was to determine whether their expression in tumor tissues is a useful indicator for prognosis in breast cancer patients. We studied 109 breast cancer patients who underwent surgery. Quantitative reverse transcription-polymerase chain reaction analysis was performed to evaluate the expression of these genes. The results were confirmed with immunohistochemistry. All of the carcinomas were ME491/CD63 positive. Thirty-six tumors were MRP-1/CD9 negative. The disease-free survival rate and the 5-year survival rate of patients with MRP-1/CD9-negative tumors were both significantly lower than that in patients with MRP-1/ CD9-positive tumors (P = 0.0005 and P = 0.0380, respectively). Sixty-five tumors were KAI1/CD82 negative. The disease-free survival rate of patients with KAI1/CD82-negative tumors was significantly lower than that of patients with KAI1/CD82-positive tumors (P = 0.0065). Cox regression analysis demonstrated that MRP-1/CD9 status (P = 0.0016) and KAI1/CD82 status (P = 0.0234) were useful indicators for the disease-free survival of breast cancer patients. The disease-free survival rate and 5-year survival rate of patients with either MRP-1/CD9-negative or KAI1/CD82-negative tumors were both significantly lower than patients who were positive for both genes (P = 0.0003 and P = 0.0292, respectively). The expression of MRP-1/CD9 and KAI1/CD82 genes are useful indicators of a poor prognosis in breast cancer patients.

Novel staging protocol for non-small-cell lung cancers according to MRP-1/CD9 and KAI1/CD82 gene expression.

PURPOSE: The transmembrane-4 superfamily (TM4SF) is a recently discovered family of genes. Of the TM4SF members, MRP-1/CD9, KAI1/CD82, and ME491/CD63 have been reported to modulate tumor progression or metastasis. In this study, we investigated the relationships between these three genes, MRP-1, KAI1, and ME491, in patients with non-small-cell lung cancers (NSCLCs). Moreover, we assessed the prognostic value of evaluating the expressions of MRP-1, KAI1, and ME491 simultaneously in NSCLCs. PATIENTS AND METHODS: One hundred seventy-two patients up to stage IIIB NSCLC underwent radical surgery during the period of January 1991 through June 1994. Using a quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis, we studied the expression of MRP-1, KAI1, and ME491 genes in these patients. RESULTS: We found that 109 patients (63.4%) had MRP-1-positive tumors and 42 patients (24.4%) had KAl1-positive tumors. Conversely, all 172 patients expressed ME491. No relationship was found between MRP-1 expression and KAI1 expression. We classified these patients into three groups. The 36 patients who were positive for both MRP-1 and KAI1 were defined as group A; the 79 patients with reduced expression of either MRP-1 or KAI1 were defined as group B, and the remaining 57 patients with reduced expression of both MRP-1 and KAI1 were defined as group C. This new classification was correlated with nodal status, tumor status, and pathologic stage (P = .0056, P = .0003, and P < .0001, respectively). In NSCLC patients, the 5-year survival rate of group A patients was significantly better than that of group B patients and much better than that of group C patients (86.8%, 53.9%, and 31.5%, respectively; P < .0001). Cox multivariate regression analysis showed that this new classification in NSCLCs was a significant prognostic factor, as was the nodal status (P < .0001). CONCLUSION: Our results suggest that a low MRP-1 and KAI1 expression by tumors of the lung may be associated with poor prognosis. It is conceivable that the evaluation for MRP-1 and KAI1 expression may identify node-negative lung cancer patients who are at high risk for early disease recurrence, and thus need intensive adjuvant therapy.

Expression of human islet amyloid polypeptide/amylin impairs insulin secretion in mouse pancreatic beta cells.

Non-insulin-dependent diabetes mellitus (NIDDM) is associated histopathologically with islet amyloid deposits of which a major component is islet amyloid polypeptide (IAPP)/amylin. We examined whether endogenous IAPP controls insulin secretion via a local effect within pancreatic islets and whether overexpression of this peptide contributes to pancreatic beta-cell dysfunction in this disease. Transgenic mice expressing human IAPP in pancreatic beta cell were used in this study. Human IAPP expression did not influence the mouse proinsulin mRNA level and insulin content. Glucose-induced insulin secretion was decreased in the isolated pancreatic islets of transgenic mice. MIN6, a glucose-responsive pancreatic beta-cell line, was transfected with human IAPP cDNA by a lipofectin method. Human IAPP expression was confirmed by RNA blot and immunohistochemical analysis. In two transfectants expressing the largest amount of human IAPP, insulin secretion was increased in response to glucose stimulation; however, the magnitude of the insulin response in cells transfected with human IAPP was smaller than in control clones. Insulin content was not influenced by the expression. We conclude that endogenous IAPP inhibits insulin secretion via an autocrine effect within pancreatic islets, and that the impaired insulin secretion in this disease may be partly caused by overexpression of IAPP.

Role of foramen ovale electrodes in presurgical evaluation of intractable complex partial seizures.

BACKGROUND: The value of intracranial electrodes such as depth electrodes and subdural grids for intracranial electroencephalographic (EEG) recording in patients with intractable epilepsies has been well recognized. A new technique, foramen ovale electrode (FOE) implantation, was first introduced by Wieser in 1984 for the lateralization of bilateral mesiotemporal lobe (MTL) onset of seizures. METHODS: Since October 1993, a multipolar, three-contact FOE has been used in 12 intractable epileptic patients for presurgical evaluation. The reasons for FOE implantation included bilateral MTL onset of seizures recorded by extracranial EEGs in nine patients, and extracranial EEG abnormalities inconsistent with the results of magnetic resonance imaging (MRI), positron emission tomogram (PET) or Wada test in three patients. Under general anesthesia, the FOEs were implanted according to the technique introduced by Kirschner, using Barters landmarks. RESULTS: After long-term telemetry recording with FOE, seven patients revealed clear onset of seizures originating from one side of the MTL and underwent anterior temporal lobectomy (ATL). Two patients had seizures of bilateral MTL onset. However, they received ATL due to predominantly unilateral interictal epileptiform discharges (EDs) and/or MRI and PET abnormalities. Seven (78%) of the nine operated patients became seizure-free after ATL. Three patients were considered not operable because two had multifocal onset of seizures and one had seizures with independent bilateral MTL onset. No serious complication resulted from implantation of FOE in this series. CONCLUSIONS: The semi-invasive technique of FOE is reliable for lateralization of bilateral MTL onset of seizures which are often not clearly recorded by extracranial EEGs. This procedure is safe and can be an alternative to invasive implantation of depth electrodes and subdural grids.

Atlantoaxial arthrodesis using Halifax interlaminar clamps reinforced by halo vest immobilization: a long-term follow-up experience.

Thirty-two patients who underwent atlantoaxial arthrodesis using Halifax interlaminar clamps and halo vests between January 1989 and December 1992 were reviewed. The atlantoaxial instabilities were related to trauma in 16 patients, including 14 patients with unstable odontoid fractures, 1 patient with a complex C2 fracture, and 1 patient with a disrupted transverse ligament. Of the other 16 patients, whose atlantoaxial instabilities were nontraumatic in origin, 9 had instabilities that were secondary to rheumatoid arthritis, 1 had instability that was secondary to tuberculous infection, and 6 had instabilities that were caused by os odontoideum. The patients were followed postoperatively with lateral cervical radiographs for an average of 37 months (range, 16-59 mo). Solid atlantoaxial arthrodeses were achieved in all (100%) of these 32 patients after 32 to 111 days (average, 84.5 d) of halo immobilization, indicating atlantoaxial arthrodeses can be reasonably anticipated when Halifax interlaminar clamps with autogenous iliac bone grafting are reinforced by halo vest immobilization for 3 months.

Alteration of cerebral microcirculation by hemodilution with hemosome in awake rats.

Our study showed that hemodilution with modified fluid gelatin resulted in an increase in local cerebral blood flow (LCBF), but no change at all in local cerebral oxygen delivery (LCOD) in rats. Hemosome, a lecithin encapsulated hemoglobin having the oxygen-carrying capacity, was developed to improve LCOD by hemodilution. Therefore, we have hypothesized that LCBF & LCOD would be increased by hemodilution with hemosome. To test this hypothesis, adult male Sprague-Dawley rats weighing approximately 350g were used and divided into the hemodilution and the control groups. Hemosome was made from pig red blood cells and lecithin. It's mean diameter was approximately 0.3 um and hemoglobin concentration was approximately 4g/dl. Isovolemic hemodilution, which lowered the systemic hematocrit from approximately 50% to approximately 30%, was achieved by rapidly replacing blood with the same volume of hemosome. Ten min later, LCBF in 14 brain structures were measured using the 14C-iodoantipyrine technique. Our results showed that LCBF of the control group ranged from 115 +/- 11 ml/100g/min in the medulla to 260 +/- 31 ml/100g/min in the occipital cortex. LCBFs were generally higher (p < 0.05, MANOVA) by 16% in the hemodilution group than in the control group. However LCODs were generally decreased (p < 0.05, MANOVA) by 18% in the hemodilution group than in the control. In conclusion, hemodilution with hemosome indeed improves LCBF but lowers LCOD in awake rats.