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.

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.

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.

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.

Formation of islet amyloid fibrils in beta-secretory granules of transgenic mice expressing human islet amyloid polypeptide/amylin.

To investigate the relationship between human islet amyloid polypeptide (IAPP)/amylin expression and islet amyloid deposits in the pathogenesis of human non-insulin-dependent diabetes mellitus (NIDDM), we developed transgenic mice using a human IAPP cDNA connected to an insulin promoter. Ribonucleic acid blotting and immunohistochemistry revealed the expression of the transgene in the pancreatic beta cells. Immunogold electron microscopy showed that beta-secretory granules contained the human C-terminal flanking peptide of the IAPP precursor. Reverse-phase HPLC demonstrated human and mouse IAPP amide in the pancreas. Electron microscopy showed the accumulation of fibril-like material in a considerable number of beta-secretory granules. These results suggest that in transgenic mice, the human IAPP precursor is expressed in beta cells and becomes normally sorted into beta-secretory granules in which normal conversion to mature human IAPP takes place. The human IAPP molecules, because of their amyloidogenesis, aggregate into amyloid fibrils in secretory granules. Glucose tolerance was normal at 7 months old and islet amyloid was not observed. A longer time may be required for islet amyloid deposits and hyperglycemia to develop in mice. Our working hypothesis is that in human NIDDM, IAPP aggregates into amyloid fibrils in beta-secretory granules, and that the fibrils are released into the extracellular space and islet amyloid deposits become substantial with time.

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.

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.

The pituitary mass after transsphenoidal hypophysectomy.

To understand the natural changes in the CT appearance of a pituitary mass after transsphenoidal hypophysectomy of a pituitary tumor, we obtained CT follow-up studies in 12 patients with pituitary adenoma. The heights of the pituitary masses on the coronal sections of each CT study were measured. It was found that the height of the pituitary mass did not return to normal immediately after the operation, despite complete removal of the pituitary tumor. Instead, the height gradually returned to normal between 3 and 4 months after the operation. Results of this study suggest that follow-up CT study of pituitary masses is best performed 3-4 months after transsphenoidal hypophysectomy.

Occlusion of arteriovenous malformations of the cavernous sinus via the superior ophthalmic vein.

The treatment of five patients with dural arteriovenous malformations (AVMs) of the cavernous sinus via the superior ophthalmic vein (SOV) is reported. The procedure was performed by transcutaneous puncture of the SOV under the guidance of real-time digital subtraction angiography. Complete resolution of the ocular symptoms was achieved in all cases. Angiograms after embolization showed complete obliteration of the malformation in four cases and partial obliteration in one. This method can cure dural AVMs of the cavernous sinus, with preservation of blood flow in the internal carotid artery. It is particularly indicated when the SOV is enlarged and when (1) dural AVMs of the cavernous sinus are fed by small branches of the internal carotid artery or direct carotid cavernous fistulas with small tears; (2) dural AVMs of the cavernous sinus are fed by multiple branches from both the internal and external carotid arteries, one or both sides; or (3) dural AVMs of the cavernous sinus or direct carotid cavernous fistulas recur after trapping of the internal carotid artery. Transcutaneous puncture and catheterization of the SOV was performed safely with the aid of digital subtraction angiography. The SOV approach was able to treat the fistula with preservation of the internal carotid artery.

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.

Microvascular decompression for hemifacial spasm: analyses of operative findings and results in 310 patients.

The operative findings and results of microvascular decompression (MVD) on 310 Chinese patients with hemifacial spasm are analyzed in this report. The operations were performed at the Neurological Institute of the Veterans General Hospital-Taipei between January 1983 and June 1990. The length of follow-up ranged from 6 months to 8 years (mean, 4.3 years); 273 patients (88%) had complete relief of spasm within 3 days after one MVD, and the remaining 37 patients (12%) showed no immediate postoperative improvement. Sixteen (5.2%) of these 37 initially unresponsive patients subsequently experienced complete relief, which occurred from 4 days to 22 months (median, 21 days) after one MVD; 13 others (4.2%) had complete relief immediately after the second MVD; another 3 (1%) had delayed complete relief 6, 9, and 11 months after the second MVD, respectively; and the remaining 5 (1.6%) only had delayed partial relief, which occurred 2 to 9 weeks after one MVD. Late recurrence occurred in three patients (1%). These immediate and long-term results lend support to the conclusion that the timing of reoperation can be postponed for a period of 3 to 4 weeks in the event of an initial failure to get improvement, and that a second MVD may be of value.

Spinal cord proliferative sparganosis in Taiwan: a case report.

A 43-year-old woman suffered from low back pain and bilateral footdrop. A cisternal myelogram unexpected revealed multiple filing defects in the spinal canal extending from the lower cervical region to the caudal equina. Diagnostic exploration revealed numerous cystic organisms adhering to the spinal cord and nerve roots. Histopathological examination showed these organisms to be proliferative sparganum cestode larvae. Although these cestode larval infections have been reported a dozen times in humans from various parts of the world, this is probably the first reported case of spinal cord infection.

Islet amyloid polypeptide and its N-terminal and C-terminal flanking peptides' immunoreactivity in islet amyloid of diabetic patients.

We determined immunohistochemically whether the islet amyloid polypeptide (IAPP)/amylin precursor is one component of islet amyloid, using polyclonal antibodies specific for human IAPP8-17 and amino (N)-terminal and carboxy (C)-terminal flanking peptides. To enhance immunostaining of the amyloid, we pretreated the pancreatic tissue sections with 100% formic acid. In three non-diabetic subjects, pancreatic islet cells were immunoreactive to anti-IAPP8-17 and anti-N-terminal and C-terminal flanking peptide antibodies and the reactivity was enhanced with formic acid pretreatment. In six type 2 diabetic subjects and a subject with type A insulin resistance, islet amyloid deposits were reactive to anti-IAPP8-17 antibody, but not to anti-N-terminal and C-terminal flanking peptide antibodies. Formic acid pretreatment markedly enhanced the reactivity to anti-IAPP8-17 antibody; however, it failed to show the reactivity to anti-N-terminal and C-terminal flanking peptide antibodies. Formic acid pretreatment of pancreatic tissue sections prepared for immunostaining is useful for visualization of buried epitopes of mature IAPP and its precursor molecules, either in islet amyloid deposits or in the islet cells. We conclude that the IAPP precursor and N-terminal and C-terminal flanking peptides are not constituents of human islet amyloid.

Parathyroid carcinoma in a patient with non-secretory pituitary tumor: a variant of multiple endocrine neoplasia type-I?

We report a case of pituitary adenoma in association with parathyroid carcinoma as an unusual combination of multiple endocrine neoplasia (MEN). A 48-year-old man had a trans-sphenoidal hypophysectomy and transcranial partial removal of a recurrent pituitary chromophobe adenoma followed by a course of radiotherapy in 1980. Four years later, he developed hypercalcemic crisis from a parathyroid carcinoma with invasion to the adjacent thyroid gland and skeletal muscle. A hemithyroidectomy and resection of the left lower parathyroid gland was performed. Three years later, he had local recurrence and anterior chest wall metastasis accompanied by hypercalcemia. After resection of the remnant and metastatic lesion, eucalcemia was achieved. There was no family history of endocrine tumors. This case illustrates the rare association of a malignant parathyroid tumor and a chromophobe adenoma of the pituitary as a variant of MEN syndrome.

Effect of acute administration of 2,5-hexanedione on nociception in rats.

Hexacarbon compounds are neurotoxic to man and animals. These substances also inhibit various enzymes in vitro, including acetylcholinesterase. Since some cholinesterase inhibitors alter nociception we determined the effect of acute ip administration of 2,5-hexanedione on nociception in female Wistar rats (75-90 days old, 170-200 g; 15-17 rats in each group) using a tail-flick apparatus. The rats were injected ip with vehicle solution (120 mM NaCl containing 10 mM potassium phosphate buffer, pH 7.2) and 200, 400 or 800 mg/kg of 2,5-hexanedione in a volume of 1 ml/kg body weight. Tail-flick latencies were obtained 10, 30, 60 and 90 min after drug administration. All doses of 2,5-hexanedione caused antinociception (P less than 0.001) but the appearance and duration of the analgesia varied according to the dose of the drug. The highest dose tested (800 mg/kg) caused analgesia from 10 to 60 min, 400 mg/kg caused analgesia at 30 and 60 min, and 200 mg/kg produced antinociception only at 60 min after drug injection (P less than 0.05 for all the above comparisons). These results suggest that 2,5-hexanedione induces antinociception in rats. Whether this effect is mediated by a cholinergic mechanism is under investigation.

Long-term treatment with 2,5-hexanedione has no effect on the specific activity of some brain and liver glycolytic enzymes of adult rats.

Prolonged exposure to hexacarbon compounds is neurotoxic to humans and animals. As various hexacarbon compounds inhibit glycolytic enzymes in vitro, it has been suggested that this may underlie their neurotoxic effects in vivo. In the present investigation we examined whether long-term treatment with 2,5-hexanedione (200 mg/kg,sc) for 40 days affects the specific activity of brain and liver enolase, lactic dehydrogenase and malate dehydrogenase in female Wistar rats (150-170 g). Glycemia and liver glycogen levels were also determined. The specific activity of all enzymes tested, liver glycogen content and glycemia were not affected by chronic treatment with 2,5-hexanedione. Rats treated with 2,5-hexanedione weighed significantly less than control rats starting on day 18 of treatment (183 +/- 3.4 g for the vehicle group vs 171 +/- 3.2 g for the 2,5-hexanedione group). 2,5-Hexanedione also increased water intake (46% when compared to vehicle-treated rats). Prolonged treatment of rats with the non-neurotoxic hexacarbon 1,6-hexanediol (207 mg/kg, sc) significantly increased liver glycogen content (5.9 +/- 0.6 g/100 g for the vehicle group vs 9.0 +/- 1.1 g/100 g for the 1,6-hexanediol group) as well as food intake (44.0 +/- 1.5 g 100 g-1 6 days-1 for the vehicle vs 50.0 +/- 1.1 g 100 g-1 6 days-1 for the 1,6-hexanediol group).(ABSTRACT TRUNCATED AT 250 WORDS)