The important role of the gut in initiating the hyperdynamic response during early sepsis

BACKGROUND: Although the initial response to sepsis includes a hyperdynamic phase and although the increased hepatic perfusion in early sepsis is due solely to the increased portal blood flow, it remains unknown whether the gut plays an important role in producing such a response. MATERIALS AND METHODS: Adult male Sprague-Dawley rats underwent a complete enterectomy (ER) before being subjected to sepsis by cecal ligation and puncture (CLP; the cecum was excised from the removed gut and stitched to the posterior peritoneum in ER groups) or sham operation. At 2 h after CLP (i.e., the early, hyperdynamic phase of sepsis), cardiac output and heart performance (+/-dP/dt(max)), as well as hepatic and renal blood flow, were measured. Systemic and regional oxygen delivery (DO(2)) and oxygen consumption (VO(2)) were also determined. RESULTS: Cardiac output, heart performance, organ blood flow, as well as DO(2) and VO(2), increased significantly 2 h after CLP. ER prior to the onset of sepsis, however, prevented the elevation of those parameters. ER in sham animals did not alter the measured parameters with the exception that portal blood flow decreased by 85% and hepatic arterial blood flow increased by 368%, resulting in no significant reduction in hepatic DO(2) and VO(2). There were no changes in circulating blood volume among groups, indicating that the effect of ER on hemodynamics after CLP was not due to alterations in blood volume. CONCLUSION: Since ER immediately before the onset of sepsis prevents the increase in cardiac output and regional hemodynamics, the gut appears to play an important role in producing the hyperdynamic response during the early stage of polymicrobial sepsis.     

Value of lying-down nystagmus in the lateralization of horizontal semicircular canal benign paroxysmal positional vertigo.

BACKGROUND: Horizontal canal benign paroxysmal positional vertigo is characterized by horizontal direction-changing nystagmus induced by lateral head turning in supine position. According to Ewald's second law, the direction of head turning that creates a stronger response represents the affected side in geotropic nystagmus and the healthy side in apogeotropic nystagmus. However, it may not always be possible to lateralize the involved ear only by comparing the intensity of the nystagmus. We studied the values of nystagmus induced by position change from sitting to supine in the lateralization of horizontal canal benign paroxysmal positional vertigo. METHODS: A retrospective study of 54 patients who had been diagnosed as having horizontal canal benign paroxysmal positional vertigo at the Dizziness Clinic of Seoul National University Bundang Hospital from May 2003 to February 2004 was performed. The directions of the nystagmus induced by lying down were compared with those determined by Ewald's second law. RESULTS: Of the 54 patients, 32 (20 apogeotropic and 12 geotropic) showed horizontal nystagmus induced by lying down. The nystagmus tended to be ipsilesional in apogeotropic patients (80%) and contralesional in their geotropic counterparts (75%). CONCLUSION: In horizontal canal benign paroxysmal positional vertigo, lying-down nystagmus mostly beats toward the involved ear in the apogeotropic type and directs to the healthy ear in the geotropic type. The direction of lying-down nystagmus may help lateralizing the involved ear in horizontal canal benign paroxysmal positional vertigo.     

What constitutes a true hyperdense middle cerebral artery sign?

OBJECTIVES: The 'hyperdense MCA sign' refers to an appearance of increased attenuation of the proximal middle cerebral artery (MCA) that is often associated with thrombosis of the M1 MCA segment and may be the only diagnostic feature on computed tomography early after ischaemic stroke. False positives are recognized, and correct recognition of this sign has, therefore, assumed greater importance with the advent of thrombolytic therapy for stroke. We sought to define objective criteria for hyperdensity of the MCA. METHODS: Brain computed tomographs obtained by a standard protocol in a neuroradiology department were analyzed by a single observer. All consecutive scans reported as exhibiting a hyperdense MCA were compared to controls reported as having normal scans. Ovoid regions of interest were placed over the vessels and cerebral cortices, and the attenuation in Hounsfield units (HU) measured. Absolute attenuation and ratios of one side to the other were compared. RESULTS: MCA attenuation was unrelated to age in cases (n = 18) and controls (n = 80). The mean MCA attenuation was greater in the affected MCA of cases as compared with controls [54.0 HU (99% confidence interval CI 46.7-61.2) vs. 41.3 HU (99% CI 39.7-43.0); p < 0.00001]. Cases were subdivided into true and false positives by the ratio of denser:less dense MCA (within or without the 95% prediction interval for controls). In all true positives, the MCA ratio was > 1.2. 9 of 10 true positives had acute ischaemic stroke; 1 patient had herpes simplex encephalitis, but had MCA attenuation within the 95% CI for controls. False positives had mature cerebral infarction or non-ischaemic pathologies. The ratio of MCA attenuation to adjacent cerebral cortex was significantly higher in both true and false positives than in controls. CONCLUSIONS: Hyperdense MCAs associated with acute ischaemic stroke can be distinguished from normal vessels and false positives by measurement of absolute attenuation of affected and normal vessels: an absolute density of >43 HU and a MCA ratio of >1.2 defined hyperdensity and excluded all other pathologies. Confirmation in other centres is required.     

Population genetics of the hypervariable locus D12S391 in Koreans

The hypervariable short tandem repeat (STR) locus D12S391 was investigated in a Korean population and 34 fragments were sequenced to confirm the structure of alleles. From these sequenced fragments an allelic ladder containing 13 sequenced alleles was constructed. From 595 unrelated Koreans, 14 alleles were detected and one variant allele 19.3 was observed. The observed heterozygosity was 0.795 and no deviation from Hardy-Weinberg equilibrium was observed in the Korean population (p = 0.606). The allele frequency distribution in the Korean population was not similar to other racial or ethnic groups except for Egyptians, Yemenis, Japanese and Caucasoids from the Rhine area. No mutations were observed in the 702 meioses from 144 Korean families. This study demonstrates that the STR locus D12S391 is a useful tool for forensic identification and parentage testing. Received: 15 September 1999 / Accepted: 18 December 1999     

The ‘natural’ body,God and contraceptive use in the southeastern United States

Data collected among African‐American and Caucasian women and men in the southeastern USA indicate that participants' perceptions of nature, God's will and the human body influence reproductive health and decision‐making. Attitudes about the health care system, pharmaceutical companies and government programmes for fertility regulation reinforce these views and may negatively affect willingness to use contraceptive methods consistently and correctly.     

The expression of metabolism-related proteins in phyllodes tumors

The purpose of this study was to investigate the association between the expression of hypoxia-inducible factor (HIF)-1α, insulin-like growth factor (IGF)-1, glucose transporter 1 (Glut-1), carbonic anhydrase IX (CAIX), and monocarboxylate transporter (MCT)4, which are metabolism-related proteins in phyllodes tumors (PTs), and clinicopathologic factors and its implication. We used tissue microarrays to analyze 207 PTs and performed immunohistochemical staining against the glycolysis-related molecules HIF-1α, IGF-1, Glut-1, CAIX, and MCT4. We then compared the immunohistochemical results and clinicopathologic parameters. The expressions of HIF-1α, Glut-1, CAIX, and MCT4 in the stromal component of PTs increased (P?=?0.019, P?<?0.001, P?=?0.045, and P?<?0.001, respectively) with increasing tumor grade. According to univariate analysis, factors associated with shorter disease-free survival were Glut-1 expression (P?=?0.001) and MCT4 expression (P?<?0.001) in the stromal component, and the factors associated with shorter overall survival were IGF-1 expression (P?=?0.012), Glut-1 expression (P?<?0.001), CAIX expression (P?=?0.039), and MCT4 expression (P?<?0.001) in the stromal component. Our investigation of stromal expression of the metabolism-related proteins HIF-1α, IGF-1, Glut-1, CAIX, and MCT4 revealed that, as the PT grade increased, the stromal expression of HIF-1α, Glut-1, CAIX, and MCT4 significantly increased. This result suggested that increasing PT grade is associated with increased glycolysis in the stromal component.     

ΔFosB Induction in Prefrontal Cortex by Antipsychotic Drugs is Associated with Negative Behavioral Outcomes

ΔFosB, a FosB gene product, is induced in the prefrontal cortex (PFC) by repeated exposure to several stimuli including antipsychotic drugs such as haloperidol. However, the functional consequences of increased ΔFosB expression following antipsychotic treatment have not been explored. Here, we assessed whether ΔFosB induction by haloperidol mediates the positive or negative consequences or clinical-related actions of antipsychotic treatment. We show that individuals with schizophrenia who were medicated with antipsychotic drugs at their time of death display increased ΔFosB levels in the PFC, an effect that is replicated in rats treated chronically with haloperidol. In contrast, individuals with schizophrenia who were medication-free did not exhibit this effect. Viral-mediated overexpression of ΔFosB in the PFC of rodents induced cognitive deficits as measured by inhibitory avoidance, increased startle responses in prepulse inhibition tasks, and increased MK-801-induced anxiety-like behaviors. Together, these results suggest that ΔFosB induction in the PFC by antipsychotic treatment contributes to the deleterious effects of these drugs and not to their therapeutic actions.