Measurement of pitch perception as a function of cochlear implant electrode and its effect on speech perception with different frequency allocations.

OBJECTIVE: An experiment was conducted to investigate the possibility that speech perception could be improved for some cochlear implant (CI) users by adjustment of the frequency allocation to the electrodes, following assessment of pitch perception along the electrode array. STUDY SAMPLE: Thirteen adult CI users with MED-EL devices participated in the study. DESIGN: Pitch perception was assessed for individual CI electrode pairs using the Pitch Contour Test (PCT), giving information on pitch discrimination and pitch ranking for adjacent electrodes. Sentence perception in noise was also assessed with ten different frequency allocations, including the default. RESULTS: Pitch perception was found to be poorer for both discrimination and ranking scores at either end of the electrode array. A significant effect of frequency allocation was found for sentence scores [F(4.24,38.2) = 7.14, p < 0.001] and a significant interaction between sentence score and PCT ranking score for basal electrodes was found [F(4.24,38.2) = 2.95, p = 0.03]. Participants with poorer pitch perception at the basal end had poorer scores for some allocations with greater basal shift. CONCLUSIONS: The results suggest that speech perception could be improved for CI users by assessment of pitch perception using the PCT and subsequent adjustment of pitch-related stimulation parameters.

Point of care optical diagnostic technologies for the detection of oral and oropharyngeal squamous cell carcinoma.

BACKGROUND: Despite significant advances in treatment modalities, the 5 year survival rate in oral and oropharyngeal squamous cell carcinoma (SCC) is less than 60%. Clinical examination, white light endoscopy followed by blind biopsies and histopathological analysis remains the gold standard for diagnosis and surveillance. These modalities continue to have a limited diagnostic accuracy of less than 55%. METHODS: Novel optical-based diagnostic methods are promising new technologies for improving both screening and detection of cancer. This review will discuss their role in oral and oropharyngeal cancer detection with particular emphasis on optical imaging in oral and oropharyngeal cancer diagnosis, including the use of surface enhanced Raman spectroscopy, optical coherence tomography, fluorescence diagnosis, confocal laser endomicroscopy, confocal reflectance microscopy and narrow band imaging. RESULTS: Aided by the use of differing wavelengths of light, these methods are capable of detecting physical and biochemical changes that precede and mirror malignant change within tissue. CONCLUSION: Our review of the currently utilized optical diagnostic modalities suggests the possibility of a cost effective, point of care diagnosis that could facilitate early detection, reduce healthcare costs and improve patient survival and quality of life.

betaA- and betaC-activin, follistatin, activin receptor mRNA and betaC-activin peptide expression during rat liver regeneration.

The mRNA expression of two activin growth factor subunits (betaA- and betaC-activin), activin receptor subunits (ActRIIA, ActRIIB) and the activin-binding protein follistatin, and peptide expression of betaA-activin and betaC-activin subunits, were examined in regenerating rat liver after partial hepatectomy (PHx). Liver samples were collected from adult, male Sprague-Dawley rats, 12-240 h (n=3-5 rats per time point) after PHx or from sham-operated controls at the same time points. Hepatocyte mitosis and apoptosis were assessed histologically and by in situ cell death detection. RT and PCR were used to assess relative gene expression. betaA- and betaC-activin peptide immunoreactivity was assessed in liver and serum samples by western blotting, whereas cellular expression was investigated by immunohistochemistry, using specific monoclonal antibodies. betaA- and betaC-activin mRNA dropped to < 50% of sham control values 12 h after PHx and remained at this level until 168 h post-PHx, when betaA-activin expression increased to three times sham control values and betaC-activin mRNA returned to pre-PHx levels. A peak in follistatin expression was observed 24-48 h post-PHx, coincident with an increase in hepatocyte mitosis. No changes were observed in ActRIIA mRNA, whereas ActRIIB expression paralleled that of betaA-activin mRNA. betaC-activin immunoreactive homo- and heterodimers were observed in regenerating liver and serum. Mitotic hepatocytes frequently contained betaC-activin immunoreactivity, whereas apoptotic hepatocytes were often immunoreactive for betaA-activin. We conclude that betaA- and betaC-activin subunit proteins are autocrine growth regulators in regenerating liver and when expressed independently lead to hepatocyte apoptosis or mitosis in a subset of hepatocytes.

Successful hepatic grafting after partial portal vein ligation in the rat: complete reversal of hemodynamic abnormalities.

BACKGROUND: Partial portal vein ligation (PPVL) is an established approach in the study of prehepatic portal hypertension in animals. The effect of orthotopic liver transplants (OLT) on hemodynamics in PPVL animals has not been investigated to date. The aim of this study was to develop a model of OLT in PPVL rats and to investigate its hemodynamic consequences. METHODS: Three groups of male Lewis rats were investigated (1) control animals (n=7), (2) PPVL (n=9), and (3) PPVL/OLT (n=16). Three weeks after PPVL, 9 animals were taken for hemodynamic measurements. OLT was performed in the remaining 16 PPVL rats (PPVL/OLT), and, 4 weeks later, hemodynamic measurements were made. Blood biochemical analysis was performed at different time points in all 3 groups. RESULTS: The PPVL animals presented with hyperdynamic systemic circulation, extensive collateral vascularization in the hilar region, and portal-systemic shunting (portal systemic shunting; 35.3+/-5.5%). In the PPVL/OLT group, 15 rats survived for 4 weeks (survival: 93.8%, 15 of 16). Of these PPVL/OLT rats, 3 died during the blood sampling protocol. In 3 PPVL/OLT rats, abnormal liver function and histology were found and deranged systemic and hepatic hemodynamics persisted after OLT. In the remaining 9 PPVL/OLT rats, systemic and hepatic hemodynamics had returned to normal at 4 weeks and portal systemic shunting was markedly reduced (2.5+/-0.9%). Liver function was in the normal range. CONCLUSIONS: (1) The possibility of performing OLT in PPVL rats with a high rate of survival has been confirmed. (2) In the majority of cases, complete reversal of hemodynamic abnormalities in the PPVL animals occurs after OLT (3). PPVL/OLT represents a new and important model in OLT research.

Endotelin ETA and ETB receptor antagonism during cold preservation in renal transplantation.

BACKGROUND: In this study, we investigated the effects of selective endothelin (ET) receptor antagonism during different periods of cold ischemia on glomerular and tubular function and long-term survival in renal transplantation. METHODS: Left renal transplantation was performed in Lewis rats after 2 hr of cold ischemia without (n=8) and with (n=6) ETA receptor antagonism and after 16 hr of cold ischemia without treatment (n=6), with ETA receptor antagonism (n=8) and with ETB receptor antagonism (n=6). A control group (n=8) underwent right nephrectomy and left renal denervation. The ETA and ETB receptor antagonists (BQ-610 and A-192621, respectively) were added to the preservation solution (EuroCollins). After transplantation, renal glomerular and tubular functions were monitored for up to 60 days or death. RESULTS: All animals in the control and 2-hr groups survived the follow-up protocol, with early postoperative recovery of glomerular and tubular function while the entire untreated 16-hr group died between day 3-6 postoperatively. BQ-610 treatment had no measurable effect on the renal function in the 2-hr group, however, it improved glomerular and tubular functions and led to 50% long-term survival (60 days) in the 16-hr group. A-192621 treatment had no effect on long-term survival or renal parameters. CONCLUSION: ETA receptor antagonism had protective renal effects after prolonged ischemic preservation in renal transplantation while ETB receptor antagonism had not.

Effect of ischemia-reperfusion injury on the microcirculation of the steatotic liver of the Zucker rat.

BACKGROUND: Much discussion has been focused on the use of steatotic livers for transplantation due to the prevalence of steatosis in the potential donor liver pool (1). The aim of this study was to investigate the possibility that the microcirculation of steatotic liver is more sensitive to the ischemia-reperfusion (IR) injury than normal liver. METHODS: The left liver lobe of obese (n=9) and lean Zucker rats (n=9) were subjected to 40 min of warm ischemia followed by 60 min of reperfusion. Fluorescent probes rhodamine 123 (Rh123), bisbenzimide (Bis), and rhodamine 6G (Rh6G) were administered for the identification by intravital fluorescence microscopy (IVFM) of mitochondrial membrane potential, hepatocyte nuclei and leukocytes, respectively before hepatic ischemia and at 15, 30, 45, and 60 min after reperfusion. Blood samples were obtained before and after 60 min of reperfusion. Liver tissue was taken at the end of experiment for histological analysis. RESULTS: The liver of the obese rats showed prominent macro- and microvesicular fatty changes (MAFC and MIFC) and hepatocyte swelling. Under IVFM, the obese animals had significantly wider hepatic cords (23.1+/-0.8 microm) than the lean ones (15.9+/-0.5 microm) (P<0.01), whereas no significant difference in sinusoidal diameters was noted. The number of functional sinusoids significantly decreased after 30 min of reperfusion in both groups but no significant change was noted in the nucleus count throughout the experiment. Rh123 fluorescence intensity dropped significantly in the obese group after 60 min of reperfusion but not in the lean rats. Leukocyte adherence showed a significant rise after reperfusion in both groups. Plasma AST and ALT levels were 40- and 24-fold higher respectively for the obese animals after IR compared with their preischemic values, whereas the corresponding increase were 4.2- and 3.4-fold for the lean animals, respectively. CONCLUSIONS: Our results indicate that the liver of the obese Zucker rat is steatotic and presents with an abnormal microcirculation manifested by a reduced sinusoidal density. IR led to significantly greater hepatic injury in the steatotic than in the normal liver. This injury was accompanied by a significant reduction in the functional sinusoidal density and mitochondrial membrane potential as assessed by Rh123-associated fluorescence in the steatotic liver. In conclusion, the increased sensitivity of the steatotic liver to IR injury would appear to involve both alterations in blood flow in the microcirculation and to cellular changes.

Effect of orthotopic liver transplantation and chemical denervation of the liver on the activities of hepatic monoamine oxidase and catechol-O-methyltransferase.

The denervation of some tissue is associated with a fall in the activities of monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). Here we report on the effect of orthotopic liver transplantation and chemical denervation of the liver on the enzymes. Liver transplantation was performed on Lewis rats (n = 7). Denervation (n = 8) was by intraportal injection of 6-hydroxydopamine (75 mg/kg). A control group (n = 8) was also included. The norepinephrine content of the transplanted and denervated livers was reduced by greater than 99% (P < 0.001) and 95% (P < 0.001), respectively. The activity of hepatic COMT (substrate: catechol [5 mM] was not affected by transplantation or denervation. The activity of MAO with 0.1 mM 5-hydroxytryptamine (5-HT) (substrate for MAO-A) and with 0.01 mM 2-phenylethylamine (substrate for MAO-B) were not affected by denervation. In the transplanted liver, the activity of MAO with 5-HT and 2-phenylethylamine was increased by 26% (P < 0.05) and by 53% (P < 0.001), respectively. The ratios of the activities of the A to B forms of MAO (approximately 70% A to 30% B) was not affected by either procedure. Enzyme sensitivity for MAO inhibitors clorgyline and deprenyl were not significantly altered by transplantation. The concentration of plasma norepinephrine in the transplantation group was significantly lower than either the control (P < 0.001) or denervation groups (P < 0.05). We conclude from our results that the metabolism of circulating catecholamines by the liver is unlikely to be impaired after liver transplantation.

Randomized trial of duodenum-preserving pancreatic head resection versus pylorus-preserving Whipple in chronic pancreatitis.

BACKGROUND: In about 30% of patients, chronic pancreatitis leads to an inflammatory enlargement of the pancreatic head with subsequent obstruction of the pancreatic duct, common bile duct, and duodenum. METHODS: In a prospective, randomized controlled trial, we compared duodenum-preserving pancreatic head resection (DPPHR) with pylorus-preserving Whipple (PPW) operation to define the advantages of each operation with regard to (1) postoperative complications, (2) glucose tolerance and induction of diabetes mellitus, and (3) postoperative pain and quality of life up to 6 months after operation for chronic pancreatitis. RESULTS: The two study groups of 20 patients were both well balanced with regard to sex, age, history of chronic pancreatitis, and indication for surgery. Postoperative mortality was zero. After duodenum-preserving and pylorus-preserving resection, morbidity was 15% and 20%, respectively. After 6 months, patients who underwent the duodenum-preserving resection had less pain, greater weight gain, a better glucose tolerance, and a higher insulin secretion capacity. CONCLUSION: The DPPHR compares favorably with the standard PPW operation and should be considered as an alternative procedure in the treatment of chronic pancreatitis.

The effect of anaesthetics on the concentration of creatine phosphate, adenosine triphosphate and lactate in brain and skeletal muscle of the rat.

Rats were anaesthetized with ten anaesthetics. Ketamine and enflurane gave the lowest concentration of creatine phosphate and ATP and the highest of lactate in brain, while giving the highest concentration of the high-energy phosphates and the lowest of lactate in skeletal muscle. In general, intraperitoneally-administered anaesthetics gave higher concentrations of creatine phosphate and ATP and lower concentrations of lactate in brain than did the inhalant anaesthetics. The most rapid induction of anaesthesia was achieved with halothane and enflurane, while ketamine gave variable induction times and poor analgesia. Halothane stimulated glycolysis and lowered the concentrations of high-energy phosphates in skeletal muscle.

Redistribution of portal venous but not hepatic arterial flow is induced by hepatic nerve stimulation in the perfused rat liver.

The effects of hepatic nerve stimulation, norepinephrine and 6-hydroxydopamine (6-OHDA) on hepatic hemodynamics were investigated in rat livers perfused in situ via both the portal vein and hepatic artery. Nerve stimulation caused a significant fall in total liver blood flow and an increase in portal and arterial pressures. Norepinephrine and 6-OHDA in addition to causing a fall in flow caused significant pressure increases in the bed perfused (arterial or portal). Under basal conditions, the inter- and intra-lobar distribution of microspheres (113Sn- or 57Co-labelled) introduced via the portal vein or via the hepatic artery was homogeneous in all 6 liver lobes. During nerve stimulation, homogeneity of interlobular microsphere distribution was maintained. However, the intralobar distribution of microspheres introduced via the portal vein displayed a significant redistribution from the periphery to the core of each of the four largest lobes studied (p < 0.05). In contrast, when microspheres were introduced via the hepatic artery, there was no universal redistribution of microspheres with only one lobe demonstrating a significant decrease in flow to the periphery (p > 0.05). Infusion of norepinephrine (10(-8) M) or 6-OHDA (1 mg.kg-1 body weight) via either the hepatic artery or the portal vein was without effect on the intrahepatic distribution of the microspheres. We conclude from our results that during hepatic nerve stimulation there is a significant redistribution of portal venous but not hepatic arterial flow from the periphery to the core of the liver lobe. The persistence of hepatic arterial flow during nerve stimulation may represent a protective mechanism by which the periphery of the liver, especially the bile ducts, remains perfused during a reduction in total liver blood flow.

Bosentan normalizes the GFR response to renal nerve stimulation following reversible unilateral ureteric obstruction in the rat.

We investigated the renal response to direct renal nerve stimulation, 2 weeks following reversal of 24-h unilateral (left) ureteric obstruction. Renal nerve stimulation caused a 13-15 % fall in renal blood flow, in 4 groups of anesthetized rats following ureteric obstruction (n=9) or a sham operation (n=7) both with (n=9) and without (n=7) treatment with the mixed ET(A/B) receptor antagonist, bosentan. In the sham-operated rats, renal nerve stimulation did not change glomerular filtration rate but reduced urine flow rate (37+/-3 %, P<0.001), and absolute (38+/-4 %, P<0.001) and fractional (35+/-5 %, P<0.01) sodium excretion. Following unilateral ureteric obstruction, renal nerve stimulation increased glomerular filtration rate by 22+/-3 % (P<0.01), but reduced urine flow rate (14+/-2 %, P<0.001) and fractional sodium excretion (23+/-5 %, P<0.01). Bosentan treatment had no effect on baseline or renal responses to renal nerve stimulation in the sham group but normalized the renal response to renal nerve stimulation in the unilateral ureteric obstruction group. We conclude that 14 days after a 24-h period of unilateral ureteric obstruction there is an increase in GFR in response to direct renal nerve stimulation, which is due, in part, to the actions of endothelin at the time of obstruction.

Effect of hepatic nerve stimulation and norepinephrine on the laser Doppler flux signal from the surface of the perfused rat liver.

The effect of hepatic nerve stimulation and norepinephrine (NE) on the laser Doppler signal from the surface of the perfused rat liver was tested. The livers from male Wistar rats were perfused in situ via the portal vein with Krebs-Henseleit buffer containing 20% bovine erythrocytes (37 degrees C, pH 7.4) and total liver blood flow (TLBF) was by timed collection of effluent. Portal vascular resistance (PVR) was calculated from the pressure difference across the liver. Linearity of laser Doppler flowmetry (LDF) with TLBF was confirmed in all preparations. Stimulation of the hepatic nerves (2 ms, 20 V) was performed at frequencies between 0.5 and 20 Hz (n = 11). NE was added to the buffer at concentrations between 10(-10) and 10(-6) M (n = 8). A stimulus-dependent rise in PVR occurred during hepatic nerve stimulation (basal, 3.11 +/- 0.26 dyn s cm-5) and NE administration (basal, 2.62 +/- 0.29 dyn s cm-5), with a maximum effect at 20 Hz (311 +/- 45%) and 10(-6) M (591 +/- 72%), respectively. Both LDF and TLBF fell during nerve stimulation and NE. A linear relationship (r = 0.99; p < 0.001) between change in TLBF (%) and LDF flux (%) was found for NE (10(-10) to 10(-6) M). During nerve stimulation, the fall in TLBF and LDF flux was linear with the logarithm of stimulus frequency and reached a maximum at 10 and 20 Hz, respectively. At a stimulus frequency of 20 Hz, the change in LDF was significantly different from the change in TLBF (p < 0.001). We conclude from our findings that during high-frequency hepatic nerve stimulation, LDF underestimates TLBF.

Measurement of hepatic perfusion in rats by laser Doppler flowmetry.

Little is known about the performance of the laser Doppler flowmeter (LDF) with changes in flow characteristics in the hepatic microcirculation. Red blood cell (RBC) flux, as measured by LDF, is sensitive to alterations in RBC velocity and RBC concentration, and both parameters must be considered when evaluating the technique. In vitro, linearity of LDF signal with RBC velocity up to 4 mm/s (r greater than 0.99) and RBC volume fractions up to 1.5% were demonstrated (r greater than 0.98). At higher velocities and volume fractions, RBC flux was underestimated. In portally perfused rat liver, LDF output was linearly related to total liver blood flow (TLBF; r greater than 0.9) for perfusate hematocrits between 2.5 and 40%, although the slope varied between preparations. At constant TLBF (2 ml.min-1.g-1), the LDF output changed linearly with perfusate hematocrit up to 20% (r greater than 0.99) but underestimated the increase at 40%. These results suggest that the LDF responds linearly to velocity-mediated flow changes but that it may underestimate a change if mediated through alteration in tissue RBC concentration. With hepatic nerve stimulation, TLBF fell to 51 +/- 14% of prestimulation (P less than 0.001), whereas the LDF output and superficial flow measured by 85Kr clearance fell to 12 +/- 10 and 14 +/- 10% (both P less than 0.01 vs. TLBF), respectively, suggesting that the LDF may be used to follow rapid flow changes in the periphery of the liver.

Application of a new sleeve anastomosis technique to graft rearterialization in rat liver transplantation.

A new rearterialized orthotopic liver transplant (OLT) model in the rat is described. The model involved performing a novel sleeve anastomosis technique for graft rearterialization which consisted of three extraluminal suture anastomoses between the recipient's proper and the donor's common hepatic artery. The total surgical time and in particular the time required to perform the arterial anastomosis was significantly reduced with the utilization of this technique. Hepatic artery patency was 100% and the 4-week survival rate was greater than 90%. Applying this novel sleeve anastomosis technique not only simplifies the rearterialized rat OLT but also ensures that blood flow to all vascular beds is undisturbed.

The effect of external calcium concentration on the negative inotropic action of dantrolene in isolated hyperthyroid and euthyroid heart.

The effect of altering external calcium concentration [Ca2+]o on the negative inotropic action of dantrolene was tested in Langendorff-perfused hearts from euthyroid and hyperthyroid rats. Elevated contractility was demonstrated in the hyperthyroid hearts at all the [Ca2+]o tested. At a [Ca2+]o of 1.25 mM (physiological), dantrolene (5 x 10(-5) M) significantly reduced contractility (dP/dtmax) in hyperthyroid but not in euthyroid hearts (-42% and -4% of zero-time values at 12 min perfusion, respectively). When hearts from both groups were paced at 375 beats/min, dantrolene again exerted a greater negative inotropic action in the hyperthyroid preparations, showing that the effect was not heart rate related. Elevating the [Ca2+]o did not further affect the time course of dantrolene action in hyperthyroid hearts. In euthyroid hearts, however, raising the [Ca2+]o to 2.5 and 3.75 mM caused a progressive increase in the negative inotropic action of dantrolene (-15% and -56% of zero-time values at 12 min perfusion, respectively). Our results demonstrate that dantrolene exerts a negative inotropic action which at physiological [Ca2+]o is greater in the hyperthyroid than in the euthyroid heart thus indicating that calcium handling by the myocardium is altered in the hyperthyroid state. However, dantrolene action in the rat myocardium is more complex than was at first believed; as in euthyroid hearts, its negative inotropic action appears to be increased rather than reduced by increases in [Ca2+]o.

The effect of haloperidol, spiperone and dantrolene on the concentrations of creatine phosphate, ATP and lactate in brain and skeletal muscle of the rat during halothane anesthesia.

The concentrations of creatine phosphate, ATP and lactate were measured in the brain and skeletal muscle of rats under halothane anesthesia (1 to 2% in oxygen) and in animals either premedicated with haloperidol or spiperone (200 mg kg-1 and 2 mg kg-1) or treated with dantrolene (860 mg kg-1). Haloperidol and spiperone had no effect on ATP or lactate in skeletal muscle, but caused more than a 30% increase in the concentration of creatine phosphate (p less than 0.01). With dantrolene, an 80% increase in creatine phosphate (p less than 0.0001) and a significant decrease in lactate (p less than 0.0001) were found. Haloperidol caused a significant decrease in brain creatine phosphate concentration (p less than 0.05) while at a dosage of 2 mg kg-1, the ATP concentration was higher (p less than 0.05). Spiperone (2 mg kg-1) caused a 19% increase in creatine phosphate (p less than 0.005) as well as a significant decrease in lactate (p less than 0.005). Dantrolene had no significant effect on the concentration of any brain metabolite. Our results indicate that the effect of anesthetics on the concentration of energy metabolites in tissues can be influenced by drug treatment, which may have implications in the choice of an anesthetic regimen to be used in tissue harvesting.