Assessment of the cut-off value of quantitative liver-portal vein contrast ratio in the hepatobiliary phase of liver MRI.

AIM: To calculate the quantitative liver-portal vein contrast ratio (Q-LPC) cut-off value based on tumour detectability by using receiver operating characteristic (ROC) curves. MATERIALS AND METHODS: Seventy-four patients with tumours (46 men and 28 women; age, 71 ± 8.1 years), who underwent liver magnetic resonance imaging (MRI) using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) were enrolled. Some patients were found to have multiple tumours. In total, 102 tumour images were evaluated for quantitative liver-spleen contrast ratio (Q-LSC) and Q-LPC 10 minutes after the administration of Gd-EOB-DTPA. Q-LPC and Q-LSC were compared to assess the cut-off values and usefulness. The ROC curve was evaluated using the method for continuously distributed test results, with a free scale of 50 mm. A score of ≥30 out of 50 points was considered good. Cut-off values of Q-LPC and Q-LSC were then calculated. The areas under the ROC curve (AUCs) were also examined and compared. RESULTS: The AUC-ROC for Q-LPC was 0.858 (95% confidence interval [CI], 0.783-0.933). The cut-off value was determined to be at 1.462. Sensitivity was 0.747, and specificity was 0.852 at the cut-off value. The AUC-ROC for Q-LSC was 0.710 (95% CI, 0.597-0.822). The cut-off value was at 1.543, the sensitivity was 0.560, and the specificity was 0.778 at the cut-off value. A significant difference was noted between the AUCs (p=0.0016). CONCLUSION: Q-LPC can be used for hepatobiliary phase MRI evaluation.

Observation of Spin-Dependent Charge Symmetry Breaking in ΛN Interaction: Gamma-Ray Spectroscopy of _{Λ}

The energy spacing between the spin-doublet bound state of _{Λ}^{4}He(1^{+},0^{+}) was determined to be 1406±2±2 keV, by measuring γ rays for the 1^{+}→0^{+} transition with a high efficiency germanium detector array in coincidence with the ^{4}He(K^{-},π^{-})_{Λ}^{4}He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus _{Λ}^{4}H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in ΛN interaction. By combining the energy spacings with the known ground-state binding energies, it is also found that the CSB effect is large in the 0^{+} ground state but is vanishingly small in the 1^{+} excited state, demonstrating that the ΛN CSB interaction has spin dependence.

Differences between primary care physicians and specialised neurotologists in the diagnosis of dizziness and vertigo in Japan.

OBJECTIVE: Vertigo and dizziness are frequent symptoms in patients at out-patient services. An accurate diagnosis for vertigo or dizziness is essential for symptom relief; however, it is often challenging. This study aimed to identify differences in diagnoses between primary-care physicians and specialised neurotologists. METHOD: In total, 217 patients were enrolled. To compare diagnoses, data was collected from the reference letters of primary-care physicians, medical questionnaires completed by patients and medical records. RESULTS: In total, 62.2 per cent and 29.5 per cent of the patients were referred by otorhinolaryngologists and internists, respectively. The cause of vertigo or dizziness and diagnosis was missing in 47.0 per cent of the reference letters. In addition, 67.3 per cent of the diagnoses by previous physicians differed from those reported by specialised neurotologists. CONCLUSION: To ensure patient satisfaction and high quality of life, an accurate diagnosis for vertigo or dizziness is required; therefore, methods or materials to improve the diagnostic accuracy are needed.

Exposure-Response Analysis for Efficacy of Daclatasvir, Asunaprevir, and Beclabuvir Combinations in HCV-Infected Patients.

The combination regimen of daclatasvir, asunaprevir, and beclabuvir (3DAA regimen) was developed as a fixed-dose combination for the treatment of hepatitis C virus (HCV) infection in Japan. The objectives of this analysis were to characterize the relationship between drug exposure and sustained virologic response at posttreatment week 12 (SVR12) in HCV-infected subjects and to evaluate the impact of demographic covariates and clinical factors on the exposure-response (E-R) relationship. The E-R efficacy analysis was performed with data from phase 2 and phase 3 studies in HCV-infected subjects treated with the 3DAA regimen. The relationship between the probability of achieving SVR12 and exposure to daclatasvir, asunaprevir, and beclabuvir was described using a logistic regression model and included assessments of the potential covariate effects. The impacts of the covariates on the rate of SVR12 and interactions of covariates with the individual drug effects were tested. The final model for SVR12 included effects of non-genotype-1a status, resistance-associated NS5A-Q30 substitution in genotype-1a subjects, and baseline RNA level on the intercept, and effect of prior peg-interferon failure on the beclabuvir slope. Sex, race, age, weight, fibrosis score, alanine transaminase, and cirrhosis status had no statistically significant impact on the rate of SVR12. The individual E-R relationships with each drug, were relatively flat, and the effects of exposure were not significant. With the exception of the NS5A-Q30 substitution in genotype-1a subjects, statistically significant covariate effects had little impact on SVR12 rates. Overall, the E-R model was developed that captured the high SVR12 rates and the effect of covariates for the 3DAA regimen in HCV-infected patients.

Comparison of myocardial blood flow during dobutamine-atropine infusion with that after dipyridamole administration in normal men.

OBJECTIVES: The present study was designed to compare the absolute myocardial blood flow (MBF) after intravenous dipyridamole infusion with that during dobutamine-atropine administration in normal healthy male volunteers. BACKGROUND: Both safety and usefulness of dobutamine-atropine stress in myocardial perfusion imaging have been reported. However, no information exists on whether the magnitude ofhyperemia achieved with dipyridamole and dobutamine-atropine is comparable. METHODS: Myocardial blood flow was measured with positron emission tomography and 15O-labeled water in 20 healthy young men (23 +/- 3 years) 1) at baseline, 2) after dipyridamole infusion (0.56 mg/kg over 4 min), and 3) during dobutamine (40 microg/kg/min) and atropine (0.25 to 1.0 mg) infusion. RESULTS: The MBF was significantly increased during dipyridamole infusion and during dobutamine-atropine stress compared with at rest (4.33 +/- 1.23 and 5.89 +/- 1.58 vs. 0.67 +/- 0.16 ml/min/g, respectively, p < 0.0001). Moreover, dobutamine-atropine infusion produced greater MBF compared with dipyridamole (p = 0.0011), while coronary vascular resistance did not differ significantly after dipyridamole administration and during dobutamine-atropine infusion (17.6 +/- 7.9 vs. 18.6 +/- 5.6 mm Hg/[ml/min/g], respectively). CONCLUSIONS: Near maximal coronary vasodilatation caused by dipyridamole is attainable using dobutamine and atropine in young healthy volunteers. Dobutamine in conjunction with atropine is no less effective than dipyridamole in producing myocardial hyperemia.

Interaction of alpha subunit of GTP-binding protein Go with a 20-kDa Triton-insoluble membrane protein in bovine brain.

Heterotrimeric Go bound to the membranes of bovine brain, but Go alpha remained bound to the membranes even after activation with GTP gamma S. Furthermore, Go alpha bound to a Triton X-100-insoluble fraction of the membranes in a saturable manner. However, the 37-kDa Go alpha eliminated by trypsin at the amino-terminus could not bind to the fraction. Using a blot overlay approach of the Triton-insoluble fraction, only a 20-kDa protein was identified that interacts with Go alpha. These results indicate that Go alpha binds to a 20-kDa Triton-insoluble protein in the bovine brain membranes.

Brain arteriolosclerosis and hemodynamic disturbance may induce leukoaraiosis.

OBJECTIVE: To investigate whether internal carotid artery (ICA) occlusive disease-induced hemodynamic disturbance is associated with extensive white matter high-intensity lesions (WMLs) on T2-weighted MR images in the hemisphere with lacunar infarct in the basal ganglia. BACKGROUND: Hemodynamic disturbance in the brain with arteriolosclerosis may be one of the mechanisms by which ischemic injury induces extensive WMLs. METHODS: The authors used MRI and PET to study 21 patients with unilateral ICA occlusion or stenosis and lacunar infarct in the bilateral basal ganglia. In hemispheres with ICA disease, the association of WMLs with the mean hemispheric values of oxygen extraction fraction (OEF)-an index of hemodynamic compromise-measured with the 15O-labeled gas steady-state technique was analyzed. Twenty-five patients with ICA occlusive disease without lacunar infarct were studied as control subjects. RESULTS: In the hemispheres with ICA disease, patients with lacunar infarct had a significantly greater severity of WMLs than control subjects, although the mean hemispheric values of the OEF showed no significant difference. The severity of WMLs correlated significantly with the mean hemispheric values of the OEF in patients with lacunar infarct, but not in control subjects. Multivariate analysis revealed that lacunar infarcts and increased OEF were independent predictors of extensive WMLs, with lacunar infarcts the most heavily weighted factor. CONCLUSION: Internal carotid artery occlusive disease-induced hemodynamic disturbance is associated with extensive WMLs in hemispheres with lacunar infarct. Hemodynamic disturbance may contribute to the development of extensive WMLs, although brain arteriolosclerosis may be a major contributing factor.

Noninvasive estimation of FDG input function for quantification of cerebral metabolic rate of glucose: optimization and multicenter evaluation.

UNLABELLED: The aims of this study were to determine whether body weight or body surface area (BSA) should be used for noninvasive measurement of the cerebral metabolic rate of glucose (CMRGlc) by FDG PET with a standardized input function (SIF) and an autoradiographic method and to validate the procedure in a large population from different PET centers. METHODS: Plasma input functions measured by intermittent arterial blood sampling after intravenous injection of FDG, in 101 patients from 1 institution who were fasting for at least 4 h, were used to generate the SIF. The SIF was generated by averaging over 101 patients the input function normalized with the net injected dose and initial distribution volume (DV) of FDG estimated by the formula c x Ha x Wb, where H is body height and W is body weight. To evaluate the estimation of DV by BSA or body weight, the coefficient of variation (CV) of the ratio of Ha x Wb to the measured DV was calculated by changing a and b independently. Estimation of the CMRGlc with SIF based on the formula for DV was validated with an additional 192 subjects from 3 institutions who underwent FDG PET while fasting. The result of simulation was compared with the results of 4 previously published formulas for BSA and body weight. RESULTS: The optimal set of parameters, in which a was 0.80 and b was 0.35, minimized the CV. The averaged percentage error of the CMRGlc based on the optimal set of parameters for DV estimation and SIF was 8.9% for gray matter and 10.6% for white matter. Four BSA formulas brought about a similar error, which was significantly smaller than that based on body weight (P < 0.001, ANOVA). CONCLUSION: Noninvasive estimation of CMRGlc is made possible by careful measurement of the net injected dose and BSA.

Delayed hemispheric neuronal loss in severely head-injured patients.

Recent experimental studies have revealed that traumatic brain injury as well as ischemic brain injury can cause chronic progressive neuronal damage. In the present study, we demonstrate previously unreported delayed cerebral atrophy on computerized tomography (CT) scans in severely head-injured patients. Seventeen severely head-injured patients who required mild hypothermia to control intracranial hypertension after the failure of conventional therapies were retrospectively analyzed. All 17 patients survived more than 1 year. Delayed neuronal loss (DNL) was observed in only eight of the 17 patients. Eight patients with DNL required longer durations of mild hypothermia to control intracranial hypertension than nine patients without DNL. Six of these eight patients with DNL achieved functional recovery despite progressive atrophic changes demonstrated on CT scans. On CT scans, DNL was characterized by (1) the sudden appearance at several months postinjury of a low-density area in the hemisphere ipsilateral to the injury; (2) the preservation of essential cortical structure although related white matter structures showed severe atrophic changes; and (3) no spread of the low-density area to the contiguous territory of the other main cerebral artery. It is concluded that focal primary injury to underlying brain, if severe enough, can result in delayed hemispheric atrophy.

Low oxygen extraction despite high oxygen delivery causes low oxygen consumption in patients with burns recovering slowly from operative hypothermia.

BACKGROUND: Patients with burns who eventually succumbed to their injuries tended to recover more slowly from operative hypothermia than those who survived. Slower recovery was associated with a lower postoperative oxygen consumption (VO2). We have now investigated whether this was due to impairment of oxygen delivery or extraction. METHODS: This study was performed in 13 adult patients with severely burns. One hundred four measurements of VO2 by indirect calorimetry were made during recovery from 23 episodes of operative hypothermia in 11 patients. Sixty-six measurements of oxygen transport variables by balloon-tipped pulmonary artery catheter were made after 17 episodes of operative hypothermia in six patients. Body temperature was monitored in the urinary bladder. RESULTS: The rate of temperature rise (T) showed a strong positive correlation with VO2 measured both by indirect calorimetry (r = 0.91, p < 0.001) and by balloon-tipped pulmonary artery catheter (r = 0.83, p < 0.001). Oxygen delivery (DO2) was above normal in nearly all patients. Oxygen extraction was low in patients recovering slowly (T < 1.0 degree C/hr) and high in those recovering quickly (T > or = 1.0 degree C/hr). During fast recovery VO2 (373 +/- 77 ml.min-1.m-2; mean +/- SD) was approximately three times normal and was independent of DO2. In contrast, a strong linear relationship existed between VO2 and DO2 during slow recovery (r = 0.76, p < 0.001). CONCLUSIONS: Patients with burns with slow recovery from operative hypothermia exhibited impaired oxygen extraction and dependence of VO2 on DO2 over a wide range. This picture resembles that in patients with critical illness.

Paradoxical positive nitrogen balance in burn patients receiving high-dose administration of insulin for nutritional care.

BACKGROUND: Nitrogen balance in patients who need high-dose administration of insulin has not been evaluated clinically. The purpose of this study was to compare the difference in nitrogen balance between burn patients who received high-dose administration of insulin and those who did not. METHODS: This study was performed in 19 severely burned adults with no liver or kidney failure. Patients were divided into two groups on the basis of the mean ratio of administered insulin and calorie intake (I/C) for the initial 4 weeks, a high I/C group (n = 9) and a low I/C group (n = 10). There were no significant differences between the two groups regarding age, percentage of area burned, and body weight. Nitrogen balance, blood urea nitrogen, and urine urea nitrogen were measured in all patients. Plasma concentrations of glucose, insulin, glucagon, cortisol, and urinary excretion of 3-methyl-histidine were measured in 12 patients (six in each group). RESULTS: Until day 10 both groups exhibited similar changes in plasma concentrations of glucose, insulin, glucagon, and cortisol. Subsequently, plasma concentrations of insulin and glucagon began to decrease in the low I/C group, whereas a high level was sustained in the high I/C group (p < 0.05). Plasma glucose and cortisol measurements showed no significant differences between the two groups. Blood urea nitrogen levels and urinary excretion of 3-methyl-histidine were not different between the two groups. Urine urea nitrogen excretion in the high I/C group, however, was significantly lower than that in the low I/C group from day 8 (p < 0.05). Thus the high I/C group achieved positive nitrogen balance more quickly than the low I/C group. Paradoxically, however, the high I/C group was at higher risk of septic complications and exhibited higher mortality than the low I/C group (p < 0.05). CONCLUSIONS: These results indicate that an improvement in nitrogen balance, which is accepted as a good thing in the management of critically ill patients, is not necessarily good in the high I/C group and that residual nitrogen was retained within the body in the high I/C group.

Asymmetrical regulation of blood pressure in the rat medulla.

The effects of microinjection of serotonin-1 (5-HT1) antagonist methiothepin and 5-HT1 agonist buspirone into the nucleus reticularis parvocellularis were investigated in the anaesthetized rats. Methiothepin produced an increase in arterial blood pressure when injected into the left side, but it did a decrease when injected into the right side. On the contrary, buspirone produced a decrease in arterial blood pressure when injected into the left side, but it did an increase when injected into the right side. These findings provide the clue to clarify that there is a reciprocal regulation of arterial blood pressure between the left and right sides in the rat medulla.

Effect of chronic (-)-nicotine treatment on rat cerebral benzodiazepine receptors.

The purpose of this study was to clarify the effect of (-)-nicotine on cerebral benzodiazepine receptors (BzR) with radiotracer methods. The effect of (-)-nicotine on BzR was examined in in vitro studies using chronic (-)-nicotine-treated rats using 3H-diazepam. The in vitro radioreceptor assay showed a 14% increase in the maximum number of binding sites of BzR in chronic (-)-nicotine-treated rats in comparison with the control rats. Moreover, a convenient in vivo uptake index of 125I-iomazenil was calculated and a higher uptake of the radioactivity was observed in the chronic (-)-nicotine-treated group than in the control group. Although further studies of the mechanism of (-)-nicotine on such BzR changes are required, an increase in the amount of BzR in the cerebral cortex was found in rats that underwent chronic (-)-nicotine treatment, and this result contributed to the understanding of the effects of (-)-nicotine and smoking on neural functions.

Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury.

Recent experimental studies have demonstrated that mild hypothermia at about 34 degrees C can be effective in the control of intracranial hypertension. A randomized controlled study of mild hypothermia was carried out in 33 severely head-injured patients. All patients fulfilled the following criteria: 1) persistent intracranial pressure (ICP) greater than 20 mm Hg despite fluid restriction, hyperventilation, and high-dose barbiturate therapy; 2) an ICP lower than the mean arterial blood pressure; and 3) a Glasgow Coma Scale score of 8 or less. The patients were divided into two groups: one received mild hypothermia (16 patients) and one served as a control group (17 patients). Mild hypothermia significantly reduced the ICP and increased the cerebral perfusion pressure. Eight patients (50%) in the hypothermia group and three (18%) in the control group survived (p < 0.05), while five (31%) in the hypothermia group and 12 (71%) in the control group died of uncontrollable intracranial hypertension (p < 0.05). In five patients in the hypothermia group, cerebral blood flow was measured by the hydrogen clearance method and arteriojugular venous oxygen difference was evaluated before and during mild hypothermia. Mild hypothermia significantly decreased the cerebral blood flow, arteriojugular venous oxygen difference, and cerebral metabolic rate of oxygen (p < 0.01). The results of this preliminary investigation suggest that mild hypothermia is a safe and effective method to control traumatic intracranial hypertension and to improve mortality and morbidity rates.

Transient and repetitive rises in blood pressure synchronized with plasma catecholamine increases after head injury. Report of two cases.

The authors report two patients with repetitive episodes of acute transient rise in blood pressure synchronized with increases in plasma catecholamine after severe head injury. In both cases, the paroxysmal hypertension occurred suddenly on the 2nd day posttrauma, and its frequency declined gradually, disappearing with time. The pathophysiological basis of this peculiar clinical manifestation is discussed.

Little benefit from mild hypothermia therapy for severely head injured patients with low intracranial pressure.

OBJECT: This study was performed to determine whether mild hypothermia therapy is essential for the treatment of severely head injured patients in whom intracranial pressure (ICP) can be maintained below 20 mm Hg by using conventional therapies. METHODS: Sixteen consecutive severely head injured patients fulfilled the following criteria: the patient's ICP was maintained below 20 mm Hg by using fluid restriction, hyperventilation, and high-dose barbiturate therapy; and the patient had a Glasgow Coma Scale score of 8 or less on admission. After conventional therapies had been applied, the patients were divided randomly into two groups: the mild hypothermia group (HT group; eight patients) and the normothermia group (NT group; eight patients). The HT group received mild hypothermia (intracranial temperature 34 degrees C) therapy for 48 hours followed by rewarming at 1 degree C per day for 3 days, whereas the NT group received normothermia (intracranial temperature 37 degrees C) therapy for 5 days. Specimens of cerebrospinal fluid (CSF) taken from an intraventricular catheter every 24 hours were analyzed for the presence of excitatory amino acids ([EAAs] glutamate, aspartate, and glycine) and cytokines (tumor necrosis factor-alpha, interleukin [IL]-1beta, IL-6, IL-8, and IL-10). The two groups did not differ significantly in patient age, neurological status, or level of ICP. There were no significant differences in daily changes in CSF concentrations of EAAs and cytokines between the two groups. The incidence of pneumonia was slightly higher in the HT group compared with the NT group (p = 0.059). The incidence of diabetes insipidus associated with hypernatremia was significantly higher in the HT group compared with that in the NT group (p < 0.01). The two groups did not differ with respect to their clinical outcomes. CONCLUSIONS: The authors recommend normothermia therapy for the treatment of severely head injured patients in whom ICP can be maintained at lower than 20 mm Hg by using conventional therapies, because mild hypothermia therapy does not convey any advantage over normothermia therapy in such patients.

Selection of severely head injured patients for mild hypothermia therapy.

OBJECT: The authors have analyzed the efficacy of inducing mild hypothermia (34 degrees C) in 62 severely head injured patients to control fulminant intracranial hypertension. METHODS: All 62 patients fulfilled the following criteria: 1)persistent intracranial pressure (ICP) greater than 20 mm Hg despite fluid restriction, hyperventilation, and high-dose barbiturate therapy; 2) an ICP lower than the mean arterial pressure; and 3) a Glasgow Coma Scale (GCS) score of 8 or less on admission. The patients were divided into three groups based on computerized tomography findings: extracerebral hematoma (34 patients with subdural and/or epidural hematoma), focal cerebral lesion (20 patients with localized brain contusion and/or intracerebral hematoma), and diffuse swelling (eight patients with no focal mass lesion). Mild hypothermia prevented ICP elevation in 35 (56.5%) of the 62 patients whose ICP was greater than 20 mm Hg despite conventional therapies. Among those 35 patients whose ICP was controlled by mild hypothermia, 12 (34.3%) achieved functional recovery (good outcome or moderate disability). However, functional recovery was observed in only five (10.9%) of the 46 patients whose ICP was greater than 40 mm Hg after conventional therapies. Of 40 patients with an admission GCS score of 5 to 8, there were 11 (27.5%) who achieved functional recovery. On the contrary, mild hypothermia was not effective in 22 patients with an admission GCS score of 3 or 4. In the patients with focal cerebral lesions, ICP was controlled by mild hypothermia in 17 patients (85%) and patient outcome was intimately related to the extent of the damage. Among 18 patients with extracerebral hematoma who had a midline shift of 9 to 12 mm, raised ICP could be successfully controlled by mild hypothermia in 16 patients (88.9%) and three (16.7%) achieved functional recovery. However, ICP could not be controlled in patients with extracerebral hematoma who had a midline shift of 13 mm or more. In patients with diffuse swelling, ICP elevation could not be prevented at all by mild hypothermia. CONCLUSIONS: The authors conclude that mild hypothermia is effective for preventing ICP elevation in patients without diffuse brain swelling in whom ICP remains higher than 20 mm Hg but less than 40 mm Hg after conventional therapies.

A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure. Mild Hypothermia Study Group in Japan.

OBJECT: The criteria for the use of mild hypothermia (34 degrees C) in severely head injured patients have not been standardized. A prospective randomized controlled trial was conducted to determine whether mild hypothermia is essential in the treatment of severely head injured patients with low intracranial pressure (ICP). METHODS: At 11 medical centers, 91 severely head injured patients with an admission Glasgow Coma Scale score of 8 or less in whom ICP could be maintained below 25 mm Hg by conventional therapies were divided randomly into two groups: the mild hypothermia group (HT group, 45 patients) and the normothermia group (NT group, 46 patients). Patients in the HT group were exposed to mild hypothermia (34 degrees C) for 48 hours, followed by rewarming at 1 degrees C per day for 3 days, whereas patients in the NT group were exposed to normothermia (37 degrees C) for 5 days. The two groups were similar with respect to prognostic factors, and there was no difference in clinical outcome at 3 months postinjury. During treatment, there was a significantly greater use of neuromuscular blocking agents in the HT group (p = 0.011). During the initial 2 weeks postinjury, the incidences of pneumonia, meningitis, leukocytopenia, thrombocytopenia, hypernatremia, hypokalemia, and hyperamylasemia were significantly higher in the HT than in the NT group (p < 0.05). CONCLUSIONS: Mild hypothermia should not be used for the treatment of severely head injured patients with low ICP because this therapy conveys no advantage over normothermia in such patients.

Recovery from postoperative hypothermia predicts survival in extensively burned patients.

To clarify the cause of postoperative hypothermia in extensively burned patients, factors affecting postoperative hypothermia were studied in 16 extensively burned adult patients (8 survivors and 8 nonsurvivors) with a burn index greater than 35. Body temperature was monitored continuously in either the urinary bladder or rectum. Hypothermia of less than 35 degrees C occurred in 89% (66 of 74) of the total operations performed in these 16 patients. The rate of temperature rise (RTR) was significantly lower in nonsurvivors (0.4 +/- 0.2 degrees C/h) than in survivors (1.7 +/- 0.9 degrees C/h; p < 0.001). Continuous indirect calorimetry performed in seven patients (four survivors and three nonsurvivors) demonstrated that RTR was determined primarily by heat production. The measured energy expenditure reached only 1.7 +/- 0.2 times the basal energy expenditure during rewarming in nonsurvivors, whereas it was 2.7 +/- 0.9 times the basal energy expenditure in survivors (p < 0.01). Surprisingly, in nonsurvivors, the RTR was significantly decreased even during the first 2 weeks. These findings suggest that those who cannot generate heat well in postoperative hypothermia are unable to produce the additional energy required to overcome sepsis.

The dimer and trimer of 3-hydroxybutyrate oligomer as a precursor of ketone bodies for nutritional care.

BACKGROUND: Ketone bodies have been considered as a means of providing energy because of their good penetration and rapid diffusion in peripheral tissues. However, because the currently available form of 3-hydroxybu-tyrate is the sodium salt, the sodium load is problematic. To avoid it, a mixture of dimer and trimer has been prepared as a precursor of D-3-hydroxybutyrate. The purpose of this study was to investigate whether and how the solution would be converted to monomers. METHODS: The plasma concentration of 3-hydroxybutyrate monomer was measured in 10 rats during infusion of dimer and trimer. Stepwise dilutions of the solution were incubated with serum and liver homogenates from five rats, serum samples from five volunteers, and a liver sample from one patient with liver injury. The solution also was incubated with carboxylesterase and triacylglycerol lipase. The concentration of monomer in the medium was measured after incubation. RESULTS: The plasma concentration of 3-hydroxybutyrate monomer reached 572 +/- 11 micromol/L 15 minutes after beginning infusion of the mixture at a rate of 25 micromol x kg(-1) x min(-1) and 270 +/- 40 micromol/L at a rate of 12.5 micromol x kg(-1) min(-1). The solution was converted completely to monomers when incubated with rat serum or liver homogenate for 10 minutes. The mixture also was hydrolyzed by human liver homogenate but not by serum. CONCLUSIONS: The dimer and trimer of 3-hydroxybutyrate can be converted rapidly to monomer in rat and human tissues. 3-Hydroxybutyrate oligomers could be an energy substrate for injured patients.