Circulating activated protein C levels are not increased in septic patients treated with recombinant human soluble thrombomodulin.

BACKGROUND: Recombinant human soluble thrombomodulin (rTM) has been used for the treatment of disseminated intravascular coagulation in Japan, and an international phase III clinical trial for rTM is currently in progress. rTM mainly exerts its anticoagulant effects through an activated protein C (APC)-dependent mechanism, but the circulating APC levels after rTM treatment have not been clarified. This prospective observational study investigated plasma APC levels after rTM treatment. METHODS: Plasma levels of soluble thrombomodulin, thrombin-antithrombin complex (TAT), protein C, and APC were measured in eight septic patients treated with rTM. APC generation in vitro was assessed in the presence or absence of rTM. RESULTS: rTM significantly increased thrombin-mediated APC generation in vitro. In septic patients, soluble thrombomodulin levels were significantly increased during a 30-60-min period of rTM treatment and TAT levels were decreased. However, APC activity was not increased during the treatment period. CONCLUSIONS: Plasma APC activity is not increased in septic patients treated with rTM. It is possible that APC acts locally and does not circulate systemically.

Monitoring of Brain Oxygenation During and After Cardiopulmonary Resuscitation: A Prospective Porcine Study.

This study aimed to evaluate the usefulness of near-infrared time-resolved spectroscopy (TRS) for the monitoring of post-resuscitation encephalopathy. Cardiac arrest (CA) was induced in pigs by electrical stimuli; then, return of spontaneous circulation (ROSC) was achieved by direct current. The changes in cerebral oxygenation were analyzed by two methods: (1) the time-independent calculation based on the modified Beer-Lambert law (MBL), and (2) the curve-fitting method based on the photon diffusion theory (DT). The changes in reduced scattering coefficient (µs') in DT were also calculated. Post-resuscitation encephalopathy was evaluated by MRI findings. During CA, cerebral oxygen saturation (ScO2) decreased to the lowest level, and then gradually increased during the chest compression period. When ROSC was achieved, ScO2 (DT) increased further, but ScO2 (MBL) decreased transiently. This strange phenomenon disappeared when the scalp was peeled off and the probes were directly fixed to the cranial bone. In some cases, a sustained decrease in µs' was observed several hours after ROSC and, in such cases, MRI Diffusion Enhancement Image (DWI) showed findings suggestive of post-resuscitation encephalopathy. In conclusion, simultaneous monitoring of cerebral oxygenation with MBL and DT may provide more information about the vascular response of different layers. Also, the monitoring of µs' may help us to recognize the occurrence of post-resuscitation encephalopathy in real time.

Involvement of orexin neurons in fasting- and central adenosine-induced hypothermia.

We examined whether orexin neurons might play a protective role against fasting- and adenosine-induced hypothermia. We first measured body temperature (BT) in orexin neuron-ablated (ORX-AB) mice and wild-type (WT) controls during 24 hours of fasting. As expected, the magnitude of BT drop and the length of time suffering from hypothermia were greater in ORX-AB mice than in WT mice. Orexin neurons were active just before onset of hypothermia and during the recovery period as revealed by calcium imaging in vivo using G-CaMP. We next examined adenosine-induced hypothermia via an intracerebroventricular administration of an adenosine A1 receptor agonist, N6-cyclohexyladenosine (CHA), which induced hypothermia in both ORX-AB and WT mice. The dose of CHA required to initiate a hypothermic response in ORX-AB mice was more than 10 times larger than the dose for WT mice. Once hypothermia was established, the recovery was seemingly slower in ORX-AB mice. Activation of orexin neurons during the recovery phase was confirmed by immunohistochemistry for c-Fos. We propose that orexin neurons play dual roles (enhancer in the induction phase and compensator during the recovery phase) in adenosine-induced hypothermia and a protective/compensatory role in fasting-induced hypothermia.

Non-invasive Monitoring of Hepatic Oxygenation Using Time-Resolved Spectroscopy.

UNLABELLED: The aim of the present study was to investigate whether changes in hepatic oxygenation can be detected by time-resolved spectroscopy (TRS) placed on the skin surface above the liver. METHODS: With approval of the local Hospital Ethics Committee and informed consent, six healthy volunteers aged 28.8 (25-36) years, and five patients with chronic renal failure aged 70.6 (58-81) years were studied. In six healthy volunteers, following echography, TRS (TRS-10, Hamamatsu Photonics K.K., Hamamatsu, Japan) probes consisting of a near-infrared light (at 760, 800, 835 nm) emitter and a receiver optode, were placed 4 cm apart on the abdominal skin surface above the liver or at least 10 cm distant from the liver. In five patients with chronic renal failure, following echography, TRS probes were placed 4 cm apart on the skin surface above the liver during hemodialysis (HD). RESULTS: In six healthy volunteers, the values of abdominal total hemoglobin concentration (tHb) were significantly higher in the liver area than in the other area (80.6±26.81 vs 44.6±23.1 µM, p=0.0017), while the value of abdominal SO2 in the liver area was nearly the same as that in the other area (71.5±3.6 vs 73.6±4.6%, p=0.19). The values of mean optical pathlength and scattering coefficient (µ's) at 800 nm in the liver area were significantly different from those in the other area (21.3±4.9 vs 29.2±5 cm, p=0.0004, and 7.97±1.14 vs 9.02±0.51 cm(-1), p=0.015). One of five patients with chronic renal failure complained of severe abdominal pain during HD, and abdominal SO2 decreased from 53 to 22%; however, pain relief occurred following cessation of HD, and SO2 recovered to the baseline level. CONCLUSIONS: Our data suggest that the optical properties of the liver may be measured by the TRS placed on the skin surface, and the hepatic oxygenation may act as a non-invasive monitoring for early detection of intestinal ischemia.

Intermittent but not sustained hypoxia activates orexin-containing neurons in mice.

Hypothalamic orexin-containing neurons are activated by CO2 and contribute to hypercapnic ventilatory activation. However, their role in oxygen-related regulation of breathing is not well defined. In this study, we examined whether an experimental model mimicking apnea-induced repetitive hypoxemia (intermittent hypoxia [IH]) activates orexin-containing neurons. Mice were exposed to IH (5×5min at 10% O2), intermittent hyperoxia (IO; 5×5min at 50% O2), sustained hypoxia (SH; 25min at 10% O2), or sham stimulation. Their brains were examined using double immunohistochemical staining for orexin and c-Fos. The results indicated that IH (25.8±3.0%), but not SH (9.0±1.5%) activated orexin-containing neurons when compared to IO (5.5±0.6%) and sham stimulation (5.9±1.4%). These results correlate with those of our previous work showing that IH-induced respiratory long-term facilitation is dependent on orexin-containing neurons. Taken together, orexin contributes to repetitive hypoxia-induced respiratory activation and the hypoxic activation of orexin-containing neurons is pattern dependent.

Two autopsy cases of severe fever with thrombocytopenia syndrome (SFTS) in Japan: a pathognomonic histological feature and unique complication of SFTS.

We report two autopsy cases of severe fever with thrombocytopenia syndrome (SFTS) with a high fatality rate in aged Japanese patients. Both cases were caused by a tick-bite. The pathognomonic histological feature was necrotizing lymphadenitis of systemic lymphoid tissue with SFTS viruses and SFTSV-RNA copies. Marked fungal infections were also observed in the lungs of both patients. Since cellular immune function may be suppressed in SFTS patients, physicians should be aware of possible fungal infections.

[Spinal instrumentation and spinal fusion surgery].

In this article, we review the potential complications of spinal instrumentation discussing various types of postoperative complications. Surgical implants in spinal surgeries are used to stabilize the spine, replace the defective parts and maintain anatomic reduction. Internal spinal instrumentation has undergone considerable advances during the last century. However, the spinal instrumentation is an invasive surgery, and postoperative complications occur frequently after the spinal deformity surgery. Elderly patients, who may have many histories of medical complications and osteoporosis, have a higher complication rate. Pulmonary complications are the most common life-threatening postoperative complications. The acute onset of neurologic symptoms in the immediate postoperative period should arouse clinical suspicion about the possible formation of a hematoma. Such occurrences require urgent surgical decompression. Better recognition of postoperative risk factors and early detection of urgent signs may lead to decrease complication rates and may improve outcomes. Although the latest monitoring system is very useful we should recognize that the observation of the patients by the five senses is the most important way to detect the postoperative medical complications early.