The Contactless Vital Sensing System Precisely Reflects R-R Interval in Electrocardiograms of Healthy Subjects.

BACKGROUND: The aim of the present study was to investigate the validity of the contactless vital sensing system that we previously developed. METHODS: A total of 111 healthy Japanese subjects were recruited from the University of Occupational and Environmental Health and the Panasonic Corporation AVC Networks Company. All subjects underwent an evaluation using the contactless vital sensing system and electrocardiography (ECG). We compared the R-R interval obtained using the new contactless sensing system to that obtained using ECG. RESULTS: A very strong correlation was observed between the instruments. CONCLUSIONS: This result confirms the validity of the new contactless sensing system in evaluating healthy subjects.

Copy numbers of telomeric repeat sequences of human herpesvirus 6B in clinical isolates: possibility of mixed infections.

In order to determine whether mixed infections of human herpesvirus 6B (HHV-6B) occur in immunocompetent and immunocompromised individuals, we examined the copy numbers of telomeric repeat sequences (TRS) of clinical isolates. In clinical isolates obtained from patients with exanthem subitum caused by primary HHV-6B infection, PCR products with HHV-6B TRS ranging between 400 and 800 bp were amplified. PCR products of various sizes were amplified in four clinical isolates from drug-induced hypersensitivity syndrome (DIHS) patients and 15 isolates from hematopoietic stem cell transplant (HSCT) recipients with HHV-6B reactivation. Based on the sequence analysis of the PCR products, the copy numbers of TRS in DIHS and HSCT patients were between 42 and 82 and 22 and >90, respectively. For two of the HSCT recipients, HHV-6B TRS PCR products of different sizes were detected in several isolates from each patient, which suggests mixed HHV-6B infections. In two of the posttransplant HHV-6B encephalitis patients, the sizes of the TRS nested PCR products amplified from the reactivated virus detected in the central nervous system differed from those of the virus detected in initial isolates from peripheral blood mononuclear cells. Taken together, these results suggest that PCR analysis of TRS copy number is a reliable tool for the discrimination of HHV-6B clinical isolates. Additionally, mixed HHV-6B infections occurred in HSCT recipients, and in some cases, compartmentalization of the HHV-6B strains to the central nervous system versus the blood compartment occurred in posttransplant HHV-6B encephalitis patients.

Cytokine and chemokine responses in the blood and cerebrospinal fluid of patients with human herpesvirus 6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion.

Acute encephalopathy with biphasic seizures and late reduced diffusion has become increasingly common among various types of human herpesvirus 6B (HHV-6B) encephalitis at the time of primary viral infection. The aim of the present study is to explore the pathophysiology of HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion. Five cytokines and five chemokines were measured in serum and cerebrospinal fluid (CSF) obtained from 12 HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion patients and 19 control exanthem subitum (without complications) patients. Serum interleukin (IL)-10 (P = 0.007) and IL-8 (P = 0.025) were significantly higher in the patients with the disease than controls. Serum IL-1ß (P = 0.034) and monocyte chemoattractant protein (MCP)-1 (P = 0.002) were significantly higher in the controls than patients with the disease. In patients with the disease, IL-10 (P = 0.012), regulated on activation normal T cell expressed and secreted (RANTES; P = 0.001), and monokine induced by interferon γ (MIG; P = 0.001) were significantly higher in serum than CSF, meanwhile IL-6 (P = 0.034), IL-8 (P = 0.034), and MCP-1 (P = 0.001) were significantly higher in CSF than serum. Additionally, serum IL-10 was significantly higher in the disease patients with sequelae than those without sequelae (P = 0.016). Several cytokines and chemokines may be associated with the pathogenesis of acute encephalopathy with biphasic seizures and late reduced diffusion. Moreover, the regulation of cytokine networks appears to be different between peripheral blood (systemic) and central nervous system.

Spread of herpes simplex virus to the spinal cord is independent of spread to dorsal root ganglia.

Levels of herpes simplex virus 1 (HSV-1) and HSV-2 DNA in dorsal root ganglia (DRG) and spinal cord (SC) were quantified after inoculation of guinea pig genitals and footpads. In genital infection, viral DNA reached SC and DRG simultaneously (at 2 to 3 days after inoculation) but was more abundant in SC than in DRG. After inoculation of footpads, which lack parasympathetic innervation, the viruses spread more efficiently to DRG than to SC. These results show important differences between genital and footpad infections, including independence of spread to DRG and SC, and imply that autonomic neurons may play an important role in the pathogenesis of viral latency after genital inoculation.

Correlation between serum matrix metalloproteinase and antigenemia levels in patients infected with rotavirus.

Rotavirus (RV) antigenemia has been reported in patients with gastroenteritis; however, the exact mechanism remains unclear. In order to elucidate the mechanism of RV antigenemia, an association between RV antigenemia and matrix metalloproteinase (MMP) were analyzed. The object of this study was to elucidate the role of MMPs and tissue inhibitors of metalloproteinases (TIMPs) in the pathogenesis of RV antigenemia. Forty children admitted to hospital with RV gastroenteritis were enrolled in this study. Paired serum samples were collected at the time of admission and discharge. Enzyme-linked immunosorbent assays (ELISA) were used to detect serum concentrations of viral antigens, MMP-1, -2, -9, -13, TIMP -1, and -2. Cytokines were measured using flow cytometric beads array. RV antigens were significantly higher in serum collected at the time of admission than discharge (P < 0.001). MMP-9 concentrations were significantly higher in serum collected at the time of admission than discharge (P < 0.001). MMP-2 concentrations were significantly lower in serum collected at the time of admission than discharge (P < 0.001). A weak but a significantly positive association (P = 0.034) was observed between RV antigen and MMP-9 in serum collected at the time of admission, and inverse association was observed between RV antigen and MMP-2. In addition, a weak but significantly positive association (P = 0.002) was observed between IL-6 and MMP-9. These data suggest that MMPs may contribute to the pathogenesis of RV antigenemia.

Cytokine and chemokine responses in pediatric patients with severe pneumonia associated with pandemic A/H1N1/2009 influenza virus.

Severe pneumonia and leukocytosis are characteristic, frequently observed, clinical findings in pediatric patients with pandemic A/H1N1/2009 influenza virus infection. The aim of this study was to elucidate the role of cytokines and chemokines in complicating pneumonia and leukocytosis in patients with pandemic A/H1N1/2009 influenza virus infection. Forty-seven patients with pandemic A/H1N1/2009 influenza virus infection were enrolled in this study. Expression of interleukin (IL)-10 (P = 0.027) and IL-5 (P = 0.014) was significantly greater in patients with pneumonia than in those without pneumonia. Additionally, serum concentrations of interferon-γ (P = 0.009), tumor necrosis factor-α (P = 0.01), IL-4 (P = 0.024), and IL-2 (P = 0.012) were significantly lower in pneumonia patients with neutrophilic leukocytosis than in those without neutrophilic leukocytosis. Of the five serum chemokine concentrations assessed, only IL-8 was significantly lower in pneumonia patients with neutrophilic leukocytosis than in those without leukocytosis (P = 0.001). These cytokines and chemokines may play important roles in the pathogenesis of childhood pneumonia associated with A/H1N1/2009 influenza virus infection.

Host factors associated with the kinetics of Epstein-Barr virus DNA load in patients with primary Epstein-Barr virus infection.

The aims of this study were to elucidate the kinetics of Epstein-Barr virus (EBV) DNA load in serially collected peripheral blood mononuclear cells of patients with primary EBV infection, and to determine the correlated host factors. Blood samples were collected from 24 patients with primary EBV infection. EBV DNA copy numbers were measured using real-time polymerase chain reaction. Based on the kinetics of EBV DNA load, the 24 patients were divided into two groups: rapid regression and slow regression. Eighteen of the 24 patients (75%) were included in the slow regression and 6 (25%) in the rapid regression group. No statistically significant differences were observed between the two groups in clinical features and laboratory findings. However, acute phase (3 to 10 days after the onset of the illness) serum samples from six children in the slow regression and four in the rapid regression group revealed significantly higher serum interleukin (IL)-1ß (P= 0.018), IL-12 (P= 0.009), tumor necrosis factor-α (P= 0.019), interferon-inducible protein 10, and monokine induced by interferon γ concentrations in the rapid regression than the slow regression group. On the other hand, sera from six children in the slow regression and four in the rapid regression group in the convalescent phase (14 to 21 days after the onset of the illness) showed no statistically significant differences between the two groups in these biomarker concentrations. Based on this, it was concluded that the kinetics of EBV DNA load can be divided to two different patterns after primary EBV infection, and immune response might be associated with viral clearance.

Direct detection of human herpesvirus 6 DNA in serum by the loop-mediated isothermal amplification method.

BACKGROUND: A more rapid and easier method is needed for monitoring human herpesvirus 6 (HHV-6) infections. The loop-mediated isothermal amplification method (LAMP) can detect viral DNA with high specificity, efficiency, and speed under isothermal conditions. LAMP requires only simple equipment that is available in hospital laboratories. OBJECTIVES: We evaluated LAMP as a means of detecting HHV-6 DNA directly from patients' sera. RESULTS: The sensitivity of the HHV-6 LAMP protocol without heat denaturation was 1000 copies/tube; with heat denaturation 10 copies/tube were detected. Three hundred serum samples from children with fever were analyzed. Using HHV-6 isolation as a definition of HHV-6 infection, the sensitivity, specificity, positive predictive value, and negative predictive value of the HHV-6 LAMP method without DNA extraction were 95.5%, 95.2%, 94.0%, and 96.4%, respectively. CONCLUSION: Direct detection of HHV-6 DNA in serum with a modified HHV-6 LAMP could be used for rapid diagnosis of exanthem subitum (ES).

Effectiveness of a comprehensive day treatment program for rehabilitation of patients with acquired brain injury in Japan.

OBJECTIVE: To assess the effectiveness of a day treatment program with a comprehensive team approach for treating outpatients with acquired brain injury, which is offered by the Kanagawa Rehabilitation Hospital. DESIGN: Non-randomized controlled study. SUBJECTS: Twenty-five program graduates and 12 control patients with acquired brain injury. METHODS: A prospective study using 25 brain-injured patients with cognitive dysfunction who were provided with a comprehensive day treatment program at Kanagawa Rehabilitation Hospital. The 25 enrolled patients had treatment sessions lasting 2-4 hours for 2 days a week over a 3-6-month period. Functional Independence Measure/Functional Assessment Measure (FIM/FAM) and the Community Integration Questionnaire (CIQ) were administered before and after the program to compare outcomes between the 25 program participants and the 12 control patients who did not receive the day treatment program. RESULTS: Significant improvements in speech intelligibility, problem solving, memory, attention and social integration scores in the FIM/FAM and scores in social integration and productive activity in the CIQ were evident in the enrolled subjects. In addition, 9 of the 25 patients returned to work or school. CONCLUSION: These results demonstrate the effectiveness of this program in helping to rehabilitate patients with acquired brain injury.

How great is willingness to pay for recovery from sequelae after severe traumatic brain injury in Japan?

OBJECTIVE: To evaluate the burden on families with a family member suffering traumatic brain injury sequelae in Japan. DESIGN: Cross-sectional study. METHODS: Family members' burden from the sequelae of traumatic brain injury was estimated by use of willingness-to-pay models and the contingent valuation method. A national survey among 1707 members of the Japan Traumatic Brain Injury Association was conducted by postal questionnaire with open-ended questions. A total of 509 (29.8%) of the family members responded (405 men and 104 women). Mean age of patients with traumatic brain injury was 33.4 (SD 14.3) years and of responding family members 53.3 (SD 14.5) years. RESULTS: Willingness-to-pay for the family member's recovery from sequelae of traumatic brain injury (8,694,502 Japanese yen; 79,134 US dollars/year) was similar to that reported for a family member's survival from incurable terminal disease (8,342,953 Japanese yen; 75,934 US dollars/year). CONCLUSION: The data indicate that family members perceive the burden of a family member with traumatic brain injury sequelae as similar to what would have been caused by an incurable terminal disease.

Universal varicella vaccine immunization in Japan.

In 1974, Japanese scientists developed a live attenuated varicella vaccine based on the Oka strain. The efficacy of the vaccine for the prevention of varicella has been primarily demonstrated in studies conducted in the United States following the adoption of universal immunization using the Oka strain varicella vaccine in 1996. Although the vaccine was developed by Japanese scientists, until recently, the vaccine has been administered on a voluntary basis in Japan resulting in a vaccine coverage rate of approximately 40%. Therefore, Japan initiated universal immunization using the Oka strain varicella vaccine in November 2014. Given the transition from voluntary to universal immunization in Japan, it will also be important to monitor the epidemiology of varicella and herpes zoster. The efficacy and safety of co-administration of the varicella vaccine and measles, mumps, and rubella vaccine have been demonstrated in many countries; however, there was no data from Japan. In order to adopt the practice of universal immunization using the Oka strain varicella vaccine in Japan, data demonstrating the efficacy and safety of co-administration of varicella vaccine and measles and rubella (MR) vaccine were required. Additionally, we needed to elucidate the appropriate time interval between the first and second administrations of the vaccine. It is also important to differentiate between wild type and Oka vaccine type strains in herpes zoster patient with past history of varicella vaccine. Thus, there are many factors to consider regarding the adoption of universal immunization in Japan to control varicella zoster virus (VZV) infections.

Severe acute tonsillitis caused by Rothia dentocariosa in a healthy child.

A 4-year-old Japanese girl developed a sore throat and high fever. Her tonsils were enlarged, red and covered with a thick white membrane. There was marked leukocytosis (26,600 leukocytes per mm) and elevated C-reactive protein levels (23.3 mg/dL). Rothia dentocariosa was recovered from the throat swab; many Gram-positive cocci were observed in the smear from the pseudomembrane covering the tonsil.

Pathogenesis of Severe Neutropenia in Patients With Primary Human Herpesvirus 6B Infection.

BACKGROUND: Although myelosuppression caused by human herpesvirus 6B (HHV-6B) reactivation in transplant recipients has been extensively investigated, the pathophysiological mechanisms of severe neutropenia in primary HHV-6B infection remain unclear. PROCEDURE: Fifty-four patients with primary HHV-6B infection were evaluated. Hematological examinations and blood sampling were conducted on days 1-4 (pre) and 5-10 (post) after the onset of illness. Severe neutropenia was defined as a neutrophil count less than 500 cells/µL. Patient characteristics, clinical data, and cytokines and chemokines levels were compared between the patients with (n = 16) and without (n = 38) severe neutropenia. RESULTS: Severe neutropenia was detected in samples that were collected between days 5 and 10 after illness. Significantly lower platelet counts (pre, P = 0.048; post, P = 0.032) and regulated on activation, normal T cell expressed and secreted levels (post, P = 0.007) were detected in the patients with neutropenia. Aspartate aminotransferase levels (P = 0.008), and interferon γ-inducible protein-10 (P < 0.0001), monocyte chemoattractant protein-1 (P = 0.005), and monokine induced by interferon γ (P = 0.011) levels were significantly higher in post samples collected from the patients with neutropenia. No differences were observed in any patient characteristics and serum cytokines levels. No bacterial infections were detected during the observation period. CONCLUSIONS: Chemokines may play an important role in the pathogenesis of severe neutropenia in patients with primary HHV-6B infection.

Guillain-Barré syndrome after exanthem subitum.

A female infant developed Guillain-Barré syndrome 20 days after having exanthem subitum confirmed serologically as human herpesvirus 6 infection. DNA of human herpesvirus 6 was detected in peripheral blood mononuclear cells collected on admission.

Monitoring herpesvirus DNA in three cases of acute retinal necrosis by real-time PCR.

BACKGROUND: It is not clear whether quantitative analysis of viral DNA in ocular specimens is correlated with disease activities of acute retinal necrosis (ARN). OBJECTIVES: To monitor viral load in ocular specimens collected from patients with ARN by real-time polymerase chain reaction (PCR). STUDY DESIGN: Ocular samples (aqueous humor and vitreous) were serially collected from three patients with ARN. Viral load in those samples was evaluated by real-time PCR. RESULTS AND CONCLUSION: In case 1, large amounts of varicella zoster virus (VZV) DNA (4.8 x 10(6) to 5.5 x 10(6) copies/ml) were detected in aqueous humor during the first 2 weeks after admission. The viral load in vitreous was higher than that in aqueous humor at the time of vitrectomy. As ophthamoscopic findings and visual acuity improved through acyclovir (ACV) treatment, the viral load in aqueous humor decreased dramatically. In case 2, the patient was treated with intravenous ACV at first, but clinical features did not improve. The herpes simplex virus (HSV)-2 viral load in aqueous humor remained stable (2.3 x 10(3) to 2.8 x 10(3) copies/ml) during the first 3 weeks after admission. The amount of HSV-2 DNA in vitreous was again higher than that in aqueous humor. Although neither clinical features nor viral load had changed by ACV, intra-ocular ganciclovir (GCV) injection improved clinical features, and decreased viral load to undetectable levels. In case 3, the patient developed ARN within 1 month after the onset of varicella and demonstrated only mild clinical symptoms. She was treated with ACV administration alone and recovered quickly. In contrast to case 1, the copy number of VZV DNA at the time of admission was low (9 x 10(2) copies/ml), and decreased quickly in response to the treatment. Correlation between viral load in ocular specimens and clinical course of the disease was demonstrated in these patients.

Role of brain perfusion single-photon emission tomography in traumatic head injury.

This investigation examined the role of brain perfusion single-photon emission tomography (SPET) in traumatic head injury in 35 patients. The results were compared with those of X-ray computerized tomography (CT) and magnetic resonance imaging (MRI). CT and MRI detected brain contusions in seven patients, subarachnoid haemorrhage in one patient and both in nine patients. In 16 of the 17 subjects (94%), SPET with technetium-99m-hexamethylpropyleneamine oxime (Tc-HMPAO) revealed CT/MRI-negative abnormalities, such as hypoperfusion in the contre-coup region, frontal hypoperfusion related to personality change and cerebellar hypoperfusion associated with vertigo. In two patients presenting with diffuse axonal injury in the brainstem, hypoperfusion in the frontal cortex on the affected side was observed on SPET. SPET demonstrated hypoperfusion in the adjacent cortex, with no abnormality on either CT or MRI, in six of seven patients exhibiting acute epidural haematoma. SPET failed to provide additional information in two of five patients with acute subdural haematoma and in one of two patients displaying chronic subdural haematoma. In four of nine patients with post-traumatic amnesia, SPET detected hypoperfusion in the temporal lobe, with no abnormality on either CT or MRI. In five of eight patients with vertigo, SPET detected hypoperfusion in the morphologically normal cerebellum. In seven cases involving personality change, frontal hypoperfusion was observed in four; moreover, a markedly non-homogeneous pattern was evident in the remaining three. Overall, SPET afforded additional information in 26 patients (74%). CT possesses an advantage with respect to the detection of haemorrhagic lesions. MRI provides more precise information regarding contusions and axonal injury. Frequently, SPET may be the only examination to reveal perfusion abnormalities which are related to symptoms in the absence of other objective findings, such as post-traumatic amnesia, vertigo or personality change.

Thallium-201 brain SPECT to diagnose aggressiveness of meningiomas.

This investigation was conducted to determine the ability of 201Tl brain SPECT with respect to preoperative prediction of lesional aggressiveness of meningioma. Fifty-nine lesions in 42 patients were examined. Early (15 min) and late (3 h) SPECT were obtained. Early uptake ratio (ER; lesion to normal brain average count ratio), late uptake ratio (LR) and the ratio of LR to ER (L/E ratio) were calculated. Twenty-three lesions exhibited malignant features based on histologic or clinical course such as recurrence or skull invasion. Both ER and LR of malignant meningiomas were significantly higher than those in thirty-six benign lesions. Benign lesions were classified into two groups for further analysis: meningotheliomatous type, which is the most common histology, and benign lesions other than the meningotheliomatous (other benign) type. ER in other benign type was lower than the meningotheliomatous and the malignant type. LR afforded differentiation of the malignant type from the two benign types. These two benign types could be distinguished on the basis of the L/E ratio. These results indicate that high pre-operative ER and LR values in patients with meningioma are indicators of the aggressiveness of lesions, i.e., malignant meningioma, recurrence or skull invasion.

Differential diagnosis in patients with ring-like thallium-201 uptake in brain SPECT.

UNLABELLED: This study was performed to investigate lesions with ring-like thallium-201 (201Tl) uptake and to determine whether SPECT provides any information in differential diagnosis. METHODS: A total of 244 201Tl SPECT images were reviewed. In each study, early (15 min postinjection) and late (3 hr) brain SPECT images were obtained with 111 MBq of 201Tl. The early uptake ratio (ER; lesion to normal brain average count ratio) and the late uptake ratio (LR) and the L/E ratio (ratio of LR to ER) were calculated. RESULTS: Ring-like uptake was observed in pre-therapeutic 26 SPECT images, including ten glioblastoma multiformes (ER, 3.45 +/- 0.64; LR, 2.74 +/- 0.54; L/E ratio 0.80 +/- 0.13), five meningiomas (6.48 +/- 2.34; 4.41 +/- 1.41; 0.72 +/- 0.19), four metastatic lung cancers (3.47 +/- 1.23; 2.40 +/- 0.98; 0.70 +/- 0.14), four brain abscesses (2.48 +/- 1.06; 1.59 +/- 0.30; 0.78 +/- 0.15), one invasive lesion of squamous cell carcinoma from the ethmoid sinus (1.54; 1.52; 0.99), one medulloblastoma (3.53; 3.52; 1.00) and one hematoma (3.32; 2.36; 0.71). The ER of meningioma was significantly higher than those of glioblastoma multiforme (p < 0.0005), metastatic lung cancer (p < 0.005) and brain abscess (p < 0.0005). There were no significant differences among these three entities. The LR of meningioma was significantly higher than those of glioblastoma multiforme (p < 0.005), metastatic lung cancer (p < 0.005) and brain abscess (p < 0.0001). The LR of brain abscess was significantly lower than that of glioblastoma multiforme (p < 0.05). The L/E ratio could not differentiate these four entities. CONCLUSION: High ER and high LR in a lesion with ring-like uptake is likely an indicator of meningioma. The LR of brain abscess was significantly lower than that of glioblastoma multiforme, but 201T1 SPECT has still difficulty in differentiating abscess from brain tumor.

[Cognitive dysfunction in 32 diffuse axonal injury cases].

In acute stage of traumatic brain injury, it is not easy to diagnose diffuse axonal injury (DAI) by computer imaging. Even in chronic stage, DAIs occasionally show no remarkable abnormality by ordinal CT or MRI images. We retrospectively studied 32 DAI cases by the Functional Independence Measure (FIM), a battery of neuropsychological tests and CT or MRI films of acute and chronic phase. The result showed decrease of cognitive function in 32 DAI cases. The degree of enlargement of the ventricles in chronic stage did not correlate with cognitive dysfunction.

[Lowered VIQ level following traumatic brain injury].

A patient with traumatic brain injury (TBI) is often associated with incidence of cognitive dysfunction as a sequela. We have conducted WAIS-R to 237 patients who were diagnosed as TBI at the Kanagawa Rehabilitation Hospital in order to assess their intellectual function. Twelve patients, whose VIQ being marked significantly lower than PIQ, were retrospectively analyzed in terms of their Functional Independence Measure (FIM), neuropsychological test results and lesions found in diagnostic images. In consequence, presence of a patient group whose VIQ level is significantly lowered due to the TBI sequela is recognized, in addition to a finding that trauma sites of cerebral contusion or other incidents are not necessarily corresponding to the results of neuropsychological test. Furthermore, based on an observation that those patients with lowered VIQ level are also associated with aggravation of PIQ 'digit symbol', Trail Making Test, or word fluency levels. This result was before similar with the result of "32 cases of DAI (diffuse axonal injury)" which authors reported, and it was guessed anew that the main factor of a cognitive dysfunction was damage on axon.