Effectiveness of nanoparticle albumin-bound paclitaxel plus carboplatin in non-small lung cancer patients with malignant pleural effusion.

Malignant pleural effusion (MPE) is a common complication occurring in cancer patients, and its management affects the prognosis of these patients. Preclinical and clinical studies have reported that treatment with nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin (CBDCA) is effective against intraperitoneal malignant tumors. To investigate the effectiveness of nab-paclitaxel plus CBDCA therapy for MPEs arising in patients with non-small cell lung cancer (NSCLC), we retrospectively analyzed the clinicopathological characteristics of 40 patients with stage IIIb or IV NSCLC who were treated with nab-paclitaxel plus CBDCA from 2013 to 2016. Out of 26 patients with MPEs who were treated with nab-paclitaxel plus CBDCA in this study, 21 patients (80.8%) had effective responses in MPEs; 6 of 21 patients exhibited complete responses (23.1%) and 15 of 21 had partial responses (57.7%). Kaplan-Meier survival curves and log-rank tests to evaluate the effectiveness of nab-paclitaxel plus CBDCA therapy against MPEs showed longer median progression-free survival (323 days vs. 26 days; p=0.009) and overall survival (not reached vs. 199 days; p=0.047) in patients with complete responses compared with those who achieved no response. There were no statistical differences between therapeutic effects on MPEs and those on systemic lesions. Nab-paclitaxel plus CBDCA therapy may be a preferred therapeutic option for patients with NSCLC who experience MPEs, and its effectiveness in treatment of MPEs may need to be evaluated separately from its therapeutic responses in systemic lesions.

[Mucinous bronchiolo-alveolar cell carcinoma with marked serum elevation of CA19-9: report of a case].

An 83-year-old woman was referred to our hospital to examine for an infiltration shadow in the right lower lobe with progressive bronchorea Computed tomography showed an infiltration lesion with the longest diameter of 10 cm in the right lower lobe and a tumor with the longest diameter of 3 cm in the middle lobe. Serum level of carbohydrate antigen (CA) 19-9 markedly increased to 37,670 U/ml over a period of 3 months. The pathologic study obtained by a transbronchial tumor biopsy revealed a mucinous adenocarcinoma The patient underwent video-assisted thoracoscopic right middle and lower bi-lobectomies with nodal sampling. Postoperative course was uneventful Pathologic study revealed an adenocarcinoma with mixed subtypes, predominantly composed of mucinous bronchiolo-alveolar cell carcinoma (BAC). Immunohistochemical study showed CA19-9 positivity in the apical surface of some tumor cells and diffuse patterns of other tumor cells. Postoperative course was uneventful and serum CA19-9 levels decreased within the normal range. Clinico-pathologic features of the lung cancer patients with serum elevation of CA19-9 and CA19-9 positivity in the cancer cells was discussed. CA19-9 can be an useful tumor marker in the selected patients with mucinous BAC.

[Hemoptysis one year after video-assisted thoracoscopic bullectomy for spontaneous pneumothorax: report of a case].

A 63-year-old man who had underwent video-assisted thoracoscopic bullectomy for left spontaneous pneumothorax 1 year before developed recurrent hemoptysis. Chest computed tomography showed previous stapling of the subsegmental bronchus in the left apico-posterior segment Bronchial arteriography showed hypervascularization of bronchial artery in the left upper segment and pooling of contrast medium along the staple-suture line. Video-assisted thoracoscopic apico-posterior segmentectomy was performed successfully. Pathological examination revieled hemosiderin lining along the surgical stump of B(1+2)cii, neither with infection nor infarction. These findings suggest that mechanical stapling of B(1+2)cii induced ischemia in the peripheral lung parenchyma causing bronchial hypervascularization. Late onset hemoptysis should be kept in mind as a complication after bullectomy with a mechanical stapler.

[Video-assisted thoracoscopic left upper lobectomy for lung cancer patients: bronchial dissection technique prior to pulmonary artery dissection].

BACKGROUND: Dissection of anterior segmental artery anatomically crossing over apico-posterior segmental bronchus during left upper lobectomy may sometime cause life-threatening vascular injury. PATIENTS AND TECHNIQUE: Between August 2006 and July 2007, 12 patients with clinical stage IA-lung cancer underwent the video-assisted thoracoscopic left upper lobectomy with bronchial dissection prior to anterior and apico-posterior pulmonary artery dissections following dissection of lingular segmental artery. RESULTS: Operation time ranged from 75 minutes to 190 minutes (average 132 +/- 39 minutes). Operative blood loss ranged from 10 ml to 400 ml (124 +/- 112 ml). Postoperative course was uneventful except 1 patient who had left recurrent nerve palsy. CONCLUSIONS: Bronchial dissection prior to the upper segmental pulmonary artery dissections can produce better surgical field around left main pulmonary artery, leading to safe pulmonary arterial dissection during video-assisted thoracoscopic left upper lobectomy.

Long-term synaptic alteration in the rat hippocampal CA3 field following an entorhinal cortex lesion.

The entorhinal cortex is a key initial relay for cortical input to the hippocampus. To better understand hippocampal dysfunction resulting from early entorhinal cortex involvement in Alzheimer's disease, we stereotaxically injected ibotenic acid to produce unilateral entorhinal cortex lesions in rats. We then serially examined the CA3 hippocampal region by neuronal counts, histochemistry for acetylcholinesterase, and synaptophysin immunohistochemistry. Over 12 months, the neuronal counts did not change. Acetylcholinesterase-positive fibers were persistently but non-progressively beginning at 3 months. Synaptophysin immunoreactivity progressively declined over 12 months. Since much of the entorhinal cortex output proceeds to CA3 via the dentate gyrus, transsynaptic degeneration is suspected.

Skin sympathetic neuroeffector response is attenuated dose-dependently by systemic prostaglandin E1 injection in humans.

To clarify the effects of prostaglandin E1 (PGE1) on the vasoconstrictive responses, we compared the correlation between the amplitude of integrated skin sympathetic nerve activity (SSNA) and per cent reduction in skin blood flow (SBF) before and after the infusion of lipo PGE1 and placebo (bolus one-shot infusion, single blind study), and constant rate infusion of PGE1 (10 and 50 ng kg(-1) min(-1) by infusion pump, dose-dependency study) in ten healthy men. SSNA was recorded microneurographically from the median nerve simultaneously with SBF by laser Doppler flowmetry at the index fingertip. The measurement was conducted 30 min after injection of lipo PGE1 or placebo, and during the drip infusion of 10 and 50 ng kg(-1) min(-1) of PGE1 with maneuvers to enhance SSNA. The resting and activated skin blood flow were not significantly different between 10 ng lipo PGE1 and placebo administration, and between baseline and 10, 50 ng kg(-1) min(-1) of PGE1 injection. The vascular response, defined as the slope of regression line between logarithm of amplitude of integrated SSNA bursts and the reduction in SBF, was significantly suppressed by injection of lipo PGE1 as compared with that by placebo. It was also decreased dose-dependently by the constant rate infusion of PGE1 (10 and 50 ng kg(-1) min(-1)). We concluded that the intravenous injection of PGE1 attenuates vasoconstrictive responses to SSNA, and analysis of the relations between SSNA and vasoconstrictive response, i.e. the neuroeffector response, is suggested to be an important tool to assess the drug effect.

Depression in multiple system atrophy: a case report.

A 53-year-old woman who developed depression as the first symptom of multiple system atrophy was treated. Depression was followed successively by autonomic failure, parkinsonism and cerebellar ataxia. Treatment with L-DOPA, L-threo-DOPS, and thyroid releasing hormone was associated with improvement of autonomic failure and parkinsonism. As for depression, scores on the Zung scale and the Hamilton scale improved from 58 to 49 and from 30 to 22, respectively, This case is remarkable in that depression preceded neurologic dysfunction and was managed successfully by antiparkinsonian medication. A common underlying disturbance may be responsible for the depression and neurologic dysfunction in multiple system atrophy.

Effects of aging on cardiovascular responses to gravity-related fluid shift in humans.

BACKGROUND: Fluid shift induced by postural change causes autonomic neural responses of the cardiovascular system that buffer blood pressure fluctuation. The aim of the study was to clarify the effects of aging on cardiovascular autonomic functions in response to gravity-related fluid shift that unloads or loads the baroreceptors in human subjects. METHODS: A chest electrocardiogram, blood pressure by Finapres, and stroke volume by impedance method were measured in healthy young men (23-31 years old) and healthy elderly men (74-80 years old) during supine rest, at 90 degrees head-up tilt and thermoneutral head-out water immersion. Spectral analysis was applied to the time series data of the R-R intervals (heart rate variability [HRV]) and systolic blood pressure (blood pressure variability [BPV]). The arterial baroreflex gain for heart rate was estimated using frequency transfer function analysis. RESULTS: The young subjects had stable blood pressure, despite the larger amount of fluid shift induced by both tilt and immersion, and had marked changes in HRV and BPV. The elderly subjects failed to maintain stable blood pressure during these perturbations, despite less fluid shift and no significant changes in HRV and BPV. The arterial baroreflex gain for heart rate was not changed in the elderly subjects, whereas the gain decreased with upright in the young subjects and showed an increasing tendency during immersion compared with upright posture. CONCLUSIONS: These findings suggest that the adaptivity of the autonomic nervous system to gravity-related fluid shift is reduced in elderly people, and this may cause blood pressure instability.

Effects of three days of dry immersion on muscle sympathetic nerve activity and arterial blood pressure in humans.

The present study was performed to determine how sympathetic function is altered by simulated microgravity, dry immersion for 3 days, and to elucidate the mechanism of post-spaceflight orthostatic intolerance in humans. Six healthy men aged 21-36 years old participated in the study. Before and after the dry immersion, subjects performed head-up tilt (HUT) test to 30 degrees and 60 degrees (5 min each) with recordings of muscle sympathetic nerve activity (MSNA, by microneurography), electrocardiogram, and arterial blood pressure (Finapres). Resting MSNA was increased after dry immersion from 23.7+/-3.2 to 40.9+/-3.0 bursts/min (p<0.005) without significant changes in resting heart rate (HR). MSNA responsiveness to orthostasis showed no significant difference but HR response was significantly augmented after dry immersion (p<0. 005). A significant diastolic blood pressure fall at 5th min of 60 degrees HUT was observed in five orthostatic tolerant subjects despite enough MSNA discharge after dry immersion. A subject suffered from presyncope at 2 min after 60 degrees HUT. He showed gradual blood pressure fall 10 s after 60 degrees HUT with initially well-maintained MSNA response and then with a gradually attenuated MSNA, followed by a sudden MSNA withdrawal and abrupt blood pressure drop. In conclusion, dry immersion increased MSNA without changing MSNA response to orthostasis, and resting HR, while increasing the HR response to orthostasis. Analyses of MSNA and blood pressure changes in orthostatic tolerant subjects and a subject with presyncope suggested that not only insufficient vasoconstriction to sympathetic stimuli, but also a central mechanism to induce a sympathetic withdrawal might play a role in the development of orthostatic intolerance after microgravity exposure.

Postural modulation of soleus H-reflex under simulated hypogravity by head-out water immersion in humans.

To test our hypothesis that somatosensory inputs would influence postural modulation of soleus H-reflex, eleven subjects were investigated under the head-out water immersion (HOWI) conditions. Subjects were supine or standing on a tilting bed in each condition. They were instructed to maintain an upright posture with both legs. The water was filled to the subject's neck level in a test tank to reduce 95% of the gravitational effect by buoyancy. Surface electromyography of the soleus and tibialis anterior was measured. The soleus H-reflex was elicited at a stimulation intensity of 1.05 times the motor threshold. The recruitment profile of the motor response was unchanged between the conditions. The background activities of the soleus and tibialis anterior were not detected in any condition. The peak-to-peak amplitude of the H-reflex was significantly different between the conditions while the stimulation intensity (small M size) was not different. The soleus H-reflex during standing was significantly decreased compared with being supine in the control condition, whereas it did not in the HOWI condition. It was concluded that somatosensory inputs due to gravity exert an influence on postural modulation of the soleus H-reflex to maintain static posture in humans.

[A follow-up study on the outcome and relevant factors in senile dementia of Alzheimer type and vascular dementia].

We followed 126 patients with senile dementia of Alzheimer type (SDAT), and 129 over age 65 with vascular dementia (VD) who were diagnosed at the Center for Elderly Dementia in our institution between February 1990 and February 1993. At 5-year follow-up, 62 patients with SDAT and 71 patients with VD had died. These patients were assessed prospectively to investigate the neuropsychiatric and somatic factors related to the prognosis of SDAT and VD. There were no significant differences in the average age at onset and time of diagnosis of dementia between the SDAT and VD groups. Mean age at death, mean duration of dementia and 75% survival duration from dementia onset were shorter in patients with VD than in those with SDAT. Pneumonia was the most common cause of death in patients with either SDAT or VD, followed by geromarasmus in the SDAT group, and cerebrovascular and cardiovascular diseases in the VD group. In patients with SDAT, a poor prognosis was correlated with severe dementia, impaired intellectual function and degree of cortical atrophy. In patients with VD, physical complications, impaired motor function and hypoproteinemia enhanced the probability of death. This study confirmed that a progressive neurodegenerative course and physical conditions such as motor dysfunction or malnutrition are closely associated with the prognosis of patients with SDAT and VD, respectively.

Reinforcement enhances hippocampal acetylcholine release in rats: an in vivo microdialysis study.

Rats were trained to press a lever under a 'Multiple FI-60s and Extinction' schedule with food reinforcements. After learning the task, an in vivo microdialysis probe was inserted into the dentate gyrus and CA3 regions of the hippocampus, and the sequential changes in the dialysate acetylcholine (ACh) concentration were analyzed. In the session, two fixed-interval of reinforcement (FI) components (for 20 min) and two extinction (EXT) components (for 30 min) were alternated to examine the correlation between behavioral and neurochemical outcomes. The dialysate ACh concentration increased during the FI component and returned to the baseline during the EXT component of the schedule. Next, in order to dissociate the effect of discrimination from the effect of rewarding on the neurochemical changes in the hippocampus, we used a final TEST period (for 20 min) during which the actual schedule was extinction but the discriminative stimulus was on, i.e. the manifest condition of the test period was reinforcement. In the TEST period, the animals pressed the lever with almost the same frequency as during the FI component; however, the dialysate ACh concentration did not increase above the baseline concentration. These results suggest that ACh release in the rat hippocampus is associated with reinforcement but not with discrimination in operant conditioning.

Effect of entorhinal cortex lesion on hippocampal cholinergic system in rat in operant learning task as studied by in vivo brain microdialysis.

An in vivo microdialysis method was used to study the cholinergic alteration of the hippocampus in entorhinal cortex-lesioned rats performing a positive reinforcement operant learning task. Rats with bilateral entorhinal cortex lesions were implanted with a dialysis probe into the hippocampal CA3 after ten learning sessions. After 7 days, the bilateral entorhinal cortex-lesioned rats showed impaired acquisition of positive reinforcement operant learning. The basal level of the acetylcholine efflux decreased within 30 min before the beginning of a learning session. The hippocampal acetylcholine efflux showed a significantly diminished increase and rapidly returned to the basal level during the 60 min after the beginning of a learning session. These results suggested that enorhinal cortex lesion may cause damage to the hippocampal cholinergic system with disruption of the entorhinal cortex-hippocampus relay passage.

[Study of coxsackievirus group A. I. Serological variation of coxsackieviruses group A isolated in Gifu Prefecture].

Forty four isolated strains of Coxsackievirus group A were tested for antigenic variation with antiserum against each prototype strain by neutralization test. Isolates of type 2, type 4, type 5, type 8 and type 10 of Coxsackievirus group A, were not confirmed antigenic variation by neutralization test with immune sera to the prototype virus strain. However, 57.1% of type 9 isolates of Coxsackievirus A group were confirmed as variants. In isolates of Coxsackievirus group A type 16, the isolate in 1982 was neutralized with antiserum against the prototype strain, but the isolates after 1984 were neutralized to low titer or not at all by immune sera to the prototype virus strain. Therefore, the isolated strains were tested with immune sera against the isolated strain in 1988. So that, the isolated strains in 1982 and after 1984, were neutralized with the serum against the isolate in 1988, and moreover, the neutralizing titer of prototype strain was a third of the isolate. So that, for identification of type 16 of Coxsackievirus group A, it is necessary to use the immune sera against recently isolated strains.

[Study of coxsackievirus group A. II. Neutralization antibody positive against coxsackieviruses group A of sera of children in Gifu Prefecture].

One hundred forty seven sera of children in Gifu Prefecture, were tested for positive rate of neutralization antibody against Coxsackievirus group A (Cox. A). The results were as follows; 1. The positive rate of antibodies against Cox. A 4, Cox. A 10 and Cox. A 16 were detected in over 45%, but the positive rate of antibody against Cox. A 2 thought isolated rarely, was detected in the same rate. However, both the rate of isolation and positive rate of antibody against Cox. A 8 showed lower levels than other types. 2. The positive rate of antibodies against Coxsackievirus group A were different in every areas in the prefecture. In Seino area, the positive rate of antibodies of Cox. A 2, Cox. A 8 and Cox. A 10 were higher than in other areas. In Gifu area, the positive rate of antibodies against Cox. A 4 and Cox. A 16 were highest but the positive rate of antibody against Cox. A 8 was the lowest than other areas. In Hida(G) area, the positive rate of antibodies against Cox. A 2 and Cox. A 16 were the lowest levels than other areas. In Hide(T) area, the positive rate of antibodies against Cox. A 4 and Cox. A 10 of these viruses, were the lowest than other areas. 3. The positive rate of antibodies by age group, was showed the same pattern in Cox. A 2, Cox. A 4 and Cox. A 10, that is, there was a raise with age and reached to 80-90%. In Cox. A 8, the positive rate of antibody rose with age, but the highest positive rate of antibody reached only 35.5%. In Cox. A 16, the positive rate in 0-1 year olds showed a higher positive rate in 44%, which rose with age, but the rate dropped once at 6-7 age and again rose and reached to 86.7% in the 8-9 age group.

[A case of chronic encephalitis due to double infection with herpes simplex and measles viruses].

In a healthy 49-year-old man, a decrease in job efficiency was noticed along with bizarre behavior. On admission, he was euphoric, childish, superficial and had increased libido. Neurological findings were normal. There were no abnormal findings on routine blood tests, hematochemistry or urine analysis. MRI showed no abnormal findings. However, single photon emission CT (SPECT) showed diffuse hypoaccummulation of tracer from the temporal to frontal regions. Lumbar puncture showed clear cerebrospinal fluid (CSF) with pleocytosis and an elevated protein level. Moreover, antibody IgG titers to herpes simplex virus (HSV) and measles virus were elevated, according to EIA [serum HSV -1,202.2x, measles virus 47.1x: CSF HSV-116.1x, measles virus 9.9x]. The ratio of serum to CSF antibody titers of HSV and measles virus were 12.5 and 4.75, respectively. The antibody index values of HSV and measles virus IgG titers were 8.42 and 22.22. The ratio of albumin was 105.7. Chronic, progressive HSV encephalitis is rare, and there have been very few reports of encephalitis due to double infection by HSV and another virus. Our patient was diagnosed as having encephalitis due to double infection with HSV and measles virus, because the ratio of serum to CSF antibody titers was less than 20 and the antibody index values were over 1.91. Moreover, since the IgG index was elevated and the ratio of albumin was not low, it was suggested that the blood-brain-barrier had not been disrupted, and antibodies were being produced chronically in the medullary cavity. Hyperaccummulation of tracer on SPECT studies has been reported in the early stages of HSV encephalitis. In our case, while CT and MRI showed no abnormal findings, SPECT showed diffuse hypoaccummulation. SPECT appears to be a useful tool in the diagnosis of this disorder. In case of chronic, progressive personality change in middle-aged adults, we must be aware of double virus infection of the brain as a possible causal factor.

Sympatho-vagal responses in humans to thermoneutral head-out water immersion.

To clarify the role of autonomic nervous functions in cardiovascular adaptation to microgravity, heart rate variability (HRV) and blood pressure variability (BPV) were evaluated during thermoneutral head-out water immersion (HOI) of eight healthy young subjects 23 to 31 yr of age. The very low-frequency (VLF; 0.00-0.04 Hz) component of BPV tended to increase during HOI, whereas the low-frequency (LF; 0.04-0.15 Hz) component of BPV and the ratio of LF power to high-frequency (HF; 0.15-0.40 Hz) component (LF/HF ratio) of HRV decreased. The HF component of HRV increased in all the subjects during immersion up to the shoulder. Concomitantly, we found a decrease in heart rate and increases in stroke volume and cardiac output with no significant changes in BP and respiration rate during HOI. These results suggest that both vasomotor and cardiac sympathetic activities are suppressed and that the parasympathetic (vagal) activity is enhanced during HOI.

Synapse alteration in hippocampal CA3 field following entorhinal cortex lesion.

To model one aspect of the neurodegeneration observed in Alzheimer's disease and to investigate the synaptic alteration of the hippocampus associated with entorhinal cortex lesion, ibotenic acid was used to produce selective unilateral neuronal loss in rat entorhinal cortex. Immunohistological and microdensitometrical analyses confirmed ibotenic acid lesion of the entorhinal cortex after 3 months and showed a decrease of synaptophysin-immunoreactive substances in the stratum lucidum of the CA3 field. This study demonstrates that entorhinal cortex lesion can lead to synaptic alterations and cause damage to presynaptic terminals with projecting area in the disruption of the entorhinal cortex hippocampus relay passage.

Effects of three days of dry immersion on heart rate and blood pressure variabilities during head-up tilting in humans.

In this study we examined the effects of 3 days of dry immersion on heart rate variability (HRV) and blood pressure variability (BPV) in response to head-up tilting in 4 healthy young subjects aged 21 to 36 years. Resting value of the high-frequency (HF) power of BPV and HRV decreased, while the low-frequency (LF)/HF ratio of HRV and blood pressure increased after the dry immersion. The HF power of HRV decreased, while the LF/HF ratio of HRV and heart rate increased during head-up tilting before and after dry immersion. All powers of BPV and BP were unchanged during head-up tilting. The values of the decrease in the HF power of HRV and the increase in the LF/HF ratio during head-up tilting after dry immersion were larger than those before. These results suggest that 3 days of dry immersion altered the autonomic balance toward the sympathetic dominant at rest, and that cardiac function may play a crucial role in BP maintenance during head-up tilting compared with vasoconstrictor function.