Effects of bright light exposure on heart rate variability during sleep in young women.

To investigate the effects of evening bright light on the autonomic nervous system, heart rate variability (HRV) during sleep was analyzed in dim light (DL) and bright light (BL) conditions. We recorded polysomnography in nine healthy young women aged 20-21 years. Time series of % delta power was calculated in the 0.49-2.20 Hz band. Heart rate variability was analyzed from a 10-min segment of slow wave sleep. The low- to high-frequency ratio and the low-frequency component decreased significantly in the BL conditions compared with the DL conditions. However, the power of the high-frequency component did not change in the two conditions. These results indicate that evening BL affects the autonomic nervous system during slow wave sleep.

Interleukin-2 as a modulator of 5-fluorouracil in hepatic arterial immunochemotherapy for liver metastases.

BACKGROUND/AIMS: Hepatic arterial infusion of interleukin-2-based immunochemotherapy has yielded a high response rate (> 75%) in patients with unresectable liver metastases. In order to clarify the mechanisms that underlie the apparent benefit of combination treatment, the role of IL-2 as a modulator of 5-fluorouracil metabolism was investigated. METHODOLOGY: A single dose of 5-fluorouracil (50 mg/kg) with or without IL-2 (3500 Japan Reference Units/kg) was given via the hepatic artery to rats bearing liver metastases. Thirty minutes later samples of liver metastatic foci or surrounding normal liver tissue were removed for the measurement of thymidylate synthase, thymidine kinase and dihydropyrimidine dehydrogenase activity, and 5-fluorouracil content. RESULTS: 5-fluorouracil levels in tumor were significantly higher than in normal liver. Although the addition of IL-2 reduced 5-fluorouracil levels in both tumor and normal liver tissues by the activation of dihydropyrimidine dehydrogenase, the ratio of tumor/normal liver 5-fluorouracil levels was unchanged. Both thymidylate synthase and thymidine kinase activities were significantly inhibited in tumor tissue when the combination of 5-fluorouracil and IL-2 was administered. CONCLUSIONS: IL-2 increases 5-fluorouracil cytotoxicity through the inhibition of thymidylate synthase/thymidine kinase activities in the hepatic arterial infusion.

Autonomic nervous function after evening bright light therapy: spectral analysis of heart rate variability.

In order to investigate the effects of 5000 lx evening bright light on autonomic nervous function, a spectral analysis was used to assess heart rate variability in consecutive 5-min epochs just after 60 min of bright light therapy was given to 12 young women (range: 20-21 years of age). The study revealed that a low frequency band (LF) increased in bright light conditions (BL) in comparison with controlled conditions (CL). High frequency band (HF), LF:HF ratio and the coefficient of variance (CV R-R) were not significantly different between the two conditions. These results indicate that 5000 lx evening bright light may affect sympathetic nervous system activity in healthy women.

A new preoperative immunochemotherapy for the treatment of locally advanced esophageal cancer.

A promising preoperative immunochemotherapy regimen for locally advanced esophageal cancer is herein described. A 67-year-old man suffering from severe dysphagia was diagnosed with unresectable esophageal cancer at initial examination because of a tumor of 11 cm in length and suspicion of trachea invasion. Neoadjuvant immunochemotherapy was undertaken for the down-staging. Interleukin-2 (IL-2) (3.5 x 10(5) Japan reference units), nedaplatin (7 mg/m2) and 5-FU (300 mg/m2) were administered intravenously daily for 5 days a week for three weeks. The gross findings of a barium esophagogram and esophagoscopy revealed significant tumor regression in both size and shape. The patient underwent an esophagectomy through a laparotomy followed by a right thoracotomy. The surgical specimens were serially sectioned and examined microscopically. All of the surgical margins were clear (upper and lower margins as well as the adventitia), and there was no evidence of lymph node metastasis. The surgical specimen revealed neoplastic squamous ghost cells surrounding significant lymphocyte infiltration. This appears to be a unique feature of this particular neoadjuvant immunochemotherapy.

Involvement of liver-associated immunity in hepatic metastasis formation.

AIMS: Hepatic metastasis formation and prevention were studied from the viewpoint of liver-associated immunity. METHODS: RCN-9, a colonic cancer cell line derived from Fischer rats, and its subclone RCN-H4, in which the cancer is highly metastatic to the liver, were used. Fischer rats that were inoculated with parent RCN-9 colonic cancer cells (5 x 10(6)) via the portal vein showed liver metastasis in less than 60% of the animals. In contrast, all rats (100%) that received RCN-H4 produced multiple liver metastases. To investigate the difference of hepatic metastasis formation, we assessed the susceptibility of both cell lines against hepatic sinusoidal lymphocytes (HSL) by 51Cr-release assay, and the expression of MHC class I and class II of both cell lines by flow cytometry. In addition, we examined whether activation of HSL by interleukin-12 (IL-12) can prevent liver metastasis of highly metastatic clone RCN-H4. RESULTS: The RCN-H4 clone showed decreased susceptibility to lysis by natural cytotoxic cells in HSL. This decrease in cell susceptibility was attributable to an increase in cell surface expression of MHC class I antigen. Administration of IL-12, a potent NK/CTL stimulatory cytokine, augmented the cytotoxic activity against the RCN-H4 clone and prevented liver metastasis of RCN-H4 inoculated into the portal vein. CONCLUSIONS: Liver metastasis formation is positively correlated with the strength of the hepatic immune system which mainly consists of ontogenetically primitive T cells. As these effectors exert their cytotoxicity in a MHC-nonrestricted fashion, tumor cells that highly express MHC class I antigen can readily avoid hepatic surveillance and apt to cause liver metastasis. Augmentation of the hepatic immune system, for instance, with IL-12 administration, can prevent liver metastasis even in tumor cells with a high potential for liver metastasis.

Characteristics and treatment of temporal lobe epilepsy with a history of complicated febrile convulsion.

This study aimed to examine the close correlation between complicated febrile convulsions (CFC) and medial temporal lobe epilepsy and to delineate characteristics of temporal lobe epilepsy with CFC. Patients with temporal lobe epilepsy were divided into those with a prior episode of CFC (n=52), those with febrile convulsions other than CFC, and those without either (n=345). Clinical constellations, neuroimaging, drug resistance, and effects of temporal lobectomy of the three groups were compared. A close association between CFC and temporal lobe epilepsy was confirmed. The salient features of temporal lobe epilepsy with CFC were early age at onset of habitual seizures (about 10 years), the predominance of autonomic auras, and a high incidence of MRI evidence of unilateral medial temporal sclerosis. Patients with temporal lobe epilepsy with prior CFC had an excellent outcome after surgery, by contrast with an unfavourable response to drug therapy. The surgical results were discouraging in patients with temporal lobe epilepsy without history of any febrile convulsions and without solid brain tumours. These results indicate surgical intervention as the choice of therapy in a substantial number of patients with temporal lobe epilepsy with a history of CFC.

Characteristics of temporal lobe epilepsy with mesial temporal sclerosis, with special reference to psychotic episodes.

This study investigates the histories and the clinical course of 111 patients who had nonlesional temporal lobe epilepsy. We compared 61 patients with unilateral hippocampal sclerosis (UHS group) and 50 patients with minimal change (MRI negative group) assessed on the basis of MRI. In agreement with previous reports, we confirmed statistically that patients in the UHS group strongly tended to have had febrile convulsive status during early childhood or infancy and that habitual seizures tended to begin at a younger age than the other subset of nonlesional temporal lobe epilepsy. Strikingly, episodes of psychoses, especially postictal psychoses, occurred significantly more often in the UHS group than in the MRI negative group. Additional involvement of temporal neocortex further augmented this association. We stress the role of mesial temporal pathology, and its linkage to the temporal neocortex, in the genesis of postictal psychoses.

Postictal psychosis: a comparison with acute interictal and chronic psychoses.

We studied 30 patients with postictal psychosis and compared them with 33 patients with acute interictal psychosis and 25 patients with chronic psychosis. All patients had either complex partial seizures (CPS) or EEG temporal epileptogenic foci. Patients with postictal psychosis had a high incidence of psychic auras and nocturnal secondarily generalized seizures. The most striking feature that distinguished postictal psychosis from both acute interictal and chronic psychoses was phenomenological: the relatively frequent occurrence of grandiose delusions as well as religious delusions in the setting of markedly elevated moods and feeling of mystic fusion of the body with the universe. In addition, postictal psychosis exhibited few schizophreniform psychotic traits such as perceptual delusions or voices commenting. Reminiscence, mental diplopia, and a feeling of impending death were also fairly frequent complaints of patients with postictal psychosis. Interictal acute psychosis and chronic epileptic psychosis were psychopathologically similar. Although acute interictal and chronic epileptic psychoses could simulate schizophrenia, postictal psychosis results in a mental state quite different from that of schizophrenic psychosis.

Peri-rolandic and fronto-parietal components of scalp-recorded giant SEPs in cortical myoclonus.

Scalp topography of giant SEPs to median nerve stimulation was studied in 4 patients with cortical myoclonus of various etiology. The positive peak (P30) at the contralateral parietal area was simultaneously accompanied by a negative peak at the frontal area (N30), and at least one of these two peaks was enhanced in 2 patients. Another positive peak (P25) and a negative peak (N35) were also identified at the peri-rolandic area with different latency from P30 and N30, respectively, in all patients. N35 was enhanced in 3 patients, and P25 in 2 patients. It is concluded that, as seen in normal subjects, tangential (P30-N30) and radial (P25 and N35) components of SEPs are most likely distinguishable in giant SEPs, and that either one or both of those components is enhanced in different ways depending on the patients.

[Thyroid hormones and thyroid-stimulating hormone in patients with chronic heart failure--relationship between primary hypothyroidism with iodine organification defect and chronic heart failure].

Serum concentrations of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were measured in 127 patients with chronic heart failure (CHF) (left ventricular ejection fraction; 40% < or = and NYHA; III-IV), and 1,079 patients without CHF (non-CHF) (left ventricular ejection fraction; 40% < or = and NYHA; I-II). Serum-T3, T4 and free-T4 were significantly decreased in patients with CHF. The prevalence of slight increase of serum TSH (5 < or = TSH < 15 microU/ml) were 20.5% in CHF and 4.08% in non-CHF. There was a statistically significant difference in the prevalence of slight increase of TSH (p < 0.01). In the patients with slight increase of serum TSH, the 123I-thyroid scintigraphy and perchlorate test were performed 12 patients with CHF and 19 patients with non-CHF. The incidences of iodine organification defect were 33.3% in CHF and 5.26% in non-CHF. There was a statistically significant difference in the incidence of iodine organification defect (p < 0.05). The histologic examination of thyroid biopsy specimen obtained 12 patients with CHF and primary hypothyroidism, these revealed only non-specific mild atrophic changes. Follicular damage and lymphocyte-infiltration were not evident. These findings suggest that the primary hypothyroidism were frequently complicated in CHF and associated with iodine organification defect by reduction of thyroid-peroxidase activity or decrease of hydrogen peroxidase. We conclude that the primary hypothyroidism with iodine organification defect was probably developed as a result of CHF.

[Changes in biological rhythm and sleep structure during the menstrual cycle in healthy women].

It is well known that clinical symptoms such as psychosis, epileptic seizures and sleep disturbances aggravate around the time of menstruation. In some healthy women, subjective sleep feelings or moods have been reported to change throughout the menstrual cycle, which suggests that sleep structure and sleep-wake rhythm may change during the menstrual cycle. We investigated a circadian pattern of plasma melatonin, sleep-wake rhythm and sleep characteristics in the different phases of the menstrual cycle in young healthy women under controlled environmental conditions. The subjects were seven healthy women, aged 18 to 19, with regular menstrual cycles. They stayed in an experimental facility, where temperature and humidity were kept within a narrow range, for three days in successive five weeks. They got up and went to bed at their preferable time. Polysomnography was performed using ambulatory cassette EEG system on the first and second night. Sleep stages were scored according to Rechtshaffen and Kales' criteria. Plasma melatonin was measured at 1-hour intervals for 24 hours on the third day. The menstrual cycle was divided into four phases (menstruation, follicular, early luteal and late luteal). Although the plasma melatonin level in the late luteal phase tended to be higher than in other phases, no significant difference was observed across four phases. The phase in plasma melatonin level did not change. As for sleep-wake rhythm, the time of getting up on the first day was significantly late in the late luteal phase (p < 0.05), although it showed no significant change on the second day. The time of going to bed did not change. Sleep characteristics changed during the menstrual cycle. There was a significant difference in the amount of stage 3 + 4, slow wave sleep (p < 0.05), which was more abundant in the follicular phase than in the luteal phase. TIB (time in bed), SPT (sleep period time), TST (total sleep time) seemed to increase in the menstrual and follicular phases, while stage W increased in the early and late luteal phases. However, there were no significant differences in these parameters. The other parameters did not show any changes. The changes in amount of stage 3 + 4 throughout the menstrual cycle seem to be due to endogenous factors, because environmental factors were controlled in this experiment. It is possible that the menstrual cycle also affect the plasma melatonin level and sleep-wake rhythm.

[The significance of repeated users of geriatric health care facility].

Our geriatric health care facility was established 3 years ago. The real number of users since April 1989 to March 1991 amounts to 519, of which 62 have been admitted 3 times or more (defined as repeated here). At the same time, this facility has a day care activity 6 times a week. The utilization rate of day care activity was 14.8% for total users, while it was 59.7% for repeaters. These results indicate that repeaters actively utilize day care activity as well as geriatric health care facility. In other words, repeaters usually reside at home and their home cares are greatly supported by both repeated admissions to the facility and daily utilization of day care activity which are effective in improving ADL of the disabled elderly. It is concluded that geriatric health care facility plays an important part in supporting home care of the disabled elderly as well as transitional step from hospital to their own home.

[Assessment of coronary hemodynamics and myocardial perfusion in patients with syndrome X by digital subtraction angiography and 201Tl-myocardial scintigraphy].

To evaluate coronary hemodynamics and myocardial perfusion, left coronary digital subtraction angiography (DSA) and Tl-201 myocardial scintigraphy were performed in patients with syndrome X. The coronary circulation time (CCT) was significantly prolonged after the injection of isosorbide dinitrate and contrast medium i.c. Apical T1/2 was also prolonged on ergonovine malate provocation test. We suspected that the vascular response of the coronary peripheral artery was impaired, and microvascular spasm probably existed in patients with syndrome X. The prevalence of abnormal myocardial perfusion defect on exercise Tl-201 SPECT in syndrome X was very high, and coronary hemodynamics was significantly disturbed in the group of syndrome X with abnormal Tl-201 SPECT. Tl-201 lung/heart count ratio significantly increased in syndrome X on treadmill test. Because of this, exercise induced left ventricular dysfunction was suspected. We concluded that the main pathophysiological finding of impaired coronary circulation in syndrome X was microvascular spasm.

Epileptic seizures in the 4p- syndrome: report of two cases.

We report ictal phenomena in two patients with the 4p- syndrome captured on simultaneous video-EEG monitor. One patient, diagnosed as having partial epilepsy, had complex partial seizures and hemiconvulsive status epilepticus. This was associated with more severe mental retardation. The second patient was diagnosed as having the West syndrome and exhibited tonic spasms with a cluster formation. We conclude that various types of epileptic seizures may occur in patients with the 4p- syndrome, including grand mal and myoclonic seizures.

[Coronary hemodynamics in vasospastic angina: quantitative analysis by digital subtraction angiography].

To evaluate the coronary circulation and myocardial perfusion dynamics, we performed left coronary digital subtraction angiography (DSA) in 35 patients with vasospastic angina. The left coronary circulation time (CCT) measured from the proximal left coronary artery to the coronary sinus was 5.77 +/- 0.86 sec, and the left epicardial conducting artery transmission time (CAT) measured from the proximal left coronary artery to the apical area was 2.65 +/- 0.82 sec in normal controls. The CCT and CAT were significantly prolonged in patients with vasospastic angina, indicating that the coronary peripheral vascular resistance is probably greater after the cessation of nitrates and Ca(++)-antagonists. After the intracoronary injection of ergonovine malate, the CCT was slightly shortened, but the apical T1/2 was significantly prolonged in patients with vasospastic angina. This suggested that coronary vasospasm is present not only in the epicardial arteries but also in coronary arteries with peripheral resistance. These phenomena were not observed in normal controls. We performed left coronary DSA after conventional left coronary cineangiography. When the CCT exceeded 6.7 sec, we considered that the coronary circulation was significantly impaired. We concluded that the coronary DSA is very useful for evaluating abnormal coronary circulation in patients with vasospastic angina during myocardial perfusion.