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Background Collagen fibres in the dermis play an important structural role in the skin. Age-related changes to these fibres cause wrinkles and slackness of facial skin. However, it is not clear how dermal collagen fibres affect skin colour. The purpose of this study was to clarify the influence of altered collagen fibres on skin colour, using both experimental measurement of fibre density and Monte Carlo simulations in an optical model of skin. Methods Reflection spectra were measured from the cheeks of 12 Japanese women (22-65 years old) by spectral colorimeter. Two-dimensional autocorrelation functions were calculated from second harmonics generation (SHG) images acquired from the same locations and used to calculate collagen density indices. Monte Carlo simulations of light reflectance by skin were performed using a nine-layered model that precisely imitates skin structure. The relationship between dermal collagen fibre density and skin reflection spectra was analysed. Results A positive correlation was found between collagen density and skin brightness, as measured by the colour value, L* (using the L*a*b* colour space). In addition, collagen density showed a strong inverse correlation with age and with the optical absorption of dermis. The Monte Carlo simulations showed that the reflection spectrum of skin changes when the scattering coefficient of the dermis is altered. These changes were the same for simulated and experimentally measured reflection spectra. Conclusion When collagen fibre density in the upper dermis is decreased with age, skin colour becomes less bright because light scattering in the skin is decreased.

Background: The purpose of this study was to evaluate whether oral clonidine premedication becomes an alternative to N2O in terms of shortening the induction time and attenuation of the adrenergic response to tracheal intubation during inhalation induction with sevoflurane, and to evaluate the quality of anesthetic induction according to the patient's satisfaction. Methods: We studied 84 female patients who were randomly allocated into four study groups: Groups I and II received a placebo orally, and Groups III and IV received clonidine at 150 and 300 µg, respectively, 90 min before induction of anaesthesia. Patients were anesthetized using a triple-deep-breath technique with 5% sevoflurane in Groups I, III and IV, and with 60% N2O−5% sevoflurane in group II. Results: Induction time was significantly longer (P

Summary ONO-4641 is a next-generation sphingosine 1-phosphate (S1P) receptor agonist selective for S1P receptors 1 and 5. The objective of the study was to characterize the immunomodulatory effects of ONO-4641 using preclinical data. ONO-4641 was tested in both in-vitro pharmacological studies as well as in-vivo models of transient or relapsing–remitting experimental autoimmune encephalomyelitis (EAE). In vitro, ONO-4641 showed highly potent agonistic activities versus S1P receptors 1 and 5 [half maximal effective concentration (EC50) values of 0·0273 and 0·334 nM, respectively], and had profound S1P receptor 1 down-regulating effects on the cell membrane. ONO-4641 decreased peripheral blood lymphocyte counts in rats by inhibiting lymphocyte egress from secondary lymphoid tissues. In a rat experimental autoimmune encephalomyelitis (EAE) model, ONO-4641 suppressed the onset of disease and inhibited lymphocyte infiltration into the spinal cord in a dose-dependent manner at doses of 0·03 and 0·1 mg/kg. Furthermore, ONO-4641 prevented relapse of disease in a non-obese diabetic mouse model of relapsing-remitting EAE. These observations suggest that ONO-4641 may provide therapeutic benefits in the treatment of multiple sclerosis.

Resistin is an adipocytokine that induces insulin resistance and is predominantly expressed in adipocytes and peripheral blood mononuclear cells. Resistin expression increases in inflammatory diseases as well as diabetes mellitus, and is upregulated by bacterial pathogens and proinflammatory cytokines. The aim of this study was to identify resistin in human gingival crevicular fluid, to compare the resistin levels in gingival crevicular fluid between subjects with and without periodontitis and diabetes mellitus and to investigate the regulation of resistin release from human neutrophils by Porphyromonas gingivalis lipopolysaccharide (P-LPS).Gingival crevicular fluid samples were collected from patients with chronic periodontitis (n = 24), patients with diabetes mellitus-related periodontitis (n = 18) and healthy subjects (n = 21). Resistin in gingival crevicular fluid was determined using western blot analysis and an ELISA kit. The glycated hemoglobin (HbA(1c)) value was obtained from patients with diabetes mellitus-related periodontitis by a medical interview. Human neutrophils were cultured with P-LPS (0-1000 ng/mL), or incubated with inhibitors of actin or microtubule polymerization in the absence or presence of P-LPS. The medium and cellular fractions were used for determination of resistin by ELISA.The resistin level in gingival crevicular fluid from patients with periodontitis or diabetes mellitus-related periodontitis was significantly higher than that of healthy subjects. The resistin level in gingival crevicular fluid was correlated with gingival index score, but not blood HbA(1c) value. The P-LPS increased resistin release from human neutrophils, and its induction was decreased by actin polymerization inhibitors.We show, for the first time, the presence of resistin in gingival crevicular fluid. A high resistin level in gingival crevicular fluid samples from periodontitis patients may to some extent be related to P-LPS-induced resistin release from neutrophils.

Pigment epithelium-derived factor (PEDF) has recently been shown to be the most potent inhibitor of angiogenesis in the mammalian eye. We, along with others, have very recently found that loss of PEDF is involved in the development and progression of diabetic retinopathy. However, there are no studies on the allelic effects of PEDF gene polymorphism in diabetic retinopathy. In this study, we investigated whether a functional amino acid change, a methionine to threonine polymorphism (Met72Thr polymorphism) of the PEDF gene, is associated with microangiopathy in 143 patients with diabetes. We found that there were no significant associations between PEDF Met72Thr gene polymorphism and diabetic microangiopathy. These observations suggest that these genetic variants might not be involved in the mechanism of diabetic microangiopathy in patients with diabetes.

Reducing sugars can react nonenzymatically with the amino groups of proteins to form Amadori products and subsequently cross-linked, heterogeneous fluorescent derivatives called advanced glycation end products (AGE). AGE can arise in vivo from various types of reducing sugars or dicarbonyl compounds and their formation and accumulation are known to progress during normal aging. In individuals with diabetes mellitus, this progression is greatly accelerated. The aim of the present study was to investigate which kinds of serum AGE components were associated with the severity of diabetic retinopathy in 72 type 2 diabetic patients without renal dysfunction. Serum levels of glucose-, glyceraldehyde- or methylglyoxal-derived AGE (methyl-AGE) were measured by an enzyme-linked immunosorbent assay. No significant correlations were found between serum levels of various AGE and HbA1c level, current age, systolic and diastolic pressure, diabetes duration, serum creatinine or blood urea nitrogen level in type 2 diabetic patients. A significant elevation of serum glucose-AGE was found to be associated with severity of diabetic retinopathy. While no differences in serum methyl-AGE levels were found between patients with diabetic retinopathy and those without, serum levels of glyceraldehyde-AGE showed a tendency to increase as normal retinal status advanced to simple and proliferative retinopathy (p = 0.06). The present results suggest that among various types of AGE, glucose-AGE serum levels may be a useful marker of diabetic retinopathy in type 2 diabetic patients without renal dysfunction.

Brotizolam and zopiclone have a common ability to bind to the benzodiazepine recognition site and have been used as useful preoperative hypnotics. The aim of the present study was the quantitative evaluation of the preoperative hypnotic effects of brotizolam and zopiclone by actigraphy. Forty patients received brotizolam 0.25 mg (group B) or zopiclone 7.5 mg (group Z) in randomized manner at 21:30 on the night before surgery. Sleep and awake was identified by wrist activity measured with a motion-logger actigraph. Sleep time was assessed in total period from 22:00 to 6:00 and its 4 subdivided 2-hour periods (22:00-24:00, 24:00-2:00, 2:00-4:00, 4:00-6:00). The total sleep time in group B (448 +/- 23 min) was significantly longer than that in group Z (416 +/- 43 min). Group Z showed a significant reduction in sleep time in period 4 (4:00-6:00), compared with other periods, whereas group B did not show any difference among 4 periods. In comparison of each period between 2 groups, group B showed significant longer sleep time in period 4. An actigraphic assessment of sleep time has demonstrated the quantitative difference of the effects of brotizolam and zopiclone as preoperative hypnotics.

To investigate the effect of simultaneous bolus injection of 2% lidocaine 2 ml on preventing the pain on propofol injection, 80 patients were randomly assigned to one of four study groups; Group I received simultaneous bolus injection of 2% lidocaine 2 ml with infusion of propofol; Group II received bolus injection of saline 2 ml, 10 s before the start of infusion of propofol-lidocaine mixture; Groups III and IV received bolus injections of lidocaine and saline, separately 10 s before starting propofol infusion. Incidence of propofol-induced pain was significantly more frequent (P0.001) in Group IV (70%) than in the other groups (20% each). Number of patients who were satisfied with this anesthetic induction and requested for the same induction method in the next anesthesia was significantly larger in the groups receiving lidocaine (P0.05). Simultaneous bolus injection of lidocaine with propofol showed a similar clinical efficacy compared with both preadministration and premixing of lidocaine in preventing the propofol-induced pain.

The development of retinal lesions induced by a uniform regimen of interferon-alpha therapy for chronic hepatitis C was prospectively investigated.Eighty-one patients received 6 mega units of natural interferon-alpha intramuscularly daily for 2 weeks and then 3 times a week for 22 weeks. The total dose of interferon-alpha administered was uniformly 478 mega units per patient. Two expert ophthalmologists prospectively examined the patients for retinal lesions before, during and after the therapy.Retinopathy was not found in comparison groups or any of the patients before treatment. In total 34.6% (28/81) of the patients showed cotton-wool spots or minor retinal hemorrhage, or both lesions, during therapy, but these lesions were reversed during or after interferon therapy. The occurrence rates of cotton-wool spots alone, retinal hemorrhage alone and both lesions were 13.6% (11/81), 6.2% (5/81), and 14.8% (12/81), respectively. The appearance of retinopathy did not correlate with patients' background including viral loads and response to the therapy, but was more frequently found in older patients and patients with hypertension and/or diabetes mellitus; disappearance of retinopathy was more prolonged than in patients without these complications. Almost all the lesions appeared 2-4 months after the start of the therapy, and the severity of the lesions did not differ between patients with and without hypertension and/or diabetes mellitus.Although it is not clear if interferon-associated retinopathy occurs in a dose-dependent manner, the present study shows a standard pattern of the occurrence of retinopathy in patients with chronic hepatitis C receiving a uniform dosage of natural interferon-alpha.

Children who experienced the Hanshin-Awaji Earthquake Disaster were followed to ascertain how the psychological and physical reactions after this disaster changed. Changes observed in the symptoms of children at one and two years after the earthquake were compared between those who had lived in severely damaged area (level 7 on the Japan Meteorological Agency intensity scale) and those who had lived in mildly damaged area (less than 5 on the same scale). The survey was conducted using a questionnaire filled out by the children's parents. Two years after the earthquake, the children had returned to normal in terms of their physical conditions, even in the severely damaged area. However, symptoms of PTSD (Post-Traumatic Stress Disorder) such as persistent reexperiencing, persistent avoidance, and increased arousal were significantly more frequently found among children from the severely damaged area than among those from the mildly damaged area. To evaluate the psychological and physical reactions after the disaster is very important in order to support the children when large-scale disasters occur.

To clarify the relationship between the epidemics of severe invasive group A streptococcal infections (streptococcal Toxic Shock-Like Syndrome: TSLS) and common group A streptococcal infections in Japan, we examined the T serotypes of S. pyogenes strains (group A streptococci) isolated from clinical specimens of the streptococcal infections (17999 cases) in the period 1990-5, including the severe infections (TSLS) (29 cases) in the period 1992-5. Characteristic points of the analyses were: (1) dominant serotypes of the infections in these periods were T12, T4, T1, T28 and TB3264, which were consistently isolated; (2) isolates of T3 rapidly increased through 1990 to 1994 while T6 decreased in the period 1990-3; (3) when Japanese area was divided into three parts, T3 serotype tended to spread out from the north-eastern to the south-western area; (4) strains of T3 and T1 serotypes were dominant in the TSLS. Dominant-serotype strains of streptococcal infections did not always induce severe infections and dominance of T3 serotype in the TSLS seemed to be correlated with the increase of T3 in streptococcal infections. These results may indicate that certain clones of S. pyogenes are involved in the pathogenesis of the TSLS.

Systemic hypertension is a constant feature of chronic renal failure, mediated by renin and exacerbated by salt and fluid loading. Vascular atherosclerosis appears to accelerate in patients on long-term dialysis. Therefore, it is important to control hypertension and keep appropriate renal blood flow during living renal transplantation surgery. Amrinone, a phosphodiesterase inhibitor, produces vasodilation in arterial smooth muscle as well as venodilation in the capacitance bed. By increasing myocardial contractility it increases inotropic effect. Amrinone has potent inodilator effects because of its dual mechanism of action. The current study is aimed to compare hemodynamic effects between amrinone (3-5 mg.kg-1.min-1) (AMR group, n = 4) and nitroglycerin (0.3-1.0 mg.kg-1.min-1) (NTG group, n = 5), combined with dopamine (3-5 mg.kg-1.min-1) in nine patients undergoing living renal transplantation. Increase in cardiac index in AMR group was significantly larger than that in NTG group. Values of systemic and pulmonary vascular resistance in AMR group were significantly smaller than those in NTG group. No significant difference was found in renal function in the post-operative period.

The action of efonidipine hydrochloride ((+/-)-2-[benzyl(phenyl)-amino]ethyl 1,4-dihydro-2,6-dimethyl-5-(5,5-dimethyl-2-oxo-1, 3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxy late hydrochloride ethanol, CAS 1110011-76-8, NZ-105) a new dihydropyridine calcium antagonist, on cardiac hemodynamics at rest and during exercise as well as plasma concentration and pharmacokinetic parameters were studied in 9 patients with angina pectoris. NZ-105 was administered 40 mg once daily for a week and cardiac hemodynamics parameters were measured at rest and during exercise using a bicycle ergometer before and after treatment. All patients showed anginal symptoms during exercise before treatment, while only 4 showed anginal symptoms during exercise after treatment. Improvement on electrocardiograms (ECG) (0.1 treatment mV) was detected in 4 out of 9, and NZ-105 was recognized to have an anti-anginal action. The mean plasma concentration of NZ-105 at the time was 14.5 ng/ml. At rest, reduction in blood pressure and decrease in total peripheral vascular resistance were observed, however, NZ-105 showed no effect on heart rate, cardiac index, pulmonary arterial pressure and central venous pressure. During maximum exercise, a decrease in total peripheral vascular resistance, reduction in pulmonary arterial pressure and central venous pressure, increasing tendency of left ventricular ejection fraction, and increase in cardiac index were observed. However, NZ-105 showed no effect on heart rate and blood pressure. Based on the results mentioned above, cardiac hemodynamics of NZ-105 during exercise, featured primarily, reduction of afterload and improvement of cardiac functional deterioration due to exercise. In conclusion, NZ-105 is useful in patients with ischemic cardiac diseases by improving hemodynamics and ECG findings during exercise in patients with effort angina.

Twenty-two very low birth weight infants at preschool ages of 5-6 years were studied to clarify the correlation between cognitive function and MRI findings. Cognitive function was evaluated by the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Frostig developmental test of visual perception. Ventricular enlargement, assessed by the bioccipital index (B. I.) measured on MRI, was correlated to cognitive disorders. Children with periventricular high intensity areas (T2-weighted images) extending from the posterior periventricular region to the parietal lobe tend to highly suffer from cerebral palsy and visuo-perceptual impairment. These results indicate that the disorders of cognitive function in very low birth weight infants were caused by a damage of association fibers in periventricular areas which was detectable by MRI.

To determine the prognostic factors for splenectomy in patients with chronic idiopathic thrombocytopenic purpura (ITP), 26 consecutive patients who had undergone splenectomy as a treatment for ITP in the last 20 years were investigated retrospectively. Predictive values of age, sex, the interval between diagnosis and surgery, presence of antiplatelet antibodies or accessory spleen, bleeding time, response to corticosteroids, response to high-dose immunoglobulin, weight of spleen, serum platelet-associated immunoglobulin G, preoperative maximal platelet count, and preoperative minimal platelet count were examined with multivariate analysis by multiple regression. Age less than 50 years at surgery, platelet count of 100 x 10(9)/l or more in response to high-dose immunoglobulin, and a maximal platelet count of 100 x 10(9)/l or more before splenectomy were favorable prognostic factors (p0.05). The correlation coefficient, sensitivity, specificity, and positive-predictive value of the analyzed multiple regression based on prognostic factors were 0.885, 68.8%, 85.7% and 91.7%, respectively. In conclusion, splenectomy is an effective treatment for younger patients, large maximal preoperative platelet counts and preoperative immunoglobulin dependence. Multivariate function analysis was useful for predicting outcome.

Immediate hypersensitive reactions induced by buckwheat ingestion are considered to be IgE-mediated. Some subjects, however, develop no immediate adverse reactions after buckwheat ingestion despite high levels of buckwheat-specific antigens IgE. The mechanism is unknown.To investigate the mechanisms.RAST for buckwheat and rice and RAST inhibition between these antigens were performed using sera from 23 buckwheat-sensitive subjects and 30 buckwheat-tolerant subjects who had IgE antibodies for both buckwheat and rice.RAST values for buckwheat and rice were significantly correlated with each other (P.01) in the buckwheat-tolerant group, but not in the buckwheat-sensitive group. This suggests the IgE antibodies from the subjects without any overt symptoms after buckwheat ingestion recognize the cross-reactive epitope between buckwheat and rice, whereas the IgE antibodies from those with immediate reactions to buckwheat ingestion do not. RAST inhibition assays were performed to evaluate this. RAST inhibition of heterogeneous combination of inhibitor and disc antigen such as rice and buckwheat was significantly smaller than that of homologous combination of rice and rice or buckwheat and buckwheat in the group with immediate symptoms after buckwheat ingestion. There was no significant difference in RAST inhibition between homologous and heterogeneous combinations in the group without the symptoms.There was cross-reactivity with IgE antibodies between buckwheat and rice and IgE antibodies from the buckwheat-tolerant subjects with high levels of IgE antibodies from the buckwheat might recognize the epitopes on buckwheat antigens which cross-react with rice antigens, whereas IgE antibodies from the buckwheat-sensitive subjects might bind to buckwheat-specific epitopes.

There has been a rapid increase in the number of patients with hepatocellular carcinoma (HCC) in Japan. This may be the result of an increased number of patients with hepatitis C virus (HCV)-related liver disease, and of prolonged survival of these patients due to improvement in the management of cirrhosis. Indeed, 96% of recent HCC patients admitted to our hospital were related to viral hepatitis B or C, and HCV infection accounted for three-fourths of these cases. Since most HCCs develop in the course of chronic liver disease, it is important to identify high risk groups for HCC development and to detect small HCCs early. We have established a screening method by combining various imaging studies and the measurement of serum alpha-fetoprotein; this combination has markedly increased the detection of small HCCs less than 2 cm in diameter. Multiple HCCs can occur in the same patient, either simultaneously or successively. Partly for this reason, the cumulative recurrence rate of HCC is very high even after surgical resection. In order to determine whether such HCCs arise from the common or different clonal origins, we have utilized the restriction landmark genomic scanning method. It remains to be clarified whether HCV plays a direct role in hepatocarcinogenesis, and whether antiviral treatments such as interferon eventually will decrease the incidence of HCC among patients with chronic HCV infection.

To ascertain the effect of local treatment for unresectable primary liver tumor, 59 patients were investigated retrospectively. Patients were classified into four groups; transcatheter arterial embolization (TAE) group, intermittent intra-arterial infusion chemotherapy group, combined therapy group (TAE+intermittent intra-arterial infusion chemotherapy) and a group without adjuvant therapy. The results revealed that TAE and intermittent intra-arterial infusion chemotherapy both prolonged the survival period. We found that the survival rate depends largely on the therapeutic method. No correlations were confirmed with the liver function nor stage grouping of the tumor. Therefore, we concluded that intermittent intra-arterial infusion chemotherapy is a beneficial treatment, considering its minimal adverse effect, broad indication and the fact that it does not require hospitalization.

IgE is considered to be involved in immediate hypersensitive reactions (IHR) following egg ingestion. IgE antibody levels to egg-white (EW) antigens in the IHR-positive group (n = 19, mean age +/- SD = 5.2 +/- 4.5 yr) were higher than those in the IHR-negative group (n = 13, mean of age +/- SD = 3.6 +/- 2.2 yr). However, even in the IHR-negative group, some patients showed high IgE to EW. RAST inhibition tests with heat-treated (100 degrees C, 5, 10, and 30 min) egg-white antigens were performed on 13 serum samples from subjects with IHR and 9 serum samples from subjects without IHR. Heat treatment decreased the IgE-binding activity of egg white and it was speculated that IgE from IHR-negative subjects bound to relatively heat-unstable sites of egg-white antigens. Furthermore, we selected IHR-negative subjects (n = 8, mean of age +/- SD = 3.0 +/- 1.7 yr) with higher IgE antibody levels than the lowest limit of IgE to EW of the IHR-positive group and compared IgE to ovomucoid (OM), ovalbumin (OA), conalbumin (CA), and lysozyme (Ly) between these IHR-negative and positive groups. IgE-binding activities to egg-white components, including OA, CA, and Ly but not OM, were significantly decreased with heat treatment. The IHR-negative group showed significantly lower IgE to OM (untreated, 5, 10, 30 min treatment) and 5 min treated OA alone than the IHR-positive group, while no difference was found in IgE to other components between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

We report on two cases of rheumatoid arthritis (RA) presenting autoimmune hepatic diseases. The first patient, who had been diagnosed as RA at the age of 63, was hospitalized in order to undergo surgery for total left knee replacement at the age of 69. She acquired acute serum hepatitis as a result of blood transfusion she received during the operation. Five years later, she visited our clinic suffering from polyarthritis. She was found to have hyper-alkaline phosphatase (ALP) and hyper rGTP, but no AMA. The second patient, a 60-year-old female whose onset of RA was at the age of 45, complained of general fatigue, and was admitted to the hospital because of persistent liver dysfunction. When corticosteroid was administered to these patients, ALP and rGTP levels in the first case, and AST and ALT levels in the second case were reduced to values in the normal range. ANA in the first case continued to register negative, but ANA in the second case became positive after the patient developed acute hepatitis. Both patients were found to have anti-p25 triplet liver/kidney microsome antibody. We discuss the clinical significance of this antibody.

There is evidence from animal models that the iodine content of thyroglobulin (Tg) may influence its antigenicity in thyroid autoimmunity. To elucidate the effect of iodination of hormonogenic sites of human Tg (hTg) on its autoantigenicity, a synthetic peptide (TB: hTg 2546-2571), containing two hormonogenic tyrosine residues of hTg, and a chemically-iodinated peptide (TB-I) were prepared. We immunized C3H/He (H-2k) mice, a high responder strain to Tg, and BALB/c (H-2d), a low responder strain, with TB or TB-I plus lipopolysaccharide. Lymph node cells from the two strains immunized with TB or TB-I proliferated in response to both TB and TB-I. Anti-Tg autoantibodies were detected in both strains when immunized with TB-I, while immunization with TB failed to produce anti-Tg antibodies. Furthermore, one of the C3H/He mice immunized with TB-I developed diffuse thyroiditis, but BALB/c mice did not. These findings indicate that the iodination of the hormonogenic tyrosine residues of hTg, in other words, the synthesis of mono- and di-iodotyrosine (MIT and DIT) residues, is necessary for the production of anti-Tg autoantibodies in high and low responder mice and for the induction of autoimmune thyroiditis in high responder mice.

Immediate hypersensitive reactions (IHR) induced by buckwheat ingestion are considered to be IgE-mediated. However we found 28 subjects without IHR to buckwheat ingestion out of 46 subjects who had positive RAST values for both buckwheat and rice antigens. The IHR-positive group showed significantly higher RAST values for buckwheat antigens (p0.01) but lower RAST values for rice antigens (p0.01) than did the IHR-negative group. RAST values for buckwheat and rice were significantly correlated with each other (p0.01) in the IHR-negative group, but not in the IHR-positive group. An effective dose-dependent inhibition was obtained in a RAST inhibition assay between homologous combinations of inhibitor and disc antigens such as rice and rice or buckwheat and buckwheat. The IHR-positive group showed no significant RAST inhibition between heterogeneous combinations of rice and buckwheat antigens. In contrast, the IHR-negative group showed a significant decrease in IgE binding even in the RAST inhibition assay between heterogenous combinations. These results led to the conclusion that there is cross-reactivity with IgE antibodies between buckwheat and rice and that IgE antibodies from IHR-negative subjects might recognize the epitopes on buckwheat antigens which cross react with rice antigens, whereas IgE antibodies from IHR-positive subjects might bind to buckwheat-specific epitopes.

To investigate the involvement of the sympathetic nervous system and cell membrane sodium transport in hypertensive cardiac hypertrophy, we divided 51 middle-aged male patients with essential hypertension into cardiac hypertrophy and noncardiac hypertrophy groups. We then compared the plasma noradrenaline concentration after exercise, the cardiovascular response to exercise and sympathomimetic agents, and cell membrane sodium transport in the two groups. There were differences between the cardiac hypertrophy and noncardiac hypertrophy groups with regard to the pressor response to exercise and noradrenaline (i.e. the response to sympathetic alpha-receptor stimulation) as well as the intracellular sodium concentration and cell membrane sodium transport. We concluded that there were abnormalities of the pressor response to alpha-receptor stimulation and of intracellular sodium concentration and cell membrane sodium transport in patients with hypertension and cardiac hypertrophy. These abnormalities might play some role in the pathogenesis of hypertensive cardiac hypertrophy.

Sarcoidosis is a multisystem disorder of unknown etiology presenting most frequently with bilateral hilar lymphadenopathy (BHL), pulmonary infiltration, and ocular and skin lesions. Neurological manifestations are found in about 5% of patients with systemic sarcoidosis. We report the case of a 58-year-old woman with neurosarcoidosis manifesting as isolated, peripheral polyneuropathy. This is a rare neurological manifestation. Two years before admission, she was found to have an abnormal chest radiograph showing BHL, and pulmonary sarcoidosis was diagnosed by lung biopsy. Six months later, she noted facial erythematous lesions, and lupus pernio was confirmed by skin biopsy. Fifteen months before admission, she developed visual disturbance of the right eye caused by sarcoid-uveitis. Two months before admission, she complained of paresthesia and weakness of limbs. She was admitted for nerve-biopsy. Sural nerve biopsy revealed sarcoid granulomas in the epineurial space, periangitis and axonal degeneration. Neurologically, the diagnosis of mononeuritis multiplex without cranial nerve palsy was made. Treatment with 30 mg prednisolone daily was initiated, and neurological and extraneurological improvement was noticeable within two weeks of treatment. The dose was carefully lowered over several months.

Recent advances in both diagnosis and treatment of hepatocellular carcinoma (HCC) have improved the prognosis and changed the clinical significance of the subsequently increasing distant metastases. Of 163 patients with HCC, 76 (47%) were treated successfully. The cumulative recurrence rate in these patients was 65% after 3 years, and 82% after 5 years. Six patients with HCC in whom distant metastases were detected after successful treatment of the primary lesion, are reported. Two patients underwent curative surgical resection, and four cases were treated medically, resulting in a 31.9 to 94.3% reduction in tumor size in the CT scan image. Distant metastases without intrahepatic recurrence were diagnosed 10 to 46 months after the treatment of the primary lesions. The sites of the metastases included bone 3; lung 2; and adrenal gland 1. Distant metastases found after successful treatment of the primary lesions are of great clinical significance for the treatment of HCC.

To clarify the site and potency of the analgesic and anesthetic action of epidurally administered morphine, we investigated the effects of epidurally and intravenously administered morphine (100 micrograms/kg) on change in the pressure pain threshold (PPT) and the minimum alveolar concentration (MAC) of halothane. Epidural morphine (EM) increased PPT significantly (P0.01) at the points around the surgical incision by 40% and 60% from baseline compared with intravenous morphine (IM) with which PPT remained at baseline 1 and 2 h after administration, respectively. Duration of analgesia was much longer in EM than in IM (18 h vs 1.7 h). EM increased PPT from preoperative value at the forehead and the points around the surgical incision by 9.9% and -24.9% at 1 h, by 10.9% and 3.8% at 4 h, and by -19.5% and -50.4% at 12 h after administration at mean values, respectively. Halothane MAC in EM and IM were 0.54% and 0.57%, respectively, 40 min after administration. Halothane MAC in EM at 4 h and 12 h after administration were 0.45% and 0.70%, respectively. The results suggest that EM provides long-lasting analgesia by its time-related differential effects on the neuraxis.

The blood flow in aortic aneurysms and dissections was evaluated using cine MR imaging which depicts turbulent blood flow as a signal loss within a high-intensity blood pool or flowing blood. Six patients with 8 aortic aneurysms ranging 38 to 70 mm in diameter, and 16 patients with aortic dissections were imaged with a 0.5 or 1.5 T superconducting magnet using an ECG-gated fast field echo technique. Circulating flows were observed in 3 of 8 aortic aneurysms. This suggests that turbulent blood flow did not occur prominently in the relatively small aortic aneurysms imaged in this study. The false lumens were thrombosed in 2 of 16 aortic dissections. In 13 of the remaining 14 dissections jet flows were observed through the entry into the false lumen. In 2 of these cases the jet flows moved to and fro through the entry. The entry was not detected in a small abdominal aortic dissection. Re-entry was seen in one case. Using a spin-echo imaging technique, the entry can be diagnosed by detecting the interruption of the intimal flap and the flow void within the false lumen. However, the entry was more clearly depicted and the direction of blood flow better determined by cine MR imaging compared with the conventional spin-echo imaging technique. Cine MR imaging provides useful information about the blood flow in aortic aneurysms and dissections noninvasively.

A C15O2 continuous inhalation and a steady-state theory using positron emission tomography (PET) have been used to quantitate regional cerebral blood flow. We extended this method for quantitative regional myocardial blood flow (RMBF) measurement. Forty-three patients, involving 4 normal volunteers, 16 patients with coronary heart disease (CHD), 20 patients with hypertrophic cardiomyopathy (HCM), and 3 patients with dilated cardiomyopathy (DCM), were studied. 6 min-scan was recorded in the steady-state condition during C15O2 continuous inhalation. A C15O inhalation scan was required to obtain the blood pool image. The subtracted image showed myocardial perfusion image. These images demonstrated homogeneous accumulation in normal volunteers. Reduced accumulation were detected in patients with myocardial infarction. Hypertrophied myocardium was demonstrated in patients with HCM. Diffuse heterogeneous accumulation was demonstrated in patients with DCM. Fourteen patients with HCM, whose left ventricular myocardial thicknesses were more than 20 mm, were selected for the RMBF measurement to minimize errors due to the partial volume effect. The arterial blood activity was measured by assigning a region of interest to the left atrial cavity on PET images. RMBF was calculated using the steady-state theory. Calculated flow values ranged from 21.2 to 152.6 ml/min/100 g. The good correlation was obtained between RMBF using 13NH3 first pass method and RMBF using gas inhalation method in six patients. These results indicate that C15O2 PET has the potential capability for the noninvasive quantitation of RMBF.

The purpose of this study is to compare the characteristics of images obtained by positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) in the fasted state (6 hours) and in the glucose-loaded state (oral 50 g glucose load). In the both condition FDG-PET were performed in 18 cases with old myocardial infarction. PET images in the fasted state were divided into 2 groups (Group A; 12 cases and Group B; 6 cases). FDG uptake of normal region was visually absent (grade 0) in group A, whereas it was visually apparent (grade 1-3) in group B. Serum free fatty acid in group B was significantly lower than that in group A. In the 7 cases, the relation between myocardial FDG uptake of the infarcted regions and reversibility after coronary intervention was studied. Both in the fasted and in the glucose-loaded state, postoperative improvement was observed in the segments, in which myocardial uptake of FDG were visually apparent (glucose-loaded state, 11/13 segments; fasted state, 6/8 segments). Therefore FDG-PET images appeared to be useful for evaluating myocardial viability.

To evaluate the effect of smoking on nonrespiratory function in the lung, a dynamic PET with 13NH3 in the lung was performed in 18 normal volunteers without lung disease nor congestion (9 non-smokers, 4 exsmokers, 5 smokers). After intravenous bolus injection of 13NH3, twenty serial 5.5-second scans followed by six 30-second scans were performed. Regions of interests were assigned on the ventral, lateral and dorsal part of the right lung and time-activity curves were generated through 26 images. The activity curve demonstrated a biexponential clearance from the lung with fast and slow component. The retention fraction (RF), fractional size of the slow component, was calculated, and the half-times (t 1/2) of both components were also evaluated. A significant increase of RF and prolongation of t 1/2 of slow component were observed in smokers compared to non-smokers and exsmokers. However, no significant difference of RF nor t 1/2 of both components was observed between non-smokers and exsmokers. These results suggest that long term smoking may modify the pulmonary kinetics of 13NH3, but the change is reversible after cessation of smoking for one year or longer.

Neuroblastoma is the most common solid tumour in infancy and childhood. The tumour usually produces large amounts of catecholamines. Few patients with neuroblastoma, however, were reported to have become hypertensive because of catecholamine metabolism within the tumour itself. This is one of the most important differences compared with pheochromocytomas. We experienced a hypertensive crisis accompanied by tachycardia and an increase in the plasma catecholamine concentration during surgery in a patient with neuroblastoma. The plasma catecholamine level was comparable to that of pheochromocytoma. Phentolamine and propranolol were effective to control the hypertension and tachycardia.

The morphological examination of the left ventricular trabeculae was performed using MRI (0.5T) in 14 normal volunteers, 12 patients with dilated cardiomyopathy (DCM), and 9 patients with old myocardial infarction (OMI). Left ventricular trabeculae were observed at the free walls of the left ventricle in all subjects, but not at the septal wall. Left ventricular trabeculae were larger in DCM than in the normals. The trabeculae were scarce in OMI and inner sides of the infarcted myocardium were very smooth. The development of the left ventricular trabeculae was graded as diminished, ordinary, and marked. Ordinary trabeculae were seen in 86% of the normals, whereas; marked trabeculae in 75% of DCM, and diminished trabeculae in 78% of OMI. In patients with DCM, the mean area of the left ventricle with marked trabeculae was greater than that with ordinary trabeculae. The more dilated left ventricle, the thinner the anterior wall was and the lower the ejection fraction was in DCM and OMI, though there were no significant differences in values of these 3 items between DCM and OMI. The MRI findings on the development of the trabeculae were confirmed in patients with DCM at autopsy. Thus, the MRI findings were very useful in the differential diagnosis between DCM and OMI.

Cross-reactivity between rice, wheat, corn, Japanese millet and Italian millet in Poaceae family were studied by absorption test, radioallergosorbent test (RAST), and RAST inhibition assay. In absorption test using Phadebas RAST discs, more than 50% absorption of IgE antibodies was observed between rice, wheat and corn. There were significant correlations of RAST values for cereal grains including rice, wheat, corn, Japanese millet and Italian millet. RAST inhibition assay between every combinations of these cereals showed dose-dependent decrease in IgE-binding. These data indicated cross-reactivity with IgE antibodies between the five cereals in Poaceae family. RAST values for RP16KD significantly correlated with those for Italian millet as well as rice but not with those for corn and wheat. There was a trend of positive correlation between RAST values for RP16KD and Japanese millet. In RAST inhibition assay using sera with positive RAST for these five cereal grains and RP16KD, RP16KD inhibited IgE-binding to these all cereal discs in dose-dependent manner. Similarly, all of five cereal grain extracts showed an effective diminution in IgE-binding to RP16KD disc. These results indicated possible participation of IgE-binding structure on RP16KD in cross-reactivity between these cereal grains in Poaceae family.

In primary Sjögren's syndrome, various cutaneous manifestations may become apparent: annular erythema or eruptions reminiscent of erythema multiforme, lichen planus or erythema nodosum (dermo-panniculitis), chilblain-like erythema, purpura, cheilitis, and xerosis, are some of them. In the clinical diagnosis, the following laboratory tests are of value: Schirmer test, rose bengal test, fluorescence staining techniques, gum test, sialography, sialoscintigraphy, lip biopsy. In some cases, dryness can be absent though the above-mentioned skin manifestations are observed. Mothers with Sjögren's syndrome can deliver babies with neonatal lupus erythematosus. Serological testing almost always reveals anti-Ro/SSA-autoantibody and the more specific anti-La/SSB in the sera of patients. The sensitivity of detection can be enhanced by using the immunoblotting technique and the two-dimensional immunoblotting method. In some cases, a new antibody against carbonic anhydrase has been detected.

The purpose of this study is to evaluate the long-term results of medical treatment for a dissecting aorta and to detect the risk factors that determine the prognosis of medically treated patients. During the past 10 years, 228 patients with aortic dissections were admitted to our hospital and affiliated hospitals. One hundred thirty-four patients, including 60 with proximal type (Stanford, type A) and 74 with peripheral type (Stanford, type B) dissections, were treated by medical means alone. The survival rates of medically treated patients with type A dissections at 24 hours, 2 weeks, and 5 and 10 years after the onset of the disease were 72, 43, 34, and 28%, respectively, and the survival rates in type B dissections were 100, 92, 76, and 56%, respectively. The risk factors that determine poor prognosis in the acute phase of dissections were type A dissection and serious complications (rupture of the aorta, shock, cerebral accident, myocardial infarction, severe aortic regurgitation, renal failure, mesenteric infarction, and arterial occlusion in the extremities). The risk factors in the chronic phase were serious complications, excluding shock and rupture in the acute phase, the large diameter of the dissecting aorta, and increasing age. These results show that emergency surgical intervention is indicated in the patients with acute type A dissections and in those who had acute type B dissections with these serious complications. Medical treatment may be tentatively recommended for the patients with uncomplicated type B dissections until the operative death rate in these patients becomes less than presently identified.

Postoperative course including serial changes in values of liver function tests and occurrence of hepatic failure was investigated in 59 patients with hepatocellular carcinoma. Eleven cases out of 59 patients were associated with chronic hepatitis (CH group), while remained 48 cases were with liver cirrhosis (25 cases of group A and 23 of group B in Child's classification). There was no significant difference in survival rate or recurrence rate after operation among these three groups. Hepatic failure within one year after hepatectomy was observed in 9%, 28% and 91% of patients in groups CH, Child's A and Child's B, respectively, and the frequency of occurrence of hepatic failure in Child's B group was significantly higher than those of groups CH and Child's A. Hepaplastin test and serum albumin levels recovered from the decline after hepatectomy in groups CH and Child's A. On the other hand, no recovery was found in Child's B group as well as lower levels before operation and that was thought to be the major reason for the frequent occurrence of hepatic failure in Child's B group.