Effect of exercise training on the density of endothelial cells in the white adipose tissue of rats.

We examined the effects of a 9-week exercise training (TR) in Wistar male rats, beginning at 4 weeks of age, on the density of endothelial cells (ECs) in epididymal white adipose tissue (WAT) and the mRNA expression of angiogenic factors in adipose tissue stromal vascular fraction (SVF) cells. The number of ECs and mRNA expressions were assessed by lectin staining and real-time reverse transcriptase-polymerase chain reaction, respectively. Compared with control (CR) rats, TR rats gained weight more slowly and had significantly lower final weight of WAT due to the reduction in the size and the number of adipocytes. TR significantly increased the number of ECs per square millimeter and per adipocyte (1.37- and 1.23-fold, respectively) in WAT. This is probably because the number of adipocytes is fewer while the number of ECs is constant in the WAT of TR rats, because the regression line of TR rats for adipocyte number-dependent EC number was shifted toward the left without significant differences in the slopes between groups. TR also induced the upregulation of mRNA expression of vascular endothelial growth factor (Vegf)-A and Vegf-receptor-2 in SVF cells, thereby retaining a constant number of ECs in the WAT.

Angiotensin II receptor blockade prevents microangiopathy and preserves diastolic function in the diabetic rat heart.

BACKGROUND: Cardiac microangiopathy may be involved in the development of heart failure in diabetes mellitus. OBJECTIVE: To evaluate the effect of angiotensin II receptor blockade on cardiac function and fine structures in diabetes. METHODS: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats (n = 30), a model of spontaneously developing diabetes mellitus, and their diabetes resistant counterparts (n = 20) were used. At 30 weeks of age, when the OLETF rats show hyperglycaemic obesity with hyperinsulinaemia, the animals were divided into two groups and given candesartan, an angiotensin II receptor blocker, 0.2 mg/kg/day, or vehicle for six weeks. Capillary density was evaluated in the left ventricular myocardium by electron microscopy, matrix metalloproteinase (MMP) activity by zymography, and cytokines by reverse transcriptase polymerase chain reaction. RESULTS: Compared with the control rats, the OLETF rats at 36 weeks showed decreased peak negative dP/dt (mean (SD): 2350 (250) v 3492 (286) mm Hg/s) and increased cardiomyocyte diameter (24.3 (0.6) v 18.9 (0.6) microm) (both p < 0.05). Thickening of the capillary basement membranes and decreased capillary density were observed. Angiotensin receptor blockade improved almost all the haemodynamic variables, and the histological findings became similar to those of the controls. Angiotensin receptor blockade also activated MMP-2 and prevented an increase of inflammatory cytokines, especially interleukin (IL)-1beta and IL-6, in the diabetic heart. CONCLUSIONS: Angiotensin II receptor blockade preserved left ventricular diastolic function. It was also potent at improving cardiomyocyte diameter and the thickening of the capillary basement membrane, increasing MMP-2 activity, and decreasing inflammatory cytokines. With all these changes, candesartan could contribute to cardioprotection in diabetes mellitus.

Possible involvement of mast-cell activation in aspirin provocation of aspirin-induced asthma.

BACKGROUND: Although there is increasing evidence of the importance of cysteinyl leukotrienes (LT) as mediators of aspirin-induced bronchoconstriction in aspirin-sensitive asthma, the cellular origin of the LT is not yet clear. METHODS: Urinary concentrations of leukotriene E4 (LTE4), 11-dehydrothromboxane B2, 9alpha,11beta-prostaglandin F2, and Ntau-methylhistamine were measured during the 24 h following cumulative intravenous administration of increasing doses of lysine aspirin to asthmatic patients. In addition, the urinary concentrations of these metabolites were measured on 5 consecutive days in a patient who suffered an asthma attack after percutaneous administration of nonsteroidal anti-inflammatory drugs. RESULTS: In aspirin-induced asthma patients (AIA, n=10), the basal concentration of urinary LTE4, but not the other metabolites, was significantly higher than that in aspirin-tolerant asthma patients (ATA, n=10). After intravenous aspirin provocation, the AIA group showed a 13.1-fold (geometric mean) increase in excretion of LTE4 during the first 3 h, and 9alpha,11beta-prostaglandin F2 also increased in the AIA group during the first 0-3 h and the 3-6 h collection period. Ntau-methylhistamine excretion was also increased, but to a lesser degree. Administration of aspirin caused significant suppression of 11-dehydrothromboxane B2 excretion in both the AIA and ATA groups. When the percentage of maximum increase of each metabolite from the baseline concentrations was compared between the AIA group and the ATA group, a significantly higher increase in excretion of LTE4, 9alpha,11beta-prostaglandin F2, and Ntau-methylhistamine was observed in the AIA group than the ATA group. An increased excretion of LTE4 and 9alpha,11beta-prostaglandin F2 has been detected in a patient who suffered an asthma attack after percutaneous administration of nonsteroidal anti-inflammatory drugs. CONCLUSIONS: Considering that human lung mast cells are capable of producing LTC4, prostaglandin D2, and histamine, our present results support the concept that mast cells, at least, may participate in the development of aspirin-induced asthma.

An anaphylactic reaction possibly associated with an intraoperative coronary artery spasm during general anesthesia.

We report a case of anaphylactic reaction occurring during general anesthesia that may have been accompanied by a coronary artery spasm. The present case and a review of the medical literature suggest that coronary artery spasm is evoked by common vasoactive mediators with anaphylactic reactions. Coronary artery spasm should be counted as a symptom of the cardiovascular manifestation of anaphylaxis. Clinicians should be aware of this possible complication when treating an anaphylactic reaction, especially in patients at risk for atherosclerosis. Early recognition of ST segment elevation is essential for diagnosis and treatment of coronary artery spasm.

Lack of B cell leakiness in BALB/cA-nu, scid double mutant mice.

BALB/cA mice homozygous for both nu and scid mutations (BALB/cA-nu/nu, scid/scid) were developed by mating between BALB/cA-scid and BALB/cA-nu. These mice have greater longevity than C.B-17-scid because no thymic lymphoma occurs in them unlike in the latter. C.B-17-scid is known to show the leaky phenomenon in which a few clones of functional T and B cells develop in aged C.B-17-scid. Unexpectedly, the leaky B cells and T cells were absent or suppressed in BALB/cA-nu, scid mice when cytokine expressions were determined by RT-PCR, lymphocyte phenotypes by flow cytometry and serum immunoglobulin levels by ELISA. These results indicate that B cell leakiness may be induced by leaked T cells. BALB/cA-nu, scid mice may be useful as a recipient in allo- and xeno-transplantation experiments because of the absence of both thymic lymphomas and leakiness, in addition to lack of hair.

Calculation and visualization of Lamb wave motion

Lamb wave propagation was calculated by using hybrid boundary element method (HBEM) that is the combination of the analytical mode expansion and boundary element method. HBEM makes it possible to simulate Lamb wave propagation in large plates with shorter computational time. The numerical results, e.g. displacements and stresses, were collected at every time step for the inner grid points and visualized as mpeg movies or jpeg pictures. The generation mechanism of Lamb waves is investigated as a numerical example.

Circulating biochemical marker levels of collagen metabolism are abnormal in patients with abdominal aortic aneurysm.

Changes in extracellular matrix composition induced by abnormal collagen metabolism in the aortic wall may be an important factor in the progression of aortic structural changes. The authors have measured several types of biochemical marker for collagen metabolism in plasma: carboxyterminal propeptide of type Icollagen (PICP) for a pure collagen synthesis marker, matrix metalloproteinase-1 (MMP-1) for a degradation marker of collagen matrix, and tissue inhibitors of metalloproteinase-1 (TIMP-1) as a native inhibitor of MMP-1. Subjects of this study were 17 patients with abdominal aortic aneurysm (AAA), 14 patients with atherosclerosis obliterans (ASO), and 22 age/sex-matched healthy controls (HC). Blood samples were drawn from a forearm vein and measured by radioimmunoassay or enzyme-linked immunosorbent assay. Plasma concentrations of PICP in patients with AAA were significantly decreased compared to those in HC patients (82.0 +/- 16.4 vs 111.3 +/- 40.3 ng/mL; p < 0.01), but those in patients with ASO (105.4 +/- 55.4 ng/mL) were comparable to control concentrations. Although no differences in plasma concentrations of MMP-1 were observed among the three subject groups (HC, 20.0 +/- 5.6 ng/mL; ASO, 21.4 +/- 13.8 ng/mL; AAA, 24.5 +/- 11.7 ng/mL; NS), MMP-1/PICP ratio as an index of collagen degradation to collagen neosynthesis in AAA was significantly elevated compared to HC (0.32 +/- 0.18 vs 0.20 +/- 0.08; p < 0.01). Plasma concentrations of TIMP-1 in patients with AAA (293.8 +/- 61.2 ng/mL) or ASO (327.6 +/- 54.9 ng/mL) were significantly higher than in HC (227.3 +/- 60.2 ng/mL; both p < 0.01). In conclusion, these data suggest that although a compensatory mechanism such as increased TIMP-1 may be activated, collagen neosynthesis may decrease with relatively increased collagen degradation in patients with AAA.

Spontaneous intracranial hypotension successfully treated by epidural patching with fibrin glue.

We report a case of spontaneous intracranial hypotension due to a cerebrospinal fluid leak at the C2 level, which was successfully treated by epidural fibrin glue patching. Epidural blood patching was performed twice, first with 6 mL of autologous blood and then with 10 mL, but the intracranial hypotension was unresponsive. Although successful treatment of postdural puncture headache and persistent leak after intrathecal catheterization by epidural patching with fibrin glue has been reported, fibrin glue has not been previously applied in spontaneous intracranial hypotension. Our observation suggests that epidural patching with fibrin glue should be considered in patients with spontaneous intracranial hypotension, if epidural blood patching fails to resolve the symptoms.

Thrombosed dissection of the ascending aorta complicating extravasation.

This report presents 2 patients with thrombosed dissection of the ascending aorta complicating extravasation. The first case was an 85-year-old male admitted with shock due to cardiac tamponade. Plain computed tomography (CT) demonstrated a dilated ascending aorta without clear evidence of aortic dissection. The second case was a 77-year-old female presenting with shock, in whom an enhanced CT scan demonstrated a dilated ascending aorta and periaortic effusion. However, dissection of the distal ascending aorta was not identified in either case before emergency surgery. In case 1, soon after the bloody pericardial effusion was decompressed during the operation, bleeding from the ascending aorta occurred. A small intimal tear was found in the distal ascending aorta, and in each case the pseudolumen was filled with fresh thrombus. The ascending aorta was replaced. Each patient had an uneventful postoperative recovery. Based on this experience, it is suggested that patients with thrombosed ascending aortic dissection complicating extravasation should undergo early graft replacement.

[Measurement of theophylline concentrations by AccuMeter--comparison with the EIA method].

Theophylline is widely used for treating patients with bronchial asthma. However, since the therapeutic concentration range is narrow, adverse reactions are frequent and often difficult to control, making monitoring of theophylline concentration mandatory for its efficient and safe use. In this study, we employed the AccMeter which allowed us to measure theophylline concentrations quickly and with ease, and compared it with EIA method. AccMeter is a kit which consists of two parts. One part consists of a chromatopaper with antitheophylline mouse monoclonal antibody fixed on it, on which a smaple is applied with enzyme-linked theophylline. The other part consists of a coloring solution. We used a part of arterial blood samples collected for gas analysis as trial samples. Both whole blood and plasma from 50 patients who did or did not receive theophlline were analysed. Plasma portions were also used for measurements by the EIA method. Results from all three measurements were almost identical, and showed good correlation. The time necessary for measurement using AccMeter was about 20 minutes. We consider this method to be useful for clinics due to its simplicity and ease of handling, and the accuracy of the results obtained.

[A new device for allergen skin testing].

We have made a new device for allergen skin testing, which can be used easily. It consists of two parts. One, several gears are fixed on a board in a row, and when one gear goes round, other gears also go round simultaneously. A disposable needle is attached to each gear. A semi-spherical hole is made in the lower surface of a disposable needle, and a sharp needle is fixed in, but not at the centre of the hole. The other, small tanks are arranged in a row at the same distance as the gears. When the disposable needles are inserted to the tanks filled with allergen extract, it is hold in a semi-spherical hole by surface tension. The allergen extracts go intradermally, when the needles move semi-circular on a human skin. We performed skin tests to 23 patients with this device, and got satisfactory results as screening tests.

Lidocaine increases the ventricular fibrillation threshold during bupivacaine-induced cardiotoxicity in pigs.

Ventricular fibrillation (VF) is a cause of death in bupivacaine-induced cardiovascular toxicity. We have examined the therapeutic effects of lidocaine on the threshold for bupivacaine-induced VF in in situ beating swine hearts. Twenty-four animals were allocated to one of three groups: 0.25% bupivacaine, 1% lidocaine or 0.25% bupivacaine with 1% lidocaine were infused into the left anterior descending coronary artery in increasing doses of 0, 1, 2, 4, 8 and 16 ml h-1 for 15 min, respectively. ECG and haemodynamic variables were monitored continuously during infusion. Regional myocardial function in the area supplied by the left anterior descending coronary artery was assessed using the sonomicrometry technique. VF did not occur in the lidocaine group. VF developed at higher infusion rates in animals given bupivacaine with lidocaine (in one animal at an infusion rate of 8 ml h-1 and in seven at 16 ml h-1) compared with animals given bupivacaine alone (in one at an infusion rate of 4 and in seven at 8 ml h-1). Although regional myocardial function decreased with increases in the infusion rate in each group, the depressant effects of the bupivacaine solution (medial inhibitory infusion rate of systolic shortening: IR50 = 2.43 (0.43) ml h-1) were significantly greater than those of the lidocaine solution (IR50 = 5.83 (0.87) ml h-1), but did not differ from those of the bupivacaine with lidocaine solution (IR50 = 3.54 (0.56) ml h-1). This study indicates that a combination of lidocaine and bupivacaine increased the threshold for bupivacaine-induced VF without further depressing myocardial contractility.

Three-month effects of candesartan cilexetil, an angiotensin II type 1 (AT1) receptor antagonist, on left ventricular mass and hemodynamics in patients with essential hypertension.

Using cine magnetic resonance imaging (MRI) and echocardiography, we investigated the effects of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on left ventricular (LV) mass and hemodynamics in patients with essential hypertension. Ten patients (four men and six women) with essential hypertension received candesartan cilexetil 2-8 mg/day orally for 8-12 weeks. After drug administration, systolic blood pressure (BP) decreased from 178.9 +/- 17.2 mmHg (mean +/- SD) to 150.2 +/- 14.3 mmHg (P < 0.0001) and diastolic BP from 101.4 +/- 6.5 mmHg to 87.8 +/- 11.9 mmHg (P = 0.0021). Both MRI and echocardiography revealed a significant decrease in LV mass index (LVMI) after candesartan cilexetil. MRI indicated that LVMI decreased from 111.3 +/- 31.3 g/m2 to 102.6 +/- 32.1 g/m2 (P = 0.0484) and echocardiography that LVMI decreased from 123.9 +/- 31.1 g/m2 to 115.8 +/- 31.4 g/m2 (P = 0.0316). Total systemic vascular resistance decreased significantly during treatment with candesartan cilexetil in both MRI and echocardiography assessment, from 1847.2 +/- 636.3 dynes.s.cm-5 to 1540.4 +/- 432.0 dynes.s.cm-5 (P = 0.0034) on MRI and from 1820.4 +/- 318.8 dynes.s.cm-5 to 1659.0 +/- 317.7 dynes.s.cm-5 (P = 0.0060) on echocardiography. These findings suggest that candesartan cilexetil 2-8 mg/day orally for 8-12 weeks is beneficial in the regression of cardiac hypertrophy in patients with essential hypertension.

Submillimeter-pixel MR images of hepatic cavernous hemangiomas.

Several criteria have been used for differentiating hepatic cavernous hemangioma from other tumors at magnetic resonance imaging (MRI). Included are signal intensity and lobulation of the tumor. We counted the frequency of presence of lobulation of liver hemangiomas on T2-weighted images (T2WI), and measured the signal-intensity ratio (SIR) on T1-weighted images (T1WI) and on T2WI with a 0.9 mm x 0.9 mm pixel size using a 0.5 T magnetic resonance system. Eighty-three cavernous hemangiomas in 44 patients and 67 malignant tumors in 44 patients were retrospectively studied. Seventy-five of the cavernous hemangiomas (90%) exhibited lobules of various sizes, and four of the malignant tumors (6%) exhibited lobulations. The cavernous hemangiomas had a significantly higher SIR than the malignant tumors on T2WI: 3.0 +/- 0.7 and 1.9 +/- 0.8 (p < 0.001), respectively. The presence of lobulation together with a high SIR was a useful measure for differentiating cavernous hemangiomas from other liver tumors.

Clinical utility of three-dimensional time-of-flight magnetic resonance angiography for the evaluation of intracranial aneurysms.

Magnetic resonance (MR) angiographic studies of 14 patients with intracranial aneurysms (AN) were analyzed retrospectively as compared with contrast angiographic studies. Eighteen of 19 (95%) lesions were detected, and the relation between AN and their parent vessels was precisely assessed. The diameter of the smallest aneurysm detected in our case was 3 mm. However, small vessels around AN were not visualized. Therefore, MR angiography (MRA) is definitely not a substitute for preoperative contrast angiography. MRA is a useful screening tool for nonruptured AN, but further refinement is required to evaluate emergency ruptured AN.

[Three patients from two families with familial Creutzfeldt-Jakob disease having a point mutation in the prion protein gene at codon 200 (Glu-->Lys)].

We present three patients with Creutzfeldt-Jakob disease (CJD). They lived in Fuji city and its neighboring towns in the eastern part of Shizuoka prefecture. Patient 1 and patient 2 were cousins. Patient 1 developed the illness at the age of 50 in 1987 and died 13 months later. Patient 2 became ill at the age of 73 in 1989 and died seven months later. Patient 3 was related to a familial CJD cases in Yamanashi prefecture, known as Akai's "H" family (Akai et al in 1979, Yamamoto et al in 1986). She became ill at the age of 78 in 1990 and died four months later. Their clinical features were common; rapidly progressive dementia, generalized myoclonus, and periodic synchronous discharges on electroencephalographies. They were autopsied and neuropathologically diagnosed as typical CJD. Molecular genetic analysis of the prion protein (PrP) gene was performed on patient 2 and patient 3 using their frozen brain sections. The results showed a point mutation in the PrP gene at codon 200; GAG to AAG (Glu-->Lys). The eastern part of Shizuoka prefecture is adjacent to Yamanashi prefecture where a large number of patients with CJD including familial cases has been found during the recent 15 years. This study suggests that the patients with CJD in both Yamanashi and Shizuoka prefecture should be re-evaluated by analysis of the PrP gene.

Evaluation of left ventricular mass: comparison of ultrafast computed tomography, magnetic resonance imaging, and contrast left ventriculography.

We measured and compared left ventricular mass in 20 patients by ultrafast computed tomography (UFCT), magnetic resonance imaging (MRI), and contrast left ventriculography (LVG). Left ventricular mass was calculated by UFCT and MRI in two ways: (1) excluding papillary muscles and trabeculae (LV mass), and (2) including papillary muscles and trabeculae (LV mass + PM&T) by Simpson's method. Left ventricular mass excluding papillary muscles and trabeculae (LV mass) in LVG was calculated by Rackley's method by biplane angiocardiography. LV mass was significantly larger in LVG than in MRI and UFCT (p < 0.01). Although LV mass was significantly larger in MRI than in UFCT (p < 0.01), there was no significant difference in LV mass + PM&T between UFCT and MRI. Interobserver and intraobserver variability showed good correlation of coefficient in both UFCT and MRI. We therefore conclude that left ventricular mass is best measured by including papillary muscles and trabeculae by Simpson's method in UFCT or MRI.

Labile 50S ribosome from partial macrolide-resistant Staphylococcus aureus.

Staphylococcus aureus S704 and 8325MMT7 show constitutive resistance to macrolide antibiotics such as erythromycin (EM), oleandomycin, spiramycin, rosamicin and josamycin, except for tylosin, rokitamycin (RKM), and mycinamicin as well as lincosamide and streptogramin type B antibiotics (PM-resistance). Whenever 70S ribosomes from either of them were dissociated into 30S and 50S subunits in a 10-28%(W/W) linear sucrose gradient, the latter subunit was further cleaved into two small apparently equal particles (about 40S). RKM could no longer bind to either of the small particles. A prior exposure of 8325MMT7's 50S subunit to RKM (except EM) did not cause cleavage in any small particles. The largest component (M.W. 33.0kDa) of 50S ribosomal proteins was absent in at least the small particles. The first finding suggests that the lability of the 50S ribosome may be responsible for PM-resistance.

Significance of different levels of the Edinburgh 2 coma scale calculated from the outcome of neurosurgical patients.

In the management of patients with acute cerebral disturbances, it is essential to determine precisely the degree of impaired consciousness. In order to secure the accuracy of observations, one must use a reliable coma scale. We have evaluated the Edinburgh 2 coma scale (E2CS) and explored the relationship between levels of the E2CS and the final outcome. Case notes and observation charts of the past 7 years were reviewed, covering neurosurgical operations on 406 patients, in each of whom the postoperative course was evaluated periodically by the E2CS and the outcome was determined by the Glasgow outcome scale. By matching the outcome with each level of impaired consciousness, about 22,000 pairs of data were obtained. In order to quantify the morbidity rate, different stages of the Glasgow outcome scale were rated from 100 through 0, arbitrarily. It was proved that levels of the E2CS were arranged in the correct order in respect to both mortality and morbidity rates. It was shown at the same time that each level has different prognostic significance and that the distance between each level is not identical. The recommendation is made to separate the levels on a chart not by an ordinal number but by the distance calculated on the basis of either mortality or morbidity rates. This will make it possible to get a rough estimate of the patients' prognoses by simply looking at a daily clinical chart.