Effects of macronutrient intake on thigh muscle mass during home-based walking training in middle-aged and older women.

We examined whether post-exercise macronutrient supplementation during a 5-month home-based interval walking training (IWT) accelerated exercise-induced increases in skeletal muscle mass and strength in healthy middle-aged and older women. Thirty-five women (41-78 years) were randomly divided into two groups: IWT alone (CNT, n = 18) or IWT plus post-exercise macronutrient (7.6 g protein, 32.5 g carbohydrate, and 4.4 g fat) supplementation (NUT, n = 17). For IWT, all subjects were instructed to repeat five or more sets of 3-min low-intensity walking at 40% peak aerobic capacity (Vo2 peak ), followed by a 3-min high-intensity walking above 70% Vo2 peak per day for 4 or more days per week. We determined Vo2 peak , thigh muscle tissue area by computer tomography, and thigh muscle strength in all subjects before and after IWT. We found that an increase in hamstring muscle tissue area was 2.8 ± 1.2% in NUT vs -1.0 ± 0.7% in CNT and that in isometric knee flexion force was 16.3 ± 3.7% in NUT vs 6.5 ± 3.0% in CNT; both were significantly higher in NUT than in CNT (both, P < 0.001). Thus, post-exercise macronutrient supplementation enhanced the increases in thigh muscle mass and strength, although partially, in home-based IWT in middle-aged and older women.

Treatment with cyclosporine A improves SLE disease activity of Japanese patients with diffuse proliferative lupus nephritis.

AIMS: Cyclosporine A (CyA), a representative calcineurin inhibitor, may be useful for the treatment of lupus nephritis. In contrast to knowledge about its strong effects against proteinuria, however, there is little information about the beneficial effects of CyA against clinical disease activity of diffuse proliferative lupus nephritis. METHODS: To elucidate this issue, we investigated the effects of low-dose CyA treatment (< 2.5 mg/kg/d) in 11 Japanese adult patients (1 male, 10 female) with uncontrolled diffuse proliferative lupus nephritis with severe clinical SLE disease activity. RESULTS: In addition to amelioration of the proteinuric state, the clinical SLE disease activities, estimated by serological markers and the SLE disease activity index (SLEDAI), were significantly improved in all patients within 1 month. The required amounts of corticosteroid were decreased in these patients. These favorable effects continued for 2 y without serious adverse effects. Kidney function was not changed in the patients with satisfactory kidney function prior to CyA therapy (serum creatinine < 1.1 mg/dl, and eGFR > 45 ml/ min/1.73 m2). CONCLUSION: The current study results suggest that low-dose CyA treatment could ameliorate the severe clinical SLE disease activity as well as improve proteinuria in Japanese patients with diffuse proliferative lupus nephritis. This treatment would be safe and useful for SLE patients with satisfactory kidney function.

Physical fitness and indices of lifestyle-related diseases before and after interval walking training in middle-aged and older males and females.

HYPOTHESIS: Whether increasing peak aerobic capacity for walking (VO(2peak)) by interval walking training (IWT) is closely linked with decreasing the indices of lifestyle-related diseases (LSDs) in middle-aged and older people were examined. METHODS: For 4 months from April to September 2005 or 2006, 246 males and 580 females (∼65 years) performed IWT consisting of ≥5 sets of fast walking at ≥70% VO(2peak) for 3 min followed by slow walking at ≤40% VO(2peak) for 3 min ≥4 days/week. Before and after IWT, we measured VO(2peak), body mass index (BMI), %body fat, arterial blood pressure, thigh muscle strength and blood parameters. We analysed 198 males and 468 females who had undergone all the measurements both before and after IWT. To examine the hypothesis, we divided the subjects equally into three groups according to their pretraining VO(2peak): low, middle and high groups for each sex. RESULTS: Before training, it was found that thigh muscle strength and blood high-density lipoprotein cholesterol concentration were lower, whereas body weight, BMI, %body fat, arterial blood pressure and blood glucose were higher in the low group than the high group (all, p<0.05). After training, although VO(2peak) and thigh muscle strength increased and body weight, BMI, %body fat, blood pressure and blood glucose concentration decreased in all groups (all, p<0.05), the changes were greatest in the low group for both sexes. CONCLUSION: VO(2peak) at baseline and changes in response to training were closely linked with indices of LSDs.

Estimating nurses' workload using the Diagnosis Procedure Combination in Japan.

AIM: To examine the methods used to estimate nurse staffing levels in acute care settings with Diagnosis Related Groups, which in Japan are called the Diagnosis Procedure Combination (DPC). METHODS: For estimating staffing requirements, the study used four DPC groups: (1) acute or recurrent myocardial infarction (AMI) with stenting, (2) angina pectoris with coronary artery bypass grafting (CABG), (3) sub-arachnoid haemorrhage (SAH) with clipping surgery, and (4) cerebral infarction with carotid endarterectomy (CEA). Registered nurses with more than 3-year nursing experience in nine university hospitals in the Tokyo metropolitan area completed self-report questionnaires in order to obtain nursing care time and care intensity per each DPC. The concordance rate was measured by Kendall's coefficient of concordance. The relationship between the care time and the care intensity was examined by a time series graph per DPC. Care intensity consisted of professional judgement, mental effort for helping patients, professional skill, physical effort for providing activities of daily living support, and nurse stress, based on the Hsiao and colleagues' model of resource-based relative value scale. RESULTS: Twenty-five nurses in nine university hospitals answered for a hypothetical typical patient with AMI and with CABG, and 28 nurses in nine university hospitals answered for a hypothetical typical patient with SAH and with CEA. Kendall's coefficient of concordance was 0.896 for AMI, 0.855 for CABG, 0.848 for SAH, 0.854 for CEA. The time series data of the care time and the care intensity items showed different patterns for each DPC. CONCLUSION: The DPC for cardiovascular and cerebral surgical procedures can be used for estimating nurses' workload.

Significance of chemokine receptor expression in aggressive NK cell leukemia.

Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL). One reason for the poor outcome in ANKL is leukemic infiltration into multiple organs. The mechanisms of cell trafficking associated with the chemokine system have been investigated in NK cells. To clarify the mechanism of systemic migration of leukemic NK cells, we enrolled nine ANKL and six CNKL cases, and analyzed the expression profiles and functions of chemokine receptors by flowcytometry and chemotaxis assay. CXCR1 was detected on NK cells in all groups, and CCR5 was positive in all ANKL cells. Proliferating NK cells were simultaneously positive for CXCR1 and CCR5 in all ANKL patients examined, and NK cells with this phenotype did not expand in CNKL patients or healthy donors. ANKL cells showed enhanced chemotaxis toward the ligands of these receptors. These results indicated that the chemokine system might play an important role in the pathophysiology of ANKL and that chemokine receptor profiling might be a novel tool for discriminating ANKL cells from benign NK cells.

The effect of a hemofilter during extracorporeal circulation on hemodynamics in patients with SIRS.

OBJECTIVE: To evaluate the hypothesis that extracorporeal hemopurification with a hemofilter contributes to the stabilization of hemodynamics in patients with systemic inflammatory response syndrome (SIRS) due to a mechanism other than the removal of cytokines. DESIGN: Prospective study. SETTING: Intensive care unit (ICU) in a university hospital. PATIENTS: Seven critically ill patients who met criteria for SIRS with unstable hemodynamics requiring vasopressors after emergency surgery. INTERVENTIONS: Before initiation of continuous hemofiltration (CHF) extracorporeal circulation through the hemofilter (ECC) with a hollow-fiber polyacrylonitrile hemofilter was performed for 6 h. MEASUREMENTS AND RESULTS: Vital signs were monitored continuously and hemodynamics were evaluated intermittently. The blood level of endotoxin and the plasma levels of cytokines were measured at 0 and 6 h. Changes in plasma levels of cytokines passing through the hemofilter were evaluated at 3 h. A significant decrease of body temperature (P < 0.05 at 3 and 6 h vs 0 h), a significant elevation of mean arterial pressure (P < 0.05 at 0.5 h, P < 0.01 at 3 and 6 h vs 0 h), and a significant increase of urinary flow rate (P < 0.05 at 0 to 3 h vs -3 to 0 h) were observed with ECC. Neither the blood level of endotoxin nor the plasma levels of cytokines decreased. A significant increase of plasma IL-6 as it passed through the hemofilter was noted. CONCLUSIONS: The beneficial effects of hemopurification with a hemofilter on SIRS patients are possibly due to mechanisms other than the elimination of cytokines with ultrafiltration, diffusion, or adsorption.

Thermoregulatory and aerobic changes after endurance training in a hypobaric hypoxic and warm environment.

Plasma volume (PV) expansion by endurance training and/or heat acclimatization is known to increase aerobic and thermoregulatory capacities in humans. Also, higher erythrocyte volume (EV) fractions in blood are known to improve these capacities. We tested the hypothesis that training in a hypobaric hypoxic and warm environment would increase peak aerobic power (VO(2)(peak)) and forearm skin vascular conductance (FVC) response to increased esophageal temperature (T(es)) more than training in either environment alone, by increasing both PV and EV. Twenty men were divided into four training regimens (n = 5 each): low-altitude cool (610-m altitude, 20 degrees C ambient temperature, 50% relative humidity), high-altitude cool (2,000 m, 20 degrees C), low-altitude warm (610 m, 30 degrees C), and high-altitude warm (HW; 2,000 m, 30 degrees C). They exercised on a cycle ergometer at 60% VO(2)(peak) for 1 h/day for 10 days in a climate chamber. After training, PV increased in all trials, but EV increased in only high-altitude trials (both P < 0.05). VO(2)(peak) increased in all trials (P < 0.05) but without any significant differences among trials. FVC response to increased T(es) was measured during exercise at 60% of the pretraining VO(2)(peak) at 610 m and 30 degrees C. After the training, T(es) threshold for increasing FVC decreased in warm trials (P < 0.05) but not in cool trials and was significantly lower in HW than in cool trials (P < 0.05). The slope of FVC increase/T(es) increase increased in all trials (P < 0.05) except for high-altitude cool (P > 0.4) and was significantly higher in HW than in cool trials (P < 0.05). Thus, against our hypothesis, the VO(2)(peak) for HW did not increase more than in other trials. Moreover, slope of FVC increase/T(es) increase in HW increased most, despite the similar increase in blood volume, suggesting that factors other than blood volume were involved in the highest FVC response in HW.

Plasma lactate concentration and muscle blood flow during dynamic exercise with negative-pressure breathing.

This study assessed the hypothesis that increasing cardiac filling pressure (CFP) would enhance contracting muscle blood flow (MBF) by stretching cardiopulmonary baroreceptors and attenuate the increase in plasma lactate concentration ([Lac(-)](p)) during dynamic exercise. Continuous negative-pressure breathing (CNPB) (-15 cmH(2)O) was used to increase the CFP by accelerating the venous return to the heart. In the first series of experiments, 10 men performed a graded exercise seated on a cycle ergometer with (N1) and without CNPB (C1). The increase in [Lac(-)](p) for N1 was attenuated at 60%, 90%, and 100% of maximal exercise intensity compared with that in C1 (P < 0.001). Also, the increases in mean arterial pressure (MAP) and plasma catecholamine concentrations were attenuated in N1 compared with those in C1 throughout the graded exercise (P < 0.05). However, heart rate and pulse pressure were not significantly influenced by CNPB. Second, we studied the impact of CNPB on forearm MBF during a rhythmic handgrip exercise in 5 of the 10 subjects. Forearm MBF was measured immediately after cessation of the exercise by venous occlusion plethysmography at rest, 30%, 50%, and 70% of maximal work load (WL(max)) with (N2) and without CNPB (C2). Forearm MBF and vascular conductance for both trials increased with the increase in intensity, but forearm skin blood flow measured by laser-Doppler flowmetry remained unchanged. MBF and vascular conductance in N2, however, increased more than in C2 at every intensity (P < 0.01) except for MBF at 70% WL(max), whereas the increase in MAP for N2 was attenuated compared with that in C2 (P < 0.05). Thus augmented active muscle vasodilation occurred in N2 with a lower increase in MAP compared with that in C2. These findings suggest that the stretch of intrathoracic baroreceptors, such as cardiopulmonary mechanoreceptors, by CNPB increased MBF by suppressing sympathetic nerve activity. The attenuation of the increase in [Lac(-)](p) might be caused, at least partially, by the increased MBF.

Regenerative process of the facial nerve: rate of regeneration of fibers and their bifurcations.

After the main trunk of the mouse facial nerve was injured by crushing, a fiber tracing method was used to quantify the facial motor neurons that extended regenerating nerve fibers to the specific site of the facial nerve branch. The total number of motor neurons retrogradely labeled with a fluorescent tracer, Fluoro-Gold (FG), were 0 on postsurgical days (PSDs) 1 and 2, 75+/-25 on PSD3, 264+/-21 on PSD4, 378+/-19 on PSD6, 428+/-19 on PSD8, 491+/-13 on PSD12 and 532+/-15 on PSD16. Assuming that the FG-positive neurons (535+/-11) of the control mice represent 100%, the FG-labeled neurons accounted for 0, 14, 49, 71, 80, 92 and 99% on the corresponding days. Two different fluorescent tracers were applied to the different facial nerve branches 16 days after facial nerve injuries. Double-labeled neurons were consistently found in the nerve-crushed facial nucleus (3.2%), and their number increased in the nerve-transected facial nucleus (12.2%). The present study indicates that the regenerating facial nerve consists of heterogeneous nerve fibers with varying growth rates and that excessive axonal branching occurs more frequently in the nerve-transected than in the nerve-crushed injuries.

Human chorionic gonadotropin produced by ectopic pinealoma in a girl with precocious puberty. Case report.

A case is reported in which a human chorionic gonadotropin (HCG-)-producing ectopic pinealoma was found in a 5-year-old girl with precocious puberty. Physical examination revealed abnormal breast enlargement. Endocrinological study disclosed a high plasma HCG concentration of 1192 ng/ml with a normal follicular stimulating hormone (FSH) level. The HCG content of the tumor was as high as 400 ng/mg of acetone dried tissue, but no FSH was detectable. This is the first reported case of precocious puberty associated with pineal tumor in a female.

Effect of neutral endopeptidase inhibitor on bradykinin-induced bronchoconstriction.

To evaluate whether neutral endopeptidase (NEP) inhibitors have adverse respiratory effects, the influence of a NEP inhibitor on bradykinin (BK)-induced bronchoconstriction was investigated. In anesthetized and artificially ventilated guinea pigs, changes in airway opening pressure (Pao) were measured as an index of bronchoconstriction. An infusion of phosphoramidon (3 mg kg(-1) h(-1)), a NEP inhibitor, significantly enhanced the bronchoconstriction induced by high-dose BK (30 nmol kg(-1), i.v.). Capsaicin (0.1 mg kg(-1), i.v.) and SR48968 (0.3 mg kg(-1), i.v.), an NK2 receptor antagonist, significantly inhibited the phosphoramidon-induced enhancement of BK-induced bronchoconstriction, although FK888 (3 mg kg(-1), i.v.), an NK1 receptor antagonist, did not. Both neurokinin A (NKA) (0.1-3 nmol kg(-1), i.v.) and substance P (SP) (0.1-3 nmol kg(-1), i.v.) induced dose-dependent bronchoconstriction which was enhanced by phosphoramidon infusion, although these enhancements were more prominent in the NKA series. Phosphoramidon partially inhibited BK degradation in lung homogenate, and both NKA and SP degradation in the lung homogenate were significantly suppressed by phosphoramidon. In bronchoalveolar lavage fluid (BALF), levels of NKA and SP were significantly elevated after a bolus of BK with a phosphoramidon infusion. These results suggest that NEP inhibitors may have adverse respiratory effects resulting from inhibition of the degradation of neurokinins, but mainly of NKA, when a large amount of BK is generated.

Younger onset myeloperoxidase-specific antineutrophil cytoplasmic antibody- (MPO-ANCA) related glomerulonephritis accompanied with nephrotic syndrome.

It is known that nephrotic syndrome rarely accompanies myeloperoxidase-specific antineutrophil cytoplasmic antibody- (MPO-ANCA) related glomerulonephritis. We present a case of younger onset MPO-ANCA-related glomerulonephritis accompanied with nephrotic syndrome in a female patient. It was diagnosed through the renal biopsy and the detection of a high titer of MPO-ANCA and steroid therapy (intravenous steroid pulse therapy and oral administration), anticoagulant therapy and antiplatelet therapy were initiated. Since her nephrotic syndrome persisted in spite of the decrease of MPO-ANCA, we conducted a second renal biopsy. We found active necrotizing crescentic glomerulonephritis with a small deposition of immunoglobulin and fibrinogen on the glomeruli. To suppress her disease activity, we administered second steroid-pulse therapy and MPO-ANCA titer disappeared. However, as her nephrotic syndrome, which was accompanied by severe hyperlipidemia, persisted, we tried to treat her using low-density lipoprotein (LDL) apheresis. It was effective temporarily, but she finally fell into end-stage renal failure. We discuss here the possibility of double nephropathy by considering her clinical and renal pathologic features.

Massive noninflammatory periportal liver necrosis following concentrated acetic acid ingestion.

In a fatal occurrence of massive liver necrosis following ingestion of concentrated (90%) acetic acid, the patient showed evidence of hemolysis, disseminated intravascular coagulation, and liver dysfunction at only 45 minutes after exposure. With refractory to vigorous supportive care, the patient s condition deteriorated until death occurred 39 hours after ingestion, despite some improvement of coagulopathy. Autopsy revealed corrosive injuries in the upper gastrointestinal tract and massive hepatic necrosis in a periportal distribution without significant inflammation. A direct effect of the noxious agent on hepatocytes involving the portal circulation is suggested.

Determination of (+)- and (-)-bromoisovalerylurea in sera of overdosed subjects.

Bromoisovalerylurea (bromisovalum) is a sedative-hypnotic given orally as a racemic mixture of optical isomers (i.e., (+)- and (-)-enantiomer) and frequently taken in overdose in order to commit suicide. Sera from 16 overdosed subjects were analyzed for each enantiomer by high-performance liquid chromatography on chiral stationary phases. The (+)-enantiomer concentration was lower than the (-)-enantiomer concentration in all specimens, that is, the ratio of the (+)-enantiomer to the total concentration ranged from about 50% to 0%. The ratio of the (+)-enantiomer was continuously decreasing in each subject. The data indicate that the drug in gastrointestinal tract was absorbed into blood nonstereoselectively and that the drug in blood was eliminated stereoselectively. The enantioselective determination of this drug will give useful information on absorption and elimination.

Myocardial infarction with acute insulin poisoning--a case report.

A 36-year-old woman without overt coronary risk factors was admitted to hospital with coma about 9 hours after mass self-injection of insulin (1,500 units). Laboratory investigation revealed severe hypoglycemia and hyperinsulinemia. During the treatment of her hypoglycemia, circulatory collapse occurred. The ECG, echocardiogram, and elevation in troponin T suggested a diagnosis of myocardial infarction. Although the patient became apallic and developed systemic spasticity due to hypoglycemic brain damage, her hemodynamics improved with supportive care alone. Coronary angiography and myocardial scintigraphy performed later demonstrated a broad area of myocardial damage despite intact coronary artery circulation. The authors hypothesize that temporary coronary arterial narrowing or coronary arterial vasospasm induced by severe hyperinsulinemia contributed to the pathogenesis of the myocardial infarction. The possibility of myocardial infarction should be considered in patients with acute insulin poisoning.

Thrombosed aneurysm of the middle cerebral artery with occlusion of the distal parent artery--case report.

A 54-year-old female presented with subarachnoid hemorrhage due to rupture of a small middle cerebral artery aneurysm, found to be thrombosed at surgery and not visualized on the preoperative angiograms. One major branch of the middle cerebral artery was found to be occluded near the trifurcation. The lumen of the branch proximal to the occlusion had appeared as the aneurysmal opacification on the preoperative angiograms.

[Studies on neurinomas and neurofibromas in tissue culture (author's transl)].

10 acoustic neurinomas, 2 spinal cord neurinomas and 3 neurofibromas of von Recklinghausen's disease were elaborately studied by monolayer tissue culture method and Gelfoam organ culture method. Four morphological types were found in the acoustic and spinal cord neurinoma. (1) multinucleated cells (type I), dividing into bipolar spindle-shaped cells. (2) bipolar spindle-shaped cells (type II), forming of palisade fashion in the monolayer tissue culture method. (3) fibroblastic cells (type III), tending to predominate in the long-term cultures. (4) round cells (type IV), gathering to the Gelfoam mesh in the organ culture method. Neurofibroma of von Recklinghausen's disease was divided into cells of two types in the tissue culture. (1) spindle-shaped cells, rarely observed, and have been thinking that the cells originated from schwann cells. (2) round cells, having the macrophagic character, are predominant in the long-term culture.

[A case of HCG-producing ectopic pinealoma in a girl with precocious puberty (author's transl)].

HCG-producing ectopic pinealoma of two cell pattern type was demonstrated in a 5-year old girl who presented precocious puberty and bilateral choked discs. The tumor was localized at the anterior third ventricle and suprasellar region. Endocrinological findings are as following: Plasma basal LH was markedly elevated to 306 mIU/ml and HCG was elevated to 1,192 ng/ml. Provocative test of hypophyseal function revealed low response. Plasma estrogen was not detectable. HCG content of resected tumor tissue was elevated to 400 ng/mg. FSH, however, was not detectable. Histological findings of this tumor showed atypical teratoma, so-called two cell pattern pinealoma. Electron microscopic findings revealed two types of cells, dark and clear cells. Many secreting granules were found in the dark cells. In this case, HCG in plasma, CSF and tumor tissue was remarkably elevated. In addition, plasma FSH was also elevated to 8.9 mIU/ml. Precocious puberty associated with tumor in the pineal-suprasellar region has been seen only in boys. There has been no case report of precocious puberty in girls. This case is the first female case is which HCG-producing ectopic penealoma is caused in precocious puberty.

[Growth hormone, prolactin, LH and FSH secretion in tissue culture of pituitary adenomas (author's transl)].

We have performed tissue culture of pituitary adenomas (5 acromegalies, 7 non-acromegalies) and measured GH, PRL, LH and FSH in the media of tissue culture by radioimmunoassay (RIA) for 30-40 days. In addition, GH, PRL, LH and FSH were measured in the plasma and tumor tissue by RIA. GH concentration in the culture media was markedly high in all cases with acromegaly and high also in 2 out of 7 non-acromegaly cases (case 6 and 7). GH concentration in the media rapidly decreased almost as a straight line on a semilogarithmic scale until the 30-40 in day, when GH level became less than 10 ng/ml. PRL concentration in the culture media was high in 5 patients (3 acromegalies, 2 non-acromegalies). PRL concentration regressed more slowly than GH, but still remained higher than 10 ng/ml in all of the patients on the 25-40th day when the studies were discontinued. LH and FSH concentrations in the culture media was high in two patients. One patient was a pituitary adenoma secreting LH and FSH, and another case was a false high secreting one, possibly contaminated with gonadotropin in normal pituitary gland at surgical operation. LH and FSH concentrations rapidly decreased as that of GH. A rare case of primary LH and FSH secreting pituitary adenoma was demonstrated.