Urinary tract management in patients with incomplete cervical cord injury during the recovery phase.

PURPOSE: For patients with incomplete cervical cord injuries, appropriate urinary management based on an assessment of voiding and storage function of the bladder is necessary for a better prognosis, especially during the recovery phase. In our review of medical records of such patients, we identified factors related to recovery of bladder function and parameters for predicting prognosis. METHODS: In this study, we included 234 patients with incomplete cervical cord injuries admitted to Kanagawa Rehabilitation Hospital. Their medical records were retrospectively reviewed for various parameters related to final urinary management measures at discharge. Parameters included age, severity of paralysis, bladder function over time, urinary sensation and cystometry results. RESULTS: Patients were managed using urethral catheterization, suprapubic cystostomy, clean intermittent catheterization (CIC) by oneself or care givers, CIC with occasional spontaneous voiding, or spontaneous voiding alone. Bladder function improved in majority of the patients during hospitalization. The severity of paralysis and urinary sensation are predictive parameters for improvement in voiding function. In patients who were admitted with catheterization but were discharged with spontaneous voiding, the period for recovery was 85.2 days on average (range 16-142 days). CONCLUSIONS: Selection of urinary management measures for patients with incomplete cervical cord injuries can be performed adequately by considering the severity of paralysis and urinary sensation.

Usefulness of anaerobic threshold in estimating intensity of exercise for diabetics.

We examined the utility of the anaerobic threshold (AT) for quantifying the intensity of exercise that a diabetic patient is capable of handling. Thirteen diabetic patients treated with buformin exercised on a bicycle ergometer, and comparison was made with 20 healthy subjects matched for age and sex. The AT was determined from VO2 and VE with a personal computer. The intensity of exercise at the AT was 93 +/- 6 W in diabetic men and 80 +/- 10 W in diabetic women, values that were less than those of healthy subjects (P less than 0.05). There was a negative correlation between the intensity of exercise at the AT and the plasma concentration of buformin (P less than 0.01). There were no significant differences in either plasma lactic acid or pyruvic acid concentration at the AT between healthy subjects and diabetics. The plasma glucose at the AT or after exercise was lower than the baseline values in all subjects (P less than 0.01). The plasma insulin at the AT was lower than the baseline values in healthy subjects (P less than 0.01), but not in diabetics. There were no changes in plasma glucagon in any group. We concluded that determination of the AT is a simple, non-invasive procedure useful for ascertaining the optimal intensity of exercise for diabetics.

Relationship between age-adjusted heart rate and anaerobic threshold in estimating exercise intensity in diabetics.

We compared heart rates at the anaerobic threshold (AT) with age-adjusted heart rates in two groups of diabetics (DMY, mean age 31; and DMO, mean age 48) to ascertain whether the AT is useful for evaluating the intensity of exercise therapy for diabetics. In both the DMY and DMO groups the AT was reached at lower heart rates than in control groups of healthy subjects, indicating that the metabolism of diabetics may become anaerobic if their age-adjusted heart rate is higher than their heart rate at the AT. In this study, 86% of the DMY and 50% of the DMO group had age-adjusted heart rates, at 70% of maximum, that were higher than the heart rates at the AT. Thus, exercise intensity with an age-adjusted heart rate at 70% of maximum may induce anaerobic metabolism in some diabetics. We also studied the relationship between exercise intensity and the glycosylated hemoglobin (HbA1c) level at the AT in order to understand why the heart rate at the AT in diabetics was less than in healthy subjects. Exercise intensity at the AT in both diabetic groups was less than in healthy groups, and so did not increase the heart rates. Both exercise intensity and the heart rate at the AT were inversely related to the HbA1c level, suggesting that HbA1c may be important for keeping low the exercise intensity and the heart rate at the AT. As far as possible, we excluded cardiovascular autonomic neuropathy, so that it could not explain the mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)

[Inhibition of eosinophil peroxidase release by chymotrypsin type protease inhibitors from activated human eosinophils].

Eosinophils contain many cytotoxic mediators including eosinophil peroxidase (EPO) in their granules and these mediators are released by various pathophysiological stimuli, resulting in severe damage to various epithelia. However, little is known about the intracellular mechanism of the degranulation. Here we report that eosinophils isolated from patients with bronchial asthma who were not taking corticosteroid hormone had significant amidolytic activities on Suc-Ala-Ala-Pro-Phe-MCA, and also that the activity was completely inhibited by chymostatin (1 x 10(-4) M), eglin C (1 x 10(-4) M), and peptide boronic acid (1 x 10(-4) M), indicating that eosinophils contain a chymotrypsin-like serine protease in the fraction eluted in 50 mM potassium phosphate buffer, pH 8.0 containing 2 M NaCl. Among the various types of protease inhibitors examined, one of the chymotrypsin-type proteases chymostatin (1 x 10(-4) M), but none of the other types of proteases such as leupeptin and E-64, markedly inhibited the EPO release (c.a. 60%) from eosinophils stimulated by immunoglobulin-G (2.5 mg protein/ml beads) in the presence of rhIL-5 (10 ng/ml) or platelet-activating factor (1 x 10(-7) M), although it had no effect on the release by calcium ionophore A23187 (1 x 10(-7) M).

[Clinical evaluation of irinotecan combined with cisplatin by divided administration in patients with untreated primary non-small cell lung cancer].

The efficacy and safety of irinotecan (CPT-11) combined with cisplatin (CDDP) were assessed in 24 previously untreated patients with primary non-small cell lung cancer. CPT-11 (60 mg/m2) and CDDP (30 mg/m2) were administered in combination at weekly intervals, on days 1.8, and 15 of the treatment course. During treatment, the patients were evaluated for adverse drug reactions and response. The response rate was 58.3% for all patients and 60.9% for the patients who completed the full treatment course. The median survival time was 13.0 months. The major adverse reactions were myelosuppression and gastro-intestinal disorders, but no treatment-related deaths were observed. Myelosuppressions included grade 3 or 4 leukopenia (25.0%) and anemia (33.3%). Grade 3 and higher gastro-intestinal reactions included nausea and vomiting (8.3%), diarrhea (12.5%), and anorexia (16.7%). These results suggest that combined weekly CPT-11 and CDDP therapy is capable of achieving a favorable tumor response with less toxicity, and thus worth consideration as a treatment option. Given that only 33.3% of the patients finished the full treatment course, further study should be devoted to the subject of CDDP and/or CPT-11 dosages.

[Increased granulocyte/macrophage colony stimulating factor production by mononuclear cells from patients with bronchial asthma].

The in vitro production of granulocyte/macrophage colony stimulating factor (GM-CSF) by mononuclear cells from the peripheral blood of patients with bronchial asthma (BA) was examined by enzyme-linked immunosorbent assay (ELISA). In 3 of 12 cases studied, mononuclear cells from BA patients produced GM-CSF without stimulation. And in 5 of 12 cases studied, mononuclear cells from BA patients produced GM-CSF in response to IL-2. Mononuclear cells from patients with other diseases (n = 13) and healthy volunteers (n = 6) did not release any detectable (> or = 7.5 pg/ml) GM-CSF. The culture media of mononuclear cells from BA patients showed activities for stimulating the proliferation and survival of eosinophils, and these activities were partially inhibited by anti-GM-CSF antibodies. GM-CSF production by mononuclear cells from BA patients treated with prednisolone was lower than that of mononuclear cells from untreated BA patients. And prednisolone showed a reduction in the GM-CSF production from mononuclear cells in response to IL-2. These results suggest that GM-CSF production by mononuclear cells may play a role in the pathogenesis of BA.

[An elderly case of small cell lung cancer showing a good partial response by chronic daily administration of oral etoposide].

An 86-year-old man was admitted to our hospital with complaints of dyspnea and productive cough, and diagnosed as small cell lung cancer with sputum cytology. We concluded that he was unsuitable for standard aggressive intravenous chemotherapy because of an old age, a poor performance status and cardiac complication. He was treated with oral etoposide (100 mg/day x 16.5 days), and showed a good partial response and improvement of clinical symptoms. Toxicities were leukopenia, alopecia, and anorexia. Daily oral administration of etoposide is considered to be effective and useful for elderly patient with small cell lung cancer.

Inhibitors of chymotrypsin-like proteases inhibit eosinophil peroxidase release from activated human eosinophils.

Eosinophils contain many cytotoxic mediators including eosinophil peroxidase (EPO) in their granules; on degranulation, these mediators are released by various pathophysiological stimuli, resulting in severe tissue damage. However, little is known about inhibitors of degranulation. Here, we report that eosinophils isolated from patients with bronchial asthma have significant chymotrypsin-like serine protease activity in the high salt extract fraction. The protease partially purified and labeled with [3H]diisopropylfluorophosphate has an apparent molecular mass of 28 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The chymotrypsin-like protease was not immunoreactive with antibodies against chymase and atypical chymase from rat mast cells or with an antibody against cathepsin G from human neutrophils. Studies on the subcellular distribution of the chymotrypsin-like protease indicated that the enzyme is mainly localized with EPO in eosinophil granules. Chymostatin, an inhibitor of the chymotrypsin-like protease(s), but not an inhibitor of other types of proteases, markedly inhibited the EPO release from eosinophils that was induced by immunoglobulin G plus rIL-5 or platelet-activating factor, although it had no effect on the release of EPO induced by the calcium ionophore A23187. These results suggest that proteolytic activation by chymotrypsin-like serine protease(s) in eosinophils plays some role in the process of receptor-mediated EPO release from the granules.

Role of calcium in suppression of glucagon release from isolated diabetic rat pancreata.

To investigate the role of extracellular Ca2+ (Ca2+) in suppression of glucagon release in diabetic animals, pancreata were isolated from streptozotocin-diabetic rats and perfused with a 15 mM glucose solution containing one of the following: (1) Ca2+ 2.1 mM and insulin 22 microU/ml, (2) Ca2+ 2.1 mM and insulin 110 microU/ml, (3) Ca2+ 2.1 mM and insulin (-) or (4) Ca2+ 0.2 mM and insulin 110 microU/ml. Although perfusion with 22 microU/ml of insulin did not alter glucagon release, perfusion with 110 microU/ml of insulin in the presence of Ca2+ and glucose significantly reduced the release of glucagon from 1.9 +/- 0.3 ng/min to 1.2 +/- 0.3 ng/min for the first 3 min. The absence of insulin enhanced glucagon release from the baseline level of 1.0 +/- 0.1 ng/min to 1.6 +/- 0.3 ng/min at 11 min and to 1.4 +/- 0.2 ng/min at 21 min. Deprivation of Ca2+ in the perfusate also enhanced glucagon release from the baseline level of 0.8 +/- 0.1 ng/min to 1.2 +/- 0.3 ng/min for the first 4 min. It is concluded that insulin suppresses glucagon release and Ca2+ is needed for the suppression of glucagon release in the presence of both insulin and glucose in streptozotocin-diabetic rat pancreata.

Production of interleukin-5 and granulocyte/macrophage colony-stimulating factor by T cells of patients with bronchial asthma in response to Dermatophagoides farinae and its relation to eosinophil colony-stimulating factor.

We investigated the effects of Dermatophagoides farinae (Df) and interleukin (IL)-2 on the release of eosinophil colony-stimulating factor (Eo-CSF) activity from mononuclear cells (MNC) and lymphocytes of patients with bronchial asthma (BA) who were sensitive to Df to clarify its relationship with IL-5 and granulocyte/macrophage colony-stimulating factor (GM-CSF). MNC and T cells of patients cultured with IL-2 and Df released Eo-CSF activity. These Eo-CSF activities were partially inhibited by anti-IL-5 and anti-GM-CSF antibodies. In 11 of 15 cases studied, MNC from patients produced GM-CSF in response to IL-2. In four of 15 cases studied, MNC from patients produced GM-CSF in response to Df. On culture with IL-2 or Df, the releases of IL-5 into the medium by MNC from individual patients varied. The results indicate that in BA responsiveness of lymphocytes to Df is increased, and suggest that IL-5 and GM-CSF produced by T cells play a role in the induction of eosinophilia and the pathogenesis of BA.

[Measurement of CA19-9 in bronchial lavage fluid from patients with lung cancer].

Carbohydrate antigen 19-9 (CA19-9) was measured in bronchial lavage fluid in 21 patients with lung cancer and 4 patients with benign lung diseases (2 patients with DPB, 2 patients with BE). Bronchial lavage of the tumor-related bronchus was performed. In normal subjects, levels of CA19-9 in lavage fluid were less than 1000 IU/ml. On the other hand, in 6 patients with lung cancer, levels of CA19-9 were higher than 1000 IU/ml, and in 3 of these cases, CA19-9 levels were higher than 8000 IU/ml. All six three cases were histologically diagnosed as adenocarcinoma. Tumor resected at operation was then stained by antibody recognizing CA19-9. Tumor in cases with high levels of CA19-9 was stained immunohistochemically. These results indicate that measurement of CA19-9 in bronchial lavage fluid of the tumor-related bronchus is a useful auxiliary method in the diagnosis of lung cancer.

Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum.

The molecular mechanisms that govern the coordinated programs of axonogenesis and cell body migration of the cerebellar granule cell are not well understood. In Pax6 mutant rats (rSey2/rSey2), granule cells in the external germinal layer (EGL) fail to form parallel fiber axons and to migrate tangentially along these fibers despite normal expression of differentiation markers. In culture, mutant cells sprout multiple neurites with enlarged growth cones, suggesting that the absence of Pax6 function perturbs cytoskeletal organization. Some of these alterations are cell-autonomous and rescuable by ectopic expression of Pax6 but not by co-culture with wild-type EGL cells. Cell-autonomous control of cytoskeletal dynamics by Pax6 is independent of the ROCK-mediated Rho small GTPase pathway. We propose that in addition to its roles during early patterning of the CNS, Pax6 is involved in a novel regulatory step of cytoskeletal organization during polarization and migration of CNS neurons.

Increased granulocyte/macrophage colony-stimulating factor production by mononuclear cells from peripheral blood of patients with bronchial asthma.

The in vitro production of granulocyte/macrophage colony-stimulating factor (GM-CSF) by mononuclear cells (MNC) from the peripheral blood of patients with bronchial asthma (BA) was examined by enzyme-linked immunosorbent assay (ELISA). GM-CSF concentrations in the media of MNC from patients with BA cultured with interleukin-2 (IL-2) was 80.2 +/- 52.0 pg/ml (mean +/- SE, n = 12), and that in cultures without a stimulant was 12.1 +/- 11.3 pg/ml. The GM-CSF concentrations in the media of MNC from patients with other diseases (n = 13) and from healthy volunteers (n = 6) cultured with or without IL-2 were less than 7.5 pg/ml (the minimum detectable value). The culture media of MNC from patients with BA demonstrated activities for stimulating the proliferation and survival of eosinophils, and these activities were partially inhibited by anti-GM-CSF antibodies. GM-CSF production by MNC of patients with BA treated with glucocorticoids was lower than that of MNC from untreated patients with BA, and it was inhibited by coculture with glucocorticoids in vitro. These results suggest that GM-CSF production by MNC is increased in patients with BA, is modulated by glucocorticoids, and may play an important role in the pathogenesis of BA.

Factors that stimulate the proliferation and survival of eosinophils in eosinophilic pleural effusion: relationship to granulocyte/macrophage colony-stimulating factor, interleukin-5, and interleukin-3.

To investigate the mechanism of eosinophilia in patients with eosinophilic pleural effusions, we measured the activities of eosinophil colony-stimulating factor (Eo-CSF) and stimulating factor for eosinophil survival in the eosinophilic pleural fluids of six patients (two with tuberculous pleuritis, two with drug allergy, and one each with chronic eosinophilic pneumonia and pleuritis associated with rheumatoid arthritis). The number of eosinophil colonies formed by the pleural fluid of patients with eosinophilic pleural effusions significantly exceeded that of control patients with noneosinophilic pleural effusions (7.5 +/- 1.9 colonies/10(5) bone marrow cells, n = 6, versus 0.3 +/- 0.1 colonies/10(5) bone marrow cells, n = 6, P < 0.01). Similarly, eosinophil survival evaluated on day 4 of culture with pleural fluid of patients with eosinophilic pleural effusions significantly exceeded that of patients with noneosinophilic pleural effusions (83.9 +/- 9.8% versus 46.1 +/- 11.2%, P < 0.001). Both activities were inhibited mainly by anti-IL-5 antibody and partially by anti-GM-CSF antibody and anti-IL-3 antibody. Mononuclear cells obtained from eosinophilic pleural fluid released the activities of Eo-CSF and stimulating factor for eosinophil survival in vitro. These findings suggest that GM-CSF, IL-5, and IL-3 are important to eosinophil accumulation in pleural cavity as stimulators of proliferation and survival of eosinophils.

[C5 contents and neutrophil chemotactic activities in bronchiolar and alveolar regions].

To clarify the localization and mechanism of neutrophil infiltration in the lower respiratory tract, we measured neutrophil number, neutrophil chemotactic factor (NCF) activity and content of C5 in bronchial lavage (BL) fluid and bronchoalveolar lavage (BAL) fluid. Numbers of neutrophils, NCF activity and C5 content were higher in the BL fluid from normal volunteers (NV) and control patients (CP) than those in the BAL fluid from the same subjects. The NCF activity in the BL fluid was inhibited approximately 40% by anti-C5 antiserum, and correlated with C5 content in the BL fluid. In the BAL fluids of patients with chronic airway diseases (CAD) and patients with idiopathic interstitial pneumonia (IIP), neutrophil number, NCF activity and C5 content were increased compared to those in BAL fluid from NV or CP. These results indicated that neutrophils are predominant in the bronchial region compared to the alveolar region, and that C5-derived NCF play important roles in the accumulation of neutrophils in the bronchial region. Also C5-derived NCF are thought to be related to, at least, a part of the neutrophil infiltration in the respiratory tract of patients with CAD and IIP.

Comparison between fenoterol and fenoterol plus oxitropium bromide delivered by metered-dose inhaler with InspirEase to relieve acute asthma attack.

Although the inhalation of beta2-agonists has frequently been used to relieve acute asthma attacks, the efficacy of anticholinergic agents for acute asthma attacks still remains unclear. This study was designed to compare the inhalation of fenoterol and the inhalation of fenoterol plus oxitropium bromide delivered by a metered-dose inhaler with holding chamber (InspirEase) to relieve acute asthma attacks. To accomplish this, 69 patients who had presented with an acute asthma attack were randomized to receive either fenoterol (1 puff [200 microg/puff] every 1 min for 5 min; total 1000 microg) or fenoterol plus oxitropium bromide (2 puffs [100 microg/puff] every 1 min for 5 min; total 1000 microg). The peak expiratory flow (PEF) and forced expiratory volume in 1 sec (FEV1) values were measured before treatment, and 1, 15, 30, and 60 min after the inhalation therapy. The ratios of improvement, PEF (or FEV1) after treatment divided by PEF (or FEV1) before treatment, were also calculated. Thirty-three patients were evaluated in the combination group and 31 patients were evaluated in the fenoterol group. The PEF value at 60 min after inhalation therapy of the fenoterol plus oxitropium bromide group (261 +/- 18 L/min, mean +/- standard error) was significantly higher compared to that of the fenoterol group (210 +/- 17 L/min). In addition, the ratios of improvement of PEF at 1, 15, 30, and 60 min after inhalation therapy were significantly higher in the fenoterol plus oxitropium bromide group compared with the fenoterol group.

[Eosinophil colony stimulating activity induced by administration of interleukin-2 into the pleural cavity of patients with malignant pleurisy].

Systemic administration of interleukin-2 (IL-2) in patients with malignant diseases induces peripheral eosinophilia. In the present study, to clarify the mechanisms of eosinophilia induced by IL-2, we examined the changes in the number of eosinophils and in eosinophil colony stimulating activity (Eo-CSA) in the pleural fluid of six patients with malignant pleurisy caused by lung cancer or malignant mesothelioma, during and after intrapleural administration of IL-2. Results showed that intrapleural administration of IL-2 induced marked eosinophilia in the pleural fluid and mild eosinophilia in the peripheral blood, and that during IL-2 administration, marked Eo-CSA appeared in the pleural fluid before increase in the number of eosinophils. The Eo-CSA seemed to be a polypeptide or protein because it was trypsin-sensitive and had a molecular weight of 40-60 kDa.