Acute hemodynamic effects of intravenous bolus injection of isosorbide dinitrate in aged patients with congestive heart failure]

In order to investigate whether intravenous bolus injection of isosorbide dinitrate (ISDN) is a safe and efficient therapy in aged patients with congestive heart failure, we studied acute hemodynamic effects in 11 patients. Peak effects on preload were observed after 5 to 10 minutes of bolus injection and unloading effects continued effectively for 60 minutes. At peak effect, pulmonary systolic pressure decreased from 50.2 +/- 2.6 to 36.2 +/- 2.6 mmHg (-28.5%, p less than 0.01) and pulmonary end diastolic pressure decreased from 25.0 +/- 2.2 to 18.5 +/- 2.1 mmHg (-26.0%, p less than 0.01). Mean pulmonary artery wedge pressure decreased from 23.4 +/- 2.2 to 16.0 +/- 2.1 mmHg (-31.6%, p less than 0.01). Mean right atrial pressure decreased from 10.5 +/- 1.8 to 7.4 +/- 2.0 mmHg (-29.5%, p less than 0.01). Blood pressure, heart rate, cardiac index, systemic and pulmonary vascular resistance showed no significant changes. Thus, intravenous bolus injection of ISDN showed a potent vasodilator effects on preload, and may be a safe and useful treatment for aged patients with acute congestive heart failure.     

A case of humidifier lung associated with BHL]

We encountered a rare case of hypersensitivity pneumonitis associated with bilateral hilar lymphadenopathy (BHL). The patient was a 53-year-old male, who developed dry cough and shortness of breath when using a humidifier since 1982. He was admitted to our hospital for further evaluation in 1987. Chest X-ray films showed BHL and ground glass appearance in the bilateral lung fields. Pulmonary function test indicated disturbance of diffusing capacity. Transbronchial lung biopsy revealed interstitial pneumonitis, and lymph node biopsy by mediastinoscopy showed lymphoid sinus histiocytosis without noncaseating granuloma. Provocation test using the humidifier was positive, and the diagnosis of humidifier lung with BHL was made.     

A case of severe summer-type hypersensitivity pneumonitis treated with high-dose administration of steroid]

A 40-year-old man who lived in a wooden house built 30 years ago presented with complaints of fever, dry cough and dyspnea. Chest X-ray findings showed interstitial shadows throughout bilateral lung fields. After admission, high-dose administration of 3000 mg of methylprednisolone was performed because of deterioration of chest X-ray shadows and symptoms. In a week, clinical data and symptoms improved. Findings of BAL fluid on admission revealed a relative increase of lymphocytes, neutrophils and mast cells, and pathological findings of transbronchial lung biopsy revealed non-caseous granulation and alveolitis. Precipitating antibodies and indirect fluorescent antibodies against Trichosporon cutaneum and Cryptococcus neoformans had positive reactions and T. cutaneum was isolated and identified from the patient's house. A diagnosis of summer-type hypersensitivity pneumonitis was made according to the criteria advocated by Ando et al. This seemed to be a rare case of summer-type hypersensitivity pneumonitis prolonged after isolation from his normal living environment, successfully treated by high-dose administration of steroid.     

Effect of KB-2796, a new diphenylpiperazine Ca antagonist, on voltage-dependent Ca currents and oxidative metabolism in dissociated mammalian CNS neurons

The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA I_Ca in a concentration-dependent manner with a threshold concentration of 10⁻⁷ M when the LVA I_Ca was elicited every 30 s in the external solution with 10 mM Ca²⁺. The concentration for half-maximum inhibition (IC₅₀) was 1.9 × 10⁻⁶M. At 10⁻⁵ M or more of KB-2796, a complete suppression of the LVA I_Ca was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca²⁺ channel for LVA I_Ca voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca²⁺ channel. KB-2796 at a concentration of3.0 × 10⁻⁶M also decreased the peak amplitude of the HVA I_Ca without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10⁻⁶M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca²⁺ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage.     

Development of an animal model for neuroleptic malignant syndrome: heat-exposed rabbits with haloperidol and atropine administration exhibit increased muscle activity, hyperthermia, and high serum creatine phosphokinase level

The neuroleptic malignant syndrome (NMS) is a life-threatening complication of neuroleptic treatment. To elucidate the pathogenesis of NMS, an animal model has been developed. Experimental rabbits treated with haloperidol (1 mg/kg) by intramuscular injection, were studied for the diagnostic symptoms of increased muscle rigidity, elevated body temperature, and high serum creatine phosphokinase (CPK) level. Administration of haloperidol (1 mg/kg) and atropine (0.4 mg/kg), and exposure to high ambient temperature (35°C) induced a significant increase in electromyographic activity with muscle rigidity similar to that observed in patients with NMS. Such rabbits also showed elevated body temperature and serum CPK value. In addition to the similarity of the signs and symptoms, all parameters measured (muscle rigidity, body temperature, and serum CPK level) were normalized by dantrolene treatment. The effectiveness of dantrolene in the experimental animal partially confirms the validity of this animal model for NMS. This experimental animal model for NMS may be useful to elucidate the pathogenesis of NMS.     

The effects of oral adsorbent (AST-120) in the experimental model of chronic renal failure--pathophysiological study on renal function, glomerular hypertrophy, mesangial function and glomerular histology

Oral adsorbent (AST-120) reduces blood levels of urea and creatinine in experimental studies. It has also been shown to retard the progression of chronic renal failure in clinical studies. In the present study, the effect of AST-120 was examined in the rat model of subtotal nephrectomy (sNPX). This experimental model of chronic renal failure is characterized by glomerular hyperfunction, glomerular hypertrophy, increased mesangial trapment of macromolecules and subsequent glomerular sclerosis. We report the effect of AST-120 on glomerular hyperfunction, glomerular hypertrophy and mesangial trapment of macromolecules in the early stage and glomerular function and histology in the late stage of the rat model of sNPX. From 2 days after sNPX, rats were fed regular rat chow with (AST group: AST) or without (control) AST-120. At 2 weeks, iron dextran (ID) was injected intravenously. Three days after the injection, mesangial trapment of ID was largely ameliorated in AST when compared with control (p less than 0.02). The value of mean planar area of glomerulus (PAmean) in AST was significantly lower than that in control (p less than 0.05). At 2 and 9 weeks, the values of GFR and RPF in AST were all statistically higher than those in control. At 9 weeks, whereas average glomerular sclerosis index (SI: 0-4 scale) was 1.07 in control, significantly lower SI (0.57) was noted in AST (p less than 0.05). Thus, AST-120 has effects on glomerular hypertrophy, increased mesangial trapment of macromoleculus and finally the progression of chronic renal failure in the rat model of sNPX. The effects are not through reducing glomerular hyperfunction.(ABSTRACT TRUNCATED AT 250 WORDS)     

HTLV-I seroprevalence in patients with malignancy

Since many malignancies often occur in patients with smoldering type adult T-cell leukemia (ATL) (5 of 18 cases in this report), the relationship between HTLV-I (human T-cell leukemia virus type I) infection, which is closely associated with ATL, with other malignancies in an HTLV-I endemic area was examined. Among the 394 patients with malignancies and who had not had blood cell transfusions, 61 (15.5%) tested positive for HTLV-I antibody. The prevalence was significantly higher in males older than age 40 years and females of all ages compared to age- and sex-matched healthy individuals. The overall seroprevalence (26.1%) in 291 patients with malignancies and who had had blood cell transfusions was higher than that of those who had not had blood transfusions. There was no significant correlation between the site of malignancy and antibody prevalence. These results suggest the possibility that development of malignancy may contribute to expression of latent HTLV-I infection and that HTLV-I infection may contribute to the risk of other malignancies.     

UFT for head and neck cancers: its tissue concentrations and effects on lymphocyte subpopulations

Summary UFT, a combination of the masked compound of 5-fluorouracil (FT-207) and uracil, was given to head and neck cancer patients for 1 week preoperatively and for 8 weeks postoperatively. Drug concentrations were examined in the surgically removed tissues. The concentrations of FT-207, 5-fluorouracil, and uracil were higher in tumor tissues than in normal tissues. The lymphocyte subpopulations were assessed by cytofluorometry with monoclonal antibodies. There was no evidence that adjuvant chemotherapy with UFT specifically suppresses immunocompetent cells. We therefore conclude that further clinical evaluation of adjuvant chemotherapy with UFT would be worthwhile.     

Clinical evaluation of tumor markers in breast cancer patients

During the past 4 years, the performances of various tumor markers such as CA15-3, CEA, ferritin, beta 2-microglobulin and TPA have been evaluated in 78 cases of mammary cancer. The results were categorised according to differences in stages, difference in values from patients with recurrent tumors, the incidence of abnormal values and differences in values before and after surgery. When the incidence of values higher than the cutoff value was determined for each of stage I, II and III + IV, the rates for CEA were 14.3%, 4.9% and 27.8%, respectively, whereas those for TPA were 25.0%, 22.2% and 26.7%, respectively. In addition, for CA15-3, the incidences were 0% in stage I, 5.0% in stage II and 57.1% for combined stages III + IV. The average values for patients with recurrent tumors were 3.2 ng/ml CEA, 194.5 ng/ml ferritin, 316.2 U/l TPA and 81.3 U/ml CA15-3. The rates of abnormal values were 40.0% for CEA, 40.0% for ferritin, 85.7% for TPA and 63.6% for CA15-3. Differences in the values after surgical removal of the tumor were observed with these tumor markers: the CEA value was reduced from 1.6 +/- 1.4 to 1.1 +/- 0.5 (p less than 0.01) and the CA15-3 value from 12.2 +/- 8.4 to 9.3 +/- 4.1 (p less than 0.05), respectively, whereas that for ferritin was conversely increased from 48.9 +/- 48.0 to 74.0 +/- 70.0 (p less than 0.01). However, the values for TPA, despite showing a tendency to decrease, did not show any statistically significant alteration. The fluctuations of these marker levels in patients with recurrent tumors reflects the progress of the disease, with a sudden elevation in values indicating imminent death. The diagnostic significance of these markers is not high, but they are considered to be useful in detecting the progress or condition of a recurrent tumor.     

A case of leiomyosarcoma of the prostate

A 50-year-old man with the symptom of anal pain was treated by pelvic exenteration, ileal conduit diversion and artificial anus. The pathologic diagnosis was leiomyosarcoma of the prostate. At 5 months post-operatively, the patient had no evidence of metastasis or recurrence.