Furosemide Given by Inhalation Ameliorates Acute Exacerbation of Asthma

Previous studies have suggested that inhaled furosemide may have a protective effect against a wide variety of bronchoconstrictor agents, but a therapeutic effect has not been established in acute exacerbation of asthma. The purpose of this study was to investigate whether inhaled furosemide would exhibit any therapeutic benefit in acute asthma. We conducted a double-blind, placebo-controlled, randomized study in 40 patients with acute mild or moderate exacerbation of asthma. All patients received intravenous (IV) aminophylline 250 mg for 90 min and IV hydrocortisone 100 mg at entry. After randomization, 3 patients were excluded from the final analysis. At 30 min after starting IV aminophylline, 20 patients were given inhaled furosemide 20 mg and 17 patients received normal saline as placebo-control. Both inhalations were given by a jet nebulizer. The baseline forced expiratory volume at 1 sec (FEV₁), peak expiratory flow rate (PEFR), and serum concentration of theophylline did not differ between the two groups. An increase in FEV₁ in the furosemide group by 28.2 ± 5.9% (mean ± SE) was noted at 60 min, and this was significantly higher than in the control group. PEFR at 60 min was also significantly higher in the furosemide group than in control group. We conclude that inhaled furosemide has a bronchodilator effect on mild to moderate exacerbation of asthma when it is used with IV theophylline. Inhaled furosemide may benefit certain acute asthma patients, especially those suffering complications from the adverse effects of β₂-agonists.     

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.     

Operative fiberoptic nephroureteroscopy: removal of upper ureteral and renal calculi

We tested 2 prototypes of an operating fiberoptic nephroureteroscope, measuring 3.5 and 4.5 mm. in diameter, that have an adequate working channel for auxiliary instruments and irrigation. Difficulty in passing the fiberscope through the ureteral orifice was overcome by dilation with balloon and polytetrafluoroethylene (Teflon) dilators. Our initial trial for stone retrieval under fiberscopic control was performed on 21 patients with upper ureteral and renal calculi. A stone was removed successfully in 15 of the 21 patients (71 per cent). After electrohydraulic lithotripsy calculi were extracted successfully in 9 of 11 patients (82 per cent). Three patients suffered ureteral perforation. The fiberscope was especially helpful when an upper ureteral stone moved back to the kidney during stone manipulation.     

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.     

A case of autoimmune hepatitis needed to be differentiated from EBV hepatitis, in that the histology of liver biopsy specimen was useful for diagnosis]

A 10-year-old girl with autoimmune hepatitis (AIH) was reported. She was admitted to our hospital because of cholestasis and elevation of liver enzymes for 2 months. Laboratory examination revealed that EBV-DNA copy number in the PBMNC (peripheral mononuclear cells) was 1.2 x 10(3) copies/microg of DNA, hypergammaglobulinemia, and positive antinuclear antibody, positive anti-smooth muscle antibody. The histology of her liver biopsy specimen revealed interface hepatitis, dense mononuclear cell infiltrates, mild fibrosis, and negative for EBV in situ hybridization assay indicating AIH and not EBV-associated hepatitis. She was treated firstly with methylprednisolone pulses, then will prednisolone p.o.+azathioprine p.o.. Intravenous cyclophosphamide pulse therapy was introduced because of her abnormal immune pathology. All abnormal laboratory parameters improved to normal levels within 2 months, and EBV-DNA copy number in the PBMNC became negative after 4 months. The histology of liver biopsy specimen was useful for the diagnosis of AIH in such a difficult case needed to be differentiated from EBV hepatitis.     

Epidemiologic background and changes in patients infected with human papilloma virus]

Contagion with certain types of HPV was supposed to have a causal relationship with cervical neoplasia of the uterus. The rate of prevalence of HPV was investigated in pre-cancer and cancer patients with uterine cervical smear using virapap or viratype. According to the cytologic classification, among those whose cytology was diagnosed as class I or II, were found a few positive HPV, however, in cases in classes cytology IIIa, III and IIIb, the positive rate turned out to be 22.5, 41 and 72.4%, respectively. About 65% of patients whose post-operative diagnosis was cervical carcinoma, had been found positive in the pre-operative HPV.DNA check up. The statistical profiles of virally infected subjects were regarded as slightly younger females with early onset of menarche. A higher positive rate was found in such groups such as unmarried single and divorced single women, career employees with special skills, housewives and dwellers in residential and commercial sections. The follow up study of HPV infection was checked with subjects with dysplasia, and no case was recognized in which initially HPV negative dysplasia turned to positive during the observation period. But, in about 50% of those checked, initially HPV positive dysplasia turned to negative, during the follow up period. In the cases with long term (more than 8 years) dysplasia which was followed up, only one out of 10 was found to be HPV positive, while in middle term (more than 2 years but less than 8 years) followed up dysplasia, the positive rate was calculated as 47.8%.     

A case-control study on factors relating to discontinuation of domiciliary care for the bedridden elderly in a metropolitan area]

A case-control study was conducted to examine factors relating to discontinuation of domiciliary care for the bedridden elderly in Shinagawa-ku, Tokyo. Cases were bedridden residents aged 65 years and over who had abandoned home care and applied for admission to live in a special nursing home for the aged between April and September in 1990 after being recipients of welfare allowances for disabled elderly. Controls were bedridden residents who continued to be given home care and matched to cases by sex, age and beginning month of the receiving of allowances. Among 50 cases and 94 controls interviewed, we obtained responses from 31 cases (62%) and 60 controls (64%). The main results were as follows: 1. During the home-care period, ADL (activities of daily living) of cases, especially walking ability, deteriorated more severely than in controls. Night delirium also appeared more frequently in cases. 2. The primary caregivers of cases were older than those of controls. Remarkable differences between cases and controls were observed in the family structure, the number of family members and the number of sub-caregivers. Cases tended to live alone or live with a spouse only, and with smaller number of family members and caregivers. 3. Case lived more frequently in houses with small numbers of rooms and without rooms of their own. 4. As regards utilization of domiciliary care services, cases used dispatch of home helpers more frequently and used day services less frequently.     

Spinal epidural stimulation for central pain caused by spinal cord lesion]

Epidural spinal cord stimulation was carried out in 4 patients with denervation caused by spinal cord lesion, and we reviewed previously reported cases. Initial result showed at 1 week in 100% of our cases, but about 1/3 of the cases, even those with the same denervation caused by spinal cord lesion, had no pain relief at this stage in previously reported cases. In our cases, excellent pain relief was gained temporarily, even though the painful area and the spinal cord lesion were separated somatotopically in 2 cases (case 3, 4). Temporary success bore no relationship to quality and duration of pain. In all cases except case 1, a rapidly decreasing effectiveness was noted, and finally no pain relief was gained at all after 4, 3 and 5 months, respectively. In case 1 there was persistent pain relief estimated at 70-80% after 19 months, only when the spinal cord was stimulated. Epidural stimulation also produced sensations in the painful area. Spinal cord stimulation would suppress at least the dorsal horn neurons which were destroyed by various kinds of diseases. A decline in effectiveness with time would occur due to essential causes of the deafferentation pain, such as anatomical and regeneration factors.