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Biomedical subjects

K Nagano

Publications and source records attributed to K Nagano.

At least 145 records · Page 8Linked to original sources

[Experimental and clinical evaluation of functional electrical stimulation of the anal sphincter].

To determine the most effective parameter of functional electrical stimulation of the anal sphincter (FES), the present study was carried out in female mongrel dogs anesthetized with alpha-chloralose urethane. When spontaneous and rhythmic micturition contractions of the bladder were present, they were more effectively inhibited by the stimulation with low frequency (5 to 10 Hz). Based on the results of this experiment 18 patients with urge incontinence were treated by maximal electrical stimulation with the following parameters. The duration for each stimulus was 0.2 msec, frequency 5 Hz, amplitude 30 to 150 volts. Every patient received ten treatments for two weeks, each lasting for 30 minutes. A clinical cure for urge incontinence was noted in 12 patients. As for urodynamic studies, FES increased significantly the volumes of the first desire to void (FDV) and maximum desire to void (MDV); however, it did not increase significantly the maximum urethral closure pressure or residual urine volume. Eighteen patients were divided into two groups; an unstable bladder group and a neurogenic bladder group. In the latter, the increases in volumes of FDV and MDV were significant. Second, 18 patients were divided into two groups according to the administration of lack of anticholinergic agents. For subjective symptoms, the rate of improvement of urge incontinence was significantly higher in the group administered the agents. These findings suggested that FES was very useful for the treatment of urge incontinence, with its efficacy augmented by the administration of anticholinergic agents.

Aged↗

[A study on the relationship between solvent abusers and alcoholism in the parental generation].

In recent years, attention has been paid to the fact that alcoholism and/or drug addiction runs in families. Few studies have investigated the relationship between solvent abuse in adolescents and alcoholism in their parents. Two hundred and ten solvent abusers who came to Serigaya-en, alcoholism and drug addiction treatment hospital, during from 1983 to 1989, were examined from the following two standpoints. The proportion of solvent abusers with alcoholic parents (A group), what characteristics the solvent abusers in A group had as compared with those whose parents were not alcoholic (NA group). The findings were summarized as follows; 21.4% of the subjects had an alcoholic (FH-RDC) parent. They were approximately two years older than those in the NA group at the first examination. The solvent abusers of the A group presented with: 1) more experiences of parental death and/or separation prior to the age of 15; 2) a higher frequency of school refusal in elementary or junior high school; 3) poorer socioeconomic status; 4) a longer duration of solvent abuse; 5) more abuse of addictive drugs other than solvent; 6) a more severe psychopathology; 7) a higher incidence of chronic organic diseases among their parents; 8) a higher incidence of solvent abuse among their siblings. The present study indicates that: 1) many a solvent abuser come from alcoholic families; 2) parental alcoholism is responsible not only for solvent abuse, but also for the development of addictions, (e.g., prolonged solvent abuse, developing into alcoholism or poly-substance abuse); 3) clinical and socioeconomic deterioration occurs not merely in the individual abusers but also in other family members, especially in the A group. The results lead the author to stress the importance of focusing the therapy upon the family itself.

Adolescent↗

The response of the detrusor muscle to acetylcholine in patients with infravesical obstruction.

We previously examined the effects of overdistension on the neuromuscular system of canine urinary bladders and reported that bladder overdistension led to nerve degeneration and subsequent supersensitivity through a decrease of blood supply to the bladder. We have accordingly in this study evaluated these changes in human subjects with infravesical obstruction. The responses to acetylcholine of bladder strips obtained from patients with detrusor instability were not significantly different from those of bladder strips from patients without detrusor instability, but the dose-response curve of these groups showed a shift to the right compared to that of the unobstructed control patients. As compared with the response of bladder strips in patients without an episode of retention, the response in patients who received prostatectomy within 30 days demonstrated no significant difference, although in patients who received prostatectomy after more than 30 days there was a statistical difference. These results indicated a significant decrease in sensitivity of the detrusor muscle in patients with infravesical obstruction and suggest that bladder overdistension caused by infravesical obstruction may lead to supersensitivity of the detrusor muscle secondary to denervation.

Acetylcholine↗

Effect of ethanol on endothelin-1 release from gastric vasculature.

The effects of ethanol on gastric vasculature in isolated vascularly perfused rabbit stomach was investigated. The isolated stomach was perfused with Krebs-Henseleit solution containing 3% dextran bubbled with 95% O2 and 5% CO2 at a rate of 12 ml/min. After mixture and perfusion of 10 mM to 400 mM of ethanol, perfusion pressure and endothelin-1 concentration in effluent from gastric vasculature were measured. Perfusion pressure and endothelin-1 concentration in effluent increased in a dose-dependent manner with increasing ethanol concentrations. In conclusion, the data suggest that ethanol may stimulate the release of endothelin from gastric vasculature and may cause gastric ischemia due to vasoconstriction resulting in acute gastric mucosal injury.

Animals↗

Prediction of efficacy of antidepressant by 1-week test therapy in depression.

Forty patients suffering from depression were treated with fixed doses of clomipramine for 4 weeks. The most effective predictor of efficacy during the 4 weeks was the percentage improvement in the Hamilton rating scale for depression during the first week. Baseline severity did not show any predictive ability. The Beck depression rating scale had only low predictive ability, and the dexamethasone suppression test did not predict the outcome at all. These results suggest the benefit of 1-week test therapy for predicting the efficacy of antidepressants.

Adolescent↗

Two-dimensional computer color graphics of gastric mucosal blood distribution in normal subjects and ulcer patients.

The mucosal blood volume in 20 to 24 different regions of stomach was estimated by reflectance spectrophotometry during endoscopy, and an image showing mucosal blood distribution was made by two-dimensional computer color graphics with the aid of a personal computer. In 55 normal controls, the estimated mucosal blood volume (EMBV) was greater in the corpus mucosa than in the antral mucosa, and less in the lesser curvature than in the greater curvature. The volume in the anterior and posterior walls was almost the same. In 15 patients with active gastric ulcers in the angular region, the EMBV was decreased in all regions in the stomach. In 37 patients with healing ulcers, the EMBV increased, resuming the same levels as in normal controls. However, the EMBV around the ulcer increased remarkably at this stage. In 35 patients with ulcers in the scarring stage, the distribution of the EMBV was similar to that in the normal controls. These hemodynamic changes were shown clearly in a color display with the aid of a personal computer. This method could offer new possibilities in endoscopic research.

Adult↗

Age-related change in human gastric mucosal energy metabolism.

Many investigators have reported a decrease in mucosal blood flow resulting in impairment of gastric mucosal energy metabolism in animal experiments. Recently, endoscopic studies using reflectance spectrophotometry and laser Doppler flowmetry have indicated that gastric mucosal blood flow in humans decreases with age. However, changes in energy metabolism in human gastric mucosa with age remains obscure. In this study, we measured adenine nucleotides in biopsy samples from human gastric mucosa, using high-performance liquid chromatography, and investigated changes in energy metabolism with age in subjects proven normal endoscopically. Energy charge (EC = (ATP + 1/2 ADP)/ATP + ADP + AMP) in the gastric antral and body mucosa showed decrease with age. When the subjects were divided into two groups, less than and more than 65 years old, the EC level was significantly lower in the latter than the former in both antral and body mucosa (0.65 +/- 0.06 versus 0.74 +/- 0.03 in the antrum, 0.73 +/- 0.04 versus 0.79 +/- 0.04 in the body) and significantly less in the antral mucosa than in body mucosa in both groups. The adenosine triphosphate (ATP) level in the older group showed a significant decrease (6.48 +/- 1.14 versus 9.63 +/- 1.92 in the antrum, 8.59 +/- 1.64 versus 10.60 +/- 2.13 in the body) compared with those less than 65 years old. In the antral mucosa of the older group the adenosine diphosphate (ADP) level was also significantly lower than that in the group less than 65. In conclusion, in the elderly, the energy metabolism in human gastric mucosa is impaired, and this may weaken their defensive mechanism.

Adenine Nucleotides↗

Double-blind study of the chronopharmacotherapy of depression.

To investigate the possibility of chronotherapy with antidepressants for patients with depression, we gave single daily doses of clomipramine 150 mg/day to 30 patients with depression at three different times of day, i.e., morning, noon, or before bedtime, using a double-blind method over a 4-week period. Beneficial effects differed according to the administration time of day, with the most effective result being found for the administration at noon. Time-dependent differences in side effects were observed in tremors and dryness of mouth. An additional 10 patients were administered their medications three times a day by traditional, equally divided doses, and the efficacy was inferior than daily single doses at noon. The study results showed the significance of the administration time of day for the benefits and side effects of antidepressant therapy for depression.

Administration, Oral↗

Augmented Na,K-ATPase gene expression in spontaneously hypertensive rat hearts.

Abnormalities in cardiovascular Na,K-ATPase ion-transport function and regulation may play an important role in the pathogenesis of hypertension. However, it is not known whether these abnormalities are secondary to the effects of hypertension, such as increased pressure, or reflect an intrinsic abnormality in Na,K-ATPase gene expression and regulation. A genetic model of hypertension was used to address this issue. Na,K-ATPase alpha subunit gene expression in hearts was compared between spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Pre-hypertensive, 4-week old SHR hearts exhibited an approximately 4 fold elevation in alpha 1 and 8 fold elevation in alpha 2 mRNA levels compared with age-matched WKY hearts. These SHR mRNA levels remained almost equivalent throughout the development of hypertension at 8 and 16 weeks of age. WKY alpha 1 and alpha 2 mRNA levels exhibited a progressive increase during the same time period. The neonatal alpha 3 mRNA isoform was detected only in pre-hypertensive (4-week) SHR hearts. We conclude that cardiac Na,K-ATPase alpha subunit gene expression is significantly altered in SHR even before the onset of hypertension. These findings suggest that an abnormality in cardiac Na,K-ATPase gene expression constitutes an early, if not primary, event in spontaneous hypertension.

Animals↗

[End-stage chronic renal failure in patients treated by antireflux operation].

We report 3 patients progressed to end-stage chronic renal failure after antireflux surgery. Preoperatively, the 3 patients had proteinuria, probably due to reflux nephropathy. Surgical procedures used were Paquin's method in 1 patient and Politano-Leadbetter's method in 2. Rapid deterioration of renal function was observed from puberty in all patients. In addition, renal hypoplasia was suspected in 2 patients. We concluded that both reflux nephropathy and renal hypoplasia played important roles in the progression of renal insufficiency.

Adolescent↗

Role of blood ethanol on gastric mucosal injury and gastric hemodynamics.

The present series of studies were performed to test the hypothesis that ethanol in the blood may play a role in the pathogenesis of gastric mucosal injury. Another hypothesis to be examined was that endothelin may be involved in ethanol-induced gastric mucosal injury. Elevated levels of blood ethanol induced by intraperitoneal infusion of ethanol increased vulnerability of the stomach to hydrochloric acid in a dose-dependent manner in rats. This may be due to impaired gastric mucosal hemodynamics and oxygenation as demonstrated by the results obtained by organ reflectance spectrophotometry (decreases in indices of mucosal hemoglobin contents and hemoglobin oxygen saturation). Ethanol infusion caused a dose-dependent increase in gastric vascular resistance in perfused rabbit stomach, which was accompanied by an increased production of endothelin-1. The results suggest that endothelin may be involved in the pathogenesis of ethanol-induced gastric mucosal injury.

Animals↗

[Laboratory and clinical studies on cefpirome in pediatrics].

Laboratory and clinical studies on cefpirome (CPR, HR 810), a newly developed cephem antibiotic, were performed. The results obtained are summarized as follows: 1. Absorption and elimination of the drug were examined in a total of 7 children including 3 cases of administered with 20 mg/kg intravenous bolus injection (i.v.), 2 cases with 20 mg/kg drip infusion (d.i.v.) for 60 minutes and 2 cases with 40 mg/kg (d.i.v.) for 60 minutes. Maximum serum levels were attained immediately after i.v. or d.i.v. Cmax's were 233 +/- 7.6, 88.5 +/- 14.5, and 116 +/- 15 micrograms/ml, respectively for the above 3 modes of administration. These values were determined using a bioassay method with Bacillus subtilis ATCC 6633. T 1/2 (beta)'s were 1.18 +/- 0.17, 1.61 +/- 0.28 and 2.68 +/- 0.83 hours, respectively. Cumulative urinary recovery rates were 40.2-69.8% in a period of 0-6 hours after admissions. 2. Clinical efficacies were evaluated in a total of 20 patients with ages ranging from 9 months to 11 years. The treated cases were 6 cases of acute pneumonia, 4 cases of acute bronchitis, 4 cases of acute purulent tonsillitis, 2 cases of acute urinary tract infections, 2 cases of cellulitis, 1 case of purulent lympadenitis and 1 case of acute otitis media. The clinical efficacy rate was 94.7%. Adverse reactions occurred in no patients. Abnormal changes in laboratory test values involved only 1 case with elevated GOT and GPT. CPR was considered to be a safe and useful drug in treating various infectious diseases in children.

Bacterial Infections↗

[A clinical study of voiding status in multiple sclerosis patients].

During a period of 4.5 years, neurological and urodynamic evaluation was done on 12 patients with multiple sclerosis between 20 and 67 years old with an average age of 47.6 years. Pyramidal dysfunction (100%), sensory disturbance (100%) and brain stem dysfunction (60%) were common neurological signs. All patients were assessed by the Kurtzke's rating of neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Of the 12 cases 6 were diagnosed as severe multiple sclerosis (EDSS greater than or equal to 4.5) and the remainders were diagnosed as relatively mild (EDSS less than 4.5). Neurourologic evaluation was performed by rapid filling carbon dioxide cystometry and sphincter electromyography. Cystometry revealed overactive bladder in 4 (33%), underactive bladder in 3 (25%) and normoactive bladder in 5 (42%) of the 12 cases. Of the 6 severe cases of multiple sclerosis, 3 (50%) showed overactive bladder, while only 1 of the 6 (17%) mild cases showed overactive bladder. Detrusor sphincter dyssynergia (DSD) was observed in 4 of the 9 (67%) severe cases and none of the 6 mild cases. The presence of overactive bladder or DSD seems to correlate with the severity of multiple sclerosis.

Adult↗

[Intracellular calcium level, lipid peroxidation, and development of gastric mucosal injury in rat hemorrhagic shock].

Although acute gastric mucosal lesions (AGMLs) develop after the mucosal ischemia and reperfusion, precise intracellular mechanism for the development of AGMLs remains unclear. In the present paper, we investigated intracellular calcium level, lipid peroxidation, and gastric mucosal lesion in rat hemorrhagic shock model. We estimated intracellular calcium by measuring phosphorylase a activity in the gastric mucosa. The mucosal phosphorylase a increased during hemorrhagic shock, while it returned to be normal after the reinfusion of shed blood. Although mucosal lipid peroxide and area of AGMLs did not increase significantly during hemorrhagic shock, they increased significantly after the reinfusion. Diltiazem, a calcium antagonist, prohibited both of the increase in mucosal phosphorylase a activity during hemorrhagic shock and the increase in lipid peroxide content and area of AGMLs after the reinfusion of the shed blood. Organ reflectance spectrophotometry revealed that the gastric corpus suffered mucosal ischemia and hypoxia during the hemorrhagic shock. The are of AGMLs had a good correlation with a level of lipid peroxidation in the gastric mucosa. These results suggest 1) that intracellular free calcium in gastric mucosa increases during the mucosal ischemia; 2) that a calcium antagonist prohibits the increased intracellular free calcium during mucosal ischemia; and 3) that a calcium antagonist prohibits the increased mucosal lipid peroxide and the development of AGMLs after the mucosal reperfusion. Thus it is concluded that the increased intracellular free calcium during ischemia plays a key role in the mucosal tissue injury in the ischemia-reperfusion state.

Animals↗

Inhibition of neutrophil migration by tumor necrosis factor. Ex vivo and in vivo studies in comparison with in vitro effect.

Coincubation of neutrophils with TNF inhibited the chemoattractant-directed migration of neutrophils under agarose and enhanced their migration in the multiwell chemotaxis chamber. To assess the physiological significance of these differing in vitro TNF effects, ex vivo and in vivo investigations were performed using animal models. Neutrophils from the peripheral blood of rabbits preadministered systemic TNF showed impaired ability to migrate toward chemoattractants in vitro. In addition, systemic TNF administration suppressed zymosan-activated plasma-induced local accumulation of leukocytes in mouse skin. The results indicate that circulating TNF may act as a suppressor for local inflammatory reaction.

Animals↗

Cloning and analysis of the 5'-flanking region of rat Na+/K(+)-ATPase alpha 1 subunit gene.

We cloned a 13.3 kilobase (kb) fragment of genomic DNA spanning at least the first two exons of the rat Na+/K(+)-ATPase alpha 1 subunit gene (NKAA1) and 1.5 kb of the 5'-flanking region. S1 nuclease mapping analysis of the 5' end of the Na+/K(+)-ATPase mRNA indicated that the transcription initiation site was located 262 base pairs (bp) upstream of the translation initiation codon. The transcription initiation site of the Na+/K(+)-ATPase alpha 1 subunit gene was identical among six tissues of adult rat (kidney, brain, heart, thyroid, liver and lung). A TATA-box-like sequence (at position -32), two Sp1 factor binding sequences (-137, -56), an active transcription factor consensus binding sequence (-71) and two glucocorticoid-responsive element half consensus sequences (-750, -481) were found in the 5'-flanking region. The sequence of the first exon and the 5'-flanking region of the rat NKAA1 was 63% homologous to that of the horse equivalent. Maximum homology (82%) between the two genes was observed in the region from 361 bp upstream of the translation initiation site to the 3' end of the first exon. The TATA-like box, Sp1 binding site and the active transcriptional factor (ATF) consensus site in this region were conserved in both rat and horse.

Animals↗