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Biomedical subjects

K Takebe

Publications and source records attributed to K Takebe.

At least 145 records · Page 8Linked to original sources

[A comparative study between cefodizime (CDZM) and cefotaxime (CTX) in respiratory tract infections].

The clinical efficacy and safety of Cefodizime (CDZM), a new cephem antibiotic, was objectively compared with that of Cefotaxime (CTX) in patients with respiratory infections under a well-controlled comparative study. Patients were administered CDZM or CTX by drip infusion b.i.d. for 14 days in principle at a daily dose of two grams. The parameters assessed were clinical efficacy, safety and clinical usefulness. The following results were obtained: 1. On the basis of committee judgement the clinical efficacy rate was 78.1% (125/160) for the CDZM group, 82.7% (124/150) for the CTX group, and no significant difference was observed between the two drug groups. On the other hand, on the basis of judgement by physicians in charge, the clinical efficacy rate was 83.1% (133/160) for the CDZM group, 83.9% (125/149) for the CTX group, and no significant difference was observed between the two groups. 2. The corresponding figures for patients with pneumonia and pulmonary suppuration were 82.4% (70/85) for the CDZM group, 79.7% (59/74) for the CTX group and no significant difference was observed according to the committee judgement. The judgement by physicians in charge also revealed 83.5% (71/85) for the CDZM group and 82.2% (60/73) for the CTX group. No significant difference was noted between the two groups. While, the committee judgement for the clinical efficacy in patients with chronic respiratory tract infections showed 73.3% (55/75) for the CDZM group, 85.5% (65/76) for the CTX group, and no significant difference was observed between the two drug groups. The corresponding figures were 82.7% (62/75) for the CDZM group, 85.5% (65/76) for the CTX group, and no significant difference was observed between the two drug groups on the judgement by physicians in charge. Furthermore, the clinical efficacy of both drugs on chronic respiratory tract infections was assessed according to "Criteria for Evaluation of Clinical Efficacy of Chemotherapeutics on Chronic Respiratory Tract Infection". It was 76.8% (53/69) for the CDZM group, 76.3% (58/76) for the CTX group, and no significant difference was observed between the two groups. 3. The bacteriological eradication rate of causative pathogens was 92.4% out of 66 patients treated with CDZM and 95.5% out of 67 patients treated with CTX in whom judgement was possible. No significant difference was observed between the two drug groups. 4. The adverse reactions occurred in 4 (2.2%) patients for the CDZM group and 8 (4.5%) patients for the CTX group respectively, with no significant inter-group difference in frequency of these reactions for all cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

Sympathetic skin response in diabetic neuropathy.

Sympathetic function test was undertaken using the sympathetic skin response (SSR), a technique for assessment of sudomotor activity, in 67 diabetics, and the results were compared with those from 45 age-matched normal subjects. The SSR was readily elicitable in normal subjects, but absent in six patients with diabetes. In 28 patients, the SSR was preserved, but their amplitude was below the normal range. The decrease in the SSR amplitude correlated well with a fall in motor and sensory conduction velocity. The SSR magnitude correlated well to the impaired R-R interval variation during deep breathing and the heart rate increase and the blood pressure change on standing, indicating a close correlation between the disturbance of sudomotor function and that of other sympathetic and parasympathetic functions. Most of the patients with clinical evidence of dysautonomia and with insulin treatment revealed diminished or absent SSR.

Adolescent↗

The biotransformed metabolite profiles in blood after intravenous administration of dehydrocholic acid.

One gram of dehydrocholic acid was injected intravenously into two patients with percutaneous transhepatic cholangial drainage, and the biotransformed metabolites profiles over a 120-min period in serum and bile were analyzed. In serum unconjugated 3 alpha-hydroxy-7,12-dioxo-cholanoic acid (3 alpha-OH-7,12-OXO) acid was markedly increased after the injection of dehydrocholic acid, and reached about 80 microM within 30 min. On the other hand, conjugated 3 alpha, 7 alpha-dihydroxy-12-oxo-cholanoic acid (3 alpha,7 alpha-OH-12-OXO) was consecutively increased with lag time to an elevation of 3 alpha-OH-7,12-OXO. In bile, the major constituent of metabolites was conjugated 3 alpha,7 alpha-OH-12-OXO (more than 90% of the excreted metabolites), while conjugated 3 alpha-OH-7,12-OXO was detected as minor constituent. Therefore, between bile and serum, there was great difference in biotransformed metabolites profiles. The mechanism of elevation of unconjugated 3 alpha-OH-7,12-OXO in serum remains obscure, but this new finding raised a question as to whether organ-reducing 3-keto group of dehydrocholic acid is restricted to the liver.

Aged↗

Enzymatic determination of serum 12 alpha-hydroxy bile acid concentration with 12 alpha-hydroxysteroid dehydrogenase.

A simple colorimetric enzymatic assay for determination of serum 12 alpha-hydroxy bile acids was developed using 12 alpha-hydroxysteroid dehydrogenase (HSD). The enzymes were extracted from Bacillus sphaericus. The principle of the method is as follows: 12 alpha-hydroxy bile acids are converted to 12-oxo bile acids using 12 alpha-HSD with the conocomitant reduction of NAD to NADH, and then the hydrogen of the generated NADH is transferred by diaphorase to NTB to yield diformazan. Finally, the color of resultant diformazan was measured. The specificity and precision of this assay method were satisfactory. A linear relationship was noted between the amount of 12 alpha-hydroxy bile acids and the degree of absorbance in the range of 6.7 to 215 microM. The fasting values for serum 12 alpha-hydroxy bile acid in 10 patients with liver diseases ranged widely from 7.6 to 91.1 microM, and values obtained with this assay agreed closely with those obtained by gas-liquid chromatography (r = 0.94, p less than 0.001). The assay is convenient, rapid, and specific for the measurement of 12 alpha-hydroxy bile acid concentrations in the serum of patients with liver diseases.

Adult↗

Spontaneous remission of acromegaly after pituitary apoplexy following head trauma.

A 34-year-old man with acromegaly was observed, and the clinical course and various endocrinological deficiencies occurring before, during and after the development of pituitary apoplexy were evaluated. Following the attack, the patient experienced acute reductions in growth hormone (GH) and other pituitary hormones, adrenohypophyseal insufficiency and transient diabetes insipidus which appeared subsequent to glucocorticoid therapy. The level of growth hormone in serum and cerebrospinal fluid (CSF) was measured synchronously, and the respective regressions of GH levels in serum and CSF were observed. The results demonstrated the utility of measuring hormonal levels in CSF in the clinical evaluation of pituitary apoplexy in a patient with a functioning pituitary tumor.

Acromegaly↗

Ectopic ACTH syndrome due to Grawitz tumor.

An extremely unusual case of adrenocorticotropin (ACTH)-producing Grawitz tumor is reported in a 56-year-old female. The clinical feature of the patient was compatible with Cushing's syndrome. The plasma levels of ACTH and cortisol were markedly elevated. At autopsy, a left renal tumor was demonstrated and its histopathological diagnosis was renal cell carcinoma (Grawitz tumor). The adrenal gland was bilaterally enlarged with diffuse hyperplasia of the fasciculate zone. The adenohypophyseal cells were atrophic and showed Crooke's degeneration. The tumor contained extremely high levels of ACTH, beta-lipotropin and beta-endorphin. The presence of large molecular weight forms of ACTH has also been demonstrated by a Sephadex G-50 gel filtration of the tumor extract. We authors believe that this is the first documented case of ACTH-producing Grawitz tumor in the literature.

ACTH Syndrome, Ectopic↗

[An autopsy case of parathyroid carcinoma with primary hyperparathyroidism].

An autopsy case of a 72-year-old woman who was determined as having had a parathyroid carcinoma with primary hyperparathyroidism is reported. On autopsy, a tumor, measuring 6 X 3 X 2 cm, was found beneath the left lobe of the thyroid gland, adherent to the left recurrent nerve and the trachea, though there was no metastasis evident. The tumor was found to be lobulated on cross section inspection. Histologically, the tumor cells were arranged in trabecular and in solid patterns with fibrous bands. A few tumor cells showed mitosis. Invasions to the capsules and the blood vessels were found present. Immunohistochemically, the parathyroid hormone was found positive in the cytoplasm of the tumor cells. Otitis fibrosa generalisata, metastatic calcification, acute pancreatitis, and core pulmonale also were observed.

Aged↗

Multiple oral doses of nicardipine, a calcium-entry blocker: effects on renal function, plasma renin activity, and aldosterone concentration in mild-to-moderate essential hypertension.

We studied the effects of nicardipine administered in a 4-week fixed oral maintenance dosage (20 or 40 mg t.i.d.) on renal function, plasma renin activity (PRA), and plasma aldosterone concentration in seven patients with mild-to-moderate essential hypertension. Glomerular filtration rate and renal blood flow were measured by means of sodium thiosulfate and para-aminohippurate, respectively. Nicardipine increased renal blood flow by 11.5% +/- 4.3% (mean +/- SE; P less than 0.05) and glomerular filtration rate by 16.3% +/- 6.4% (P less than 0.05) and decreased total renal vascular resistance by 30.0% +/- 2.7% (P less than 0.05), with a significant (P less than 0.05) reduction in systolic and diastolic blood pressure as compared with placebo values. Nicardipine increased PRA significantly (P less than 0.05), whereas plasma aldosterone concentration remained unchanged. Our results indicate that nicardipine given in a multiple oral dosage has some favorable renal effects with a concomitant hypotensive action in patients with mild-to-moderate essential hypertension. Nicardipine appears to blunt the secretion of aldosterone responding to an increased PRA possibly through its calcium-antagonizing action.

Adult↗

Postnatal ovary is necessary for the maturation of estradiol-induced luteinizing hormone and prolactin surges in female rats.

The role of postnatal ovary in the maturation of estradiol (E2)-induced luteinizing hormone (LH) and prolactin (PRL) surges was examined in female rats of Wistar-Imamichi strain. Animals were bilaterally ovariectomized at 24 h after birth, 1 week (w), 2 w, 3 w, 4 w or 6 w of age. At about 10 w of age, every group was primed with estradiol benzoate (E2B) for two days, and on the third day was decapitated at either 0900 h or 1900 h. Anterior pituitary (AP) LH and PRL content was determined in every group of no E2B treatment. Surge-like secretions of LH and PRL were observed at 1900 h, only in rats ovariectomized on or after 4 w of age. AP LH and PRL content was the higher, as ovariectomy was delayed. These results indicate that postnatal ovary is necessary for the maturation of E2-induced LH and PRL surges. Such an effect of ovary is mediated at least by its stimulation of AP LH and PRL content.

Animals↗

Role of postnatal gonadal function in the determination of thyrotropin (TSH) releasing hormone-induced TSH response in adult male and female rats.

Permanent effects of postnatal gonadal function on the hypothalamo-pituitary-thyroid axis were examined in male and female rats of the Wistar-Imamichi strain. Animals were used at the age of about 10 weeks. Neonatally castrated (NC) males showed a significantly higher plasma TSH response to TRH (10 micrograms/kg BW, ip) than males castrated at 1, 2, 3, 4, or 6 weeks of age. The TSH response in intact males was similar to that seen in NC males. Neonatal androgenization of NC males with 100 micrograms/rat of testosterone propionate decreased the TSH response in the group. The anterior pituitary (AP) TSH content was similar among all male groups. The number of AP TRH receptors was significantly higher in both NC males and intact males than in both NC + neonatal androgenization males and 6-week-castrated males. In female rats, TRH-induced TSH response, AP TSH content, and AP TRH receptor number were all unaffected by the age of castration, whereas intact females significantly exceeded 6-week-castrated females in these three variables. The circulating levels of T3 and T4 and hypothalamic TRH content were similar in all groups in each sex. These results indicate biphasic effects of postnatal testosterone on the TSH response to TRH, that is, a permanent inhibition in early postnatal days and a transient stimulation in adult age. The effects occurred not via changes in AP TSH content but via changes in AP TRH receptor number. In females, however, postnatal gonads did not exert any permanent effects on the TRH-TSH system.

Aging↗

Involvement of postnatal gonads in the maturation of dopaminergic regulation of prolactin secretion in male rats.

Permanent effects of postnatal gonads on dopamine (DA)-mediated regulation of PRL secretion were examined in adult male rats of the Wistar-Imamichi strain. Rats were bilaterally orchidectomized at varying postnatal days, i.e. 8 h after birth [neonatal castration (NC)] or at 1, 2, 3, 4, or 6 weeks of age, and subjected to experiments at the age of about 10 weeks. Ten-week-old intact adults were also examined. All groups were injected ip with saline or sulpiride (1 mg/kg BW), and blood samples were collected by rapid decapitation 20 min later. Anterior pituitaries (AP) thus obtained were subjected to determination of PRL content. The circulating level of testosterone was similar among all castrated groups. Rats castrated on or after 3 weeks of age showed a significantly smaller PRL response to sulpiride than intact adults. In turn, sulpiride-induced PRL release in rats castrated on or before 2 weeks of age was similar to that in intact adults. However, the AP PRL content of saline control was uniformly lower in castrated males than in intact adults regardless of age at castration (P less than 0.01). The value in males castrated at 1 week was 2.0-fold higher than that in NC males, but a decreasing trend was observed in groups castrated at 2 or 3 weeks. That such a stimulation of AP PRL content by the neonatal testis is not mediated by an action of estradiol converted from testosterone has been suggested by the failure of daily neonatal tamoxifen (estrogen antagonist) treatment of intact males, before castration at 1 week, to decrease AP PRL content during adulthood. Sulpiride-induced reduction of the AP PRL content was significant only in males castrated at 6 weeks and intact adults. Characteristics of AP DA receptors labeled by [3H]spiperone were not different between males castrated at 6 weeks and intact adults. However, a heterogeneity was observed between NC males and a set of males castrated at 6 weeks and intact adults. The Kd was significantly (P less than 0.05) greater in NC males (mean +/- SE, 1.19 +/- 0.22 nM) than in males castrated at 6 weeks (0.52 +/- 0.08 nM), and the number of binding sites was significantly (P less than 0.05) larger in NC males (20.4 +/- 1.6 fmol/pituitary) than in both males castrated at 6 weeks and intact adults (12.6 +/- 2.0 and 13.1 +/- 1.9 fmol/pituitary, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Involvement of postnatal gonads in the maturation of dopaminergic regulation of prolactin secretion in female rats.

Permanent effects of postnatal gonads on dopamine (DA)-mediated regulation of PRL secretion were examined in adult female rats of the Wistar-Imamichi strain. Experiments were uniformly done at the age of about 10 weeks. First, rats were bilaterally ovariectomized on varying postnatal days, i.e. 24 h after birth [neonatal castration (NC)] or at 1, 2, 3, 4, or 6 weeks of age. Intact diestrous females were also examined. All groups were injected ip with saline or sulpiride (1 mg/kg BW), and blood samples were collected by rapid decapitation 20 min later. Also, in saline control groups, the anterior pituitary (AP) PRL content was determined. In NC females, significant PRL release was not observed by either sulpiride or saline. However, stimulation of PRL release by sulpiride was observed consistently in rats ovariectomized on or after 1 week of age. Although there was not a complete correlation between the plasma PRL level attained after sulpiride treatment and the AP PRL content, the general trend was that the AP PRL content was increased as the postnatal age of the ovariectomy was delayed. Values in intact adult females exceeded those in all of the castrated groups in both parameters. Second, daily sc injection for 7 days with estradiol benzoate (E2; 2.5 micrograms/kg BW) and/or progesterone (P; 5 mg/kg BW) was given after NC to determine which ovarian secretion(s) is involved in the aforementioned findings. Sulpiride stimulated PRL release in NC females that had been treated neonatally (postnatal days 3-9) with either E2 or P. This effect was accompanied by an increase in the AP PRL content. An enhancement of both parameters was also observed when the same dose of E2 or P was given in the fourth week (postnatal days 22-28). However, neither parameter was further augmented by concurrent administration of E2 and P at either postnatal time. Characteristics of AP DA receptors were subsequently analyzed in some of the foregoing groups using [3H]spiperone. The number of binding sites, when expressed as femtomoles per pituitary, did not differ among all groups examined. However, a significant difference in the dissociation constant (Kd) was observed between NC females and females castrated at 6 weeks of age. The Kd in NC females was not altered by subsequent neonatal treatment with E2 and/or P. Nonetheless, the E2 effect on Kd was dependent on when E2 was given after NC.(ABSTRACT TRUNCATED AT 400 WORDS)

Age Factors↗

Cimetidine-induced prolactin release in rats. The effect of sex and gonadal steroids.

The cimetidine-induced plasma Prl response was examined in rats of both sexes. First, 10 week old intact adult males and females (dioestrous) were compared. There was no significant difference in the Prl response to cimetidine between the two groups, despite the fact that in adult females the anterior pituitary Prl content was 4 times greater than in males. Second, the effect of gonadal state in adult age on the Prl response to cimetidine was examined in both sexes. In male rats, gonadectomy at the age of 6 weeks significantly reduced the plasma Prl response as well as the pituitary Prl content, both of which were sufficiently restored by testosterone replacement. However, in females, neither gonadectomy at the age of 6 weeks nor subsequent oestradiol replacement affected the Prl response to cimetidine, despite the fact that gonadectomy significantly reduced and oestradiol treatment significantly enhanced the pituitary Prl content. Third, possible permanent effects of the postnatal gonadal milieu on the cimetidine-induced Prl response and the pituitary Prl content were examined in both sexes by castration at varying postnatal ages. The ratio of plasma Prl response to pituitary Prl content was similar in all castrated males. In females, however, the ratio decreased with increasing castration age. In conclusion, the mechanism of cimetidine-induced Prl release is less sex-dependent than are the mechanisms of Prl release by other Prl secretagogues. First, this may be due to a minor role of oestrogen in females in determining the Prl response to cimetidine. Second, the postnatal ovarian secretions may exert a permanent inhibition of the development of the cimetidine-mobilized anterior pituitary Prl pool.

Age Factors↗

[Clinical study of carumonam].

To evaluate the clinical efficacy of carumonam (CRMN, AMA-1080), the drug was used in the treatment of 10 patients including 4 with pneumonia and each with acute tonsillitis, chronic bronchitis, Mycoplasma pneumonia, primary atypical pneumonia (PAP), chronic pyelitis, and acute cystitis. Since beta-lactam antibiotics were not active against Mycoplasma pneumonia and PAP, these diseases were excluded from the clinical efficacy evaluation of CRMN. Responses were excellent in 1 patient and good in 7. Side effects were not observed. The laboratory test recognized slight elevations of GOT, GPT and eosinophilia in 1 patient and a slight leucopenia in another upon the administration of CRMN.

Adult↗

[Free methyltetrazolethiol concentrations in men subjected to intravenous administration of cephems with methyltetrazolethiol].

The disulfiram-like reaction due to cephems with methyltetrazolethiol (tetrazole) moiety was studied in biotransformation of these drugs. The serum tetrazole concentration was determined following intravenous administration of cefoperazone (CPZ) 1 g, latamoxef (LMOX) 1 g, or cefmetazole (CMZ) 2 g to patients suffering infections without liver dysfunction, and of CPZ 1 g to patients with liver cirrhosis. Tetrazole concentrations in normal patients were 0.5-2.0 micrograms/ml after 3 hours, and 0.14-0.26 micrograms/ml after 12 hours, and undetectable after 24 hours. On the other hand, the tetrazole concentration in cirrhotic patients was 0.143 +/- 0.07 micrograms/ml (mean +/- SD) even after 24 hours. Therefore, it is concluded that the disulfiram-like reaction due to cephems with tetrazole moiety closely related to the metabolism of these drugs in liver, and probably be caused by the inhibition of acetaldehyde dehydrogenase activity in liver by the free tetrazole group produced by the metabolism of these drugs in liver.

Aldehyde Oxidoreductases↗