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Biomedical subjects

M Nihei

Publications and source records attributed to M Nihei.

At least 19 recordsLinked to original sources

[Efficacy of combination therapy consisting of cyclophosphamide, adriamycin, UFT and oophorectomy/tamoxifen for advanced or recurrent breast cancer].

Combination therapy consisting of cyclophosphamide (CPA), adriamycin (ADR), UFT and endocrine therapy of oophorectomy or tamoxifen (TAM) was given female patients with advanced or recurrent breast cancer. Premenopausal patients initially underwent oophorectomy, then were administered 300 mg/day of CPA and 30 mg/day of ADR intravenous injection every 2 weeks, and 300 mg/day of UFT orally every day. Postmenopausal patients, on the other hand, were administered the same three chemotherapeutic drugs and 30 mg/day of TAM orally every day instead of receiving castration. A total of 10 patients were registered, and nine of them were eligible. Premenopausal cases were six, and postmenopausal cases were three. The objective response rates were 50% (3/6) for premenopausal women and 33% (1/3) for postmenopausal women. Complete response was observed in one patient and partial response in three patients. The therapy was effective for lymph nodes (2/2), lung (3/4), breast (2/3), skin or subcutis (1/2), but it showed no effect on bone, pleural effusion or ascites. The overall 5-year survival rate was 53.3%. The main side effects of more than Grade 1 were leucopenia 33% (3/9), anorexia 22% (2/9) and malaise 22% (2/9). They were relatively mild for therapy involving ADR. This therapy was considered useful for advanced or recurrent breast cancer.

Antineoplastic Combined Chemotherapy Protocols

The relationship of estrogen receptor status to DNA ploidy in breast cancer.

The relationship of estrogen receptor (ER) status to DNA ploidy was investigated in 121 patients with breast cancer who underwent surgery. Lymph node status was evaluated histologically and ER levels were determined by the dextran-coated charcoal method, with a level of 3 fmol/mg.protein being considered positive. Flow cytometric DNA content was analyzed using paraffin-embedded tissue blocks. Sixty-three percent of the specimens were ER+, while 37 percent were negative. Sixty-one patients (50.4 percent) were diploid and 60 aneuploid. A statistically significant correlation between the ER positivity rate and diploid DNA was found. Higher ER levels were seen in the postmenopausal patients with diploid tumors than in those with aneuploid tumors and there was a significant tendency for ER levels to be higher in the diploid tumors. Nodal status was not correlated with ER positivity or ploidy pattern. The present results indicate that ER levels are correlated with DNA ploidy, and reflect the degree of functional differentiation.

Biomarkers, Tumor

Evaluation of an improved dot-immunobinding assay for carcinoembryonic antigen determination in nipple discharge in early breast cancer: results of a multicenter study.

We have previously reported carcinoembryonic antigen (CEA) measurement in nipple discharge to be a useful adjunct in the diagnosis of non-palpable breast cancer. We have now developed a "microdot-immunobinding assay" using a specially constructed device to screen efficiently large numbers of patients with nipple discharge for non-palpable breast cancer. The method is as follows: a sample of nipple discharge is placed on a solid phase monoclonal anti-CEA antibody and, if CEA is present in the discharge, it will be detected by a second monoclonal anti-CEA antibody conjugated with alkaline phosphatase. The use of bromochloroindolyl phosphate as a chromogen results in a stable color reaction that can be semiquantitatively analyzed with the naked eye. CEA levels determined by this microdot assay correlated well with those determined using the earlier Elmotec assay. To determine the accuracy of the method, a collaborative study involving 11 institutes in Japan was organized. The CEA levels in nipple discharges from 77 patients undergoing surgery, 44 of whom were diagnosed as having breast cancer, were assayed. The results were that 17 of the 23 patients with palpable breast cancer, and 16 of the 21 patients with non-palpable breast cancer exhibited CEA values > 400 ng/ml, a cut-off value determined in a previous study. The overall accuracy (78%) of this test for diagnosing non-palpable breast cancer was higher than that obtained from ductography or cytology. The system may thus be of use in the screening of early breast cancer.

Breast Neoplasms

[Study of bone metabolism for breast cancer by MD (microdensitometry) method].

Bone is one of the involved organs of distant metastasis in breast cancer. We examined bone metabolism by microdensitometry (MD) method in 94 patients with breast cancer (40 with bone metastasis and 54 without it) and 10 with benign breast diseases. There was no significant difference among the three groups in the background factors of menopausal status and hormone receptors status. MCI, GSmin, sigma GS/D and bone pattern by MD method in breast cancer patients with bone metastasis were significantly lower than those in the other groups. There were slight reverse correlation between sigma GS/D and serum ALP. MCI and sigma GS/D indices corrected by ages were also significantly lower in bone metastasis (p less than 0.01). These indices in most of the patients with bone metastasis gradually decreased as the lesion progressed. The results revealed that microdensitometric analysis of bone metastasis for breast cancer was of use for the diagnosis and evaluation of therapeutic effect in the follow-up study.

Adult

[Study on carbohydrate antigen NCC-ST-439 in breast cancer].

We evaluated the clinical significance of serum NCC-ST-439 (ST439) in sera from 20 healthy women, 8 patients with benign breast disease and 105 patients with breast cancer (79 primary, 26 recurrent) by using enzyme immuno-assay (EIA). No false positive case was noted in the measuring of ST439 for healthy women and patients with benign breast disease. The positive rates of ST439 were 23% (18/79) in primary breast cancers and 50% (13/26) in recurrent breast cancers. The serum levels of ST439 in stage I breast cancer was significantly higher (p less than 0.05) than those in healthy women, but there was no significant difference among each stage. The serum levels of ST439 were not significantly different among the subsets such as T, n, m and histological types. The high levels of serum ST439 were observed in two cases with mucinous carcinoma. Although there were no relation between ST439 and receptor status, the higher serum levels of ST439 were observed in postmenopausal patients than premenopausal ones. The positive frequency of serum ST439 in stage I and II breast cancers was higher than that of CEA, TPA or CA15-3, while the positive rate in recurrent breast cancer was the lowest among 4 tumor markers. These results suggest that ST439 is a useful tumor marker for not only detecting the recurrence of breast cancer but also diagnosing primary breast cancer in early stage.

Adult

Determination of clinical accuracy and nocturnal blood pressure pattern by new portable device for monitoring indirect ambulatory blood pressure.

The accuracy and clinical application of a new portable device for measuring ambulatory blood pressure (BP) (ABPM 630, Nippon Colin, Nagoya, Japan) were assessed. The device uses a conventional arm cuff inflated by CO2 gas from a compact cartridge and is based on a cuff-oscillometric as well as a Korotkoff sound (microphone) technique. Blood pressure values obtained by ABPM 630 were compared with those measured by the auscultatory method. With the microphone method the mean differences from the auscultatory method were -0.28 +/- 6.15 mm Hg (mean +/- SD) for SBP and 0.96 +/- 6.28 mm Hg for DBP (n = 256), while for the cuff-oscillometric method the mean differences were -1.77 +/- 6.07 mm Hg for SBP and 3.06 +/- 6.87 mm Hg for DBP (n = 297). There was a highly significant correlation between BP values measured by the auscultatory method and ABPM 630. In 40 untreated subjects, 24 h BP was monitored simultaneously with the ABPM 630 and with a finger volume-oscillometric device (UBP-100, UEDA, Tokyo, Japan). The daytime average of SBP with the former (126 +/- 11.6 mm Hg) was almost the same as that with the latter (123 +/- 16.0 mm Hg), while the nighttime average in the former (117 +/- 9.7 mm Hg) was significantly higher than that in the latter (108 +/- 14.1 mm Hg, P less than .01). Only 4 out of 40 subjects experienced no sleep disturbance from the arm-cuff inflation. Five of the 40 subjects complained that their sleep was frequently interrupted by the arm-cuff inflation.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care

Influence of age on the nocturnal fall of blood pressure and its modulation by long-acting calcium antagonists.

The clinical significance of the nocturnal fall of blood pressure (BP) was examined. BP was monitored every 5 min for 24 hrs by means of a finger volume oscillometric device. The nocturnal fall was observed in all age groups (young: less than 40, n = 49; adult: 40 less than or equal to less than 60, n = 110; old: 60 less than or equal to, n = 33). The amplitude of nocturnal fall of BP (averaged daytime blood pressure--averaged nighttime blood pressure) in old patients (systolic = 13 +/- 11, diastolic = 10 +/- 8 mmHg, mean +/- SD) was similar to that in the young patients (systolic = 11 +/- 8, diastolic = 10 +/- 8 mmHg). These 192 subjects were also classified according to mean BP level (MBP) averaged for daytime in the ambulatory blood pressure monitoring records [MBP less than 85 (mmHg), n = 31; 85 less than or equal to MBP less than 100, n = 72; 100 less than or equal to MBP less than 115, n = 49; 115 less than or equal to MBP, n = 25]. BP level did not affect the pattern of circadian variation in the normal subjects or in the essential hypertensive patients at WHO stage I or II. The amplitude of the nocturnal fall in systolic BP increased with the increase in BP level, but this was not the case with diastolic BP (mean daytime BP less than 85 mmHg: systolic = 11 +/- 8, diastolic = 8 +/- 6 mmHg; 85 less than or equal to less than 100: systolic = 14 +/- 8, diastolic = 11 +/- 6 mmHg; 100 less than or equal to less than 115: systolic = 17 +/- 9, diastolic = 11 +/- 8; 115 less than or equal to: systolic 17 +/- 8, diastolic = 11 +/- 6 mmHg). Nitrendipine (8.6 +/- 5.6 mg, 22.5 +/- 11.4 days, n = 14) and nisoldipine (9.3 +/- 6.2 mg, 21.5 +/- 11.4 days, n = 15) administered once daily in the morning or nifedipine slow release tablet, 20 mg twice daily (n = 15, 17.7 +/- 5.2 days) induced a significant downward shift in the circadian BP pattern, in other words, the hypotensive effect was also observed during the night when the BP had already been low. Taken together, the information on the nocturnal behavior of BP would be valuable, especially in treating aged patients with essential hypertension with a long-acting antihypertensive drug.

Aging

[Efficacy of Cepharanthin for preventing leukopenia and thrombocytopenia induced by chemotherapy in breast cancer patient--prospective randomized study].

A prospective randomized study was carried out to evaluate the efficacy of Cepharanthin (CEP) on leukocytopenia and thrombocytopenia during chemotherapy in breast cancer patients. The CEP group (51 patients) was administered CEP by 60 mg/day p.o.. The control group (55 patients) was not administered CEP in all the times. The rate of leukocytopenia was significantly lower (p less than 0.05) in the CEP group than in the control. But the recovery periods from nadir to normal range in WBC were not significantly different between the two groups. The average of nadir of WBC in the leukocytopenia patients was higher in the CEP group than in the control, but it was not significant. In MMVC group and MMC + TAM group, the rate of leukocytopenia was significantly lower in the CEP group than in the controls. The obvious efficacy of CEP for thrombocytopenia was not obtained in this study. We conclude that CEP showed an efficacy on preventing leukocytopenia induced by chemotherapy in breast cancer patients.

Alkaloids

[Clinical evaluation of serum osteocalcin in patients with bone metastasis of breast cancer].

Bone metastasis is one of the characteristic behavior of recurrent breast cancer. Usually, X-ray detect and/or bone scintigraphy are used to evaluate bone metastasis. However, false positive cases are occasionally encountered in these modalities. This is a report of the results from the measurement of serum osteocalcin (OC) in breast cancer with bone metastasis. OC is one of the protein dependent on Vitamin K. The results were as follows: 1) Serum levels of OC in 56 patients with primary breast cancer were measured. The mean level of serum OC was significantly higher than that in patients with benign breast disease. But the comparisons in each stage were not statistically significant. 2) The mean serum OC level in patients of primary breast cancer with bone metastasis was higher than that in breast cancer without bone metastasis (p less than 0.05). This was remarkable in the patients of recurrent breast cancer (p less than 0.01). 3) Serum OC levels in bone metastasis patients were increased in group with normocalcemia, while it was normal or decreased in that with hypercalcemia. There was no significant correlation between either serum OC and ALP values, or between serum OC and serum Ca values. The slight positive and reverse correlation were observed between OC and ALP, OC and sCa, respectively. 4) In many cases with bone metastasis, serum OC levels were elevated before bone lesions were detected by bone scintigraphy. 5) In advanced stage of the patients with bone metastasis and hypercalcemia, serum OC level decreased. The increased level of serum OC was maintained when high dose of calcitonin was administered.

Biomarkers, Tumor

[A study of the number of binding sites of estrogen receptors as a malignancy factor in primary breast cancer].

Whether or not estrogen receptor (ER) is an indicator of malignancy in breast cancer remains to be clarified. Although there are a number of reports on the prognosis examined in relation to the presence or absence of ER, few studies have examined the number of ER binding sites. We investigated whether or not the number of ER binding sites could serve as an indicator of malignancy in ER positive patients. The subjects were 109 patients with primary breast cancer who underwent surgery between 1985 and 1987. The dextran-coated charcoal assay was used to determine ER. The number of ER binding sites over 5 fmol/mg cytosol protein (fmol/mg c.p.) was regarded as positive. The ER positive rate among all patients with breast cancer was 69.7%. Analysis of the relations of ER positive rate to each grade of the stage, n factor, menstruation, CA15-3 and nuclear DNA content revealed no correlation with any of these factors, except for the nuclear DNA content, suggesting that the presence or absence of ER alone does not indicate malignancy. There was a significant difference between the average number of ER binding sites of pre-climacteric patients and that of post-climacteric patients, 32.31 +/- 26.72 fmol/mg c.p. and 126.94 +/- 125.88 fmol/mg c.p., respectively. So it is considered that the analysis of the number of ER binding sites should be evaluated according to their menstrual states.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate

Modulation of cardiovascular depressant action of clonidine by pentobarbital anesthesia in rats.

The influence of pentobarbital anesthesia (5 mg/100 g, i.p.) on the cardiovascular depressor effect of clonidine administered intracerebroventricularly (i.c.v.) and intravenously (i.v.) was examined in rats. In conscious rats the hypotensive potency of i.v. clonidine [effective dose of clonidine which induced a decrease in blood pressure of 15 mmHg; ED15 = 7 (micrograms/kg)] is greater than that of i.c.v. clonidine (ED15 = 24.3), while in anesthetized rats that of i.c.v. clonidine (ED15 = 0.7 microgram/kg) was greater than that of i.v. clonidine (ED15 = 3.5 micrograms/kg). Pentobarbital anesthesia potentiated the hypotensive potency of i.c.v. clonidine in conscious rats by 50 times, while it potentiated that of i.v. clonidine only by 2 times. The bradycardic potency of i.v. and i.c.v. clonidine was also potentiated by pentobarbital anesthesia. These pieces of evidence suggest that in conscious rat, the hypotensive action of i.c.v. clonidine is opposed by a centrally mediated hypertensive effect of the drug and that pentobarbital anesthesia suppresses the clonidine sensitive pressor center and so potentiates the hypotensive effect of i.c.v. clonidine.

Anesthesia

Similarity in amplitude of the nocturnal fall in blood pressure in old and young patients with essential hypertension.

The influence of age on the nocturnal fall in blood pressure (BP) was examined in essential hypertensive patients as well as normal subjects. BP was monitored every 5 min for 24 hr by means of a finger volume oscillometric device. Average daytime BP was similar in the 3 age groups [young: less than 40 (years), n = 49, average daytime systolic BP (ASBP) = 132 +/- 20 mmHg, average daytime diastolic BP (ADBP) = 82 +/- 17 mmHg; adult: 40 less than or equal to less than 60, n = 110, ASBP = 127 +/- 19 mmHg, ADBP = 86 +/- 13 mmHg; old: 60 less than or equal to, n = 33, ASBP = 131 +/- 17 mmHg. ADBP = 83 +/- 11, mean +/- S.D.]. The nocturnal fall in BP was observed in all age groups and its amplitude (delta BP = average daytime BP - average nighttime BP) in the old patients (delta SBP = 13 +/- 11 mmHg, delta DBP = 10 + 8 mmHg) was similar to that in the young patients (delta SBP = 11 +/- 8 mmHg, delta DBP = 10 +/- 8 mmHg). The results suggests that information on the nocturnal behavior of BP is valuable in treating aged essential hypertensives to prevent cerebral and/or myocardial ischemia during sleep.

Adolescent

[Flow cytometric DNA measurements of thyroid carcinomas].

Flow cytometric DNA analysis has been performed using paraffin-embedded tissue blocks from 121 patients with thyroid carcinoma. The incidence of aneuploidy found in thyroid carcinoma was 9 (7.4%), while 112 (92.6%) were diploid. Aneuploid specimens consisted of 6 papillary, 1 follicular, 1 medullary and 1 undifferentiated carcinoma. Of 4 undifferentiated carcinoma patients who subsequently died, only 1 was aneuploid. The 5- and 7-year survival rate for diploid and aneuploid patients were 94% vs 37%, and 91% vs 37%, with significant differences (p less than 0.01). DNA measurements have been found useful in predicting the survival of aneuploid patients, though there remains some discrepancy between the DNA content and the clinical findings in cases of thyroid carcinoma.

Adenocarcinoma

[DNA analysis by flow cytometry in breast carcinoma].

Using deparaffinized tumor specimens, a flow cytometric DNA analysis was performed in 63 primary breast cancers from patients who were treated from 1976 through 1982. Fourty-three percent of the cases were found to be aneuploid, and 57% were diploid. No trend to increased aneuploid proportion with a more advanced disease was noted. There was no correlation between the level of ploidy and the clinicopathological factors. Aneuploid tumors seem to have a poorer survival, but no significant difference was found between the two patterns of ploidy. Patients with a low S-phase fraction (SPF) had a significantly longer survival than those with a high SPF. A DNA analysis of the tumor cells in breast cancer is felt to be use for a prognostic evaluation.

Aneuploidy

Exogenous glucocorticoid eliminates or reverses circadian blood pressure variations.

The effect of glucocorticoid on circadian variations of blood pressure was examined. In untreated patients with essential hypertension, a clear nocturnal fall in blood pressure and heart rate was observed and this was unaffected by combined treatment with antihypertensive drugs. The circadian blood pressure variation in patients with chronic glomerulonephritis (CGN) not receiving glucocorticoid treatment was essentially the same as that in patients with essential hypertension. In both groups there was a positive correlation between blood pressure and heart rate. On the other hand, in patients with CGN and systemic lupus erythematosus (SLE) who were treated with glucocorticoid, there was no nocturnal fall in blood pressure, and often a significant rise. In these patients the blood pressure was lowest in the afternoon and began to rise from then, and during the night, attaining a peak level in the morning. Despite this changed pattern of blood pressure variations, the heart rate in these patients was clearly reduced at night. In 10 patients with CGN and SLE, circadian rhythm of blood pressure and heart rate was examined before and during treatment with prednisolone (40.2 +/- 17.0 mg/day for 58.0 +/- 19.4 days, mean +/- s.d.). Prednisolone abolished the nocturnal fall of blood pressure, while the nocturnal fall of heart rate remained. There was no correlation between blood pressure and heart rate in patients with glucocorticoid treatment. These results suggest that the circadian blood pressure variation is influenced by the hypothalamo-pituitary-adrenal axis, probably through its action on the autonomic nervous system.

Adult

Apocrine carcinoma of the breast--a case report.

A case of apocrine carcinoma of the breast is reported herein. Apocrine carcinoma is a rare tumor characteristically composed of large cells with eosinophilic cytoplasm. This case involves a 34-year old woman who underwent a modified radical mastectomy and is now doing well with no evidence of recurrence, 10 months after her surgery.

Adult

Altered circadian blood pressure rhythm in patients with Cushing's syndrome.

The circadian blood pressure rhythm was compared in patients with Cushing's syndrome, essential hypertension, and primary aldosteronism. In patients with essential hypertension or primary aldosteronism, a clear nocturnal fall in systolic and diastolic blood pressure and heart rate was observed. This fall was seen in untreated subjects as well as in patients receiving combined treatment with a calcium antagonist, diuretic, converting enzyme inhibitor, alpha-blocker and beta-blocker, or sympatholytic drug. In these groups, there was a positive correlation between heart rate and systolic or diastolic blood pressure. On the other hand, in patients with Cushing's syndrome, there was no nocturnal fall in blood pressure but in some patients a rise was observed. In all patients there was a nocturnal fall in heart rate. Thus, there was no significant correlation between heart rate and blood pressure in these patients. Exogenous glucocorticoid eliminated the normal nocturnal fall of blood pressure in patients with chronic glomerulonephritis or systemic lupus erythematosus. These results suggest that the changed circadian blood pressure pattern in patients with Cushing's syndrome is not due to antihypertensive treatment or to the mineralocorticoid excess accompanying this disease, but it is attributable to excess glucocorticoid or the associated disturbance in the adrenocorticotropic hormone-glucocorticoid system (or both). This conclusion also implies that the normal circadian rhythm of blood pressure may be regulated at least in part by the adrenocorticotropic hormone-glucocorticoid system.

Adolescent

The hypotensive mechanism of percutaneous transluminal dilatation (PTD) in renovascular hypertension due to bilateral renal artery stenosis.

The hypotensive mechanism of percutaneous transluminal dilatation (PTD) in renovascular hypertension due to bilateral renal artery was investigated in two patients. Blood pressure was monitored continuously before, during and after PTD by use of a new automated blood pressure monitoring device based on finger volume-oscillometry. Plasma renin activity was measured repeatedly before, during and after PTD. A hypotensive effect appeared immediately after PTD and blood pressure remained low in the following observation period without any hypotensive medication. In these cases, the hypotension was accompanied by a transient decrease in heart rate immediately after PTD. The hypotensive response to PTD was not parallel to the basal plasma renin activity, suggesting that the renin-angiotensin system is not necessarily involved in the maintenance of the hypertension before PTD. The autonomic nervous system seemed to play a certain role. Since the hypotension was accompanied by a transient decrease in heart rate immediately after PTD, the hypotension may be induced either by a decrease in sympathetic tone or by an increase in vagal tone at least just after PTD. It is hypothesized that these changes in autonomic nervous activity are mediated centrally through the renal afferent mechanism in response to rapid changes in renal hemodynamics induced by PTD.

Adult