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Tetsuro Ishikawa

Publications and source records attributed to Tetsuro Ishikawa.

At least 19 recordsLinked to original sources
PubMed2006

Laparoscopic adrenalectomy on a patient with primary aldosteronism during pregnancy.

A pregnant 26-year-old woman was referred for evaluation and management of progressive hypertension and hypokalemia at 14 weeks of gestation. Her plasma aldosterone level was markedly elevated and magnetic resonance imaging showed a right adrenal tumor. Primary aldosteronism due to an aldosterone producing-adenoma was diagnosed. Because of progressive severe hypertension, a laparoscopic adrenalectomy was performed at 17 weeks of gestation. The procedure was completed without complication, and plasma aldosterone and potassium levels rapidly improved post-operatively. However, her hypertension persisted and the growth retardation of the fetus was found. Regrettably, intrauterine fetal death was confirmed at 26 weeks of gestation. Histological examination of the placenta revealed that the placental artery had very thick walls which had apparently caused a critical failure in fetal blood flow. The optimal timing of laparoscopic surgery during pregnancy and perioperative management were subsequently discussed.

Adenoma↗
PubMed2006

TIE2 gain-of-function mutation in a patient with pancreatic lymphangioma associated with blue rubber-bleb nevus syndrome: report of a case.

Abdominal lymphangioma is a rare tumor in adults. The most common location is the mesentery, but this tumor occasionally develops in the pancreas. We report a case of pancreatic lymphangioma associated with blue rubber-bleb nevus syndrome (BRBNS) in a Japanese woman. The pancreatic lymphangioma spread extensively throughout the retroperitoneum without causing any symptoms for more than 4 years after its histological diagnosis by laparoscopic biopsy. Multiple hemangiomas were also seen in the mucous membranes and on the skin. The hemangiomatosis was segregated in the dominant fashion in her family, and a germ-line gain-of-function mutation (Arg849Trp) in TIE2 gene was confirmed. To our knowledge, this is the first report of pancreatic lymphangioma occurring in association with BRBNS in a patient with genetic alteration. We describe the clinical features of this case and discuss a possible correlation between these two uncommon conditions.

Female↗
PubMed2006

Simultaneous bilateral laparoscopic adrenalectomy for adrenocorticotropic hormone-independent macronodular adrenal hyerplasia: report of a case.

Cushing's syndrome caused by adrenocorticotropic hormone (ACTH)-independent macronodular adrenal hyperplasia (AIMAH) is an extremely rare disease, which shows bilateral macronodular adrenal hypertrophy and autonomous cortisol production. We herein report a case of AIMAH treated successfully by minimally invasive simultaneous bilateral laparoscopic adrenalectomy. A 73-year-old woman with hypertension, diabetes mellitus, and osteoporosis was referred to our hospital because of an incidentally found huge bilateral adrenal mass. An abdominal computed tomography scan showed large bilateral adrenal glands with multiple nodules. A diagnosis of AIMAH was made and a simultaneous bilateral laparoscopic adrenalectomy was thus performed. The total operation time was 310 min and blood loss was 70 g. Both glands were hypertrophic (right 5 x 3 cm, 48.5 g and left 4 x 2 cm, 39.2 g) and consisted of multiple golden yellow macronodules. The postoperative course was uneventful. A simultaneous bilateral adrenalectomy for AIMAH performed by an experienced surgical team is therefore considered to be a safe and minimally invasive procedure.

Adrenal Glands↗
PubMed2006

Direct in vitro evidence of the suppressive effect of cinacalcet HCl on parathyroid hormone secretion in human parathyroid cells with pathologically reduced calcium-sensing receptor levels.

Clinical studies have been performed to determine the effect of cinacalcet HCl (cinacalcet), an allosteric modulator of the calcium-sensing receptor (CaR), on primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism of uremia (SHPT). However, no in vitro studies on human parathyroid cells have been reported to date. In this study, the inhibitory effect of cinacalcet on PTH secretion was analyzed in primary cultured parathyroid cells obtained from patients. The investigation involved three PHPT and three SHPT patients subjected to therapeutic parathyroidectomy. Notably, all SHPT patients were resistant to intravenous vitamin D analogue therapy. Removed parathyroid tumors were used for immunohistochemistry and parathyroid cell primary culture. Immunohistochemical analyses revealed diminished expression of CaR and vitamin D receptor (VDR) in all parathyroid tumors. PTH secretion from cultured parathyroid cells of PHPT and SHPT patients was suppressed by extracellular Ca2+ and cinacalcet in a dose-dependent manner. Rates of suppression of PTH secretion in PHPT and SHPT by cinacalcet (1000 nmol/l) were 61% +/- 21% and 61% +/- 19%, respectively. Cinacalcet demonstrates significant potency in the suppression of PTH secretion in primary cultured human parathyroid cells in vitro, despite reduced levels of the target protein, CaR. Data from this in vitro analysis support the clinical application of cinacalcet in PHPT and SHPT therapy.

Cinacalcet↗
PubMed2006

Regulation of plasma fibroblast growth factor 23 by calcium in primary hyperparathyroidism.

OBJECTIVE: While the importance of fibroblast growth factor (FGF)-23 is established in phosphate-wasting disorders, little is known about the mechanisms regulating its circulating level. To investigate the role of parathyroid hormone (PTH) and calcium in FGF-23 metabolism, we examined plasma FGF-23 levels in patients with primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: Fifty patients with PHPT and 52 controls were employed in this study. Plasma was obtained from 18 PHPT patients who underwent parathyroidectomy (PTX) on the first postoperative morning without vitamin D administration. Time-course samples were also obtained from 5 of 18 PTX patients without vitamin D analogs or calcium administration. The expression of Fgf23 on resected parathyroid glands was analyzed by reverse transcription (RT)-PCR and immunohistochemistry. RESULTS: FGF-23 was significantly elevated in PHPT patients compared with controls. FGF-23 levels were significantly correlated positively with serum corrected calcium and intact PTH levels, and negatively with creatinine clearance and inorganic phosphate, among which creatinine clearance and corrected calcium were independently associated factors. In 18 PTX patients, postoperative FGF-23 levels were significantly decreased compared with preoperative levels. Corrected-calcium levels were significantly decreased 1 h after PTX, and this was followed by a reduction in plasma FGF-23 levels in time-course study. In addition, postoperative FGF-23 levels in 18 PTX patients were significantly correlated with corrected calcium, consistent with a role of serum calcium as one of the major regulators of FGF-23. The absence of Fgf23 expression in parathyroid glands indicated that the parathyroid glands were not major sources of circulating FGF-23. CONCLUSIONS: Serum calcium may regulate circulating FGF-23 levels in PHPT.

Calcium↗
PubMed2005

Plasma levels of adiponectin and soluble thrombomodulin in hypothyroid patients with normal thyroid function following levothyroxine replacement therapy.

Hypothyroidism is associated with increased morbidity from cardiovascular disease, and adiponectin (ApN) is a newly-identified adipocytokine, which is expressed in human adipose cells and may have a protective effect against the development of coronary artery disease. The aim of the study was to evaluate the involvement of ApN secretion in hypothyroid patients with normal thyroid function following levothyroxine (L-T(4)) replacement therapy, and to associate plasma ApN levels with intima-media thickness (IMT) in the common carotid artery (CCA), an indicator of early atherosclerosis, and cardiovascular parameters including soluble thrombomodulin (sTM), a plasma endothelial injury marker. The CCA IMT and plasma levels of ApN and sTM were measured in 52 hypothyroid patients and in age-, sex- and body mass index (BMI)-matched normal control subjects. Thirty-six of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T(4) replacement therapy. Although the basal CCA IMT was significantly higher in hypothyroid patients [0.633 +/- 0.018 mm (mean +/- S.E.)] than in control subjects (0.552 +/- 0.022 mm, P < 0.005), both groups had similar baseline ApN and sTM levels [10.23 +/- 0.76 vs. 10.10 +/- 0.93 microg/ml: NS; and 2.58 +/- 0.14 vs. 2.68 +/- 0.20 ng/ml: NS, respectively]. Simple regression analysis revealed that plasma ApN was significantly correlated in a positive manner with age (r = 0.339, P = 0.015), HDL-cholesterol (r = 0.295, P = 0.048), and sTM (r = 0.490, P = 0.0005), but not with CCA IMT (r = 0.059, P = 0.742). In multivariate analysis, the plasma ApN level was significantly associated with that of sTM (r = 0.546, P = 0.0001) and with serum high-density lipoprotein (HDL)-cholesterol levels (r = 0.291, P = 0.029) in hypothyroid patients. During 1 year of L-T(4) replacement therapy, hypothyroid patients showed a significant decrease in CCA IMT, to 0.553 +/- 0.016 mm (P < 0.0001), a level comparable to normal controls, but no significant change in ApN (from 10.79 +/- 1.07 to 10.6 9+/- 1.14 microg/ml, NS) or sTM (from 2.59 +/- 0.15 to 2.74 +/- 0.18 ng/ml, NS). Hence, we provide evidence that ApN and sTM might not contribute to enhanced atherosclerosis, as reflected by increased CCA IMT in hypothyroid patients. However, this is the first report to demonstrate a positive and significant association of sTM with ApN. These data support the hypothesis that sTM is one of the determinant of ApN and thus suggest the presence of an sTM-associated regulatory mechanism for ApN secretion in hypothyroid patients.

Adiponectin↗
PubMed2005

Direct in vitro evidence of extracellular Ca2+-induced amino-terminal truncation of human parathyroid hormone (1-84) by human parathyroid cells.

CONTEXT: Although serum calcium (Ca2+) concentration regulates the generation of amino-terminally (N-terminally) truncated forms of human PTH (hPTH) degraded from (1-84)hPTH, no studies have yet reported whether the parathyroid gland itself is responsible for this process. OBJECTIVE: Our objective was to determine the site of N-terminal truncation and its roles in PTH metabolism in parathyroid cells in vitro. METHODS: The effect of extracellular Ca2+ concentration was examined on N-terminal truncation in primary cultured parathyroid cells. The parathyroid glands were obtained from the patients with primary and uremia-associated secondary hyperparathyroidisms who underwent therapeutic parathyroidectomies. RESULTS: The N-terminally truncated fragments were detectable with commercially available intact PTH (I-PTH) assays, but not with the bio-intact PTH (Bio-PTH) assay, which detected only the (1-84)hPTH. HPLC revealed that generation of N-terminally truncated fragments detectable by I-PTH increased with extracellular Ca2+ concentration. Suppression of PTH secretion by increasing the extracellular Ca2+ concentration was more evident with the Bio-PTH assay than with the I-PTH assay for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, which is the ratio of (1-84)hPTH to the sum of (1-84)hPTH and N-terminally truncated fragments, decreased in response to increases in extracellular Ca2+. CONCLUSIONS: These findings suggest that the N-terminal truncation is regulated by extracellular Ca2+ concentration and works to suppress the generation of (1-84)hPTH in parathyroid cells.

Calcium↗
PubMed2005

Effect of organ-specific fibroblasts on proliferation and differentiation of breast cancer cells.

Breast carcinomas contain both tumor cells and stromal cells, including fibroblasts, endothelial cells, and lymphocytes. Proliferation of breast cancer cells may be controlled partly by mesenchymal cells, especially fibroblasts. We studied effects of fibroblasts on tumorigenicity and histologic features of breast cancer cells vivo, and analyzed fibroblast-produced growth-promoting factors in vitro. Breast carcinoma cells from four lines, and fibroblasts from lines obtained from skin and breast tissue of four patients with breast cancer were used. A suitable number of breast tumor cells and fibroblasts were inoculated subcutaneously into nude mice; resulting tumors were examined. Then conditioned medium from fibroblasts was added to cultures of breast cancer cells to study growth effects, and growth-promoting factors from breast fibroblasts were analyzed. Co-inoculation of breast cancer cells with breast fibroblasts into mice significantly increased tumorigenicity and tumor size beyond those obtained with breast cancer cells alone. Histologically, tumors resulting from co-inoculation with breast fibroblasts showed a scirrhous pattern with extensive fibrosis, while those formed by breast cancer cells injected alone or co-inoculation with skin fibroblasts showed a solid pattern. Medium from breast fibroblasts significantly increased breast cancer cell growth in vitro, while the various skin fibroblasts did not all show this effect. Structural and functional interactions between organ-specific fibroblasts and breast cancer cells may importantly regulate breast cancer growth and progression.

Animals↗
PubMed2005

The significance of thyroid blood flow at the inferior thyroid artery as a predictor for early Graves' disease relapse.

OBJECTIVE: We investigated the clinical usefulness of thyroid blood-flow measurement in predicting relapse of Graves' disease (GD) in comparison with known risk factors for GD relapse. MEASUREMENT: Thyroid blood flow was measured in pulsed Doppler mode at the inferior thyroid artery (ITA), and the peak systolic velocity (PSV) calculated. PATIENTS: ITA-PSV was measured in euthyroid GD patients (n = 79) immediately before withdrawal of anti-thyroid drug (ATD) and in healthy subjects (n = 17). RESULTS: In the 79 euthyroid GD patients, the values of free triiodothyronine (FT3), TSH receptor autoantibody (TRAb), ITA-PSV and thyroid volume were significantly higher in the relapse group (n = 40) than in the nonrelapse group (n = 39) and the Youden index of ITA-PSV was significantly higher than that of FT3, TSH, TRAb and vascular endothelial growth factor (VEGF). CONCLUSION: ITA-PSV may assist in the prediction of early GD relapse after ATD withdrawal.

Adolescent↗
PubMed2005

Increased levels of serum osteoprotegerin in hypothyroid patients and its normalization with restoration of normal thyroid function.

Hypothyroidism is associated with increased morbidity from cardiovascular disease, and an increase in serum osteoprotegerin (OPG) has recently been reported to be associated with the severity of coronary heart disease and cardiovascular mortality. The present study was designed to examine whether hypothyroidism causes an increase in serum OPG, and to determine whether levothyroxine (L-T4) replacement therapy might suppress serum OPG levels in hypothyroid patients. Fifty-three hypothyroid patients with chronic thyroiditis and age- and sex-matched normal control subjects were examined for the levels of serum OPG and plasma von Willebrand factor (vWF), a vascular injury marker. Thirty-seven of the hypothyroid patients were further monitored for changes in these markers during 1 year in a euthyroid state induced by L-T4 replacement therapy. Baseline OPG was significantly higher in hypothyroid patients than in normal controls (4.51 +/- 0.50 vs 3.72 +/- 0.23 pmol/l (mean +/- S.E.); P = 0.0182). In multivariate analysis, baseline OPG was significantly associated with baseline levels of TSH (r = 0.280, P = 0.0162) and vWF (r = 0.626, P < 0.0001). During one year of L-T4 replacement therapy, hypothyroid patients showed a significant decrease in OPG levels from 4.35 +/- 0.51 to 3.48 +/- 0.26 pmol/l (P = 0.0166), a level comparable to normal controls. The change in serum OPG levels during L-T4 replacement therapy was significantly and independently associated in a negative fashion with baseline vWF (r = -0.503, P = 0.0014). This study suggested that the severity of hypothyroidism and vascular injury might have important independent roles in increasing the serum OPG level in hypothyroid patients. Furthermore, it was demonstrated that a sustained euthyroid state might have the potential to decrease the serum OPG level in hypothyroid patients and that the degree of vascular injury in the hypothyroid state is independently associated with a decrease in serum OPG during a 1-year normalization of thyroid function.

Female↗
PubMed2005

[A case of anthracycline and taxane-resistant breast cancer with life-thereatening multiple liver metastases responding to oral combination chemotherapy by UFT, cyclophosphamide and medroxyprogesterone acetate].

A 53-year-old woman presented with an advanced right breast cancer together with skin manifestations and massive axillary lymph node metastases, as well as distant metastases in the lung and the liver. The patient received surgery after 6 courses of chemotherapy with epirubicine and intravenous cyclophosphamide (80/600 mg/m2). A weekly paclitaxel regimen (80 mg/m2) was started because the tumor markers increased soon after surgery. Despite chemotherapy, no response was confirmed, then weekly docetaxel (35 mg/m2) was started. Although the tumor markers decreased after administration of docetaxel, severe liver disfunction appeared and did not improve after cessation of docetaxel. Computed tomography (CT) revealed numerous metastatic nodules in the bilateral lobes of the liver. UFT (400 mg/day) and cyclophosphamide (100 mg/day) were administered for 4 weeks followed by 2 weeks cessation and then combined with continuous medroxyprogesterone acetate (800 mg/day). Liver function tests were normalized 3 months after, and the massive metastatic liver tumors disappeared completely. Lung metastasis also subsided. In spite of these good responses, tumor markers did not normalize and skin nodules appeared around the surgical site. Administration was stopped 36 weeks after initiation of the treatment.

Adenocarcinoma, Scirrhous↗
PubMed2005

[A case of gastric cancer with peritoneal recurrence which developed during adjuvant administration of TS-1 showing complete response by weekly docetaxel regimen].

A 62-year old man had undergone total gastrectomy for Borrmann type 4 gastric cancer. No peritoneal dissemination was observed at the laparotomy. Pathological examination revealed that the tumor involved the subserosal layer, and that the lymph node metastasis extended to the left gastric nodes. Vascular and lymphatic involvement was also observed. One hundred mg/body of TS-1, an oral 5-fluorouracil (5-FU) anticancer agent, which consisted of tegafur (a prodrug of 5-FU), and two modulators (gimeracil and oteracil potassium) was given from the 16th post-operative day. A course of TS-1 consisted of consecutive administration for 4 weeks followed by 2 weeks rest. The patient complained of abdominal fullness after administration of the second course of TS-1. Computed tomography (CT) revealed massive ascites. The serum carcinoembryonic antigen (CEA) titer was elevated to 13.5 ng/ml. From these findings, the occurrence of peritoneal dissemination was suspected. Weekly docetaxel of 30 mg/m2 (40 mg/body) was given for 3 weeks followed by a week cessation. At the start of the 6th course, the serum CEA was normalized, and CT scan detected the disappearance of ascites without any new lesion. Administration of docetaxel was continued until the 10th course then stopped without relapse of the disease. No dose reduction or postponement of administration were required. The patient has survived without disease one year after cessation of the treatment. Weekly docetaxel is a safe and effective regimen for gastric cancer worth using for a second-line therapy after failure of the 5-FU-based regimen.

Adenocarcinoma↗
PubMed2005

[Effect of calcium on N-terminal truncation of PTH in human parathyroid cells].

Serum PTH (7-84) is accumulated in patients with secondary hyperparathyroidism. It is also known that serum calcium (Ca) increases the generation of N-terminally truncated forms of parathyroid hormone (PTH). In this study, we examined whether accumulation of PTH (7-84) fraction is a parathyroid glandular origin or not by using primary cultured parathyroid cells from patients with primary and secondary hyperparathyroidism. The Bio-PTH/I-PTH ratio, indicating the ratio of PTH (1-84) to the sum of (1-84) PTH and N-terminally truncated fragment, was suppressed by increase in extracellular Ca2+ concentration for both cultured parathyroid cells prepared from parathyroid adenomas and uremia-associated secondary hyperparathyroidism. There is no difference between the ratios in primary and secondary hyperparathyroidism. These findings suggest that N-terminal truncation is regulated by extracellular Ca2+ concentration in parathyroid cells, but accumulation of PTH (7-84) fragments in patients with secondary hyperparathyroidism is mainly caused by uremia.

Calcium↗
PubMed2005

[Peri-operative management of the primary hyperparathyroidism].

Surgery for primary hyperparathyroidism has become one of the least invasive and safe procedures with the recent advances in the diagnosis and surgical technique. However, it is still difficult to prospect detailed post-operative conditions of the patient from the data of pre-operative examination. Because many factors related each other to make the preoperative conditions complicated. Thus, integrated interpretation of the patient is necessary before surgery, including general condition, coincidental disease, renal function, bone mineral density and its turnover, size and location of the lesion. Prevention and proper management of postoperative complications, such as hemorrhage, hypocalcemia, hoarseness and bone disease, is important for successful treatment of the disease.

Humans↗
PubMed2004

Decrease of arterial stiffness at common carotid artery in hypothyroid patients by normalization of thyroid function.

This study examined the effect of hypothyroidism on arterial stiffening and the effect of levothyroxine (l-T(4)) replacement. The arterial stiffness index beta (stiffness beta) and intima-media thickness (IMT), a parameter of arterial stiffening and thickening, respectively, were determined in common carotid artery (CCA) by ultrasonography in 30 hypothyroid patients before and after 1 year of normalization of thyroid function by l-T(4) replacement. Baseline CCA stiffness beta and IMT was significantly higher in the hypothyroid patients than in age- and sex-matched normal controls [9.46 +/- 0.93 vs. 8.02 +/- 0.91 (mean +/- SE); P < 0.05, 0.635 +/- 0.018 mm vs. 0.541 +/- 0.019 mm; P < 0.005, respectively]. In multivariate analysis, baseline stiffness beta was significantly associated with baseline levels of IMT (r = 0.457, P = 0.0311), FT(4) (r = -0.413, P = 0.0169), and a plasma vascular injury marker, von Willebrand factor (vWF) (r = 0.412, P = 0.0261). During 1 year of euthyroidism, 22 and 29 out of 30 patients showed significant decreases of stiffness beta and IMT to normal respective level, from 9.46 +/- 0.93 to 7.58 +/- 0.34 and from 0.635 +/- 0.018 to 0.552 +/- 0.015 mm, respectively. Change in stiffness beta during l-T(4) therapy correlated significantly in a negative manner with baseline levels of age (r = -0.465, P = 0.011) and IMT (r = -0.406, P = 0.029). Stiffness beta after but not before l-T(4) therapy showed a tendency towards a positive correlation with age. This study suggested that increases of arterial thickening, and plasma vWF, and a reduction in serum FT(4) might have an important role independently in the increased arterial stiffening in hypothyroid patients. Furthermore, it was demonstrated that sustained euthyroidism might have the potential to reverse arterial stiffening in addition to thickening in hypothyroid patients.

Carotid Artery, Common↗
PubMed2004

Immunohistochemical assessment for estrogen receptor and progesterone receptor status in breast cancer: analysis for a cut-off point as the predictor for endocrine therapy.

BACKGROUND: An immunohistochemical (IHC) method is commonly used for determining estrogen receptor (ER) and progesterone receptor (PR) status in breast cancer. However, the proper cut-off points of IHC have not been established. Cut-off points for ER and PR status as predictive factors for endocrine therapy are needed. METHODS: A total of 249 cases of female breast cancer were enrolled. ER and PR status by IHC were analyzed using the proportion of stained cells and staining intensity by Allred's score. RESULTS: Proportion score (PS) and intensity score (IS) were related to enzyme immunoassay (EIA) titers, for both in ER and PR (p < 0.0001, all). PS correlated with IS in both ER and PR (R = 0.47 and 0.41, respectively). ER status by IHC was related to tumor size and lymph node status, while PR was related to tumor size and menopausal status. In 152 patients who received endocrine therapy with a median follow-up term of 38 months, differences in disease-free survival were most significant using a cut-off point of PS 3 which indicated more than 10 % of cells stained positively for both ER and PR (p = 0.0007 and 0.0087, respectively). In addition, combination analysis of ER and PR using this cut-off point revealed a notable prognostic difference. CONCLUSION: A 10 % staining proportion may be an acceptable cut-off point for both ER and PR status by IHC, in terms of predicting response to endocrine therapy in breast cancer.

Adult↗
PubMed2004

Dieulafoy's vascular malformation of the jejunum: first case report of laparoscopic treatment.

A case of Dieulafoy's vascular malformation of the jejunum treated by laparoscopic surgery is described. The patient was a 31-year-old-woman who had complained of melena and had severe anemia needing blood transfusion. Angiography revealed microaneurysms and hypervascularity of the jejunum in the area between the first and second jejunal arterial fields. Laparoscopic partial resection of the jejunum was performed. The resected specimen was histologically diagnosed as Dieulafoy's vascular malformation. Since the operation, the patient has been free of melena and anemia. Small-intestinal Dieulafoy's vascular malformation is rare, as only 41 cases have been reported during the past three decades. Almost two-thirds of the patients were under 40 years old. Most of the patients complained of melena. The lesion was preoperatively identified in 14 of the 41 patients, while angiography was useful to define the lesion. Thirty-six of 37 patients for whom treatment methods were reported were surgically treated. While there are various treatment methods for intestinal bleeding, a surgical operation is often needed. When the disease location is obvious, treatment with laparoscopic surgery can reliably produce good results, in terms of its rate of cure, minimal invasiveness, and better cosmetic effect.

Adult↗