Hideo Koshida

Genetic analysis of the cytochrome P-450c17alpha (CYP17) and aldosterone synthase (CYP11B2) in Japanese patients with 17alpha-hydroxylase deficiency.

OBJECTIVE To determine the clinical and molecular genetic characterization of two Japanese patients with 17α‐hydroxylase deficiency, we analysed the 17α‐hydroxylase/17,20‐lyase gene (CYP17). Next, to clarify the mechanism of hypoaldosteronism in 17α‐hydroxylase deficiency, we analysed the expression of aldosterone synthase (CYP11B2) messenger RNA and sequenced CYP11B2 in these patients.

Systemic and regional effects of endothelin in rabbits : effects of endothelin antibody

1. The effects of porcine endothelin‐1 (10‐12‐5 × 10‐10mol/kg) on arterial blood pressure (BP) and the renal, mesenteric and carotid blood flow (BF), and the effects of endothelin‐1 antibody were studied in rabbits.

Participation of Vascular Prostacyclin for the Pathogenesis of Experimental Glucocorticoid Hypertension in Rats

Prostacyclin (PGI2) generation in the mesenteric arteries from dexamethasone acetate (DX) and deoxycorticosterone acetate (DOCA) treated rats was assessed by ex vivo perfusion method. PGI2 generation which was measured by 6-keto-PGF1 alpha output in the perfusate was significantly reduced in DX treated rats at prehypertensive stage both under the basal conditions and in response to angiotensin (ANG) II, whereas in DOCA group rats, vascular PGI2 production was not impaired. Plasma renin activity (PRA) was significantly suppressed in DOCA but normal in DX rats. These results suggest that the reduced PGI2 generation in the resistance arteries may contribute to the development of hypertension induced by DX.

Evaluation of clonidine suppression and various provocation tests in the diagnosis of pheochromocytoma

Recent investigations have shown that the widely used Clonidine suppression test is sometimes fallible for the diagnosis of pheochromocytoma. A comparative assessment was made of the following suppression and provocation tests, the Clonidine suppression test, and the glucagon, metoclopramide, and naloxone provocation tests. The assessment was performed in 6 patients with pheochromocytoma and in 19 patients without pheochromocytoma who were initially suspected of harboring a tumor. BP response did not predict the presence of pheochromocytoma in any test. Plasma norepinephrine (NE) concentrations determined at 120 and 180 min after oral 150 μg of Clonidine gave false negative results in 2 of the 5 patients with pheochromocytoma tested. Both plasma NE and epinephrine (E) concentrations were measured before and sequentially after each provocative agent. Neither NE nor E responded to 1 mg of glucagon iv in 2 of the 4 patients with pheochromocytoma tested. Determination of the peak level, peak increment, and % peak increment of NE and E following 10 mg of naloxone iv did not distinguish the two groups. The % peak increments of both NE and E in all 4 patients with pheochromocytoma given 5 mg of metoclopramide iv exceeded the mean + 3 SD values of the patients without pheochromocytoma (25 + 28% for NE, and 25 + 42% for E). These results suggested that, when performed with judicious patient selection (ambiguous plasma or urinary catecholamine levels), the measurement of plasma catecholamines in response to metoclopramide can be a useful adjunctive tool in the diagnosis of pheochromocytoma.

Role of Intestinal Bacteria in the Metabolism of Aldosterone in Man

Urinary aldosterone metabolites were measured before and after the administration of 1 g/day of kanamycin, a nonabsorbable antibiotic, for 7 days, in 6 normal volunteers and in 11 patients with liver cirrhosis. Urinary excretion of 21-deoxytetrahydroaldosterone (21-deoxy-THAldo) decreased by 40 and 86% from the control values in normal volunteers and in patients, respectively (p less than 0.05), after kanamycin administration. Urinary excretion of 21-deoxyaldosterone (21-deoxy-Aldo) also fell by 48 and 89% in normal subjects and in patients, respectively, but the decrease was significant only in the normal subjects (p less than 0.05). In normal volunteers, urinary free aldosterone and THAldo remained constant, whereas the ratio of 21-deoxy-Aldo to aldosterone and 21-deoxy-THAldo to THAldo decreased from 10.2 to 3.7 and 2.1 to 0.3, respectively (p less than 0.01). These results indicate that intestinal bacteria participate in the metabolism of aldosterone during enterohepatic circulation in man.

Impairment of Modulating Role of Testosterone in Growth Hormone Response to Clonidine in Essential Hypertension

To investigate the effects of endogenous testosterone (T) on the responsiveness of plasma growth hormone (GH) to central alpha 2 adrenergic stimulation, we administered clonidine (0.15 mg, p.o.) to 16 male patients with essential hypertension (EHT) and 13 age-matched male normotensive controls (NT). Although the basal T level was correlated with the peak GH increment (r = 0.709, p less than 0.01) and with the area under curve of GH (r = 0.714, p less than 0.01) in the NT group, no such correlations were seen in the EHT group. The present study confirmed the potentiating role of endogenous T in GH responsiveness to clonidine in male NT. The lack of correlation between T and GH response in EHT suggests a neuroendocrine disturbance in modulation by T of the GH response to central alpha 2 adrenergic stimulation.

Effectiveness of Prospective Insulin Sliding Scale for Outpatients with Diabetes Mellitus.

外来通院中のインスリン治療糖尿病患者を通常のインスリン治療を続けるコントロール群14名 (C群) と血糖値に応じてインスリン注射量を2から4単位増量する前向きインスリンスライディングスケール併用群14名 (S群) にわけ, 6か月間Hb Alcと低血糖回数を観察し前向きインスリンスライディングスケールの有用性を検討した。C群ではHb Alc値は有意な変化はなかったが, S群ではHb Alc値は前の8.37±1.14%より1か月後より低下し始め, 2か月後には7.95±1.26%と有意に低下し (p<0.04), 5か月後には7.50±1.42%と最低値を示した。低血糖の回数は, S群では, 1か月後, 2か月後に約2倍と有意に増加したが (それぞれP<0.05, P<0.01), 重篤な低血糖は認めなかった。以上より, 前向きインスリンスライディングスケールを使った治療法は外来インスリン治療糖尿病患者において有用と考えられた。

Risk Factors of Progression of Diabetic Retinopathy in Patients with Poorly Controlled Diabetes.

糖尿病コントロール目的に当科に入院し, 入院時HbAlcが9.5%以上で, その後1年間眼底を観察できた糖尿病患者92名を対象にして, 網膜症を悪化させる危険因子を検討した。前増殖網膜症では, 悪化率は50%と有意に高値であった。未治療期間, コレステロール値, 血圧, 蛋白尿は, 悪化群では不変群に比し有意に高値であった。神経伝動速度は, 悪化群では不変群に比し有意に低値であった。入院時HbA1c値が10.1%以上では, 10%以下に比べ有意に網膜症の悪化率は上昇していた。入院時と3か月後のHbAlc値差は, 悪化群では改善群に比し有意に高値で, 3%以上では急激に網膜症の悪化率は上昇していた。また, 3か月間の改善速度のみならず, 入院時HbA1c値が12.1%以上では, 入院後1年間の平均HbA1c値が7%以下に下がり過ぎないように注意が必要と思わ

A Case of Type 1 Diabetes Mellitus with Improvement of Insulin Reserve by Glibenclamide.

一時的ではあるがSU剤にてインスリン分泌能の著明な改善をみとめた1型糖尿病を経験し, 1型糖尿病の寛解機序解明の参考になると思われたので報告する。症例は, 62歳の女性で, 1996年11月口渇, 9kgの体重減少で急激に発症した。入院時検査では, FPG320mg/dl, HbA1c13.0%, 抗GAD抗体が118.9U/mlと陽性で, 尿CPRは28.6μg/日と低値であった。以上より1型糖尿病と診断されたが, 患者の希望にてグリベンクラミド10mg/日を投与した。入院45日目の尿CPRは70.0μg/日と著明に改善していた。退院後6か月間はグリベンクラミドにてHbA1cも6%とコントロール良好であったが, 次第にコントロール不良となり1998年3月2日に再入院となった。再入院時の抗GAD抗体は138.1U/mlと増加しており, 尿CPRは24.0μg/日と低下していた。ノボレット30Rインスリンの2回注射を開始後コントロールは改善したが, 発症2年後には尿CPRは11.7μg/日と更に低下しコントロールも不良となりインスリン頻回注射に変更した。インスリン治療ではなくSU剤治療にて一時的ではあるが内因性インスリン分泌が正常まで改善された。これは, 1型糖尿病でも発症初期において糖毒性がかなり重要な因子を占めていることを示唆していると思われる。

Effective Treatment of Reactive Hypoglycemic Coma with Acarbose : A Case Report

We report a case of reactive hypoglycemic coma in a 77-year-old man. Seven months after partial gastrectomy for early gastric cancer, he presented with syncopal attacks and seizure. His plasma glucose and insulin levels at coma were 18 mg/dl and 27μU/ml. Insulinoma was neglected with computerized tomography, magnetic resonance imaging and angiography. Because dietary control was insufficient, oral diazoxide therapy was done. But diazoxide did not protectthe overresponse of the insulin and reactive hypoglycemia in 75 g GTT. Octreotide (100 micrograms IM) inhibited insulin release and prevented hypoglycemia. Acarbose delayed the response of insulin butdid not inhibited insulin release. However, acarbose also prevented reactive hypoglycemia. We concluded that acarbose is an effective therapy for reactive hypoglycemic coma.