Clinical significance of associated nodular lesions of the adrenal in patients with aldosteronoma

Thirty-seven patients with primary aldosteronism were treated by unilateral total adrenalectomy during a 7-year period (1981–1987). The 37 patients were classified into 3 groups on the basis of adrenal pathology: unilateral solitary adenoma, 23 cases (group 1); unilateral adenomas, 3 cases (group 2); and adenoma with multiple macro- or microscopic nodules, 11 cases (group 3). The preoperative conditions of the patients (age, duration of hypertension, plasma renin activity, plasma aldosterone concentration, and serum potassium concentration), postoperative sequential changes of hormone levels, and outcome of hypertension were compared among the groups in order to determine whether the differences of adrenal pathology would affect the postoperative course. The preoperative parameters excluding age at surgery did not differ significantly among the 3 groups. The mean age in group 3, however, was slightly higher than in groups 1 and 2 (47.8 versus 42.8 versus 42.7 years). Postoperative hormonal changes were also similar, particularly in groups 1 and 3, staying within the normal range throughout the follow-up period (mean, 31 months; range, 3–86 months). However, postoperative improvement of hypertension showed marked differences, being significantl retarded in patients with multinodular lesions (group 3), about half of whom remained hypertensive even after 1 year. Nodular lesions other than adenoma(s) were, therefore, thought not to contribute to hormonal excess but to result from intractable hypertension.

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Resumen Treinta y siete pacientes con aldosteronismo primario fueron tratados mediante adrenalectomía total unilateral en un período de 7 años (1981–1987). Los 37 pacientes fueron clasificados en 3 grupos con base en la patología adrenal: adenoma solitario unilateral, 23 casos (grupo I); adenomas unilaterales, 3 casos (grupo 2); y adenoma con múltiples macro-o micronódulos, 11 casos (grupo 3). Las condiciones preoperatorias de los pacientes (edad, duración de la hipertensión, actividad de renina plasmática, concentración plasmática de aldosterona, y concentración sérica de potasio), los cambios postoperatorios secuenciales en los niveles hormonales, y el resultado de la hipertensión fueron comparados en los 3 grupos, con el objeto de determinar si las diferencias en la patología adrenal podrían afectar la evolución postoperatoria. Los parámetros preoperatorios, excluyendo la edad en el momento de la cirugía, no diferieron significativamente en los 3 grupos. La edad promedio en el grupo 3, sin embargo, fue ligeramente superior en los grupos 1 y 2 (47.8 versus 42.8 versus 42.7 años).Los cambios hormonales postoperatorios también fueron similares, particularmente en los grupos 1 y 3, manteniéndose dentro del rango normal a través del seguimiento (promedio, 31 meses; rango, 3–86). Sin embargo, la mejoría postoperatoria de la hipertensión exhibió diferencias marcadas, con aparación significativamente tardía en pacientes con lesiones nodulares (grupo 3); aproximadamente la mitad de éstos permanecieron hipertensos aún después de un año. Por consiguiente, se piensa que las lesiones nodulares diferentes del adenoma(s) no contribuyen al exceso hormonal sino que resultan de la hipertensión intratable.

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Résumé Trente-sept patients ayant un hyperaldostéronisme primaire ont eu une surrénalectomie totale unilatérale entre 1981 et 1987. Ces 37 patients ont été classés en 3 groupes selon la pathologie surrénalienne: adénome solitaire unilatéral, 23 cas (groupe 1); adénome unilatéral, 3 cas (groupe 2); et adénome avec nodules micro ou macroscopiques multiples, 11 cas (groupe 3). On a comparé les données préopératoires (âge, durée de l'hypertension, activité rénine plasmatique, concentration d'aldostérone plasmatique et kaliémie), les changements hormonaux postopératoires, et l'évolution de l'hypertension afin de déterminer si des différences de pathologie surrénalienne peuvent influencer l'évolution postopératoire. Les paramètres préopératoires (excepté l'âge) ne différaient pas de façon significative parmi les 3 groupes. L'âge moyen était plus élevé dans le groupe 3 que dans les groupes 1 et 2 (47.8 versus 42.8 versus 42.7 ans).Les variations hormonales postopératoires étaient également similaires, surtout dans les groupes 1 et 3, restant dans les limites de la normale pendant la période de suivi (moyenne, 31 mois; extrêmes, 3 à 86 mois). Cependant l'amélioration de l'hypertension postopératoire était différente, retardée de façon significative chez les patients ayant des lésions multinodulaires (groupe 3), la moitié d'entre eux restant hypertendus après un an. Les lésions nodulaires, étant donné que les adénomes ne donnent pas d'hypersécrétion hormonale, peuvent traduire plutôt une hypertension prolongée.

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Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.     

Stimulation of monocyte iodination and IL-1 production by tannins and related compounds.

Various tannins and related compounds were compared for their ability to stimulate the iodination (incorporation of radioactive iodine into an acid-insoluble fraction) of human peripheral blood monocytes. The stimulating activity of most of the monomeric and dimeric hydrolyzable tannins was generally higher than that of the trimeric and tetrameric compounds. Compounds that had dehydrohexahydroxydiphenoyl or chebuloyl groups had considerably less activity than those that had other functional groups (hexahydroxydiphenoyl, valoneoyl, dehydrodigalloyl, isodehydrodigalloyl, lactonized valoneoyl, hellinoyl, euphorbinoyl, dehydroeuphorbinoyl or woodfordinoyl group). The methylated derivative, nonacosa-O-methylcoriariin A, was essentially inactive, suggesting the requirement of a phenolic hydroxyl group. Three condensed tannins ((-)-epicatechin 3-O-gallate (ECG)-dimer, ECG-trimer and ECG-tetramer) significantly stimulated both monocyte iodination and their interleukin-1-like factor production. The results suggest the dependence of stimulation of monocyte iodination by tannins and related polyphenols on molecular weight.     

A combined treatment with 8 MHz radiofrequency hyperthermia, HPC-adriamycin, immunotherapy, radiation, systemic chemotherapy and irradiation for invasive bladder carcinoma

Hyperthermia was induced for the treatment of invasive bladder carcinoma in order to study its usefulness. The subjects were 12 cases of invasive bladder cancer; including 5 cases of T2, 3 cases of T3, 2 cases of T4, and 2 cases of recurrence after total cystectomy. As previous treatment, 4 patients received radiotherapy and the other received TUR, systemic chemotherapy, and intravesical injection of anticancer drugs. For hyperthermia treatment, a Thermotron RF-8 was used for heating a deep seated tumor. Each case received hyperthermia 2 to 10 times. Combined therapy included injection of HPC-adriamycin into the urinary bladder in 5 cases, immunotherapy in 3 cases, M-VAC therapy in one case, radiotherapy in one case, radiotherapy and intra-arterial injection in one case, and Peplomycin and OK-432 local injection in one case. The treatment results showed a 75% effectiveness; with CR in 4 cases, PR in 5 cases, MR in 2 cases and PD in one case. Three patients died and 9 survived. Of four patients who had received radiotherapy as a previous treatment 3 cases obtained CR and one case MR. Therefore, it was considered that a favorable treatment effect with hyperthermia could be obtained after radiotherapy.     

Studies on the retention of the mucous-membrane-adhesive anticancer agent hydroxypropylcellulose doxorubicin.

Incorporation of hydroxypropylcellulose (HPC-)doxorubicin, which we developed as a mucous-membrane-adhesive drug preparation, was instilled into the urinary bladder in 10 clinical cases. Tumor of the urinary bladder was a single tumor in all 10 cases, and preclinical histology showed transitional cell carcinoma, grade 1 or 2, and a lower stage than T1. HPC-doxorubicin, 20 mg/20 ml, was administered in 5 cases, and the other 5 cases received the conventional aqueous doxorubicin, 20 mg/20 ml by way of a catheter and the urethra. Cold punch biopsy was performed after 3 days of instillation, and the incorporation of doxorubicin into both tumorous and normal tissue was measured by high-pressure liquid chromatography. After 3 days, it was found that in the HPC-doxorubicin-administered group, doxorubicin was detected in both tumorous and normal tissue, but it was not detected in either tissue after aqueous doxorubicin administration. In 5 cases of the HPC-doxorubicin group, doxorubicin levels in the tumorous and normal tissue were examined, and it was found that significantly more doxorubicin was detected in the tumorous tissues. Thus, it may be said that our HPC-doxorubicin remained longer within the urinary bladder than the conventional aqueous doxorubicin preparation. Instilled HPC-doxorubicin is more highly concentrated in the tumorous tissue than in the normal bladder tissue, and thus, HPC-compounded anticancer drugs may be therapeutically more useful.     

Serotonin and tryptamine metabolism in the acute hepatic failure model: changes in tryptophan and its metabolites in the liver, brain and kidney

When heat-killed Propionibacterium acnes, a gram-positive anaerobe, is intravenously injected into mice followed by an intravenous injection of gram-negative lipopolysaccharide (LPS) 7 days later, most of the mice die of massive hepatic cell necrosis within 24 hours of LPS injection. Using this experimental model, acute hepatic failure was induced in mice, and the tryptophan metabolism in the liver, brain and kidney was studied. As a result, the tryptophan level was remarkably high in all three organs, and the metabolism of both the tryptamine pathway and serotonin pathway was induced. However, in the brain, the tryptamine metabolism was more induced compared to the serotonin, suggesting that the metabolites of tryptamine, may be involved in hepatic encephalopathy.     

Study on the mass-screening of after-meal serum triglyceride concentration]

The serum triglyceride concentration (TG) tested in health checks after meals cannot properly sort out hypertriglyceridemia with reference to the upper normal limit of fasting TG (150 mg/dl) set by the Japan Arteriosclerosis Society, because TG goes up considerably after a meal. In our survey of a large number of health check examinees (free of abnormal biochemical data other than TG and diseases under medical treatment), the mean (M) of fasting TG + 2 standard deviations (SD) was close to 150 mg/dl. When the screening level was set at M + 2SD for each time span after a meal, the ratio of the screened was distributed between 19.9 and 21.8%, which was close to 23.5%, the ratio of the screened on fasting. Accordingly, the nearest round number ending with zero for the first digit is suggested to be of practical use for the screening level of after-meal TG. The average TG in females was definitely lower than that of males, though proportionately increasing with age. The ratio of the screened among females aged between 20 and 49 was 5.3% on fasting and 3.2-5.8% for after-meal time spans, and that of the screened aged in their fifties was 11.3% and 8.2-12.9% respectively.