A case of aldosterone-producing adrenocortical adenoma associated with a probable post-operative adrenal crisis: histopathological analyses of the adrenal gland.

We describe a case of aldosterone-producing adrenocortical adenoma (APA) associated with a probable post-operative adrenal crisis possibly due to subtle autonomous cortisol secretion. The patient was a 46-year-old female who suffered from severe hypertension and hypokalemia. CT and MRI scans revealed a 2-cm diameter adrenal mass. The patient's plasma aldosterone level was increased, and her plasma renin activity was suppressed, both of which findings were consistent with APA. Cushingoid appearance was not observed. Morning and midnight serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were all within the normal range. Her serum cortisol level was suppressed to 1.9 microg/dl as measured by an overnight 1-mg dexamethasone suppression test, but was incompletely suppressed (2.7 microg/dl) by an overnight 8-mg dexamethasone suppression test. In addition, adrenocortical scintigraphy showed a strong uptake at the tumor region and a complete suppression of the contra-lateral adrenal uptake. After unilateral adrenalectomy, she had an episode of adrenal crisis, and a transient glucocorticoid replacement improved the symptoms. Histopathological studies demonstrated that the tumor was basically compatible with APA. The clear cells in the tumor were admixed with small numbers of compact cells that expressed 17alpha-hydroxylase, suggesting that the tumor was able to produce and secrete cortisol. In addition, the adjacent non-neoplastic adrenal cortex showed cortical atrophy, and dehydroepiandrosterone sulfotransferase immunoreactivity in the zonae fasciculata and reticularis was markedly diminished, suggesting that the hypothalamo-pituitary-adrenal (HPA) axis of the patient was suppressed due to neoplastic production and secretion of cortisol. Together, these findings suggested that autonomous secretion of cortisol from the tumor suppressed the HPA axis of the patient, thereby triggering the probable post-operative adrenal crisis. Post-operative adrenocortical insufficiency should be considered in clinical management of patients with relatively large APA, even when physical signs of autonomous cortisol overproduction are not apparent.     

A clinical evaluation of MK-0787/MK-0791 for long-term administration in urological infections

MK-0787 (Imipenem)/MK-0791 (Cilastatin sodium), a new compound of Thienamycin, was administered in treatment of 35 patients (36 cases) with chronic complicated UTI or for prevention of serious infections with much complicated factors. The patients were principally treated at a daily dose of 1 g for over 10 days. The efficacy rate of 26 patients who were evaluable in the early phase (4-7 days) was 88.5%, while it became up to 92.3% in the final phase judgment. As for clinical usefulness, the result was obtained to be as high as that of the clinical efficacy. In bacteriological study, 35 strains were clinically isolated including 7 strains of P. aeruginosa from UTI. All the strains disappeared with an eradication rate of 100% after treatment. Strains appearing after Imipenem/Cilastatin sodium treatment mainly consisted of fungi. Usefulness judgements tended to be greater in the final phase than in the early phase. As for side effects, vomiting was recorded in one case, in which the administration was discontinued. In laboratory findings there were 3 cases with elevated GPT, 2 cases with elevated GOT, one case with elevated gamma-GTP, one with thrombocytopenia, and one with eosinophilia each, but these abnormal values were slight and transient. In summary our clinical study showed that Imipenem/Cilastatin sodium was a very effective antibiotic in treatment on moderate or serious UTI or preventive use for infections in compromised hosts. Considering the features of this agent, it might be more effective and useful for clinical use in treatment on polymicrobial infections including stubborn organisms than any other antimicrobial compounds. Furthermore, it was safe and well tolerable in a long term treatment.     

Changes in central dopaminergic systems with the expression of Shh or GDNF in mice perinatally exposed to bisphenol-A.

In the previous study, we reported that exposure to bisphenol-A induced the potentiation of dopamine receptor functions in the mouse limbic area, resulting in supersensitivity to methamphetamine-induced pharmacological actions. The present study was undertaken to investigate whether prenatal exposure to bisphenol-A could produce morphological change in dopaminergic neuron and the pattern of expression of genes regulating the dopaminergic neuron development. Here we found that prenatal and neonatal exposures to bisphenol-A increased the tyrosine hydroxylase- and dopamine transporter-like immunoreactivities in the adult mouse limbic area. The present molecular biological study shows that chronic bisphenol-A treatment produced a significant decrease in the dopaminergic neuron development factors, sonic hedgehog and glial cell line-derived neurotrophic factor, which were also decreased by prenatal exposure to bisphenol-A. These results suggest that chronic exposure to bisphenol-A could disrupt the dopaminergic neurotransmission in the process of dopaminergic neuron development.     

Invasion of the intracranial space by a malignant odontogenic mixed tumor: Report of a case

A case of an odontogenic tumor which invaded the intracranial space from the mandible is reported. Judging from the radiographic images it was similar to a malignant tumor. The patient died 17 years after the first visit. According to the final pathological diagnosis, it was malignant odontogenic mixed tumor of low grade which did not belong to any of the WHO classification.     

Portsite and intraabdominal metastases of unsuspected gallbladder carcinoma after laparoscopic cholecystectomy: Report of a case

We herein report a rare case of portsite metastasis of gallbladder carcinoma which occurred after laparoscopic cholecystectomy. A 64-year-old man underwent laparoscopic cholecystectomy at another hospital for symptomatic cholecystolithiasis. The histological examination revealed an adenocarcinoma of the gallbladder infiltrating the entire wall. Despite the physician's advice the patient refused any additional treatment. Thirteen months after surgery he visited our hospital because of a palpable mass at the scar of the right trocar incision. The nodule was removed and histological examination confirmed metastasis from the gallbladder carcinoma.     

Intraocular penetration kinetics of prednisolone after subconjunctival injection in rabbits

Prednisolone concentrations in cornea, aqueous humor, and vitreous humor and the residual amount in conjunctival tissue were assayed by high-performance liquid chromatography during a 14-hour period after subconjunctival injection of prednisolone sodium succinate in rabbits. Prednisolone was concentrated in the corneal epithelium and reached a peak within 5 min, whereas the peak level of prednisolone in stroma-endothelium was achieved 1 h after the injection. There was an apparent linear binding of prednisolone with the ocular tissue homogenates and fluids except for the vitreous humor. However, the protein binding of prednisolone with vitreous humor showed marked concentration dependency. A pharmacokinetic model involving a rapid conversion to prednisolone from its ester prodrug, first-order transfer to various tissues, and first-order elimination of unbound prednisolone from vitreous humor succeeded in predicting the observed concentration-time profiles of prednisolone in various ocular tissues and fluids after subconjunctival injection at three different doses: 0.1, 1.0, and 10.0 mg/kg. The present model predicted that absorption into precorneal area and epithelium and direct penetration into aqueous humor and vitreous humor are 1.7, 0.1, and 0.2% of the applied dose, respectively, and that almost the entire dose (98%) is absorbed into the systemic circulation, with a half-life of 38 min.     

Substance P- and calcitonin gene-related peptide-immunofluorescent nerves in the repair of experimental bone defects

Summary Healing of an experimental bony defect in the rat's tibia was studied with an immunofluorescent technique to clarify when and where substance P (SP) and calcitonin gene-related peptide (CGRP) would develop. The normal tibia showed a few SP- and CGRP-immunofluorescent nerve fibres. In the experimental tibia, the number of these fibres increased on the 6th day after operation, reached a peak of proliferation on the 15th day and reverted to normal after the 24th day. The changes were associated with the development and decay of callus tissue suggesting that harmful stimuli from the injured site in a bone could be mediated by sensory nerves throughout the repair period. Most of the SP- and CGRP-immunofluorescence was seen near the vessels, frequently in the same nerve fibres. The SP- and CGRP-immunofluorescent nerves seemed to take part jointly in callus formation through the enhancement of local blood flow.

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Résumé Le procesus de guérison d'une perte de substance osseuse expérimentale a été étudié sur le tibia du rat par immunofluorescence afin de déterminer quand et où la substance P (SP) et la calcitonine peptide d'origine génique (CGRP) se développeraient. Le tibia normal ne montre qu'un petit nombre de fibres nerveuses immunofluorescentes SP et CGRP. Dans le tibia d'expérimentation, les fibres nerveuses immunofluorescentes SP et CGRP augmentent en nombre à partir du 6ème jour, atteignent leur maximum de prolifération le 15ème jour et reviennent à l'état normal après le 24ème jour post-opératoire. Ces modifications sont étroitement associées au développement et à la disparition du cal, suggérant ainsi que les stimuli nocifs provenant de la lésion osseuse pourraient être inactivés par les nerfs sensitifs durant la période de réparation. En outre, la plus grande partie de l'immunofluorescence SP et CGRP a été observée à proximité des vaisseaux, souvent dans les mêmes fibres nerveuses. Il semble que les nerfs immunofluorescents SP et CGRP participent conjointement à la formation du cal en augmentant la vascularisation locale.