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Nonperfused retinal areas were evaluated in 60 eyes (42 cases) with diabetic retinopathy through repeated fluorescein angiography. Revascularization occurred in the nonperfused area in 40 eyes, due to recanalization in 3 and to intraretinal neovascularization (IRNV) in 39 eyes. Recanalization and IRNV developed in the same fundus in 2 eyes. IRNVs occurred during the nonproliferative state in 11 eyes, concomitant with retinal neovascularization in 14 and after manifestation of proliferative changes in 14. Typically, IRNVs originated from and drained into a retinal venule, showed hairpin-loop at their tips and manifested minimum tendency of dye leakage. No retinal hemorrhage occurred from the IRNVs. Their unexpectedly high incidence and their timely association with retinal neovascularizations point to the importance of IRNVs in the diagnosis of preproliferative diabetic retinopathy.

The case of a growth-hormone-producing pituitary adenoma which was in direct contact with a right internal carotid, medial-type aneurysm is reported. Direct clipping of the aneurysm and subcapsular removal of the adenoma were performed through a right frontotemporal craniotomy. The rarity of this direct contact and the cause of formation and enlargement of the aneurysm are discussed. The importance of angiography in cases of pituitary adenoma is stressed.

A rare case of HGH producing pituitary adenoma which was in direct contact with right IC medial type aneurysm was reported. A 60-year-old woman was admitted to our clinic in February, 1981, for the acromegalic features, who was treated by 5 mg/day of CB-154 since 1976 under the diagnosis of HGH secreting adenoma. The diagnosis of bitemporal hemianopsia was made in 1977, but it was disappeared at the time of admission to our clinic. A coronal section of computed tomography demonstrated a high contrasted tumor shadow in the sella turcica without definite suprasellar extension. A right carotid angiography showed the right IC-medial type aneurysm between the right posterior communicating artery and ophthalmic artery. In March, 2-81, direct neck clipping of the aneurysm and subcapsular removal of the adenoma were performed by the right frontal approach. From the operative findings it was concluded that the aneurysm was partially embedded in the adenoma tissue. Post operative course was uneventful except for the fact that the basal HGH level could not be normalized without CB-154 therapy. Many cases of association of cerebral aneurysm with pituitary adenoma were reported in the literature. However, direct contact between the tumor and the aneurysm could not be detected. This case seems the first report of the direct association of cerebral aneurysm with pituitary adenoma. Etiology for the unique combination of adenoma and aneurysm was discussed. It has been well known that the prolonged high level of serum growth hormone in acromegaly produces arteriosclerotic and degenerative changes in the arterial wall. It was speculated that the formation of the aneurysm in our case particular was due to the combination effects of the following events. That is, the direct mechanical pressure of pituitary adenoma to the right IC arterial wall, the arteriosclerotic or degenerative change of the arterial wall due to the prolonged exposure to the high level of HGH, and finally traction effect of the adenoma to the arterial wall because of the reduction of the size of the adenoma due to CB-154 therapy, all above mentioned influences were considered to contribute to the aneurysm formation. Finally, the preoperative bilateral carotid angiography is not unnecessary to the operative planning of the pituitary adenoma, especially when the adenoma was HGH producing one.

There have been many attempts to treat patients with malignant brain tumors represented by glioblastomas using nitrosourea (NU) derivatives such as BCNU and CCNU but the clinical results are not so remarkable compared with previous reports concerning experimental studies. The reason for an efficacy of NU derivatives in brain tumors is considered to be its higher lipid solubility which makes the drug crossing the BBB easily. On the other hand, there is some evidence that higher lipid solubility did not guarantee NU to reach always to all portions of solid tumor after systemic administration. We have performed a chemotherapy of malignant brain tumors using ACNU for five years. This drug is not only lipid but also water-soluble in some grade; therefore, the drug is administrated intravascularly and locally with ease. Nine cases of malignant gliomas were treated with local chemotherapy employing ACNU and two cases of glioblastomas are surviving now over five years and about four years, respectively. From the anatomical standpoint of view, it is considered to be necessary for local chemotherapy of brain tumors to possess some pathognomonic characters such as cyst formations, central necrosis and localized cortico-meningeal adhesions, which are rather frequently found in malignant gliomas and are suspected also easily by CT examination preoperatively. A local chemotherapy in the present study has been performed using 10 to 50 mg of ACNU through an indwelling catheter inserted during operation. No general toxicity occurred in all patients except one, who experienced purulent meningitis after long-term drainage. In our study on concentration of ACNU, intracarotid injection resulted in higher concentration in brain tumor tissue than intravenous injection, but these concentration considered to be not high enough to suppress the tumor cell growth. On the other hand, the intracavitary concentration of ACNU at 24 hr after drug administration was high enough to suppress the tumor cell growth.

In the first part of this paper, various chemotherapies were performed against oligodendrogliomas subcutaneously transplanted in to nude mice. Vincristine (VCR), adriamycin, and 1000 rads irradiation were effective against this tumors. Concerning these two drugs, dose response effect was observed. And the effect of 1 mg/kg injection of VCR roughly corresponded to that of five weekly injections of 0.2 mg/kg. In the second part of this experiment, single or combined effects of VCR and immunotherapeutic agents including OK-432 (OK), PSK, and recombinant leucocytic interferon (IFN) were examined. Two glioma lines including oligodendroglioma and glioblastoma were used. Following results were obtained from this experiment: 1) Effect of OK and VCR against oligodendrogliomas were as follows: control less than OK local injection (Local) less than OK intraperitoneal injection (IP); VCR; OK (IP X 2) less than VCR + OK(IP) less than VCR + OK (IP X 2). Effects of OK and VCR were expressed in order of their effects against glioblastomas: control less than VCR less than OK (IP); OK(IP X 2); OK(Local) less than VCR + OK (IP); VCR + OK (IP X 2). Effects of PSK and VCR against glioblastomas were as follows: control; PSK (Local) less than VCR less than VCR + PSK (Local) less than VCR + PSK (IP). Effects of IFN and VCR against oligodendrogliomas were as follows: control; IFN (IP) less than VCR less than IFN (Local) less than VCR + IFN (IP); VCR + IFN (Local). Effects of IFN and VCR against glioblastomas were as follows: control less than IFN (IP) less than VCR; IFN (Local); VCR + IFN (IP).(ABSTRACT TRUNCATED AT 250 WORDS)

The water-soluble nitrosourea compound ACNU is also lipid-soluble at normal physiological pH levels. It lacks toxic effects on vision that nitrosoureas occasionally produce following intra-arterial administration. In 28 cases of both primary and secondary malignant brain tumors, ACNU was administered at surgery or angiography by three different modes: intravenous injection in Group I (10 cases), intra-arterial injection via the carotid artery in Group II (11 cases), and intra-arterial injection via the carotid artery after opening the blood-brain barrier (BBB) by means of mannitol in Group III (seven cases). Tumor tissue and blood samples were taken serially at various time intervals after ACNU injection, and ACNU was measured by high-performance liquid chromatography. The time-concentration curve for ACNU was calculated in each case by the two- and one-compartment open models for determination of ACNU levels in blood and tissue, respectively. Pharmacokinetic parameters including biological half-life, blood and tissue levels (0-t minutes and 0-infinity minutes), total plasma clearance, and distribution volume of the beta phase were compared. Statistical analysis of tissue ACNU levels at 0-t minutes revealed higher concentrations in Group III patients than in Groups II and I: levels in Group II were significantly higher than in Group I. Mean biological half-life was 30.3, 23.0, and 38.5 minutes in Groups I, II, and III, respectively. Levels of ACNU were significantly increased in tumor tissue as well as in peritumoral tissue in one Group III patient with multiple metastatic anaplastic adenocarcinoma. In this series, treatment of malignant brain tumor by intra-arterial administration of ACNU produced significantly higher tissue levels of ACNU than did the systemic intravenous route.

The antibacterial activities of nitropyrroles, nitrothiophenes, and aminothiophenes were studied. Replacement of the nitro group with an amino group enhanced the activity of the thiophene compounds.

We evaluated the topologic distribution of vaso-occlusive and vasoformative lesions in 119 eyes with diabetic retinopathy using our newly developed super-wide (130 degrees) fluorescein angiographic montage technique. A numeric coding system was applied to assess the vaso-occlusive lesions by dividing each fundus maximally into 418 blocks. We demonstrated that the midperipheral retina was far more prone to undergo capillary nonperfusion than the posterior retina. The extent of capillary nonperfusion was more pronounced in eyes with neovascularization from (in ascending order): the retina, the optic disc, and in the chamber angle.

Thirty-two heterocyclic compounds, including 24 nitroheterocycles, 7 aminoheterocycles and derivatives, and 1 thiophene lacking a nitro group, were tested for mutagenic activity in Salmonella typhimurium TA 98 and TA 100. All the nitroheterocycles (11 new), including nitrofurans, nitrothiophenes, nitropyrroles, and 1 nitroimidazole, were mutagenic in TA 100; 13 were also mutagenic in TA 98. 5-Nitro-2-furoic acid, a noncarcinogen, was mutagenic in TA 100. Seven carcinogenic nitroheterocycles were mutagenic in both strains. Seven aminoheterocycles (4 new), aminothiophenes and aminothiazole derivatives, and 1 thiophene without a nitro group were not mutagenic. Both TA 98 and TA 100 were uvrB and lacked the ability of excision repair of DNA. Among the 24 mutagenic nitroheterocycles, only 13 compounds exhibited bacterial killing effects, suggesting that more than 1 mechanism may be involved in the interaction of nitroheterocycles with bacterial DNA.

Electron-immunocytochemical staining with lectin (concanavalin A: Con A) binding sites analysis was applied to study secretory granules of human pituitary adenomas and surrounding normal pituitary tissue using post-embedded serial ultrathin sections. Twelve cases of human pituitary adenoma and three specimens of normal pituitary tissue surrounding adenomas were studied: the cases were operated on between 1982 and 1984. The tumors consisted of four prolactin (PRL)-, six growth hormone (GH)-, and two adrenocorticotropic hormone (ACTH)-producing adenomas. In parallel with the detection of Con A binding sites of secretory granules, their secreting hormones were characterized electron-microscopically with the immunocytochemical horseradish peroxidase (HRP) labeling using the avidin-biotin technique. The two cases of ACTH-producing adenomas showed either weak or negative reactions with Con A on secretory granules, while normal ACTH-producing pituitary cells showed strong reactions with Con A on every secretory granule observed. Large secretory granules of PRL- or GH-producing cells showed negative reactions with Con A both in the pituitary adenoma and normal pituitary, while some small granulated or sparsely granulated adenoma cells also showed strong reactions with Con A. The complexity of human pituitary adenomas is illustrated as well as the difference in biochemical structure of normal pituitary cells and pituitary adenoma cells secreting the same specific hormone.

In the management of patients with acute cerebral disturbances, it is essential to determine precisely the degree of impaired consciousness. However, a coma scale for assessing impaired levels of consciousness has not yet been standardized internationally. The Edinburgh-2 coma scale (E2 CS) is introduced and compared with the Glasgow coma scale (GCS). The reliability of the E2 CS was tested by comparing levels of the E2 CS with the outcome of patients who underwent neurosurgical operations. A good correlation was observed between the levels of the E2 CS and the outcome. A change of two levels suggests that some change influencing the outcome has occurred or exists within the cranium of the patient. A correlation between the E2 CS and the GCS was proven to exist. The merits and drawbacks of both scales are discussed. One advantage of the E2 CS is that it has removed ambiguous terms, which are still present in the GCS. Also it is easier to grasp changes in a patient's condition shown on a chart because the levels of the E2 CS are arranged first-dimensionally. Use of the GCS should not preclude the use of other scales, such as the E2 CS; the E2 CS could be used together with the GCS. The accumulation of data on both scales would provide information useful in improving the existing coma scales.

A case of trigeminal neuralgia caused by a parapontine epidermal cyst is reported. The trigeminal inlet zone at the pons was completely surrounded by the tumor. No vascular element was detected around the trigeminal nerve root. Neurological symptoms were completely normal except for typical tic douloureux. Pain was controlled initially by carbamazepine, later by radiofrequency trigeminal nerve coagulation, and finally by microsurgical decompression. Review of the literature suggested the importance of lesions of the middle fossa as another etiological factor. When surgery is performed by the posterior route, the possibility of overlooking these lesions may exist.

Beraprost sodium (sodium (+/-)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2- hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H- cyclopenta[b]benzofuran-5-butyrate, TRK-100) is a chemically and biologically stable epoprostenol analogue which possesses both potent antiplatelet and peripheral vasodilating actions. Its effect on obstruction of the peripheral artery was studied in three different models: 1. acute thrombosis induced by electrical-stimulation of the femoral artery in rabbits, 2. occlusion induced by intra-arterial injection of sodium laurate in rats and 3. tail gangrene induced by subcutaneous injections of both ergotamine and epinephrine in rats. Oral administration of beraprost sodium resulted in suppression of thrombus formation in the acute thrombosis model, marked improvement of macroscopic and histological observations in the laurate-occlusion model and inhibition of tail gangrene extension. In contrast, ticlopidine improved thrombus formation in the acute thrombosis model and slightly improved histological observation in the laurate-occlusion model, but not in the tail gangrene model. Cilostazol suppressed lesions in the acute thrombosis model, but not in the tail gangrene model. These findings suggest that beraprost sodium may be very useful clinically for the therapy of peripheral circulation insufficiency diseases such as Buerger's disease and Raynaud's disease.

From the recent progress in immunological study, many authors have reported immune suppression in patients with malignant brain tumors. On the other hand, many factors are considered to influence the patterns of cellular and humoral immune parameters in patients with brain tumors, pre- and post-operatively. We treated the patients with malignant brain tumors using ACNU and PSK pre- and post-operatively, and 4 year survival rate was 35.3% (N: 17) in glioblastomas. We planned this time to measure immune parameters (Ig,lymprocyte number,Lyn and T-cell, Tn) pre- and post-operatively in order to study the immune states of patients. The results were as follows: The most significant finding was the elevated serum level of IgG in longterm survival of the patients with glioblastoma and the reduced one in patients with postoperative death. No other humoral immunocompetence existed except slightly reduced IgM level in the patients with death. Contrary to many previous studies, our research has suggested that humoral immune parameters are considered to be valuable to understand postoperative immune states of patients, and administration of PSK be effective as an immunomodulator.

This study was designed to characterize the interaction of CH3HgCl or HgCl2 with thyroid peroxidase (TPO). Two types of experiments were performed. First, the thyroids from rats that were given 5.6 mg/kg/day of either CH3HgCl or HgCl2 for 2 weeks by intubation were subjected to histochemical treatment and then to electron microscopy. TPO activities in all cell compartments were inhibited by HgCl2 but not by CH3HgCl. Morphological observation showed that taller epithelia were induced by HgCl2, whereas flattened epithelia forming large follicles were induced by CH3HgCl. The serum thyrotropin level was substantially lowered by CH3HgCl but was unchanged by HgCl2. Second, the guaiacol oxidation by TPO in isolated and ruptured pig thyroid cells was spectrophotometrically monitored in the presence of either CH3HgCl or HgCl2. The TPO was not inhibited by CH3HgCl but was inhibited by HgCl2. These results indicated that CH3HgCl induced a hypothyroid state without affecting TPO, whereas HgCl2 inhibited TPO and induced a hypertropic state owing to compensation for loss of enzyme activity, and that the lack of inhibitory activity of CH3HgCl was not due to the inability to penetrate the cells. Therefore, there appeared to be a differential interaction of organic and inorganic forms of mercurials with the thyroid.

Using composite super-wide fluorescein angiography, 152 eyes with nonproliferative diabetic retinopathy were evaluated for capillary nonperfusion. Four basic types of eyes were distinguished according to the location of capillary nonperfusion: peripheral type 4 eyes, midperipheral type 93 eyes, central type 40 eyes and generalized type 15 eyes. The rate of enlargement of nonperfused area was more rapid in peripheral type, midperipheral type, central type and the generalized type in the ascending order. Eyes belonging to midperipheral and central types evolved into other, usually generalized type during the course of observation. There is a positive correlation between the initial site of occurrence of capillary nonperfusion and its progression in nonproliferative diabetic retinopathy. A proper recognition of the typing is claimed to be of prognostic value.