Rapid and simple micro-determination of carvedilol in rat plasma by high-performance liquid chromatography.

We studied the use of high-performance liquid chromatography (HPLC) with spectrofluorometric detection, using a solid-phase extraction for a simple, rapid and sensitive determination of plasma carvedilol levels in rats. Extracted aliquots were analyzed by HPLC, using a reversed-phase octadecyl silica column. The analytical mean recovery of carvedilol added to the blank plasma was 94.2%. The detection limit was 3.6 ng/ml in the plasma. The reproducibilities (C.V.) were 2.7-7.5% for the within-day assay, and 2.6-7.4% for the between-day assay, indicating that the method was effective for the determination of carvedilol plasma levels.

Brain abscess caused by Streptococcus intermedius: two case reports.

BACKGROUND: Although Streptococcus intermedius has been recognized as an important pathogen for abscess formation outside the central nervous System, the Streptococcus milleri group, of which it is a member, has not been recognized as a specific pathogen for brain abscess, often thought to be caused by Streptococcus viridans, which includes other streptococcal species. CASE DESCRIPTION: Two cases of brain abscess in the left frontal lobe caused by S. intermedius, which responded well to antimicrobial treatment combined with needle aspiration, are presented. In the first patient, the predisposing disease was paranasal sinusitis of the frontal and ethmoid sinuses. In the second patient, the source of the pathogen was not detected despite extensive examination. The patients underwent aspiration of pus under ultrasound guidance in the first patient, and via a computed tomography-guided stereotactic procedure in the second patient. They subsequently received appropriate antimicrobial therapy against S. intermedius isolated from the pus culture. Both patients were discharged without any neurological deficits. CONCLUSION: It is important to recognize S. intermedius as a pathogen of brain abscess, and to be aware of its predisposing factors, i.e., mucosal disturbance and liver abscess.

Extensive edema in the thalamus caused by thrombosed basilar artery aneurysm.

A 69-year-old female presented with sudden onset of truncal ataxia, urinary incontinence, mental confusion, and Parinaud's sign. With conservative treatment, her ataxia and urinary incontinence resolved. Magnetic resonance (MR) imaging disclosed a round mass with laminated intramural hemorrhage in the third ventricle. Right vertebral angiography demonstrated a giant aneurysm in the distal basilar artery. Xenon-enhanced computed tomography showed that cerebral blood flow (CBF) was reduced in the thalamus bilaterally and was paradoxically decreased by acetazolamide. Two months later, MR imaging showed that the intramural hemorrhage had shrunk, and the edema in the thalamus was resolving. The CBF reduction and vascular response to acetazolamide had reversed to some extent. A partially thrombosed giant aneurysm can grow acutely as the result of fresh intramural hemorrhage. The edema is secondary to ischemia and loss of vasoresponsivity.

[A case of pulmonary tuberculosis complicated with gingival lesions].

A case of secondary gingival tuberculosis is presented. The case is 51 year-old male who had been suffering from undetected pulmonary tuberculosis visited a dentist because of chronic periodontal inflammation around the gingiva of the right upper and left lower molar teeth lasting for one year. The lesions remained unchanged and painful granulomatous swelling sustained in spite of the conservative treatment. The case was treated with the extraction of six teeth due to continued toothache. By pathohistological examination of gingiva and chest X-ray examination, the case was diagnosed as tuberculosis. Chest roentgenogram showed active pulmonary tuberculosis, and bacteriological examination of sputum showed tubercle bacilli. The administration of INH, RFP and EB was started, and the response to the treatment was good and the pain in the gingiva disappeared within three weeks. Secondary gingival tuberculosis is manifested as local granulomatous lesions with severe pain. The incidence of gingival tuberculosis is very rare, but we have to keep in mind that the oral tuberculosis secondary to pulmonary tuberculosis could occur.

Augmentation of antitumor effect of endogenously induced tumor necrosis factor by cyclophosphamide.

The antitumor effect of endogenous tumor necrosis factor (en-TNF) with cyclophosphamide (CY) was analyzed using the murine Meth A tumor model. En-TNF was induced by the administration of interferon-gamma (4 micrograms/kg: 1 x 10(4) units/ mouse) as a primer and Streptococcus preparation OK-432 (100 KE/kg) as a trigger. Seven days after inoculation of Meth A tumor in BALB/c mice, about one third of LD50 of CY or five other chemotherapeutic agents (actinomycin D, mitomycin C, tegaful, adriamycin and puromycin) was injected intravenously. En-TNF was induced 7 days after administration of these agents. A combination therapy of en-TNF with CY showed the strongest antitumor effect among several combinations and caused complete tumor regression (40-70%), while none of the combinations with the other chemotherapeutics did so. The optimal time interval to obtain this antitumor effect with CY and en-TNF induction was 7 days. The amount of en-TNF induced around a tumor lesion with CY was two fold higher than that without CY. En-TNF was observed to be induced in tumor lesion solely by CY injection. All these results suggest that the antitumor effect of en-TNF can be augmented by addition of a chemotherapeutic agent such as CY.

Rapid and simple determination of fleroxacin in rat plasma using a solid-phase extraction column.

We studied the use of high-performance liquid chromatography (HPLC) with a spectroflurometric detector, using a solid-phase extraction column (Bond Elut cartridge column), for the simple, rapid and sensitive determination of plasma fleroxacin (FLRX) levels in rats. Extracted aliquots were analyzed by HPLC, using a reverse phase octadecyl silica column. The analytical mean recovery of FLRX added to the blank plasma averaged 101.4%. The detection limit was 58 ng/ml in the plasma. The reproducibilities (C.V.) were 0.50-3.22% in the within-day assay and 2.87 C.V.% in the between-day assay, indicating that the analysis method was effective in the determination of FLRX plasma levels.

Definitions of severely mentally and physically disabled children in Japan: do the differences affect the prevalence rates of these children?

The prevalence rate of severely mentally and physically disabled children (SDC) aged 6-15 years in Okinawa prefecture on 1 May 1989 was 0.74/1000 (143/192,038) according to Oshima's classification, compared with 0.89/1000 (170/192,038) according to the Ministry of Education's classification with minor modifications. The number of children in region classes 1, 2, 3 and 4 of Oshima's classification for SDC were 100, 34, 6 and 3, respectively. The difference (n = 27) between the total numbers of SDC according to the two classifications was mainly because of 21 children categorized as "walking with support' who were included as SDC according to the Ministry of Education's classification but not as SDC according to Oshima's classification. Only region class 1 of Oshima's classification corresponded with region class 25 of the Ministry of Education's classification. The results of the present study indicate that the differences between the two definitions of SDC affect the reported prevalence rates of SDC. Therefore, changing patterns in the prevalence of SDC should be assessed by serial surveys using the same method in each district.

Antitumor effect of exogenous/endogenous TNF (EET) therapy with cyclophosphamide on C6 glioma in rat.

We earlier reported that endogenous TNF could be induced in mice as well as in patients by successive administration of exogenous TNF as a primer and OK-432 as a trigger, and we termed this exogenous/endogenous TNF (EET) therapy. We studied the effect of EET therapy with cyclophosphamide (CY) on tumor-transplanted rats. In order to induce endogenous TNF, 5 x 10(5) U/kg of recombinant human TNF-S(AM2) (rTNF; 5.6x10(6) U/mg protein) was injected intravenously (iv) as a primer followed by injection of 25 KE/kg of OK-432 as a trigger. TNF activity induced in serum was about 500 U/ml. Only 1 U/g of TNF was detected in the brain. To evaluate the antitumor effect, C6 glioma cells (1.6 x 10(4) cell/5 microliters) was transplanted into the brain. On day 7 of the transplantation, the rats were administered iv with CY (75 mg/kg), treated with EET therapy 7 days thereafter, and survival days were checked. No clear difference in survival days was observed between the rats treated with the EET and the control group. Three rats out of 6 treated with CY survived for more than 40 days, and all the rats treated with the combination of CY and EET continued to survive. The histological examination on day 44 revealed necrotic changes at the tumor lesions in all of the surviving rats, and the animals were evaluated as completely cured. These results suggest that applied treatment based on the EET therapy will be also effective against malignant brain tumors.

Branches of the persistent primitive trigeminal artery--an autopsy case.

An adult autopsy case of the persistent primitive trigeminal artery (PTA) is reported. At the origin of the PTA in the cavernous portion of the internal carotid artery, the PTA branched into the meningohypophyseal trunk and the artery of the inferior cavernous sinus. This might indicate that these arteries were formed at the same embryonic stage. At the cisternal portion of the PTA in the posterior fossa, it also branched into the trigeminal nerve root and pons on the way to the basilar artery. The PTA might have functions for the normal structures even in the case of adults. The PTA passed through the dural foramen, which was located medial to Meckel's cave, and connected with the basilar artery. The diameter of the PTA decreased markedly at the foramen. The dural foramen might be the site of regression of the PTA during the embryonic stage.

Adrenal myelolipoma associated with congenital adrenal 21-hydroxylase deficiency.

The occurrence of adrenal myelolipomas is reported in an untreated patient with congenital adrenal 21-hydroxylase deficiency. Laparotomy demonstrated the presence of two lesions, a large tumor which arose from an ectopic adrenal cortex and a smaller tumor in the left adrenal gland. Six cases of adrenal myelolipomas and congenital adrenal hyperplasia have been reported in the literature. All patients were associated with excessive ACTH secretion for a long period of time. The relative frequency of this association, coupled with the observation by Selye and Stone (Am J Pathol 26:211, 1950) that anterior pituitary extracts cause myelolipomatous changes in rats, may indicate a possible role for ACTH in the development of myelolipomas.

[Clinicopathological evaluation of EVAL embolization in arteriovenous malformations].

The clinical and pathological aspects of two large arteriovenous malformations which were removed totally after preoperative embolization using ethylene vinyl alcohol copolymer (EVAL) were studied. The material, which is not adhesive, is handled easily during the procedure of embolization. However, it involves some risks because it might migrate to and occlude the normal branches of the brain and pass through the nidus to the venous system. Histopathological study of AVM nidus which was removed showed embolic materials within the vessels and inflammatory reaction of the vessel wall and its surrounding tissue. There were patchy hemorrhages within the AVM nidus and its surrounding brain tissue. Recanalization was also found within the occluded vessels. These findings suggest that preoperative embolization has some risk of causing intracerebral hemorrhage after the embolization. AVM should be removed surgically as a radical treatment if the patient is able to tolerate the operation.

Gene assignment of Zellweger syndrome to 7q11.23: report of the second case associated with a pericentric inversion of chromosome 7.

The case of a newborn girl with Zellweger syndrome and a pericentric inversion of chromosome 7, 46,XX, inv(7)(p12q11.23), is reported. The diagnosis was confirmed by marked deficiency of peroxisomal beta-oxidation enzymes in hepatic cells from autopsy samples. This is the second case of Zellweger syndrome associated with a rearrangement of chromosome 7, the tentative gene assignment to 7q11 being further supported; the gene is probably confiend to 7q11.23.