Dopamine D-1 receptor-mediated inhibition of nucleus accumbens neurons from the ventral tegmental area.

1. Spike generation by stimulation of the parafascicular nucleus of thalamus was extracellularly recorded in the nucleus accumbens of chloral hydrate-anesthetized adult Wistar rats using a silver-wire microelectrode attached along a seven-barreled micropipette, each of which was filled with dopamine, SKF 38393 (D-1 agonist), bromocriptine (D-2 agonist), haloperidol, SCH 23390 (D-1 antagonist) and domperidone (D-2 antagonist). The drugs were microiontophoretically applied to the target neurons recorded. 2. Effects of dopamine receptor antagonists on the inhibition of the spike generation by conditioning stimuli applied to the ventral tegmental area preceding the test stimulus to the parafascicular nucleus and those of dopamine agonists on the test stimulus-induced spikes were examined. 3. The parafascicular nucleus stimulation-induced spikes were inhibited by dopamine as well as D-1 and D-2 agonists and by the conditioning stimulation of the ventral tegmental area. The conditioning stimulation-induced inhibition was antagonized by haloperidol and SCH 23390, but not by domperidone. 4. Activation of D-1 receptors, which make probably synaptic contact with dopaminergic nerve terminals from the ventral tegmental area, is considered to result in inhibition of the neuronal activity of the nucleus accumbens neurons receiving input from the parafascicular nucleus of the thalamus. In addition, D-2 receptors located extrajunctionally may be involved in the inhibition of the same neurons in the nucleus accumbens.     

First-line high-dose chemotherapy combined with peripheral blood stem cell transplantation for patients with advanced extragonadal germ cell tumors

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of first-line high-dose chemotherapy (HDCT) combined with peripheral blood stem cell transplantation (PBSCT) for patients with advanced extragonadal germ cell tumors (EGGCT). METHODS: Six male patients with advanced non-seminomatous EGGCT were treated with HDCT combined with PBSCT following 2-3 cycles of conventional-dose induction chemotherapy. The regimens used for HDCT were carboplatin, etoposide and ifosfamide (ICE) in five patients and ICE plus paclitaxel (T-ICE) in one patient, and that for induction therapy was cisplatin, etoposide and bleomycin (PEB) in all patients. As a rule, HDCT was continuously administered until alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin normalized (beta-HCG). RESULTS: Following 1-6 courses of HDCT (median, 4 courses), beta-HCG and AFP were normalized in all patients, and five and one patient were diagnosed as showing partial remission and stable disease, respectively. Five patients underwent surgical resection of residual tumors after HDCT, yielding necrotic tissue in two, mature teratoma in two, and viable cancer tissue in one, and the surgical margin was negative in all patients. At a median follow-up of 36 months, five patients were alive and disease-free, whereas the remaining one died of disease progression. Although all patients had grade 3 hematological toxicity, there was no treatment-related death by combining PBSCT. CONCLUSIONS: First-line HDCT with PBSCT could be safely administered to patients with advanced EGGCT, and the antitumor effect of this treatment was comparatively favorable. First-line HDCT therefore may represent an attractive option for patients with advanced EGGCT.     

Long-term results of first-line sequential high-dose carboplatin, etoposide and ifosfamide chemotherapy with peripheral blood stem cell support for patients with advanced testicular germ cell tumor

OBJECTIVE: Standard chemotherapy shows relatively low long-term survival in patients with poor-risk testicular germ cell tumor (GCT). First-line high-dose chemotherapy (HD-CT) may improve the result. High-dose carboplatin, etoposide, ifosfamide chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) was investigated as first-line chemotherapy in patients with advanced testicular GCT. METHODS: Fifty-five previously untreated testicular GCT patients with Indiana 'advanced disease' criteria received three cycles of bleomycin, etoposide and cisplatin (BEP) followed by one cycle of HD-CT plus PBSCT, if elevated serum tumor markers were observed after three cycles of the BEP regimen. RESULTS: Thirty patients were treated with BEP alone, because the tumor marker(s) declined to normal range. Twenty-five patients received BEP and HD-CT. One patient died of rhabdomyolysis due to HD-CT. Three and six (13% and 25%) out of 24 patients treated with BEP and HD-CT achieved marker-negative and marker-positive partial responses, respectively. The other patients achieved no change. Fifteen (63%) are alive and 14 (58%) are free of disease at a median follow-up time of 54 months. Severe toxicity included treatment-related death (4%). CONCLUSIONS: HD-CT with peripheral stem cell support can be successfully applied in a multicenter setting. HD-CT demonstrated modest anticancer activity for Japanese patients with advanced testicular GCT and was well tolerated. This regimen might be examined for further investigation in randomized trials in first-line chemotherapy for patients with poor-risk testicular GCT.     

Detection of urinary polyamine by a new enzymatic differential assay. (II). Comparison with conventional method

A new method of determining urinary polyamine concentration was compared with other techniques, namely, high pressure liquid chromatography (HPLC) and a polyamine test-enzyme kit. The values obtained by the new method, HPLC, and polyamine test-enzyme kit correlated well for all the fractions: diamine, spermidine and spermine. The correlation between the new method and the polyamine test-enzyme kit gave r = 0.9702, y = 1.1359x + 5.1266 (n = 48).     

Diagnosis of deep vein thrombosis by high resolution ultrasonography

Using high resolution ultrasonography (US), diagnostic accuracy of thrombi in each venous segment of lower limbs and qualitative evaluation of thrombi in deep vein thrombosis (DVT) were investigated. The subjects were 106 lower limbs in 81 patients. The thrombi in common femoral vein (CFV), were diagnosed by compression technique and, were qualitatively analysed by echogenicity and consistency. Venography was performed in 18 limbs and histologic tests of thrombi were made in 6 limbs. The total accuracy of US was 100% for diagnosis of DVT, but was 83% for diagnosis of its extent. The total accuracy of US in each segment was greater than 90%, but the sensitivity of iliac veins was less than 90%. The thrombi in CFV were divided into 3 types and 8 sub-types. Type A was homogenous, type B was heterogenous, and type C was contracted echo. The types of us were consistent with results of histologic tests. We concluded that high resolution US is available for screening test for diagnosis of DVT and that qualitative evaluation of thrombi by US is a useful clinical test for selection of more adequate treatments.     

Skullbase-penetrating injuries caused by umbrella tips: case reports

Two cases of skullbase-penetrating injuries caused by umbrella tips are reported. Case 1: 24-year-old male. Admitted with disturbance of consciousness, left hemiparesis, nasal bleeding, and laceration of left lower eyelid because of having been stabbed by an umbrella tip. Pupils and fundi revealed no definite findings. Plain skull X-ray showed turbid ethmoid sinus and fracture of planum sphenoidale. Cranial CT showed right putaminal hematoma with intraventricular hemorrhage and pneumocephalus. Increased ICP necessitated surgery two days after the injury. Dural laceration of planum sphnoidale, laceration of left optic nerve, right rectal gyrus contusion and rebleeding from the right lenticulostriate branch were observed. Dural plasty and removal of hematoma with external decompression were carried out. He had a good postoperative course, but left visual loss and left hemiparesis remained. Case 2: 29-year-old male. Admitted with excoriation of his right nostril because of having been stabbed by an umbrella tip, severe headache, and nasal discharge. Oculomotor palsy was observed as well as CSF rhinorrhea and meningeal irritability. Plain skull X-ray showed niveau in sphenoidal sinus, pneumocephalus, and fracture of sella turcica. His complaint disappeared after conservative therapy. We reviewed the literature and found only 4 similar cases. The skullbase, because of its anatomical character, is likely to be penetrated in orbital and periorbital injury caused by umbrella tips. Cases which include disturbance of consciousness have a poor prognosis. We hope the fact that umbrella tips can easily become life-threatening objects will come to the attention of the general public so that similar cases may be avoided.     

The kapurimycins, new antitumor antibiotics produced by Streptomyces. Physico-chemical properties and structure determination

The kapurimycins A1, A2 and A3 were revealed to be new antitumor antibiotics with molecular formula of C27H26O9, C26H24O9 and C27H24O9, respectively. The structures of the kapurimycins were determined by NMR spectroscopic analysis. The kapurimycins are new class of polycyclic microbial metabolites having the tetrahydroanthra-gamma-pyrone skeleton and the beta, gamma-unsaturated delta-keto carboxylic acid structure. The individual components of the kapurimycins differ from one another in the side chain at the pyrone ring of the molecule.