[Assessment and controversy of long-term medical treatment in ischemic heart disease--Japanese Angina and Myocardial infarction Prospective (JAMP) Study].
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Adrenergic beta-Antagonists↗
Biomedical subjects
A Sakuma
Publications and source records attributed to A Sakuma.
[Phase-I clinical study of KW-2307 combined with cisplatin in non-small cell lung cancer patients].
A phase-I clinical study with coadministration of a new vinca alkaloid derivative KW-2307 with cisplatin (CDDP) at 80 mg/m2 to patients with non-small cell lung cancer was conducted by a collaborative study among 6 institutions. CDDP was given on day 1 and KW-2307 on days 1, 8 and 15, both intravenously. One 28-day course was specified to be repeated twice. The initial dose of KW-2307 was 15 mg/m2 and increased to 20 mg/m2 and then to 25 mg/m2. The numbers of enrolled subjects for each dose were 5, 8 and 12 cases, respectively, in the total 25 cases. This regimen as well as KW-2307 monotherapy induced leukocytopenia (neutropenia) as the main adverse reaction. The coadministration with CDDP tended to increase the occurrence of anorexia and nausea/vomiting. Tumor response was obtained in 5 among 24 evaluable cases (CR1, PR 4). The response rate in the cases untreated with KW-2307 and given at 20 mg/m2 or higher doses was 29.4% (5/17, 95% confidence interval of the response rate: 10.3 to 54.7%). Considering drug compliance, etc., the maximum tolerated dose in this regimen was supposed to be 25 mg/m2, and the recommended dose in phase-II study to be 20 mg/m2.
Adenocarcinoma↗
[Massive skeletal invasion in Hodgkin's disease observed by MRI].
A 35-year-old female developed cervical adenopathy and mediastinal tumor in 1988. A lymph node biopsy specimen showed nodular sclerosing Hodgkin's disease. She received combination chemotherapy with cyclophosphamide, vincristine, adriamycin and prednisolone, and radiotherapy for mediastinal tumor. She had a complete remission (CR). In September 1990, she developed swelling of the left hip and felt pain in the left hip and thigh. She also noticed swelling of the left inguinal lymph nodes. MRI T2-weighted images showed enlargement and destruction of the fascia and hyperintense signal of the left iliac and gluteus muscle. A biopsy specimen of the inguinal lymph node showed recurrence of Hodgkin's disease of mixed cellularity. She received salvage therapy with ifosfamide, methotrexate, etoposide and procarbazine, and achieved a second CR. The clinical appearance of the skeletal muscle involvement by lymphoma is uncommon, especially in Hodgkin's disease.
Adult↗
Lipo-PGE1, a new lipid-encapsulated preparation of prostaglandin E1: placebo-and prostaglandin E1-controlled multicenter trials in patients with diabetic neuropathy and leg ulcers.
Several clinical trials have shown that prostaglandin E1 (PGE1) is effective in treating peripheral occlusive vascular disease, but not definitely for diabetic neuropathy. We developed a new preparation of PGE1 incorporated in lipid microspheres (lipo-PGE1) that was designed to accumulate at vascular lesions. The effect of lipo-PGE1 (10 micrograms/day) was compared with placebo and the normal dose of a free PGE1 preparation (PGE1-CD, 40 micrograms/day) in two studies (double-blind and well-controlled) which enrolled 364 diabetic patients with neuropathy and/or leg ulcers. The drugs were given intravenously (bolus or drip infusion) for 4 weeks. Clinical improvement was noted in 61.6% of the lipo-PGE1 group and 30.0% of the placebo group in Trial 1 (p < 0.01), while the figures were 58.3% in the lipo-PGE1 group and 37.1% in the PGE1-CD group in Trial 2 (p < 0.01). Leg ulcers became smaller in the lipo-PGE1 groups in both trials (p < 0.01). In Trial 2, motor conduction velocity improved in the lipo-PGE1 group (p = 0.016). Side effects occurred in few patients receiving lipo-PGE1 or placebo, but more patients developed local side effects in the PGE1-CD group (p < 0.01). Thus, bolus intravenous injection of lipo-PGE1 improved diabetic neuropathy and leg ulcers with minimal side effects.
Adult↗
A placebo-controlled double-blind study of epalrestat (ONO-2235) in patients with diabetic neuropathy.
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Adult↗
Recombinant tissue-type plasminogen activator ameliorates ischemic derangements induced by thrombotic occlusion in closed chest anesthetized dogs.
Effects of thrombotic coronary occlusion followed by thrombolytic reperfusion with recombinant tissue-type plasminogen activator (rt-PA) on infarct size and left ventricular function were studied in anesthetized closed chest dogs. After thrombotic occlusion of the left anterior descending coronary artery was produced by a copper coil technique, 74 dogs were randomly alloted to three groups; dogs treated with rt-PA at 90 min (n = 23) (group I) and at 180 min (n = 25) (group II) of the thrombotic occlusion, and 26 dogs treated with saline solution (permanent thrombotic occlusion, group III). The loading dose of intravenous rt-PA was 8,160 IU/kg body weight per min at the initial 60 min and the maintenance dose was 2,450 IU/kg per min continuously infused for 24 h. Thrombolytic recanalization was achieved at 15 +/- 4 and 18 +/- 6 min after rt-PA infusion in groups I and II, respectively. Infarct size and area at risk were determined by triphenyltetrazolium chloride staining and postmortem angiography; infarct size/area at risk ratio was 10 +/- 3% (n = 10), 33 +/- 7% (n = 9) and 63 +/- 3% (n = 10) in groups I, II and III, respectively (difference significant among groups). To examine whether infarct size and left ventricular function after thrombolytic reperfusion differ from those after mechanical reperfusion, 39 other dogs (group IV) underwent mechanical coronary occlusion for 106 +/- 1 min (occlusion period comparable with that of group I) and reperfusion using a balloon catheter.(ABSTRACT TRUNCATED AT 250 WORDS)
Anesthesia↗
[Complete remission with MEC regimen of acute myeloid leukemia (M4) secondary to 5-year treatment of non-Hodgkin lymphoma].
A 32-year-old woman was admitted to our hospital with pyrexia and general lymphadenopathy in July 1984. She was diagnosed as having malignant lymphoma (follicular, small cleaved cell), stage IV based on the histological findings of lymph nodes in the neck and bone marrow specimen. She was treated with melphalan orally for 3 years, followed by MACOP-B. She attained partial remission with MACOP-B. Thereafter, she received melphalan or Endoxan orally as maintenance therapy. She developed fever and swelling in the gingivae in October 1989. Peripheral blood showed WBC 80,200/microliters with 7.5% myeloblasts and 85.5% monocytes. Bone marrow aspirate revealed hypercellularity with 47.9% myeloblasts, 46.5% monoblasts and monocytes, which were positive for peroxidase and NSE stains. The karyotype of bone marrow cells showed a 46,XX,t(9;11). The lysozyme in serum was elevated. She was diagnosed having AML (M4). DCMP regimen was initiated but failed to achieve CR. Consequently she received MEC regimen and obtained complete remission, lasting for 6 months. Patients with second leukemia have a low probability of achieving complete remission using conventional chemotherapy. The MEC regimen is thought to be one of the most promising treatments for secondary leukemia.
Adult↗
[A randomized comparative study of 254-S plus vindesine (VDS) vs. cisplatin (CDDP) plus VDS in patients with advanced non-small cell lung cancer (NSCLC)].
It has been shown in phase II studies that 254-S, a new anticancer platinum complex, is effective in the treatment of various cancers. In order to more objectively evaluate the clinical usefulness of this compound, a randomized comparative study of 254-S plus VDS vs. CDDP plus VDS was conducted in patients with advanced NSCLC. 254-S or CDDP was intravenously administered at 90 mg/m2, at least 2 times at 4-week intervals. VDS was intravenously administered at 3 mg/m2 on Days 1 and 8 of each treatment of 254-S or CDDP. Of 136 patients registered, 121 (64 of the 254-S/VDS group and 57 of the CDDP/VDS group) were evaluable for tumor response (complete cases). There was no significant intergroup difference in the tumor response rate (254-S/VDS group: 12.5% [8/64], CDDP/VDS group: 15.8% [9/57]), nor by cancer staging, histological type or survival. As for toxic effects, leukopenia was significantly less frequent in the 254-S/VDS group while thrombocytopenia was significantly less frequent in the CDDP/VDS group. Nephrotoxicity such as an elevation of BUN and a decrease in serum creatinine was significantly less frequent in the 254-S/VDS group in spite of the lower volume hydration performed. In addition, nausea and vomiting as well as anorexia were observed with significantly lower incidences in the 254-S/VDS group despite the less frequent anti-emetic treatment. Based on these results, it was concluded that combination treatment with 254-S and VDS is a safe and useful regimen for treatment of NSCLC, generating antitumor effects equivalent to the CDDP/VDS regimen.
Adenocarcinoma↗
Treatment of diffuse non-Hodgkin's lymphoma with combined chemotherapy using methotrexate, adriamycin, cyclophosphamide, vincristine, prednisolone and bleomycin (MACOP-B).
Forty-nine previously untreated adult patients with diffuse non-Hodgkin's lymphoma were treated with MACOP-B (methotrexate, adriamycin, cyclophosphamide, vincristine, prednisolone and bleomycin) between December 1986 and December 1990. Forty patients (82%) achieved a complete response (CR), three (6%) a partial response (PR), while four (8%) had either no response or progression of disease, one (2%) patient ceased MACOP-B therapy and received other chemotherapy because of sustained neutropenia, and one patient (2%) died of sepsis during therapy. The factors that adversely affected the CR rate were by stage IV, the presence of B symptoms, the presence of a large mass (greater than 5 cm), and low serum total protein level. The 4-year survival for all 49 patients was 70% and the 4-year disease-free survival (DFS) for the 40 CR patients was 77%. Relapses were higher in patients whose initial serum lactic dehydrogenase (LDH) level was higher than 660 IU/1 (DSF 89% vs. 49%). Toxicity was substantial but acceptable, with neutropenia and mucositis proving to be the most frequent severe side-effects. These preliminary results confirmed the effectiveness of MACOP-B therapy for diffuse non-Hodgkin's lymphoma.
Adolescent↗
Effects of enoximone on exercise tolerance in patients with mild to moderate heart failure.
To evaluate the efficacy of enoximone on exercise tolerance in patients with mild to moderate heart failure, 33 patients underwent cardiopulmonary exercise tests before and 3 hours after placebo or after receiving 25 or 100 mg of enoximone administered randomly in a double-blind manner. The electrocardiogram was monitored and blood pressure measured every minute throughout cycle ergometer exercise testing with a ramp protocol in which the work rate increased 1 W every 6 seconds after a 4-minute 20-W warm-up. Minute ventilation, oxygen uptake (VO2), and carbon dioxide output were measured every 10 seconds in order to determine anaerobic threshold (AT) and peak VO2. Five patients were excluded from evaluation before breaking the double-blind key because of insufficient data. Heart rate increased and systolic blood pressure decreased throughout the testing only in the group taking 100 mg (n = 10). Significant increases in AT (14.4 to 16.2 ml/min/kg) and peak VO2 (20.8 to 22.9 ml/min/kg) were observed in the group taking 100 mg. The increases in AT showed a dose response, namely +0.7% in the placebo (n = 9), +6.9% in the 25-mg (n = 9) and 12.5% in the 100-mg group. The work rates at the AT point increased in the 25- and 100-mg groups. These results indicate that a single oral administration of enoximone improves exercise tolerance in patients with mild to moderate heart failure.
Aged↗
The neuronal organization of horizontal semicircular canalactivated inhibitory vestibulocollic neurons in the cat.
1. The somatic location and axonal projections of inhibitory vestibular nucleus neurons activated by the horizontal semicircular canal nerve (HCN) were studied in anesthetized cats. Cats were anesthetized with ketamine hydrochloride and pentobarbital sodium. 2. Intracellular recordings were obtained from 11 neck extensor motoneurons which were identified by antidromic activation from the dosal rami (DR) in the C1 segment. Stimulation of the ipsilateral (i-) HCN and the ipsilateral abducens (AB) nucleus evoked IPSPs in the motoneurons. These IPSPs were fully or partially occluded when they were evoked simultaneously. 3. Intracellular recordings were obtained from 8 AB motoneurons. Stimulation of the i-HCN and the i-C1DR motoneuron pool evoked IPSPs in the AB motoneurons. These IPSPs were also partially occluded when they were evoked simultaneously, which implied that some HCN-activated neurons inhibit both i-AB motoneurons and ipsilateral neck motoneurons. 4. Unit activity was extracellularly recorded from 30 vestibular neurons that were activated monosynaptically by i-HCN stimulation. Their axonal projections were determined by stimulating the i-AB nucleus and the i-C1DR motoneuron pool. Eight neurons were activated by both stimuli, and were termed vestibulooculo-collic (VOC) neurons. Their axonal branching was examined by means of local stimulation in and around the i-AB nucleus and the i-C1DR motoneuron pool. Eighteen neurons were antidromically activated from the i-C1DR motoneuron pool but not from the i-AB nucleus. These were termed vestibulo-collic (VC) neurons. Four neurons were activated from the i-AB nucleus but not from the ventral funiculus in the C1 segment, and were termed vestibulo-ocular (VO) neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
Abducens Nerve↗
In vivo effect of a large amount of allogeneic granulocytes on reconstitution of hemopoietic cells of irradiated mice.
The in vivo effects of allogeneic granulocytes on the reconstitution of splenic and bone marrow CFUs and CFUc numbers were investigated using irradiated mice. When allogeneic granulocytes were intraperitoneally injected into irradiated BDF1 mice (260 rads), the reconstitution of CFUs in both spleen and bone marrow as well as the hematocrit were enhanced, while the reconstitution of splenic or bone marrow CFUc numbers was transiently suppressed and then enhanced. The magnitude of enhancement was dose-dependent. These results suggest that granulocytes injected into irradiated mice might act as enhancing effectors on the in vivo reconstitution of hemopoietic cells.
Animals↗
Effects of irradiation on marrow stromal cells with respect to committed granulocyte-macrophage progenitor cells.
The effects of irradiation on the growth regulatory function of marrow stromal cells (MSC), and on the committed granulocyte-macrophage progenitor cells (GM-CFC), were investigated using a liquid culture system. CSF activity in the supernatant of irradiated MSC (0-900 rads) increased markedly with the increase of MSC irradiation dose. CSF-inhibitory activity in the supernatant of irradiated MSC (0-900 rads) also increased with the increase of MSC irradiation dose. Furthermore, the activity of exogenous CSF added to the supernatant of 900 rad-irradiated MSC was lost more slowly than that of non-irradiated MSC. These data suggest that irradiation affected CSF production, inhibitor production and consumption of CSF by MSC.
Animals↗
Vestibulo-thalamic neurons give off descending axons to the spinal cord.
Vestibulo-thalamic (VT) neurons were physiologically studied in the anesthetized cat. Forty-seven VT neurons were recorded extracellularly. More than half of the VT neurons responded monosynaptically to vestibular nerve stimulation while the others responded polysynaptically. They were activated antidromically from one or two sites in the VPL. VPM, VL, VM, SG, and PO of the contralateral thalamus. Four fifths of the VT neurons were activated from the C1 segment of the spinal cord. Half of them were also activated from the C4 segment, but none were activated from the L5 segment. It is suggested that most VT neurons project descending axons to the cervical spinal cord. Axonal branching was shown by means of systematic microstimulation in the thalamus and the ventral horn in the C1 segment. The VT neurons were mainly located in the descending vestibular nucleus.
Animals↗
[A double blind comparative study of 1g/day, 2g/day salazosulfapyridine and placebo in rheumatoid arthritis].
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Adult↗
[Effect of very low protein diet on the progression of chronic renal failure--a case report].
Low protein diet has been a very important clinical manipulation to delay the progression of chronic renal failure. However very low protein diet (less than 30 g/day) is not popular because of concern about malnutrition due to protein restriction, and the difficulty and trouble in making palatable dish. A 48 year old man with chronic renal failure has been on a 20-30 g protein-restricted diet more than three years with no remarkable defect in his daily life, with adequate nutrition, and with very enjoyable and variable daily menus. The rate of progression of chronic renal failure was markedly slowed. Serum creatinine level was 6.9 mg/dl when he started the diet control and it took more than three years for the creatinine level reached to 15.5 mg/dl with no troublesome clinical findings or symptoms. For successful protein restricted dietary treatment, the following several ideas have been helpful: promoting the patient's understanding of the disease and treatment; abundant use of specifically made low protein, high caloric foods such as starch noodles and rice; adoption of creative menus for the patient; and using a free diet a few days a month. The results indicate that we have to again consider the effect of the very low protein (30-20 g/day) diet in slowing the progression of chronic renal failure without nutritional disturbance or restriction of the patient's palatability.
Blood Urea Nitrogen↗
Localization and synaptic effects of inhibitory vestibulocollic neurons activated by the posterior semicircular canal nerve in the cat.
Cellular locations, axonal projections, and synaptic effects of inhibitory vestibulocollic (VC) neurons activated by the ampullary nerve of the posterior semicircular canal (PCN) were studied in anesthetized cats. The inhibitory VC neurons were identified by their monosynaptic responses to PCN stimulation and by their antidromic responses to stimulation of the ipsilateral (i-) and contralateral (c-) neck extensor motoneuron pools, which are inhibitory targets of the PCN. They were classified as VCi (vestibulocollic neuron sending an axon to the i-neck extensor motoneuron pool) and VCc (vestibulocollic neuron sending an axon to the c-neck extensor motoneuron pool) neurons. Neither VCi nor VCc neurons were activated antidromically by localized stimulation of the ascending medial longitudinal fasciculus (asc. MLF) or the 3rd nuclei. Their cell somata were localized in the rostral part of the descending vestibular nucleus and the ventral part of the lateral vestibular nucleus. VCi and VCc neurons produced unitary IPSPs in neck extensor motoneurons in the C1 segment.
Action Potentials↗
Axonal trajectories of inhibitory vestibulocollic neurons activated by the anterior semicircular canal nerve and their synaptic effects on neck motoneurons in the cat.
Somatic location, axonal trajectories and synaptic effects of inhibitory vestibulocollic neurons which were activated by selective stimulation of the anterior semicircular canal nerve (ACN) were studied in the anesthetized cat. ACN stimulation evoked disynaptic inhibitory postsynaptic potentials (IPSPs) in neck flexor motoneurons. This was seen in all the (64/64) tested motoneurons innervating the ipsilateral (i-) longus capitis (LC) and the i-sternocleidomastoideus (SCM) muscles and in 86% (38/44) of the motoneurons innervating the contralateral (c-) LC muscle. The inhibitory relay neurons, identified by orthodromic and antidromic responses to stimulation of the ACN and the i- and c-LC motoneuron pools, were classified as VCi (vestibulocollic neurons sending an axon to the i-LC motoneuron pool) and VCc (vestibulocollic neurons sending an axon to the c-LC motoneuron pool) neurons. Neither VCi nor VCc neurons were activated antidromically by localized stimulation of the ascending medial longitudinal fasciculus (asc. MLF) or the 3rd nuclei. They were located in the medial, descending and ventral lateral vestibular nuclei. It was also observed that VCi neurons produced unitary IPSPs in i-LC and i-SCM motoneurons in the C1 segment. Inhibitory synapses were estimated to be on the cell somata and/or the proximal dendrites of the motoneurons.
Animals↗