[Effects of physostigmine on arousal, respiration and circulation--double-blind studies].
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Biomedical subjects
Publications and source records attributed to K Fujii.
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A clinical trial of moderate dose methotrexate (MTX)-CF rescue was conducted in 12 institutions. Thirty-seven patients with head and neck carcinoma entered this trial, of which 32 were evaluable. MTX was administered 350 mg/m2 (500 mg/body) by i.v. drip over 6 hours. Three hours after completion of MTX infusion, CF rescue was started. There was no complete response in 32 patients. Nine patients showed partial response with the response rate of 28%. The response rates were 21% for the group of patients treated previously, and 75% for the group untreated previously. MTX concentration in plasma was determined at 6, 24, 48 and 72 hours after the initiation of MTX infusion, and the assay results revealed a safe range. GI disturbances were seen at the rates of 11 to 38%. Bone marrow suppression was mild and no renal toxicity was observed. We concluded that the moderate dose MTX-CF rescue therapy was useful for head and neck carcinoma. As a next step, we are planning to conduct a clinical trial of high-dose MTX.
Recently, a new antibiotic of cephamycins, cefmetazole (CMZ) has been developed. In our clinic, CMZ was used to examine its clinical effect and adverse reactions, and the results were herein reported. The CMZ was administered to 8 patients for the prevention of postoperative infections, 7 with genitourinary infections and 1 with maxillitis complicated with uremia. For these patients, a daily dose of 1 to 6 g of CMZ was intravenously given for a period of 4 to 12 days. Among the 8 patients who received CMZ for the prevention of postoperative infections, there were 1 case with urinary tract infection, 1 with wound infection and 2 with fever of over 38 degrees C, but they had no serious infections. In the clinical observations on 3 cases with pyelonephritis, the CMZ showed marked effectiveness in 2 cases and effectiveness in 1 case. It must be noted that CMZ was proved to be markedly effective for pyelonephritis caused by Serratia marcescens. In the cases with acute epididymitis and prostatitis, a good effect of CMZ was obtained. Similarly in the case with maxillitis complicated with uremia, the maxillitis was improved by the effect of CMZ and hemodialysis. No cases with hepatic or renal dysfunction were observed after using CMZ. It is concluded that satisfactory effect of CMZ was obtained clinically.
A total of 42 patients who were suffering from respiratory tract infections were treated with cefoxitin, and the following results were obtained. 1. Out of 32 patients clinically evaluated, excellent or good responses were observed in 30 patients (94%). 2. Presumed causative organisms were isolated in 14 patients. The organisms were eradicated in 11 patients and the eradication rate was 79% (11/14). The number of the organisms decreased or unchanged in 1 patient each. In other 1 patient the pathogenic agent was replaced with other agents during the course of treatment. 3. As for the side effects, skin eruption was observed in 3 patients. One patient received drugs other than cefoxitin concomitantly that might have caused the eruption. Another patient had an allergic history to many antibiotics. In 4 patients slight elevations of S-GOT and S-GPT were observed but improved soon after the completion of cefoxitin treatment. In 1 patient an elevation of serum creatinine was observed but this was not attributed to the administration of cefoxitin. 4. From the results stated above, cefoxitin is considered to be a safe and effective antibiotic which can be one of the first-choice antibiotics for the treatment of respiratory tract infections.
We studied cefoxitin (CFX) concentration of oro-maxillary tissues in rats and in 18 patients by means of bioassay method. In rats, the highest peak concentrations were observed in the gingiva and buccal mucosa followed by the tongue, submaxillary gland, lower jaw bone and the masseter muscle in the order listed. In patients, the highest peak concentrations were observed in the maxillary sinus mucosa and peak concentrations in oro-maxillary tissues were from 1/5 to 2/3 of the corresponding serum concentrations. Further study is needed to elucidate the reason for the high peak CFX concentration in the maxillary sinus mucosa and the apparent delayed peak concentration in the salivary gland.
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L1210 mouse leukemia cells were made cobalamin-deficient by propagation in a medium from which cyanocobalamin was omitted and fetal bovine serum (containing protein-bound cobalamins) was replaced by bovine serum albumin. These cobalamin-deficient cells exhibited a normal replication time of 12 h, provided that the medium contained excess folate or 5-formyltetrahydrofolate. The cells responded poorly, however, to 5-methyltetrahydrofolate unless exogenous cobalamin was added. A cobalamin dependency was also observed when low levels of folate or 5-formyltetrahydrofolate were used. With 5-methyltetrahydrofolate, optimal stimulation of growth was observed with free and transcobalamin-II-bound cobalamin at 4,000 pM and 2 pM, respectively. Under cobalamin-replete conditions, cells contained 2,000 to 4,000 molecules of cobalamin/cell, and in the deficient state, this value declined to less than 10 molecules/cell; optimal replication on 5-methyltetrahydrofolate required approximately 180 molecules/cell. Cobalamin-deficient cells cultured in the absence of folate reached an arrested state from which limited replication could be induced by the addition of aquacobalamin; normal replication was induced by aquacobalamin plus 5-methyltetrahydrofolate. Results of this investigation are interpreted in terms of the requirement for tetrahydrofolate in cell replication and the production of this compound from folate and 5-formyltetrahydrofolate (via cobalamin-independent pathways) and from 5-methyltetrahydrofolate (via the cobalamin-dependent methionine synthetase).
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In order to clarify the role of histamine in the neuro-humoral excitatory mechanism in the stomach, the effect of cepharanthine (an inhibitory agent of histamine release from mast cells) on excitatory response of gastric movement and increase in gastric mucosal histamine content caused by nerve stimulation (vagus and splanchnic nerves) or administration of tetragastrin were investigated in dogs. The animals were anesthetized with pentobarbital sodium and immobilized with gallamine triethiodide. The following results wee obtained. Increase of gastric mucosal histamine content caused by vagal and splanchnic nerve stimulation and administration of tetragastrin was inhibited by administration of cepharanthine. Cepharanthine inhibited the tonic contraction of the innervated antral pouch or isolated antral circular muscle strip caused by stimulation of vagus nerve. Tonic contraction of the innervated antral pouch caused by electrical stimulation of the splanchnic nerve after nicotinization of celiac and superior mesenteric ganglia was inhibited by administration of cepharanthine. Cepharanthine inhibited motor excitatory response of the denervated corpus pouch caused by stimulation of vagus and splanchnic nerves and by administration of tetragastrin. These results support the theory that cepharanthine inhibits the release of histamine from histamine-secreting cells in the gastric mucosa. It is suggested that histamine plays an important role in the neuro-humoral excitatory mechanism of gastric movement.
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