Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The comparative studies in the short term intermittent toxicity of pepleomycin (NK631) and bleomycin (BLM) were performed on 10 beagle dogs of 13 approximately 15 months old. Two dogs per group were injected intravenously with NK631 and BLM in doses 5.0 and 2.5 mg/kg body weight every fourth day for 11 treatment. Two dogs served as control and were injected with saline solution. In the group of 5.0 mg/kg of NK631, one dog was sacrificed on day 37 of the treatment and another one dog died on day 33 of the treatment. All the dogs of other group survived until the end of the treatment. The toxicity to the hepatic and renal damage caused by NK631 was stronger than the BLM. On the contrary, the toxicity to lung and various mucocutaneous regions was weaker than the BLM. The grade of pulmonary fibrosis of NK631 was about 1/2 and 2/3 of the BLM in dose of 5 mg/kg and 2.5 mg/kg, respectively. Other toxicological changes such as anorexia and weight loss were almost similar to the BLM.
 ...
PMID:[Toxicological studies of pepleomycin sulfate. V. Short term intermittent toxicity in dogs (author's transl)]. 8 8

It is impossible to accurately evaluate NK 631 as an anticancer agent from the findings only in the 7 cases; hence, the following is no more than the author's impression about the drug. However, NK 631 appeared to exert a similar anticancer effect to the currently available bleomycin. In other words, the drug will completely cure or greatly improve the early cases of squamous cell carcinoma, and bring about a transient regression in the advanced cases. The response of malignant lymphoma to this drug varied from case to case; in any event, it is impossible to anticipate a complete cure in this malignancy by single NK 631 therapy but by multiple combination chemotherapy, e.g., BEMP therapy. The adverse reactions to NK 631 that were observed included pulmonary fibrosis, though only in 1 case; hence, no conclusive opinion should be given herein about it pulmonary toxicity in comparison with the pulmonary toxicity of bleomycin. It remains a theme of the future statistic studies in a large number of cases. The other adverse reactions were anorexia and mild alopecia in some of the cases, which were similar to those to bleomycin. Pigmentation also occurred in one of the cases, but the author was impressed that this reaction was less likely to occur with NK 631.
 ...
PMID:[Clinical application of NK 631, a new derivative of bleomycin (author's transl)]. 9 Jul 42

The acute intravenous and oral toxicity of single doses of paraquat dichloride was studied in the cynomolgus monkey. Renal handling and effects upon renal function were also investigated following an oral dose of [14C]paraquat. Clinical signs consisted of vomiting, anorexia and dyspnoea. By 48 h all animals showed signs of acute renal failure with oliguria, high plasma urea and SGPT levels and metabolic acidosis. Animals dosed orally showed similar, though less severe, signs to those dosed intravenously. The oral LD50 was approx. 70 mg paraquat cation/kg. Following an oral dose plasma levels peaked by 2 h, but were constant from 12 h to 24 h. Paraquat clearance was high initially and exceeded the creatinine and urea clearance, but fell off markedly after 14 h as renal failure developed. By 18 h urine production had ceased. It is concluded that acute renal failure and acute pulmonary damage are the main causes of death, with interstitial pulmonary fibrosis being a factor in animals surviving the acute phase.
 ...
PMID:The toxicity and renal handling of paraquat in cynomolgus monkeys. 12 Jun 23

Chronic pulmonary histoplasmosis is best regarded as an opportunist or saprophytic infection of abnormal pulmonary spaces by a fungus of very low human pathogenicity. Tissue disease results from host immune response to dispersions of soluble antigen from these focal sources. There are two distinct types of clinical and radiological response. One is an acute or subacute illness manifested by often large segmental pneumonic lesions which tend to heal and are designated as early lesions. The other, usually developing as a complication of the first, is a chronic disease marked by persistent cavitation, low gard chronic illness, and a tendency to promote pulmonary fibrosis and often progressive pulmonary insufficiency. The early lesion is a segmental interstitial pneumonitis with central areas of infarct-like necrosis often adjacent to bullous disease and often outlining prominent emphysematous spaces which appear as radiolucencies. These radiological findings are further characterized by early clearing of the interstitial components, infarct-like contraction of the necrotic zones, obliteration of much of the contained emphysematous and bullous spaces, and healing attended by considerable loss of lung volume. Symptoms are variable but tend to be mild. Malaise, fatigability, low-grade fever, aching chest pain and mild cough lasting a few days to a few weeks are usual. Symptoms are ameliorated by rest. Rest and diminished activity are recommended as treatment. Under these circumstances, 80% of early lesions heal completely and probably most of these would heal spontaneously. Any subsequent course of the disease depends on whether or nor large air spaces, adjacent to or contained within the area of pneumonitis, become infected and persist as cavities. This occurs in 20% of early lesions. Once established, an infected cavity tends to persist and to be attended by symptoms of chronic bronchitis with chronic cough and sputum, fatigability, anorexia, and weight loss. Persisting thickwalled cavities often induce gradual development of pulmonary fibrosis, particulary in the lung bases, apparently from aspiration of antigenic material. This and the accelerated obstructive bronchopulmonary disease often lead to progressive pulmonary insufficiency. The use of amphotericin B is recommended for all persistent thick-walled cavities and in some circumstances surgical resection may be indicated.
 ...
PMID:Chronic pulmonary histoplasmosis. 79 26

10-Edam (10-ethyl-10-deaza-aminopterin), an antifolate derivative, was administered to 14 chemotherapy-naive patients with advanced colorectal carcinoma. The drug was given weekly by intravenous route at an initial dose of 80 mg/m2, with escalation or attenuation according to tolerance. Mucositis was dose limiting and occurred in 11 of 14 patients (78.6%). Removal from the study was required in one patient due to progressive pulmonary fibrosis that was histologically identical to methotrexate-induced lung damage. Toxicity was otherwise mild to moderate and included diarrhea, constipation, abdominal discomfort, anorexia, nausea/vomiting, rash, and fatigue. There were no responses to 10-Edam in this study, 95% confidence interval (0-0.23). Stable disease was achieved in four patients; the remaining 10 patients demonstrated progression within 9 weeks of initiating systemic therapy. 10-Edam employed at this dosage and schedule was not effective as a treatment against advanced colorectal carcinoma.
 ...
PMID:Phase II trial of 10-Edam in patients with advanced colorectal carcinoma. 230 19

Continuous subcutaneous infusion of peplomycin was performed on 17 patients with metastatic prostate carcinoma, 9 of whom were refractory to conventional hormone therapy. Peplomycin was administered 5 mg daily through a newly-developed "microinfusion pump" for 14 consecutive days. This therapy was discontinued in 3 patients at the cumulative dose of 35, 35 and 55 mg. The mean cumulative dose was 84.7 mg. One patient who received 140 mg of peplomycin developed pulmonary fibrosis which was so mild that he recovered soon after the conservative therapy was instituted. There were no other episodes of pulmonary toxicities. Other major toxicities observed were anorexia (47%) and fever (41%). Of 15 patients who were evaluable with the response criteria of NPCP, 4 patients achieved objective partial regression (two for pulmonary metastases, one for bone metastases and the other for supraclavicular lymphnode metastases) and the other 11 patients remained stable. No progression of the disease was noted. Continuous subcutaneous infusion of peplomycin is advantageous over the bolus injection for increasing its anti-tumor activity as well as for decreasing its pneumotoxicity. It can also be performed for out-patients without difficulty. We believe this therapy should be incorporated in the multidisciplinary therapy of prostatic cancer.
 ...
PMID:[Continuous subcutaneous infusion of peplomycin for advanced prostatic cancer patients]. 241 47

Twenty-three patients with squamous cell carcinoma were treated with a combination chemotherapy consisting of cisplatin, vincristine, and peplomycin. Overall response rate was over 70% including complete disappearance of tumors in one patient. Peplomycin was given by continuous i.v. or s.c. infusion using a micro-infusion pump. All the patients experienced some degree of nausea, vomiting, and hair loss. Phlebitis and induration of injection sites with subsequent local pigmentation were frequently encountered. Nausea and vomiting were caused mainly by cisplatin, but more than 60% of the patients experienced transient increase of anorexia or nausea in the period of peplomycin administration. Eruption with skin excoriation or pigmentation along scratch dermatitis were seen in 5 patients. These side effects were well tolerated, and high fever which is commonly observed in one-shot therapy did not develop in any patient. Pulmonary fibrosis was also not seen. Peplomycin should be given by low-dose continuous infusion because of its low toxicity and comparable antineoplastic activity to one-shot therapy.
 ...
PMID:[Side effects of peplomycin]. 242 49

Eight patients with metastatic transitional cell carcinoma of the urinary tract were treated with the MVP-CAB regimen. All of them had bidimensionally measurable lesions. The MVP-CAB regimen consisted of cyclophosphamide 500 mg/m2, methotrexate 20 mg/m2, adriamycin 20 mg/m2, bleomycin 30 mg/body, and vincristine 1 mg/body on day 1, cis-platinum 50 mg/m2 on day 2, and prednisolone 20 mg/body on days 1-3, given every 3-4 weeks. A partial response was seen in five patients, minor response in one patient and no change in two patients. The response rate was 63% (5/8). The main toxic effect of the MVP-CAB regimen was leucopenia. In 75% of the patients there was a decrease in white blood cell count by not more than 2,000/mm3, but no severe complication was noted. In addition, mild nausea, vomiting, mild anorexia, alopecia and fever were found. However, these symptoms were transient. One patient died of pulmonary fibrosis induced by bleomycin after 3 cycles.
 ...
PMID:[A study of the use of methotrexate, vincristine, cis-platinum, cyclophosphamide, adriamycin, bleomycin (MVP-CAB) in metastatic transitional cell carcinoma]. 244 83

The VPM-CisA (vincristine (VCR), peplomycin (PLM), methotrexate (MTX), cisplatin (CDDP) and doxorubicin (ADM), regimen was used to treat 33 patients with urothelial tract tumors. Twenty-two patients had bi-dimensionally measurable disease parameters and 11 patients with locally advanced tumors were given postoperative adjuvant chemotherapy. The protocol consisted of 0.6 mg/m2 VCR on days 1 and 3, 3 mg/m2 PLM on days 1 to 4, 3 mg/m2 MTX on days 2 and 4, 35 mg/m2 CDDP on day 4, and 20 mg/m2 ADM on day 5. These doses were adjusted for each case: the above mentioned dose x [(80/(40+Age]2 +[(Karnofsky's performance status/100)2]. Of these patients, 28 (86 percent) were treated adequately, including 8 (36 per cent) who achieved a complete (2) or partial (6) remission. The mean duration of survival was 65.2 weeks for complete and partial responders, and 48.8 weeks for non-responders, which was not a statistically significant difference. Of 11, who were given post-operative adjuvant chemotherapy (mean observation period: 83.5 weeks) 9 were alive without evidence of disease, 1 had a recurrence 8 months after first chemotherapy, 1 died due to pulmonary and liver metastasis 2 years after the chemotherapy. Toxicity included mild myelosupression, moderate anorexia, vomiting, and severe gastric ulcer, pulmonary fibrosis.
 ...
PMID:[Sequential combination chemotherapy consisting of vincristine, peplomycin, methotrexate, cis-diamminedichloroplatinum (II) and adriamycin in urothelial cancer]. 247 48

Seventeen patients with malignant lymphoma were entered into a phase II study of peplomycin (PEP) to determine the efficacy of the drug. There were 8 males and 9 females with a median age of 64 yrs (range 3-74 yrs) and a median PS 3 (range 2-4). Three of these were children. At first PEP was given intermittently and intramuscularly (8 cases) at a dose of 10 mg every one (3 cases) or two (5 cases) weeks, and then intravenously by 22-hr continuous infusion (9 cases) at a dose of 5 mg per day for 5 days. Mean cumulative dose was 78 mg. Objective responses were obtained in 6 patient (35%). CR lasting 4 weeks was obtained in one patient with diffuse mixed-type lymphoma. Five patients, one with diffuse medium-sized cell type and 3 with diffuse large cell type, had PR, lasting 6, 7, 7, 9, and 50+ weeks, respectively. Pulmonary fibrosis was found in two patients on autopsy and interstitial pneumonia in two patients clinically. Temporary high fever occurred in 7 patients, stomatitis in 3 patients and anorexia in 3 patients.
 ...
PMID:[Phase II trial of peplomycin in non-Hodgkin's lymphoma]. 258 13


1 2 Next >>