Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amphethinile is a new spindle poison with a novel structure that has shown activity in the L1210, ADJ/PC6 and Walker carcinoma rodent tumours. In addition the agent appeared to have an improved therapeutic ratio compared to existing spindle poisons and is well absorbed when administered orally. The starting dose for the phase I study was 40 mg m-2 (1/10th mouse LD10) and further patients were studied at 200, 400, 800 and 1200 mg m-2, dose escalation being based on pharmacological monitoring. Significant toxic effects were seen only at 800 and 1200 mg m-2. At these doses patients experienced nausea and vomiting, light headedness during the infusion and varying degrees of lethargy following therapy. Two of six patients at 800 mg m-2 developed severe pain in the tumour bearing area 1-2 h after treatment and one experienced colicky abdominal pain. At 1200 mg m-2 two patients died within 48 h of treatment from what appeared to be vascular causes. Following these episodes the trial was discontinued. Neutropenia and alopecia occurred in two patients, one at 800 and one at 1200 mg m-2. These patients achieved the highest drug exposure in terms of area under the concentration x time curve. It was not possible to achieve an AUC consistently high enough to produce cytotoxic effects due to the occurrence of dose limiting toxicities thus amphethinile cannot at present be recommended for phase II testing by the i.v. route. The dose escalation scheme based on pharmacological monitoring resulted in a considerable saving in the duration of the trial. Further evaluation of this methodology is recommended.
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PMID:A phase I and pharmacokinetic study of amphethinile. 340 47

The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on radiation-induced neutropenia and on growth of transplanted tumors treated by irradiation was investigated using tumor-bearing rats as a model for radiation therapy. In a preliminary study using normal rats, neutropenia induced by upper hemi-body irradiation at 3 Gy/day 5 times a week for 3 weeks was prevented by consecutive subcutaneous injections of rhG-CSF at 100 micrograms/kg/day. Rats bearing Walker-256, a mammary tumor, were scheduled to receive upper hemibody irradiation at 3 Gy/day for 15 times in 3 weeks if white blood cell (WBC) counts were maintained above 3,000/microliters. In control tumor-bearing rats not receiving rhG-CSF, irradiation was often withheld because of the decrease in WBC counts below 3,000/microliters. In contrast, a decrease in WBC counts below 3,000/microliters was rarely found in tumor-bearing rats injected daily with rhG-CSF. The average number of radiation treatments in control rats and rats treated with rhG-CSF was about 8 and 14, respectively, out of the scheduled 15 treatments in 3 weeks. Treatment with rhG-CSF made it possible to complete the radiation therapy regimen and thus inhibit the growth of the transplanted tumor more effectively. These results suggest that rhG-CSF may be useful to ensure radiation therapy on schedule in cancer patients.
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PMID:Effect of recombinant human granulocyte colony-stimulating factor on efficacy of radiation therapy in tumor-bearing rats. 751 51

A 1-year-old male Foxhound/Walker Hound mix was presented to the small animal internal medicine service at Louisiana State University School of Veterinary Medicine with a 6-week history of progressive, multifocal, ulcerative and draining, well-circumscribed lesions in a generalized distribution. Prior to referral, a presumptive diagnosis was made of sterile pyogranulomatous disease; immunosuppressive therapy was instituted but resulted in clinical deterioration. At presentation, the dog had marked neutropenia (1100 neutrophils/microL), and a mild toxic left shift (400 bands/microL). Cytologic findings in the exudates from a draining skin lesion included high numbers of markedly degenerate neutrophils (about 95% of nucleated cells) as well as low numbers of macrophages, small mature lymphocytes, and eosinophils. Low numbers of intracellular (within neutrophils and macrophages) and extracellular, pleomorphic, cigar-to-ovoid shaped organisms ( approximately 3x9 microm) consistent with Sporothrix were observed. Histopathologic examination of a skin biopsy showed marked, chronic, active, ulcerative, pyogranulomatous dermatitis and panniculitis, with intralesional yeast consistent with Sporothrix sp. The etiologic agent was confirmed as Sporothrix schenckii by macerated tissue fungal culture. The patient was treated with itraconazole, enrofloxacin, and clindamycin, with clinical resolution occurring over a 3-month period. This case is a rare example of the cytologic diagnosis of Sporothrix schenckii in a canine patient. Diagnosis of canine sporotrichosis is often challenging and usually requires tissue culture, as infected dogs typically harbor very few organisms. The patient's prior immunosuppressive therapy likely contributed to higher numbers of organisms in exudates from the cutaneous lesions, facilitating cytologic diagnosis.
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PMID:Cytologic diagnosis of generalized cutaneous sporotrichosis in a hunting hound. 1731 Dec 2