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)

Two children, aged 3 months and 4 years, respectively, were treated with ten weeks of amphotericin B for culture proved pulmonary blastomycosis. Organisms were easily demonstrated in nasopharyngeal or sputum specimens on admission. Although organisms were present until the 12th and 19th days of therapy, respectively, they were viable through only the seventh and 12th days of therapy. Both patients had thrombophlebitis, anemia, neutropenia, hypokalemia, fever, and vomiting develop during therapy. The less toxic drug hydroxystilbamidine isethionate, given for only 17 to 30 days, has been used successfully in at least six previously reported cases. Long courses of amphotericin B therapy may not be necessary for the treatment of pulmonary blastomycosis in selected children.
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PMID:Pulmonary blastomycosis in children. Amphotericin B therapy and a review. 58 93

The infectious complications associated with implantation of 1,088 Hickman catheters (HCs) in 992 patients reported in 18 published series are presented (including data on 129 previously unreported HCs from our own institution). HCs allow reliable long-term venous access (mean, 92.4 days) with low complication and infection rates (0.30 and 0.14 cases per 100 catheter days, respectively). Exit site infections were the most common form of infection encountered (45.5%), followed by septicemia alone (30.8%), tunnel infections (20.3%), and septic thrombophlebitis (3.5%). Staphylococcus epidermidis (54.1%) and S. aureus (20.0%) were the most common pathogens responsible for catheter infections. HC infections were associated with a low mortality rate (maximum rate of 0.5%). Risk factor analysis of 129 HCs demonstrated that catheter thrombosis was the major risk factor associated with development of catheter infection. Presence of fever, distant infection, neutropenia or antibiotic administration on the day of catheter insertion was not significantly associated with HC infection in this series (although there was a trend suggesting an increased risk of infection of HCs inserted during febrile episodes). Based on observations at our institution and from a review of the literature, tentative recommendations for management of the various types of HC infections are outlined.
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PMID:Hickman catheter infections in patients with malignancies. 637 3

We have developed a regimen incorporating multiple cycles of high-dose carboplatin and fixed-dose paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with granulocyte colony-stimulating factor and peripheral blood stem cell support given every 21 days for up to four cycles. Our phase I study of this regimen has treated 26 patients with good performance status and histologically documented unresectable or metastatic carcinoma, sarcoma, or melanoma, 21 of whom received all planned courses every 21 days. Paclitaxel 250 mg/m2 was infused over 24 hours, followed by a 1-hour carboplatin infusion, with doses escalated between area under the concentration-time curve (AUC) targets of 8 and 20. Considering the carboplatin doses administered (two to three times those generally achieved with growth factor support), toxicity has been relatively modest. The median duration of grade 4 neutropenia and thrombocytopenia was not significantly different between the AUCs of 8 and 18, which proved to be the maximum tolerated carboplatin dose. Twelve courses were associated with hospitalization for neutropenic fever or catheter-related thrombophlebitis. One treatment-related death occurred, and severe toxicity caused withdrawal of two patients treated at the AUC of 20. Peripheral neuropathy was the most common serious nonhematologic complication. Pharmacokinetic analysis showed significantly lower measured versus predicted AUC values. Among 25 evaluable patients, preliminary results show one complete response (ovarian cancer) and 11 partial responses, including four in patients with non-small cell lung cancer. Additional issues to be addressed include the effect of a shorter (or longer) paclitaxel infusion on the carboplatin AUC (and the incidence of toxicity) and whether the discrepancy between actual and predicted AUCs (greater in our study than reported elsewhere) is due to the variability of creatinine clearance-determined glomerular filtration rate or to altered carboplatin pharmacokinetics when a short high-dose infusion follows paclitaxel. Additional patients are being accrued at the AUC of 18.
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PMID:A clinical and pharmacokinetic study of high-dose carboplatin, paclitaxel, granulocyte colony-stimulating factor, and peripheral blood stem cells in patients with unresectable or metastatic cancer. 748 67

Retrospective analysis of detailed patient and tumour factors associated with a complete response to combination inductive chemotherapy with CDDP-5FU (96 or 120 hour continuous infusion) was performed using data from 147 patients with a previously untreated squamous cell carcinoma of the oral cavity, oropharynx or pharyngo-larynx following completion of two (29 patients) or three (118 patients) cycles. Adverse reactions to chemotherapy were documented for all 164 patients included in the study. Eight drug-related deaths occurred due to: acute myocardial infarction (five patients), peptic ulcer disease (two patients) and severe neutropenia with sepsis (one patient). Severe non-lethal complications included marrow depletion (14 patients), peptic ulcer (two patients), thrombophlebitis (seven patients), angina pectoris (two patients), stroke (one patient), pulmonary oedema (one patient) and convulsions (one patient). Six patients refused further treatment because of untoward side effects and tumoral progression was observed in three cases. Separate response rates for the primary site and nodes were determined and analysis of respective predictive factors of response was performed. Complete response was obtained in 31 per cent at the primary site versus 18 per cent for the nodes (p < 0.05). The combined (primary site + nodes) overall complete response rate was 22 per cent. Among 11 factors studied (age, sex, performance status, primary site, tumour differentiation, initial resectability, 5FU dosage per cycle, number of cycles, T, N and TN stages), only performance status, N stage, resectability and number of cycles were associated with a combined complete response. Multivariate analysis showed performance status, N stage, TN stage and resectability to be significant predictive factors of a combined complete response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Predictive factors of a complete response to and adverse effects of a CDDP-5FU combination as primary therapy for head and neck squamous carcinomas. 826 92

While classifications into generations according to antimicrobial activity has helped clinicians incorporate the increasing number of cephalosporins into their pharmacological repertoire, adverse effects among the different agents fail to follow similar categories. In general, cephalosporins are fairly well tolerated antibiotics, and toxicity has been limited to specific agents. Subtle differences in chemical structure and pharmacokinetics can influence the potential for adverse effects. The route of administration may result in minor adverse reactions, including thrombophlebitis and pain. The most common adverse effects of cephalosporins are allergic reactions, occurring in 0.9 to 3.2% of patients. Cephalosporins have very rarely been associated with haematological toxicity (less than 1% of patients), but specific agents have been associated with neutropenia, hypoprothrombinaemia, haemolytic anaemia, and problems with platelet production and function. Other reactions include localised gastrointestinal disturbances, hepatotoxicity (e.g. biliary sludging), nephrotoxicity and mild central nervous system effects. The cephalosporins are generally well tolerated in the paediatric population. Very few interactions have been observed between cephalosporins and other drugs, largely because cephalosporins do not affect the microsomal P450 hepatic enzyme system. While cephalosporins are considered to be relatively 'safe' drugs, the introduction of newer members warrants continued careful observation for reporting of adverse drug reactions.
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PMID:Adverse effects of newer cephalosporins. An update. 839 90

The purpose of this study was to examine coagulase-negative staphylococcal infections in bone marrow transplantation (BMT) patients with central vein catheters by investigating incidence, clinical relevance, risk factors, methicillin resistance, clinical impact of initial empiric antimicrobial therapy without vancomycin, and management of documented catheter-related infections. A 5-year prospective study was conducted with daily evaluation of 242 BMT patients during hospitalization, including clinical assessment and blood culture via the Hickman/Broviac catheter. If fever or infected appearance occurred, peripheral blood cultures or exit site cultures, respectively, were done. Results showed a septicemia incidence of 7.0%, including in 6 patients following colonization, in 1 patient with tunnel infection, in 1 patient with thrombophlebitis, in 1 patient with exit site infection, and in 8 patients with septicemia of unknown origin. Total colonization incidence was 7%, with colonization only in 11 patients who had 16 episodes; incidence of exit site infection was 3.7%. Age > or = 18 years was the only identified risk factor for developing staphylococcal infection (P = 0.03). Despite a methicillin resistance rate of 45% and omission of vancomycin from the routine initial empiric antimicrobial regimen, the clinical course of coagulase-negative staphylococcal infections was relatively benign. A single patient, who experienced marrow rejection, died on day +31 with septicemia and only one patient experienced microbiological failure with recurrent colonization. Bacteria grown in both aerobic and anaerobic bottles were more likely true bacteremia than contaminant (P = 0.03). We conclude that the hazard of coagulase-negative staphylococcal infection does not mandate inclusion of a glycopeptide in the initial empiric antimicrobial regimen in BMT patients, even during febrile neutropenia. Hickman/Broviac-related staphylococcal infections, except for tunnel infection or thrombophlebitis, can usually be treated successfully without removing the catheter.
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PMID:Nosocomial coagulase-negative staphylococcal infections in bone marrow transplantation recipients with central vein catheter. A 5-year prospective study. 861 Mar 56

Pamidronate (APD) is a potent inhibitor of bone resorption that is useful in the management of patients with osteolytic bone metastases from breast cancer or multiple myeloma, tumour-induced hypercalcaemia or Paget's disease of bone. After intravenous administration, the drug is extensively taken up in bone, where it binds with hydroxyapatite crystals in the bone matrix. Matrix-bound pamidronate inhibits osteoclast activity by a variety of mechanisms, the most important of which appears to be prevention of the attachment of osteoclast precursor cells to bone. In patients with osteolytic bone metastases associated with either breast cancer or multiple myeloma, administration of pamidronate together with systemic antitumour therapy reduces and delays skeletal events, including pathological fracture, hypercalcaemia and the requirement for radiation treatment or surgery to bone. Pamidronate generally improves pain control. Quality-of-life and performance status scores in pamidronate recipients were generally as good as, or better than, those in patients who did not receive the drug. Overall survival does not appear to be affected by pamidronate therapy. Tumour-induced hypercalcaemia also responds well to pamidronate therapy: 70 to 100% of patients achieve normocalcaemia, generally 3 to 5 days after treatment. Response durations vary, but are commonly 3 weeks or longer, In comparative studies, pamidronate produced higher rates of normocalcaemia and longer normocalcaemic durations than other available osteoclast inhibitors, including intravenous etidronate, clodronate and plicamycin (mithramycin). In most patients with Paget's disease of bone, intravenous pamidronate reduces bone pain and produces biochemical response. Serum alkaline phosphatase levels generally fall 50 to 70% from baseline 3 to 4 months after pamidronate treatment. Biochemical response may be prolonged. Pamidronate is well tolerated by most patients. Transient febrile reactions, sometimes accompanied by myalgias and lymphopenia, occur commonly after the first infusion of pamidronate. Other reported adverse events include transient neutropenia, mild thrombophlebitis, asymptomatic hypocalcaemia and, rarely, ocular complications (uveitis and scleritis). Pamidronate should be considered for routine use together with systemic hormonal or cytotoxic therapy in patients with breast cancer or multiple myeloma and osteolytic metastases. At present, pamidronate is the drug of choice for first-line use in the management of patients with tumour-induced hypercalcaemia. It is an effective treatment for Paget's disease and is the treatment of choice where oral bisphosphonates are not an option.
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PMID:Pamidronate. A review of its use in the management of osteolytic bone metastases, tumour-induced hypercalcaemia and Paget's disease of bone. 950 93

Doxorubicin and ifosfamide are the two most active agents in the treatment of soft-tissue sarcomas. Patients whose tumors have failed these two drugs have very limited systemic therapy options. It is, therefore, important to identify newer drugs with activity against this disease. CI-980 is a synthetic mitotic inhibitor that binds to tubulin at the colchicine binding site and inhibits the polymerization of tubulin and blocks cell cycle progression in mitosis. Given its broad spectrum activity against several solid tumor models in vivo, we decided to perform a phase 2 study of this drug in previously treated soft-tissue sarcomas. A total of 18 eligible and evaluable patients were entered in the first stage of the trial. The median age was 53 yrs (range, 17-72). No objective responses have been noted. Six patients had stable disease after a median of 3.5 cycles of chemotherapy while 12 others had progressive disease. A total of 48 cycles were administered, 42 of which were administered at dose level 0 (4.5 mg/m2/d x 3). The median AGC nadir was 1.2/microl(0.1 -4.7) on day 10 and the median platelet nadir was 150,000/microl (31,000-338,000). Twenty cycles were complicated with grade 3-4 neutropenia and two cycles were complicated with FUO. There were no CNS toxicities. One patient had a grade 1 thrombophlebitis in 2 cycles and one other patient had a grade 4 thrombophlebitis in one cycle. In conclusion, CI-980 was well tolerated at this dose and schedule but inactive in soft-tissue sarcomas.
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PMID:Phase II study of CI-980 (NSC 635370) in patients with previously treated advanced soft-tissue sarcomas. 974 May 49

Infectious complications are one of the most important causes of morbi-mortality in oncology patients. Neutropenia is the most important risk factor for developing infection in the oncology patient. Although the highest mortalities continue to be associated with infections due to enterobacterias and Pseudomonas aeruginosa, the frequency of infections due to gram-positives is higher. Deep fungic infections, like those produced by resistant or infrequent bacteria usually occur in late periods of protracted neutropenias. In recent years different studies have shown the efficiency of antibiotic patterns in monotherapy in the treatment of the neutropenic patient with fever. Cellular immunosuppression is not usually as relevant as neutropenia in oncology patients without complications. However, the use of high doses of steroids in some patients and above all the use of purine analogues and monoclonal antibodies has changed this situation in recent years. With these patients it is recommendable to use prophylactic measures directed against Cytomegalovirus, Varicela-zoster virus, P.carinii (or jirovecii) and fungic infections. Bacteraemia associated with endovascular catheterisation is the principal cause of bacteraemia in these patients, above all due to gram-positive micro-organisms. In case of infection, it is always advisable to remove the catheter. However, under certain circumstances, where the placing of a new catheter might be risky given the patient's characteristics and where there are agents of low virulence (e.g. coagulase-negative staphylococcus), a conservative treatment can be tried. A persistence of fever or bacteraemia following removal of the catheter should lead to suspicion of the presence of a deep infection, fundamentally suppurated thrombophlebitis or endocarditis. An adequate understanding of the infectious complications in these patients and their correct treatment and prevention are decisive in reducing the high mortality associated with these clinical manifestations.
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PMID:[Principal infections in the oncology patient: practical treatment]. 1572 2

The still present problem of choice of a treatment method in chronic sinusitis was introduced in this study. The heterogenous etiology of chronic sinusitis and its treatment consequences were presented. The main current options in the treatment of chronic sinusitis were shown. The functional endoscopic sinus surgery was emphasized as the most important. The different courses of antibiotic therapy: nebulization, oral and intravenous were introduced as a method of choice in exacerbation of chronic process. The intravenous antibiotics were analyzed in details and it was especially based on the bacterial biofilms theory according to the newest literature. The obtaining results were good enough. They were better in children than in adults and in patients with shorter history of sinusitis, however they were not free from complications. Thrombophlebitis, allergic reaction, neutropenia were indicated as most frequent complications that caused the break in the therapy. In the conclusion the intravenous antibiotic therapy was estimated as a useful procedure, but not highly recommended due to a possibility of complications.
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PMID:[Intravenous antibiotics for rhinosinusitis]. 1635 20


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