RESUMO
Glucagonoma syndrome is an extremely rare pancreatic neuroendocrine tumour often associated with necrolytic migratory erythema. While glucagonomas are neoplasms of adulthood, we report the first case in a paediatric patient. We present the case of a 15-year-old girl with a 4-year history of a rash, consistent with necrolytic migratory erythema, found to have a localized glucagonoma. Immediately following resection of the tumour, there was complete resolution of her rash and systemic symptoms. Detection of the cutaneous rash of necrolytic migratory erythema can aid in the early diagnosis of a glucagonoma, as well as the prevention of metastatic disease. To our knowledge, this is the first reported paediatric patient with glucagonoma syndrome.
RESUMO
Objective An open-label, three-period pharmacokinetic study was conducted to investigate the drug interaction potential between fosamprenavir (FPV) and tenofovir disoproxil fumarate (TDF). Methods Thirty-six healthy subjects received TDF 300 mg once daily (qd) for 7 days (period 1), and then were randomized to 14 days of either FPV 1400 mg twice daily (bid) or FPV/ritonavir (RTV) 700/100 mg bid alone or with TDF (period 2). Subjects continued their randomized dose of FPV for 14 more days, adding or removing TDF based upon its receipt in period 2 (period 3). Twenty-four-hour pharmacokinetic sampling was carried out on day 7 of period 1 and on day 14 of periods 2 and 3. Steady-state plasma amprenavir (APV) and tenofovir (TFV) pharmacokinetics were assessed by noncompartmental analysis and parameter values observed with each regimen were compared using geometric mean ratios with 90% confidence intervals. Results After TDF coadministration, APV geometric mean minimum concentration (C(min)), maximum concentration (C(max)), and area under the plasma concentration-time curve (AUC) increased by 31, 3 and 7% above values observed with unboosted FPV alone; they also increased by 31, 4 and 16% above values observed with FPV/RTV alone. TFV C(min), C(max) and AUC decreased by 12, 25 and 15% after FPV coadministration and by 9, 18 and 7% after FPV/RTV coadministration. No significant changes in RTV pharmacokinetics were observed. No differences were noted in adverse events among dosing periods. Conclusions In this evaluation of the interaction between FPV and TDF, increases in APV exposures and modest decreases in TFV exposures were observed. These were unlikely to be clinically significant.
Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/farmacocinética , Carbamatos/farmacocinética , Organofosfatos/farmacocinética , Organofosfonatos/administração & dosagem , Organofosfonatos/farmacocinética , Ritonavir/farmacocinética , Sulfonamidas/farmacocinética , Adenina/administração & dosagem , Adenina/efeitos adversos , Adenina/farmacocinética , Adenina/farmacologia , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Carbamatos/administração & dosagem , Carbamatos/efeitos adversos , Estudos Cross-Over , Esquema de Medicação , Toxidermias/epidemiologia , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Furanos , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Organofosfatos/administração & dosagem , Organofosfatos/efeitos adversos , Organofosfonatos/efeitos adversos , Organofosfonatos/farmacologia , Pró-Fármacos/administração & dosagem , Ritonavir/administração & dosagem , Ritonavir/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Tenofovir , Adulto JovemRESUMO
OBJECTIVES: Use of proton pump inhibitors in HIV-infected patients is common. The purpose of this study was to determine the steady-state pharmacokinetics of once-daily (qd) fosamprenavir/ritonavir (FPV/r) and atazanavir/ritonavir (ATV/r) alone and in combination with 20 mg qd omeprazole (OMP) in healthy volunteers. DESIGN AND METHODS: A prospective, open-label, single-site, two-period, crossover pharmacokinetic study was carried out in healthy volunteers. Subjects received either qd FPV/r 1400 mg/200 mg or ATV/r 300 mg/100 mg in the morning for 14 days and then 20 mg OMP in the evening for an additional 7 days. The pharmacokinetics were assessed over 24 h on days 14 and 21. Following a 2-week washout, subjects repeated the process with the other regimen. Trough protease inhibitor (PI) concentrations were taken on day 16 of each period to assess the impact of a single dose of OMP on ATV and amprenavir (APV) concentrations. Plasma ATV and APV pharmacokinetic parameters were assessed by noncompartmental analysis; geometric mean ratios (GMRs; PI+OMP/PI; 90% confidence interval) were calculated between days 14 and 21. RESULTS: Nineteen healthy, non-HIV-infected volunteers were evaluated. OMP reduced ATV exposure [area under the concentration curve at 0-24 h (AUC0-24 h)] and the minimum drug concentration (Cmin) by 27% each. In contrast, APV exposure and Cmin were decreased by 4 and 2%, respectively. Four subjects (21%) experienced greater than 50% declines in both ATV AUC0-24 h and Cmin after the addition of OMP; this was not observed in any subject following receipt of FPV/r. No alterations in APV or ATV trough concentrations were observed following a single dose of OMP. CONCLUSIONS: The addition of 20 mg OMP administered in the evening has minimal effect on APV pharmacokinetics. In contrast, ATV pharmacokinetics were altered; a number of ATV-treated subjects experienced pronounced declines in exposures upon the addition of 20 mg OMP administered in the evening, whereas others experienced little to no change.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores da Bomba de Prótons/administração & dosagem , Adulto , Fármacos Anti-HIV/farmacocinética , Área Sob a Curva , Sulfato de Atazanavir , Carbamatos/administração & dosagem , Carbamatos/farmacocinética , Quimioterapia Combinada , Feminino , Furanos , Humanos , Masculino , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacocinética , Omeprazol/administração & dosagem , Omeprazol/farmacocinética , Organofosfatos/administração & dosagem , Organofosfatos/farmacocinética , Inibidores da Bomba de Prótons/farmacocinética , Piridinas/administração & dosagem , Piridinas/farmacocinética , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacocinéticaAssuntos
Monitoramento de Medicamentos/normas , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/sangue , Monitoramento de Medicamentos/métodos , Inibidores da Protease de HIV/administração & dosagem , Humanos , Reprodutibilidade dos Testes , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/sangueRESUMO
Procalcitonin (PCT) is a highly sensitive and specific marker of systemic bacterial infection and sepsis. In contrast to its diagnostic significance, the cellular sources of plasma procalcitonin remain to be clarified. Two forms of PCT mRNAs originate from calcitonin/calcitonin gene-related peptide gene (CALC-I gene) along with mRNA for calcitonin gene-related peptide-I (CGRP-I). Reverse transcription polymerase chain reaction with newly designed primers detecting different PCT mRNAs and CGRP-I mRNA was used to identify tissues that might contribute to PCT production. Our study indicates that a variety of human tissues (13 of the 16 analyzed overall) express PCT-I, PCT-II, and/or CGRP-I mRNAs, with the highest levels detected for liver, testis, lung, prostate, kidney, and small intestine. Various tissues differ in the proportions of PCT-I, PCT-II, and CGRP-I mRNA expression levels. Thus we demonstrate the complexity of tissue-specific regulation of CALC-I gene expression and suppose a variety of tissues as a potential source of CALC-I-encoded peptides.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/genética , Calcitonina/genética , Precursores de Proteínas/genética , RNA Mensageiro/genética , Calcitonina/sangue , Peptídeo Relacionado com Gene de Calcitonina/sangue , Primers do DNA , DNA Complementar , Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/fisiologia , Especificidade de Órgãos , Reação em Cadeia da Polimerase , Precursores de Proteínas/sangue , Mapeamento por Restrição , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica , Fator de Necrose Tumoral alfa/farmacologiaAssuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacocinética , HIV-1 , Infecções por HIV/metabolismo , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , HIV-1/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Resultado do TratamentoAssuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Padrões de Prática Médica , Complicações Infecciosas na Gravidez/tratamento farmacológico , Zidovudina/uso terapêutico , Feminino , Humanos , Recém-Nascido , Gravidez , Segundo Trimestre da Gravidez , Estados UnidosRESUMO
Ceftriaxone, although less active than standard antistaphylococcal agents, is potentially useful in the treatment of osteomyelitis. Thirty-one patients with osteomyelitis due to Staphylococcus aureus were identified, 22 of whom were treated with ceftriaxone and 9 with other agents. Of those patients treated with ceftriaxone, 17 were cured; all treatment failures were associated with chronic osteomyelitis and continued presence of necrotic bone or infected hardware. It is concluded that ceftriaxone is effective in the ambulatory treatment of S. aureus osteomyelitis.
Assuntos
Ceftriaxona/uso terapêutico , Cefalosporinas/uso terapêutico , Osteomielite/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Adulto , Idoso , Assistência Ambulatorial , Humanos , Pessoa de Meia-Idade , Osteomielite/microbiologia , Estudos Retrospectivos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate whether an antimicrobial review system is associated with a reduction in antimicrobial-associated adverse events. DESIGN: All antimicrobial medication orders for patients hospitalized over a two-year period were evaluated. High-level interventions intended to prevent adverse antimicrobial events were collated. Based on literature estimates of adverse antimicrobial events, potential reduction of high-level adverse antimicrobial events was estimated. SETTING: Department of Clinical Pharmacy and Division of Infectious Diseases at a tertiary care teaching hospital. RESULTS: A total of 452 interventions were classified as "high-level." The incidence of preventable adverse antimicrobial events requiring intervention was 16 per 1000 antimicrobial orders. The incidence of high-level errors necessitating intervention was 4.4 per 1000 antimicrobial orders. An estimated 125 to 198 high-level adverse events were avoided. CONCLUSION: An antimicrobial review program has the potential to reduce significant adverse events in hospitalized patients.
Assuntos
Antibacterianos/uso terapêutico , Monitoramento de Medicamentos , Revisão de Uso de Medicamentos , Serviço de Farmácia Hospitalar , Antibacterianos/efeitos adversos , Georgia , HumanosRESUMO
The association of amphotericin B with nephrotoxicity is well known, but risk factors for this complication are not well characterized. One hundred and seventy-eight patients who received > 3 days of intravenous amphotericin B and a minimal total cumulative dose > 100 mg were reviewed retrospectively. The mean age, average cumulative dose of amphotericin B and duration of therapy were 46 +/- 22 years, 536 +/- 547 mg and 16.6 +/- 8.2 days, respectively. Eighty-six percent of patients received amphotericin B for empirical therapy of febrile neutropenia. Various definitions of nephrotoxicity were used; these were as follows (the incidence of nephrotoxicity as determined by the given definition is given in parentheses): definition 1, a change in creatinine of > 46 mumol/L over baseline (50%); definition 2, a doubling of creatinine over baseline (49%); definition 3, a change in creatinine of > 92 mumol/L (29%); definition 4, a doubling and/or a change in creatinine of > 92 mumol/L (49%); definition 5, an increase in creatinine to > 230 mumol/L (8%). Multivariate analysis showed that nephrotoxicity was associated with a greater cumulative dose of amphotericin B and receipt of concomitant nephrotoxic drugs for all definitions (P < 0.05). In those patients who experienced severe nephrotoxicity (creatinine increased to > 230 mumol/L), cyclosporin therapy was the most significant risk factor (odds ratio 18.8, P = 0.022). Haemodialysis was necessary in one patient, but multiple concomitant risk factors for renal dysfunction were present. No patient experienced irreversible nephrotoxicity. These findings allow for stratification of patients at risk for amphotericin B-induced nephrotoxicity and rational use of alternative agents.
Assuntos
Anfotericina B/efeitos adversos , Antibacterianos/efeitos adversos , Insuficiência Renal/induzido quimicamente , Adulto , Idoso , Creatinina/metabolismo , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Insuficiência Renal/epidemiologia , Fatores de RiscoAssuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Anfotericina B/administração & dosagem , Histoplasmose/tratamento farmacológico , Hipotermia Induzida , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/fisiopatologia , Adulto , Histoplasma/isolamento & purificação , Histoplasmose/microbiologia , Histoplasmose/fisiopatologia , Humanos , Injeções Intravenosas , MasculinoRESUMO
OBJECTIVE: To discuss the antiviral activity, pharmacokinetics, clinical efficacy, and adverse effect profile of famciclovir, the oral prodrug of penciclovir (PCV), and to compare these features of famciclovir with those of acyclovir in the treatment of herpesvirus infections. DATA SOURCES: Literature was identified by MEDLINE search, and abstracts from recent meetings were included where relevant. Data provided by the manufacturer were also used. STUDY SELECTION: Data regarding antiviral activity were included if accepted and widely used methods were followed. Clinical trials in which a comparison with acyclovir or placebo was performed were given the highest priority. DATA SYNTHESIS: In comparison with acyclovir, PCV has similar antiviral activity although its mode of action is not identical. When administered orally, faMciclovir, the oral prodrug of PCV, is better absorbed than acyclovir, yielding an absolute bioavailability of PCV of 77%. The predominant route of PCV elimination is via the kidneys, with a half-life of approximately 2.5 hours. In trials comparing famciclovir with acyclovir for the treatment of herpes zoster in immunocompetent individuals, comparable results were obtained. Famciclovir is also effective as therapy for recurrent episodes of genital herpes and may prove useful for chronic suppressive therapy. The most common adverse effects of famciclovir are headache and gastrointestinal upset. The dosage of famciclovir for herpes zoster in immunocompetent individuals is 500 mg po tid for 7 days; for recurrent genital herpes a dosage of 125 mg po bid for 5 days is recommended. Dosage adjustments are necessary in patients with renal dysfunction. CONCLUSIONS: Given its comparable efficacy, similar adverse effect profile, and less frequent dosing schedule than acyclovir, famciclovir represents a viable alternative for treatment of herpes zoster and for episodic therapy of recurrent genital herpes in immunocompetent adults. Specific recommendations for other uses of famciclovir await the publication of recent clinical trial results.
Assuntos
2-Aminopurina/análogos & derivados , Antivirais/farmacologia , Antivirais/farmacocinética , Infecções por Herpesviridae/tratamento farmacológico , Pró-Fármacos/farmacologia , Pró-Fármacos/farmacocinética , 2-Aminopurina/farmacocinética , 2-Aminopurina/farmacologia , Interações Medicamentosas , Famciclovir , Infecções por Herpesviridae/metabolismo , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoAssuntos
Antibacterianos/administração & dosagem , Enterococcus faecium/efeitos dos fármacos , Vancomicina/administração & dosagem , Administração Oral , Antibacterianos/farmacologia , Resistência Microbiana a Medicamentos , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Injeções Intravenosas , Vancomicina/farmacologiaAssuntos
Tomada de Decisões , Atenção à Saúde/normas , Ética Médica , Alocação de Recursos , Valores Sociais , Atitude , Contratos , Governo Federal , Humanos , Paternalismo , Autonomia Pessoal , Papel do Médico , Resolução de Problemas , Papel (figurativo) , Confiança , Estados Unidos , Suspensão de TratamentoRESUMO
The first results in routine syphilis serology with the new solid-phase hemadsorption assay (SPHA) are presented. Sera (63019) were screened by the VDRL test and by the automated hemagglutination assay with Treponema pallidum antigen (AMHA-TP). Samples reactive to one or both of these tests were further examined by the FTA-ABS test, the IgM-FTA-ABS test, the 19S IgM-FTA-ABS test (IgM-FTA-ABS test performed with the 19S fraction of the serum after gelfiltration) and the IgM-SPHA test. IgM-SPHA reactive sera derived from patients who were in the early stage or in the phase of latency (of undefinable duration), further from patients with active neurosyphilis and from 26 patients after reinfection. Erroneous results in the IgM-FTA-ABS test caused by a competitive inhibition of IgM by IgG can be eliminated by the IgM-SPHA method. The agreement between 19S IgM-FTA-ABS test and IgM-SPHA test is above 96.3%. As compared to the fluorescence test, the IgM-SPHA test is simpler to perform and can be easily automated.