Clinical Usefulness of Prostate-specific Membrane Antigen-ligand Positron Emission Tomography/Computed Tomography for the Detection of Prostate Cancer Biochemical Recurrence after Primary Radiation Therapy in Patients with Prostate-specific Antigen Below the Phoenix Threshold: Systematic Review and Meta-analysis.

AIMS: After primary radiotherapy, biochemical recurrence is defined according to the Phoenix criteria as a prostate-specific antigen (PSA) value >2 ng/ml relative to the nadir. Several studies have shown that prostate-specific membrane antigen (PSMA)-ligand positron emission tomography/computed tomography (PET/CT) can help in detecting recurrence in patients with low PSA values. This study aimed to assess the detection rate and patterns of PSMA-ligand PET/CT uptake in patients with suspected biochemical recurrence after primary radiotherapy and with PSA levels below the Phoenix threshold. MATERIALS AND METHODS: The meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Articles providing data on patients with suspected prostate cancer recurrence after primary radiotherapy with a PSA value below the Phoenix threshold and who underwent PSMA-ligand PET/CT were included. Quality assessment was carried out using the Quality Assessment of Diagnostic Accuracy Studies-2 tool (QUADAS-2). RESULTS: In total, five studies were included, recruiting 909 patients (202 with PSA ≤2 ng/ml). The PSMA-ligand detection rate in the patients with ≤2 ng/ml ranged from 66 to 83%. The most frequent source of PSMA-ligand PET/CT uptake was local recurrence, followed by lymph node metastasis and bone metastasis. PSMA-ligand PET/CT uptake due to local-only recurrence was more likely in patients with PSA ≤2 ng/ml compared with PSA > 2 ng/ml: risk ratio 0.72 (95% confidence interval 0.58-0.89), P = 0.003. No significant differences were observed in the detection of PSMA-ligand uptake in other areas. Limitations include a lack of biopsy confirmation, cohort reports with small sample sizes and a potentially high risk of bias. CONCLUSION: A significant detection of PSMA-ligand-avid disease was observed in patients with PSA levels below the Phoenix threshold. There was a higher likelihood of detecting local-only uptake when the PSA value was ≤2 ng/ml. The findings suggest that a critical review of the Phoenix criteria may be warranted in the era of PSMA-ligand PET/CT and highlight the need for further prospective trials.

Crioterapia frente a high intensity focused ultrasound en el tratamiento del cáncer de próstata: resultados oncológicos y funcionales / Cryotherapy versus high-intensity focused ultrasound for treating prostate cancer: Oncological and functional results

Contexto y objetivo: El diagnóstico cada vez más precoz del cáncer de próstata obliga a buscar alternativas terapéuticas con buenos resultados oncológicos, que a su vez faciliten una buena calidad de vida a largo plazo. La presente revisión analiza los resultados de 2 terapias mínimamente invasivas en el tratamiento del cáncer localizado de próstata en cuanto a resultados oncológicos y funcionales, así como las complicaciones derivadas de los mismos. Adquisición de la evidencia: Revisión sistemática de la literatura referida al tratamiento del cáncer localizado de próstata con 2 técnicas ablativas como terapia primaria: la criocirugía o crioterapia y el high intensity focused ultrasound (HIFU). Se incluyen pacientes con procedimientos que incluían la totalidad de la glándula, con hemiablación o con terapia focal e indicados en cáncer de próstata de bajo riesgo o riesgo intermedio según criterios D'Amico. Se excluyen pacientes con cáncer de próstata de alto riesgo, o aquellos que hayan recibido cualquier tratamiento previo para el cáncer de próstata. Síntesis de la evidencia: Tras la búsqueda y exclusión de estudios que no cumplían los criterios del protocolo, se revisan un total de 14 estudios, con un total de 350 pacientes tratados mediante crioterapia, y un total de 1.107 pacientes tratados con HIFU. En todos los casos se trataron de estudios prospectivos o retrospectivos, no aleatorizados. La edad media de los pacientes fue de menos de 75 años. En global la tasa de recidiva anatomopatológica en los pacientes tratados con crioterapia oscila entre el 13,2% y el 26%, mientras que en el HIFU oscilan entre el 7,3% y el 67,9%. La continencia global mostrada fue de un 97,6-100% en el caso de la crioterapia, y un 96-100% en el HIFU a los 12 meses. Respecto a las tasas de potencia sexual la crioterapia muestra una potencia completa del 86-100% a los 12 meses en pacientes tratados con crioterapia focal, y algo menores en la hemiablación (76,9-100%) y en la terapia total (39%). El HIFU reporta tasas de potencia del 89% 52-80% y 33-78% en terapia focal, hemiablación y terapia total respectivamente. Conclusiones: Ambas técnicas presentan unos resultados funcionales equiparables, si bien los resultados oncológicos algo más pobres en el HIFU son reflejo de una curva de aprendizaje más complicada, que puede abocar su uso a centros con alto volumen de pacientes

Context and objective: The increasingly early diagnosis of prostate cancer requires a search for therapeutic alternatives with good oncological results that in turn facilitate a good long-term quality of life. This review analyses 2 minimally invasive therapies for treating localised prostate cancer in terms of oncological and functional results, as well as the complications resulting from the therapies. Acquisition of evidence: A systematic literature review was conducted of the treatment of localised prostate cancer with 2 ablative techniques as the primary therapy: cryosurgery or cryotherapy and high intensity focused ultrasound (HIFU). We included patients who underwent procedures that included the entire gland, with hemiablation or focal therapy, which were indicated for low to intermediate-risk prostate cancer according to the D’Amico criteria. We excluded patients with high-risk prostate cancer and those who underwent any prior treatment for prostate cancer. Synthesis of the evidence: After conducting the literature search and excluding the studies that did not meet the protocol criteria, we reviewed a total of 14 studies, with a total of 350 patients treated using cryotherapy and 1107 treated with HIFU. All studies were either prospective or retrospective and were not randomised. The patients' mean age was younger than 75 years. Overall, the rate of disease recurrence in the patients treated with cryotherapy varied between 13.2% and 26%, while the rate for those treated with HIFU varied between 7.3% and 67.9%. The overall demonstrated continence at 12 months was 97.6-100% for cryotherapy and 96-100% for HIFU. In terms of sexual potency rates, cryotherapy showed complete potency at 12 months for 86-100% of the patients treated with focal cryotherapy and slightly lower rates for hemiablation (76.9-100%) and total therapy (39%). HIFU showed potency rates of 89%, 52-80% and 33-78% for focal therapy, hemiablation and total therapy, respectively. Conclusions: Both techniques have comparable functional results, although the somewhat poorer oncological results for HIFU reflect a steeper learning curve, which could lead to its use in centres with high volumes of patients

Cryotherapy versus high-intensity focused ultrasound for treating prostate cancer: Oncological and functional results. / Crioterapia frente a high intensity focused ultrasound en el tratamiento del cáncer de próstata: resultados oncológicos y funcionales.

CONTEXT AND OBJECTIVE: The increasingly early diagnosis of prostate cancer requires a search for therapeutic alternatives with good oncological results that in turn facilitate a good long-term quality of life. This review analyses 2 minimally invasive therapies for treating localised prostate cancer in terms of oncological and functional results, as well as the complications resulting from the therapies. ACQUISITION OF EVIDENCE: A systematic literature review was conducted of the treatment of localised prostate cancer with 2 ablative techniques as the primary therapy: cryosurgery or cryotherapy and high intensity focused ultrasound (HIFU). We included patients who underwent procedures that included the entire gland, with hemiablation or focal therapy, which were indicated for low to intermediate-risk prostate cancer according to the D'Amico criteria. We excluded patients with high-risk prostate cancer and those who underwent any prior treatment for prostate cancer. SYNTHESIS OF THE EVIDENCE: After conducting the literature search and excluding the studies that did not meet the protocol criteria, we reviewed a total of 14 studies, with a total of 350 patients treated using cryotherapy and 1107 treated with HIFU. All studies were either prospective or retrospective and were not randomised. The patients' mean age was younger than 75 years. Overall, the rate of disease recurrence in the patients treated with cryotherapy varied between 13.2% and 26%, while the rate for those treated with HIFU varied between 7.3% and 67.9%. The overall demonstrated continence at 12 months was 97.6-100% for cryotherapy and 96-100% for HIFU. In terms of sexual potency rates, cryotherapy showed complete potency at 12 months for 86-100% of the patients treated with focal cryotherapy and slightly lower rates for hemiablation (76.9-100%) and total therapy (39%). HIFU showed potency rates of 89%, 52-80% and 33-78% for focal therapy, hemiablation and total therapy, respectively. CONCLUSIONS: Both techniques have comparable functional results, although the somewhat poorer oncological results for HIFU reflect a steeper learning curve, which could lead to its use in centres with high volumes of patients.

Influence of practitioner expertise during early pregnancy diagnosis on pregnancy loss rate: A controlled, blinded trial.

A controlled field trial was conducted to assess the potential influence of practitioner inexperience during early pregnancy diagnosis with ultrasound (PD-US) on the risk of pregnancy loss. A veterinarian with more than 10 years' experience in PD-US (Vet-A) and a veterinarian with fewer than 12 months' experience at the start of the study (Vet-B) visited the same dairy farm once a week for 33 and 26 weeks, respectively. The two veterinarians did not interact with each other at any time during the study, nor did they know that their data would later be used in this study. Using the same farm scanner, they performed PD-US at 28-34 day after breeding, together diagnosing 915 pregnancies. All cows were re-checked at 49-56 day after artificial insemination, and cows no longer pregnant were recorded as having suffered pregnancy loss. Although Vet-A and Vet-B diagnosed a similar proportion of pregnancies (58.44 ± 16% vs 56.96 ± 18%, p > .05), the rate of pregnancy loss was significantly higher among cows diagnosed by Vet-B (10.41 ± 11.2% vs 4.87 ± 9.0, p = .029). In addition, among cows diagnosed by Vet-B, the rate of pregnancy loss was significantly higher among cows diagnosed, while he had fewer than 12 months' PD-US experience (11.17 ± 12.14%) than among cows that he diagnosed later (7.14 ± 11.01%, p = .038); in fact, this latter loss rate was comparable to that among cows diagnosed by Vet-A during the same period (3.51 ± 9.83%, p = .620). These results suggest that inexperience with PD-US during the late embryonic period can increase risk of early pregnancy loss, supporting the need for proper training.

Neuroinvasive St. Louis Encephalitis Virus Infection in Solid Organ Transplant Recipients.

In summer 2015, three unrelated solid organ transplant recipients in Phoenix, Arizona, had meningoencephalitis suggestive of West Nile virus (WNV) infection. Testing was inconclusive but was later confirmed as St. Louis encephalitis (SLE). We retrospectively reviewed clinical manifestations, treatment, and outcomes of these transplant recipients. Common symptoms were fever, rigors, diarrhea, headache, and confusion. One patient died 3 days after hospitalization. Therapy for the other two patients was initiated with interferon α-2b (IFN) and intravenous IgG (IVIG; IFN plus IVIG in combination). Both patients tested positive for WNV by serologic assay, but SLE virus (SLEV) infection was later confirmed by plaque reduction neutralization test at a reference laboratory. Clinical improvement was observed within 72 h after initiation of IFN plus IVIG. SLEV has been an uncommon cause of neuroinvasive disease in the United States. Accurate, timely diagnosis is hindered because of clinical presentation similar to neuroinvasive WNV and SLE, serologic cross-reactivity, and lack of a commercially available serologic assay for SLEV. There is currently no approved therapy for flaviviral neuroinvasive disease. Anecdotal reports indicate varying success with IFN, IVIG, or IFN plus IVIG in WNV neuroinvasive disease. The same regimen might be of value for immunocompromised persons with neuroinvasive SLEV infection.

Searching for genes responsible for patulin degradation in a biocontrol yeast provides insight into the basis for resistance to this mycotoxin.

Patulin is a mycotoxin that contaminates pome fruits and derived products worldwide. Basidiomycete yeasts belonging to the subphylum Pucciniomycotina have been identified to have the ability to degrade this molecule efficiently and have been explored through different approaches to understand this degradation process. In this study, Sporobolomyces sp. strain IAM 13481 was found to be able to degrade patulin to form two different breakdown products, desoxypatulinic acid and (Z)-ascladiol. To gain insight into the genetic basis of tolerance and degradation of patulin, more than 3,000 transfer DNA (T-DNA) insertional mutants were generated in strain IAM 13481 and screened for the inability to degrade patulin using a bioassay based on the sensitivity of Escherichia coli to patulin. Thirteen mutants showing reduced growth in the presence of patulin were isolated and further characterized. Genes disrupted in patulin-sensitive mutants included homologs of Saccharomyces cerevisiae YCK2, PAC2, DAL5, and VPS8. The patulin-sensitive mutants also exhibited hypersensitivity to reactive oxygen species as well as genotoxic and cell wall-destabilizing agents, suggesting that the inactivated genes are essential for tolerating and overcoming the initial toxicity of patulin. These results support a model whereby patulin degradation occurs through a multistep process that includes an initial tolerance to patulin that utilizes processes common to other external stresses, followed by two separate pathways for degradation.

Superiority of entangled measurements over all local strategies for the estimation of product coherent states.

It is shown that the ensemble {P(alpha),|alpha|alpha;{*}}, where P(alpha) is a Gaussian distribution of finite variance and |alpha is a coherent state, can be better discriminated with an entangled measurement than with any local strategy supplemented by classical communication. Although this ensemble consists of products of quasiclassical states without any squeezing, it thus exhibits a purely quantum feature. This remarkable effect is demonstrated experimentally by implementing the optimal local strategy on coherent states of light together with a global strategy that yields a higher fidelity.

Long-term outcome of a phase II study of weekly docetaxel with a short course of estramustine and enoxaparine in hormone-resistant prostate cancer patients.

OBJECTIVE: The objective was to define the toxicity and activity of weekly docetaxel administered with a short course of estramustine and enoxaparine in patients with hormone-resistant prostate cancer (HRPC). PATIENTS AND METHODS: Twenty-four patients were treated with the next regimen: weekly docetaxel 36 mg/m(2) iv for three consecutive weeks every 28 days, and estramustine 280 mg three times a day for three consecutive days beginning the day before docetaxel (days 1-3, 8-10 and 15-17). In order to prevent thromboembolic events, 40 mg of subcutaneous enoxaparine was administered daily sc on the same days as estramustine. Primary endpoints were: toxicity, especially the presence of thromboembolic events, PSA response rate and response in measurable disease. Secondary endpoints were: time to PSA progression and overall survival. RESULTS: Nineteen of 24 patients (79.1%, 95% CI 71-87%) had a PSA response = or >50%. Four of the eleven patients with measurable disease had a partial response. The median time to PSA progression was 7 months (CI 95%: 6.5-9) and the median survival was 19 months (IC 95%: 11-24). Toxicity was manageable with no treatment- related mortality. Only two patients had grade 4 neutropenia. Two patients had thrombotic events, one deep venous thrombosis and one stroke. The main grade 3 non-haematologic toxicity was diarrhoea and asthenia, both in 25% of patients. CONCLUSIONS: Weekly docetaxel with a short course of estramustine and enoxaparine is active and tolerable in HRPC patients. The observed incidence of thrombosis was lower than previously reported but the association of enoxaparine was not enough to completely prevent the thromboembolic events.

Long-term outcome of a phase II study of weekly docetaxel with a short course of estramustine and enoxaparine in hormone-resistant prostate cancer patients

OBJECTIVE: The objective was to define the toxicity and activity of weekly docetaxel administered with a short course of estramustine and enoxaparine in patients with hormone-resistant prostate cancer (HRPC). PATIENTS AND METHODS: Twenty-four patients were treated with the next regimen: weekly docetaxel 36 mg/m(2) iv for three consecutive weeks every 28 days, and estramustine 280 mg three times a day for three consecutive days beginning the day before docetaxel (days 1-3, 8-10 and 15-17). In order to prevent thromboembolic events, 40 mg of subcutaneous enoxaparine was administered daily sc on the same days as estramustine. Primary endpoints were: toxicity, especially the presence of thromboembolic events, PSA response rate and response in measurable disease. Secondary endpoints were: time to PSA progression and overall survival. RESULTS: Nineteen of 24 patients (79.1%, 95% CI 71-87%) had a PSA response = or >50%. Four of the eleven patients with measurable disease had a partial response. The median time to PSA progression was 7 months (CI 95%: 6.5-9) and the median survival was 19 months (IC 95%: 11-24). Toxicity was manageable with no treatment- related mortality. Only two patients had grade 4 neutropenia. Two patients had thrombotic events, one deep venous thrombosis and one stroke. The main grade 3 non-haematologic toxicity was diarrhoea and asthenia, both in 25% of patients. CONCLUSIONS: Weekly docetaxel with a short course of estramustine and enoxaparine is active and tolerable in HRPC patients. The observed incidence of thrombosis was lower than previously reported but the association of enoxaparine was not enough to completely prevent the thromboembolic events (AU)

No disponible

[Renal synchronous tumor: association of renal adenocarcinoma and transitional tumor of renal pelvis, in the same kidney, an exceptional discovery]. / Tumor sincrónico renal: asociación de adenocarcinoma renal y tumor transicional de pelvis renal, en el mismo riñón, un hallazgo excepcional.

The renal cell tumour supposes 1% of the adult's tumors, while the transitional carcinoma has an incidence of 7%. The simultaneous appearance of a carcinoma of renal cells, and a transitional tumour of pelvis in the same kidney, they suppose an exceptional fact not existing but of 30 cases published in the world, presenting an approximate incidence of 0.14% of the pathology renal tumoral. We present a new case of this unusual association that supposes the 4 case indexed in the literature in Spanish.

Tumor sincrónico renal: asociación de adenocarcinoma renal y tumor transicional de pelvis renal, en el mismo riñón, un hallazgo excepcional / Renal synchronous tumor: association of renal adenocarcinoma and transitional tumor of renal pelvis, in the same kidney, an exceptional discovery

El tumor de células renales supone el 1% de los tumores del adulto, mientras que el carcinoma transicional tiene una incidencia del 7%. La aparición simultánea de un carcinoma de células renales, y un tumor transicional de pelvis en el mismo riñón, suponen un hecho excepcional no existiendo más de 30 casos publicados en el mundo, presentando una incidencia aproximada del 0,14% de la patología tumoral renal. Presentamos un nuevo caso de esta inusual asociación que supone el 4caso referenciado en la literatura en español (AU)

The renal cell tumour supposes 1% of the adult’s tumors, while the transitional carcinoma has an incidence of 7%. The simultaneous appearance of a carcinoma of renal cells, and a transitional tumour of pelvis in the same kidney, they suppose an exceptional fact not existing but of 30 cases published in the world, presenting an approximate incidence of 0.14% of the pathology renal tumoral. We present a new case of this unusual association that supposes the 4 case indexed in the literature in Spanish (AU)

[Benign retroperitoneal schwannoma. Incidental diagnostic in patient with hematuria of the percusionist]. / Schwannoma retroperitoneal benigno. Diagnostico incidental en paciente con hematuria del percusionista.

The incidence of retroperitoneal primitive tumour varies from the 0.3 to 3%. The sarcomas suppose the group but it frequents of retroperitoneal tumour, being the Schwannoma an unusual tumour with an incidence from 1% to 50% of the retroperitoneal primary tumours. The schwannoma also denominated neurinoma or neurolenoma, it is a derived tumour of the cells of Schwann of the outlying nerves. It is characterized by their clinical and radiological inespecify, being the diagnose pathological, with intense positive inmunohistoquimics to the protein S-100. The election treatment is the surgical remove, with wide margins; not being described cases of malignización neither of metastasis at distance, but if the recurrence existence at probably secondary local level to incomplete resection.

Schwannoma retroperitoneal benigno. Diagnostico incidental en paciente con hematuria del percusionista / Benign retroperitoneal schwannoma, I diagnose incidental in patient with hematuria of the percusionist

La incidencia de neoplasias retroperitoneales primitivos varía del 0,3 al 3%. Los sarcomas suponen el grupo mas frecuente de neoplasias retroperitoneales, siendo el Schwannoma un tumor inusual con una incidencia del 1% al 5% del los tumores retroperitoneales primarios. El schwannoma también denominado neurinoma o neurolenoma, es un tumor derivada de las células de Schwann de los nervios periféricos. Se caracteriza por su inespecificidad clínica y radiológica, siendo el diagnostico patológico, con intensa positividad inmunohistoquímico a la proteína S-100. El tratamiento de elección es la exéresis quirúrgica, con márgenes amplios; no estando descrito casos de malignización ni de metástasis a distancia, pero si la existencia de recurrencia a nivel local probablemente secundaria a resección incompleta (AU)

The incidence of retroperitoneal primitive tumour varies from the 0,3 to 3%. The sarcomas suppose the group but it frequents of retroperitoneal tumour, being the Schwannoma an unusual tumour with an incidence from 1% to 5% of the retroperitoneal primary tumours. The schwannoma also denominated neurinoma or neurolenoma, it is a derived tumour of the cells of Schwann of the outlying nerves. It is characterized by their clinical and radiological inespecify, being the diagnose pathological, with intense positive inmunohistoquimics to the protein S-100. The election treatment is the surgical remove, with wide margins not being described cases of malignización neither of metastasis at distance, but if the recurrence existence at probably secondary local level to incomplete resection (AU)

Proposal for a loophole-free Bell test using homodyne detection.

We propose a feasible optical setup allowing for a loophole-free Bell test with efficient homodyne detection. A non-Gaussian entangled state is generated from a two-mode squeezed vacuum by subtracting a single photon from each mode, using beam splitters and standard low-efficiency single-photon detectors. A Bell violation exceeding 1% is achievable with 6 dB squeezed light and a homodyne efficiency around 95%. A detailed feasibility analysis, based upon the recent experimental generation of single-mode non-Gaussian states, suggests that this method opens a promising avenue towards a complete experimental Bell test.

[Primary testicular lymphoma. Report of a new case and review of the literature]. / Linfoma testicular primario. Aportación de un nuevo caso y revisión de la literatura.

Primary testicular lymphoma is an uncommon testicular tumour that accounts for no more than 9% of all testicular tumours in those series with higher incidence; testicular lymphoma as haematopoietic tumours are also rare accounting for just 1% of all lymphomas; but due to their highly malignant histopathology they may become highly aggressive tumours. Patient age at presentation is over 60 years old which makes it the most frequent tumour for this age group. There is no standard protocol to treat this malignancy due to lack of extensive series. We contribute one case and make a literature review discussing the current therapeutic trends for this disease.

Linfoma testicular primario. Aportación de un nuevo caso y revisión de la literatura / Primary testicular lymphoma. Contribution of one case and literature review

El linfoma testicular primario es un tumor testicular infrecuente, suponiendo no más del 9 por ciento de los tumores testiculares en las series con mayor incidencia; a su vez el linfoma testicular como tumor hematopoyético es infrecuente, con una incidencia del 1 por ciento de los linfomas, pero debido a su histopatología en la mayoría de los casos de alta malignidad, les hace ser de los tumores testiculares más agresivos. La edad de aparición es por encima de los 60 años, convirtiéndose en el tumor más frecuente para este grupo de edad. La falta de series amplias, hace que no exista un protocolo establecido para el tratamiento de esta patología. Presentamos un nuevo caso, realizando revisión de la bibliografía presentando las tendencias terapéuticas actuales para este tipo de patología (AU)

No disponible

[Sarcomatoid carcinoma of the kidney. Report of a new case and review of the bibliography]. / Carcinoma sarcomatoide de riñón. Aportación de un nuevo caso, y revisión de la bibliografía.

We report a new case of sarcomatoid renal cell carcinoma, in a male of 67 years old, with locoregional recidive four months after first surgery, with two episodes of retroperitoneal hemorrhage after second surgery. The objective of this work is to contribute a new case and of doing one revision.

Carcinoma sarcomatoide de riñón. Aportación de un nuevo caso,y revisión de la bibliografía / Renal sarcomatoid carcinoma. A new case contribution and bibliographic revission

Se presenta un nuevo caso de carcinoma renal sarcomatoide, en un varón de 67 años con recidiva locorregional a los 4 meses de la cirugía, con dos episodios de hemorragia retroperironeal tras la segunda intervención. El objetivo de este trabajo es aportar un nuevo caso y hacer una revisión de la bibliografía (AU)

No disponible

The putative role of botrydial and related metabolites in the infection mechanism of Botrytis cinerea.

Phytotoxic assays, performed both in vitro and in vivo on leaves of Phaseolus vulgaris, with metabolites excreted by the fungus B. cinerea are evaluated. Exogenous application of the phytotoxin botrydial has been found to produce severe chlorosis and cell collapse and facilitated fungal penetration and colonization of plant tissue. The results also show a light-dependent action mechanism for the phytotoxin and seem to indicate that botrydial is a non-host-specific toxin involved in fungal infection of B. cinerea.

Pharmacokinetic Interaction between amprenavir and rifabutin or rifampin in healthy males.

The objective of this study was to determine if there is a pharmacokinetic interaction when amprenavir is given with rifabutin or rifampin and to determine the effects of these drugs on the erythromycin breath test (ERMBT). Twenty-four healthy male subjects were randomized to one of two cohorts. All subjects received amprenavir (1,200 mg twice a day) for 4 days, followed by a 7-day washout period, followed by either rifabutin (300 mg once a day [QD]) (cohort 1) or rifampin (600 mg QD) (cohort 2) for 14 days. Cohort 1 then received amprenavir plus rifabutin for 10 days, and cohort 2 received amprenavir plus rifampin for 4 days. Serial plasma and urine samples for measurement of amprenavir, rifabutin, and rifampin and their 25-O-desacetyl metabolites, were measured by high-performance liquid chromatography. Rifabutin did not significantly affect amprenavir's pharmacokinetics. Amprenavir significantly increased the area under the curve at steady state (AUC(ss)) of rifabutin by 2.93-fold and the AUC(ss) of 25-O-desacetylrifabutin by 13.3-fold. Rifampin significantly decreased the AUC(ss) of amprenavir by 82%, but amprenavir had no effect on rifampin pharmacokinetics. Amprenavir decreased the results of the ERMBT by 83%. The results of the ERMBT after 2 weeks of rifabutin and rifampin therapy were increased 187 and 156%, respectively. Amprenavir plus rifampin was well tolerated. Amprenavir plus rifabutin was poorly tolerated, and 5 of 11 subjects discontinued therapy. Rifampin markedly increases the metabolic clearance of amprenavir, and coadministration is contraindicated. Amprenavir significantly decreases clearance of rifabutin and 25-O-desacetylrifabutin, and the combination is poorly tolerated. Amprenavir inhibits the ERMBT, and rifampin and rifabutin are equipotent inducers of the ERMBT.