Phylogeny and historical biogeography of neotropical catfishes Trichomycterus (Siluriformes: Trichomycteridae) from eastern Brazil.

The catfish subfamily Trichomycterinae is widely distributed in South America inhabiting several habitats, but specially mountain streams. Trichomycterus is the most speciose trichomycterid genus and recently due to his paraphyletic condition has been restricted to a clade from eastern Brazil called Trichomycterus sensu stricto comprising around 80 valid species distributed in seven areas of endemism of eastern Brazil. This paper aims to analyse the biogeographical events responsible for the distribution of Trichomycterus s.s., by reconstructing the ancestral data based on a time-calibrated multigene phylogeny. A multi-gene phylogeny was generated using 61 species of Trichomycterus s.s. and 30 outgroups, with divergence events calculated based on the estimated origin of Trichomycteridae. Two event-based analyses were applied to investigate the biogeographical events responsible the present distribution of Trichomycterus s.s. and suggest that the modern distribution of the group is a result of different vicariance and dispersal events. The diversification of Trichomycterus s.s. subgenera occurred in the Miocene, except for Megacambeva, with different biogeographical events shaping its distribution in eastern Brazil. An initial vicariant event split up the Fluminense ecoregion from the Northeastern Mata Atlantica + Paraíba do Sul + Fluminense + Ribeira do Iguape + Upper Paraná ecoregions. Dispersal events occurred mainly between Paraíba do Sul and neighboring river basins, with additional dispersal events from Northeastern Mata Atlantica to Paraíba do Sul, from São Francisco to Northeastern Mata Atlântica, and from Upper Paraná to São Francisco.

Prostate cancer treatment and the relationship of androgen deprivation therapy to cognitive function.

Prostate cancer is the second most common form of cancer in men. For advanced, high risk prostate cancer, androgen deprivation therapy (ADT) is the preferred treatment and can induce remission, but resistance to ADT brings biochemical recurrence and progression of cancer. ADT brings adverse effects such as erectile dysfunction, decreased libido, and diminished physical strength. It is estimated that between 25 and 50% of men on ADT manifest some form of cognitive dysfunction that may be self-reported or reported by a family member. There is concern that impaired cognitive function with ADT is due to loss of testosterone support. Testosterone and its metabolites are known to possess neuroprotective properties. While a direct causal relationship between ADT and cognitive decline in prostate cancer patients has not been established, this review describes the controversy surrounding the possible connection between ADT and neurocognitive deterioration. The cellular and molecular mechanisms believed to underlie the protection of neuronal integrity by androgens are discussed. Results from animal models and human clinical studies are presented. Finally, we call attention to lifestyle modifications that may minimize cognitive issues in prostate cancer patients.

Gastric and endobronchial metastases in a case of lobular breast cancer.

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histological type of invasive breast carcinoma, preceded only by infiltrating ductal carcinoma, which has clinical, biological and molecular distinctions. These distinctions imply a different metastatic behavior between the histology of these 2 types of breast cancer. CASE PRESENTATION: We report the case of a 51-year-old woman with breast cancer with ILC histology, diagnosed at an early stage. In the course of her disease, recurrences in the gastric mucosa and endobronchial area occurred. The treatment she received is described herein. CONCLUSION: This is a case of ILC with unusual metastases. The absence of E-cadherin is related to the carcinogenesis of ILC and probably to these patterns of metastasis as well.

Progression-free survival as surrogate and as true end point: insights from the breast and colorectal cancer literature.

Significant achievements in the systemic treatment of both advanced breast cancer and advanced colorectal cancer over the past 10 years have led to a growing number of drugs, combinations, and sequences to be tested. The choice of surrogate and true end points has become a critical issue and one that is currently the subject of much debate. Many recent randomized trials in solid tumor oncology have used progression-free survival (PFS) as the primary end point. PFS is an attractive end point because it is available earlier than overall survival (OS) and is not influenced by second-line treatments. PFS is now undergoing validation as a surrogate end point in various disease settings. The question of whether PFS can be considered an acceptable surrogate end point depends not only on formal validation studies but also on a standardized definition and unbiased ascertainment of disease progression in clinical trials. In advanced breast cancer, formal validation of PFS as a surrogate for OS has so far been unsuccessful. In advanced colorectal cancer, in contrast, current evidence indicates that PFS is a valid surrogate for OS after first-line treatment with chemotherapy. The other question is whether PFS sufficiently reflects clinical benefit to be considered a true end point in and of itself.

Progression-free survival and time to progression as primary end points in advanced breast cancer: often used, sometimes loosely defined.

BACKGROUND: The growing availability of active agents makes the development of novel therapies increasingly complex and the choice of end points critical. We assessed the frequency of use of efficacy end points in advanced breast cancer. METHODS: We searched PubMed for randomized trials published between 2000 and 2007 in 10 leading medical journals. We abstracted data on progression-free survival (PFS), time to tumor progression (TTP), response rate (RR) and overall survival. RESULTS: A total of 58 studies enrolled 23,371 assessable patients in 122 treatment arms. The primary end points most frequently used were RR and TTP (n=21 each), followed by PFS (n=14). In five of the trials using TTP as the primary end point, no definition of TTP was reported; in 13 of the other 16 cases, death was counted as an event, making TTP indistinguishable from PFS. Trials having PFS, TTP or time to treatment failure as the primary end point (n=36) had a higher mean number of patients than those using RR (P=0.061). CONCLUSION: Investigators seem to be frequently using PFS and TTP interchangeably in advanced breast cancer. Such use of terms may lead to confusion when results of different trials are compared, and uniform use of definitions seems in order.

Quality-of-life benefits and evidence of antitumour activity for patients with brain metastases treated with gefitinib.

Brain metastases are a common complication of non-small-cell lung cancer (NSCLC). The role of chemotherapy in the treatment of brain metastases has not been clearly defined. Emerging case reports of patients with recurrent NSCLC treated as part of the Expanded Access Programme reveal that gefitinib ("Iressa", ZD1839) has clinical activity in some patients with brain metastases. Here, we describe a number of case studies documenting the response of patients with brain metastases to treatment with gefitinib. Many of these patients had quality-of-life benefits with improvement of neurological and systemic symptoms; some had a partial response of their brain metastases and even complete responses have been seen in a few patients. One case report also describes a durable long-term response with concurrent treatment with gefitinib and radiotherapy. Such results call for larger trials designed to evaluate and define the role of gefitinib in the treatment of brain metastases in NSCLC patients, either as a single agent or in combination with radiation therapy.

Cardiac malposition, redistribution of fetal cardiac output, and left heart hypoplasia reduce survival in neonates with congenital diaphragmatic hernia requiring extracorporeal membrane oxygenation.

OBJECTIVE: To evaluate cardiac position, left ventricular (LV) mass, and distribution of fetal cardiac output in infants with congenital diaphragmatic hernia (CDH) who required extracorporeal membrane oxygenation (ECMO), and in control subjects. STUDY DESIGN: Echocardiograms were performed on 23 neonates with CDH shortly after birth, and repeated within 5 days of repair on ECMO in 21 infants,aand on 12 infants receiving ECMO for other diagnoses, and on 10 healthy, term neonates. Cardiac angle between the midline saggital plane and the interventriculak septum was measured, and deviation from normal (45 degrees) was determined. The ratio of cross-sectional areas (proportional to flows) across the pulmonary (PV) and aortic (AV) valves was determined (PV2/AV2) in 19 infants with CDH and in the healthy control subjects. RESULTS: Thirteen (57%) infants with CDH survived and 10 (43%) died, with no difference in cardiac deviation before surgical repair (35 +/- 13 degrees vs Cardiac deviation persisted after repair in nonsurvivors (27 +/- 14 degrees vs 800.01 and LV mass was significantly less (1.68 +/- 0.39 vs 3.05 +/- 1.20 gm/kg, p00.0005). Neonates requiring ECMO for other diagnoses and well term babies did not have cardiac angle deviations; both these groups had a greater LV mass than did the infants with CDH. The PV2/AV2 flow ratios were higher in infants with CDH (median, 1.73; range, 1.25 to 16.50) compared with those of the healthy infants (0.96, 0.79 to 1.69, p < 0.0002). CONCLUSIONS: Cardiac malposition persisted despite CDH repair in nonsurvivors with low LV mass, and fetal cardiac output was redistributed away from the left ventricle. Lung hypoplasia with reduced pulmonary flow returning to the left atrium and altered left atrial hemodynamics may result in LV hypoplasia

[Superior vena cava and right atrium thrombosis successfully treated with streptokinase]. / Trombose da veia cava superior e do átrio direito tratada com sucesso com estreptoquinase.

The case of a 56 year-old male with acute lymphoid leukemia and no signs of activity for the last four months is reported. He presented with superior vena cava thrombosis caused by a Hickman catheter, and had positive blood cultures for Candida albicans and Staphylococcus epidermidis. Despite adequate antimicrobial therapy, the fever persisted, and the patient was submitted to surgical thrombectomy. One week following the procedure, the fever returned, and thrombosis of the superior vena cava extending to the right atrium was identified by transesophageal echocardiography (TEE). The patient underwent thrombolytic therapy with streptokinase, and no thrombus could be identified in the control TEE. No hemorrhagic or thromboembolic complication occurred. The patient was discharged with oral anticoagulation.

Focal bacterial nephritis (lobar nephronia) in children.

We report 13 patients with 16 episodes of acute lobar nephronia diagnosed in a prospective study that was conducted among 210 hospitalized children with urinary tract infection. In 30 episodes of urinary tract infection, a hypoechogenic or hyperechogenic lesion was found. Twenty patients underwent computed tomography, and in 16 of them acute lobar nephronia was diagnosed. Evolution to renal abscess occurred in 25%. Prolonged intravenous antibiotic treatment was sufficient in all cases.

A prospective randomized evaluation of three schedules of mesna administration in patients receiving an ifosfamide-containing chemotherapy regimen: sustained efficiency and simplified administration.

Chemotherapy with oxazaphosphorines, such as ifosfamide, is often limited by unacceptable urotoxicity. Without uroprotection hemorrhagic cystitis becomes dose-limiting. Mesna, a thiol compound, is a drug able to bind the toxic metabolites, forming nontoxic compounds in the urine. A total of 122 patients were enrolled in this study and 228 chemotherapy cycles with an ifosfamide-containing regimen were performed (225 evaluable). Mesna was given at the same total dose as the ifosfamide in all arms. On arm A, mesna was given i. v. in equal doses 15 min before and 4 h and 8 h following the ifosfamide dose. On arm B, mesna was given in three equivalent doses 15 min before (i.v.) and 4 h (i.v.) and 8 h (p.o., double dose) following ifosfamide. On arm C, mesna was given i.v. in two equal doses given 15 min before and 4 h following. The incidence of urotoxicity was very low (lower than 15%) in the three arms, 0% in A, 1.36% in B and 2.70% in C. All three arms were equally efficient. Schedule C was considered superior to the others, since it was equally effective, simpler and more convenient.

Tetracycline-induced esophagitis in adolescent patients.

Ulcerative esophagitis may be caused by corrosive agents and by commonly prescribed medications. We report severe esophagitis in five adolescents after ingestion of tetracycline preparations with minimal water immediately before going to bed.

Strongyloides hyperinfection in two patients with lymphoma, purulent meningitis, and sepsis.

Strongyloides stercoralis hyperinfection syndrome is a rare complication of strongyloidiasis that occurs in immunosuppressed patients. It is caused by increasing autoinfection of the host by the nematode, leading to serious superimposed enterobacterial sepsis. Once established, it has a high fatality rate. Two cases are reported of Strongyloides hyperinfection in patients with lymphoma who presented with purulent meningitis. Both were receiving combination chemotherapy that included high-dose corticosteroids, and neither was granulocytopenic at infectious onset. The patients had respiratory insufficiency that required mechanical ventilation and serious septic episodes. Both were treated with thiabendazole, and one survived with clearance of the larvae. These cases illustrate the possibility of strongyloidiasis hyperinfection as an underlying diagnosis of purulent meningitis and serious septic episodes in lymphomatous patients. It may occur even without granulocytopenia.

Phase II trial of etoposide (V), adriamycin (A), and cisplatinum (P) in patients with metastatic gastric cancer.

The efficacy and toxicity of a combination of etoposide (100 mg/m2 i.v. on days 1 to 3), Adriamycin (20 mg/m2 i.v. on days 1 and 8) and cisplatinum (40 mg/m2 i.v. on days 2 and 8) repeated every 4 weeks as an outpatient regimen were assessed in 29 consecutive patients with metastatic gastric cancer with measurable disease. Five of these patients were refractory to 5-Fluorouracil, Adriamycin, and Mitomycin C. Three of these previously treated patients responded to the etoposide. Adriamycin, cisplatinum (VAP) therapy. An overall objective response rate of 72.5% was achieved, including 14% that were complete responses. The median duration of response was 6.0 months; median overall survival was 7.2 months, overall one-year survival was 34.4%. Hematologic toxicity was intense, particularly among patients with lower performance status. Three patients died as a consequence of nadir sepsis episodes.

Pleural effusion as the initial manifestation of disseminated cryptococcosis in acquired immune deficiency syndrome. Diagnosis by pleural biopsy.

Pleural effusion is an unusual presentation of cryptococcal infection in the acquired immune deficiency syndrome. Previous investigators have established the diagnosis of cryptococcal pleural disease by culturing pleural fluid, bronchial washings, and extrapulmonary sources. We report the first case of cryptococcal pleural effusion proved by closed pleural biopsy. Pleural biopsy may be an effective and rapid method of determining the etiology of pleural effusion in the acquired immune deficiency syndrome.

Pneumonia por Pneumocystis carinii em paciente de "AIDS". / Pneumonia due to Pneumocystis carinii in patients with AIDS

Os autores estudam em um paciente de pneumonia por Pneumocystis carinii os aspectos propedeuticos e terapeuticos desta infeccao, ao tempo em que definem a incompetencia imunitaria do hospedeiro, caracterizando atraves de extensa investigacao a sindrome de imunodeficiencia adquirida ("AIDS")