Long-term oncologic outcome after laparoscopic radical nephroureterectomy for upper tract transitional cell carcinoma

OBJECTIVE: To assess the long-term oncologic efficacy of laparoscopic radical nephroureterectomy (RNU). METHODS: Between August 1993 and May 2001, 39 patients underwent laparoscopic RNU for upper tract transitional cell carcinoma (TCC) at our institution. The medical records of these patients were retrospectively reviewed. RESULTS: Clinical outcomes were available in all 39 patients with an actual follow-up ranging from 60 to 148 mo (median: 74). During this time 27 patients (69%) developed at least one TCC recurrence. Eighteen patients had urothelial recurrences, and 9 patients had nonurothelial recurrences. Of these latter patients, 2 patients (5%) had local recurrences. No patient developed a port site metastasis. Eleven patients ultimately had disease progression and died from TCC 7-59 mo (median: 31) after the operation. On statistical analysis, tumor stage was the only factor significantly associated with death from the disease, and tumor location (ureter) was the only factor significantly associated with disease recurrence. CONCLUSIONS: The long-term overall and disease-specific survival rates after laparoscopic RNU for upper tract TCC are well within the range of results reported after open surgery. Thus, the results of the present study support the continued development of laparoscopic techniques in the management of this aggressive disease.     

Lippia sidoides and Myracrodruon urundeuva gel prevents alveolar bone resorption in experimental periodontitis in rats

In Brazilian folk medicine, Lippia sidoides (Ls) and Myracrodruon urundeuva (Mu) have gained popularity and reputation as effective antimicrobial and anti-inflammatory agents. This work aimed to evaluate the effect of topical herbal gel from Ls 0.5% (v/w) and Mu 5% (w/w) in experimental periodontal disease (EPD) in rats. Wistar rats were subjected to ligature placement around the second upper left molars. Animals were treated topically with Ls and/or Mu-based gel, immediately after EPD induction and three times/day for 11 days until the rats were sacrificed (11th day). Saline-based gel was utilized as control for all experiments and doxycycline based gel 10% (w/w) was utilized as reference substance. Animals were weighed daily. Alveolar bone loss was measured as the difference (in millimeters) between the cusp tip and the alveolar bone. The periodontum and the surrounding gingivae were examined at histopathology, as well as the neutrophil influx into the gingivae was assayed using myeloperoxidase activity and cytokine production mainly tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) levels by ELISA method. The local bacterial flora was assessed through culture of the gingival tissue in standard aerobic and anaerobic media. Alveolar bone loss was significantly inhibited by Ls and Mu combined treatment compared to the saline control group. Ls and Mu combined treatment reduced tissue lesion at histopathology, with partial preservation of the periodontum, coupled to decreased myeloperoxidase activity as well as significantly inhibited TNF-alpha and IL-1beta production in gingival tissue compared to the saline control group. Ls and Mu combined treatment also prevented the growth of oral microorganisms and the weight loss. Ls and Mu combined based gel treatment preserved alveolar bone resorption and demonstrated anti-inflammatory and antibacterial activities in experimental periodontitis.     

Molecular epidemiology of rabies from Maranhão and surrounding states in the northeastern region of Brazil

Although many outbreaks of rabies have been reported in northern Brazil, few epidemiological studies of these outbreaks have been undertaken. In this study, molecular epidemiological analyses were performed using 41 rabies virus samples isolated in the Maranh?o (MA), Pará (PA), and Tocantins (TO) states of northeastern Brazil. A 599-bp region of the glycoprotein (G) gene was first amplified from each sample by RT-PCR, then sequenced and subjected to phylogenetic analysis. A phylogenetic tree divided the 41 isolates into two clades: Clade I was associated with terrestrial carnivores and Clade II was associated with vampire bats. The Clade I isolates were further sub-divided into two groups. The first group was closer to carnivore isolates that predominate in central Brazil, whereas the second group more closely resembled wild fox isolates from the northeastern coastal state of Paraíba (PB). MA isolates of Clade II formed an entirely separate group. These results demonstrate that bat- and dog-transmitted rabies occur in northwestern Brazil.     

GSK1562590, a slowly dissociating urotensin-II receptor antagonist, exhibits prolonged pharmacodynamic activity ex vivo

BACKGROUND AND PURPOSE

Recently identified antagonists of the urotensin–II (U-II) receptor (UT) are of limited utility for investigating the (patho)physiological role of U-II due to poor potency and limited selectivity and/or intrinsic activity.

EXPERIMENTAL APPROACH

The pharmacological properties of two novel UT antagonists, GSK1440115 and GSK1562590, were compared using multiple bioassays.

KEY RESULTS

GSK1440115 (pK_i= 7.34–8.64 across species) and GSK1562590 (pK_i= 9.14–9.66 across species) are high affinity ligands of mammalian recombinant (mouse, rat, cat, monkey, human) and native (SJRH30 cells) UT. Both compounds exhibited >100-fold selectivity for UT versus 87 distinct mammalian GPCR, enzyme, ion channel and neurotransmitter uptake targets. GSK1440115 showed competitive antagonism at UT in arteries from all species tested (pA₂= 5.59–7.71). In contrast, GSK1562590 was an insurmountable UT antagonist in rat, cat and hUT transgenic mouse arteries (pK_b= 8.93–10.12 across species), but a competitive antagonist in monkey arteries (pK_b= 8.87–8.93). Likewise, GSK1562590 inhibited the hU-II-induced systemic pressor response in anaesthetized cats at a dose 10-fold lower than that of GSK1440115. The antagonistic effects of GSK1440115, but not GSK1562590, could be reversed by washout in rat isolated aorta. In ex vivo studies, GSK1562590 inhibited hU-II-induced contraction of rat aorta for at least 24 h following dosing. Dissociation of GSK1562590 binding was considerably slower at rat than monkey UT.

CONCLUSIONS AND IMPLICATIONS

Whereas both GSK1440115 and GSK1562590 represent high-affinity/selective UT antagonists suitable for assessing the (patho)physiological role of U-II, only GSK1562590 exhibited sustained UT residence time and improved preclinical efficacy in vivo.     

Mycetoma caused by Nocardia caviae in the first Brazilian patient

Background  Mycetoma is a chronic subcutaneous mycosis caused by exogenous fungi or actinomycetes. This infection has a progressive course and shows a typical clinical characteristic of tumefaction, draining sinuses, and grains. Infection initiation is related to local trauma and can spread to muscle, underlying bone, and adjacent organs. Nocardia brasiliensis is the most frequent actinomycete isolated, while N. caviae is a rare agent. Methods  We present a case of mycetoma in a 37‐year‐old African‐American man on the right hand. The infection had been apparent for four years prior to the consultation. When the infection did not respond to antibiotic therapy, the patient was referred to the Dermatology department. Routine laboratory studies were normal. X‐ray examination of the hand showed an osteolytic lesion on the hand bones. On skin biopsy culture, on Sabouraud Dextrose Agar at 28 °C, a colony was isolated which was further identified as N. caviae by biochemical and hydrolysis testing. Results The patient was treated with oral trimethoprim/sulfamethoxazole (TMP/SMZ) 160/800 mg twice a day for 10 months. Four months after the beginning of the therapy, the subject exhibited clinical improvement and functional recovery of the hand. Five‐year follow‐up X‐ray examination of the hand showed no osteolytic lesion on the hand bones. Conclusion We report the first mycetoma case caused by N. caviae in our country with an unusual location on the hand. The patient showed clinical improvement with oral TMP/SMZ.     

Pericardial breast cancer metastasis 25 years after mastectomy

Pericardial effusion in a patient with a history of cancer should always prompt a hypothesis of malignant involvement. We report the case of a 66-year-old white woman presenting with pericardial effusion 25 years after a mastectomy for ductal breast carcinoma. This is one of the cases with the latest recurrence ever reported.     

Growth status and academic performance in Brazilian school age children: growth retardation impairs mathematical, but not reading and spelling abilities

AIM: To assess the effect of child growth status on academic achievement and the association between child growth and academic standing. METHOD: The heights of 722 middle-school children were measured using standard procedures and height-for-age z (HAZ) scores were calculated based on an international reference. Academic performance was assessed by an adaptation of the Wide Range Achievement Test (WRAT3) composed of Reading, Arithmetic and Spelling. RESULTS: Children in the group with higher HAZ scores performed better than children in the group with lower HAZ scores only on the Arithmetic subtest. This finding was confirmed by a multiple regression model analysis of the data. In addition, only performance on the Arithmetic subtest was positively associated with HAZ. CONCLUSION: These results indicate that growth retardation impacts specifically on the development of arithmetic (numeracy) skills and are consistent with a three-fold model of life course influences on health including latency, cumulative and pathway effects.     

Antimony in plasma and skin of patients with cutaneous leishmaniasis – relationship with side effects after treatment with meglumine antimoniate

Objective  To evaluate the levels of antimony in plasma and skin of patients being treated with pentavalent antimonials (Glucantime^®) and their relationship with side effects.
Methods  We evaluated 19 patients treated endovenously at the conventional dose (20 mg Sb^v/kg/day), two at a smaller dose (5 mg Sb^v/kg/day) and three treated intralesionally (up to 4.0 ml/week). During treatment, patients underwent periodic blood exams and were interviewed weekly about the incidence of adverse symptoms. The levels of antimony in plasma and skin samples were determined by Inductively Coupled Plasma with Mass Spectrometry (ICP-MS).
Results  The patients under conventional treatment presented a mean initial antimony plasma concentration of 3.39 μg/l; at the end of treatment, these levels were 0.21 before Glucantime^® application and 125.8 mg after Glucantime^® application. The mean antimony level in their skin at the end of the treatment was 9.24 μg/g. The main adverse symptoms were arthralgia and myalgia; laboratory results showed mainly lymphocytosis and eosinophilia.
Conclusions  We found some significant correlations between antimony concentrations, adverse symptoms and laboratory alterations, strengthening the hypothesis of a dose–dependent relationship between antimony concentration in plasma and skin and side effects.     

Unconjugated bilirubin activates and damages microglia

Microglia are the resident immune cells of the brain and are the principal source of cytokines produced during central nervous system inflammation. We have previously shown that increased levels of unconjugated bilirubin (UCB), which can be detrimental to the central nervous system during neonatal life, induce the secretion of inflammatory cytokines and glutamate by astrocytes. Nevertheless, the effect of UCB on microglia has never been investigated. Hence, the main goal of the present study was to evaluate whether UCB leads to microglial activation and to the release of the cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. Additionally, we investigated the effects of UCB on glutamate efflux and cell death. The results showed that UCB induces morphological changes characteristic of activated microglia and the release of high levels of TNF-alpha, IL-1beta, and IL-6 in a concentration-dependent manner. In addition, UCB triggered extracellular accumulation of glutamate and an increased cell death by apoptosis and necrosis. These results demonstrate, for the first time, that UCB is toxic to microglial cells and point to microglia as an important target of UCB in the central nervous system. Moreover, they suggest that UCB-induced cytokine production, by mediating cell injury, can further contribute to exacerbate neurototoxicity. Interestingly, microglia cells are much more responsive to UCB than astrocytes. Collectively, these data indicate that microglia may play an important role in the pathogenesis of encephalopathy during severe hyperbilirubinemia.