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OBJECTIVES: The objective of this study was to evaluate the ability of a muscular index (Barrett's Index), calculated with multidetector computed tomography, to detect dysthyroid optic neuropathy in patients with Graves' orbitopathy. METHODS: Thirty-six patients with Graves' orbitopathy were prospectively studied and submitted to neuro-ophthalmic evaluation and multidetector computed tomography scans of the orbits. Orbits were divided into two groups: those with and without dysthyroid optic neuropathy. Barrett's index was calculated as the percentage of the orbit occupied by muscles. Sensitivity and specificity were determined for several index values. RESULTS: Sixty-four orbits (19 with and 45 without dysthyroid optic neuropathy) met the inclusion criteria for the study. The mean Barrett's index values (± SD) were 64.47% ± 6.06% and 49.44% ± 10.94%in the groups with and without dysthyroid optic neuropathy, respectively (p<0.001). Barrett's index sensitivity ranged from 32% to 100%, and Barrett's index specificity ranged from 24% to 100%. The best combination of sensitivity and specificity was 79%/72% for BI=60% (odds ratio: 9.2). CONCLUSIONS: Barrett's Index is a useful indicator of dysthyroid optic neuropathy and may contribute to early diagnosis and treatment. Patients with a Barrett's index >60% should be carefully examined and followed for the development of dysthyroid optic neuropathy.

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OBJECTIVE: To implement a selective and sensitive analytical method to quantify morphine in small volumes of plasma by gas-liquid chromatography-mass spectrometry (GC-MS), aimed at post-operatively monitoring the drug. METHOD: A gas-liquid chromatographic method with mass detection has been developed to determine morphine concentration in plasma after solid phase extraction. Morphine-d3 was used as an internal standard. Only 0.5 mL of plasma is required for the drug solid-phase extraction in the Bond Elut-Certify®, followed by the quantification of morphine derivative by GC-MS using a linear temperature program, a capillary fused silica column, and helium as the carrier and make-up gas. The method was applied to determine morphine content in plasma samples of four patients during the postoperative period of cardiac surgery. Patient-controlled analgesia with morphine was performed by a venous catheter, and a series of venous blood samples were collected. After the oro-After the orotracheal extubation, morphine plasma levels were monitored for up to 36 hours. RESULTS: The run time was 16 minutes because morphine and the internal standard were eluted after 8.8 minutes. The GC-MS method had 0.5 -1000 ng/mL linearity range (r²=0.9995), 0.1 ng/mL limit of detection, intraday and interday precision equivalent to 1.9% and 6.8%, and 0.1% and 0.8% systematic error (intraday and interday, respectively). The analytical method showed optimal absolute (98%) and relative (100.7%) recoveries. Morphine dose requirements and plasma levels are discussed. CONCLUSION: The analytical gas-liquid chromatography-mass spectrometry method is selective and adequate for morphine measurements in plasma for applications in clinical studies.

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PURPOSE: To evaluate the influence of the urologist's experience on the surgical results and complications of transurethral resection of the prostate (TURP). PATIENTS AND METHODS: Sixty-seven patients undergoing transurethral resection of the prostate without the use of a video camera were randomly allocated into three groups according to the urologist's experience: a urologist having done 25 transurethral resections of the prostate (Group I - 24 patients); a urologist having done 50 transurethral resections of the prostate (Group II - 24 patients); a senior urologist with vast transurethral resection of the prostate experience (Group III - 19 patients). The following were recorded: the weight of resected tissue, the duration of the resection procedure, the volume of irrigation used, the amount of irrigation absorbed and the hemoglobin and sodium levels in the serum during the procedure. RESULTS: There were no differences between the groups in the amount of irrigation fluid used per operation, the amount of irrigation fluid absorbed or hematocrit and hemoglobin variation during the procedure. The weight of resected tissue per minute was approximately four times higher in group III than in groups I and II. The mean absorbed irrigation fluid was similar between the groups, with no statistical difference between them (p=0.24). Four patients (6%) presented with TUR syndrome, without a significant difference between the groups. CONCLUSION: The senior urologist was capable of resecting four times more tissue per time unit than the more inexperienced surgeons. Therefore, a surgeon's experience may be important to reduce the risk of secondary TURP due to recurring adenomas or adenomas that were incompletely resected. However, the incidence of complications was the same between the three groups.

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OBJECTIVE: The objective of this study was to determine the effect of nonspecific phosphodiesterase inhibition on transcription factor activation and tumor necrosis factor-alpha (TNF-a) production in lipopolysaccharide (LPS)-stimulated human mononuclear cells. INTRODUCTION: The production of TNF-a following LPS stimulation is one of the key steps in bacterial sepsis and inflammation. The mechanism by which phosphodiesterase inhibition alters TNF-a production in the presence of LPS remains unclear. METHODS: Human mononuclear cells were stimulated with LPS (1 µg/mL), in the presence and absence of Pentoxifylline (PTX; 20 mM), a nonspecific phosphodiesterase inhibitor. Western blotting of phosphorylated cytoplasmic I-kBa, nuclear factor-kB p65 (NF-kB), and nuclear cAMP-response element binding protein (CREB) was performed. DNA binding of NF-kB and CREB was verified by electrophoretic mobility shift assay. TNF-a levels were determined in the supernatant of stimulated cells in the presence and absence Protein kinase A inhibition by an enzyme-linked immunosorbent assay (ELISA). RESULTS: PTX was demonstrated to significantly reduce cytoplasmic I-kBa phosphorylation, nuclear p65 phosphorylation, and the DNA binding activity of NF-kB. In contrast, PTX markedly enhanced the phosphorylation and DNA binding activity of CREB. Cells concomitantly treated with PTX and LPS secreted similar levels of TNF-a in the presence and absence Protein kinase A inhibition. DISCUSSION: The increased level of cAMP that results from phosphodiesterase inhibition affects cytoplasmic and nuclear events, resulting in the attenuation of NF-kB and the activation of CREB transcriptional DNA binding through pathways that are partially Protein kinase A-independent. CONCLUSION: PTX-mediated phosphodiesterase inhibition occurs partially through a Protein kinase A-independent pathway and may serve as a useful tool in the attenuation of LPS-induced inflammation.

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OBJECTIVE: The aim of this study was to determine the prevalence of open angle glaucoma in first-degree relatives accompanying POAG patients during routine examination in a reference hospital. METHOD: First-degree relatives of primary open angle glaucoma patients who accompanied their relatives to the glaucoma service of a reference hospital were screened for glaucoma. RESULTS: One-hundred and one first-degree relatives were examined, of which 56.4% had never had their intraocular pressure measured. 10.9% had previously been diagnosed with glaucoma, and 5.9% were newly diagnosed during this study. CONCLUSIONS: The eye examination of first-degree relatives identified a significant percentage of individuals with glaucoma. Despite being first-degree relatives of glaucoma patients, 56.4% of the companions had never had their eye pressure measured, demonstrating a lack of awareness about this disease.

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OBJECTIVE: To compare 4 analytic algorithms for interpretation of the Swedish Interactive Threshold Algorithm. INTRODUCTION: Analytic algorithms were initially developed for interpretation of standard automated perimetry (using a full threshold strategy). The Swedish interactive threshold algorithm is a novel strategy that was developed to shorten test duration. METHODS: One hundred forty-three printouts of normal and glaucomatous patients were analyzed using Caprioli's (strict, moderate and liberal) criteria and Anderson's modified criteria for perimetric defect. Areas under the receiver operator characteristics (ROC) curves, sensitivity, and specificity for each criteria were calculated. RESULTS: Caprioli's strict and Anderson's modified criteria presented similar sensitivity (94.5% and 92.3%, respectively) and specificity (63.5% and 61.5%, respectively). Caprioli's liberal criteria were more sensitive (98.9%) and less specific (42.5%) than the other three criteria. CONCLUSION: Both Caprioli's and Anderson's modified criteria can be used for interpretation of the Swedish interactive threshold algorithm.

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INTRODUCTION: Sextant prostate biopsy remains the standard technique for the detection of prostate cancer. It is well known that after a diagnosis of small acinar proliferation (ASAP) or high grade prostate intraepithelial neoplasia (HGPIN), the possibility of finding cancer is approximately 40% and 30%, respectively. OBJECTIVE: We aim to analyze follow-up biopsies on patients who initially received a benign diagnosis after exclusion of HGPIN and ASAP. METHODS: From July 2000 to December 2003, 1177 patients were submitted to sextant extended prostate biopsy in our hospital. The mean patient age was 65.5 years old, and the median number of fragments collected at biopsy was 13. HGPIN and ASAP were excluded from our study. We only considered patients who had a diagnosis of benign at the first biopsy and were subjected to rebiopsies up until May 2005 because of a maintained suspicion of cancer. RESULTS: Cancer was initially detected in 524 patients (44.5%), and the diagnosis was benign in 415 (35.3%). Rebiopsy was indicated for 76 of the latter patients (18.3%) because of a persistent suspicion of cancer. Eight cases of adenocarcinoma (10.5%) were detected, six (75%) at the first rebiopsy. Six patients were submitted to radical prostatectomy, and all tumors were considered clinically significant. CONCLUSION: Our data indicate that in extended prostate biopsy, the first biopsy detects more cancer, and the first, second, and third rebiopsies after an initial benign diagnosis succeed in finding cancer in 7.9% (6/55), 5.9% (1/15) and 20% (1/4) of patients, respectively.

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INTRODUCTION: Acute kidney injury usually develops in critically ill patients in the context of multiple organ dysfunctions. OBJECTIVE: To evaluate the effect of changes in associated organ dysfunctions over the first three days of renal replacement therapy on the outcomes of patients with acute kidney injury. METHODS: Over a 19-month period, we evaluated 260 patients admitted to the intensive care units of three tertiary-care hospitals who required renal replacement therapy for > 48 h. Organ dysfunctions were evaluated by SOFA score (excluding renal points) on the first (D1) and third (D3) days of renal replacement therapy. Absolute (A-SOFA) and relative (D-SOFA) changes in SOFA scores were also calculated. RESULTS: Hospital mortality rate was 75%. Organ dysfunctions worsened (A-SOFA>0) in 53%, remained unchanged (A-SOFA=0) in 17% and improved (A-SOFA<0) in 30% of patients; and mortality was lower in the last group (80% vs. 84% vs. 61%, p=0.003). SOFA on D1 (p<0.001), SOFA on D3 (p<0.001), A-SOFA (p=0.019) and D-SOFA (p=0.016) were higher in non-survivors. However, neither A-SOFA nor D-SOFA discriminated survivors from non-survivors on an individual basis. Adjusting for other covariates (including SOFA on D1), A-SOFA and D-SOFA were associated with increased mortality, and patients in whom SOFA scores worsened or remained unchanged had poorer outcomes. CONCLUSIONS: In addition to baseline values, early changes in SOFA score after the start of renal replacement therapy were associated with hospital mortality. However, no prognostic score should be used as the only parameter to predict individual outcomes.

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AIMS: Our primary aimwas to evaluate whether there is really less bleeding in patients for whom the minimally invasive posterior approach is used in comparison with the direct lateral approachfor primary total hip arthroplasty. Our secondary aim was to evaluate the clinical functional results after six months as well as the postoperative radiographic result. METHODS: In a comparative non-random prospective study, 76 adult patients underwent elective total hip arthroplasty using one of two approaches. The minimally invasive posterior approach (34 cases; mini-incision group) was compared with the standard direct lateral approach (42 cases; control group). RESULTS: Lower total estimated bleeding (means of 1083.5 ml versus 1682.3 ml; p < 0.001) and lower intraoperative bleeding (means of 745.6 ml versus 1282.8 ml; p < 0.001) were found in the mini-incision group. There was, however, no difference in the volume of blood drained after the operation (means of 340 ml and 399 ml; p = 0.77). There was also a difference between the two groups regarding the need for allogenic transfusion (8.8% in the mini-incision group versus 28.6%, p = 0.02). We observed a better clinical result in the mini-incision group (p = 0.002) despite the lack of difference between the two groups in relation to the radiographic result. DISCUSSION: Our results draw attention to the possibility that other authors may have underestimated blood losses when using minimally invasive approaches. CONCLUSION: The minimally invasive approach gave rise to a positive final impression with regard to lower blood loss.

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Critical illness has a major impact on the nutritional status of both children and adults. A retrospective study was conducted to evaluate the incidence of hospital malnutrition at a pediatric tertiary intensive care unit (PICU). Serum concentrations of IL-6 in subgroups of well-nourished and malnourished patients were also evaluated in an attempt to identify those with a potential nutritional risk. METHODS: A total of 1077 patients were enrolled. Nutritional status was evaluated by Z-score (weight for age). We compared mortality, sepsis incidence, and length of hospital stay for nourished and malnourished patients. We had a subgroup of 15 patients with severe malnutrition (MN) and another with 14 well-nourished patients (WN). Cytokine IL-6 determinations were performed by enzyme-linked immunosorbent assay. RESULTS: 53% of patients were classified with moderate or severe malnutrition. Similar amounts of C- reactive protein (CRP) were observed in WN and MN patients. Both groups were able to increase IL-6 concentrations in response to inflammatory systemic response and the levels followed a similar evolution during the study. However, the mean values of serum IL-6 were significantly different between WN and MN patients across time, throughout the study (p = 0.043). DISCUSSION: a considerable proportion of malnourished patients need specialized nutritional therapy during an intensive care unit (ICU) stay. Malnutrition in children remains largely unrecognized by healthcare workers on admission. CONCLUSIONS: The incidence of malnutrition was very high. Malnourished patients maintain the capacity to release inflammatory markers such as CRP and IL-6, which can be considered favorable for combating infections On the other hand, this capacity might also have a significant impact on nutritional status during hospitalization.

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OBJECTIVES: Aiming to improve the anatomical resolution of electrical impedance tomography images, we developed a fuzzy model based on electrical impedance tomography's high temporal resolution and on the functional pulmonary signals of perfusion and ventilation. INTRODUCTION: Electrical impedance tomography images carry information about both ventilation and perfusion. However, these images are difficult to interpret because of insufficient anatomical resolution, such that it becomes almost impossible to distinguish the heart from the lungs. METHODS: Electrical impedance tomography data from an experimental animal model were collected during normal ventilation and apnea while an injection of hypertonic saline was administered. The fuzzy model was elaborated in three parts: a modeling of the heart, the pulmonary ventilation map and the pulmonary perfusion map. Image segmentation was performed using a threshold method, and a ventilation/perfusion map was generated. RESULTS: Electrical impedance tomography images treated by the fuzzy model were compared with the hypertonic saline injection method and computed tomography scan images, presenting good results. The average accuracy index was 0.80 when comparing the fuzzy modeled lung maps and the computed tomography scan lung mask. The average ROC curve area comparing a saline injection image and a fuzzy modeled pulmonary perfusion image was 0.77. DISCUSSION: The innovative aspects of our work are the use of temporal information for the delineation of the heart structure and the use of two pulmonary functions for lung structure delineation. However, robustness of the method should be tested for the imaging of abnormal lung conditions. CONCLUSIONS: These results showed the adequacy of the fuzzy approach in treating the anatomical resolution uncertainties in electrical impedance tomography images.

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OBJECTIVE: To examine the epidermis in induced phytophotodermatitis using transmission electron microscopy in order to detect histologic changes even before lesions are visible by light microscopy. INTRODUCTION: In the first six hours after the experimental induction of phytophotodermatitis, no changes are detectable by light microscopy. Only after 24 hours can keratinocyte necrosis and epidermal vacuolization be detected histologically, and blisters form by 48 hours. METHODS: The dorsum of four adult rats (Rattus norvegicus) was manually epilated. After painting the right half of the rat with the peel juice of Tahiti lemon, they were exposed to sunlight for eight minutes under general anesthesia. The left side was used as the control and exposed to sunlight only. Biopsies were performed immediately after photoinduction and one and two hours later, and the tissue was analyzed by transmission electron microscopy. RESULTS: No histological changes were seen on the control side. Immediately after induction, vacuolization in keratinocytes was observed. After one hour, desmosomal changes were also observed in addition to vacuolization. Keratin filaments were not attached to the desmosomal plaque. Free desmosomes and membrane ruptures were also seen. At two hours after induction, similar changes were found, and granular degeneration of keratin was also observed. DISCUSSION: The interaction of sunlight and psoralens generates a photoproduct that damages keratinocyte proteins, leading to keratinocyte necrosis and blister formation. CONCLUSIONS: Transmission electron microscopy can detect vacuolization, lesions of the membrane, and desmosomes in the first two hours after experimental induction of phytophotodermatitis.

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OBJECTIVES: The pharmacological effects of methylprednisolone (MP) and ganglioside GM-1 on spinal injuries have been thoroughly investigated, but only a few studies have evaluated the interaction between these two drugs. METHODS: Twenty-four Wistar rats were subjected to contusive injury of the spinal cord produced by the NYU system. These animals were divided into four groups: group I was injected with MP; group II was injected with GM-1; group III was injected with MP together with GM-1; and group control received physiological serum. The animals were evaluated with regard to their recovery of locomotive function by means of the BBB test on the second, seventh and fourteenth days after receiving the contusive injury to the spinal cord. They were sacrificed on the fourteenth day. RESULTS: This study demonstrated that the MP and GM-1 groups presented functional results that were better than those of the control group, although the enhanced recovery of group II (GM-1) relative to the control group was not statistically significant (p>0.05). The most notable recovery of locomotive function was observed in the group that received MP alone (p<0.05). The group that received MP together with GM-1 presented results that were better than those of the control group (p<0.05). CONCLUSION: Administration of methylprednisolone alone or with GM-1 was shown to be effective for recovery of locomotive function. Combined administration of these drugs resulted in better outcomes than administration of methylprednisolone alone.

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OBJECTIVE: To evaluate the effect of different concentrations of estrogen on the ovarian superficial epithelium in senile female rats. Design: Fifty female rats at 15 months of age and with irregular estrous cycles were selected and randomly divided into five experimental groups containing equal numbers of animals in each: GPROP, control group receiving vehicle only; GE0.05mg, group receiving conjugated equine estrogens (CEE) at a dose of 50 µg/kg; GE0.5mg, group receiving CEE at 500 µg/kg; GE1mg, group receiving CEE at 1 mg/kg; and GE2mg, receiving CEE at 2 mg/kg. The length of treatment was 21 days. After this period, the animals were anesthetized and the ovaries were fixed in 10% formaldehyde and processed for routine histology. Histomorphology was analyzed by light microscopy, and histomorphometrics were evaluated using the Imagelab program. RESULTS: In the GPROP and GE0.05mg groups, the superficial epithelium of the ovary had a simple cuboidal shape, and as the estrogen dose increased, the epithelium thickened, with pseudo-stratified or stratified epithelium appearing in the GE2mg group. The animals in the group given the highest estrogen dose (GE2mg) showed the thickest ovarian epithelium and the largest perimeter and surface area of the surface ovarian epithelium (P < 0.01). However, the difference in epithelium thickness between the GE0.5mg and GE1mg groups was only slight. CONCLUSION: Our data suggest that CEE at a dose of 2 mg/kg may induce marked proliferation of rat ovarian epithelium.

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Approximately 1% of the population has epilepsy, the most common neurological disorder. Moreover, people with epilepsy are more likely to die prematurely than those without epilepsy, and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, number of antiepileptic drugs and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. This review discusses the epidemiology, risk factors, etiology, and preventative measures in the management of SUDEP.

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Infertility affects 10-15% of couples who are trying to conceive, and half of the cases are due to male infertility. Intracytoplasmic sperm injection is increasingly being used to overcome multiple sperm deficiencies. Due to its effectiveness, some have proposed ICSI as a solution for all cases of male infertility, regardless of the cause. Hence, even men with potentially treatable causes of infertility have sought the aid of assisted reproductive technology, rather than undergo specific therapies to treat their infertility. Varicoceles are the most frequent physical finding in infertile men; indeed, they may be responsible for nearly one-third of cases of male infertility. Varicocele management, however, has always been a controversial issue because very few randomized, controlled studies have been performed to examine varicocelectomy as an infertility treatment. Significant evidence suggests that varicoceles have a harmful effect on the testis and that varicocelectomy can not only prevent progressive decline in testicular function but also reverse the damage. However, the degree to which varicocele repair improves pregnancy rates and the success of assisted reproductive technology remains controversial.