Neurosarcoidosis Presented as an Isolated Brain Lesion.

Sarcoidosis is a multisystemic, noncaseating granulomatous disease of unknown etiology. Neurosarcoidosis (NS) is the involvement of the central nervous system (CNS) in sarcoidosis, and it occurs in approximately 5%-10% of cases. NS can present with a variety of clinical features, making diagnosis challenging. A comprehensive diagnostic approach is required to obtain a definitive diagnosis. In this case we present a 13-year-old boy with diabetes mellitus presented with acute right-sided weakness, paresthesia, headaches, and episodes of loss of consciousness, followed by confusion and aggressive behavior. Neurological examination revealed right-sided motor and sensory deficits, as well as abnormal reflexes. Cranial imaging revealed a solitary lesion in the left centrum semi-ovale. Cerebrospinal fluid (CSF) analysis showed lymphoblastic leukocytosis, increased CSF angiotensin-converting enzyme (ACE), and a high IgG index. Extensive laboratory and imaging studies ruled out other potential etiologies. This case presented with a unique set of clinical features, including a mass lesion effect and seizures, which are uncommon in isolated NS. The patient responded well to high-dose corticosteroid therapy, with resolution of his symptoms. Levetiracetam was used to effectively manage his seizures.

Rectal Gastrointestinal Stromal Tumors.

Rectal gastrointestinal stromal tumors (GISTs) are rare types of tumors, but the incidence is increasing, and we now know more about the pathogenesis and management of rectal GIST. The main goal is to resect the tumor with negative microscopic margins. With the development of neoadjuvant Imatinib therapy, preoperative reduction in tumor size has become possible, thus introducing the chance for anus-preserving surgery, with better quality of life. We present a case of a 55-year-old female who presented to the emergency department with complaints of bleeding per rectum, abdominal pain, and pain on defecation. A 6-cm mass was detected during the rectal examination and a biopsy confirmed the diagnosis of GIST. The patient was given neoadjuvant imatinib chemotherapy for four months followed by trans-anal resection of the mass. The procedure was done successfully, and she received further adjuvant imatinib for a course of three years. Follow-up by magnetic resonance imaging and a colonoscopy after two years showed no recurrence. The patient is living healthily and doing well.

Androgen downregulates desmocollin-2 in association with induction of mesenchymal transition of breast MDA-MB-453 cancer cells.

Desmosomes are cellular structures that are critical in cell-cell adhesion and in maintaining tissue architecture. Changes in the expression of desmocollin-2 (DSC2) have been noted during tumor progression into an invasive phenotype and as cells undergo epithelial-mesenchymal transition. We have previously reported that breast MDA-MB-453 cancer cells, a luminal androgen receptor (AR) model of triple-negative breast cancer, acquire mesenchymal features when treated with the AR agonist, dihydrotestosterone (DHT). We have therefore investigated androgen regulation of the expression and cellular localization of DSC2 in MDA-MB-453 cells. Treatment of the cells with DHT resulted in a dose-dependent reduction in DSC2 protein levels and dispersion of its membrane localization concomitant with AR- and ß-catenin-mediated mesenchymal transition of cells. A significant correlation was revealed between decreased expression of AR and increased expression of DSC2 in patient samples. In addition, whereas lower expression of AR was associated with a reduced overall and recurrence-free survival of breast cancer patients, higher expression of DSC2 was found in invasive breast tumors than in normal breast cells and was correlated with lower patient survival. Upon knocking down DSC2, the cells became elongated, mesenchymal-like, and slightly, but insignificantly, more migratory. The addition of DHT further stimulated cell elongation and migration. DSC2 siRNA-transfected cells reverted to a normal epithelial morphology upon inhibition of ß-catenin. These results highlight the role of DSC2 in maintaining the epithelial morphology of MDA-MB-453 cells and the negative regulation of the desmosomal protein by DHT during stimulation of the androgen-induced, ß-catenin-mediated mesenchymal transition of the cells.

Prevalence and types of high-risk human papillomaviruses in head and neck cancers from Bangladesh.

BACKGROUND: There is a dramatic rise in the incidence of Human papillomavirus (HPV) - associated head and neck squamous cell carcinoma (HNSCC) in the world, with considerable variation by geography, gender and ethnicity. Little is known about the situation in Bangladesh, where tobacco- and areca nut-related head and neck cancers (HNCs) are the most common cancers in men. We aimed to determine the prevalence of HPV in HNSCC in Bangladesh and to explore the possible value of cell cycle markers in clinical diagnostic settings. METHODS: One hundred and ninety six archival HNSCC tissue samples were analysed for the presence of HPV DNA. The DNA quality was assured, and then amplified using a nested PCR approach. The typing of HPV was performed by automated DNA sequencing. Cellular markers p53, Cyclin D1 and pRb were tested on all samples by immunohistochemistry (IHC), as well as p16 as a putative surrogate for the detection of HPV. RESULTS: HPV DNA was detected in 36/174 (~21%) samples: 36% of cancers from the oropharynx; 31% of oral cancers, and 22% from the larynx. HPV-16 was most common, being present in 33 samples, followed by HPV-33 (2 samples) and HPV-31 (1 sample). Twenty-eight out of 174 samples were positive for p16, predominantly in HPV-positive tissues (p < 0.001). No statistically significant association was observed between the cellular markers and HPV DNA positive cases. However, p16 positivity had excellent predictive value for the presence of HPV by PCR. CONCLUSION: There is a significant burden of HPV-associated HNSCC in Bangladesh, particularly in the oropharynx but also in oral and laryngeal cancers. Whilst a combination of PCR-based DNA detection and p16 IHC is useful, the latter has excellent specificity, acceptable sensitivity and good predictive value for carriage of HPV in this population and should be used for prognostic evaluation and treatment planning of all HNSCC patients in South Asia, as in the Western world.

Surfactant for meconium aspiration syndrome in full term/near term infants.

BACKGROUND: Surfactant replacement therapy has been proven beneficial in the prevention and treatment of neonatal respiratory distress syndrome (RDS). The deficiency of surfactant or surfactant dysfunction may contribute to respiratory failure in a broader group of disorders, including meconium aspiration syndrome (MAS). OBJECTIVES: To evaluate the effect of surfactant administration in the treatment of term/near-term infants with MAS. SEARCH STRATEGY: Searches were made using The Cochrane Library (Issue 4, 2006), MEDLINE and EMBASE (1985 to December 2006), previous reviews including cross-references, abstracts, conference and symposia proceedings, expert informants, and journal hand searching. No language restrictions were applied. Authors were directly contacted to provide additional data. SELECTION CRITERIA: Randomised controlled trials which evaluated the effect of surfactant administration in term infants with meconium aspiration syndrome are included in the analyses. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including mortality, treatment with extracorporeal membrane oxygenation (ECMO), pneumothorax, duration of assisted ventilation, duration of supplemental oxygen, intraventricular haemorrhage (any grade and severe IVH), and chronic lung disease, and were excerpted from the reports of the clinical trails by the review authors. Data analyses were done in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Four randomised controlled trials met inclusion criteria. The meta-analysis of 4 trials enrolling 326 infants showed no statistically significant effect on mortality (typical relative risk 0.98 (95% CI 0.41, 2.39), typical risk difference 0.00 (95% CI -0.05, 0.05). The risk of requiring extracorporeal membrane oxygenation was significantly reduced in a meta-analysis of two trials (n = 208); (typical relative risk 0.64, 95% CI 0.46, 0.91; typical risk difference -0.17, 95% CI -0.30, -0.04); number needed to treat to benefit 6 (95% CI 3, 25). One trial (n = 40) reported a statistically significant reduction in the length of hospital stay [mean difference - 8 days (95% CI -14, -3 days)]. There were no statistically significant reductions in any other outcomes studied (duration of assisted ventilation, duration of supplemental oxygen, pneumothorax, pulmonary interstitial emphysema, air leaks, chronic lung disease, need for oxygen at discharge or intraventricular haemorrhage). AUTHORS' CONCLUSIONS: In infants with MAS, surfactant administration may reduce the severity of respiratory illness and decrease the number of infants with progressive respiratory failure requiring support with ECMO. The relative efficacy of surfactant therapy compared to, or in conjunction with, other approaches to treatment including inhaled nitric oxide, liquid ventilation, surfactant lavage and high frequency ventilation remains to be tested.

Follicular thyroid cancer presenting as a sellar mass: case report and review of the literature.

OBJECTIVE: To describe an uncommon initial manifestation of well-differentiated follicular carcinoma of the thyroid in an unusual metastatic site. METHODS: We present clinical, laboratory, and imaging findings in our patient and review related data from the literature. RESULTS: A young healthy woman presented with headache and diplopia. Magnetic resonance imaging of the brain showed a complex mass in the sellar region. Endocrine evaluation was remarkable only for a modestly high serum prolactin level. Transsphenoidal biopsy of the sellar mass revealed metastatic follicular thyroid carcinoma. On subsequent examination, a thyroid nodule was palpated. She underwent total thyroidectomy and ablative therapy with 131I, after which her symptoms gradually subsided and the sellar mass ultimately decreased in size. Although well-differentiated thyroid cancer generally manifests as a thyroid nodule, metastatic disease is present at the time of initial assessment in approximately 1% of cases, and the lungs and the skeleton are the most frequent sites of involvement. Only a few cases of thyroid cancer metastasizing to the sella have been reported. Described cases occurred mainly in elderly patients with previously diagnosed thyroid cancer. The most common malignant tumors that metastasize to the sella and pituitary are lung cancer in men and breast cancer in women. Metastatic tumors frequently manifest with cranial nerve palsies or diabetes insipidus and occur in elderly patients. CONCLUSION: Follicular thyroid cancer can manifest initially as a distant metastatic tumor in young patients. Metastatic lesions should always be in the differential diagnosis of a sellar mass, even in young patients.

Antifibrotic role of inducible nitric oxide synthase.

Long-term treatment in rats with l-NAME, an isoform-non-specific inhibitor of nitric oxide synthase (NOS), leads to fibrosis of the heart and kidney, suggesting that nitric oxide (NO) may play a role in preventing tissue fibrosis. In this process, a likely target of NO is the quenching of reactive oxygen species (ROS) through peroxynitrite formation, and one possible source for this NO is inducible NOS (iNOS). Using Peyronie's disease (PD) tissue from both human specimens and from a rat model of PD as the source of fibrotic tissue, we investigated if NO derived from iNOS could act as such an antifibrogenic defense mechanism by determining whether: (a) tunical ROS and iNOS are increased in PD; and (b) the long-term inhibition of iNOS activity decreases the NO/ROS balance in the tunica albuginea thereby promoting collagen deposition. It was determined that in the human PD plaque, iNOS mRNA and protein, ROS, collagen, and the peroxynitrite marker, nitrotyrosine, were all increased in comparison to the normal tunica. In the rat model of PD, the fibrotic plaque also showed significant increases in iNOS mRNA and protein, nitrotyrosine, ROS as measured by heme oxygenase-1, and collagen when compared with the normal control tunica. When a selective inhibitor of iNOS, L-NIL, was given to rats with the PD-like plaque, this resulted in a decrease in nitrotyrosine levels but intensified ROS levels and collagen deposition. These data demonstrate that: (a) iNOS induction occurs in both the human and rat PD fibrotic plaque; and (b) that the NO derived from iNOS appears to counteract ROS formation and collagen deposition. Because the inhibition of iNOS activity leads to a decrease in the NO/ROS ratio, thereby favoring the development of fibrosis, it is proposed that iNOS induction in this tissue may be a protective mechanism against fibrosis and abnormal wound healing.

Correlation of beta-endorphin and prostaglandin E2 levels in prostatic fluid of patients with chronic prostatitis with diagnosis and treatment response.

PURPOSE: The chronic pelvic pain syndrome is a clinically defined symptom complex of unclear etiology. We have noted increased oxidative stress in the prostatic fluid of these patients, implying an active inflammatory response. Immune cells can produce the natural opioid beta-endorphin at the site of injury, which may modulate pain. We measured beta-endorphin and the inflammatory marker prostaglandin E2 in the expressed prostatic secretions of men with prostatitis, and correlated the results with symptoms. MATERIALS AND METHODS: Expressed prostatic secretions samples from 70 patients and 8 asymptomatic controls were collected and frozen. beta-Endorphin and prostaglandin E2 were measured by enzyme-linked immunosorbent assay. Results were stratified according to prostatitis category and compared in individuals before and after therapy. RESULTS: In symptomatic patients beta-endorphin and prostaglandin E2 were not significantly different in categories II, IIIa and IIIb expressed prostatic secretions but they were higher than in controls. The mean beta-endorphin level plus or minus standard error of mean in symptomatic patients was significantly higher (23.8 +/- 11 ng./ml. versus 8.7 +/- 4.7, p = 0.0001) and mean prostaglandin E2 was lower (6.01 +/- 2.9 ng./ml. versus 3.01 +/- 2.9, p = 0.001) after successful therapy with antibiotics or antioxidant phytotherapy, Prosta-Q (Farr Laboratories, Santa Clarita, California). CONCLUSIONS: We observed a correlation of higher prostaglandin E2 and lower beta-endorphin in symptomatic men with chronic prostatitis. Increased oxidative stress and inflammation may induce prostaglandin E2 production that would inhibit beta-endorphin release. Treatment with therapeutic agents that decrease oxidative stress, such as antibiotics and antioxidant phytotherapy, may function at least partially by increasing beta-endorphin and decreasing prostaglandin E2.

Delayed graft function. Influence on outcome and strategies for prevention.

Delayed graft function remains a prevalent problem in cadaveric renal transplantation that increases rejection, decreases graft and patient survival, increases the cost of transplantation, and complicates patient management. Although current medical and surgical strategies can reduce the incidence of DGF to 20% or less, newer therapies that focus on nonimmune and immune forms of renal injury are needed to improve outcomes further.

Oxidative stress in prostatic fluid of patients with chronic pelvic pain syndrome: correlation with gram positive bacterial growth and treatment response.

The etiology of chronic pelvic pain syndrome (CPPS)/chronic prostatitis category III remains unknown. Whereas a subset of men respond to antimicrobial therapy, gram positive bacteria isolated from expressed prostatic secretions (EPS) are often considered to be commensal rather than pathogenic. We wished to study oxidative stress as a marker of tissue injury and response in EPS of men with CPPS to determine whether infection with gram positive bacteria is associated with increased oxidative stress. A total of 300 EPS specimens from 100 men with CPPS were collected for microscopy, culture, and biochemical and molecular assays. Oxidant injury was measured by 8-isoprostane F2alpha (IsoP) levels and total antioxidant capacity as Trolox equivalents. Total RNA from EPS was used for gene expression of heme oxygenase-1 (HO-1) and granzyme B. The only bacteria found in EPS were gram positive. For our analysis, these men were classified as having chronic bacterial prostatitis (category II). IsoP levels (pg/mL) were highest in men with category II prostatitis (7315 +/- 1428) followed by nonbacterial prostatitis (category IIIa, 2043 +/- 561), prostatodynia (category IIIb, 319 +/- 81), and asymptomatic controls (298 +/- 99). IsoP levels decreased significantly after successful treatment with antibiotics or an antioxidant supplement (Prosta-Q). Antioxidant capacity was detected in 11 out of 18, 4 out of 16, and 1 out of 16 men tested with category II, IIIa, and IIIb prostatitis, respectively. No correlation was observed between IsoP levels and the number of white blood cells in EPS. HO-1 and granzyme B expression was highest in men with category II prostatitis than in men with either category III prostatitis or asymptomatic controls. On the basis of elevated oxidative stress, clinical response to antibiotics, and post-treatment reduction in oxidative stress, we conclude that gram positive bacteria in some men with CPPS may be pathogens. It is speculated that oxidative stress may be a key pathway in some men with CPPS that can be targeted with antioxidant therapy.

Modulation of apoptotic and inflammatory genes by bioflavonoids and angiotensin II inhibition in ureteral obstruction.

OBJECTIVES: Ureteral obstruction results in an injury response that can progress to irreversible renal fibrosis and tubular atrophy by apoptosis. The molecular events leading to apoptosis from obstruction are not well understood. We investigated the effect of bioflavonoids and angiotensin II inhibition on apoptotic and inflammatory gene expression in a model of unilateral ureteral obstruction (UUO). METHODS: Complete UUO was produced in rats by ureteral ligation. The rats were treated with dimethyl sulfoxide (control), enalapril, losartan, curcumin, or quercetin. The animals were killed on day 7 and both obstructed and contralateral unobstructed kidneys were harvested. Expression of the inflammatory chemokine monocyte chemotactic protein-1, apoptosis effector genes Fas and Fas ligand, and oxidative stress gene HO-1 was evaluated by reverse transcriptase-polymerase chain reaction. RESULTS: Ureteral obstruction was associated with a 6.3-fold increase in monocyte chemotactic protein-1 expression compared with sham-operated rats (P = 0.01). Monocyte chemotactic protein-1 expression was severely attenuated in all other treatment groups (P <0.05). Similarly, Fas and Fas ligand expression were increased in control UUO kidneys compared with sham-operated ones (P <0.05). Fas gene expression was significantly inhibited by quercetin but not enalapril, losartan, or curcumin compared with the control. The induction of Fas ligand was attenuated in all treatment groups (P <0.05). HO-1 was expressed at low levels in both unobstructed and obstructed kidneys. Treatment with curcumin increased HO-1 expression fourfold (P <0.05). CONCLUSIONS: The expression of apoptotic and chemokine genes is significantly upregulated in UUO. Bioflavonoids and angiotensin inhibitors are able to attenuate the expression of these genes and thus may be beneficial in renal protection.

Detection of bacterial signal by 16S rRNA polymerase chain reaction in expressed prostatic secretions predicts response to antibiotic therapy in men with chronic pelvic pain syndrome.

PURPOSE: Some men with chronic pelvic pain syndrome (CPPS) have evidence of bacteria in their prostatic fluid (expressed prostatic secretions [EPS]) detected by 16S rRNA techniques. In this study, we correlate presence of bacterial signal with response to therapy. MATERIALS AND METHODS: EPS and first voided urine (VB1) from 47 men with CPPS were analyzed by polymerase chain reaction (PCR) for bacterial signal using universal primers specific for bacterial 16S rRNA. Signal was considered positive if found only in the EPS sample, or if at least 10x stronger in the EPS than in VB1. All patients were treated with antibiotic therapy. RESULTS: Thirty-three patients were category IIIa (nonbacterial prostatitis) and 14 were category IIIb (prostatodynia). Seventeen of the 33 category IIIa patients had positive localizing cultures for gram-positive bacteria. However, a positive bacterial signal was detected in 23 EPS samples by 16S rRNA PCR. This signal was found in 14 of 17 culture-positive patients, 7 of 16 of the remaining category IIIa patients, and 2 of 14 of category IIIb patients. No patient with negative bacterial signal improved with antibiotic therapy (negative predictive value 100%). Thirteen patients with positive bacterial signal improved with antibiotic therapy. CONCLUSIONS: In men with category III chronic prostatitis/CPPS, bacterial signal detected by PCR can help predict response to antimicrobial therapy.

Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial.

OBJECTIVES: The National Institutes of Health (NIH) category III chronic prostatitis syndromes (nonbacterial chronic prostatitis and prostatodynia) are common disorders with few effective therapies. Bioflavonoids have recently been shown in an open-label study to improve the symptoms of these disorders in a significant proportion of men. The aim of this study was to confirm these findings in a prospective randomized, double-blind, placebo-controlled trial. METHODS: Thirty men with category IIIa and IIIb chronic pelvic pain syndrome were randomized in a double-blind fashion to receive either placebo or the bioflavonoid quercetin 500 mg twice daily for 1 month. The NIH chronic prostatitis symptom score was used to grade symptoms and the quality-of-life impact at the start and conclusion of the study. In a follow-up unblind, open-label study, 17 additional men received 1 month of a supplement containing quercetin, as well as bromelain and papain (Prosta-O), which enhance bioflavonoid absorption. RESULTS: Two patients in the placebo group refused to complete the study because of worsening symptoms, leaving 13 placebo and 15 bioflavonoid patients for evaluation in the blind study. Both the quercetin and placebo groups were similar in age, symptom duration, and initial symptom score. Patients taking placebo had a mean improvement in NIH symptom score from 20.2 to 18.8 (not significant), while those taking the bioflavonoid had a mean improvement from 21.0 to 13.1 (P = 0.003). Twenty percent of patients taking placebo and 67% of patients taking the bioflavonoid had an improvement of symptoms of at least 25%. In the 17 patients who received Prosta-Q in the open-label study, 82% had at least a 25% improvement in symptom score. CONCLUSIONS: Therapy with the bioflavonoid quercetin is well tolerated and provides significant symptomatic improvement in most men with chronic pelvic pain syndrome.

Prevalence of corynebacterial 16S rRNA sequences in patients with bacterial and "nonbacterial" prostatitis.

The etiology of chronic prostatitis syndromes in men is controversial, particularly when positive cultures for established uropathogens are lacking. Although identification of bacteria in prostatic fluid has relied on cultivation and microscopy, most microorganisms in the environment, including some human pathogens, are resistant to cultivation. We report here on an rRNA-based molecular phylogenetic approach to the identification of bacteria in prostate fluid from prostatitis patients. Positive bacterial signals were seen for 65% of patients with chronic prostatitis overall. Seven of 11 patients with bacterial signals but none of 6 patients without bacterial signals were cured with antibiotic-based therapy. Results indicate the occurrence in the prostate fluid of a wide spectrum of bacterial species representing several genera. Most rRNA genes were closely related to those of species belonging to the genera Corynebacterium, Staphylococcus, Peptostreptococcus, Streptococcus, and Escherichia. Unexpectedly, a wide diversity of Corynebacterium species was found in high proportion compared to the proportions of other bacterial species found. A subset of these 16S rRNA sequences represent those of undescribed species on the basis of their positions in phylogenetic trees. These uncharacterized organisms were not detected in control samples, suggesting that the organisms have a role in the disease or are the consequence of the disease. These studies show that microorganisms associated with prostatitis generally occur as complex microbial communities that differ between patients. The results also indicate that microbial communities distinct from those associated with prostatitis may occur at low levels in normal prostatic fluid.