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A supernumerary frenulum on the dorsal aspect of the penis, without penile torsion, is a rare condition. The present case report presents a 29-year-old male who experienced pain during sexual intercourse. He noticed a band of tissue on the underside of his foreskin that prevented the retraction of his prepuce during his first attempted sexual intercourse. The present case illustrates a supernumerary frenulum, which is an additional band of tissue on the dorsal side of the penis, alongside the normally positioned frenulum. It is a natural anatomical variation. The high prevalence of neonatal religious circumcision and general ignorance likely contribute to the under-reporting of this anomaly. This condition can significantly impact an individual’s sexual life and personal hygiene. The present case was aimed to enhance understanding of the embryology, prevalence, clinical implications and management of this anomaly.

Stock split means division of the face value of the stock. Stocks are basically split to increase the supply of stocks in the market. Stock splits do not change the capital structure and capitalization but they only readjust them and thereby increase or decrease number of outstanding shares of the company. Stock splits are different from other corporate actions like buyback of shares, bonus issues and right issues. This research article concentrates on the concept of stock splits - a theoretical framework including guidelines for stock splits in India. The present research article does not employ any specific tool for organizing the existing literature on the stock splits. The research article concludes that the companies in India like the companies in advanced countries should split their stocks only when they are sure that their stock splits will ensure abnormal returns, increase in the volume of trading and signal the better prospectus for the company in the future. The companies in India should not frequently split their stocks to manipulate the share price and confuse the market. [ABSTRACT FROM AUTHOR]

Lipoma is the most common benign tumour in hand. Lipoma in hand of size more than 5 cm is classified as Giant Lipoma. Lipoma of larger sizes is rare in hand because of accessibility and lesser subcutaneous tissues. Large lipoma interferes in the hand functions. Lipoma in dominant hand is usually noted early and gets operated. This case is of 65 year old female patient who reported with the swelling in right hand for past 25 years. The size of the lipoma was big and asymptomatic till the presentation. The swelling was investigated and surgically removed which was diagnosed histopatholoically as Intermuscular Thenar Lipoma .

We present a discrete-event simulation model of the kidney transplantation system in an Indian state, Rajasthan. Organs are generated across the state based on the organ donation rate among the general population, and are allocated to patients on the kidney transplantation waitlist. The organ allocation algorithm is developed using official guidelines published for kidney transplantation, and model parameters were estimated using publicly available data to the extent possible. Transplantation outcomes generated by the model include: (a) the probabilities of a patient receiving an organ within one to 5 years of registration and (b) the average number of deaths per year due to lack of donated organs. Simulation experiments involving observing the effect of increasing the organ arrival rate and establishing additional transplantation centres on transplantation outcomes are also conducted. We also demonstrate the use of such a model to optimally locate additional transplantation centres using simulation optimisation methods., Competing Interests: No potential conflict of interest was reported by the authors., (© Operational Research Society 2020.)

Acute febrile illness is a common entity in tropics and often is challenging due a host of pathogenic bacteria, viruses and fungi. Extensive work up is required for better management. Rickettsiosis is uncommon and hence comes lower down in the differentials of multiorgan failure being superseded by the more common diseases as malaria, enteric fever and Dengue. We document a case of young male presenting with high grade fever, multiorgan dysfunction (hepatic, renal, neurological and respiratory involvement), conjunctival suffusion, retiform rash and without lymphadenopathy. The diagnosis was further challenging because the rashes appeared late at 8th day in the course of illness, unlike the typical disease where rashes come on early in day 3-6 of the disease. Patient responded to timely treatment with doxycycline. Thus, a high index of suspicion is needed to diagnose Rickettsiosis in geographical areas apparently free of the disease.

Background: Interleukin-6 (IL-6) is associated with prostate cancer morbidity. In several experimental models, IL-6 has been reported to have anti-apoptotic and pro-angiogenic effects. Siltuximab (CNTO 328) is a monoclonal anti-IL-6 antibody which has been successfully applied in several models representing prostate cancer. This study was designed to assess preliminary safety of siltuximab in patients with early prostate cancer., Patients and Methods: Twenty patients scheduled to undergo radical prostatectomy received either no drug or siltuximab (6 mg/kg, five patients per group with administration once, two times, and three times prior to surgery). Blood samples were collected for pharmacokinetic and pharmacodynamic analyses. Expression of elements of IL-6 signaling pathways was analyzed in tumor tissue by immunohistochemistry. Gene analysis in tumor specimens was performed with the DASL array., Results: No adverse events related to siltuximab were observed. Patients treated with siltuximab presented with higher levels of proliferation and apoptosis markers. Following a single dose, serum concentrations of siltuximab declined in a biexponential manner. This study revealed a decrease in phosphorylation of Stat3 and p44/p42 mitogen-activated protein kinases. In addition, gene expression analyses indicate down-regulation of genes immediately downstream of the IL-6 signaling pathway and key enzymes of the androgen signaling pathway., Conclusions: Preliminary safety of siltuximab is favorable. Future studies in which siltuximab could be combined with androgen-deprivation therapy and experimental therapies in advanced prostate cancer are justified., (Copyright © 2011 Wiley-Liss, Inc.)

Ustekinumab, a human anti-interleukin (IL)-12/IL-23p40 monoclonal antibody has demonstrated significant efficacy in patients with moderate-to-severe psoriasis. Skin lesion biopsies, cell surface markers on peripheral blood lymphocytes, and ex vivo T-helper (Th)1/Th2 cytokine responses from peripheral blood mononuclear cells (PBMC) from patients receiving ustekinumab 45 or 90 mg, or placebo were evaluated at baseline and week 12. Inflammatory serum protein levels were measured at baseline, week 2 and week 12. At week 12, median epidermal thickness decreased from 312.1 to 132.7 microm, and median levels of cellular proliferation (Ki67) and T-cell infiltration (CD3) decreased by 84.3% and 70.7%, respectively, in the combined ustekinumab group (all P < or = 0.002). Serum levels of tumor necrosis factor (TNF)-alpha, C-C motif ligand 27 (CCL27) and other inflammatory cytokines remained unchanged. Minimal variation in the percentage of T cells expressing cutaneous lymphocyte antigen (CLA) was observed following ustekinumab treatment, with no significant variation in the percentage of cells expressing CD45RA, CD45RO, CD25, human leukocyte antigen-DR (HLA-DR), and C-X-C motif receptor 3 (CXCR3). No apparent effect on the magnitude of Th1/Th2 responses to external stimuli in PBMC was observed following placebo or ustekinumab treatment. Ustekinumab improves histological psoriasis measures, with minimal impact on the systemic immune system.

Purpose: Interleukin-6 (IL-6) induces tumor growth, invasion, metastasis, and angiogenesis. Siltuximab (CNTO 328) is a chimeric, murine-human monoclonal antibody that specifically binds human IL-6 with high affinity. C-reactive protein (CRP) can be a pharmacodynamic (PD) marker of IL-6 bioactivity. Reductions in CRP may correlate with clinical activity and IL-6 bioactivity., Experimental Design: Starting-dose selection for this study was based on a previous siltuximab study in multiple myeloma patients. Pharmacokinetic (PK)/PD modeling explored the relationship between siltuximab PK and CRP suppression following i.v. siltuximab infusion in a three-part phase I/II study in 68 metastatic renal cell carcinoma patients. Modeling results were then used to simulate and determine which siltuximab dosage regimens would maintain CRP suppression below the lower limit of quantification (4 mg/L). Siltuximab was given at 1, 3, 6, or 12 mg/kg at weeks 1 and 4 and then every 2 weeks for 2 cycles in part 1; at 3 or 6 mg/kg every 3 weeks for 4 cycles in part 2; and at 6 mg/kg every 2 weeks for 6 cycles in part 3., Results: A two-compartment PK model adequately described the serum siltuximab concentration-time data. An inhibitory indirect response PD model examined the relationship between siltuximab concentrations and CRP suppression. PD parameter estimates seemed reliable and physiologically relevant. Simulations showed that 6 mg/kg siltuximab every 2 weeks or 9 mg/kg every 3 weeks would reduce serum CRP to below 4 mg/L., Conclusions: Using a stepwise design, PK/PD modeling was used to select the dose levels in this study. Furthermore, PK/PD modeling results were used to help select doses to be used in future siltuximab clinical development.

Background: Monocyte chemotactic protein-1 (MCP-1) is a chemokine ligand that has been associated with aggressive behavior in breast and prostate cancer. The present study was performed to determine if there is a relationship between the expression of MCP-1 in papillary thyroid carcinoma (PTC) and factors indicative of aggressive behavior in this disease., Methods: The subjects of this study were 115 patients with PTC. MCP-1 expression was determined using a semiquantitative scoring system for immunohistochemical staining of MCP-1 in resected PTC samples. There were four levels of immunohistochemical staining intensity, and the population of cells that positively stained for MCP-1 was graded at four levels. The scores for the intensity of immunohistochemical staining for MCP-1 and for the percentage of cells that stained for MCP-1 were used to generate a range from 0 to 9 for scoring MCP-1 expression., Results: Positive staining for MCP-1 was observed in the cytoplasm of PTC cells and stroma cells in 79.2% of the specimens. Expression levels of MCP-1 in PTC cells were positively correlated with tumor size (p < 0.05) and lymph node involvement (p < 0.05). In addition, the expression of MCP-1 in PTC cells level was an independent predictive factor for recurrence of PTC in an analysis that included age, sex, tumor size, extrathyroidal infiltration, and lymph node involvement (p < 0.005)., Conclusions: MCP-1 expression in PTC may stimulate the aggressive behavior of this tumor or it may be a marker for aggressive behavior. Previous reports with non-thyroid tumor cells favor the hypothesis that MCP-1 expression promotes aggressive behavior in PTC.

To evaluate the safety and efficacy of infliximab administered with gemcitabine to treat cancer cachexia and to explore a functional measure of clinical benefit, investigators involved in this multicenter, phase II, placebo-controlled study randomized 89 patients with stage II-IV pancreatic cancer and cachexia to receive either placebo or 3 mg/ kg or 5 mg/kg of infliximab at weeks 0, 2, and 4 and then every 4 weeks to week 24; patients also received 1,000 mg/m2 of gemcitabine weekly from weeks 0-6 and then for 3 of every 4 weeks until their disease progressed. The primary endpoint was change in lean body mass (LBM) at 8 weeks from baseline; major secondary endpoints included overall survival, progression-free survival, Karnofsky performance status, and 6-minute walk test distance. In addition, quality of life was measured. The mean change in LBM at 8 weeks was +0.4 kg for patients receiving placebo, +0.3 kg for those receiving 3 mg/kg of infliximab, and +1.7 kg for those receiving 5 mg/kg of infliximab. No statistically significant differences in LBM or secondary endpoints were observed among the groups. Safety findings were similar in all groups. Adding infliximab to gemcitabine to treat cachexia in advanced pancreatic cancer patients was not associated with statistically significant differences in safety or efficacy when compared with placebo.

Integrins are heterodimeric cell adhesion receptors that mediate intercellular communication through cell-extracellular matrix interactions and cell-cell interactions. Integrins have been demonstrated to play a direct role in cancer progression, specifically in tumor cell survival, tumor angiogenesis, and metastasis. Therefore, agents targeted against integrin function have potential as effective anticancer therapies. Numerous anti-integrin agents, including monoclonal antibodies and small-molecule inhibitors, are in clinical development for the treatment of solid and hematologic tumors. This review focuses on the role of alpha(v) integrins in cancer progression, the current status of integrin-targeted agents in development, and strategies for the clinical development of anti-integrin therapies.

Cytokines interleukin (IL)-12 and IL-23 are implicated in the pathogenesis of psoriasis. IL-12 causes differentiation of CD4+ T cells to interferon-gamma (IFN-gamma)-producing T helper 1 (Th1) cells, while IL-23 induces differentiation to IL-17-producing pathogenic Th17 cells. The effects of the monoclonal antibody to IL-12/23 p40 subunit (CNTO 1275) on IL-12 receptor (IL-12R) expression, markers associated with skin homing, activation, and cytokine secretion were investigated in vitro using human peripheral blood mononuclear cells (PBMCs) from healthy donors. PBMCs were activated in the presence or absence of recombinant human (rh) IL-12 or rhIL-23, with or without CNTO 1275. CNTO 1275 inhibited upregulation of CLA, IL-12R, IL-2Ralpha and CD40L expression and also inhibited IL-12- and IL-23-induced IFN-gamma, IL-17A, tumor necrosis factor (TNF)-alpha, IL-2, and IL-10 secretion. Thus, the therapeutic effect of CNTO 1275 may be attributed to the IL-12/23 neutralization, resulting in decreased expression of skin homing and activation markers, and IL-12- and IL-23-induced cytokine secretion.

Purpose: A fully human monoclonal antibody to anti-alpha(v) integrins (CNTO 95) has been shown to inhibit angiogenesis and tumor growth in preclinical studies. We assessed the safety and pharmacokinetics of CNTO 95 in patients with advanced refractory solid tumors., Experimental Design: In this phase I trial, CNTO 95 (0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg) was infused on days 0, 28, 35, and 42, and clinical assessments, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and [(18)F]-2-fluorodeoxyglucose positron emission tomography (FDG-PET) were done. Patients achieving stable disease or better were eligible for extended dosing every 3 weeks for up to 12 months., Results: Among the 24 enrolled patients, CNTO 95 was associated with one episode of grade III and four episodes of grade II infusion-related fever (all responded to acetaminophen). Of the six patients who received extended dosing, one patient (10.0 mg/kg), with cutaneous angiosarcoma, had a 9-month partial response. Pre- and post-treatment lesion biopsies confirmed tumor cell alpha(v) integrin expression, as well as CNTO 95 penetration of the tumor and localization to tumor cells in association with reduced bcl-2 expression. A lesion in one patient (10.0 mg/kg) with stable ovarian carcinosarcoma was no longer detectable by FDG-PET by day 49. Exposure to CNTO 95 seemed to increase in a greater-than-dose-proportional manner; dose-dependent mean half-life ranged from 0.26 to 6.7 days., Conclusions: CNTO 95 was generally well tolerated. Six patients received extended therapy, including one patient with a prolonged response. Biopsy data confirmed tumor localization and pharmacodynamic activity.