A systematic review and meta-analysis of predictors of recurrence in patients with Solid Pseudopapillary Tumors of the Pancreas.

BACKGROUND: The recurrence rates and predictors of recurrence in patients with Solid Pseudopapillary tumors (SPT) are unclear, which makes it challenging to determine the duration of follow-up. The aim of the current study was to perform a systematic review and meta-analysis to determine the recurrence rates and pathologic factors associated with recurrence in patients with SPT. METHODS: A PubMed, Scopus, and Web of Science search was conducted to identify studies of SPT published during the last 15 years: (09/2002-09/2017). Studies reporting on patients with SPT and follow-up of >5 years were included. The search strategy was conducted per 2009 PRISMA guidelines. RESULTS: A total of 103 studies reporting on 2599 non-metastatic SPT patients were identified. Sixty-nine patients (2.6%) developed recurrence during follow-up. Pooled estimates from studies with a sample size >20 (N = 33) noted an overall recurrence rate of 2% (95% CI 1-2%). Male gender (OR 1.960), positive lymph nodes (OR 11.9), R1 margins (OR 11.1), and LVI (OR 5.5), were associated with a significantly (all p < 0.05) increased risk of recurrence. CONCLUSION: Current meta-analysis suggests that only 2% of patients with SPT experience recurrence after resection. These data will guide the treating physicians and patients regarding recurrence rates and help identify patients at increased risk of recurrence during follow-up.

Green tea extract prolongs allograft survival as an adjunctive therapy along with low dose cyclosporine A.

The current immunosuppressive drugs are successful in prolonging allograft survival but fail to achieve transplantation tolerance or prevent chronic rejection. Consequently, there is ongoing research to develop novel combinatorial therapies that are more efficacious in prolonging allograft survival as well as induce tolerance toward the transplanted organ. The present study aims to study the efficacy of green tea extract (GTE) in combination with low dose cyclosporine A (CyA) in prolonging allograft survival in mice. Numerous studies have reported the anti-inflammatory and immunomodulatory properties of GTE and its various catechin components. GTE is also known to attenuate CyA induced nephrotoxicity. Therefore, we hypothesized that GTE alone or in combination with CyA will prolong graft survival. Our study demonstrates that GTE in combination with low dose CyA significantly prolongs graft survival as well as increase the production of immunosuppressive cytokine, IL-10. GTE also decreases CyA induced high TGF-beta production, which is incriminated in CyA induced nephrotoxicity. We also observed that GTE inhibits both nonspecific and antigen-specific proliferation of T cells in vitro. These results indicate the potential of GTE as an adjunctive therapy in combination with CyA to prolong allograft survival and to reduce CyA induced nephrotoxicity.

Deep venous thrombosis in surgical intensive care unit: prevalence and risk factors.

BACKGROUND: Critically ill patients are at high risk for developing venous thromboembolism. The objective of this study was to determine the prevalence of, and risk factors for, lower extremity deep vein thrombosis (DVT) among critically ill surgical patients in Thailand. MATERIALS AND METHODS: Patients older than 15 years who were admitted to a surgical intensive care unit (ICU) of a tertiary care hospital were enrolled. Bilateral lower extremity compression Doppler ultrasonographic examination was performed to detect DVT within 14 days of ICU admission. Demographic data, primary disease, operative intervention, co-morbidities, acute physiology and chronic health evaluation (APACHE) II score and the length of ICU stay were tested for association with the presence of DVT. RESULTS: Among the 190 first-time admitted ICU patients with a mean APACHE II score of 9.2 +/- 6.0 (range, 0-29), 20 patients had DVT (prevalence of 10.5%). Thromboprophylaxis was not given to any patient. The only independent and significant risk factor for DVT was a longer ICU stay. Age, sex, APACHE II score, presence of comorbidities and operative intervention were not associated with the presence of DVT. CONCLUSION: The prevalence of DVT in critically ill patients in a Thai surgical ICU was approximately 10.5%. Further research is needed to evaluate the risks and benefits of venous thromboprophylaxis in Thai patients.

An interleukin-6-neutralizing antibody prevents cyclosporine-induced nephrotoxicity in mice.

INTRODUCTION: Chronic use of cyclosporine A (CyA) induces nephrotoxicity primarily due to endothelial dysfunction. In our previous studies, potential mechanisms were identified in vitro and implicated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and interleukin-6 (IL-6) as key components in causing endothelial dysfunction. In this study, we tested the hypothesis that NADPH oxidase activity and IL-6 are key components in renal damage in an in vivo model. METHODS: Male mice C57B/6 mice from Jackson Laboratory (Bar Harbor, ME) at 6-8 wks were subjected to a low-salt diet throughout the trial. After 1 week on a low-salt diet, the mice were injected daily with treatments in 50 muL vehicle composed of 75% cremaphor (Sigma, St. Louis, MO) and ethanol for 5 wks. A vehicle-alone group was also set aside. Mice were weighed and 25 mg/kg/day cyclosporine (Novartis Pharma, St. Louis, MO) was injected daily. Apocynin (Calbiochem, Gibbstown, NJ) 20 mg/kg were injected either alone or concomitantly with CyA. Another group of mice were administered IL-6 antibody (Cat no. MAB406; R&D Systems, Minneapolis, MN) at 2 mug/day along with CyA. The kidneys were removed en bloc immediately and submitted in formalin for paraffin sections. Trichrome stains were performed. Slides were blinded and 10 photographs of cortical areas per treatment group were taken, which covered an estimate of 10% surface area in random fashion. Areas of renal damage, which were determined by tubular necrosis, were identified and quantified by amount of necrosis per photograph. Each photograph was divided into 10 blocks, and the number of blocks that contained necrotic tubules per photo was recorded. RESULTS: The two control mice (low salt only) had no damage. The four vehicle mice had trace amounts of tubular necrosis. CyA treatment group demonstrated the highest amount of damage (29/70; 41%). CyA with apocynin, a specific NADPH oxidase inhibitor, was found to have 36% (22/60) damage, whereas the CyA with IL-6 antibody only was observed to have 15% (6/40) damage. Comparing imaging analysis, there was no difference between mice treated with CyA alone and with CyA with apocynin. However, the amount of damage in mice treated with CyA and IL-6 antibody was found to be significantly lower than both CyA and CyA with apocynin. CONCLUSIONS: CyA action as a calcineurin inhibitor has allowed prolongation of kidney transplants, but its chronic use has led to devastating consequences such as allograft nephropathy. Previously, we have identified potential mechanisms of CyA-induced endothelial dysfunction in vitro. The current study identifies increased IL-6 expression as a mechanism by which CyA induces renal damage and that the use of an IL-6-neutralizing antibody may be useful in reducing CyA-induced renal damage.

Cyclosporine inhibition of angiogenesis involves the transcription factor HESR1.

PURPOSE: Angiogenesis is critical in normal development and in tumor growth. Experimentally, cyclosporine A (CyA) inhibits angiogenesis in an in vivo mouse model and an in vitro capillary tube model. The mechanisms behind its antiangiogenic effects are not well characterized. To determine which nuclear factor, if any, may be involved in the antiangiogenic effects of CyA, we performed a microarray analysis of human aortic endothelial cells (HAEC) subjected to CyA and another calcineurin inhibitor, FK 506. METHODS: HAEC were divided into four groups: (1) HAEC incubated with CyA 2 microg/mL; (2) HAEC incubated with CyA 10 microg/mL; (3) HAEC incubated with FK 506 1 microg/mLl for 24 h; and (4) HAEC as control. We used Affymetrix GeneChip U133-A for gene expression analysis and validated our results with quantitative reverse transcription-polymerase chain reaction. RESULTS: At a 2 microg/mL dose, CyA treated HAEC revealed a 44-fold increase in the expression of hairy enhancer of split-related protein 1 (HESR1) and 1.73-fold down-regulation of transcripts encoding for the vascular endothelial growth factor (VEGF) receptor (VEGFR2). At 10 microg/mL, the expression of the HESR1 transcript was 57-fold higher than control, and VEGFR2 exhibited a 1.93-fold down-regulation. Quantitative reverse transcription-polymerase chain reaction confirmed a significant (P < 0.0001) increase in expression of HESR1 in CyA treated cells. In contrast, the expression level of HESR1 was not affected by the FK 506 treatment. CONCLUSION: CyA demonstrate antiangiogenic activities linked to an overexpression of HESR1 transcription factor, and down-regulation of VEGFR2. Thus, use of high-dose CyA may provide a novel treatment in angiogenesis dependent disease.

Ginger extract inhibits LPS induced macrophage activation and function.

BACKGROUND: Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. METHODS: Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. RESULTS: We observed that ginger extract inhibited IL-12, TNF-alpha, IL-1beta (pro inflammatory cytokines) and RANTES, MCP-1 (pro inflammatory chemokines) production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-gamma and IL-2 production by T cells in response to allostimulation was also observed. CONCLUSION: In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

Nonoperative Management May Be a Viable Approach to Plexiform Neurofibroma of the Porta Hepatis in Patients with Neurofibromatosis-1.

BACKGROUND: Plexiform neurofibroma (PNF) in the porta hepatis (PH) is an unusual manifestation of neurofibromatosis-1 (NF-1). Resection is often recommended given the risk of malignant transformation. We encountered a challenging case in clinical practice which prompted us to report our findings and perform a systematic review on the management of these tumors. METHODS: We reported the case of a 31-year-old woman with NF-1 and PNF of the PH. PRISMA 2009 guidelines were followed for systematic review. RESULTS: Our patient was found to have unresectable disease at exploration. After >5 years of follow-up, she continued to have stable disease on imaging. We identified 12 studies/case reports including 10 adult and 6 pediatric patients with PNF of PH. None of the 7 adult patients with NF-1 and PNF of PH underwent a successful tumor resection. All pediatric patients were managed with surveillance alone. All but one pediatric patient had NF-1. None of the reported cases of PNF of PH had malignant transformation. CONCLUSION: Our findings suggest that PNFs of PH in the setting of NF-1 are often unresectable and may have an indolent course. Surveillance alone may be a reasonable option in some patients; however, further studies are needed.

Neurotrophic and neuroprotective effects of milk thistle (Silybum marianum) on neurons in culture.

Herbal products are being increasingly used as dietary supplements and therapeutic agents. However, much more research must be performed in order to determine the biological basis for their putative clinical effects. We tested the effects of milk thistle (Silybum marianum) extract on the differentiation and survival of cultured neural cells. Milk thistle enhanced nerve growth factor (NGF)-induced neurite outgrowth in PC-12 neural cells and prolonged their survival in culture. Milk thistle extract also protected cultured rat hippocampal neurons against oxidative stress-induced cell death. Our data demonstrate that milk thistle extract can promote neuronal differentiation and survival, suggesting potential benefits of chemicals in this plant on the nervous system.

Locally derived cytokines and upregulation of MHC class II genes in allografts.

BACKGROUND: In vitro, various cytokines can modulate the level of expression of major histocompatibility complex (MHC) Class II antigens. Major histocompatibility complex Class II hyperexpression occurs in many immunologic disorders in vivo, but the cytokines that affect this are difficult to analyze because they are produced in small amounts, they act locally, and their mRNAs have short half-lives. METHODS: We studied the expression of cytokines known to up-regulate MHC Class II genes in heart allografts in mice from B10.BR donors to B10.D2 recipients by reverse transcription of mRNA and polymerase chain reaction amplification. The I-Abeta(k) gene expression was also studied in the same fully MHC incompatible strain combination. RESULTS: Messenger RNA for interferon (INF)-gamma, interleukin (IL)-4, and tumor necrosis factor (TNF)-alpha, known inducers of MHC Class II expression in vitro, could be detected in allografts either 24 hours before or simultaneously with massive induction of graft specific I-Abeta mRNA. Interleukin-6 mRNA could be detected as early as 1 day after grafting. CONCLUSION: These data suggest that known cytokine up-regulators of MHC Class II genes, i.e., IFN-gamma, IL-4, and TNF-alpha may contribute to the upregulation of graft-specific MHC Class II antigens during an allograft reaction. Also, IL-6 expression in allografts may result from the stress of the grafting procedure, as it is evident very early after grafting.

Resident perceptions of the impact of work-hour restrictions on health care delivery and surgical education: time for transformational change.

BACKGROUND: The Accreditation Council for Graduate Medical Education has recently enacted an 80-hour workweek, which has been in effect in New York State for several years. We surveyed surgical residents from all four State University of New York (SUNY) surgical programs to determine their perceptions of the impact of the 80-hour workweek on patient care, surgical education, and personal life. METHODS: A survey instrument to address the three areas of concern was developed and administered to all surgical residents at the four SUNY programs. Anonymity of the responders was maintained. Responses to the questions were in numeric rank scores and were analyzed by descriptive statistics, chi-square analysis, and analysis of variance. RESULTS: Response rate was 59%. Factors perceived to be affected negatively by the residents were continuity and safety of care, their operative experience, and their relations with attendings. The factors affected positively were increased personal time and decreased fatigue at work. Interestingly, the latter did not appear to decrease the rate of medical errors in their perception. CONCLUSIONS: The 80-hour workweek has the potential to have adverse effects on patient care despite improving the level of fatigue at work. Reengineering the surgical residencies will be needed to take full advantage of the restricted work hours.

beta1-integrin-ligand disengagement induces in vitro capillary tube disruption mediated by p38 MAPK activity.

BACKGROUND: Disrupting cell-matrix interactions may lead to capillary injury as seen in sepsis and transplant rejection. Previously, we demonstrated capillary disruption mediated by beta1-integrin-ligand disengagement. We now determine whether p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) pathways are involved in this capillary injury. METHODS: Endothelial capillaries on Matrigel were preincubated with a p38 MAPK inhibitor (SB203580), ERK pathway inhibitor (PD98059), or dimethyl sulfoxide. Subsequently, a beta1-integrin blocking (P5D2) or an irrelevant antibody was added. After 24 hours, capillary integrity was quantified as capillary intersections/well. Antibody-treated cell lysates then were immunoprecipitated with either a phospho-p38 MAPK or phospho-ERK1/2 antibody. Kinase activity was measured with ATF-2 and Elk-1 fusion proteins as substrates for p38 MAPK and ERK, respectively, followed by Western blotting. RESULTS: P5D2 disrupted capillary tubes. Increased p38 MAPK activity at 8 hours and ERK activity at 2 and 8 hours were seen in P5D2-treated lysates. Preincubation with SB203580, but not with PD98059 or DSMO, significantly reduced capillary tube disruption. CONCLUSIONS: The beta1-integrin-ligand disengagement resulted in capillary disruption and stimulated p38 MAPK and ERK activity. In spite of activation of both pathways, the p38 MAPK but not the ERK pathway inhibitor prevented beta1-integrin antibody effects. Inhibiting p38 MAPK may mitigate capillary injury associated with sepsis and transplant rejection.

Amelioration of cyclosporin A effect on microvasculature by endothelin inhibitor.

BACKGROUND: We have previously shown that endothelial injury by cyclosporin A (CyA) is associated with an increased endothelin-1 (ET-1) release. We now sought to determine, in an animal model of angiogenesis, if inhibiting the effect of ET-1 on endothelial cells (ECs) would reverse the CyA-mediated endothelial injury in an animal model of angiogenesis. METHODS: An angiogenic mixture of Matrigel (0.5 ml), fibroblast growth factor (1 ng/ml), vascular endothelial growth factor (100 ng/ml), and heparin (64 unit/ml) was injected as a subcutaneous plug in the flank of C3H mice (n = 5). In experimental groups CyA (20 mg/ml), CyA, and BQ 123 (ET-A receptor antagonist), CyA and PD 142893 (ET-A and ET-B receptor antagonist), or CyA and ET-1 antibody were added to the angiogenic mixture. Angiogenesis in the mixture was quantified by modified planimetric point counting method in skin/Matrigel cross-sections stained with factor VIII to highlight endothelial neocapillaries. Mean +/- SD of angiogenic area was analyzed with analysis of variance and Bonferroni test. The survival curves obtained by Kaplan-Meier analysis were compared between the groups, and the statistical significance of survival and mortality rates was computed by log rank's and Fisher's exact test, respectively. RESULTS: The mean +/- SD of angiogenic area in control animals (without CyA in the angiogenic mixture) was 56.76 +/- 4.2. CyA inhibited angiogenesis in the subcutaneous angiogenic plug. Adding CyA to the angiogenic mixture significantly reduced angiogenic area (5.33 +/- 1.4, P <.001) while vehicle for CyA had no such effect (56.33 +/- 3.8, P =.10). Polyclonal ET-1 antibody or PD 142893 ameliorated the effect of CyA, whereas BQ 123 did not. The mean angiogenic areas in animals with ET-1 antibody, PD 142893, or BQ 123 in the angiogenic mixture were 57.20 +/- 7.5 (P =.06), 46.00 +/- 11.5 (P = 1.0), 8.60 +/- 2.9 (P <.001), respectively. CONCLUSIONS: Our data show that blocking ET-B receptors specifically ameliorates the microvascular injury to the neocapillaries in angiogenesis caused by CyA. Antiendothelin-1 antibody and ETR antagonist (PD 142893) could, therefore, reduce the ill effects of CyA on microvascular endothelium.

Role of endothelin-1 in microvascular dysfunction caused by cyclosporin A.

BACKGROUND: Endothelin-1 (ET-1), a potent vasoconstrictive peptide, is implicated in cyclosporin A (CyA) vasculopathy. Previously we have demonstrated, in an in vitro model of endothelial capillaries, that CyA inhibits the formation of the capillaries and, in high doses, disrupts the capillaries. This study addresses the role of ET-1 in CyA-induced endothelial dysfunction of the in vitro capillaries. STUDY DESIGN: Endothelial cells (ECs) were cultured on a laminin-rich matrix, Matrigel, to form capillary-like networks. The ECs were treated with CyA either before capillary tube formation or after capillary tubes had formed. ppET-1 gene expression was studied by reverse transcriptase polymerase chain reaction. To determine if ET-1 was involved in the CyA-mediated disruption of the in vitro capillaries, ET-1 binding to the endothelial cells was blocked by ET-1 antibody and ET receptor antagonists. The effects of exogenous ET-1 were also studied. The results were quantified by counting the number of capillary networks, and the statistical significance was determined with ANOVA. RESULTS: ppET-1 was expressed in ECs during capillary tube formation, but disappeared once capillary tubes had matured. The ppET-1 gene expression reappeared when the capillary tubes were exposed to CyA. Exogenous ET-1 partially reversed the inhibition of tube formation by cyclohexamide, allowing initiation of tube formation. CyA-mediated capillary dysfunction was completely prevented by an anti-ET-1 antibody and an ET-B receptor antagonist. CONCLUSIONS: Endothelin-1 plays a significant role in CyA-induced endothelial dysfunction and may play a role in allograft vasculopathy. Blocking of ET-1 is a strategy to prevent endothelial dysfunction caused by CyA.

Signal transduction pathway in endothelial dysfunction.

BACKGROUND: Endothelial dysfunction is an important feature of sepsis, acute respiratory distress syndrome (ARDS), and other infectious conditions. Previously, we reported an in vitro model to study endothelial dysfunction, in which endothelial cells are induced to form capillary tube networks by culturing on a basement membrane matrix (Matrigel). In this study, we defined the signal transduction pathways that lead to endothelial cell function and capillary disruption characteristic of sepsis and other infectious conditions. METHODS: Human aortic endothelial cells (HAEC) were cultured on a laminin-rich matrix to form capillary-like networks. The HAECs were treated with a protein tyrosine phosphatase inhibitor (sodium orthovanadate), a phosphoinositon-3-phosphate inhibitor (wortmannin), or a protein kinase C inhibitor (bisindolylmaleimide) before capillary tubes had formed or after the capillary tubes had matured. The degree of capillary tube formation was quantified by counting the intersection of capillary networks in triplicate wells. Statistical significance was determined by analysis of variance. RESULTS: Endothelial dysfunction occurred after inhibition of protein tyrosine phosphatase or protein kinase C. Whereas inhibition of phosphoinositon-3-phosphate did not cause endothelial dysfunction, sodium orthovanadate (2-20 microM) and bisindolylmaleimide (2-10 microM) significantly reduced capillary networks. The mean +/- SD of the number of capillary tubes in the control, sodium orthovanadate-treated, and bisindolylmaleimide-treated groups were 251.0 +/- 7.0, 65.6 +/- 9.9 (p < 0.001), and 181.7 +/- 0.1 (p < 0.001), respectively. Sodium orthovanadate (20-200 microM) and bisindolylmaleimide (10-100 microM) inhibited capillary tube formation. At higher concentrations, sodium orthovanadate (> 200 microM) and bisindolylmaleimide (>100 microM) disrupted mature capillary tubes. CONCLUSIONS: Our results suggest that PKC and protein tyrosine phosphatase play a role in endothelial dysfunction by interfering with the phosphorylation signals within endothelial cells. These mechanisms may be important in the endothelial dysfunction in sepsis and other infectious conditions.

A new perspective in appendicitis: calculation of half time (T(1/2)) for perforation.

Appendicitis is generally a more serious disease in the elderly than in the young. In the former, perforation is seen commonly leading to the belief that the appendix perforates more readily and rapidly in the elderly. A competing view is that the appendix perforates relatively more frequently in the elderly than in the young. To distinguish between these two views we analyzed 126 cases of acute appendicitis stratified by age group. The time between onset of symptoms and perforation was calculated with a novel method that utilized the biological concept of T(1/2) for perforation. Our findings suggest that the rate of perforation in the elderly is not significantly different from that in the young but the frequency of perforation is higher in the elderly. We concluded that appendicitis carries a graver prognosis in the elderly because the frequency of appendiceal perforation is higher in the elderly.

Augmentation of ischemia/reperfusion injury to endothelial cells by cyclosporin A.

Ischemia/reperfusion (I/R) carries significant injury to endothelial cells in transplanted organs and is an important factor in chronic rejection. Immunosuppressive drugs, notably cyclosporin A (CyA) and FK506, can potentially augment this injury. Here, our goal was to determine the combined effects of I/R and CyA or FK506 on endothelial cells. Transformed mouse endothelial cells (SVEC 4-10) were subjected to ischemia or I/R for 2-24 hours by incubating cells in 100 per cent N2 (ischemia) followed by 5 per cent CO2 and 95 per cent O2 (reperfusion) for 24 hours. In separate experiments, CyA or FK506 was added to cells subjected to ischemia or I/R. Nonviable cells were determined by Trypan blue exclusion assay. All experiments (done in triplicate) were analyzed by Student's t test. Increasing ischemia times resulted in a greater number of nonviable cells (2% nonviable cells at 0 hours and 57% at 24 hours of I/R). Addition of CyA significantly increased the number of nonviable cells when compared with the control (I/R only) group (P = 0.014). Interestingly, FK506 did not increase the percentage of nonviable cells compared with the control group (P = 0.2). Unlike FK506, CyA augments I/R injury to endothelial cells in vitro. These findings could be relevant in chronic rejection and transplantation.

In vitro immunomodulatory effects of herbal products.

Immunosuppressive drugs have been developed from natural products such as soil and fungi, which are also the sources of some commonly used herbal products. However, the effect of herbal products on immune response has not been investigated. Because these products can affect the host immune system they can induce either rejection or tolerance after a transplant procedure. To investigate the effects of ten commonly used herbal products on transplant-related immune function we performed in vitro lymphocyte proliferation tests using phytohemagglutinin, mixed lymphocyte culture (MLC) assay, and interleukin (IL)-2 and IL-10 production from MLC. Dong quai, ginseng, and milk thistle had nonspecific immunostimulatory effects on lymphocyte proliferation, whereas ginger and green tea had immunosuppressive effects. Dong quai and milk thistle increased alloresponsiveness in MLC, whereas ginger and tea decreased these responses. The immunostimulatory effects of dong quai and milk thistle were consistently seen in both cell-mediated immune response and nonspecific lymphoproliferation, whereas that of ginseng was not. The immunosuppressive effect of green tea and ginger were mediated through a decrease in IL-2 production, but the immunostimulatory effects of dong quai and milk thistle were not. We conclude that green tea, dong quai, ginseng, milk thistle, and ginger have effects on in vitro immune assays that may be relevant in transplantation in humans.

In vitro immunomodulatory effects of ten commonly used herbs on murine lymphocytes.

OBJECTIVES: Physicians are increasingly encountering patients who use herbal products. Some of these products are known to modulate the immune system but their scientific basic is not well established. Because these products can affect the host immune system, they could be beneficial in the treatment of immune-related diseases, or alternatively, they could cause inadvertent side-effects. The purpose of this study was to determine which of these common herbal products modulate lymphocyte proliferation in vitro. METHODS: Lymphocyte proliferation assays using concanavalin A (mitogen stimulation) and mixed lymphocyte culture (alloantigen stimulation) were used as in vitro tests to investigate the immunomodulatory effects of 10 commonly used herbal products. RESULTS: Ginger and tea were consistently immunosuppressive while dong quai, milk thistle, and St. John's wort were consistently immunostimulatory in vitro. Ginseng enhanced lymphocyte proliferation only in the mitogen-stimulation assay. The magnitude of the enhancement or suppression of the individual herbal products was different in the two assays. CONCLUSION: Our study provides a uniform survey of the immunomodulatory properties of 10 commonly used herbal products and paves the way for testing these effects in vivo and in clinical setting.

Long-term survival in a patient with metastatic oropharynx squamous cell carcinoma to liver.

The traditionally held view is that the patients with metastatic disease cannot be cured and should be treated palliatively as it was believed that the patients will eventually succumb to the disease progression due to lack of effective treatments for systemic disease. In this article, we report our experience in a patient who was diagnosed with metastatic oropharynx squamous cell carcinoma to the liver, who has now survived five years since the original diagnosis, and is three years disease free. This case report illustrates the curative potential in selected patients with limited burden of metastatic disease with aggressive local therapy to all known sites of disease. It underscores the importance of imaging modalities in monitoring progression of disease, and most importantly illustrates the importance of multidisciplinary care for oncology patients.

A novel robotic monofilament test for diabetic neuropathy.

OBJECTIVE: The use of the Semmes-Weinstein (SW) monofilament test is recommended as a screening method for diabetic neuropathy. It offers an important chance to prevent further complications of diabetic foot. We aimed to develop a prototype Robotic Monofilament Inspector that can be used as a standard machine for screening of diabetic neuropathy. METHODS: Development was divided into three parts: computer software, control box, and Robotic Monofilament Inspector. The examiner conducted the SW test (by hand and by robotic inspector), vibration perception threshold, and Toronto Clinical Scoring System without knowledge of patient information. The unpaired t test or Wilcoxon rank-sum test was used to determine the differences between independent groups in terms of continuous outcomes, while the χ(2) test was used to determine categorical outcomes. Agreement between the various diabetic neuropathy tests was measured using the kappa statistic. RESULTS: The SW test and vibration perception threshold were more valid tests for neuropathy than the Toronto test. The robotic test was in excellent agreement with the two former tests and appeared to be valid (kappa statistic, 0.35-0.81). Another indirect evidence for the validity of the robotic test was the finding that diabetic patients with foot ulcers had a higher prevalence of neuropathy (77%vs. 38%). This might indicate that the robotic test was more valid than the manual test. CONCLUSION: The Robotic Monofilament Inspector could be used as a simple screening machine. This prototype may be developed further for routine clinical use.