Increased ß-haemolytic group A streptococcal M6 serotype and streptodornase B-specific cellular immune responses in Swedish narcolepsy cases.

BACKGROUND: Type 1 narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy associated with the HLA allele DQB1*06:02. Genetic predisposition along with external triggering factors may drive autoimmune responses, ultimately leading to the selective loss of hypocretin-positive neurons. OBJECTIVE: The aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFNγ) production from immune cells in response to molecularly defined targets. METHODS: Cellular reactivity defined by IFNγ production was examined in blood from 38 (HLA-DQB1*06:02(+) ) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA-DQB1*06:02(+) and 53 HLA-DQB1*06:02(-) ) control subjects, matched for age, sex and exposure, using a variety of different antigens: ß-haemolytic group A streptococcal (GAS) antigens (M5, M6 and streptodornase B), influenza (the pandemic A/H1N1/California/7/09 NYMC X-179A and A/H1N1/California/7/09 NYMC X-181 vaccine antigens, previous Flu-A and -B vaccine targets, A/H1N1/Brisbane/59/2007, A/H1N1/Solomon Islands/3/2006, A/H3N2/Uruguay/716/2007, A/H3N2/Wisconsin/67/2005, A/H5N1/Vietnam/1203/2004 and B/Malaysia/2506/2004), noninfluenza viral targets (CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue). RESULTS: IFN-γ production was significantly increased in whole blood from narcolepsy cases in response to streptococcus serotype M6 (P = 0.0065) and streptodornase B protein (P = 0.0050). T-cell recognition of M6 and streptodornase B was confirmed at the single-cell level by intracellular cytokine (IL-2, IFNγ, tumour necrosis factor-alpha and IL-17) production after stimulation with synthetic M6 or streptodornase B peptides. Significantly, higher (P = 0.02) titres of serum antistreptolysin O were observed in narcolepsy cases, compared to vaccinated controls. CONCLUSION: ß-haemolytic GAS may be involved in triggering autoimmune responses in patients who developed narcolepsy symptoms after vaccination with Pandemrix in Sweden, characterized by a Streptococcus pyogenes M-type-specific IFN-γ cellular immune response.

Effects of Oral Streptokinase-Streptodornase on Remnant Chronic Subdural Hematomas / 대한신경손상학회지

OBJECTIVE: In most cases, the postoperative course of a chronic subdural hematoma (CSDH) is good, but CSDHs sometimes remain after the inserted catheter is removed, and the outcomes of such remnant hematomas are unclear. As oral streptokinase-streptodornase (OSS) has anti-inflammatory and hematologic effects, we assessed the effects of OSS on remnant CSDHs through a retrospective analysis of clinical data. METHODS: This study included 101 patients with traumatic CSDH who had remnant CSDH after burr-hole trephination with the closed drainage system between October 2009 and December 2012. We assessed the clinical outcomes, remnant CSDH volume, and recurrence rate from computed tomography scans in order to evaluate the effects of OSS. RESULTS: No significant differences were found in the changes in remnant hematoma volume between the OSS-treated and non-treated groups (p=0.531). The reoperation rate because of was 5.4% (2 patients) in the OSS-treated group and 6.3% (4 patients) in the non-treated group. The number of patients requiring reoperation did not differ between the groups (p=0.658). CONCLUSION: OSS treatment was not associated with a significant reduction in the remnant CSDH volume or recurrence rate after burr-hole drainage. Thus, there seems to be no basis for using OSS in CSDH patients.

Debridement for surgical wounds.

BACKGROUND: Surgical wounds that become infected are often debrided because clinicians believe that removal of this necrotic or infected tissue will expedite wound healing. There are numerous methods available but no consensus on which one is most effective for surgical wounds. OBJECTIVES: To determine the effect of different methods of debridement on the rate of debridement and healing of surgical wounds. SEARCH METHODS: In March 2013, for this third update, we searched the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; and EBSCO CINAHL. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with outcomes including at least one of the following: time to complete debridement or time to complete healing. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the abstracts and titles obtained from the search, extracted data independently using a standardised extraction sheet and independently assessed methodological quality. One review author was involved in all stages of the data collection and extraction process, thus ensuring continuity. MAIN RESULTS: Five RCTs (159 participants) were eligible for inclusion; all compared treatments for infected surgical wounds and reported time required to achieve a clean wound bed (complete debridement). One trial compared an enzymatic agent (streptokinase/streptodornase) with saline-soaked dressings. Four trials compared the effectiveness of dextranomer beads or paste with other products (different comparator in each trial) to achieve complete debridement. Meta-analysis was not possible due to the unique comparisons within each trial. One trial reported that dextranomer achieved a clean wound bed significantly more quickly than Eusol, and one trial comparing enzymatic debridement with saline-soaked dressings reported that the enzyme-treated wounds were cleaned more quickly. However, methodological quality was poor in these two trials. AUTHORS' CONCLUSIONS: There is a lack of large, high-quality published RCTs evaluating debridement per se, or comparing different methods of debridement for surgical wounds, to guide clinical decision-making.

[Conservative treatment of subcapsular hematoma in preeclampsia and HELLP syndrome: a case report]. / Tratamiento conservador del hematoma hepático subcapsular en pacientes con preeclampsia y síndrome de HELLP coexistentes: reporte de caso y revisión bibliográfica.

BACKGROUND: Liver hematoma is a rare and serious complication of pregnancy associated with preeclampsia-eclampsia and HELLP syndrome. CASE REPORT: 27 years old patient with two pregnancies, first pregnancy with eclampsia, admitted with 36.5 weeks of gestation, blood pressure of 140-100 mmHg, epigastric pain, shoulder pain without peritoneal irritation and increased tendon reflexes. The requested preeclamptic profile supports the diagnosis of severe preeclampsia and HELLP syndrome. It was decided to terminate the pregnancy by abdominal route. Male product was obtained alive, 2,060 g, Apgar 8/9, gestational age of 38.2 weeks Capurro. A review did not report liver parenchymal. The evolution during mediate puerperium was torpid, the patient presented epigastric pain and shoulder pain, and there was a rise in transaminases (AST 687 U/L, ALT 813 U/L), progressive thrombocytopenia (113, 103/ pL), decreased hemoglobin, proteinuria and hypovolemic shock. Abdominal CT scan was requested, and it confirmed a heterogeneous liver image (117 x 85 x 104 mm) with a volume of 694 cc, suggesting hepatic hematoma. Serialized control of abdominal CT indicated liver hematoma resorption after 25 days of hospitalization. Seven days after discharge transaminase levels were normal. CONCLUSION: To consider in the diagnosis of preeclampsia and HELLP syndrome the likelihood of liver hematoma as an acute complication; early treatment improves the prognosis.

Debridement for surgical wounds.

BACKGROUND: Surgical wounds that become infected are often debrided because clinicians believe that removal of this necrotic or infected tissue will expedite wound healing. There are numerous methods available but no consensus on which one is most effective for surgical wounds. OBJECTIVES: To determine the effect of different methods of debridement on the rate of debridement and healing of surgical wounds. SEARCH STRATEGY: For this second update we searched the Cochrane Wounds Group Specialised Register (searched 13 April 2011); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1); Ovid MEDLINE (2007 to March Week 5 2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, April 11, 2011); Ovid EMBASE (2007 to 2011 Week 14); and EBSCO CINAHL (2007 to 8 April 2011). SELECTION CRITERIA: We included randomised controlled trials (RCTs) with outcomes including at least one of the following: time to complete debridement or time to complete healing. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed the abstracts and titles obtained from the search, extracted data independently using a standardised extraction sheet and independently assessed methodological quality. One review author was involved in all stages of the data collection and extraction process, thus ensuring continuity. MAIN RESULTS: Five RCTs (159 participants) were eligible for inclusion; all compared treatments for infected surgical wounds and reported time required to achieve a clean wound bed (complete debridement). One trial compared an enzymatic agent (streptokinase/streptodornase) with saline-soaked dressings. Four trials compared the effectiveness of dextranomer beads or paste with other products (different comparator in each trial) to achieve complete debridement. Meta-analysis was not possible due to the unique comparisons within each trial. One trial reported that dextranomer achieved a clean wound bed significantly more quickly than Eusol, and one trial comparing enzymatic debridement with saline-soaked dressings reported that the enzyme-treated wounds were cleaned more quickly. However, methodological quality was poor in these two trials. AUTHORS' CONCLUSIONS: There is a lack of large, high-quality published RCTs evaluating debridement per se, or comparing different methods of debridement for surgical wounds, to guide clinical decision-making.

A comparison between ((3)H)-thymidine incorporation and isothermal microcalorimetry for the assessment of antigen-induced lymphocyte proliferation.

Lymphocyte transformation tests (LTT) are time-consuming radioactive assays used in the clinic for the determination of allergic drug reactions and extensively in basic immunological research. In the present study we propose an alternative method in the monitoring of T-cell responses by isothermal microcalorimetric (IMC) measurements of overall cellular heat production as a function of time. For mitogen-induced lymphocyte proliferation, we analyzed a concentration dependent effect of phytohemaglutinin (PHA) and both tests showed a good correlation. This was also the case for specific antigenic stimulation with Varidase(R) or tetanus toxoid. On the other hand, antigen-induced lymphocyte proliferation analyzed by pre and post influenza vaccine (Inflexal(R) V) samples, showed no such correlation. Our study suggests that IMC measurements, despite the advantages of simplicity, on-line recording of metabolic activity and no use of radioactivity, may be limited to monitoring mitogen-induced lymphocyte proliferation.

The value of debridement and Vacuum-Assisted Closure (V.A.C.) Therapy in diabetic foot ulcers.

BACKGROUND: Treatment of diabetic foot ulcers includes a number of different regimes such as glycaemic control, re-vascularization, surgical, local wound treatment, offloading and other non-surgical treatments. Although considered the standard of care, the scientific evidence behind the various debridements used is scarce. This presentation will focus on debridement and V.A.C. Therapy, two treatments widely used in patients with diabetes and foot ulcers. METHODS: A review of existing literature on these treatments in diabetic foot ulcers, with focus on description of the various types of debridements used, the principles behind negative pressure wound therapy (NPWT) using the V.A.C. Therapy system and level of evidence. RESULTS: Five randomized controlled trials (RCT) of debridement were identified; three assessed the effectiveness of a hydrogel as a debridement method, one evaluated surgical debridement and one evaluated larval therapy. Pooling the three hydrogel RCTs suggested that hydrogels are significantly more effective than gauze or standard care in healing diabetic foot ulcers. Surgical debridement and larval therapy showed no significant benefit. Other debridement methods such as enzyme preparations or polysaccharide beads have not been evaluated in RCTs of people with diabetes. More than 300 articles have been published on negative pressure wound therapy, including several small RCTs and a larger multi-centre RCT of diabetic foot ulcers. Negative pressure wound therapy seems to be a safe and effective treatment for complex diabetic foot wounds, and could lead to a higher proportion of healed wounds, faster healing rates, and potentially fewer re-amputations than standard care. CONCLUSIONS: Although debridement of the ulcer is considered a prerequisite for healing of diabetic foot ulcers, the grade of evidence is quite low. This may be due to a lack of studies rather than lack of effect. Negative pressure wound therapy seems to be safe and effective in the treatment of some diabetic foot ulcers, although there is still only one well-performed trial that evaluates the effect.

Debridement methods in wound care.

Wound debridement is an essential part of effective wound care. There are many methods of debriding wounds and it is important that patients are involved in the decision so that they are able to give informed consent. To make effective clinical decisions and ensure patients are fully informed it is essential that nurses are aware of the different methods of debriding wounds. The nurse should also be aware of the professional requirements for competence and the risks and benefits of each method. A guideline for conservative sharp debridement has recently been published by the Tissue Viability Nurses Association (TVNA 2005), and this article reviews the issues related to the procedure and the alternatives available.

The in vitro efficacy of varidase versus streptokinase or urokinase for liquefying thick purulent exudative material from loculated empyema.

Patients with loculated parapneumonic effusion or empyema are sometimes treated with streptokinase or urokinase in an attempt to facilitate pleural fluid drainage by liquefying the pleural exudate and destroying the fibrin membranes producing the loculation. This study evaluated the effectiveness of streptokinase, urokinase, and Varidase (the combination of streptokinase and streptodornase) in liquefying gummy, purulent, exudative material from loculated empyemas. An empyema was created by injecting 10(8) Pasteurella multocida bacteria into the pleural space of New Zealand white rabbits. Twenty specimens, each containing 0.5 g of purulent material obtained 5 days after empyema induction, were placed in test tubes. Streptokinase (15,000 IU), urokinase (10,000 IU), Varidase (4,000-15,000 IU streptodornase + 15,000 IU streptokinase) or saline was added to five sets of four test tubes each. The amount of nonliquefied material that remained after incubation with the fibrinolytic agents was quantitated. Over the 6-h incubation period, the amount of nonliquefied material decreased from 0.5 g to 0.02 g in the Varidase group but never decreased to less than 0.4 g in any of the other three treatment groups. Liquefaction of thick pleural exudates from rabbits with empyema can be achieved with Varidase but not with streptokinase or urokinase.

Effect of Varidase (streptokinase) on biofilm formed by Staphylococcus aureus.

Staphylococcus aureus forms a fibrin-rich biofilm in the presence of plasma which is highly resistant to attack by the human immune system and to chemotherapy. Varidase, composed mainly of streptokinase, is used for hydrolyzing clots. In this study, we attempted to destroy the biofilm of S. aureus with Varidase and to apply this drug in the treatment of staphylococcal infections. Four clinical isolates were used in the experiments. These organisms formed a several-millimeter-thick biofilm on type IV collagen coated coverslips in trypticase soy broth containing 50% human plasma. The biofilm was composed of bacterial cell which adhered to fibrillar fibers and of sediment derived from plasma. 10,000 U/ml of Varidase, the dose which is used clinically, removed the sediment and reduced the number of live bacteria in biofilms to less than 20% of control. 200 U/ml of Varidase was also effective against biofilms of the organisms. An equal combination of Varidase and ofloxacin had an additive effect on the bacteria. The results of this study demonstrate that Varidase is highly effective in destroying biofilms of S. aureus in vitro and suggest that this drug would be useful for treating staphylococcal infections.

Varidase: the science behind the medicament.

Varidase is used throughout the world for the topical treatment of purulent and suppurating wounds. Its efficacy is centred on two enzymes, streptokinase and streptodornase. However, these represent only a small proportion of the bulked solid. This article gives an overview of the preparation and mode of action of Varidase, as well as showing some of the research and development that has gone into improving the assessment of its quality and composition.

Reduced in vivo cell-mediated immune responses to mumps, tuberculin, and streptokinase/streptodornase but not to Candida albicans in oral lichen planus.

Oral lichen planus is considered to be a T-cell-mediated disease. The purpose of this study was to investigate the capacity of T-lymphocytes in oral lichen planus patients to respond to a number of commonly encountered environmental antigens in vivo. To do this, we assessed dermal delayed-type hypersensitivity responses to mumps, streptokinase/streptodornase, Candida albicans, and purified protein derivative of tuberculin (PPD) in 17 oral lichen planus patients and in matched controls. Reduced induration in response toward mumps, PPD, and streptokinase/streptodornase was demonstrated in oral lichen planus patients compared with controls. In addition, the total sum of induration diameters was decreased in the patients. However, C. albicans stimulation resulted in similar levels of response in both groups. The differences in induration size between matched patients and controls for mumps and PPD were thus significantly greater than the corresponding differences for the C. albicans antigen. This suggests that a selective difference in the response to these antigens exists in oral lichen planus patients. The results may point to a loss of memory T-helper function to infrequently encountered environmental antigens, represented by mumps, PPD, and streptokinase/streptodornase, contrarily to memory function to common antigens (C. albicans), which seem to be unaffected.

Circulating T cells of patients with active psoriasis respond to streptococcal M-peptides sharing sequences with human epidermal keratins.

Psoriasis is a T-cell mediated inflammatory skin disease which has been associated with group A, beta-haemolytic streptococcal infections. Four 20 a.a. long M6-peptides sharing 5-6 a.a. sequences with human epidermal keratins were identified. To investigate the role of potentially cross-reactive T cells in the pathogenesis of psoriasis, interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) responses of circulating T cells to these peptides were analysed by ELISPOT and RT-PCR in 14 psoriatic patients, 12 healthy individuals and six patients with atopic dermatitis (AD). Untreated psoriatic patients' responses were significantly higher to these peptides than healthy and AD controls, while responses to a control M6-peptide, not sharing sequences with keratin, were negligible in all groups. No difference was found in response to streptokinase/streptodornase (SK/SD). M6-protein and peptides exclusively elicited IFN-gamma production, with little IL-4 production, even in AD patients. Interferon-gamma responses to all the M6-peptides were abolished after successful treatment of psoriatic patients, but responses to SK/SD were unaffected. The results indicate that active psoriasis is associated with Th1-like cells responding to streptococcal M6-peptides sharing sequences with human epidermal keratin. This is consistent with the hypothesis that psoriasis may be induced and exacerbated in susceptible individuals by M-protein specific Th1-like cells that cross-react with human epidermal keratin.

Enzymatic debridement for necrotic wounds.

In a randomised, double-blind, controlled trial, a comparison was made of the relative efficacy of using streptokinase/streptodornase (Varidase) in a hydrogel (KY Jelly) or the hydrogel alone in the debridement of Grade IV pressure sores. Seventeen subjects aged 57-94 years (mean age 81) took part; 21 sores were studied, 11 of which were randomised to the enzyme treatment regime. Both treatments led to eschar removal; fewer days were needed in the hydrogel-only group (mean 8.1 days, sd 1.8) compared to the enzyme/hydrogel group (mean 11.8 days, sd 2.9), but this was not statistically significant. The results suggest that the use of hydrogel alone may be a cost-effective alternative to the use of streptokinase/streptodornase and hydrogel in the treatment of these wounds.

Cavity foot ulcers in diabetic patients: a comparative study of cadexomer iodine ointment and standard treatment. An economic analysis alongside a clinical trial.

Diabetic foot ulcers with exposure of tendon, muscle, or bone imply a high probability for deep infections and amputations. Delayed healing times are often described. The aim of this study was to compare the clinical effect and economic cost of cadexomer iodine with standard treatment in diabetic feet with cavity ulcers. Patients with deep, exudative foot ulcers were included in a 12-week open, randomised, comparative study. When ulcers stopped exudating, vaseline gauze was used in both groups until the end of the study. Costs were estimated for dressing material, staff and transportation. Clinically relevant improvement was seen in 12 patients treated with cadexomer iodine and in 13 patients treated with standard treatment. The average weekly cost was SEK 903 and SEK 1,421, respectively, of which the major part was costs for staff and transportation related to frequency of dressing changes. Treatment with cadexomer iodine ointment (Iodosorb) showed no clinical difference compared to topical treatment consisting of gentamicin solution, streptodornase/streptokinase, or dry saline gauze but was associated with considerably lower weekly treatment costs.

Evaluation of multi skin test in colorectal cancer patients and effects of serum immunosuppressive factor and cytokine production of peripheral mononuclear cells.

Decreased skin reactions using five kinds of recall antigens correlate d with the stage of colorectal cancer. Immunosuppressive factors in the serum (IS index) increased with the progression of the stage in cancer patients, but interleukin (IL)-I and IL-2 production in peripheral mononuclear cells (PBMC) did not correlate with the advance of the disease. In patients with low immunosuppressive factors, the score of skin reactions was significantly higher than that in patients with high immunosuppressive factors. Increased serum immunosuppressive factors seem to reduce skin reactions in the patients. Furthermore, significant difference in skin reaction score was observed between patients with high IL-1 production of PBMC and patients with low IL-1 production of PBMC. These results suggest that skin reaction might be controlled by serum immunosuppressive factors and IL-1 production of PBMC, and that the score of skin reaction using multirecall antigens is a useful parameter to learn the host immunity in colorectal cancer.