Use Of Large Doses Research Articles

N-Acetyl-l-Cysteine and Cysteamine as New Strategies against Mixed Biofilms of Nonencapsulated Streptococcus pneumoniae and Nontypeable Haemophilus influenzae.

Acute otitis media, a polymicrobial disease of the middle ear cavity of children, is a significant public health problem worldwide. It is most frequently caused by encapsulated Streptococcus pneumoniae and nontypeable Haemophilus influenzae, although the widespread use of pneumococcal conjugate vaccines is apparently producing an increase in the carriage of nonencapsulated S. pneumoniae Frequently, pneumococci and H. influenzae live together in the human nasopharynx, forming a self-produced biofilm. Biofilms present a global medical challenge since the inherent antibiotic resistance of their producers demands the use of large doses of antibiotics over prolonged periods. Frequently, these therapeutic measures fail, contributing to bacterial persistence. Here, we describe the development of an in vitro nonencapsulated S. pneumoniae-nontypeable H. influenzae biofilm system with polystyrene or glass-bottom plates. Confocal laser scanning microscopy and specific fluorescent labeling of pneumococcal cells with Helix pomatia agglutinin revealed an even distribution of both species within the biofilm. This simple and robust protocol of mixed biofilms was used to test the antimicrobial properties of two well-known antioxidants that are widely used in the clinical setting, i.e., N-acetyl-l-cysteine and cysteamine. This repurposing approach showed the high potency of N-acetyl-l-cysteine and cysteamine against mixed biofilms of nonencapsulated S. pneumoniae and nontypeable H. influenzae Decades of clinical use mean that these compounds are safe to use, which may accelerate their evaluation in humans.

ГЕМАТОЛОГІЧНІ ТА МІКРОБІОЛОГІЧНІ ПОКАЗНИКИ, СТАН ПРИРОДНИХ МЕХАНІЗМІВ ЗАХИСТУ У КОРОПА ЗА ДІЇ ПРЕПАРАТУ «ФЛЮМЕК»

In the article presented results of own researches on the impact of antibacterial drug «Flyumek» on microbiological, hematological and immunological parameters of fish.The study was conducted in three groups of healthy age–2 carp, it was six animals each groups. The first group – research, through which the probe within 7 days of antibiotic «Flyumek» at 10 mg/kg of fish with 3% starch suspension, the second experimental group – 20 mg/kg of fish, the third group – control, received only 3% in starch suspension. Fish was kept in special trays under conditions of continuous closed system of water circulation. The material for the research served fish blood, which was taken after the experiment.For determine the sensitivity of pathogenic microorganisms of fish to the drug «Flyumek» was taken biological material from external integument, gills and internal organs (kidneys) carp with signs of the most common infectious diseases – Aeromonas infection. It was found a high antibacterial activity of the drug – diameter zone growth retardation culture around the disc was 25 mm.Investigated hematological parameters, particularly the number of red blood cells and hemoglobin concentration in the blood of carp experimental and control groups were within standard values for the age and species of fish. Not recorded probable changes in the number of red blood cells and hemoglobin concentration in the blood of experimental carp groups compared to control. This suggests no violation of the oxygen–transport function of red blood cells and hemolysis .Was studied parameters characterizing humoral nonspecific resistance – lysozyme and bactericidal activity of serum and content of circulating immune complexes. Stated that the fish that received study drug in an amount of 10 mg / kg, the content of circulating immune complexes was 51.7 ± 1.78 mmol/l and virtually no different from the control group, where their content – 50.3 ± 1.78 mmol/l, and the application of higher doses – 20 mg/kg, recorded an increase in their level to 60.3 ± 2.16 mmol/l, indicating a tendency to increase the antigenic load on the carp body . As a result dose of the drug «Flyumek» 10 mg/kg caused increase lysozyme and serum bactericidal activity of fish according to 10.0 (p < 0.05) and 11.5%. However, the use of larger doses – 20 mg/kg caused a downward trend bactericidal activity, but did not significantly affect the activity lysozyme serum.The results of the research indicate a high antibacterial activity of the drug «Flyumek» and no immunosuppressive action of investigational drug on humoral non–specific resistance of the organism carp. In this case, the drug dose of 10 mg/kg causes immune–stimulating effects on the natural defense mechanisms of fish.

Trends in the use of antipsychotics in the Israeli inpatient population, 2004-2013.

BackgroundAlthough serious mental illneses are treated with both typical and atypical antipsychotic grugs, trends in their use in psychiatric inpatient population in Israel are unrecognized. The aim of this study was to detect trends in the use of typical and atypical antipsychotic drugs in the Israeli inpatient psychiatric population throughout the last decade.MethodsData regarding allocation of typical and atypical antipsychotics, over the period 2004 to 2013, were extracted from the electronic records of SAREL, Israel’s largest private supplier of drugs to healthcare and medical facilities. The data were converted to defined daily doses (DDD) per 1000 inpatients per day.ResultsUsage of the ten atypical antipsychotic agents allocated through Israel’s national health care system increased by 73 %, from 128.09 DDD/1000 inpatients/day in 2004 to 221.69 DDD/1000 inpatients/day in 2013. This rise from 2004 to 2013 was largely due to a 1.6-fold increase in the administration of olanzapine (48.31 to 79.57 DDD/1000 inpatients/day), a 4.4-fold increase of quetiapine (9.74 to 43.04 DDD/1000 inpatients/day) and 3.7-fold increase of amisulpride (5.54 to 20.38 DDD/1000 inpatients/day). At the same period, the total utilization of 12 main typical antipsychotics decreased by 15.5 %, from 148.67 DDD/1000 inpatients/day in 2004 to 125.57 DDD/1000 inpatients/day in 2013. Over the entire period, total DDDs of both classes of antipsychotics (typical and atypical) increased by 38 %.ConclusionsSimilar to trends in the treatment of psychiatric outpatients in other countries, there was a substantial increase in the administration of atypical antipsychotic drugs to the Israeli psychiatric inpatient population across the study period. A decrease in the use of typical antipsychotics (substitution), polypharmacy, administration for more indications (supplementation) and the use of larger doses of antipsychotics may account, in part, for this increase. The findings have implications for mental health policy in the context of the Mental Health Care System Reform. Systematic studies on appropriate dosing of antipsychotics and augmentation strategies are warranted.

Severe rhabdomyolysis from red-bellied black snake (Pseudechis porphyriacus) envenoming despite antivenom

Envenoming by the Australian red-bellied black snake (Pseudechis porphyriacus) causes non-specific systemic symptoms, anticoagulant coagulopathy, myotoxicity and local effects. Current management for systemic envenoming includes administration of one vial of tiger snake antivenom within 6 h of the bite to prevent myotoxicity. We present a case of severe rhabdomyolysis in a 16 year old male which developed despite early administration of one vial of tiger snake antivenom. Free venom was detected after the administration of antivenom concurrent with rapidly decreasing antivenom concentrations. The case suggests that insufficient antivenom was administered and the use of larger doses of antivenom need to be explored for red-bellied black snake envenoming.

Review of vancomycin-induced renal toxicity: an update.

In recent times the use of larger doses of vancomycin aimed at curbing the increasing incidence of resistant strains of Staphylococcus aureus has led to a wider report of acute kidney injury (AKI). Apart from biological plausibility, causality is implied by the predictive association of AKI with larger doses, longer duration, and graded plasma concentrations of vancomycin. AKI is more likely to occur with the concurrent use of nephrotoxic agents, and in critically ill patients who are susceptible to poor renal perfusion. Although most vancomycin-induced AKI cases are mild and therefore reversible, their occurrence may be associated with greater incidence of end-stage kidney disease and higher mortality rate. The strategy for its prevention includes adequate renal perfusion and therapeutic drug monitoring in high-risk individuals. In the near future, there is feasibility of renoprotective use of antioxidative substances in the delivery of vancomycin.

Single-Center Open-Label Randomized Study of Anemia Management Improvement in ESRD Patients with Secondary Hyperparathyroidism

Background Whether anemia and mineral bone abnormalities (chronic kidney disease–mineral bone disorder [CKD-MBD]) are associated still remains to be elucidated. Both anemia and CKD-MBD have been associated with adverse cardiovascular outcome and poor quality of life. However, recent evidence suggests that use of large doses of erythropoietin-stimulating agents (ESAs) to correct hemoglobin (Hb) may be detrimental in CKD. The Optimal Anemia Treatment in End Stage Renal Disease (ESRD) (Optimal ESRD Treatment) study will assess whether lowering of parathyroid hormone (PTH) is associated with a reduction in ESA consumption. Methods The Optimal ESRD Treatment study is a pilot single-center open-label study with blinded end point (a prospective randomized open blinded end-point [PROBE] design) enrolling 50 patients on maintenance dialysis. Eligible patients with intact PTH (iPTH) 300–540 pg/mL and Hb 10–11.5 g/dL will be randomized 1:1 to strict PTH control (150–300 pg/mL) versus standard care (PTH range 300–540 pg/mL). Available drugs for CKD-MBD and anemia treatment will be managed by the attending physician to maintain the desired levels of PTH (according to study arm allocation) and Hb (10–11.5 g/dL). Echocardiographic data for cardiac structure and function as well as arterial stiffness will be assessed at study inception and completion. Conclusions The Optimal ESRD Treatment study should shed light on the complicated interplay of anemia and CKD-MBD and on the feasibility of clinical trials in this domain. The study results are expected in the spring of 2017.

Evaluation of therapeutic gain for fractionated carbon-ion radiotherapy using the tumor growth delay and crypt survival assays

Background and purposeThe aim of the study was to evaluate the therapeutic gain of carbon ion (C-ion) radiotherapy using a mouse model. Materials and methodsTransplanted fibrosarcoma (NFSa) growing in C3H/He mice and murine small intestine were irradiated with 290MeV/nucleon C-ion beams (C-ions) in 1–12 fractions separated by 4h. The cell killing efficiencies of C-ions were measured using jejunum crypt survival and tumor growth delay (TGD) assays. ResultsThe equieffect dose for crypt survival and TGD increased with increasing number of fractions after X-rays and 20keV/μm C-ions, whereas TGD after 77keV/μm C-ions rather decreased. Crypts showed stronger LET-dependent increase in α terms than the tumor while β terms less depended on LET irrespective of tissues. Therapeutic gain factor, i.e., a ratio of tumor RBE over crypt RBE, of 77keV/μm C-ions was more than unity at any doses while that of 20keV/μm C-ions increased with an increase in dose per fraction. ConclusionsThese specific data imply that use of large dose per fraction would be suitable for C-ion radiotherapy irrespective of LET from the point of view of therapeutic gain, though small dose per fraction by high-LET radiation decreases total dose for tumor.

Incidence and risk factors of delirium in patients after cardiac surgery: Modifiable and non-modifiable factors

BackgroundPost cardiac surgery delirium is a severe complication. This study tried to evaluate the early postoperative delirium risk factors and to identify which of them can be modified in order to optimize perioperative management. MethodsIt is a prospective observational study. 250 consecutive cardiac surgery patients took part in the study. Cardiac surgery, the anesthetic regiment and the postoperative management were standardized. The incidence and the risk factors of the postoperative delirium were analyzed by univariate and multivariate analysis. Delirium was assessed with screening scale – The Confusion Assessment Method for the intensive care unit every 12h postoperatively. ResultsDelirium developed in 52 patients (20.8%). Univariate analysis of the variables confirmed that older age (p=0.0001), the higher EuroSCORE II value (p=0.0001), longer CPB time (p=0.0001), longer ACC time (p=0.0001), and the sufentanil dose (p=0.010) were strongly independently associated with postoperative delirium. The benzodiazepine administration was shown to be an intermediate predictor for developing postoperative delirium (p=0.055). ConclusionsAdvanced age, higher EuroSCORE II value, longer CPB and ACC times, and higher sufentanil doses during anesthesia were all predictors for the development of postoperative delirium. The only modifiable risk factor was the use of larger doses of sufentanil which is related with the duration of the operation. New preventive strategies and use of reduced dose of sufentanil intraoperatively, or the use of different opioid should be studied and applied in order to reduce the incidence of the postoperative delirium.

Morphine for the treatment of pain in sickle cell disease.

Pain is a hallmark of sickle cell disease (SCD) and its treatment remains challenging. Opioids are the major family of analgesics that are commonly used for treating severe pain. However, these are not always effective and are associated with the liabilities of their own. The pharmacology and multiorgan side effects of opioids are rapidly emerging areas of investigation, but there remains a scarcity of clinical studies. Due to opioid-induced endothelial-, mast cell-, renal mesangial-, and epithelial-cell-specific effects and proinflammatory as well as growth influencing signaling, it is likely that when used for analgesia, opioids may have organ specific pathological effects. Experimental and clinical studies, even though extremely few, suggest that opioids may exacerbate existent organ damage and also stimulate pathologies of their own. Because of the recurrent and/or chronic use of large doses of opioids in SCD, it is critical to evaluate the role and contribution of opioids in many complications of SCD. The aim of this review is to initiate inquiry to develop strategies that may prevent the inadvertent effect of opioids on organ function in SCD, should it occur, without compromising analgesia.

Stereotactic body radiation therapy for prostate cancer: Rational and reasonable

Stereotactic body radiation therapy (SBRT), a treatment procedure that uses large doses per fraction, is currently being used to treat prostate cancer with external radiation therapy in 4 to 5 treatments. Published series in the clinical use of SBRT in patients with localized prostate cancer demonstrate high efficacy within the available follow-up time periods. Rectal and sexual toxicity profiles have been favorable compared with other radiation techniques and surgery. Urinary toxicity profiles might be more comparable to those observed with brachytherapy, more pronounced in the acute setting. SBRT is technically more challenging, requiring precise geometric targeting with in-room image guidance. The use of large doses per fraction potentially provides unique biological effects on both tumor and normal tissues. Immunologic responses in normal tissues, local stromal microenvironment, and specific antigen-presenting cells induced by such high doses likely contribute to effective tumor kill. Ultimately, SBRT for prostate cancer offers significant logistical advantages, with increased convenience to patients and decreased overall cost to the health care delivery system.

<b>The effects of industrial waste from enzyme production on pasture growth and soil chemical properties

Farmers have used liquid waste from the enzyme industry as fertilizer. To determine the impact of liquid waste from enzymes (LWEs) on soil properties, plant growth and nutrient content in pasture, an experiment was conducted with five different rates of LWE application (0, 45, 90, 135 and 180 m 3 ha -1 ) to a Cambisol in August 2006. In August 2007, 60 m 3 ha -1 of LWE was applied in every treatment. Soil was sampled on four different dates and at four different depths (0-10, 10-20, 20-40 and 40-60 cm) to verify changes in its chemical properties. Soil was improved in terms of acidity and availability of Ca 2+ , Mg 2+ , K + and P in the 0-10 cm layer, indicating that the effect of LWE is corrective concerning these attributes. There was also improvement in pasture quality through increased levels of N, P and K in plants during the first year of waste application. The use of larger doses of LWE led to increases in productivity (42.6 kg dry weight m -3 residues). These results indicate that the application of LWE is feasible for the fertilization of this grassland containing low-fertility acidic Cambisol.

Introduction to the Anesthesiology Cardiac Arrest and Resuscitation Issue

ALTHOUGH anesthesiologists have recognized expertise in providing patient safety and comfort during surgical operations, their role largely extends beyond the operating room. Pain management, particularly but not exclusively in the postoperative setting, is a cornerstone of our clinical mission outside the operating theater. In many hospitals and medical centers, anesthesiologists are also heavily involved in critical care medicine. In France, they have been historically pioneers in building up the prehospital Emergency Medical System. In all these domains, academic and educational activities have been developed and promoted by anesthesiologists, as evidenced, for example, by the number of top-level publications by anesthesiologists in recent years in critical care. Bridging the gap between these domains is an urgent need for our specialty. It is from this perspective that the Journal chose to issue a call for articles and host a symposium at the American Society of Anesthesiologists Annual Meeting on the topic of Cardiac Arrest and Resuscitation in 2013.In 2014, cardiac arrest remains a common and life-threatening disease with poor outcome. During the past years, strategies based on translational approaches from the bench to the bedside have successfully improved mortality in other common, life-threatening diseases such as myocardial infarction, cancer, or stroke. There is no reason why cardiac arrest, through more effective resuscitation, should not benefit from these previous success stories. However, examination of the international literature on cardiac arrest and resuscitation reveals a striking paucity of groups having developed experimental models on cardiac arrest. Yet, a better understanding of the pathophysiology of altered organ perfusion (such as the brain and the kidney), as well as of reperfusion-induced injury is key to developing concepts or feasibility of organ-protective approaches or testing new drugs. In this themed issue, the reader will find a selection of high-quality experimental articles that bring original contributions in these domains. Also, robust epidemiological data on the incidence and outcome of in-hospital cardiac arrests, primarily but not exclusively those occurring in the operating room, are mandatory to identify possible unmet needs in providing care, and this statement also applies to out-of-hospital cardiac arrest. The reader will find here a panel of research articles dedicated to this task in important domains of the practice of anesthesiology, that is, anesthesia-related cardiac arrest and in hospitalization for labor and delivery. As illustrated in the themed Literature Review section included in this issue, a remarkable effort has been made by the international community toward addressing therapeutic issues related to cardiac arrest and reperfusion. As a result, robust clinical trials are now challenging previously well-accepted concepts in the clinical setting, such as the benefits of mild hypothermia or the use of large doses of epinephrine. A challenge for anesthesiologists is to lead some of these major clinical trials in future. The risk/benefit of new devices for cardiac resuscitation requires evaluation as well. These include automatic cardiac massage and extracorporeal circulation devices that may be crucial for refractory cardiac arrest. Research cooperation between emergency physicians, intensivists, and anesthesiologists, particularly those routinely using extracorporeal circulation devices, may provide important breakthroughs in this domain. Finally, a major goal successfully achieved in this issue of the Journal is to provide high-quality educational material in form of editorials, general reviews, Images in Anesthesiology, a case scenario, and some excellent case reports.We believe that this Cardiac Arrest and Resuscitation Theme Issue in Anesthesiology succeeds in highlighting the strengths and weaknesses of our specialty in this worldwide domain of interest for all physicians as it is to the general public. We hope our readers will take time to review some of this content on a problem they infrequently encounter and find material that can help them in their daily practice, just as we believe that this issue will succeed in promoting new research concepts and paradigms.The authors are not supported by, nor maintain any financial interest in, any commercial activity that may be associated with the topic of this article.

Effects of acute hypervolemic hemodilution and intra-operative cell salvage on orthopedic surgery patients

Objective To evaluate impacts of acute hypervolemic hemodilution (AHH) and intra-operative cell salvage (ICS) with 6％ volume fraction of hydroxyethyl starch (HES) on hemodynamics,blood saving efficiency and renal function of orthopedic surgery patients.Methods A total of 58 patients from orthopedic surgery were involved and randomly divided into AHH + ICS group (30 cases) and control group (28 cases).Changes of hemodynamic indices (HR,MAP and CVP) and renal function indices (BUN,BCr,UCr and ALB) in both groups were compared before operation (T0),immediately after operation (T1) and at postoperative 4 hours (T2),1 day (T3) and 2 days (T4).CCr was counted and intraoperative blood conservation was observed at each time point as well.Results HR,MAP and CVP of the two groups had no significant differences.Both groups showed some drop of HR (P ＜ 0.05),but an increase of MAP and CVP at T1-T4 (P ＜ 0.05),in contrast with levels at TO.BUN,BCr and ALB also showed insignificant differences between groups or within group at each time point.CCr in the control group showed no significant difference at each time point.On the contrary,CCr in the AHH + ICS group had a fall at T1-T4 and was declined to the lowest level at T2.CCr in the AHH + ICS group showed a recovery at T3-T4 and its level at T4 was still lower than that at TO,with no significant difference.CCr in the two groups showed insignificant difference at TO,but its level in the AHH + ICS group was lower than that in the control group at T1-T4,at T2 in particular (P ＜0.01).Moreover,CCr in the two groups was still significantly different at T4 (P ＜ 0.05).Renal function indices of the two groups were all within normal range at each time point.Intraoperative blood loss and unrine volume of the two groups had no significant differences,but intraoperative fluid requirement,allogenic blood transfusion volume and transfusion rate of AHH + ICS group were notably lower than those of control group (P ＜ 0.05 or P ＜0.01).Conclusions AHH plus ICS using HES are safe,effective and promising integrated blood conservation measures,which significantly reduces intraoperative allogenic blood transfusion volume and transfusion rate and has few impacts on fundamental vital signs and renal function.However,prolonged use of large dose of HES may do harm to renal function and therefore should be carefully considered in treatment of patients with severe renal dysfunction. Key words: Hemodilution; Renal circulation; Intraoperative cell salvage

Nanosuspensions: a new approach for organ and cellular targeting in infectious diseases

Most of the infectious diseases depending upon the stage of infection need treatment at least for a month to several years e.g. tuberculosis, acquired immunodeficiency syndrome. Medication by oral administration is of choice in all treatments, but unfortunately use of large doses resulting from drug poor solubility and bioavailability leads to toxicity. The problem of solubility should be solved in easiest way to reduce dose and to increase bioavailability thereby decreasing the unnecessary exposure of other organs than the targeted one without increasing the cost of treatment. Nanosuspensions offer a simple, easy and cost effective solution to solve all above issues, without exposing body to extra drug dose. They can also serve as industrially relevant formulation approach by overcoming problems associated with other drug delivery systems like low entrapment, polymer toxicity, biocompatibility and stability issues. In this paper, applications of nanosuspensions are discussed in detail focusing particularly treatment of infectious diseases. Furthermore, potential of them in targeting at organ, cellular and subcellular levels is debated.

In Response

Our systematic review1 was created as outlined in our search strategy by an experienced information specialist. The PRISMA guidelines published in 2009 do not endorse searching clinical trial registries.2,3 Recently, the Methodological Expectations of Cochrane Intervention Reviews4 has been updated with the following statement: Searches for studies should be as extensive as possible in order to reduce the risk of publication bias and to identify as much relevant evidence as possible. Although ClinicalTrials.gov is included as one of the registers within the WHO ICTRP portal, it is recommended that both ClinicalTrials.gov and the ICTRP portal are searched separately due to additional features in ClinicalTrials.gov. However, prompted by Dr. Chelly’s comments5 we have conducted an updated analysis using the ClinicalTrials.gov data to determine whether: (1) there is evidence of a publication bias and (2) the positive effects of pregabalin we reported are maintained. With the new data sets included from the 3 unpublished Pfizer pregabalin studies using participants that received 300 mg of pregabalin 3 months after surgery on the incidence of chronic postsurgical pain after total knee arthroplasty (22/59 pregabalin vs 27/61 placebo),6 total abdominal hysterectomy (22/127 pregabalin vs 14/141 placebo),7 and inguinal hernia repair (5/101 pregabalin vs 3/101 placebo),8 the pooled odds ratio for the incidence of chronic postsurgical pain with the 5 pregabalin studies becomes an odds ratio 0.73 (0.28–1.89, P = 0.51). These new data question the positive pregabalin findings published to date with respect to the prevention of chronic postsurgical pain. We are supportive of the position that IRB-approved clinical trials should be registered and reported to ensure that publication bias is minimized when assessing clinical trials and meta-analyses. However, and in view of the fact that it is unlikely that the unpublished Pfizer data will ever become part of the peer-reviewed literature, it remains to be determined how data not undergoing the scrutiny of rigorous peer review should be weighed against published studies. Our review article was written to examine the use of this class of medication in the perioperative setting for the prevention of chronic postsurgical pain based on the published literature available at that time. Studies evaluating the effectiveness of these agents in the acute and chronic postoperative pain settings continue to be published with mixed results.9,10 It remains to be seen what the final verdict will be with respect to the benefits versus risks of these medications in the perioperative setting. Some institutions have adopted them routinely in a multimodal perioperative care pathway, whereas others have stepped away given the side-effect profiles of these medications. To that end, Dr. Chelly reiterates our cautionary note regarding the use of larger doses of the α-2-Δ ligands given the increase in sedation and somnolence in the acute postoperative period seen most often in the elderly population and patients with compromised renal function. Once again, given the limited number of studies identified in our review, the clinical heterogeneity of the trials identified, and the now documented evidence of a pregabalin publication bias,2 future well-designed, appropriately powered studies are needed to clarify whether the α-2-δ calcium channel blockers have a role in the prevention of chronic postsurgical pain. Hance Clarke, MD, MSc, FRCPC Duminda N. Wijeysundera, MD, PhD, FRCPC Department of Anesthesia and Pain Management Toronto General Hospital, University Health Network, Merit Award Recipients Department of Anesthesia University of Toronto Toronto, Ontario [email protected] Robert P. Bonin, PhD Centre de Recherche Université Laval Robert-Giffard Université Laval, Québec Beverley Orser, MD, PhD, FRCPC Department of Anesthesia Sunnybrook Health Sciences Centre, Toronto Marina Englesakis, BA, MLIS Information Specialist for Surgical Division, Neurosciene, and Medical Education University Health Network, Toronto Joel Katz, PhD Department of Psychology York University, Toronto, Ontario, Canada

Toxic Megacolon due to Fulminant Amebic Colitis in a non Endemic Area

We report a case of fulminant necrotizing colitis and toxic megacolon in a middle-aged woman, due to infection with Entamoeba histolytica acquired in a non endemic zone of amebiasis, and requiring emergent total colectomy due to the occurrence of colon perforation and peritonitis. Fulminant colitis is a rare complication of amebiasis, which has been only exceptionally reported in the absence of a recent travel in endemic areas. In the case presented herein, we discuss the possible role of the use of large doses of loperamide, as well as that of a co-infection with Norovirus, in triggering the fulminant course of the disease. doi: http://dx.doi.org/10.4021/jmc900w

Analysis of risk factors of pulmonary infection in critically ill ICU patients with tracheotomy and nursing countermeasures

Objective To analyze the risk factors of pulmonary infection for critically ill ICU patients with tracheotomy,and investigate the methods to prevent nosocomial lung infection. Methods 94 patients in ICU with pulmonary infection after tracheotomy from March 2008 to March 2010 were analyzed retrospectively,they were set as the observation group.100 patients in synchronization without pulmonary infection after tracheotomy were set as the control group.The general condition,diagnosis and treatment methods and care,the environment,etc.were studied,the risk factors for nosocomial pulmonary infections after tracheotomy were analyzed.The care methods and points to prevent lung infections for critically ill ICU patients after tracheotomy were summarized. Results The study showed that the respiratory system diseases in critically ill patients,smoking history,low seniority of nursing staff,long-term use of large dose of antibiotics,application of H2 blockers and antacids,and many patients in the same ward were risk factors for critically ill patients with pulmonary infection. Conclusions Lung infection after tracheotomy in critically ill ICU patients was affected by many factors.In the actual operation,we should targeted to avoid infection led by treatment and care factors,environmental factors,control and prevention measures should especially be strengthened for patients with respiratory diseases to prevent lung infection. Key words: Critically ill patients; Tracheotomy; Lung infection; Risk factors; Care strategy

Short-Term Effects on Bone Turnover Markers of a Single High Dose of Oral Vitamin D3

Vitamin D deficiency is often treated or prevented by high intermittent doses of vitamin D to achieve a better treatment adherence, but treatment outcomes were contradictory, and even a transient increase in fracture and fall risk was reported. The objective of the study was to investigate the short-term effects on bone turnover markers of a single bolus of vitamin D₃. Twelve elderly subjects (eight women, four men; mean age 76 ± 3 yr) were given a single oral bolus of 600,000 IU vitamin D₃. Blood samples were taken at baseline and 1, 3, 7, 14, 30, 60, and 90 d after vitamin D₃ administration. Twenty-four subjects served as controls. Changes in serum levels of 25-hydroxyvitamin D (25OHD), 1,25-dihydroxyvitamin D, PTH, C-terminal-telopeptides of type I collagen, cross-linked N-telopeptide of type I collagen (sNTX), osteocalcin, and bone-specific alkaline phosphatase. No relevant changes in 25OHD and bone turnover markers were observed in the controls. In treated subjects, serum 25OHD attained a peak increment to 67.1 ± 17.1 ng/ml (P < 0.001) at d 3. Subsequently it slowly decreased to 35.2 ± 5.8 ng/ml (P <0.01 vs. a baseline value of 21.7 ± 5.6 ng/ml). Mean serum PTH concentration decreased by 25-50% and serum 1,25-dihydroxyvitamin D rose by 25-50%. Serum CTX and sNTX rose significantly at d 1 (P < 0.01), they attained a peak increment greater than 50% at d 3, and they subsequently decreased almost back to baseline values at d 90. Serum osteocalcin slightly rose within the first 3 d and then declined by d 60. No changes were observed in serum bone-specific alkaline phosphatase. Our results indicate that the use of large doses of vitamin D may be associated with acute increases in C-terminal-telopeptides of type I collagen and sNTX, which may explain the negative clinical results obtained by using intermittent high doses of vitamin D to treat or prevent vitamin D deficiency.

Implantation Techniques

ABSTRACT Decades of research and improving technology have taken in vitro fertilization techniques to a highly sophisticated level. Attention in the later twentieth century was increasingly paid to the endocrine stimulation of follicle growth and oocyte maturation. Hormonal stimulation became more complex. Methods for ovarian hyperstimulation became complex. GnRH agonists and antagonists came into play to provide a better control over FSH and LH concentrations during follicular and luteal phases of stimulated cycles including the correction of premature LH surges. A lot of stress is being paid nowadays on natural remedies to replace the high tech treatment modalities and so also evolved the so called natural cycle in vitro fertilization, the drug free or minimal drug fertility treatment. There are opinions worldwide of experts that the methods that are currently being used for ovulation and to stimulate growth of the follicle in infertile women are too expensive in addition to being extreme measures. Not only are they costly but the effect on the human body has given rise for the need for a more nature-friendly method. Alternative approaches are therefore being sought including minimal stimulation IVF, natural cycle IVF and maturing human oocytes in vitro to prepare them for fertilization in vitro. Each of these approaches avoids the use of large doses of human menopausal gonadotrophin (HMG) that have become essential for routine IVF. This article reviews the available literature on these methods and also their fallacies, if any.

Propofol infusion syndrome in patients with refractory status epilepticus: An 11-year clinical experience*

Propofol is a sedative, anesthetic, and antiepileptic agent that is frequently used in patients with refractory status epilepticus. Propofol infusion syndrome is a feared complication of propofol use, especially at high infusion rates for prolonged periods. The present study describes the use of propofol and its associated complications in patients with refractory status epilepticus. : Retrospective study with outcome assessment. Intensive care units at Mayo Clinic. Intensive care unit admissions with refractory status epilepticus. None. A computer-assisted search identified 41 consecutive patients from January 1997 to September 2008 admitted to our intensive care unit with refractory status epilepticus, defined by the need for continuous intravenous infusion of anesthetic agents to control seizures. Propofol infusion syndrome was defined per previously published criteria. The study population consisted of 24 males and 17 females with a median age of 51 yrs (range, 0.25- 80). Propofol was used in 31 (76%) of these patients (propofol group), and other agents like midazolam, lorazepam, and pentobarbital were used in the other ten (24%) patients (nonpropofol group). Median hospital (12 days; range, 2-112) and intensive care unit length of stay (9 days; range, 2-95) did not differ among the two groups. Propofol was used for a median of 63 hrs (range, 2-391) with a median cumulative dosage of 12,750 mg (range, 336-57,545). The median peak infusion rate was 67 microg/kg/min (range, 19-200). There were three sudden unexplained cardiorespiratory arrests in the propofol group (3 of 31, 10%), of which two were fatal. These three patients were aged 37, 46, and 55 yrs and had no prior cardiopulmonary disease. Eleven additional patients (11 of 31, 35%) had non-life-threatening features of propofol infusion syndrome. There were no such events noted in the nonpropofol group. The prolonged use of large doses of propofol to treat refractory status epilepticus was associated with significant mortality and morbidity.