Scabies-An ancient itch that is still rampant today.

WHAT IS KNOWN AND OBJECTIVE: Scabies is recognized as a neglected tropical disease responsible for a substantial health and economic burden, especially in resource-poor communities around the world. COMMENT: There are relatively few current treatment options for scabies, and they possess important limitations. The treatments are ineffective in preventing relapse, inflammatory skin reactions and associated bacterial skin infections. There are also safety concerns, especially in children and pregnant women. Furthermore, there has been the emergence of resistance among scabies mites to the classical acaricides. WHAT IS NEW AND CONCLUSION: More research needs to be devoted to developing new treatments for scabies.

Can bilateral varicose vein surgery be performed safely in an ambulatory setting?

OBJECTIVES: Surgery for varicose veins is still the method of choice worldwide. When varicose veins require bilateral surgery, a single procedure often is the preferred choice by the patient. Today, unilateral varicose vein surgery is frequently performed as an outpatient procedure, while in many institutions bilateral surgery is done as an in-hospital procedure. DESIGN: Retrospective comparative study. METHODS: Between 1 October 2004 and 31 October 2006, 433 patients underwent surgery for the great saphenous vein as in-patient procedure (303 unilateral and 130 bilateral), period 1. From 1 November 2006 until 31 December 2009, 825 patients had ambulatory great saphenous vein surgery (550 unilateral and 275 bilateral), period 2. We have compared unilateral and bilateral varicose vein surgery (high ligation and stripping of the great saphenous vein) and in-hospital procedures with ambulatory surgery, with regard to postoperative complications, postoperative pain and midterm follow-up. RESULTS: Operation time and total length of stay in the institution following varicose vein surgery were significantly shorter for period 2 compared with period 1 for both unilateral and bilateral surgery, without other differences between the groups. There were few postoperative complications without differences between periods, and between unilateral and bilateral surgery (wound infection 0.5%, haematoma requiring drainage 0.2%, transient paraesthesia 1.1%, superficial localised thrombophlebitis 0.6% and deep vein thrombosis in one unilaterally operated case only). CONCLUSIONS: Bilateral varicose vein surgery can be safely performed as an outpatient procedure, without increased risk of postoperative complications, increased postoperative discomfort or midterm adverse effects compared with unilateral surgery.

Survival and variability over time from out of hospital cardiac arrest across large geographically diverse communities participating in the Resuscitation Outcomes Consortium.

BACKGROUND: The Resuscitation Outcomes Consortium (ROC)epidemiological registry (Epistry) provides opportunities to assess trends in out-of-hospital cardiac arrest treatment and outcomes. METHODS: Patient, event, system, treatment, and outcome data from adult (≥18 years) out-of-hospital cardiac arrest (OHCA) from 10 geographically diverse North American ROC sites over four 12-month epochs, from July 1, 2011 to June 30, 2015, were assessed. Descriptive statistics were used to characterize the sample and logistic regression assessed the association of study epoch and key covariates on survival. RESULTS: Overall, 85,553 patients were assessed by Emergency Medical Services (EMS) and 45,516 (53.2%, site range 30.4%-69.9%) had resuscitation attempted by EMS. Patient and event characteristics were consistent except for increases in bystander CPR (41.3%-44.9%) and bystander AED application (3.9%-5.2%). EMS CPR depth and compression fraction increased while pre-shock pause interval decreased. Targeted temperature management was performed in 51.1% of admitted patients and early coronary angiography in 30.2%. Survival to hospital discharge improved (from 10.9% to 11.3% across epochs) with epoch significantly associated with survival (p < 0.001) showing an increasing trend in survival over time. (p = 0.02). Marked site variation in survival persisted within and across epochs (overall site range: 4.2%-19.8%). Patients with an initially shockable rhythm (VT/VF) had an overall survival of 32.2% (site range: 11.9%-47.1%) while survival in bystander witnessed VT/VF was 35.8% (site range: 12.9%-53.1%). CONCLUSIONS: Survival from adult OHCA in multiple large geographically-separate sites improved over the study period. Marked site differences in survival persist and addressing this variation is essential to improve outcomes from OHCA across North America.

Public-access defibrillation and survival after out-of-hospital cardiac arrest.

BACKGROUND: The rate of survival after out-of-hospital cardiac arrest is low. It is not known whether this rate will increase if laypersons are trained to attempt defibrillation with the use of automated external defibrillators (AEDs). METHODS: We conducted a prospective, community-based, multicenter clinical trial in which we randomly assigned community units (e.g., shopping malls and apartment complexes) to a structured and monitored emergency-response system involving lay volunteers trained in cardiopulmonary resuscitation (CPR) alone or in CPR and the use of AEDs. The primary outcome was survival to hospital discharge. RESULTS: More than 19,000 volunteer responders from 993 community units in 24 North American regions participated. The two study groups had similar unit and volunteer characteristics. Patients with treated out-of-hospital cardiac arrest in the two groups were similar in age (mean, 69.8 years), proportion of men (67 percent), rate of cardiac arrest in a public location (70 percent), and rate of witnessed cardiac arrest (72 percent). No inappropriate shocks were delivered. There were more survivors to hospital discharge in the units assigned to have volunteers trained in CPR plus the use of AEDs (30 survivors among 128 arrests) than there were in the units assigned to have volunteers trained only in CPR (15 among 107; P=0.03; relative risk, 2.0; 95 percent confidence interval, 1.07 to 3.77); there were only 2 survivors in residential complexes. Functional status at hospital discharge did not differ between the two groups. CONCLUSIONS: Training and equipping volunteers to attempt early defibrillation within a structured response system can increase the number of survivors to hospital discharge after out-of-hospital cardiac arrest in public locations. Trained laypersons can use AEDs safely and effectively.

A randomized trial of the effects of early cardiac serum marker availability on reperfusion therapy in patients with acute myocardial infarction: the serial markers, acute myocardial infarction and rapid treatment trial (SMARTT).

OBJECTIVES: The purpose of this study was to assess whether the immediate availability of serum markers would increase the appropriate use of thrombolytic therapy. BACKGROUND: Serum markers such as myoglobin and creatine kinase, MB fraction (CK-MB) are effective in detecting acute myocardial infarction (AMI) in the emergency setting. Appropriate candidates for thrombolytic therapy are not always identified in the emergency department (ED), as 20% to 30% of eligible patients go untreated, representing 10% to 15% of all patients with AMI. Patients presenting with chest pain consistent with acute coronary syndrome were evaluated in the EDs of 12 hospitals throughout North America. METHODS: In this randomized, controlled clinical trial, physicians received either the immediate myoglobin/CK-MB results at 0 and 1 h after enrollment (stat) or conventional reporting of myoglobin/CK-MB 3 h or more after hospital admission (control). The primary end point was the comparison of the proportion of patients within the stat group versus control group who received appropriate thrombolytic therapy. Secondary end points included the emergent use of any reperfusion treatment in both groups, initial hospital disposition of patients (coronary care unit, monitor or nonmonitor beds) and the proportion of patients appropriately discharged from the ED. RESULTS: Of 6,352 patients enrolled, 814 (12.8%) were diagnosed as having AMI. For patients having AMI, there were no statistically significant differences in the proportion of patients treated with thrombolytic therapy between the stat and control groups (15.1% vs. 17.1%, p = 0.45). When only patients with ST segment elevation on their initial electrocardiogram were compared, there were still no significant differences between the groups. Also, there was no difference in the hospital placement of patients in critical care and non- critical care beds. The availability of early markers was associated with more hospital admissions as compared to the control group, as the number of patients discharged from the ED was decreased in the stat versus control groups (28.4% vs. 31.5%, p = 0.023). CONCLUSIONS: The availability of 0- and 1-h myoglobin and CK-MB results after ED evaluation had no effect on the use of thrombolytic therapy for patients presenting with AMI, and it slightly increased the number of patients admitted to the hospital who had no evidence of acute myocardial necrosis.

Altered neuronal activity rhythm and glutamate receptor expression in the suprachiasmatic nuclei of Trypanosoma brucei-infected rats.

The parasites Trypanosoma brucei cause African trypanosomiasis (sleeping sickness), a severe neuropsychiatric disease with marked disturbances of sleep-wake alternation. The sites of brain lesions are not well characterized. The present experimental investigation is focused on the hypothalamic suprachiasmatic nuclei, which play a role of a biological clock entraining endogenous rhythms in the mammalian brain. The electrophysiological properties of these neurons were analyzed in slice preparations from trypanosome-infected rats. The neuronal spontaneous activity, which shows a circadian oscillation, was markedly altered in the infected animals, displaying a reduced firing rate and phase advance of its circadian peak. The direct retinal fibers, which play a pivotal role in entrainment of the circadian pacemaker, displayed a normal density and distribution in the suprachiasmatic nuclei of infected animals after intraocular tracer injections in vivo. At the postsynaptic level, immunohistochemistry and Western blotting revealed in the suprachiasmatic nuclei of infected rats a selective decrease of the expression of glutamate AMPA GluR2/3 and NMDAR1 receptor subunits that gate retinal afferents. These data disclose an impairment of the neuronal functions in the biological clock in African trypanosomiasis, and may serve to unravel functional and molecular mechanisms behind endogenous rhythm disturbances.

Discriminators between hantavirus-infected and -uninfected persons enrolled in a trial of intravenous ribavirin for presumptive hantavirus pulmonary syndrome.

To provide a potentially therapeutic intervention and to collect clinical and laboratory data during an outbreak of hantavirus pulmonary syndrome (HPS), 140 patients from the United States with suspected HPS were enrolled for investigational intravenous ribavirin treatment. HPS was subsequently laboratory confirmed in 30 persons and not confirmed in 105 persons with adequate specimens. Patients with HPS were significantly more likely than were hantavirus-negative patients to report myalgias from onset of symptoms through hospitalization, nausea at outpatient presentation, and diarrhea and nausea at the time of hospitalization; they were significantly less likely to report respiratory symptoms early in the illness. The groups did not differ with regard to time from the onset of illness to the point at which they sought care; time from onset, hospitalization, or enrollment to death was significantly shorter for patients with HPS. At the time of hospitalization, patients with HPS more commonly had myelocytes, metamyelocytes, or promyelocytes on a peripheral blood smear, and significantly more of them had thrombocytopenia, hemoconcentration, and hypocapnia. Patterns of clinical symptoms, the pace of clinical evolution, and specific clinical laboratory parameters discriminated between these 2 groups.

Possible morphological substrates for GABA-mediated presynaptic inhibition in the lamprey spinal cord.

Gamma-aminobutyric acid (GABA) neurons intrinsic to the lamprey spinal cord are known to modulate synaptic transmission from interneurons active during locomotion and from mechanosensory dorsal cells. Many of these physiological effects are presynaptic. To establish the morphological substrates for these axo-axonic interactions, an ultrastructural analysis was performed with an antiserum to fixed GABA. The GABA immunoreactivity (ir) was detected by postembedding peroxidase-antiperoxidase and immunogold techniques. GABA-ir terminals were found to make appositions with unlabelled axons located in the dorsal columns and in the ventrolateral aspect of the spinal cord. In the ventrolateral part of the cord, similar appositions between different GABA-ir terminals were also observed. The immunolabelled terminals contained spherical to pleomorphic synaptic vesicles, and also glycogen granules and dense core vesicles. In some cases, the fine structure of the contacts between immunogold-labelled terminals and unlabelled axons suggested a synaptic relationship. Such a relation was found in a relatively small proportion (2-3%) of the appositions studied. These specializations were always observed in close relation to an output synapse of the postsynaptic axon. It is suggested that the axo-axonal contacts described may provide an effective modulation of the synaptic transmission from axons in the lamprey spinal cord.

Intravenous ribavirin for hantavirus pulmonary syndrome: safety and tolerance during 1 year of open-label experience. Ribavirin Study Group.

Intravenous ribavirin was provided non-selectively for investigational open-label use among persons with suspected hantavirus pulmonary syndrome (HPS) in the United States between 4 June 1993 and 1 September 1994. Therapy was initiated prior to laboratory confirmation of hantavirus infection because most deaths from HPS occur within 48 h of hospitalization. Thirty patients with confirmed HPS, 105 patients without HPS and 5 patients without adequate diagnostic testing for HPS were enrolled. This observational study arguably provides the most complete information available on ribavirin-associated adverse effects. Although ribavirin was generally well tolerated, 71% of recipients became anaemic and 19% underwent transfusion. An apparent excess of hyperamylasaemia/pancreatitis was either therapy-associated or due to enrollment bias. The 30 enrolled HPS patients had a case-fatality rate of 47% (14/30). It is not possible to assess efficacy with this study design. However, comparison of survival curves for the 30 enrolled HPS patients and 34 patients who developed HPS during the same time period but were not enrolled did not suggest an appreciable drug effect. A randomized, placebo-controlled trial that enrolls patients during the prodrome phase would be necessary to assess the efficacy and further define the safety of intravenous ribavirin for HPS.

Interpretation of susceptibility testing of ceftriaxone.

Susceptibility of a variety of bacterial isolates to ceftriaxone was determined by Kirby-Bauer assays using 30 micrograms ceftriaxone disks and by microdilution (MIC) assays using standard procedures. The relation between zones of inhibition and MICs was expressed by the following regression equation: zone diameter = 22.98-2.653 In (MIC). Using this regression line and the breakpoints estimated from ceftriaxone concentrations in plasma 12 to 24 hours after 1- and 2-g doses, the susceptibility of a pathogen to ceftriaxone was classified as follows: susceptible-zone 16 mm or greater, MIC 16 micrograms/ml or less; moderately susceptible-zone 13 to 15 mm, MIC 17 to 63 micrograms/ml; resistant-zone 12 mm or less, MIC 64 micrograms/ml or greater. These breakpoints were used to determine the susceptibility of organisms isolated during clinical studies in the United States. The correlation between the in vitro results and the bacteriologic outcomes achieved in the clinical cases was analyzed to assess the suitability of the chosen breakpoints. The results of the disk assays were correctly predictive of bacteriologic responses with 1,388 of 1,513 organisms (91.7 percent), whereas the results of dilution assays correctly predicted the response with 897 of 941 organisms (95.3 percent). The correlation between in vitro results and bacteriologic outcome in patients treated with ceftriaxone was equivalent or superior to that achieved in patients treated with the comparative agents cefamandole and cefazolin. Thus, the chosen cutoff points for indicating susceptibility and resistance to ceftriaxone appear to be suitable and highly predictive of clinical success.

Pharmacokinetics of amdinocillin and pivamdinocillin in normal volunteers.

The pharmacokinetic parameters of amdinocillin and pivamdinocillin were studied in 12 normal volunteers. Plasma amdinocillin concentrations were determined by microbiologic assay and urine concentrations by high performance liquid chromatography. Pharmacokinetic parameters were calculated by a two-compartment open model for the intravenous infusion and by a one-compartment model with zero-order absorption for the oral doses. The mean peak serum level after the intravenous infusion of 500 mg was 39 micrograms/ml. At one and a half hours after the oral administration of 250 mg and 500 mg doses, mean peaks were 1.93 and 2.66 micrograms/ml respectively. Half-life was one hour for all doses. Maximal plasma concentration did not increase proportionally with dose. Bioavailability was 45 percent after the 250 mg dose and 38 percent after the 500 mg dose.

Dual-action cephalosporins: cephalosporin 3'-quinolone carbamates.

A series of cephalosporins has been prepared in which the 3'-position was linked to the nitrogen of the antibacterial quinolone ciprofloxacin through a carbamate function. Like the ester-linked and quaternary-linked dual-action cephalosporins reported earlier, these carbamate-linked compounds exhibited a broad antibacterial spectrum derived from both cephalosporin-like and quinolone-like activities, suggesting a dual mode of action. Studies to elucidate details of the mechanism of action have been inconclusive. Ciprofloxacin liberated as a consequence of bacterial enzyme-mediated reactions may contribute to the second mode of action, although some evidence indicates that the intact carbamate-linked bifunctional molecules may possess intrinsically both beta-lactam and quinolone activities.

Dual-action cephalosporins: cephalosporin 3'-quaternary ammonium quinolones.

When cephalosporins exert their biological activity by reacting with bacterial enzymes, opening of the beta-lactam ring can lead to expulsion of the 3'-substituent. A series of cephalosporins was prepared in which antibacterial quinolones were linked to the 3'-position through a quaternary nitrogen. Like the 3'-ester-linked dual-action cephalosporins reported earlier, these compounds demonstrated a broad spectrum of antibacterial activity derived from cephalosporin-like and quinolone-like components, suggesting a dual mode of action.

Cephalosporin 3'-quinolone esters with a dual mode of action.

According to the generally accepted mechanism by which bacterial enzymes react with cephalosporins, opening of the beta-lactam ring can lead to the expulsion of a 3'-substituent. A series of dual-action cephalosporins was prepared in which antibacterial quinolones were linked to the cephalosporin 3'-position through an ester bond in the expectation that, in addition to exerting their own beta-lactam activity, these cephalosporins would act as prodrugs for the second antibacterial agent. Compared to parent cephalosporins in which the 3'-substituent was acetoxy, the bifunctional cephalosporins exhibited a broadened antibacterial spectrum, suggesting that a dual mode of action may indeed be operative.

Dual-action cephalosporins incorporating a 3'-tertiary-amine-linked quinolone.

We have previously reported that linking quinolones to the cephalosporin 3'-position through an ester bond, a carbamate function, or a bond through a quaternary nitrogen produced cephalosporins with a dual mode of antibacterial action. We now describe a new class of dual-action cephalosporins, with greater chemical stability than those previously reported, in which the basic nitrogen of ciprofloxacin is bonded directly to the 3'-cephalosporin position, i.e., the two moieties are linked through a tertiary amine function. These compounds have demonstrated potent activity against a broad spectrum of Gram-positive and Gram-negative bacteria, including beta-lactam-resistant strains.

Platelet adhesion in polytetrafluoroethylene (PTFE) vascular grafts in vivo and the influence of increased intramuscular pressure--an experimental model.

Thrombogenicity of graft material is involved in early graft failure in small diameter grafts. The frequently seen postoperative swelling of the leg after distal revascularization may cause an increased intramuscular pressure and early graft failure. Pairs of 4 mm polytetrafluoroethylene (PTFE) grafts were implanted. Autologous platelets were labeled with 111In-oxine. Platelet adhesiveness onto the grafts were analyzed from gamma camera images. Intramuscular pressures were measured with wick technique. Blood flow was measured. One graft served as control the other as test graft. Ninety minutes after declamping the i.m. pressure was increased in the test-leg to 30 mmHg, and later to 60 mmHg. In the control-graft platelet uptake increased to a maximum 60 min after declamping. Blood flow and i.m. pressure remained uneffected. The test-grafts were initially similar but when i.m. pressure was increased to 30 mmHg activity in the grafts increased significantly. Blood flow decreased with 12% of initial flow. When i.m. pressure was raised to 60 mmHg platelet uptake continued to increase. An increased intramuscular pressure of 30 mmHg or more significantly increase the amount of platelets adhering onto PTFE grafts, emphasizing the need for measuring intramuscular pressures after lower limb vascular revascularizations.

Growth failure, intracranial calcifications, acquired pancytopenia, and unusual humoral immunodeficiency: a genetic syndrome?

We report on two children who may represent a novel syndrome consisting of a deficiency of immunoglobulin-bearing B lymphocytes and serum antibody, deficient intrauterine and/or postnatal growth, intracranial calcifications, and acquired pancytopenia. Poor growth, intracranial calcifications, developmental delay, and hematological abnormalities are common manifestations of congenital infection. However, humoral immunodeficiency is not characteristic in these infections, and no infection was found on extensive evaluation. Rare genetic syndromes may mimic intrauterine infections and may also include immunodeficiency. However the children reported here lack important characteristics or share distinctive manifestations not described in these disorders. Infants presenting with apparent congenital infections in whom a specific infectious cause cannot be identified should be followed carefully with immunological evaluations since this disorder may be progressive and considerable morbidity is attributable to hematological and immunological manifestations.

Gastrointestinal complications after coronary artery bypass grafting.

Clinical variables were studied in 3129 patients undergoing coronary artery bypass grafting to identify patients at risk of abdominal complications and common etiologic factors in the development of such complications. Seventy-three gastrointestinal complications occurred (2.3%), with an overall mortality rate of 16.4% compared with a mortality rate of 3.4% for all patients undergoing bypass grafting (p < 0.001). Cholecystitis and intestinal ischemia were the most frequently encountered complications. Multivariate analysis demonstrated that preoperative hypertension, New York Heart Association classes III and IV, preoperative left ventricular ejection fraction less than 40%, age greater than 70 years, reoperation, and urgent operation as independently and significantly associated with gastrointestinal complications. In contradiction to previous reports, no significant correlation existed between gastrointestinal complications and cardiopulmonary bypass time, 99.8 +/- 35.8 versus 101.2 +/- 39.8 minutes. Perioperative myocardial infarction and immediate postoperative hypotension with low cardiac output necessitating substantial inotropic pharmacologic support or intraaortic balloon pumping were significantly more prevalent in patients who had gastrointestinal complications (all p < 0.001). Furthermore, multivariate analysis revealed that postoperative low cardiac output was a significant, independent predictor in the development of gastrointestinal complications of any kind after coronary artery bypass grafting. Postoperative splanchnic hypoperfusion could therefore be a common etiologic factor.

The incidence of and clinical variables associated with vancomycin-resistant enterococcal colonization in mechanically ventilated patients.

STUDY OBJECTIVES: (1) To determine in our ICU the incidence of vancomycin-resistant enterococcus (VRE) colonization in mechanically ventilated patients without a history of VRE infection or colonization; and (2) to determine the risk factors and outcome variables associated with VRE colonization in these patients. DESIGN: A prospective cohort study conducted between January 1996 and March 1998. SETTING: Medical and cardiac critical care units in a tertiary care urban university hospital. PATIENTS: Mechanically ventilated patients without evidence of pneumonia at the onset of ventilation. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients underwent rectal cultures by standard methods on day 1, day 3 or 4, day 6 or 7, and day 14 of intubation to detect VRE. Thirteen of 83 patients (16%) had rectal cultures positive for VRE (VRE+) at some point while being mechanically ventilated during their stay in the ICU. In comparison, approximately 15 of 2,100 medical ICU patients (0.7%) had clinical VRE infections as determined by the hospital's infection control program during a 2-year period. VRE+ patients had a higher incidence of immunosuppression than patients who had rectal cultures negative for VRE (VRE-) (9 of 13 [69%] vs 16 of 70 [23%], respectively; p < 0.01) and neutropenia (4 of 13 [31%] vs 5 of 70 [7%], respectively; p < 0.01). Hospital length of stay (LOS) was longer in VRE+ patients than in VRE- patients (27+/-17 days vs 17+/-14 days, respectively; p = 0.05), whereas pre-ICU hospital LOS and ICU LOS were similar in both patient groups. Five of 67 patients (7%) were VRE+ on day 1 of intubation, suggesting colonization at a prior site of care. Three of 29 patients who had subsequent rectal cultures converted to VRE+ while in the ICU. This group had a higher incidence of immunosuppression and neutropenia, and received more vancomycin compared with the patients who remained VRE- (p < 0.01). However, there was no significant difference in the use of other broad-spectrum antibiotics (such as antipseudomonal penicillins, third-generation cephalosporins, quinolones, and clindamycin), enteral tube feedings, or sucralfate between the two groups. In addition, a topical antibiotic paste (a gentamicin, nystatin, polymixin slurry) that was placed in the oropharynx to prevent bacterial overgrowth was not found to increase the incidence of VRE colonization in this patient population. CONCLUSIONS: The incidence of VRE colonization was surprisingly high: 16% in mechanically ventilated patients in a hospital in which VRE was not previously known to be endemic. Risk factors for the acquisition of VRE colonization included immunosuppression, neutropenia, and vancomycin use. Increased LOSs and hospital costs were seen in VRE+ patients compared to VRE- patients. Whether VRE colonization is a contributor to severe disease that leads to prolonged hospitalization and increased resource allocation or whether it is simply a marker of disease severity cannot be determined from this study. To the extent that specific antibiotic protocols are used to reduce antibiotic-resistant flora in the ICU, monitoring the incidence of VRE in the stool specimens of immunocompromised, mechanically ventilated patients can be a simple and useful tool to assess one effect of these strategies.