High incidence of pandrug-resistant Acinetobacter baumannii isolates collected from patients with ventilator-associated pneumonia in Greece, Italy and Spain as part of the MagicBullet clinical trial.

OBJECTIVES: To investigate the molecular epidemiology, antimicrobial susceptibility and carbapenem resistance determinants of Acinetobacter baumannii isolates from respiratory tract samples of patients diagnosed with ventilator-associated pneumonia (VAP) who were enrolled in the MagicBullet clinical trial. METHODS: A. baumannii isolates were prospectively cultured from respiratory tract samples from 65 patients from 15 hospitals in Greece, Italy and Spain. Susceptibility testing was performed by broth microdilution. Carbapenem resistance determinants were identified by PCR and sequencing. Molecular epidemiology was investigated using rep-PCR (DiversiLab) and international clones (IC) were identified using our in-house database. RESULTS: Of 65 isolates, all but two isolates (97%) were resistant to imipenem and these were always associated with an acquired carbapenemase, OXA-23 (80%), OXA-40 (4.6%), OXA-58 (1.5%) or OXA-23/58 (1.5%). Resistance to colistin was 47.7%. Twenty-two isolates were XDR, and 20 isolates were pandrug-resistant (PDR). The majority of isolates clustered with IC2 (n = 54) with one major subtype comprising isolates from 12 hospitals in the three countries, which included 19 XDR and 16 PDR isolates. CONCLUSIONS: Carbapenem resistance rates were very high in A. baumannii recovered from patients with VAP. Almost half of the isolates were colistin resistant, and 42 (64.6%) isolates were XDR or PDR. Rep-PCR confirmed IC2 is the predominant clonal lineage in Europe and suggests the presence of an epidemic XDR/PDR A. baumannii clone that has spread in Greece, Italy and Spain. These data highlight the difficulty in empirical treatment of patients with A. baumannii VAP in centres with a high prevalence of carbapenem-resistant A. baumannii.

Relationships between glucose variability and conventional measures of glycemic control in continuously monitored patients with type 2 diabetes.

Given the importance of glucose variability in the development of diabetic complications, the present study used continuous glucose monitoring (CGM) to determine various indices of glucose variability and to investigate their relationships with conventional measures of chronic sustained hyperglycemia. We examined 53 women and 61 men, aged 36-79 years afflicted with type 2 diabetes for 1-24 years. The following indices of glycemic variability were computed from CGM data sets: mean amplitude of glycemic excursions (MAGE), CGM glucose range, interquartile range (IQR), SD-score, and average daily risk range (ADRR). CGM measurements and self-monitored blood glucose (SMBG) records were used to calculate mean CGM sensor glucose and mean SMBG, respectively. In simple correlation analysis, the indices of glucose variability showed weak correlations with HbA1c: MAGE (r=0.27, p <0.01), CGM glucose range (r=0.21, p <0.05), IQR (r=0.31, p <0.01), SD-score (r=0.34, p<0.001), and ADRR (r=0.24, p<0.05). These indices were found to differ at identical HbA1c among several patients, as reflected by diurnal excursions of different frequency and magnitude. With the exception of ADRR, stronger correlations were found between mean SMBG and the other variability indices (r=0.51-0.63, p<0.01 for all). CGM provides various indices of glycemic variability not captured by conventional measures of glycemic control. Detection of the location and the magnitude of glucose fluctuations by CGM should aid in optimal treatment of glycemic disorders in type 2 diabetes.

Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder.

Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology.

Use of the artificial B-cell (Biostator) in improving insulin therapy in unstable insulin-dependent diabetes.

The present study was designed to improve the conventional subcutaneous insulin treatment of labile insulin-dependent diabetic patients by means of the artificial B-cell (Biostator) during a combination of conventional treatment and a glucose-controlled insulin infusion. Eleven patients with no residual B-cell function and poor metabolic control were studied. All patients were treated as effectively as possible by conventional methods using a combination of regular and intermediate insulin under clinical conditions. In order to determine the inadequacy of previous insulin treatment, all patients were connected to the Biostator, and the profile of daily physical activity was simulated using a bicycle ergometer. Metabolic control was compared during a 6-day period before and after a 30-50-h connection to the artificial B-cell. Using a preselected blood glucose level of 80 mg/dl (4.44 mmol/L), the additional insulin requirement amounted to 45.5 +/- 11.1 U/24 h (N = 6). The day after connection to the artificial B-cell, the patients received a new insulin regimen according to the additional insulin delivery determined by the Biostator. No better metabolic control was achieved and frequent hypoglycemic episodes occurred in this group. Another group (N = 5) was therefore studied at a preselected blood glucose level of 130 mg/dl (7.22 mmol/L). The mean additional insulin delivery by the Biostator was lower (17.2 +/- 2.1 U/24 h; P less than 0.05) and all patients were significantly better equilibrated after the new insulin regimen derived from data given by the Biostator. The ratio of short-acting to intermediate-acting insulin was 3:1; 40% of the total dosage was given in the morning. This study demonstrates that using the Biostator in addition to subcutaneous insulin allows determination of the amount of additional regular insulin that should be administered to improve glycemic control in labile diabetes.

Importance of cardiovascular autonomic dysfunction in IDDM subjects with diabetic nephropathy.

Diabetic nephropathy (DNP) is associated with increased cardiovascular mortality. This may be contributed to by associated cardiovascular autonomic dysfunction (CAD). The aim of this study was to investigate the prevalence of CAD in patients with insulin-dependent diabetes mellitus (IDDM) at different stages of DNP. We studied patients with incipient DNP (group 1, n = 10), overt DNP (group 2, n = 20), renal insufficiency (group 3, n = 27), and end-stage renal failure (group 4, n = 12) and compared them with 30 IDDM patients without clinical signs of DNP (group 5) and with 17 nondiabetic controls (group 6). All groups were matched for age and diabetic groups were matched for duration of diabetes. Assessments of CAD included beat-to-beat variation during forced respiration, heart-rate response to standing, heart-rate response to Valsalva maneuver, basal heart rate, and blood pressure response to standing. Clinical evaluation included assessment of the history and an examination for peripheral polyneuropathy. We found mean impairment of heart-rate variation during respiration, in response to Valsalva maneuver, and in heart-rate response to standing in all diabetic groups compared with nondiabetic controls (P less than .01). Heart-rate responses differed significantly between patients with renal insufficiency (groups 3 and 4) and with other patient groups (group 5; P less than .01). CAD was shown to be more prevalent in patients with DNP, more so as DNP progresses. To some extent, it is already present in the early stages of DNP. CAD may be a contributory factor for increased cardiovascular mortality in patients with DNP.(ABSTRACT TRUNCATED AT 250 WORDS)

How the brain processes complex words: an event-related potential study of German verb inflections.

Event-related brain potentials (ERPs) were recorded as German-speaking subjects read verbs in correct and incorrect participle forms. The critical words were presented in three different versions to three different groups of subjects, as part of a simple sentence, in a word list, and embedded in a story; for each version separate ERPs were recorded. Three types of verbs were investigated, regulars, irregulars and nonce verbs. We compared correct regular and irregular participles with incorrect ones; the latter had -(e)n on verbs that actually take -t participles (* getanz-en), or -(e)t on verbs that require -(e)n (* gelad-et). For the nonce verbs, we compared participles with the unexpected -(e)n ending with the expected -t participle forms. The ERP responses were very consistent across the three versions of the experiment: (i) incorrect irregular participles (* gelad-et) elicited a left frontotemporal negativity; (ii) incorrect regulars (* getanz-en) produced no differences to the correct ones; (iii) nonce verbs were associated with an N400 component but did not show a difference between expected and unexpected endings. We will interpret these findings with respect to psycholinguistic models of morphological processing and argue that the brain processes regularly inflected words differently from irregularly inflected ones, the latter by accessing full-form entries stored in memory and the former by a computational process that decomposes complex words into stems and affixes.

Treatment of acne vulgaris with salicylic acid pads.

Most cases of acne vulgaris are either mild or moderate in severity and well-suited for treatment with nonprescription agents that are safe, effective, and convenient to use. A review of four clinical studies and a comedolytic assay attests to the efficacy and safety of 0.5% and 2% solutions of salicylic acid for the treatment of acne vulgaris. In three placebo-controlled studies and a comedolytic assay, salicylic acid pads reduced the number of primary lesions and thereby the number and severity of all lesions associated with acne. Comparative studies of salicylic acid have shown it to be superior to benzoyl peroxide in reducing the total number of acne lesions. Adverse reactions to salicylic acid are generally limited to mild, local irritation occurring in a minority of patients.

Maculopathy in patients with diabetes mellitus type 1 and type 2: associations with risk factors.

AIM: To examine possible relation between diabetic maculopathy and various risk factors for diabetic complications in patients with diabetes mellitus type 1 and type 2. METHODS: Cross sectional study of two cohorts of diabetic patients, comprising 1796 patients with type 1 diabetes (mean age 47 years, mean duration of diabetes 24 years) and 1563 patients with type 2 diabetes (mean age 62 years, mean duration of diabetes 16 years). Retinopathy levels (R0-RV) and maculopathy were assessed by fluorescence angiography and fundus photography and binocular biomicroscopy. Diabetic neuropathy was assessed by means of computer assisted electrocardiography and by thermal and vibratory sensory examination. Patients were classified as normoalbuminuric (<20 microg/min) or microalbuminuric (20-200 microg/min) according to their albumin excretion rates measured in urine collected overnight. Using univariate analyses, the effects of selected patient characteristics on the presence of maculopathy were evaluated. Multiple logistic regression analyses were performed to determine independent effects of risk variables on diabetic maculopathy. RESULTS: Background retinopathy (RII) was found to be present in 28% of type 1 diabetic patients and in 38% of type 2 diabetic patients. The prevalence of maculopathy in these patients was remarkably high (42% in type 1 and 53% in type 2 diabetic patients). Patients with maculopathy had significantly impaired visual acuity. Multiple logistic correlation analysis revealed that in both types of diabetes maculopathy exhibited independent associations with duration of diabetes and with neuropathy (p <0. 01); in type 1 diabetic patients there were significant associations with age at diabetes onset, serum triglyceride and total cholesterol levels (p <0.05); in type 2 diabetes with serum creatinine levels and with hypertension (p <0.05). CONCLUSIONS: Irrespective of the type of diabetes, diabetic patients with long standing diabetes have a high risk for the development of diabetic maculopathy. Diabetic maculopathy is closely associated with diabetic nephropathy and neuropathy and with several atherosclerotic risk factors which suggests that these factors might have an important role in the pathogenesis of maculopathy. However, prospective trials are necessary to evaluate the predictive value of such factors. The findings of the present cross sectional study reinforce the arguments of previous studies by others for tight control of hypertension and hyperglycaemia.

Increased prevalence of elevated urinary albumin excretion rate in type 2 diabetic patients suffering from ischemic foot lesions.

UNLABELLED: Present cross-sectional clinical study was aimed at the evaluation the prevalence of cardiovascular risk factors in Type 2-diabetics suffering from different clinical manifestations of diabetic foot lesions due to peripheral vascular disease and/or diabetic neuropathy. 1025 non-insulin-dependent (Type 2) diabetics (NIDDM) of both sexes were investigated. Patients were classified in Type II diabetes without peripheral vascular disease and foot lesions (group 0, controls), with macroangiopathic related foot lesions (group 2), with neuropathic foot lesions (group 3), and with mixed neuropathic-ischemic foot lesions (group 4). Apart from urinary albumin excretion rate (UAE), the following micro- and macroangiopathic risk factors and diseases were taken into account: Hypertension, degree of metabolic control (HbA1c), lipid concentrations, duration of diabetes, retinopathy, clinical nephropathy. RESULTS: In the total population the UAE was significantly (p < 0.01) correlated with duration of diabetes, serum creatinine, hypertension, age, lipid concentrations, HbA1c and insulin requirement. In comparison to Type II diabetic patients without peripheral vascular disease (group 0) and with neuropathic foot lesions (group 3), subjects with ischemic (group 2) and mixed neuropathic-ischemic foot lesions demonstrated an increased prevalence of pathological UAE, which was associated with a higher frequency of clinical nephropathy, retinopathy, an older age and longer duration of diabetes. It is concluded that microalbuminuria in Type 2 diabetes reflects both the existence of diabetic nephropathy and peripheral vascular disease which is often associated with the insulin resistance syndrome.

Relations between diabetic retinopathy and cardiovascular neuropathy--a cross-sectional study in IDDM and NIDDM patients.

The pathogenetic process of diabetic retinopathy and the role of different systemic risk factors in IDDM and NIDDM is not completely understood. The aim of the present cross-sectional clinical study was (1) to compare the prevalence of systemic risk factors for diabetic retinopathy in IDDM and NIDDM patients, (2) to determine relations between these risk factors and the degree of retinopathy and (3) to evaluate the relationship between retinopathy and neuropathy. The study included 1,218 IDDM and 784 NIDDM patients attending our hospital during 1994. The mean diabetes duration was 15.4 and 13.2 years, respectively. IDDM patients with proliferative retinopathy were characterized by higher mean age of 46.4 +/- 1.08 vs. 21.8 +/- 0.42 years and longer diabetes duration of 30.0 +/- 0.79 vs. 7.7 +/- 0.26 years. Among the NIDDM patients, those ones with proliferative retinopathy had the lowest mean age of 40.5 +/- 1.42 vs. 49.7 +/- 0.61 years (p < 0.01) at diabetes manifestation. There was no statistical difference between mean HbA1c concentrations in relation to retinopathy stages. Albumin excretion was increased in both IDDM and NIDDM patients with proliferative retinopathy (p < 0.01) along with increased BMI of IDDM and increased insulin requirement of NIDDM patients (p < 0.01). Multiple regression analysis showed that proliferative retinopathy with the inclusion of non-proliferative retinopathy of IDDM and NIDDM patients was significantly correlated with diabetes duration, albumin excretion, somatic and autonomic neuropathy (p < 0.01). In NIDDM patients proliferative retinopathy with the inclusion of non-proliferative retinopathy was correlated with the age at diabetes manifestation and with cholesterol levels (p < 0.05). In IDDM and NIDDM patients proliferative retinopathy was found to be correlated with somatic and autonomic neuropathy, albumin excretion (p < 0.01) and hypertension (p < 0.05). The importance of the significant correlation of autonomic neuropathy both with background and proliferative retinopathy in IDDM and NIDDM patients needs to be prospectively investigated.

The syringo-hydromyelia and its surgical treatment.

In this communication, we present a homogeneous series of 12 cases out of 25 patients having undergone a surgical operation on the posterior fossa for troubles of the cranio-rachidian junction, between 1967 and 1973. Each of these 12 cases presented an Arnold Chiari's malformation and either a "syringo-hydromyelia" (6 times), or "bulbie" (6 times) communicating with the IVth cerebral ventricle. Two cases with hydrocephaly and HIC were drained before the operation on the posterior fossa. Two cases had a ventriculo-atrial drainage 4 and 11 years after the operation for a hydrocephaly revealed by cerebral scanning done in 8 out of 12 of our cases, while the axial transversal tomography of the cervical column and the base of the skull showed a large medulla on the 7 examined cases. Two exitus have to be mentioned 3 and 9 years after the operation, respectively after a cardiac infarction and a pulmonary embolism. With a recoil of 6 to 12 years, we can speak of an improvement and a stabilisation of our cases with the technique chosen.

Intracranial sarcoidosis presenting angiographically as a sub-dural hematoma.

Intracranial sarcoidosis is rare. Usually it involves the cranial nerves and presents with symptoms of meningeal irritation, convulsive seizures, hydrocephalus, hemiparesis, mental changes and hypothalamic dysfunction. A case in which the condition simulated a subdural hematoma is reported.

Brain abscess after transnasal intracranial penetration of a paint-brush.

The case of a brain abscess caused by intracranial, transnasal penetration of a paint-brush is presented. The danger that such foreign bodies may remain unnoticed, especially in children, is stressed. Cure was achieved by total resection of the abscess capsule.

Immune complexes associated with brain tumors: correlation with prognosis.

The presence of circulating immune complexes in the sera of 208 patients with intracranial space occupying lesions was assayed using the C1 q binding test. Twenty-eight percent of 96 high grade glioma patients had immune complexes as compared to 14% of 28 low grade glioma patients. The incidence of immune complexes was found to decrease in the first post-operative month. The presence of immune complexes correlated with shorter survival in a group of malignant glioma patients tested preoperatively. Nineteen patients without immune complexes had a mean survival of 8.6 months as compared to 13 patients with immune complexes who had a mean survival of 4.7 months. These results confirm similar observations in other types of malignancies.

Peripheral arterial disease in diabetes mellitus type 1 and type 2: are there different risk factors?

BACKGROUND: Diabetic patients have increased prevalence of peripheral arterial disease (PAD). It is not clearly shown whether the prognostic factors are identical in relation to the type of diabetes. This study was done to compare the associations of PAD with risk factors and with micro- and macrovascular complications of inpatients with type 1 and type 2 diabetes. METHODS: In a retrospective cross-sectional study 1087 patients with type 1 diabetes and 1060 patients with type 2 diabetes were examined. PAD was diagnosed when ankle-brachial-pressure-index (ABI) was < 1.0. In cases with incompressible arteries (mediasclerosis) pulse wave forms were analyzed. Multivariate logistic regression analysis was applied to evaluate the impact of different variables on PAD risk, after adjusting for different variables separately. RESULTS: In both types of diabetes (type 1 vs. type 2) PAD risk (odds ratio; OR) was increased in the presence of coronary heart disease (OR 9.3 vs. 3.5), diabetic nephropathy (OR 3.0 vs. 2.8), neuropathy (OR 7.9 vs. 1.8), foot ulceration (OR 8.9 vs. 5.5), increased daily insulin requirement > 0.6 mu/kg b.w. (OR 5.2 vs. 2.9), diabetes duration of 20-29 years (OR 28.9) and > 30 years (OR 51.1) in type 1 diabetes, and diabetes duration of 10-19 years (OR 3.8) and > 20 years (OR 4.3) in type 2 diabetes. In type 2 diabetes, PAD risk was associated with microalbuminuria (OR 2.1), macroalbuminuria (OR 3.3), background retinopathy (OR 1.9), proliferative retinopathy (OR 2.8), increased triglycerides (TG) (OR 1.7) and decreased HDL-cholesterol (HDL-C > 0.90 mmol/l: OR 0.49). CONCLUSIONS: PAD risk factors and micro- and macrovascular comorbidity are very similar in type 1 and type 2 diabetes.

[Anomia and alexia during a closed craniocerebral injury]. / Anomie et alexie lors d'un traumatisme cranio-cérébral fermé

Observation of a traumatic aphasia in a young man. After a coma and a period of mental confusion, language difficulties are limited, during a few weeks, to a severe global deficit in reading and naming. Meanwhile objects and pictures are perfectly recognized and the meaning of some words can be understood correctly. The commentary is made with reference to previous reports of similar case histories. Clinical and neuropsychological data suggest a focal lesion in the left temporal lobe, probably on the 2nd and the 3rd gyri.

[Follow-up of 12 cases of communicating cervico-bulbar syringo-hydromelia, 6 and 12 years after surgical treatment]. / Catamnèse de 12 cas de syringo-hydromyélies cervico-bulbaires communicantes, 6 et 12 ans après traitement chirurgical.

In this report, we present a series of twelve homogeneous cases among twentyfive patients having undergone, between 1967 and 1973, a surgical operation of the posterior fossa for disturbances in the cranio-spinal junction. All the twelve cases presented a malformation of Arnold Chiari, and a "syringo-hydromyelia" (6 times) or "bulbia" (6 times) communicating with the IVth ventricle. Two cases with hydrocephalus and H.I.C. have been drained before the operation of the posterior fossa. Two cases out of 12 have been shunted for hydrocephalus revealed by a cerebral scanning 4 and 11 years after the operation. Tranverse axial tomography showed an enlarged medulla in seven out of 12 examinated cases. Two deaths have to be noted, 3 and 9 years after the operation, due to cardiac failure and lung-embolism. After a period from 6 to 12 years after the operation, we may speak of improvement and stabilisation in our cases. We think that these results are due to the operative technique we have chosen following the theoretical considerations of Gardner.

[Bilateral cervical internal carotid artery aneurysms (author's transl)]. / Anévrismes extra-craniens bilatéraux de la carotide interne : observation d'un cas d'origine traumatique.

Aneurysms of the cervical internal carotid artery are not rare lesions although they often remain symptomless. The authors describe the case of an eighteen-year-old boy presenting bilateral cervical internal carotid artery aneurysms of probable traumatic origin and treated conservatively. Etiology, pathogenesis, difficulties in diagnosis and choice of treatment are discussed.

[Telemetric measurement of intracranial pressure with the help of an electromagnetic detector implanted within the epidural space. Tolerance and reliability verified in 16 cases (author's transl)]. / Mesure télémétrique de la pression intracranienne par un capteur électromagnétique implanté dans l'espace épidural. Tolérance et fiabilité vérifiées sur une série de 16 cas.

After a detailed description of the technique the authors report the clinical results obtained in a series of 16 patients upon whom the new detector has been implanted and comparative measurements of the intracranial pressure by lumbar puncture were effected. The length of implantation of the detector which was of the order of several months in a majority of cases permitted to verify the stability and tolerance of the device as well as its long-term reliability since the length of functionning was of more than 6 months in half of the patients. Quantitatively, the instantaneous value of the intracranial pressure could be evaluated with the standard deviation of 17 mm of water in comparison to the values obtained by lumbar puncture. While being acceptable in clinical practice, this margin of error can be reduced in the future. The authors intend to utilize this detector at first for the monitoring of intracranial pressure before advocating its use in prolonged surveillance of intracranial pressure.

Control of an outbreak of Acinetobacter baumannii infections using vaporized hydrogen peroxide.

BACKGROUND: Multidrug-resistant Acinetobacter baumannii (MRAB) is a serious nosocomial pathogen characterized by its survival on inanimate surfaces for long periods, making control of outbreaks difficult. AIM: To analyse two hospital outbreaks caused by MRAB, determine their epidemiology, carbapenem-resistance mechanisms and assess the effectiveness of surface disinfection by vaporized hydrogen peroxide (VHP). METHODS: MRAB strains were isolated from patients in two intensive care units (ICUs). Antimicrobial susceptibility testing was performed by E-test. Polymerase chain reaction (PCR) was used to detect the presence of the most common A. baumannii carbapenemases. Epidemiological typing was performed by rep-PCR (DiversiLab) and pulsed-field gel electrophoresis. VHP was used to decontaminate the affected ICUs. FINDINGS: MRAB was isolated from 28 patients between January 2009 and September 2010. All isolates were resistant to ciprofloxacin and gentamicin. Twenty-one were also resistant to carbapenems. Carbapenem resistance was associated primarily with the acquired OXA-23-like enzyme. Genotyping revealed three clones; the predominant clone corresponded to the international clone (IC) 2. Typing of the isolates pointed to a multifocal outbreak without a single source of infection, with horizontal spread of the dominating clone among ICU patients. A combination of rigorous infection control measures including strict isolation, education of staff, hand hygiene and surface decontamination using VHP halted the outbreak. CONCLUSION: The results of this study confirm the importance of rigorous infection prevention and control measures, combined with VHP decontamination in controlling an outbreak of MRAB.