Simultaneous onset and similar course of type 1 diabetes mellitus in monozygotic twins (a 4-year follow-up)

We report a rare case of monozygotic (MZ) twins who developed simultaneous onset of type 1 diabetes mellitus (T1DM). Laboratory finding showed similar values of blood sugar, pH, glycosylated hemoglobin, and C-peptide. Urinary sugar and ketones were detected in both. Endocrine and immunological assessment showed similar results. No evidence (clinical or serological) of recent viral or bacterial infection was found. In the 4 years of follow-up, the twins also showed a similar course of disease. Concordance rates for T1DM are high in MZ twins; nevertheless, a simultaneous onset and a similar course of disease are unusual, as well as the HLA allelic variants of our patients. This extraordinary concordance in a pair of MZ twins could be the consequence of a greater environmental similarity or the role of genetic factors other than HLA genes in our twins.     

Population Pharmacokinetics of Ceftazidime in Intensive Care Unit Patients: Influence of Glomerular Filtration Rate,Mechanical Ventilation,and Reason for Admission

The aim of this study was to develop a population-pharmacokinetic model of ceftazidime in intensive care unit patients to include the influence of patients'' characteristics on the pharmacokinetics. Forty-nine patients for model building and 23 patients for validation were included in a randomized study. They received ceftazidime at 2 g three times a day or as 6 g per day continuously. A NONMEM pharmacokinetic model was constructed, and the influences of covariates were studied. The model was validated by a comparison of the predicted and observed concentrations. A final model was elaborated from the whole population. Total clearance (CL) was significantly correlated with the glomerular filtration rate (GFR) calculated by modification of the diet in renal disease (MDRD), the central volume of distribution (V1) with intubation, and the peripheral volume of distribution (V2) with the reason for admission. The mean pharmacokinetic parameters were as follows: CL, 5.48 liters/h, 40%; V1, 10.48 liters, 34%; V2, 32.12 liters, 59%; total volume, 42.60 liters, 45%; and intercompartmental clearance, 16.19 liters/h, 42%. In the polytrauma population (mechanically ventilated), the time above the MIC at steady state never corresponds to 100% for discontinuous administration, and the target concentration of five times the MIC was reached with a 6-g/day dose only for patients with an MDRD of <150 ml/min. We showed that the GFR-MDRD, mechanical ventilation, and the reason for admission may influence the achieved concentrations of ceftazidime. Our model allows the a priori dosing to be adjusted to the individual patient.Ceftazidime is a broad-spectrum cephalosporin generally used in the treatment of severe Pseudomonas aeruginosa infections. Since ceftazidime exhibits time-dependent killing of gram-negative bacteria in vitro or in critically ill patients, studies involving continuous administration of cephalosporin confirm that the steady-state concentration in blood should be four to five times higher than the bacterial MIC (6, 27). When the MIC is not available, the European breakpoint is used to calculate the target concentration (8). In patients with sepsis syndrome, ceftazidime plasma concentrations after a 2-g dose of ceftazidime every 8 h or 4 g by continuous infusion may be inadequate (42).Intensive care unit (ICU) patients represent a highly heterogeneous population ranging from young trauma patients to elderly medical patients and postsurgical patients. This heterogeneity is well known to produce high variability in pharmacokinetic parameters, as was previously demonstrated for the clearance and the total volume of distribution (15, 26, 36). Ceftazidime pharmacokinetics in critically ill patients is altered by an increased volume of drug distribution and a longer elimination half-life (16).In order to determine interindividual pharmacokinetic variability and the influence of some patient characteristics on the pharmacokinetics of ceftazidime, we conducted a population pharmacokinetic study to develop and validate a model to enable an adequate individual dosing strategy to be put in place (3). We used rich data collected in a prospective study comparing continuous infusion versus intermittent administration of ceftazidime, along with the demographic, clinical, and biological characteristics of these ICU patients. This study used the nonlinear mixed-effect model as implemented in the NONMEM program for pharmacostatistical analysis (4).     

Results of short-term training of naïve physicians in focused general ultrasonography in an intensive-care unit

Rationale and objectives  

To evaluate limited training of ICU physicians without knowledge of ultrasound in performing basic general ultrasonography.     

Comparison of acceptability, skin tolerance, and compliance between handwashing and alcohol-based handrub in ICUs: results of a multicentric study

Objective  We compared handwashing (HW) and alcohol-based handrub (ABH) for skin tolerance, acceptability, and hand hygiene compliance in health-care workers (HCWs) in a multicentric study. Design and setting  Before/after study over two periods (P1 and P2) in seven ICUs. Monitoring of methicillin-resistant Staphylococcus aureus (MRSA) acquisition in two ICUs (U4 and U6). Subjects and patients  All HCWs of the seven ICUs, and the patients of U4 and U6 without MRSA carriage on admission. Interventions  Handwashing was available in P1 and P2. ABH was introduced after P1 and available throughout P2. HCWs completed questionnaires on skin tolerance in P1 and P2, and on acceptability in P2. Compliance with hand hygiene was assessed in P1 and P2 using a standardized method. ICU-acquired MRSA colonization/infection in U4 and U6 was recorded. Measurements and main results  Hand erythema was reported during P1 and P2 by 21.7 and 11% of HCWs, respectively (P = 0.01), itching by 15.8 and 7.1% (P = 0.02), oozing by 0.8 and 1.1% (P = 0.82), and bleeding by 4.2 and 1.1% (P = 0.1). ABH was considered easier and quicker than HW (P < 0.01), but overall acceptability did not differ between the two. Compliance increased from 51% (334/647) in P1 to 60% (251/418) in P2, P < 0.01. No significant reduction in MRSA colonization/infection between P1 and P2 (P = 0.30) was observed, but the study was underpowered. Conclusions  Self-report questionnaires show that when ABH is available in ICUs, fewer unpleasant skin sensations are reported. ABH is considered to be easier and quicker to use than HW and compliance is improved after glove removal.     

Nystagmus induced by high frequency vibrations of the skull in total unilateral peripheral vestibular lesions

CONCLUSION: The skull vibration-induced nystagmus test (SVINT) is a useful complementary test to the caloric test, which evaluates very low frequencies, and the head shaking test (HST), which explores medium range frequencies. These three tests are fully correlated in total unilateral vestibular lesions (tUVL) with a sensitivity of 98% and a specificity of 94% for the SVINT. The results of the interference of the SVINT with the cold caloric test on the intact ear suggest that different vestibular sensory cells are involved in these two tests. The stimulus location optimization suggests that vibrations directly stimulate the inner ear on the intact side. OBJECTIVES: The aim of this study was to establish the effectiveness of a rapid, non-invasive test used to detect vestibular asymmetry at 30, 60 and 100 Hz stimulation in tUVL. PATIENTS AND METHODS: The high frequency vibration test applied to the skull using the SVINT was compared to the results of HST and caloric test in 134 patients and 95 normal subjects: 131 patients had a total unilateral vestibular dysfunction and 3 had a bilateral total lesion (tBVL). The effects of stimulus frequency, topography and head position were studied using a video-nystagmograph. RESULTS: In tUVL, the SVINT always revealed a lesional nystagmus beating toward the healthy side at all frequencies. The mastoid site was more efficient than the cervical and vertex sites (p0.005). The mean skull vibratory nystagmus (SVN) slow phase velocity (SPV) is 10.7 degrees (SD =7.5; n=20). Mastoid stimulation efficiency was not correlated with the side of stimulation. SVN SPV was correlated with the total caloric efficiency on the healthy ear (p=0.03). The interference of the SVINT during the cold caloric test on the intact ear demonstrated a reversal of the caloric nystagmus at each application of the vibrator. In tBVL, SVINT revealed no nystagmus.     

TGF-β activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II–infused mice

Complicated abdominal aortic aneurysm (AAA) is a major cause of mortality in elderly men. Ang II–dependent TGF-β activity promotes aortic aneurysm progression in experimental Marfan syndrome. However, the role of TGF-β in experimental models of AAA has not been comprehensively assessed. Here, we show that systemic neutralization of TGF-β activity breaks the resistance of normocholesterolemic C57BL/6 mice to Ang II–induced AAA formation and markedly increases their susceptibility to the disease. These aneurysms displayed a large spectrum of complications on echography, including fissuration, double channel formation, and rupture, leading to death from aneurysm complications. The disease was refractory to inhibition of IFN-γ, IL-4, IL-6, or TNF-α signaling. Genetic deletion of T and B cells or inhibition of the CX3CR1 pathway resulted in partial protection. Interestingly, neutralization of TGF-β activity enhanced monocyte invasiveness, and monocyte depletion markedly inhibited aneurysm progression and complications. Finally, TGF-β neutralization increased MMP-12 activity, and MMP-12 deficiency prevented aneurysm rupture. These results clearly identify a critical role for TGF-β in the taming of the innate immune response and the preservation of vessel integrity in C57BL/6 mice, which contrasts with its reported pathogenic role in Marfan syndrome.     

The higher the educational level of the first-time mother,the lower the fetal and post-neonatal but not the neonatal mortality in Belgium (Flanders)

Objective

To assess, in a homogenous population of primiparous women, how fetal and infant (=first year of life) mortality varied by the mothers’ level of education.

Study design

We conducted an observational study in Flanders (Northern Belgium) involving 170,948 primiparous women who delivered in Flanders during the period 1999–2006, and their 174,495 babies. We linked the maternal education (3 levels) with a series of obstetrical and perinatal events, with special emphasis on fetal and infant death. A logistic regression analysis was performed to adjust for confounders.

Results

The incidence of fetal (0.21% – high level of education; 0.35% – medium level; 0.84% – low level) and infant mortality (0.32%; 0.41%; 0.70%, respectively), followed an inverse maternal educational gradient: higher with a lower level of education. However, neonatal death (0–27 days) was independent of the educational level of the mother. The age of the woman at delivery, the use of assisted reproductive technology and the incidence of twin birth increased while the rates of preterm birth (7.7% – high level; 8.9% – medium level; 10% – low level) and low birth weight (7.2%; 9.5%; 11.8%, respectively) decreased with the mother's educational level.

Conclusion

Perinatal and obstetrical outcome differ according to the level of the education of the mother, which is a determinant of the incidence of fetal and post-neonatal death but not of early and late neonatal death (0–27 days).     

Treatment of vocal fold scar by carbon dioxide laser and collagen injection: retrospective study on 12 patients

Vocal fold scars are the result of injury to the vocal fold lamina propria. This condition leads to an impaired vibration and usually to poor voice quality. The purpose of our study was to compare the pre- and posttreatment voice assessment scores in patients treated by CO₂ laser-assisted freeing of the scar followed by collagen injection. A group of 12 patients (10 women and 2 men) with vocal fold scars was studied retrospectively. Voice assessment was based on stroboscopy and on perceptual scores using the Grade (G) of the GRABS scale, subjective evaluation by the use of the Voice Handicap Index (VHI), aerodynamic measurements [maximum phonation time (MPT) and phonation quotient (PQ)], and acoustical measurements (frequency range and low intensity). Stroboscopy showed an improvement on the mucosal vocal fold wave and on the glottic competence. The mean VHI was improved from 63.16 to 45.5; G from 2 to 1.41; MPT from 7.05 to 8.62 s; and PQ from 463.02 to 358.54 ml/s. CO₂ laser freeing of vocal fold scars followed by collagen injection, combined with speech therapy, improved significantly the aerodynamic parameters (efficiency of voice), but not the acoustical scores.