Influence of fibrin glue on seroma formation after breast surgery

BACKGROUND: This study was designed to determine the effectiveness of Hemaseel APR fibrin sealant versus conventional drain placement in the prevention of seromas after breast procedures. METHODS: A prospective, randomized, controlled study of subjects who were randomized into control (drain) and experimental (fibrin) groups was conducted. RESULTS: Analysis of 82 patients showed similarly matched groups. Seroma formation rate was 45.5% in the control group and 36.8% in the fibrin glue group (P = 0.43). The rate of wound complications was similar. Aspirate volumes were significantly greater in the fibrin glue group. Drain placement saved patients >366 US dollars over fibrin glue. CONCLUSIONS: Although use of fibrin sealant resulted in a nonsignificant decrease in seroma formation rate compared with that of drain placement, the higher cost involved, cumbersome technique, and higher aspirate volumes tend to indicate that there is no advantage to using fibrin glue over drain placement with the technique described.     

Virological and pharmacological parameters predicting the response to lopinavir-ritonavir in heavily protease inhibitor-experienced patients

The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate drug exposure and genotypic resistance to protease inhibitors and can be useful to enhance the predictivity of virologic response for boosted protease inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in 116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline to month 6 was a median of -1.50 log(10) copies/ml and 40% of patients had plasma HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study-state C(min) concentration was 5,856 ng/ml. Using univariate linear regression analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were highly associated with virologic response through 6 months. In the multivariate analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease inhibitors were significantly associated with response. When the analysis was limited to patients with more highly mutant viruses (three or more lopinavir mutations), only lopinavir GIQ remained significantly associated with virologic response. This study suggests that GIQ could be a better predictor of the virologic response than virological (genotype) or pharmacological (minimal plasma concentration) approaches used separately, especially among patients with at least three protease inhibitor resistance mutations. Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses.     

bla(SHV) Genes in Klebsiella pneumoniae: different allele distributions are associated with different promoters within individual isolates

Extended-spectrum β-lactamases (ESBLs) emerge by point mutation from non-extended-spectrum precursors. The aims of this study were to reveal the basis for variations in resistance levels found in a collection of 21 Klebsiella pneumoniae clinical isolates from Brisbane, Australia. Previous studies have shown that 20 of these isolates possess bla_SHV-11, bla_SHV-2a, and/or bla_SHV-12, and there is an association between the copy numbers of the ESBL-encoding genes and resistance levels. In this study, a real-time PCR method for interrogating the polymorphic sites at codons 238 and 240 was developed, and this confirmed the relationship between mutant gene copy numbers and resistance levels. The bla_SHV promoter region was cloned from one of the ESBL-expressing isolates, and this showed that bla_SHV genes exist downstream of two different promoters within this single isolate. These promoters have both been reported previously, and they differ by virtue of the presence or absence of an IS26 insertion. The bla_SHV copy numbers in cis with the different promoters were measured, and the copy number of the IS26 promoter was correlated with resistance levels. Cloning and analysis of PCR products showed that different bla_SHV variants existed in cis with individual promoters in individual isolates but that mutant genes were more abundant downstream of the IS26 promoter. There were no ESBL-positive isolates without this promoter. It was concluded that bla_SHV in cis with the IS26 promoter is located on an amplifiable replicon, and the presence of the IS26 insertion may facilitate the acquisition of an ESBL-positive phenotype.     

Assessment of cerebral autoregulation from ectopic heartbeats

Transfer function analysis of spontaneous fluctuations in BP (blood pressure) and CBFV (cerebral blood flow velocity) has been widely used to study dynamic CA (cerebral autoregulation). The inverse Fourier transform and its integral, giving the impulse and step responses, have been used to gain perspective of the state of dynamic CA from the frequency and time domains respectively. The occurrence of ectopic heartbeats in the data has usually been treated as an artefact. Data containing multiple ectopic heartbeats were selected from a data set compiled for an acute stroke study which also included bilateral middle CBFV, concurrent surface ECG and non-invasive beat-to-beat BP recordings. Transfer function analysis and impulse and step responses were calculated from these data by (i) retaining ectopic heartbeats, (ii) after removal of ectopic heartbeats and replacement by linear interpolation, and (iii) using a narrow window of data surrounding selected ectopic heartbeats. Coherent averaging of the raw data of the selected ectopic heartbeats also allowed direct visualization of the relationship between BP changes and CBFV. The impulse and step responses were similar in shape whether or not ectopic heartbeats had been removed and showed characteristics of active dynamic CA. Removal of ectopic heartbeats from the CBFV and BP tracings, by linear interpolation or other methods, is not necessary to provide reliable estimates of dynamic autoregulation in subjects with ectopic heartbeat rates of up to eight per min. Additionally, impulse-like disturbances of BP induced by single-beat ectopic heartbeats provide enough information to characterize the autoregulatory response of the subject in agreement with more traditional methods of dynamic autoregulation assessment.     

Variation in non-invasive measurements of vascular function in healthy volunteers during daytime

Although it is often recommended to standardize the time of day when performing non-invasive measurements of vascular function, the exact influence of the time of day on the outcome of IMT (intima-media thickness), PWV (pulse wave velocity), AIX (augmentation index) and FMD (flow-mediated dilatation) measurements has not been reported before. Nineteen healthy volunteers visited our department on two different occasions: the first visit was at 09:00 hours after an overnight fast, and the second visit was at 14:00 hours after a standardized breakfast. Non-invasive measurements of atherosclerosis were performed twice at 09:00 hours and once on the second visit at 14:00 hours. Measurement of IMT, PWV, AIX and FMD was reproducible according to the method of Bland and Altman. The absolute difference between repeated measurements at 09:00 hours showed no significant difference compared with the absolute difference between 09:00 and 14:00 hours for IMT (0.029+/-0.014 compared with 0.021+/-0.014 mm; P = 0.27), PWV (0.63+/-0.50 compared with 0.75+/-0.74 m/s; P = 0.52), AIX (4.0+/-4.0 compared with 5.5+/-5.2%; P = 0.35) and FMD (3.8+/-3.7 compared with 4.2+/-2.9%; P = 0.70). In conclusion, our results show that, in healthy volunteers during the daytime, IMT, PWV, AIX and FMD outcomes are not confounded by variation in the exact time of the examination as long as other (exogenous) conditions, including food intake, smoking and intake of alcohol, are carefully controlled for.     

Proinsulin concentration is an independent predictor of all-cause and cardiovascular mortality: an 11-year follow-up of the Hoorn Study

OBJECTIVE: High proinsulin concentration may be a better predictor for cardiovascular disease (CVD) mortality than insulin concentration. Previous observations may have been confounded by glucose tolerance status or lack of precision because of high intraindividual variability. We investigated the longitudinal relation of means of duplicate measurements of insulin and proinsulin with all-cause and CVD mortality in a population-based cohort taking glucose tolerance status into account. RESEARCH DESIGN AND METHODS: Fasting and post-75-g glucose-load (2-h) glucose, insulin, and proinsulin values were determined in duplicate on separate days in 277 participants with normal glucose metabolism, 208 participants with impaired glucose metabolism, and 119 newly detected patients with type 2 diabetes of the Hoorn Study. Insulin resistance and beta-cell function were estimated by homeostasis model assessment (HOMA-IR and HOMA-B, respectively), and the fasting proinsulin-to-insulin ratio was calculated. Subjects were followed with respect to mortality until January 2003. RESULTS: Fasting proinsulin levels were significantly associated with all-cause and CVD mortality. The hazard ratios (HRs) per increase in interquartile range adjusted for age and sex were 1.21 (95% CI 1.04-1.42) for all-cause mortality and 1.33 (1.06-1.66) for CVD mortality. Adjustment for glucose tolerance status and HOMA-IR did not substantially change the associations. CONCLUSIONS: Fasting proinsulin was associated with all-cause and CVD mortality, independent of glucose tolerance status and insulin resistance and largely independent of other CVD risk factors. Proinsulin might play a role in the relationship between insulin resistance and CVD.