Quantification of alkylresorcinol metabolites in urine by HPLC with coulometric electrode array detection

BACKGROUND: Whole-grain rye and wheat cereals contain high amounts of alkylresorcinols (ARs), phenolic lipids. ARs can be quantified in plasma. Two recently identified urinary AR metabolites, 3,5-dihydroxyphenylbenzoic acid (DHBA) and 3-(3,5-dihydroxyphenyl)-1-propanoic acid (DHPPA), may be useful as biomarkers of intake of whole-grain rye and wheat. METHODS: We evaluated 4 pretreatment protocols for quantifying urinary DHBA and DHPPA using HPLC coupled with a coulometric electrode array detector. Syringic acid was used as the internal calibrator. RESULTS: Measured urinary concentrations of DHBA and DHPPA were 0.8-115 micromol/L. The mean recoveries of all added concentrations were 85%-104% for DHBA and 86%-99% for DHPPA, depending on the degree of the purification. The protocol versions with less purification correlated well with the protocol including highest purification. The correlation coefficients (r(2)) were 0.9699-0.8153 for DHBA and 0.9854-0.8371 for DHPPA. CONCLUSION: Although the protocol with the most purification steps was most specific, all protocols were suitable for measuring DHBA and DHPPA in urine. The rapid protocol with simple hydrolysis could be used in large-scale clinical studies. Additional investigation is needed to clarify whether these metabolites are useful biomarkers of whole-grain intake and helpful in the exploration of its association with human diseases.     

What Are the Interobserver and Intraobserver Variability of Gap and Stepoff Measurements in Acetabular Fractures?

BackgroundGap and stepoff values in the treatment of acetabular fractures are correlated with clinical outcomes. However, the interobserver and intraobserver variability of gap and stepoff measurements for all imaging modalities in the preoperative, intraoperative, and postoperative phase of treatment is unknown. Recently, a standardized CT-based measurement method was introduced, which provided the opportunity to assess the level of variability.Questions/purposes(1) In patients with acetabular fractures, what is the interobserver variability in the measurement of the fracture gaps and articular stepoffs determined by each observer to be the maximum one in the weightbearing dome, as measured on pre- and postoperative pelvic radiographs, intraoperative fluoroscopy, and pre- and postoperative CT scans? (2) What is the intraobserver variability in these measurements?MethodsSixty patients with a complete subset of pre-, intra- and postoperative high-quality images (CT slices of < 2 mm), representing a variety of fracture types with small and large gaps and/or stepoffs, were included. A total of 196 patients with nonoperative treatment (n = 117), inadequate available imaging (n = 60), skeletal immaturity (n = 16), bilateral fractures (n = 2) or a primary THA (n = 1) were excluded. The maximum gap and stepoff values in the weightbearing dome were digitally measured on pelvic radiographs and CT images by five independent observers. Observers were free to decide which gap and/or stepoff they considered the maximum and then measure these before and after surgery. The observers were two trauma surgeons with more than 5 years of experience in pelvic surgery, two trauma surgeons with less than 5 years of experience in pelvic surgery, and one surgical resident. Additionally, the final intraoperative fluoroscopy images were assessed for the presence of a gap or stepoff in the weightbearing dome. All observers used the same standardized measurement technique and each observer measured the first five patients together with the responsible researcher. For 10 randomly selected patients, all measurements were repeated by all observers, at least 2 weeks after the initial measurements. The intraclass correlation coefficient (ICC) for pelvic radiographs and CT images and the kappa value for intraoperative fluoroscopy measurements were calculated to determine the inter- and intraobserver variability. Interobserver variability was defined as the difference in the measurements between observers. Intraobserver variability was defined as the difference in repeated measurements by the same observer.ResultsPreoperatively, the interobserver ICC was 0.4 (gap and stepoff) on radiographs and 0.4 (gap) and 0.3 (stepoff) on CT images. The observers agreed on the indication for surgery in 40% (gap) and 30% (stepoff) on pelvic radiographs. For CT scans the observers agreed in 95% (gap) and 70% (stepoff) of images. Postoperatively, the interobserver ICC was 0.4 (gap) and 0.2 (stepoff) on radiographs. The observers agreed on whether the reduction was acceptable or not in 60% (gap) and 40% (stepoff). On CT images the ICC was 0.3 (gap) and 0.4 (stepoff). The observers agreed on whether the reduction was acceptable in 35% (gap) and 38% (stepoff). The preoperative intraobserver ICC was 0.6 (gap and stepoff) on pelvic radiographs and 0.4 (gap) and 0.6 (stepoff) for CT scans. Postoperatively, the intraobserver ICC was 0.7 (gap) and 0.1 (stepoff) on pelvic radiographs. On CT the intraobserver ICC was 0.5 (gap) and 0.3 (stepoff). There was no agreement between the observers on the presence of a gap or stepoff on intraoperative fluoroscopy images (kappa -0.1 to 0.2).ConclusionsWe found an insufficient interobserver and intraobserver agreement on measuring gaps and stepoffs for supporting clinical decisions in acetabular fracture surgery. If observers cannot agree on the size of the gap and stepoff, it will be challenging to decide when to perform surgery and study the results of acetabular fracture surgery.Level of EvidenceLevel III, diagnostic study.     

Continuous Absorbable Intradermal Sutures Yield Better Cosmetic Results than Nonabsorbable Interrupted Sutures in Open Appendectomy Wounds: A Prospective,Randomized Trial

Background

Acute appendicitis is the most common reason for abdominal surgery in young adults and children. Open appendectomy is still the treatment often chosen because it is simple, safe, and effective. Our aim was to study whether cosmetic results of appendectomy wounds are better after using continuous absorbable intradermal (A) sutures compared with wound closure with interrupted nonabsorbable (NA) sutures.

Methods

A total of 206 adult patients with clinically suspected appendicitis were allocated to the study and prospectively randomized into two wound-closure groups: the interrupted NA suture group and the A suture group. Of these, 193 patients with sufficient data were invited to the outpatient clinic for cosmetic analysis. Cosmetic results were evaluated after a median of 14 months. For subjective scar assessment, the Vancouver scar scale, the patient and observer scar assessment scale (POSAS), and a visual analog scale (VAS) were used. Objective evaluation was carried out by measuring surface area, average width, and estimated concentration change (ECC) of hemoglobin and melanin in the scar using spectrocutometry. For statistical analyses we used the Mann–Whitney test and Student’s t test.

Results

Both objective and subjective analyses showed better cosmetic results for absorbable intradermal suturing. The difference between the two groups was statistically significant as regards POSAS in both patient (p = 0.032) and observer scales (p = 0.001), and VAS (p = 0.002). Scar surface area was significantly smaller in group A than in group NA (p = 0.002). ECC measurements showed higher values for melanin in group NA than in group A (p = 0.034).

Conclusion

Continuous intradermal absorbable suturing yields a better cosmetic result than interrupted nonabsorbable suturing in lower abdominal transverse appendectomy.     

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

Bipolar disorder (BD) is characterized by mood swings between manic and depressive states. The etiology and pathogenesis of BD is unclear, but many of the affected cognitive domains, as well as neuroanatomical abnormalities, resemble symptoms and signs of small vessel disease. In small vessel disease, cerebrospinal fluid (CSF) markers reflecting damages in different cell types and subcellular structures of the brain have been established. Hence, we hypothesized that CSF markers related to small vessel disease may also be applicable as biomarkers for BD. To investigate this hypothesis, we sampled CSF from 133 patients with BD and 86 healthy controls. The concentrations of neurofilament light chain (NF-L), myelin basic protein (MBP), S100B, and heart-type fatty acid binding protein (H-FABP) were measured in CSF and analyzed in relation to diagnosis, clinical characteristics, and ongoing medications. Hereby we found an elevation of the marker of subcortical axonal damage, NF-L, in bipolar subjects. We also identified positive associations between NF-L and treatment with atypical antipsychotics, MBP and lamotrigine, and H-FABP and lithium. These findings indicate axonal damage as an underlying neuropathological component of bipolar disorder, although the clinical value of elevated NF-L remains to be validated in follow-up studies. The associations between current medications and CSF brain injury markers might aid in the understanding of both therapeutic and adverse effects of these drugs.     

Serum oncostatin M in multiple myeloma: impact on disease severity and prognosis

Since high levels of serum IL-6 predict a poor prognosis of patients with multiple myeloma (MM), we investigated if a related cytokine, oncostatin M (OSM), correlates with clinical or biochemical findings or has prognostic significance in patients with MM. Among 82 newly diagnosed MM patients, OSM was detected in the sera in 45 (55%). Serum OSM had a borderline statistical correlation with serum IL-6 (r = 0.198, p = 0.074) and C-reactive protein (r = 0.199, p = 0.074) concentrations. However, OSM did not have prognostic significance alone or in combination with other factors. The median survival of patients with detectable serum OSM concentration was 41 months (range 2-124 months) and of OSM negative patients 35 months (1-75 months). Serum OSM concentration was not associated with clinical factors or severity of bone disease at diagnosis. We conclude that serum OSM concentration is not a prognostic factor in MM patients.     

Teenage asthma after severe early childhood wheezing: an 11-year prospective follow-up

The role of factors related to early wheezing and their associations with subsequent development of asthma are controversial. We reevaluated 81 children who had been prospectively followed up since hospitalization for wheezing at less than 2 years of age. The baseline data on characteristics of the children, family-related factors, and viral causes of wheezing were collected on entry into the study. At the median age of 12.3 years, current symptoms suggestive of asthma and allergy were recorded. As part of the clinical examination, an outdoor exercise challenge test and skin prick tests to common inhalant allergens were performed. Asthma, as indicated by current inhaled anti-inflammatory medication or repeated wheezing and positive result in the challenge test, was present in 32 (40%) children, and 90% of them were sensitized to at least one allergen. Early asthma-predictive factors were atopic dermatitis (odds ratio (OR), 3.5; 95% confidence interval (CI), 1.2-10.1) and the presence of specific IgE to inhalant allergens (OR, 11.3; 95% CI, 1.9-67.6). Respiratory syncytial virus (RSV) identification during wheezing in infancy was relatively rare (20%) among later asthmatics compared with other or no viral identification (52%) or rhinovirus identification (58%). Since the prevalence of childhood asthma in our area is 4.0-5.0%, we conclude that the increased risk of asthma persists until the teenage years after hospitalization for wheezing in infancy. The risk was about 5-fold after respiratory syncytial virus-induced wheezing, and more than 10-fold after rhinovirus-induced wheezing in the present study.     

Exclusion of coronary artery disease by exercise thallium-201 tomography in patients with aortic valve stenosis.

In many patients with valvular aortic stenosis (AS), management decisions may be possible without invasive studies if coexistent coronary artery disease (CAD) can be ruled out noninvasively. The use of thallium-201 single-photon emission computed tomography to the exclusion of CAD was studied in 44 patients aged 41 to 78 years with AS. In addition to cardiac catheterization and selective coronary angiography, patients underwent a cardiac ultrasound study and thallium-201 myocardial perfusion imaging at rest and after bicycle ergometer exercise. Two thirds of the patients had critical AS (valve area index less than or equal to 0.5 cm2/m2) but none had left ventricular systolic dysfunction. Twenty-one patients had angiographically significant CAD (greater than or equal to 50% diameter stenosis in greater than or equal to 1 coronary artery), whereas 23 had either a fully normal angiogram (n = 17) or mild (less than 50%) stenoses (n = 6). Each patient with significant CAD had an abnormal thallium-201 tomogram, either a strictly segmental perfusion defect (n = 19), or a patchy nonsegmental abnormality (n = 2); however, 10 of 23 patients free of significant CAD had similar results. Thus, the sensitivity and specificity of an abnormal scintigram were 100 and 57%, respectively. If only segmental perfusion defects typical of CAD had been considered abnormal, then the sensitivity of the test would have been 90% and the specificity 70%. Patients with false abnormal scintigrams had more severe AS and more angiographically nonsignificant CAD than those with true normal findings.(ABSTRACT TRUNCATED AT 250 WORDS)     

Visual field findings after a ruptured intracranial aneurysm

Background

Visual field defects (VFDs) negatively affect activities of daily living and rehabilitation following aneurysmal subarachnoid haemorrhage (aSAH). The aim here was to assess VFDs in patients with aSAH and their associations with age, gender, aSAH severity, and clinical outcome.

Methods

Patients admitted to Helsinki University Central Hospital and treated during 2011 were participants in this prospective study. Findings obtained with the Octopus 900 perimeter (Haag-Streit Inc, Koenic, Switzerland), the Goldmann perimeter (Haag-Streit Inc, Bern, Switzerland), or the confrontation visual field test on admission and 3 days, 14 days, 2 to 4 months, and 6 months postoperatively were assigned to 16 classes. Associations between post-chiasmal VFDs and relevant clinical, radiological, and demographic data were analysed with uni- and multivariate logistic regression.

Results

Of 105 survivors at 6 months, 20 (19 %) had VFDs occurring for aneurysm- or operation-related reasons; homonymous hemianopias or quadrantanopias were the most common finding, occurring in 16 patients (15 %). Posterior ischaemic optic neuropathy presented in two patients (2 %). Ten survivors (10 %) no longer fulfilled visual field requirements for driving licences. Significant associations emerged between VFDs at 6 months and the Hunt and Hess (H&H), World Federation of Neurosurgical Societies (WFNS), and Fisher grades on admission, presence of intracerebral haemorrhage (ICH), hydrocephalus, or postoperative infarction, and higher modified Rankin Scale scores at 6 months. Multivariate logistic regression showed the H&H grade and presence of ICH to independently predict VFDs.

Conclusions

Assessing VFDs is advisable, especially among patients with poor-grade aSAH (H&H grade IV or V) and ICH.     

Periodic properties of the histaminergic system of the mouse brain

Brain histamine is involved in the regulation of the sleep–wake cycle and alertness. Despite the widespread use of the mouse as an experimental model, the periodic properties of major markers of the mouse histaminergic system have not been comprehensively characterized. We analysed the daily levels of histamine and its first metabolite, 1‐methylhistamine, in different brain structures of C57BL/6J and CBA/J mouse strains, and the mRNA level and activity of histidine decarboxylase and histamine‐N‐methyltransferase in C57BL/6J mice. In the C57BL/6J strain, histamine release, assessed by in vivo microdialysis, underwent prominent periodic changes. The main period was 24 h peaking during the activity period. Additional 8 h periods were also observed. The release was highly positively correlated with active wakefulness, as shown by electroencephalography. In both mouse strains, tissue histamine levels remained steady for 24 h in all structures except for the hypothalamus of CBA/J mice, where 24‐h periodicity was observed. Brain tissue 1‐methylhistamine levels in both strains reached their maxima in the periods of activity. The mRNA level of histidine decarboxylase in the tuberomamillary nucleus and the activities of histidine decarboxylase and histamine‐N‐methyltransferase in the striatum and cortex did not show a 24‐h rhythm, whereas in the hypothalamus the activities of both enzymes had a 12‐h periodicity. These results show that the activities of histamine‐metabolizing enzymes are not under simple direct circadian regulation. The complex and non‐uniform temporal patterns of the histaminergic system of the mouse brain suggest that histamine is strongly involved in the maintenance of active wakefulness.     

Non-neurological surgery and cerebrospinal fluid biomarkers for neuronal and astroglial integrity

Non-neurological surgery has both acute and long-term effects on the brain. Markers for Alzheimer pathology may be used to study surgically induced neurological changes relevant for postoperative confusion, asthenia or cognitive decline. Inflammatory biomarkers, total tau (T-tau) and phosphorylated tau (P-tau) were recently shown to increase progressively in the cerebrospinal fluid (CSF) during surgery for nasal CSF leak, suggesting a neuroinflammatory response with signs of neuronal damage. We used a study group of 35 patients, undergoing knee arthroplasty with a spinal blockade and propofol sedation, to replicate this finding. Five CSF biomarkers were analyzed before, 3 h after and on the morning after the interventions: T-tau and P-tau for cortical axonal integrity and tangle pathology, respectively, the 42 amino acids form of amyloid β (Aβ42) for plaque formation, neurofilament light (NFL) for the integrity of large-caliber myelinated axons and glial fibrillary acidic protein (GFAp) for astroglial cell integrity. CSF T-tau concentrations increased significantly during and after surgery (p = 0.028) and were significantly correlated with the administered doses of bupivacaine. P-tau, Aβ42 and NFL remained unchanged, while the mean GFAp concentration increased with a large standard deviation. CSF T-tau and P-tau correlated significantly with the CSF/serum albumin ratios as an indicator of blood–brain barrier permeability. Findings from earlier studies showing a significant increase in biomarkers for Alzheimer’s pathology during surgery were partly replicated, as neurochemical signs of impaired cortical axonal integrity during non-neurological surgery were detected. Bupivacaine may be involved in these reactions.