Estimation of antiphospholipid antibodies in a prospective longitudinal study of children with migraine

The aim of this study was to determine the prevalence and clinical significance of antiphospholipid antibodies (aPL) in children with migraine. The values of anticardiolipin (aCL) and antibeta2 glycoprotein I (antibeta2GPI) antibodies were assayed by an ELISA method in 52 children with migraine and 22 children with tension-type headache. The control group consisted of 61 apparently healthy children at regular preventive visits. Two monoclonal beta2GPI dependent aCL (HCAL and EY2C9) were used as calibrators. Lupus anticoagulant (LA) was determined by a modified dilute Russell viper venom time test. Persistently positive aPL were observed during the follow-up in 16.3% of children with migraine (9.3% for aCL, 7.0% for antibeta2GPI and 0% for LA) and in 16.7% of children with tension-type headache (11.1% for aCL, 5.6% for antibeta2GPI and 0% for LA). The prevalence of aPL did not differ significantly between patient groups and healthy children. The prevalence of aPL does not appear to be increased in an unselected group of children with migraine, however, the possible role of aPL in individual cases of paediatric migraine can not be excluded.     

Matrix metalloproteinase-9 and cell kinetics during the collection of peripheral blood stem cells by leukapheresis.

The plasma levels of matrix metalloproteinase-9 (MMP-9) were determined during 41 collections of peripheral blood stem cells (PBSC) by standard volume (two blood volumes) leukaphereses (SVL) in 29 donors (7 allogeneic and 22 autologous) mobilized with the granulocyte-colony stimulating factor (G-CSF). The association between MMP-9 levels and cell counts in donor's blood was explored. During the processing of the first blood volume (BV), MMP-9 levels declined on average by 31% and persisted at the same level during the processing of the second BV. During the collection, a slight decline of white blood cells (WBC), polymorphonuclear neutrophils (PMN) and platelets (PLT) in donor's blood was accompanied by a significant drop of CD34+ cells by 37% after 1 BV and by 44% after 2 BV had been processed (p=0.001). The drop of MMP-9 plasma levels showed a loose correlation with the decrease of WBC (r=0.68, p=0.002) and PMN counts (r=0.67, p=0.001). We conclude that the levels of MMP-9 that have been elevated by the mobilization of donors with G-CSF, decrease during the collection of PBSC by 4h SVL. The observed decrease was indirectly related to the drop of WBC and PMN counts, suggesting that certain other factors have an influence on MMP-9 kinetics during PBSC collection.     

Influence of foot pain on walking ability of diabetic patients.

OBJECTIVE: To assess foot pain and its correlation with walking ability in diabetic patients. SUBJECTS: Two groups of type 2 diabetic patients (30 with symptomatic neuropathy and 30 without symptomatic neuropathy) and 30 healthy volunteers were studied. METHODS: Pain was assessed by the pain sub-scale of the Foot Function Index. Internal consistency for the pain sub-scale was tested. Walking ability was assessed by the 6-minute walking test. RESULTS: The pain was worse in diabetic patients, the pain sub-scale scores differed between the groups (p < 0.05). High internal consistency was found for the pain sub-scale of the Foot Function Index. Results of the 6-minute walking test differed among the 3 groups: healthy volunteers performed best, and diabetic patients with symptomatic neuropathy worst (p < 0.001). Foot pain correlated moderately with the result of walking test (r = -0.449, p < 0.001). CONCLUSION: The pain sub-scale of the Foot Function Index is suitable for the assessment of pain in diabetic patients. Patients with severe foot pain have more difficulties when walking long distances than patients with less severe or without any pain.     

Circadian regulation of the hepatic endobiotic and xenobitoic detoxification pathways: the time matters

Metabolic processes have to be regulated tightly to prevent waste of energy and to ensure sufficient detoxification. Most anabolic processes operate in a timely manner when energy intake is the highest, while catabolism takes place in energy spending periods. Endobiotic and xenobiotic metabolism are therefore under circadian control. Circadian regulation is mediated through the suprachiasmatic nucleus (SCN), a master autonomous oscillator of the brain. Although many peripheral organs have their own oscillators, the SCN is important in orchestrating and entraining organs according to the environmental light cues. However, light is not the only signal for entrainment of internal clocks. For endobiotic and xenobitoic detoxification pathways, the food composition and intake regime are equally important. The rhythm of the liver as an organ where the major metabolic pathways intersect depends on SCN signals, signals from endocrine tissues, and, importantly, the type and time of feeding or xenobiotics ingestion. Several enzymes are involved in detoxification processes. Phase I is composed mainly of cytochromes P450, which are regulated by nuclear receptors. Phase II enzymes modify the phase I metabolites, while phase III includes membrane transporters responsible for the elimination of modified xenobiotics. Phases I-III of drug metabolism are under strong circadian regulation, starting with the drug-sensing nuclear receptors and ending with drug transporters. Disturbed circadian regualtion (jet-lag, shift work, and dysfunction of core clock genes) leads to changed periods of activity, sleep disorders, disturbed glucose homeostasis, breast or colon cancer, and metabolic syndrome. As many xenobiotics influence the circadian rhythm of the liver, bad drug administration timing can worsen the above listed effects. This review will cover the major hepatic circadian regulation of endogenous and xenobiotic metabolic pathways and will provide examples of how good timing of drug administration can change drug failure to treatment success.     

Allogeneic platelet gel with autologous cancellous bone graft for the treatment of a large bone defect

BACKGROUND/AIMS: A 50-year-old type 2 diabetic male with a comminuted fracture of the tibia and delayed union after insufficient initial osteosynthesis with a resulting pseudoarthrosis was treated operatively by using a graft composed of platelet gel mixed with autologous cancellous bone. The essential idea of this therapy was to combine the healing capacities of platelet-derived growth factors and osteogenic stem cells and the modeling capacity of the gel. Due to a history of diabetes, allogeneic instead of autologous platelets were used. METHODS: The allogeneic platelet concentrate was ABO- and RhD-matched, leukocyte-depleted, irradiated and activated by human thrombin. The defect of 45 ml was filled with the graft mixture and fixed with an external fixator. RESULTS: Postoperative care was uneventful. After 6 months the graft was incorporated, the bone defect was fully bridged and full weight-bearing capacity was achieved. No side effects were observed and no platelet or HLA class I antibodies were detected. CONCLUSION: This case report shows that the clinical use of allogeneic platelet-derived growth factors is feasible and that a prospective study is necessary to prove the effectiveness and reproducibility of this therapeutic approach.     

Relationship between aryl hydrocarbon receptor-affinity and the induction of EROD activity by 2,3,7,8-tetrachlorinated phenothiazine and derivatives

Reported herein are semi-empirical calculations of the molecular geometry of TCDD, TCPT, TCPT-sulfoxide (TCPT-O), TCPT-sulfone (TCPT-O(2)), N-methyl-TCPT (Me-TCPT), N-methyl-TCPT-sulfoxide (Me-TCPT-O), and N-methyl-TCPT-sulfone (Me-TCPT-O(2)), the characterization of their AhR binding affinity in rat hepatic cytosol, and their ability to induce EROD activity in a rat hepatoma cell line in vitro. Semi-empirical calculations yielded detailed information about the stereochemistry and the preferred conformation of each of these compounds. These results in combination with observations reported in this paper were used to determine structure-activity relationships. In vitro displacement of (3)H-TCDD was measured by increasing concentrations of the respective ligands. This assay revealed a strong binding affinity of TCPT to the AhR with a K(i) value of 1.08 nM. TCDD had a K(i) value of 0.54 nM. The affinity of TCPT derivatives for the AhR decreased with increasing degree of oxidation. Moreover, N-methylation further lowered the affinity, so that the N-methyl sulfone derivative of TCPT displayed the highest K(i) at approximately 1200 nM (=460.4 ng/ml). A corresponding trend was observed regarding the potency of TCPT and derivatives to induce EROD activity in vitro. However, the potencies were considerably lower than that of TCDD. Enzyme induction was measured in a rat hepatoma cell line H4IIEC/T3 by quantification of ethoxyresorufin-O-deethylase (EROD) activity. Induction was measured at 12, 24, 48 and 72 h to determine time dependence. Sulfoxidated and N-methylated phenothiazines displayed a lower potency than their respective parent compounds. TCPT and all derivatives induced enzyme activity at an efficacy similar to TCDD at all time points measured. The reported findings clearly separate the induction of EROD activity by TCPT and derivatives from their binding affinities to the AhR. In contrast, a direct correlation between the two is generally assumed in drug development, leading to - in our view - unwarranted termination of drug candidates. Therefore, a lack of such a correlation for TCPT and derivatives in fact supports their further development as possible drug leads.     

The Importance of Flaps in Reconstruction of Locoregionally Advanced Lateral Skull-base Cancer Defects: a Tertiary Otorhinolaryngology Referral Centre Experience

BackgroundThe aim of the study was to identify the value of extensive resection and reconstruction with flaps in the treatment of locoregionally advanced lateral skull-base cancer.Patients and methodsThe retrospective case review of patients with lateral skull-base cancer treated surgically with curative intent between 2011 and 2019 at a tertiary otorhinolaryngology referral centre was made.ResultsTwelve patients with locoregionally advanced cancer were analysed. Lateral temporal bone resection was performed in nine (75.0%), partial parotidectomy in six (50.0%), total parotidectomy in one (8.3%), ipsilateral selective neck dissection in eight (66.7%) and ipsilateral modified radical neck dissection in one patient (8.3%). The defect was reconstructed with anterolateral thigh free flap, radial forearm free flap or pectoralis major myocutaneous flap in two patients (17.0%) each. Mean overall survival was 3.1 years (SD = 2.5) and cancer-free survival rate 100%. At the data collection cut-off, 83% of analysed patients and 100% of patients with flap reconstruction were alive.ConclusionsFavourable local control in lateral skull-base cancer, which mainly involves temporal bone is achieved with an extensive locoregional resection followed by free or regional flap reconstruction. Universal cancer registry should be considered in centres treating this rare disease to alleviate analysis and multicentric research.Key words: temporal bone, microsurgery, parotid region, free tissue flaps, neoplasm staging, ear