One-stage Method Research Articles

Dual innervation method using one-stage reconstruction with free latissimus dorsi muscle transfer for re-animation of established facial paralysis: simultaneous reinnervation of the ipsilateral masseter motor nerve and the contralateral facial nerve to improve the quality of smile and emotional facial expressions

One-stage microneurovascular free muscle transfer is a common surgical procedure for re-animation of established facial paralysis. However, innervation of the transferred muscle by the contralateral facial nerve prevents smile and other facial expressions on one side, and reinnervation requires about 7 months. To overcome these drawbacks, we report a dual innervation method using one-stage reconstruction with free latissimus dorsi muscle transfer. Three patients were treated with the dual innervation method, which is based on the one-stage method with some modifications: the soft tissue present over the ipsilateral masseter muscle and the hilum where the thoracodorsal nerve proceeds into the muscle segment is removed; the muscle is harvested to locate the hilum in the cranial one-third of the segment; and the muscle is transferred to the malar pocket of the paralysed face such that the hilum contacts the masseter muscle. On average, muscle movement was recognised on voluntary biting at 3.4 months and on spontaneous smiling at 5.9 months after surgery. A dual innervation sign was recorded on electromyographs 6.4 months after surgery. The patients developed a spontaneous symmetrical smile and facial expressions on one side with minimum synkinesis after postoperative mirror rehabilitation. The advantages of the dual innervation method include faster reinnervation of the transferred muscle compared to one-stage options; achievement of spontaneous smile and voluntary smile on each side; augmentation of neural signals to the muscle for more symmetrical smiling; minimum synkinesis of the transferred muscle on biting for eyelid closure and emotional facial re-animation through a learning program to enhance cerebral cortical reorganisation.

Combined Models for Data from In Vitro–In Vivo Correlation Experiments

A method is presented to describe the in vitro–in vivo correlation (IVIVC) of an extended release drug formulation. This extended release drug product is overencapsulated with immediate release material. The heterogeneity of the capsule is modelled using a combined model of an extended release and an immediate release pharmacokinetic profile. Whereas an IVIVC is conventionally performed using a two-stage procedure, the model uses a one-stage convolution-based method. The method is applied to a Galantamine controlled release formulation, an acetylcholinesterase inhibitor for the treatment of Alzheimer's disease. The average percentage prediction error indicated a good fit of the new model.

Frequency of intron 1 inversion of factor VIII gene in Chinese hemophilia A patients with case report of a female patient with heterozygous intron 1 inversion

To investigate the frequency of intron 1 inversion (inv1) in FVIII gene in Chinese hemophilia A (HA) patients and to investigate the mechanism of pathogenesis. Peripheral blood samples were collected from 158 unrelated HA patients, aged 20 (1 - 73), including one female HA patient, aged 5, and several family members of a patient positive in inv1. One-stage method was used to assay the FVIII activity (FVIII:C). Long distance PCR and multiple PCR in duplex reactions were used to screen for the intron 22 inversion (inv22) and inv1 of the FVIII coding gene (F8). The F8 coding sequence was amplified with PCR and sequenced with an automatic sequencer. Two unrelated patients (pedigrees) were detected as inv1 positive with a positive rate of 1.26%. A rare female HA patient with inv1 was also discovered in a positive family (3 HA cases were found in this family and regarded as one case in calculating the total detection rate). The full length of FVIII was sequenced, and no other mutation was detected. There frequency of FVIII inv1 is low in Chinese HA patients compared with other populations. Female HA patients are heterozygous for FVIII inv1 and that may be resulted from nonrandom inactivation of X chromosome.

One‐stage and chromogenic FVIII:C assay discrepancy in mild haemophilia A and the relationship with the mutation and bleeding phenotype

The discrepancy of the levels of factor VIII activity (FVIII:C) by different assays in some mild and moderate haemophilic A patients has been long known. Specific mutations affecting FVIII:C discrepancies have been described. No consensus exit as to which method most accurately represents the FVIII cofactor function in vivo and which has a better correlation with the haemorrhagic clinical expression. We studied 163 mild A haemophiliacs, and detected discrepancies in 20% of the patients, most of whom presented higher levels of FVIII:C with the one-stage assay. In nine families, the FVIII mutation was found, while three showed mutations not previously described (Leu1978Phe and Ser1791Pro associated with higher levels of FVIII:C by one-stage method; Arg1639His in a patient with low level of FVIII:C by the one-stage, but normal, chromogenic assay). Assessing the level of FVIII:C by different methods could help to learn the possible haemorrhagic expressions of patients.

SIMULTANEOUS HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION OF DAPSONE AND MONOACETYLDAPSONE IN HUMAN PLASMA AND URINE

A rapid, specific and a one-stage protein precipitation method for simultaneous estimation of dapsone (DDS) and monoacetyldapsone (MAD) concentration in plasma and urine using high performance liquid chromatography (HPLC) is described. The applicability of the method for monitoring DDS and MAD blood levels in two different acetylator phenotype volunteers following the administration of 100-mg oral dose of DDS was shown. Cumulative urinary excretion of DDS and MAD were studied in the same volunteers.

A Scalarizing One-Stage Algorithm for Efficient Multi-Objective Optimization

A novel kriging-assisted algorithm is proposed for computationally expensive multi-objective optimization problems, such as those which arise in electromagnetic design. The algorithm combines the multiple objectives into a single objective, which it then optimizes using a one-stage method from single-objective optimization. Inequality and equality constraint handling techniques are included, as is a method for dealing with failed iterations. Its efficiency is demonstrated on the constrained optimization of a pair of Helmholtz coils.

Reconstruction of Advanced-Stage Electrical Hand Injury in a One Stage Procedure Using a Prefabricated Medial Lateral Crural Composite Flap

To explore the possibility of a one stage restoration of protective sensation and finger flexion after electrical burn of the hand, 5 patients with electrical injuries at the wrist were treated by a new free composite flap, originating from the medial lateral crural skin flap. This flap can repair skin, blood vessels, tendons, and nerves in a one-stage procedure. The harvest of the medial lateral crural flap is described. The posterior tibial vessels provide the arterial supply. The perforators to the flap and the branches to the plantaris tendon and the sural nerve were preserved, and the nerve and tendon were kept within the flap by careful dissection of the crural fascia. At the same time, 3 to 4 tendons of extensor digitorum longus were inserted into the layer between superficial and profundus crural fascia. Thus, blood vessels, nerves, and tendons were combined into the flap before transplantation. The composite flap was then transplanted into the recipient site of the injured hand to repair the complex defects in a single operation. Flexion and extension function of the fingers was evaluated. Sensory function was tested by the standards recommended by the British Medical Research Council System for evaluating sensibility. Follow-up ranged from 18 to 24 months. Results revealed all flaps survived. The flexion distance from tip to palmar crease and extension distance from tip to horizontal level of 3 patients were 4 to 5 cm and 3 to 4 cm, respectively. At 6 months, 2 patients improved from 6 cm and 5 cm to 4 cm and 4 cm, respectively. The sensation reached to S2 level, and skin temperature rose. The medial lateral crural composite flap is an ideal, one-stage method to restore protective sensation and finger flexion for advanced-stage patients who have suffered severe high voltage electrical injuries in the wrist.

The inferior labial artery island flap

The Abbe flap procedure has typically been indicated in cases of tissue defects of the upper lip after injury or tumour excision. However, this method requires two-stage reconstruction. In this report, we describe for the first time a novel one-stage reconstruction method using the inferior labial artery island flap. A 54-year-old man presented with a left upper lip defect and a scar contracture between the upper lip and the left cheek. We planned to reconstruct the lip defect using the inferior labial artery island flap. The inferior labial artery island flap was harvested with a vascular pedicle, and the vascular pedicle was returned through the inside of the flap. The flap survived completely, and liquid leakage from the lip and the appearance of the injured area were clearly improved. For this new technique, we converted the inferior labial flap to a vascular pedicled island flap, which increased its flexibility. This long vascular pedicle could be returned through the inside of the flap. Thus, this flap appears to be ideal for one-stage reconstructions of full-thickness upper lip defects.

Genome-wide association tests by two-stage approaches with unified analysis of families and unrelated individuals.

Multiple testing is a problem in genome-wide or region-wide association studies. In this report, we consider a study design given by the Genetic Analysis Workshop 15 (GAW15) Problem 3 - nuclear families (parents with their affected children) and unrelated controls. Based on this design, we propose three two-stage approaches to deal with the problem of multiple testing. The tests in the first stage, statistically independent of the association test used in the second stage, are used to screen or select single-nucleotide polymorphisms (SNPs). Then, in the second stage, a family-based association test is performed on a much smaller set of selected SNPs. Thus, the problem of multiple testing is much less severe. Our simulation studies and application to the dense SNP data of chromosome 6 in the GAW15 Problem 3 show that the two-stage methods are more powerful than the one-stage method (using the family-based association test only).

Study on graded therapy of hemophilic arthritis by integrative traditional Chinese and Western medicine

To study the effect and safety of graded therapy featuring integrative traditional Chinese and Western medicine for the treatment of hemophilic arthritis. Forty patients with hemophilic arthritis were hospitalized randomly, with their blood coagulation factor activity determined by one-stage method and their arthritis classified into 4 stages. The treatment was applied according to the stage of arthritis and finding of intra-articular cavity puncture. For stage I, based on the principle of RICE (rest, ice, compression and elevation), 1.8 g of Xuefuda was medicated orally once per day, intravenous dripping of 250 mL of hemostasis mixture twice a day and 1.2 g of clindamycin per day were also given for hemostasis and anti-inflammation. For stage II-III, Kangyanling was additionally administered via intra-articular cavity injection twice a week, 2 mL every time, for 5-6 times in total. For stage IV, the drug for intra-articular cavity injection was replaced with 25 mg of sodium hyaluronate and the frequency of injection reduced to every two weeks, for 5-6 times in total. Coagulation factors III and IV as well as blood plasma were not given in the whole treatment course. Short-term therapeutic effects and adverse reaction in patients were evaluated, and the long-term effects were followed-up after patients left the hospital with 6-month consolidation therapy by Xuefuda. After a 3-week treatment, 33 patients (82.5%) were completely remitted; 5 (12.5%) were partially remitted and 2 (5.0%) un-remitted, setting the short-term effective rate at 95.0% (38 cases). The 6-month follow-up showed that except for a relapse in 2 and 4 patients of stage III and IV respectively, long-term remission displayed in all the other 34 patients, with the remission sustaining rate being 85.0%. No complication such as an infection, bleeding or aggravating pain occurred in the 215 times intra-articular puncturing conducted in the 40 patients. Normal figures were shown in liver and kidney function, electrolytes, ECG, blood glucose and routine test of blood and urine throughout the course. The graded treatment of integrative medicine for hemophilia with non-blood preparation has a favorable effect and is safe or without any adverse reaction, which opens a high efficacy and new safe path and thinking for the treatment of and deformity prevention in the hemophilic patients.

Primary Repair in Adult Patients with Untreated Cleft Lip–Cleft Palate

The authors have volunteered their services as plastic surgeons in several countries, such as Nepal and Cambodia. In these programs, the authors saw many adults with cleft lips or palates who could not have primary repair at the proper time. The purpose of this report is to discuss the primary repair of untreated cleft lips or palates in adult patients. Subjects were older than 17 years. In Nepal, primary repairs were performed in 129 adults with untreated clefts over the past 11 years. Unilateral cleft lips were repaired by rotation advancement with the small triangular flap method or the straight method with a small triangular flap. Bilateral clefts were repaired using a one-stage repair method. Cleft palates were repaired by a mucoperiosteal push-back or Furlow technique. Differences between primary cleft repair for infants and for adults were as follows: (1) in adults, aggressive correction was possible, as maxillary growth was not a consideration; (2) correction of the anterior part of the nasal deformity was more difficult than in infants, as adults showed less elasticity and a more severe deformity of the nasal cartilages; (3) simultaneous palatoplasty should be chosen judiciously, as it is more invasive and results in higher morbidity; and (4) cheiloplasty under local anesthesia can reduce cost, time, and manpower. These observations should be useful for the local and foreign surgeons who treat clefts in developing regions.

A Limited Sampling Strategy for Estimating Individual Pharmacokinetic Parameters of Coagulation Factor VIII in Patients With Hemophilia A

Therapeutic drug monitoring of factor VIII is well established in the treatment of patients with hemophilia attributable to important interindividual variability. The individual initial factor VIII dosage is usually calculated according to individual pharmacokinetic parameters obtained after a dose test administered before the surgery, using at least five-concentration data. The authors proposed a limited sampling strategy to estimate individual pharmacokinetic parameters from one- or two-concentration data in patients with hemophilia A before surgery. The mean population pharmacokinetic parameters and the interindividual variability (CV) were obtained from a group of 33 patients according to a two-compartment model using NONMEM. Eighteen additional patients were used to estimate the predictive performances of the population parameters and to evaluate the limited sampling strategies. Population parameters were clearance 2.6 mL/h per kilogram (CV 45.4%), initial volume of distribution 2.8 L (CV 21.1%). From two sampling times (0.5 and 6 hours or 0.5 and 8 hours after the end of infusion), the estimation of pharmacokinetic parameters was precise and not biased. Until now, in the hemophilic center of Lyon, the factor VIII dosage before surgery was based on the determination of the clearance, estimated from five- to nine-concentration data and on the target concentration (infusion rate = clearance x target). Ruffo et al proposed a limited sampling strategy (two-stage method) to estimate pharmacokinetic parameters from two concentration measurements drawn 3 and 9 hours after the dose. No information was given on the bias and precision of the estimation. This paper reports a one-stage method for a population pharmacokinetic study of factor VIII. The Bayesian estimation of individual pharmacokinetic parameters based on only two sampling times (0.5 and 6 hours or 0.5 and 8 hours after the end of infusion) is useful to define the best factor VIII dosage in hemophilic patients before surgery.

Inhibitor development in one patient and laboratory discrepancies in several families with both mild haemophilia and Arg531Cys mutation

Certain mutations in mild haemophilia A have been associated with a greater risk of inhibitor development, especially when associated with intense treatment. We present a patient with both mild haemophilia A and Arg531Cys mutation, which developed lowtitre inhibitors and was not seen to be related to the intense substitute treatment. The inhibitor has a greater effect on the exogenous factor VIII, permiting an adequate response to treatment with desmopressin. A discrepancy exists in the factor VIII activity in this our patient and in the haemophiliacs of another two families with the same mutation when determination is performed with one-stage or chromogenic method.

Iodine status of Tasmanians following voluntary fortification of bread with iodine

To describe changes in the iodine status of Tasmanians following voluntary fortification of bread with iodine in October 2001. Post-intervention, cross-sectional urinary iodine surveys of Tasmanian schoolchildren aged 8-11 years were used to assess population iodine status. Participants were selected using a one-stage cluster sampling method. The sampling frame comprised classes containing fourth-grade children from all Tasmanian government, Catholic and independent schools. Results were compared with pre-intervention survey results. Median urinary iodine concentration (UIC) and percentage of UIC < 50 microg/L ascertained from spot urine samples. Median UIC was 75 microg/L in 1998, 72 microg/L in 2000, 105 microg/L in 2003, 109 microg/L in 2004 and 105 microg/L in 2005. Median UIC in post-intervention years (2003-2005) was significantly higher than in pre-intervention years. The percentage of UIC results < 50 microg/L was 16.9% in 1998, 18.7% in 2000, 10.1% in 2003, 10.0% in 2004 and 10.5% in 2005. Despite methodological differences between the pre- and post-intervention surveys, switching to iodised salt in bread appears to have resulted in a significant improvement in iodine status in Tasmania. Given iodine deficiency has been identified in other parts of Australia and in New Zealand, mandatory iodine fortification of the food supply in both countries is worthy of consideration. As voluntary fortification relies on industry goodwill, mandating fortification could be expected to enhance population reach and give a greater guarantee of sustainability in Tasmania.

Impaired endothelial antithrombotic activity following short-term interruption of continuous subcutaneous insulin infusion in type1 diabetic patients

Review of literature has shown an increased rate of thrombotic complications in diabetic patients with frequent episodes of hyperketonemia. However, the mechanisms by which ketosis promotes vascular disease in diabetic patients are unclear. It was the aim of this study to investigate early changes in haemostatic parameters and oxidative stress markers during the hyperketonemic status which follows the interruption of continuous subcutaneous insulin infusion (CSII) in type I diabetic patients. Eight CSII-treated type I diabetic patients underwent a 4-hour pump arrest. Blood glucose, insulin and 3-hydroxybutirate were measured to verify the metabolic response. A vein-occlusive (VO) test was performed for the determination of tPA and PAI-1 activities and their antigen levels before and after the CSII arrest. Coagulation factor VII and VIII were evaluated by one-stage PT and PTT method, respectively. TF, vWF, tPA and PAI-1 antigens were determined by ELISA, whereas tPA and PAI-1 activities using chromogenic methods. Plasma malondialdehyde (MDA) and protein carbonyl groups (PCG) levels were determined by HPLC and spectrophotometry, respectively. After the insulin deprivation phase, post-VO tPA antigen level significantly decreased (P = 0.0391), whereas TF and post-VO PAI-1 activity and antigen levels significantly increased (P = 0.0156 and P = 0.0234, respectively). Plasma MDA and PCG levels were 1.88-fold and 1.74-fold higher than baseline values, respectively. In conclusion, the impairment of the fibrinolytic potential and the increases in TF, MDA and PCG levels may enhance the risk of both arterial and venous thrombosis during ketosis. Thus, early detection of hyperketonemia in DM patients could contribute to the prevention of life-threatening vascular events.

Synthesis and Kinetics of Generation of MMS/MFI Materials Prepared on the Basis of Ti-Aerosil

The one-stage bitemplate synthesis method for obtaining mesoporous zeolite-containing materials was used to prepare Ti-aerosil (Ti-MZ). The formation kinetics and the textural features of this material were also studied. The products were characterized by IR spectroscopy (FT-IR), X-ray diffraction (XRD) and nitrogen adsorption methods. Hydrothermal processing (HTP) for relatively short time periods (ca. 8 h) led to the formation of zeolite nano-domains in the amorphous titanium-silica matrix exhibiting perfect two-dimensional hexagonal packing without destruction of the mesopore framework. Increasing HTP time was accompanied by the formation of a highly crystalline zeolite framework in the titanium-silica matrix which exhibited increasing microporosity accompanied by the destruction of the mesoporous framework.

Professional Exposure to Microorganisms and Microbial Volatile Organic Compounds (MVOC) in a Composting Facility

P-611 Introduction: Composting has become an expanding branch of waste management in the recent years. Irritative effects and asthma are nevertheless described and can be related to micro-organisms as well as MVOC exposure. The aim of this study was to simultaneously compare exposure levels to microorganisms and MVOC and to study the influence of sampling time, season, nature of waste composted and step of the process on these levels. Methods: 2 units were studied: green waste and compostable household waste. 4 different sampling campaigns were carried out during summer and winter between 2004 and 2005. Ambient and individual MVOC air samples were taken using active air sampler (adsorbent tubes filled with Tenax TA) and passive diffusion badges. Ketones, Terpenes and alcohols were identified and analyzed by a combination of gas chromatography and mass spectrometry. Viable bacteria and fungi were sampled using one-stage Andersen impaction method (1 min) and also filtration method (aerosol monitors loaded with polycarbonate filters) (6h). Bacterial and fungal colonies were identified and quantified. Correlations between microorganisms and MCOV were estimated with non parametric tests. Results: Most of the sampling sites show high bacterial and fungal concentrations (103 to 106 cfu/m3) independently of waste's nature, mainly during operations generating organic dust (grinding and sieving). We were unable to give prominence to season's influence on such levels. The highest MCOV concentrations (40 mg/m3) were noted during biowaste fermentation stages handled in enclosed area, and were mainly composed of terpenes and alcohols. Individual exposure levels almost reach ambiant ones during manual tasks realized without respirators. Concerning greenwaste, high concentrations (up to 30 mg/m3) were only noted during grinding, and were mainly represented by terpenes. Individual exposure remained low thanks to the use of front end loaders equipped with air filters. No significative correlation was found between microorganisms and MVOC, probably because of numerous influence factors (waste, season, process, stage of biodegradation). Discussion/Conclusion: From this study, some agents are likely to be of interest as exposure indicators: Aspergillus fumigatus for microorganisms, limonene/3-methyl-1-butanol/2-pentanone for MVOC. Microbial levels observed with filtration method confirm levels revealed with impaction reference method. 6h MVOC active samplings also match one-week passive samplings. Such high concentrations (at main sampling sites for microorganisms, during some activities for MVOC) request better air filtration in trucks cabins and the use of respirators for particular manual operations.

Population-based survey on prevalence of adult patients with epilepsy in Taiwan (Keelung community-based integrated screening no. 12)

Purpose To determine the prevalence rate and patterns of adult patients with epilepsy in Taiwan, we conducted a community-based neuroepidemiological survey. Methods Epilepsy was detected by neurologists using one-stage method. It was integrated into a community health screening service and performed from 1 January 2001 to 31 December 2001 in Keelung, a northern city in Taiwan. A total of 13,663 subjects aged 30 years or older participated in this survey. Results There were 52 patients with epilepsy in this study. Among them, 37 were patients with active epilepsy. The age-adjusted prevalence rate of active epilepsy above 30 years old was 2.77/1000 (to the 1980 US population) with the highest rate in subjects aged 40–49 years (4.0/1000). There was a trend of higher prevalence rate in male than in female. The most common seizure type was complex partial seizure (46.0%). Using one-stage detection method, we found nine (24.3%) patients with active epilepsy who had never been diagnosed before. Among the patients with active epilepsy, 35.1% were symptomatic cases. Head injury (13.5%) is the leading cause, followed by CNS infection (8.1%), stroke (5.4%) and perinatal insult (5.4%). The lifetime prevalence rate of epilepsy (including active epilepsy and epilepsy in remission) was 3.14/1000 for age above 30 years. Conclusions Comparing to previous epilepsy survey in 1993, our results showed that the prevalence rate of epilepsy was rather stable over the past decade in northern Taiwan. Head injury is the leading cause responsible for active epilepsy. Improving public safety is an important public health issue which may help to reduce occurrence of epilepsy.

Heterocyclization of N‐Phenylanthranylamide Effected by Aroyl Ketenes.

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Accuracy of FVIII: C assay by one-stage method can be improved using hemophilic plasma as diluent.

the basic prerequisite of Factor VIII clotting assay (FVIII:C) by One-Stage Method is that all other than FVIII clotting factors are present in constant concentration in each dilution of both standard reference and patient's plasma curves. On the contrary, the plasma content of each dilution is decreasing as the dilution factor increases. to keep exactly constant the plasma content in each mixture, we performed all dilutions of both standard reference and patient's plasma with FVIII deficient plasma and further with a fixed amount of buffer (method B). To show the discrepancies between this method and regular method A, using buffer to make dilutions, a comparative study was conducted on FVIII: C assay on samples at known FVIII concentration and in patients' plasma. Imidazole or Owren's buffers and five different aPTT reagents were employed, both in method A and B. a discrepancy between FVIII: C assays obtained by method A and B was observed, mainly when Pathrontin SL and Imidazole buffer were used. The assays derived from method B always better fit with the expected, calculated, values of FVIII:C concentrations. Furthermore, FVIII: C was assayed in 60 patients: the outcome of method A was always higher than values of method B. The discrepancy between the two methods was higher at FVIII concentrations below 50 U/dL but null at 100 U/dL. The A slope was steeper than B slope and the difference was statistically significant starting from the 1/10 dilution. Accordingly, FVIII: C of patients' plasma obtained by method A was always higher that those obtained by method B, even 2 or 3 times for FVIII level < or = 10 U/dL or 1.4-1.6 times for FVIII levels between 10 and 25 U/dL. only method B is able to give FVIII: C assays in agreement with the expected values. The dilution of reference standards and samples with FVIII deficient plasma is crucial to accurately evaluate the post-infusion FVIII concentrations in pharmacokinetic studies or the trough level during prophylactic therapy and to investigate the discrepancy among different FVIII: C assays. In addition, the assessment of severity and classification of hemophilia should be reviewed.