Lip symmetry following rotation advancement cleft lip repair in 5-year-old children treated by Ralph Millard and Ron Pigott.

Objective: To compare the symmetry of the lip following Rotation-Advancement cleft lip repair by Millard and Pigott and to investigate the effect on the symmetry of cleft side and gender by using different surgical protocols. Symmetry following cleft surgery was compared to that of non-cleft children. Design: Retrospective study of photographs of children aged 5 years. Setting: Three decades of post-operative photographs of children treated by Millard and Pigott. Patients: Eighty-nine children treated by Millard, 87 by Pigott and 91 non-cleft children. Interventions: Photographs were assessed using the Symnose Computer program, a rapid semi-objective quantitative assessment of lip symmetry. Main Outcome Measures: Asymmetry score for each surgeon, and non-cleft children. Results: There was no significant difference in the median lip % mismatch score of Millard, 36.65% and Pigott, 38.52%. Right-sided clefts showed better symmetry than left-sided clefts for Millard (p<.001). This was reversed for Pigott (P=.0121). There was a difference (P<.001) between the symmetry of the two cleft cohorts and the non-cleft children (asymmetry 19.9%), and between Millard's outcomes following different lip surgical protocols (P < .0001), but no difference between Pigott's outcomes using different palate surgical protocols (P = 0.59). Conclusions: Cleft lip repair by Millard and Pigott resulted in similar lip asymmetry (37% and 39% symmetry mismatch, respectively). Lip surgical protocol and cleft side may affect lip asymmetry. Palate surgery did not affect lip asymmetry. Following cleft surgery, children were more asymmetric than non-cleft children.

Longitudinal Study of Caries Development from Childhood to Adolescence.

The World Health Organization (WHO) stated that globally, dental caries is the most important oral condition. To develop effective prevention strategies requires an understanding of how this condition develops and progresses over time, but there are few longitudinal studies of caries onset and progression in children. The aim of the study was to establish the pattern of caries development from childhood into adolescence and to explore the role of potential risk factors (age, sex, ethnicity, and social deprivation). Of particular interest was the disease trajectory of dentinal caries in the permanent teeth in groups defined by the presence or absence of dentinal caries in the primary teeth. Intraoral examinations to assess oral health were performed at 4 time points by trained and calibrated dentist examiners using a standardized, national diagnostic protocol. Clinical data were available from 6,651 children. Mean caries prevalence (% D3MFT > 0) was 16.7% at the first clinical examination (ages 7-9 y), increasing to 31.0%, 42.2%, and 45.7% at subsequent examinations. A population-averaged model (generalized estimating equations) was used to model the longitudinal data. Estimated mean values indicated a rising D3MFT count as pupils aged (consistent with new teeth emerging), which was significantly higher (4.49 times; 95% confidence interval, 3.90-5.16) in those pupils with caries in their primary dentition than in those without. This study is one of the few large longitudinal studies to report the development of dental caries from childhood into adolescence. Children who developed caries in their primary dentition had a very different caries trajectory in their permanent dentition compared to their caries-free contemporaries. In light of these results, caries-free and caries-active children should be considered as 2 separate populations, suggesting different prevention strategies are required to address their different risk profiles.

Characteristics and products of the reductive degradation of 3-nitro-1,2,4-triazol-5-one (NTO) and 2,4-dinitroanisole (DNAN) in a Fe-Cu bimetal system.

It has been shown previously that, under acidic conditions, 3-nitro-1,2,4-triazol-5-one (NTO) and 2,4-dinitroanisole (DNAN) degrade in the presence of iron/copper bimetal particles; the reactions can be modeled by pseudo-first-order kinetics. This study investigates the reaction mechanisms of the degradation processes under different conditions. Batch studies were conducted using laboratory-prepared solutions and an industrial insensitive munition-laden (IMX) wastewater. The influence of parameters such as initial pH of the solution, copper/iron (Fe-Cu) contact, and solid/liquid ratio were systematically investigated to assess their impact on the reaction kinetics. These parameters were subsequently incorporated into pseudo-first-order decomposition models for NTO and DNAN. The activation energies for the degradation reactions were 27.40 and 30.57 kJ mol-1, respectively. Degradation intermediates and products were identified. A nitro-to-amino pathway, which ultimately may lead to partial mineralization, is postulated. The amino intermediate, aminonitroanisole, was detected during DNAN degradation, but for NTO, aminotiazolone is suggested. Additionally, urea was identified as a degradation product of NTO.

Facial aesthetic outcome analysis in unilateral cleft lip and palate surgery using web-based extended panel assessment.

BACKGROUND AND AIM: The reproducible measurement of aesthetic outcomes after cleft lip and palate (CLP) surgery remains elusive, and there is no internationally recognised system. The aim of this pilot study was to better understand how humans rate post-operative aesthetic outcome after unilateral cleft lip and palate (UCLP) repair using a novel web-based rating platform with an extended panel of surgeon raters. METHODS: Cropped images of 5-year-old UCLP patients were arranged in a randomly generated sequence within a web-based aesthetic scoring tool as part of an agreement/reliability study. Assessors rated the appearances of patients using a five-point Likert-type scale on two occasions. A mixed-effect statistical model was adopted to analyse the effects of rater, image and timing. RESULTS: Images of 76 patients were scored by 29 UK-based cleft surgeons. Intra-rater variability was found, and the linear weighted kappa was 0.56. This allowed identification of the most and least consistent raters. The random image effect (p < 0.001) suggested that a broad range of aesthetic outcomes were included in the current study. Surgeon raters in this study were likely to score the images more preferably at the second assessment. CONCLUSIONS: A web-based scoring system provides extended data capture, and mixed-effect statistical modelling reveals the effect that time, image and rater have on the scorings. The selection and training of raters, in combination with an exemplary yardstick, might improve inter- and intra-rater agreement. The development of objective measures based upon digital facial recognition can replace the highly variable subjective human influence on rating the aesthetic outcome.

Multidrug-resistant cells overexpressing P-glycoprotein are susceptible to DNA crosslinking agents due to attenuated Src/nuclear EGFR cascade-activated DNA repair activity.

We synthesized several novel bifunctional alkylating derivatives of 3a-aza-cyclopenta[a]indene (BO-1012, BO-1005, BO-1099 and BO-1101) that are potent DNA interstrand crosslinking agents. In in vitro cytotoxicity assay, these compounds were more cytotoxic to multidrug-resistant (MDR) cells, such as KBvin10, KBtax50 and CEM/VBL, than their parental cells. Using a xenograft model, BO-1012, at a dose of 5 mg/kg, partially suppressed the growth of parental KB cells but completely suppressed the growth of KBvin10 cells in nude mice. In exploring the possible mechanism, we found that DNA double-strand break (DSB) repair activity in MDR cells, KBvin10 and CEM/VBL, was significantly reduced compared with their parental cells, KB and CEM. Reduced DSB repair activity in KBvin10 cells was likely due to a defect in nuclear translocation of DNA-dependent protein kinase (DNA-PK), a component of the non-homologous end-joining repair machinery. Furthermore, BO-1012-induced DNA-PK translocation from the cytosol into the nucleus in KB cells is associated with the activation of the Src/nuclear epidermal growth factor receptor (EGFR) cascade, which is defective in MDR cells. As knockdown of P-glycoprotein (P-gp) by siRNA reactivated the Src/nuclear EGFR cascade, DNA-PK translocation and DNA repair activity in MDR cells, overexpression of P-gp attenuates the activity of DNA DSB repair through suppression of Src/nuclear EGFR cascade. Therefore, DNA interstrand crosslinking agents may have potential therapeutic use against P-gp-overexpressing MDR cells.

Laboratory measurements of the volatilization of PCBs from amended dredged material.

Since 1997, over 6 million cubic meters of material dredged from the navigation channels of NY/NJ Harbor has been amended with Portland cement and then used as fill and capping material at landfill and brownfield sites in New Jersey, New York, and Pennsylvania. Previous studies have determined that polychlorinated biphenyls (PCBs) will volatilize from this material as it dries. In the present study, time constants for the decay of the volatilization rate were determined taking into account the degree of stabilization. The experiments were conducted in a laminar flow flux chamber in which air was drawn past the dredged material and then through a polyurethane foam (PUF), sample matrix. The concentration of PCBs on the PUF found at various time increments at the downstream end of the chamber was compared to that found for the same time increments in a PUF installed in an air sampler at the upstream end of the chamber in order to calculate the flux. The time constant determined for raw dredged material was about 4 times greater than material stabilized with 8% Portland cement. The average time constants for the decay of flux rates from raw dredged material were 56, 67, and 60h for the di-, tri-, and tetra-chlorinated homologues, respectively. These times decreased with increasing proportion of Portland cement in the mixture. When stabilized with 8% Portland cement, the average time constants were 14, 13, and 19h, respectively. The effects of temperature on PCB flux rate were also investigated. The results suggest that a 3 degrees C temperature increase will more than double the flux rate.

Kinetics of the alkaline hydrolysis of nitrocellulose.

Cellulose nitrate (nitrocellulose) is an explosive solid substance used in large quantities in various formulations of rocket and gun propellants. Safe destruction of nitrocellulose can be achieved by alkaline hydrolysis, which converts it to biodegradable products that can then be treated by conventional biological processes. The kinetics of the alkaline hydrolysis of munitions-grade nitrocellulose in sodium hydroxide solutions were investigated in completely mixed batch reactors. Experiments were conducted using solutions of alkaline strength ranging from 0.1 to 15% by mass and temperatures in the range of 30 to 90 degrees C. Regression analysis of the kinetic data revealed that alkaline hydrolysis of nitrocellulose is of the order 1.0 and 1.5 with respect to nitrocellulose and hydroxide concentration, respectively. The activation energy of the hydrolysis reaction was found to be 100.9 kJ/mol with a preexponential Arrhenius constant of 4.73 x 10(13). Nitrite and nitrate, in a 3:1 ratio, were the primary nitrogen species present in the posthydrolysis solution. The kinetic information is pertinent to the development and optimization of nitrocellulose chemical-biological treatment systems.

Synthesis and autoxidation of new tetracyclic 9H,10H-indolizino[1,2-b]indole-1-ones.

The new tetracyclic 9H,10H-indolizino[1,2-b]indole-1-one derivatives (7a-d, 7ea, 7eb) have been synthesized by modified Fischer indole synthesis from the enol ether of 2,5-dihydroxy-7-methyl-6-cyano-indolizine (3) and arylhydrazines (4a-g). Attempted N-methylation of 7a-d produced a series of autoxidized products including 10-hydroperoxy-1-methoxyindolizino[1,2-b]indole (9a-d) as the major product accompanied with methylperoxides (10a-d and 11a-d) and 2-formyl-3-(pyridine-2-yl)indole (12a, 12c) derivatives as the minor products. A plausible mechanism of the autoxidation is postulated based on the isolation of some intermediates. The reaction is thought to proceed through azaenolate/enamine intermediates following a novel type of autoxidation.

Methods for conducting sensitivity analysis of trials with potentially nonignorable competing causes of censoring.

We consider inference for the treatment-arm mean difference of an outcome that would have been measured at the end of a randomized follow-up study if, during the course of the study, patients had not initiated a nonrandomized therapy or dropped out. We argue that the treatment-arm mean difference is not identified unless unverifiable assumptions are made. We describe identifying assumptions that are tantamount to postulating relationships between the components of a pattern-mixture model but that can also be interpreted as imposing restrictions on the cause-specific censoring probabilities of a selection model. We then argue that, although sufficient for identification, these assumptions are insufficient for inference due to the curse of dimensionality. We propose reducing dimensionality by specifying semiparametric cause-specific selection models. These models are useful for conducting a sensitivity analysis to examine how inference for the treatment-arm mean difference changes as one varies the magnitude of the cause-specific selection bias over a plausible range. We provide methodology for conducting such sensitivity analysis and illustrate our methods with an analysis of data from the AIDS Clinical Trial Group (ACTG) study 002.

Synthesis of biotinylated glyfoline for immunoelectron microscopic localization.

Antineoplastic glyfoline (1) has potent antitumor efficacy against various murine and human solid tumors. To elucidate the actual mechanism of action, we synthesized biotinylated glyfoline (B-Gly) and used it for the visualization of glyfoline-binding sites in nasopharyngeal carcinoma (NPC) cells. Under the electron microscope (EM), after cells were incubated for 6-36 h, the reaction products of anti-B-Gly were seen on some areas of the external cell surface and on the outer and inner membranes of the mitochondria. Pure EM morphology of NPC cells after glyfoline treatment revealed the similar morphological change of mitochondria. These findings indicate that the binding site of glyfoline in NPC is the inner membrane of the mitochondria, suggesting that B-Gly can be used as a marker for glyfoline localization.

Synthesis and structure-activity relationships of potential anticancer agents: alkylcarbamates of 3-(9-acridinylamino)-5-hydroxymethylaniline.

A series of potential 9-anilinoacridine antitumor agents, 3-(9-acridinylamino)-5-hydroxymethylaniline (AHMA) derivatives with monosubstituent at C4' and disubstituents at C4' and C5' of the acridine ring and their alkylcarbamates, were synthesized for evaluation of their antitumor activity. A structure-activity relationship (SAR) study showed that the AHMA-alkylcarbamates were more potent than their corresponding parent AHMA compounds. In addition, the cytotoxicity of the AHMA-alkylcarbamate decreased with increasing length and size of the alkyl function. Among these compounds, AHMA-ethylcarbamate (18) and 4'-methyl-5'-dimethylaminoethylcarboxamido-AHMA-ethylcarb amate (34) possess potent cytotoxicity on the inhibition of human leukemic HL-60 cell growth in culture. Further in vivo studies of these compounds displayed significant anticancer therapeutic effects in mice bearing sarcoma 180, Lewis lung carcinoma, and P388 leukemia.

Alien hand syndrome: report of two cases.

Alien hand syndrome (AHS) refers to the occurrence of apparently purposeful movements in the hand which are independent of volitional control. Two subtypes of AHS have been proposed: frontal AHS, with grasp reflex and compulsive manipulation of tools by the dominant hand, and callosal AHS, which occurs in the nondominant hand and is characterized mainly by intermanual conflict. Here, we report two cases of frontal-type alien hand syndrome with symptoms of reflexive grasping, impulsive groping, and apraxia (in case 1), and compulsive manipulation of tools (in case 2). Brain computed tomography revealed a left anterior cerebral artery (ACA) territory infarct and multiple small infarcts of both hemispheres in patient 1 and a left ACA infarct in patient 2. The involuntary movements were bothersome to these patients in their daily activities. Both patients attended conventional physical and occupational therapies, and patient 2 received additional biofeedback training. Follow-up studies showed the spontaneous grasping behavior was still present in patient 1 and AHS had subsided in patient 2. We also describe a potentially effective technique involving biofeedback for patients with alien hand syndrome.

Serum hepatocyte growth factor level associate with gastric cancer progression.

We have measured serum HGF levels from 80 gastric cancer patients and 51 normal subjects by enzyme-linked immunosorbent assay. The results showed that the mean value of serum HGF level in gastric cancer patients was significantly higher than in normal subjects (0.30 +/- 0.02 vs 0.22 +/- 0.05 ng/ml; p = 0.005). The increase was stage related. Patients with serum HGF < or = 0.30 ng/ml survived longer than those with serum HGF > 0.30 ng/ml (p = 0.02). These data suggest that HGF involve in progression of gastric cancer.

Differential paclitaxel-induced cytotoxicity in rodent and human hepatoma cell lines.

Hepatoma is the leading cause of death in male cancer patients in Taiwan. In this study, we examined the effect of Paclitaxel on the in vitro growth of 2 rodent and 4 human hepatoma cell lines. Differential Paclitaxel-induced cytotoxicity was observed among hepatoma cell lines. In Paclitaxel-sensitive Hep3B and N1S1 cells, Paclitaxel-induced cytotoxicity was dose- and time-dependent. The effective doses of Paclitaxel were in the range 0.1-1.0 microM. Flow cytometric analysis showed that Paclitaxel-treated hepatoma cells were arrested in G2-M phases prior to apoptosis. In addition, growth inhibition by Paclitaxel was accompanied by an increase in the expression of proliferating cell nuclear antigen (PCNA) in hepatoma cells. For Paclitaxel-resistant hepatoma cells, cytostatic response and/or polyploidization was observed. Our results indicated that two thirds of the hepatoma cell lines examined showed some degree of resistance to Paclitaxel treatment in vitro. The expression of p53 gene had no direct effect on Paclitaxel-induced cytotoxicity. The expression of PCNA and the development of polyploidization appear to be good markers for measuring Paclitaxel response. These findings suggest that Paclitaxel alone appears to by cytostatic to hepatoma cells, combination of Paclitaxel with other chemotherapeutic agents may show better cytotoxic effects.

The prevalence of cognitive impairment among nursing home residents in Taipei, Taiwan.

A random sample of nursing home residents over 65 years of age were interviewed. Two hundred ninety-two participants received the Short Portable Mental Status Questionnaire. Two hundred eleven were unable to answer the questionnaire, but their caregivers provided information about their daily activities and performance ability. We found that 255 (50.9%) fit our criteria of cognitive impairment and 236 (47.7%) had both impaired cognition and impaired performance in activities of daily living. Similar to statistics in the US, the prevalence of cognitive impairment in Taipei nursing home residents was much higher than that observed in the community elderly and probably in Taiwan as well. Therefore, public health care policy for cognitively impaired elderly in Taiwan should not simply rely on data from community studies.

Isolation and identification of novel protein kinase genes from the round-spotted pufferfish (Tetraodon fluviatilis) genomic DNA.

The round-spotted pufferfish Tetraodon fluviatilis has a genome size of 380 Mb which is slightly smaller than that of another pufferfish, Fugu rubripes rubripes (Fugu). Due to their compact genome and small introns, both pufferfishes have been proposed as model organisms for genome studies. In this study, we have used genomic DNA as template to perform PCR to screen for protein kinase (pk) genes. Forty-one T. fluviatilis pk genes encoding 7 receptor tyrosine kinases, 14 nonreceptor tyrosine kinases, 16 serine/threonine kinases, 1 dual kinase and 3 novel kinases have been identified. The success of this approach depends on the size and location of the introns. Most of the identified pk gene fragments contain introns, ranging from 71 to 300 bp, with an average of 120 bp. It is noteworthy that the intron/exon boundaries of certain genes which belong to the same family are identical. We also analyzed by specific RT-PCR primers the expression profile of those 3 novel genes as well as some selected pk genes in a variety of tissues. We found that erbB3, pku a, mrk, CaMK I, CaMKIIgamma, and two novel kinase genes (133 and 3-26) are expressed in all tissues examined. However, the novel clone 146 is strongly expressed in the brain and weakly in the intestine, kidney and heart.

Nutrient recovery and biodegradation of inedible tomato plant residues by activated sludge cultures and Phanerochaete chrysosporium.

The biodegradation of inedible biomass and the recovery of nutrients from hydroponically grown tomato plant material were investigated under various growth conditions of activated sludge and the fungus Phanerochaete chrysosporium. The experiments were carried out in shaker flasks at three incubation temperatures (25 degrees C, 40 degrees C, and 60 degrees C for the activated sludge and 25 degrees C, 40 degrees C, and 50 degrees C for the fungi) with heat-pretreated samples at 150 degrees C for 30 min, and without pretreatment of the inedible residues. Under the experimental conditions tested, both cultures exhibited similar performance in terms of solids reduction and nutrient recovery. Solids reduction as high as 70% was obtained in both systems. Most of the solids degradation occurred the first 16 days of incubation. Cellulose degradation reached about 90% but no significant reduction in the solids lignin content was observed. Recovery of nitrogen (as NO2-N and NO3-N) and other micronutrients was sufficiently high and was accompanied by an average 70% reduction in COD, indicating that the final effluent is suitable for hydroponic plant growth. Incubation temperature had a minimal effect on solids degradation but appeared to influence the leachability of certain nutrients.

Cyclopent[a]anthraquinones as DNA intercalating agents with covalent bond formation potential: synthesis and biological activity.

A series of mitomycin C (MMC) analogues, namely cyclopentanthraquinone derivatives, were synthesized via Diels-Alder cyclization of naphthoquinone with 1-vinylcyclopent-1-enes. These new compounds are planar structures, like MMC, and bear an aziridine ring and a methyl carbamate side chain. After bioreduction, they are anticipated to be capable of intercalating into double-stranded DNA and bind covalently. Structure-activity relationships were studied. Of these compounds, 2,3-aziridino-4-[[(methylamino)carbonyl]methyl] cyclopent[alpha]anthracene-6,11-dione (4) was shown to have inhibitory activity against several leukemic and solid tumor cell lines. Mice (BDF1) bearing Lewis lung adenocarcinoma were treated with 4 and MMC (i.p., QD x 5). At a dose of 30.0 mg/kg, compound 4 was as effective as MMC (0.8 mg/kg). Compound 4 appears to be less toxic than MMC. DNA unwinding assay indicated that 4 is able to intercalate into DNA double strands and is also a topoisomerase II inhibitor.

9-substituted acridine derivatives with long half-life and potent antitumor activity: synthesis and structure-activity relationships.

A series of DNA-intercalating 9-anilinoacridines, namely 9-phenoxyacridines, 9-(phenylthio)acridines, and 9-(3',5'-disubstituted anilino)acridines, were synthesized as potential antitumor agents with inhibitory effects on DNA topoisomerase II. Unlike amsacrine (m-AMSA), these agents were designed to avoid the oxidative metabolic pathway. These acridine derivatives were, therefore, expected to have long half-life in plasma. Both 9-phenoxyacridines and 9-(phenylthio)acridines were found to have moderate cytotoxicity against mouse leukemia L1210 and human leukemic HL-60 cell growth in culture. Among 9-(3',5'-disubstituted anilino)acridines, 3-(9-acridinylamino)-5-(hydroxymethyl)aniline (AHMA) was found to be a potent topoisomerase II inhibitor and exhibited significant antitumor efficacy both in vitro and in vivo. Chemotherapy of solid-tumor-bearing mice with 10, 10, and 5 mg/kg (QD x 4, ip) AHMA, VP-16, and m-AMSA, respectively, resulted in more tumor volume reduction by AHMA than by VP-16 or m-AMSA for E0771 mammary adenocarcinoma and B-16 melanoma. For Lewis lung carcinoma, AHMA was as potent as VP-16 but more active than m-AMSA. Structure-activity relationships of AHMA derivatives are discussed.

Synthesis of the acridone alkaloids glyfoline and congeners. Structure-activity relationship studies of cytotoxic acridones.

Glyfoline (4, 1,6-dihydroxy-10-methyl-2,3,4,5-tetramethoxyacridin-9-one) and its congeners were synthesized for evaluation of their cytotoxicity. A detailed structure-activity relationships (SAR) of these acridone derivatives were also studied. To study the SAR of glyfoline analogues, substituent(s) at C-1 and C-6 and at the heterocyclic nitrogen of glyfoline nucleus were modified. Nitro- and amino-substituted glyfoline analogues were also synthesized to study the effects of substituent(s) (electron-withdrawing vs electron-donating) on their cytotoxicity. These compounds were synthesized via the Ullmann condensation of anthranilic acids with iodobenzenes or 2-chlorobenzoic acids with aniline derivatives. The SAR studies showed that 1-hydroxy-9-acridones were more active than their 1-OMe derivatives against cell growth of human leukemic HL-60 cells in culture. Replacement of NMe of glyfoline with NH or N(CH2)2NEt2 resulted in either total loss or dramatic reduction of cytotoxicity. Glyfoline congeners with nitro function at the A-ring were inactive, while compounds with amino substituent were shown to be cytotoxic in vitro.