Can computed tomographic angiography accurately exclude digestive tract injury after penetrating cervical trauma?

BACKGROUND: Multislice computed tomographic angiography (MCTA) has become the method of choice to screen for arterial injury in penetrating cervical trauma (PCT). There is, however, limited knowledge on its accuracy in terms of digestive tract injury (DTI). Currently, our unit liberally employs both computed tomographic angiography (CTA) and contrast swallow for platysma breaching penetrating neck injuries. This study aimed to determine the accuracy of specific computed tomography findings in the diagnosis of DTI after PCT. METHODS: This was a retrospective review of all consecutive patients with PCT who had undergone MCTA that presented at a single, tertiary, high-volume trauma centre from January 2013 until December 2015. Blinded radiological review of 140 MCTA investigations (33 in the injury group and 107 in the control group) was performed in order to calculate the diagnostic accuracy of trajectory, air, and conventional MCTA signs in the diagnosis of DTI after PCT. RESULTS: Over the study period, 906 patients presenting with PCT had undergone MCTA and a total of 33 patients (3.6%) had confirmed DTI on aggregate gold standard of diagnosis. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of MCTA for detecting DTI was 100%, 65.4%, 47.1%, and 100%, respectively. No injuries were missed on MCTA. CONCLUSION: Our findings suggest that DTI can be safely excluded by means of careful assessment of specific signs on CTA in patients presenting after PCT, obviating the need for further investigation.

Time to liquid culture positivity can substitute for colony counting on agar plates in early bactericidal activity studies of antituberculosis agents.

The measurement of early bactericidal activity (EBA) is the first step in the clinical investigation of antituberculosis agents. EBA is determined by quantifying the viable sputum mycobacterial load on consecutive days of treatment. To investigate whether time to positivity (TTP) in mycobacterial liquid culture can substitute for colony forming unit (CFU) counting on agar plates we compared the error variation of TTP and CFU in 2115 pooled sputum samples collected overnight from 250 individuals included in five EBA studies. We found that the technical variation between duplicate laboratory measurements and the within-subject or day-to-day variation were similar for TTP (8.5% and 27.4% of total variation, respectively) and CFU (6.7% and 29.3% of total variation). The ability of the measurements to separate the EBA of 22 treatment arms was determined with group rank correlation of means and one-way analysis of variance. Except for the EBA over 0-2 days, individual and group EBAs measured with TTP and CFU were highly correlated. Treatment group means rank correlation coefficients were r=0.472, r=0.910 and r=0.818, respectively, for EBA 0-2 days, EBA 0-7 days and EBA 0-14 days. Analysis of variance significantly favoured TTP over CFU for discrimination between groups with F values of 6.58 and 1.87, 7.77 and 4.58, and 8.71 and 3.56, respectively. We conclude that TTP is an acceptable alternative to CFU counting for the determination of the viable sputum mycobacterial load in EBA studies of up to 14 days duration.

Pyrazinamide pharmacokinetics and efficacy in adults and children.

Pyrazinamide (PZA) is an essential sterilizing drug and with rifampicin enables six-month short-course antituberculosis chemotherapy. Despite routine use for nearly forty years uncertainty remains regarding the most appropriate PZA dosage for children. In view of this uncertainty literature relating to the efficacy and pharmacokinetics of PZA in children treated for tuberculosis and in adult volunteers and patients was reviewed. Making use of the PZA maximum concentration (C(max)) following various PZA dosages in different groups straight line regression of concentration on dosage was fitted through the origin by least squares and weighted for the numbers of subjects. The fitted line offers an approximation of the likely PZA C(max) that would result from a particular dosage. The slopes of C(max)/dosage of the fitted lines are 1.32 (SE 0.099) for paediatric patients, 1.36 (SE 0.051) for adult volunteers and 1.35 (SE 0.037) for adult patients; there is little difference between the C(max) concentrations achieved in children and adults, whether patients or healthy volunteers, following various mg/kg body weight dosages, suggesting that children and adults receiving the same mg/kg body weight PZA dosage will reach a similar C(max). Children can receive the same mg/kg body weight PZA dosage as adults.

The pharmacokinetics and pharmacodynamics of rifampicin in adults and children in relation to the dosage recommended for children.

The dosages of antituberculosis agents recommended for treatment of childhood tuberculosis often reflect those for adult patients with similar mg/kg body weight dosages and ranges advised. Literature relating to the pharmacokinetics and pharmacodynamics of rifampicin (RMP) is reviewed and the serum concentrations reached by adults, both patients and healthy volunteers and children, established or not established on RMP, compared. Straight line regression of maximum RMP serum concentrations (C(max)) on dosage, weighted for the number of individuals, found slopes (SE) of 1.025 (0.067) and 0.881 (0.046) respectively for adult volunteers not established and established on RMP (P = 0.076), and similarly 0.748 (0.057) and 0.684 (0.038) respectively for adult patients (P < 0.001) and 0.622 (0.050) and 0.368 (0.041) respectively for children (P < 0.001). These results indicate that for equivalent RMP dosages adult patients reach a lower C(max) than adult volunteers and that adults, both volunteers and patients established on RMP reach higher C(max) values than children; children established on RMP require approximately twice the mg/kg body weight dosage of RMP to reach serum concentrations equivalent to those of adults. It is noteworthy that many adult patients receiving currently recommended RMP dosages also do not reach the often recommended RMP 2 h serum concentration of 8 µg/mL.

Time to detection of the growth of Mycobacterium tuberculosis in MGIT 960 for determining the early bactericidal activity of antituberculosis agents.

Evaluation of early bactericidal activity (EBA) by the determination of a fall in viable colony-forming units (CFU) of Mycobacterium tuberculosis in sputum is a first step in the clinical study of new antituberculosis agents. The time to detection (TTD) of growth in liquid media is more sensitive and could substitute for CFU counting on solid media. Overnight sputum samples collected during the evaluation of the novel agent TMC207 in comparison to isoniazid and rifampicin were studied. For the determination of CFU, we incubated 10-fold dilutions of homogenized sputum on selective 7H10 agar. The TTD was measured by incubating decontaminated sputum in the BACTEC MGIT 960 system. The fall in bacillary load over 7 days determined by CFU counting closely matched the prolongation of the TTD in the BACTEC MGIT 960 system. The CFU counts correlated significantly with the TTD. While the ranking of agents and different dosages of TMC207 was similar, the highest dose of TMC207 showed markedly better activity when measured by the TTD than CFU counting when compared to the activity of isoniazid. Automated TTD could augment, or, in future, replace, CFU counting to determine sputum bacillary load in EBA clinical trials pending a more formal evaluation of the correlation of the measurements.

Pyridoxal-5-phosphate plasma concentrations in children receiving tuberculosis chemotherapy including isoniazid.

AIM: Little is known about pyridoxine nutriture of children treated with isoniazid (INH) regimens. This study documents plasma pyridoxal 5'-phosphate (PLP) concentrations in children, HIV-infected and HIV-uninfected, receiving INH regimens. METHODS: Children from the Western Cape of South Africa hospitalized for tuberculosis (TB) management were studied. Plasma PLP concentrations were determined on enrolment, 1-month after commencing TB treatment, and again after 4-month's treatment. The children received a supplement meeting pyridoxine requirements. RESULTS: Nineteen HIV-infected and 33 HIV-uninfected children received INH (dosage range 4-20 mg/kg) daily. Mean PLP plasma concentrations on enrolment were 8.32 (SD 6.75) ng/mL and 11.28 (SD 3.02) ng/mL in HIV-infected and HIV-uninfected children, respectively (p = 0.11) and after 4-month's treatment 6.75 (SD 2.71) ng/mL and 14.76 (SD 7.96) ng/mL (p < 0.001). On enrolment 9 (50%) HIV-infected and 5 (15%) HIV-uninfected children (p = 0.016) had suboptimal PLP concentrations (<6 ng/mL); after 4-month's treatment 8 (42%) and 2 (6%) (p = 0.004). CONCLUSION: Plasma PLP concentrations in children treated for TB were low on enrolment in HIV-infected and HIV-uninfected children; after 4-month's treatment low values were still common in HIV-infected children. Additional pyridoxine supplementation of malnourished children treated for tuberculosis is advisable, particularly those HIV-infected.

Early bactericidal activity of high-dose rifampin in patients with pulmonary tuberculosis evidenced by positive sputum smears.

We studied the early bactericidal activity of twice the standard dose of rifampin in subjects with pulmonary tuberculosis evidenced by positive smears. The observed mean 2-day activity was almost double that reported at the standard dose. Further studies are warranted to establish whether higher rifampin doses might assist in shortening tuberculosis treatment.

The influence of dose and N-acetyltransferase-2 (NAT2) genotype and phenotype on the pharmacokinetics and pharmacodynamics of isoniazid.

OBJECTIVE: This study evaluated the pharmacokinetics of isoniazid (INH) associated with optimal early bactericidal activity (EBA), defined as 90% of the maximum EBA (EBA(90)) and the influence of N-acetyltransferase-2 (NAT2) subtype on the ability of pulmonary tuberculosis (PTB) patients to reach the identified pharmacokinetic values after INH doses ranging from 0.2 to 10-12 mg/kg body weight. METHODS: INH serum concentrations and NAT2 subtype were determined during four studies of PTB patients in three of whom the EBA of INH was determined. The relationship of EBA to area under the curve (AUC) (AUC(0-infinity)) and 2-h serum concentrations was examined by exponential regression and fitted curves estimated the AUC(0-infinity) and 2-h serum concentrations at which EBA(90) was reached. RESULTS: EBA(90) was reached at an AUC(0-infinity) of 10.52 microg/ml per hour and 2-h serum concentrations of 2.19 microg/ml. An AUC(0-infinity) of 10.52 microg/ml per hour was reached by all 66 patients receiving a 10-12 mg/kg INH dose and all 21 receiving 6 mg/kg, except 1 of 10 (10%) homozygous fast (FF) acetylators; however, at 5 mg/kg, 4 of 12 (33%) FF and 26 of 27 (96%) heterozygous fast (FS), but all 21 homozygous slow (SS) acetylators did so; and 1 of 3 (33%) FF, 2 of 6 (33%) FS, but all 4 SS acetylators at dose 3 mg/kg. An INH 2-h serum concentration of 2.19 microg/ml was reached by all 66 patients receiving 10-12 mg/kg and all 21 receiving 6 mg/kg, except for 2 (20%) FF acetylators at a dose of 5 mg/kg; however, only 3 (25%) of 12 FF acetylators, but 26 (96%) of 27 FS acetylators, and all 21 SS acetylators reached this concentration; and at a dose of 3 mg/kg, 1 (33%) of 3 FF acetylators, 2 (33%) of 6 FF, but all 4 SS acetylators. CONCLUSIONS: At a 6 mg/kg dose, all except a minority of FF NAT2 acetylators, achieve an INH AUC(0-infinity) and 2-h INH serum concentrations associated with EBA(90), as did all 4 SS acetylators receiving 3 mg/kg. Any dose reduction below 6 mg/kg body weight will tend to disadvantage a significant proportion of faster acetylators, but, conversely, SS acetylators require only a 3 mg/kg dose to achieve a satisfactory exposure to INH.

Predictors of Survival in Infants with Congenital Diaphragmatic Hernia - Systemic Oxygenation Status Versus Dynamic Compliance of the Respiratory System

Objective. To compare whether early measurement of blood gases and/or dynamic compliance of the respiratory system (CRSdyn) predicts outcome in high-risk infants with unilateral congenital diaphragmatic hernia (CDH). Patients and methods. A retrospective study was performed at Tygerberg Children's Hospital between January 1992 and August 2001. High-risk infants with unilateral CDH; who presented with respiratory distress within 6 hours of birth; were included. Patients with other lethal congenital abnormalities were excluded. The first arterial blood gas value after endotracheal intubation was documented and the arterial-alveolar oxygen tension (a:A) ratio was calculated. CRSdyn was measured within 24 hours of birth. The ability of these measurements to predict outcome (survival or death during the newborn period) was determined. Results. Seventeen of 40 infants with CDH were categorised as high risk and included in the study. Eight of them (47) survived the neonatal period. The best single predictors of outcome were; in order; partial pressure of oxygen in arterial blood (PaO2); a:A ratio and dynamic compliance of the respiratory system standardised for body weight (CRSdyn/kg). The specificity and sensitivity at a PaO2 cut-off of 19.3 kPa were 7/8 (95confidence interval (CI): 0.473 - 0.997) and 9/9 (95CI: 0.634 - 1.000) respectively. Results for a:A ratio were cut-off 0.321; specificity 6/8 (95CI: 0.349 - 0.968); and sensitivity 9/9 (95CI: 0.634 - 1.000). Results for CRSdyn/kg were cut-off 0.259; specificity 6/8 (95CI: 0.349 - 0.968); and sensitivity 9/9 (95CI: 0.634 - 1.000). A linear discriminant function based on the 3 best single predictors was found to be no more effective than the first PaO2. Conclusions. Early oxygenation status predicts outcome better than the CRSdyn/kg in infants with unilateral CDH. However; both measurements predict outcome with high accuracy

Ethambutol dosage for the treatment of children: literature review and recommendations.

The currently recommended daily dose of ethambutol (EMB) for the treatment of tuberculosis (TB) in children varies from a maximum daily dose of 15 mg/kg body weight daily (without a range) to 15-20 mg/kg and 20 mg/ kg (range 15-25 mg/kg). Published evidence relating to the dosage, toxicity and pharmacokinetics of EMB in children and adults is reviewed and a dose of EMB for use in childhood is recommended. Using key words 'ethambutol', 'childhood', 'TB', 'pharmacokinetics', 'bioavailability' and 'toxicity', Medline searches were conducted; cross-references were sought from original papers, books and conference proceedings dating from 1961. When English summaries were available, data were extracted from papers in languages other than English. EMB has a dose-related efficacy best seen when given to adults alone or with a single other drug. Together with isoniazid (INH), a dose of 15 mg/kg EMB gave better results than 6 mg/kg, and 25 mg/kg better than 15 mg/kg. The occurrence of ocular toxicity was also dose-related; >40% of adults developed toxicity at doses of >50 mg/ kg, and 0-3% at a dose of 15 mg/kg/daily. Peak serum EMB concentrations increase in relation to dose, but are significantly lower in children receiving the same dosage. In only 2 of 3811 children (0.05%) receiving EMB doses of 15-30 mg/kg was EMB stopped due to possible ocular toxicity; children of all ages can be given EMB in daily doses of 20 mg/kg (range 15-25 mg/kg) and three times weekly intermittent doses of 30 mg/kg body weight without undue concern.

Strategies to improve the performance of learners in a nursing college. Part I: Issues pertaining to nursing education.

The aim of this contextual, exploratory, descriptive and qualitative study was to describe strategies to improve the performance of learners in a nursing college. The article seeks to deal with factors relating to nursing education that contribute to the poor performance of learners and to outline related strategies to improve the situation. Three focus group interviews were conducted. One group was formed by seven tutors, and the other two groups were formed by fourth-year learners following a four-year comprehensive diploma course. All participants voluntarily took part in the study. Data was analyzed using the descriptive method of open coding by Tesch (in Creswell, 1994:154-156). Trustworthiness was ensured in accordance with Lincoln and Guba's (1985:290-326) principles of credibility, conformability, transferability and dependability. The findings were categorized into issues pertaining to nursing education as follows: curriculum overload; lack of theory and practice integration; teaching and assessment methods that do not promote critical thinking; tutors' lack of skills and experience; inadequate preparation of tutors for lectures; insufficient knowledge of tutors regarding outcomes-based education approach to teaching and learning; inadequate process of remedial teaching; discrepancies between tutors' marking; lack of clinical role-models and high expectations from the affiliated university as regards standards of nursing development programme by the staff development committee of the nursing college under study for implementation. Future research should focus on the effectiveness of the described strategies to improve the learners' performance. It is also recommended that similar studies be conducted or replicated in other nursing colleges to address the problem of poor performance of learners engaged in a four-year comprehensive diploma course.

Strategies to improve the performance of learners in a nursing college. Part II: Issues pertaining to management, attitudes and values.

UNLABELLED: This article forms part two of a bigger study that was conducted in a nursing college to explore and describe the reasons for the poor performance of learners. Part one of the study dealt with the issues pertaining to education, while this article (part two) seeks to describe issues pertaining to management, attitudes and values that lead to the poor performance of learners in the nursing college under study. A qualitative, exploratory and descriptive design that was contextual in nature was employed, and three focus groups interviews were conducted. Seven tutors formed one group while other two groups were formed by fourth-year learners following a comprehensive diploma course. All participants voluntarily participated in the study. Data was analyzed using the descriptive method of open coding in accordance with Tesch's protocol (in Creswell, 1994:154-156). Trustworthiness was ensured using the following principles: credibility, conformability, transferability and dependability (Lincoln & Guba 1985:290-326). Findings were categorized into issues pertaining to management, attitudes and values that had an influence on the poor performance of learners as follows: MANAGEMENT: Inadequate resources and study facilities; policies that change frequently; tutors' dissatisfaction with regard to staff development, the lack of involvement by management and lack of management support, staff shortage and maldistribution of staff members; ineffective selection process of learners; inconsistent regulations, and too many of them; policies and procedures resulting in confusion and poor discipline. Attitudes and values: Tutors' lack of motivation and interest, lack of respect by learners and no team work among tutors. Through a conceptualization process and the recommendations by participants, strategies to improve the learners' performance were described. It is recommended that these strategies be submitted to the staff development committee for implementation and future follow-up research be undertaken to determine the effectiveness of the strategies. It is also recommended that other nursing colleges replicate the study within their context.

The effects of eicosapentaenoic acid in tardive dyskinesia: a randomized, placebo-controlled trial.

OBJECTIVE: Worldwide, conventional antipsychotic medication continues to be used extensively, and tardive dyskinesia (TD) remains a serious complication. The primary objective of the present study was to compare the efficacy of EPA versus placebo in reducing symptoms of TD. METHOD: This was a 12-week, double-blinded, randomized study of ethyl-EPA 2g/day versus placebo as supplemental medication, in patients with schizophrenia or schizoaffective disorder, with established TD. RESULTS: Eighty-four subjects were randomized, of whom 77 were included in the analysis. Both the EPA and placebo groups displayed significant baseline to endpoint improvements in Extrapyramidal Symptom Rating Scale dyskinesia scores, but there were no significant between-group differences (p=0.4). Response rates (>or=30% improvement in TD symptoms) also did not differ significantly between EPA-treated subjects (45%) and placebo-treated subjects (32%) (p=0.6). However, a post-hoc linear mixed model repeated measures analysis of variance indicated an effect for treatment group and duration of TD. The EPA-treated patients had significantly greater mean reductions in dyskinesia scores initially, although this was not sustained beyond 6 weeks. CONCLUSIONS: This trial failed to demonstrate an anti-dyskinetic effect for ethyl-EPA 2g/day on the primary efficacy measure. However, a modest and transient benefit is suggested in patients with more recent onset of TD. The lack of clear-cut efficacy could be explained on the basis of the dose of EPA being too low, the study being underpowered, TD being too chronic in the majority of cases, differences in dietary fatty acid intake, or that EPA lacks an anti-dyskinetic action.

Monitoring the ingestion of anti-tuberculosis drugs by simple non-invasive methods.

This investigation retrospectively assessed inexpensive non-invasive qualitative methods to monitor the ingestion of anti-tuberculosis drugs isoniazid, rifampicin and rifapentine. Results showed that commercial test strips detected the isoniazid metabolites isonicotinic acid and isonicotinylglycine as efficiently as the isonicotinic acid method in 150 urine samples. The presence of rifamycins in urine samples (n=1085) was detected by microbiological assay techniques and the sensitivity compared to the n-butanol extraction colour test in 91 of these specimens. The proportions detected by the two methods were significantly different and the sensitivity of the n-butanol procedure was only 63.8% (95% CL 51.2-76.4%) as compared to that of the superior microbiological method. Final validation (n=691) showed that qualitative assays measure isoniazid and rifamycin ingestion with an efficiency similar to high-performance liquid chromatography. The qualitative procedures may therefore be valuable in clinical trials and in tuberculosis clinics to confirm drug ingestion.

Pharmacological challenge with a serotonin 1D agonist in alcohol dependence.

BACKGROUND: Both animal and clinical studies have implicated serotonergic dysfunction in the pathogenesis of alcohol abuse and dependence. However the exact mechanisms involved remain unknown. Theoretically, low serotonin promotes alcohol seeking behavior. Sumatriptan is a serotonin1D agonist. It is postulated that sumatriptan's agonism at this terminal autoreceptor increases negative feedback, creating a net effect of decreased serotonergic neurotransmission. Administration of sumatriptan should therefore produce a craving for alcohol and the desire to drink. METHODS: Fifteen patients with alcohol dependence who had undergone detoxification were recruited. Sumatriptan (100 mg) and placebo was administered in cross-over fashion on 2 separate days 72 hours apart. Both patients and raters were blind to all treatments. Patients were assessed on the following scales at -30, 0, 30, 90, 150 and 210 minutes: A 6-item scale designed to rate the patient's intention to drink; The Sensation Scale; a 13-item affect analog scale designed to rate the pattern and extent of emotional changes; and an 8-item scale designed to rate the patient's craving for alcohol. RESULTS: No significant differences were found between the placebo and sumatriptan groups and no significant cross over effects were found. CONCLUSION: The general lack of efficacy of sumatriptan in producing alcohol-like symptoms or a desire to drink alcohol may suggest that the 5HT1D receptor plays little role in the pathophysiology of alcoholism.

Isoniazid pharmacokinetics in children treated for respiratory tuberculosis.

AIMS: To define the pharmacokinetics of isoniazid (INH) in children with tuberculosis in relation to the N-acetyltransferase 2 (NAT2) genotype. METHODS: The first order elimination rate constant (k) and area under the concentration curve (AUC) were calculated in 64 children <13 years of age (median 3.8) with respiratory tuberculosis from INH concentrations determined 2-5 hours after a 10 mg/kg INH dose. The NAT2 genotype was determined; 25 children were classified as homozygous slow (SS), 24 as heterozygous fast (FS), and 15 as homozygous fast (FF) acetylators. RESULTS: The mean (SD) k values of the genotypes differed significantly from one another: SS 0.254 (0.046), FS 0.513 (0.074), FF 0.653 (0.117). Within each genotype a median regression of k on age showed a significant decrease in k with age. The mean (SD) INH concentrations (mg/l) two hours after INH administration were SS 8.599 (1.974), FS 5.131 (1.864), and FF 3.938 (1.754). A within genotype regression of 2-hour INH concentrations on age showed a significant increase with age. A within genotype regression of 3-hour, 4-hour, and 5-hour concentrations on age also showed a significant increase with age in each instance. In ethnically similar adults, mean (SD) 2-hour INH concentrations (mg/l) for each genotype were significantly higher than the children's: SS 10.942 (1.740), FS 8.702 (1.841), and FF 6.031 (1.431). CONCLUSIONS: Younger children eliminate INH faster than older children and, as a group, faster than adults, and require a higher mg/kg body weight INH dose to achieve serum concentrations comparable to adults.

The influence of human N-acetyltransferase genotype on the early bactericidal activity of isoniazid.

The elimination of isoniazid is subject to the influence of the N-acetyltransferase 2 (NAT2) genotype, and individuals may be homozygotic slow, heterozygotic fast, or homozygotic fast acetylators of isoniazid. The early bactericidal activity (EBA) of an antituberculosis agent can be determined by quantitative culture of Mycobacterium tuberculosis in sputum samples obtained from patients with pulmonary tuberculosis during the first days of treatment. In these studies, the EBA of isoniazid during the first 2 days of treatment was determined for 97 patients with sputum smear-positive pulmonary tuberculosis following isoniazid doses of < or =37.5 mg, 75 mg, 150 mg, 300 mg, and 600 mg. The NAT2 genotype was determined in 70 patients, and the association between EBA and genotype was examined in this subgroup. Similarly, the relationship between EBA and isoniazid serum concentration was evaluated in 87 patients. The mean EBA of isoniazid increased with dose, but it levelled off between doses of 150 mg (mean EBA, 0.572) and 300 mg (mean EBA, 0.553). Significant differences were found in the mean EBA of isoniazid between the homozygous slow acetylator group and the heterozygous fast acetylator group and between the homozygous slow acetylator group and the homozygous fast acetylator group, but not between the heterozygous fast acetylator group and the homozygous fast acetylator group. The EBA appeared to reach a maximum at a 2-h isoniazid concentration of 2-3 microg/mL. These data confirm a significant effect of NAT2 genotype on the EBA of isoniazid over a range of doses.

Facial profile changes with various orthodontic premolar extraction sequences during growth.

The Visual Treatment Objective (VTO) is an extremely valuable tool in the process of working out the treatment plan for the individual. This is especially true for the inexperienced operator. Often it becomes clear that extractions are indicated, but there remains uncertainty as to which teeth should be chosen for extractions to give the best results. As it is necessary to express the expected change in profile due to growth of the nose and also of the chin, VTO construction is helpful in determining the extraction decision. Clinical experience and research projects have indicated that the use of mean values has definite limitations when constructing a VTO for an individual. The primary objective of this investigation was to provide formulae by means of which anteroposterior changes in the facial profile of growing individuals for whom four premolar extraction treatment is proposed can be predicted with a greater measure of certainty. The records of 248 growing Caucasian orthodontic patients (120 males and 128 females) were selected and divided into Group 44 (four first premolar extractions), Group 45 (upper first premolar and lower second premolar extractions) and Group 55 (four second premolar extractions). Formulae are presented for the prediction of the amount of incisor retraction, anteroposterior nose growth and for chin growth. The formulae were derived by regression of incisor retraction, anteroposterior nose growth and chin growth on various predictors, and could be used in the construction of VTO's for selected cases.

Incidence of tardive dyskinesia in first-episode psychosis patients treated with low-dose haloperidol.

BACKGROUND: Previous studies suggest that the risk of tardive dyskinesia is increased with higher doses of conventional antipsychotics. This study evaluates the 12-month incidence of tardive dyskinesia in subjects with first-episode psychosis who were treated with very low doses of haloperidol. METHOD: Fifty-seven subjects with first-episode psychosis and a DSM-IV diagnosis of schizophreniform disorder, schizophrenia, or schizoaffective disorder were treated according to a fixed protocol with a mean dose of haloperidol of 1.68 mg/day and prospectively studied for 12 months. Subjects were assessed for extrapyramidal symptoms and psychiatric symptoms at 3-month intervals. Data were gathered from 1999 to 2001. RESULTS: Twelve-month incidence of probable or persistent tardive dyskinesia according to Schooler and Kane criteria was 12.3% (N = 7). Subjects with tardive dyskinesia did not differ from the rest of the sample regarding gender, race, duration of untreated psychosis, or baseline clinical characteristics. Subjects with tardive dyskinesia were older compared with subjects without tardive dyskinesia (37.14 +/- 9.23 vs. 27.30 +/- 8.09 years, respectively; t = -2.77, df = 30, p = .01) and received higher mean doses of haloperidol at 12 months (2.80 +/- 1.64 vs. 1.39 +/- 0.69 mg/day, respectively; t = -3.13, df = 25, p = .004). Cox regression analysis revealed that age at inclusion (p = .031), percentage change in negative symptoms (p = .028), and dose of haloperidol at 12 months (p = .016) were significant predictors of risk for tardive dyskinesia. CONCLUSION: Incidence of tardive dyskinesia was at least as high as in other samples treated with standard doses of conventional antipsychotics. Subjects at risk for tardive dyskinesia could not be identified on the basis of initial clinical features or acute treatment response. Risk of tardive dyskinesia was related to age, antipsychotic dose, and worsening of negative, depressive, and parkinsonian symptoms.

Calcium alginate entrapment of the yeast Rhodosporidium toruloides for the kinetic resolution of 1,2-epoxyoctane.

Resting cells of the yeast Rhodosporidium toruloides (UOFS Y-0471) were immobilised in calcium alginate beads for the enantioselective kinetic resolution of racemic-1,2-epoxyoctane. The initial activity exhibited by immobilised cells was almost 50% lower than that of the free counterpart but was extremely stable when compared to the free cells. The concentration of the immobilised biomass had no effect on apparent enzyme activity but did lead to a decrease in single cell activity. An increase in both the alginate and CaCl2 concentrations used for bead preparation led to a decrease in enzyme stability. An increase in the alginate concentration led to an increase in bead diameter. The stoichiometric equation for cross-linking of alginate was only obeyed when CaCl2 concentrations higher than 0.4 M were utilised for bead preparation.