The effects of surgery on plasma/serum vitamin C concentrations: a systematic review and meta-analysis.

Vitamin C (ascorbic acid) is a water-soluble vitamin with an array of biological functions. A number of proposed factors contribute to the vitamin's plasma bioavailability and ability to exert optimal functionality. The aim of this review was to systematically assess plasma vitamin C levels post-surgery compared with pre-surgery/the magnitude and time frame of potential changes in concentration. We searched the PUBMED, SCOPUS, SciSearch and the Cochrane Library databases between 1970 and April 2020 for relevant research papers. Prospective studies, control groups and true placebo groups derived from controlled trials that reported means and standard deviations of plasma vitamin C concentrations pre- and postoperatively were included into the meta-analysis. Data were grouped into short-term (≤7 d) and long-term (>7 d) postoperative follow-up. Twenty-three of thirty-one studies involving 642 patients included in the systematic review were suitable for meta-analysis. Pooled data from the meta-analysis revealed a mean depletion of plasma vitamin C concentration of -17·99 µmol/l (39 % depletion) (CI -22·81, -13·17) (trial arms = 25, n 565, P < 0·001) during the first postoperative week and -18·80 µmol/l (21 % depletion) (CI -25·04, -12·56) (trial arms = 6, n 166, P < 0·001) 2-3 months postoperatively. Subgroup analyses revealed that these depletions occurred following different types of surgery; however, high heterogeneity was observed amongst trials assessing concentration change during the first postoperative week. Overall, our results warrant larger, long-term investigations of changes in postoperative plasma vitamin C concentrations and their potential effects on clinical symptomology.

"Let's talk about it": Black youths' perceptions on the development of a school-based social media campaign.

The increase in social media mental health (MH) campaigns provides an opportunity to improve awareness and attitudes toward MH. However, racial disparities remain in these social media campaigns. Black youth who participated in MH social media campaigns reported lower levels of improvement in stigma and help-seeking than their White peers. We employed a youth participatory action research (YPAR) process to expand on a previous community-wide MH social media campaign (A. Thompson et al., 2021), focusing on a Central Midwest community. We studied Black adolescents' perceptions of MH stigma and help-seeking to determine essential features of a culturally responsive MH social media campaign for Black youth. With a lead youth-research collaborator, the research team designed the following two-staged study. The first stage consisted of four semistructured focus group interviews (FGIs) (N = 20), analyzed by using a rapid analysis strategy to obtain results for the development of the campaign. In the second stage, using YPAR's iterative and action-based process, five youth researchers collaborated with the research team on the campaign's design. Following the two stages, the researcher's thematic analysis resulted in three themes: (a) broadening horizons for campaign designers and MH professionals; (b) considering mistrust of schools and school personnel; and (c) diverse experiences, sustainability, and accessibility in a campaign. Findings indicated that while culturally responsive social media campaigns to promote MH can be designed, mistrust of adults in schools is likely to hinder the impact of such campaigns. Implications for school psychology practice and research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Clinical outcomes of patients discharged from the Rapid Access Chest Pain Clinic with non-anginal chest pain: A retrospective cohort study.

BACKGROUND: The Rapid Access Chest Pain Clinic (RACPC) has become an important means of assessing patients who present with ischaemic or ischaemia-like symptoms of recent onset. Observations have shown that up to 70% are discharged with a diagnosis of non-anginal chest pain (NACP) and accordingly "reassured". This study aims to describe the actual clinical outcomes of this cohort of patients discharged from the RACPC. METHODS: We undertook a single centre retrospective cohort study at a tertiary cardiac hospital. The outcomes of unselected patients diagnosed with NACP and discharged from the RACPC between April 2010 and March 2013 at University Hospitals of Leicester (UHL) were recorded. Re-referrals to cardiology outpatient clinic and emergency hospital admissions for cardiovascular disease within 6 months, and the mortality rate at 12 months, were determined. RESULTS: 7066 patients were seen in the UHL RACPC during the 36-month period. 3253 (46.0%) were diagnosed with NACP and discharged. 7 (0.2%) were diagnosed with coronary artery disease (CAD) and 8 (0.25%) cases of acute coronary syndrome (ACS) identified during the review period. 11 (0.3%) patients died within 12 months of discharge from RACPC. No deaths were attributable to CAD. CONCLUSIONS: Comprehensive assessment using risk-stratification criteria in a nurse practitioner-led RACPC can accurately identify patients who are at low-risk for subsequent CAD. Despite contemporary National Institute for Health and Care Excellence (NICE) guidelines that shift focus away from a clinical judgement based approach, this strategy appears to robustly predict favourable outcomes in patients diagnosed with NACP.

The influence of motor function on processing speed in preterm and term-born children.

This study investigates the relationship between motor function and processing speed in preterm children. Processing speed was compared in 145 adolescents, born 25-41 weeks gestational age, utilizing tasks including differing motor demands. The influence of motor cortex excitability and functional motor skills on task performance was assessed. For tasks with motoric demands, differences in performance between preterm and term-born children were mediated by the relationship between gestational age, corticomotor excitability, and motor function. There were no differences in non-motor processing speed task performance between preterm and term-born children. Measures of processing speed may be confounded by a timed motor component.

Cuidados de enfermagem ao paciente com câncer colorretal em uso de bolsa de colostomia: revisão de literatura / Nursing care for colorectal cancer patients using a colostomy bag: a literature review / Atención de enfermería para pacientes con cáncer colorrectal con una bolsa de colostomía: una revisión de la literatura

Objetivo: analisar a importância da enfermagem no manejo da bolsa de colostomia em pacientes com câncer colorretal, buscando identificar o papel da enfermagem no processo de viver da pessoa ostomizada com câncer. Método: trata-se de uma revisão da literatura realizada nas bases de dados SCIELO, LILACS e BDEnf, realizada entre abril e maio de 2022 com os descritores bolsa de colostomia, câncer colorretal, enfermagem. Os artigos selecionados para análise e interpretação tinham como os seguintes critérios de inclusão: textos completos sem restrição de delineamento ou cronograma do estudo; escrito em português, disponibilizado em bases de dados gratuitamente e que contemplam o objetivo da pesquisa. Já os critérios de exclusão foram: artigos de revisão bibliográfica, com publicações anteriores a 2016 e aqueles que não contribuía para enriquecer a discussão do tema proposto. Assim, foram selecionados 10 artigos, que serviram de base para a discussão. Resultado: após a análise dos artigos foram encontrados os seguintes temas para discussão: câncer colorretal e a estomização, assistência de enfermagem à pacientes com colostomia e as percepções de pacientes estomizados com câncer colorretal. Conclusão: a sistematização da assistência de enfermagem ao estomizado e sua família é essencial para sua reabilitação, para sua autonomia e o pleno exercício de dignidade diante do enfretamento de uma doença tão estigmatizada que é o câncer colorretal.

Objective: to analyze the importance of nursing in the management of the colostomy bag in patients with colorectal cancer, seeking to identify the role of nursing in the life process of the ostomized person with cancer. Method: this is a literature review carried out in the SCIELO, LILACS and BDEnf databases, carried out between April and May 2022 with the descriptors colostomy bag, colorectal cancer, nursing. The articles selected for analysis and interpretation had the following inclusion criteria: full texts without restriction of study design or schedule; written in Portuguese, made available in databases free of charge and covering the purpose of the research. The exclusion criteria were: literature review articles, with publications prior to 2016 and those that did not contribute to enrich the discussion of the proposed topic. Thus, 10 articles were selected, which served as the basis for the discussion. Results: after analyzing the articles, the following topics were found for discussion: colorectal cancer and ostomy, nursing care for colostomy patients and the perceptions of ostomized patients with colorectal cancer. Conclusion: the systematization of nursing care for people with stomas and their families is essential for their rehabilitation, for their autonomy and for the full exercise of dignity in the face of facing such a stigmatized disease that is colorectal cancer

Objetivo: analizar la importancia de la enfermería en el manejo de la bolsa de colostomía en pacientes con cáncer colorrectal, buscando identificar el papel de la enfermería en el proceso de vida de la persona ostomizada con cáncer. Método: se trata de una revisión bibliográfica realizada en las bases de datos SCIELO, LILACS y BDEnf, realizada entre abril y mayo de 2022 con los descriptores bolsa de colostomía, cáncer colorrectal, enfermería. Los artículos seleccionados para análisis e interpretación tuvieron los siguientes criterios de inclusión: textos completos sin restricción de diseño de estudio o cronograma; escrito en portugués, disponible en bases de datos de forma gratuita y que cubre el objetivo de la investigación. Los criterios de exclusión fueron: artículos de revisión bibliográfica, con publicaciones anteriores a 2016 y aquellos que no contribuyeron a enriquecer la discusión del tema propuesto. Así, fueron seleccionados 10 artículos, que sirvieron de base para la discusión. Resultados: después del análisis de los artículos, se encontraron los siguientes temas de discusión: el cáncer colorrectal y la ostomía, la atención de enfermería a los pacientes con colostomía y las percepciones de los pacientes ostomizados con cáncer colorrectal. Conclusión: la sistematización de los cuidados de enfermería a las personas con estomas y sus familias es fundamental para su rehabilitación, para su autonomía y para el pleno ejercicio de la dignidad frente al enfrentamiento de una enfermedad tan estigmatizada como es el cáncer colorrectal

Topotecan versus paclitaxel for the treatment of recurrent epithelial ovarian cancer.

PURPOSE: Topotecan and paclitaxel were evaluated in a randomized, multicenter study of patients with advanced epithelial ovarian carcinoma who had progressed during or after one platinum-based regimen. PATIENTS AND METHODS: Patients received either topotecan (1.5 mg/m2) as a 30-minute infusion daily for 5 days every 21 days (n = 112) or paclitaxel (175 mg/m2) infused over 3 hours every 21 days (n = 114). Patients had bidimensionally measurable disease and were assessed for efficacy and toxicity. RESULTS: Response rate was 23 of 112 (20.5%) in topotecan-treated patients and 15 of 114 (13.2%) in paclitaxel-treated patients (P = .138). Disease stabilization for at least 8 weeks was noted in 30% of patients with topotecan and 33% of patients with paclitaxel. Median durations of response to topotecan and paclitaxel were 32 and 20 weeks, respectively (P = .222) and median times to progression were 23 and 14 weeks, respectively (P = .002). Median survival was 61 weeks for topotecan and 43 weeks for paclitaxel (P = .515). Response rates for topotecan and paclitaxel were 13.3% versus 6.7% (P = .303) in resistant patients (not responded to prior platinum-based therapy or progressed within 6 months of an initial response) and 28.8% versus 20.0% (P = .213) in sensitive patients (progressed > 6 months after response). Neutropenia was significantly more frequent on the topotecan arm 79% versus paclitaxel arm 23% (P < .01). It was short-lasting and noncumulative in both arms. Nonhematologic toxicities were generally mild (grades 1 to 2) for both agents. CONCLUSION: Topotecan has efficacy at least equivalent to paclitaxel manifested by the higher response rate and significantly longer time to progression.

Phase I and pharmacologic study of oral topotecan administered twice daily for 21 days to adult patients with solid tumors.

PURPOSE: Topotecan is a specific inhibitor of topoisomerase I. Recently bioavailability of an oral formulation of approximately 30% with limited variability was reported. We conducted a phase I and pharmacokinetic study of the oral formulation of topotecan to characterize the maximum-tolerated dose (MTD), toxicities, pharmacokinetics, and antitumor effects in patients with refractory malignancies. PATIENTS AND METHODS: Patients were treated with oral topotecan given twice daily for 21 days, with cycles repeated every 28 days. In subsequent cohorts, the dose was escalated from 0.15 to 0.6 mg/m2 twice daily. Pharmacokinetics were performed on day 1 and 8 of the first course using a validated high-performance liquid chromatographic assay and noncompartmental pharmacokinetic methods. RESULTS: Thirty-one patients entered the study; one patient was not assessable for toxicity and response as therapy was prematurely interrupted on request of the patient who had not experienced toxicity. Thirty patients received a total of 59 courses. The dose-limiting toxicity (DLT) was reached at a dose of 0.6 mg/m2 twice daily and consisted of diarrhea, which started subacutely at a median onset on day 15 (range, 12 to 20) and resolved after a median of 8 days (range, 7 to 16). Other toxicities were mild, including leukocytopenia, thrombocytopenia, nausea, and vomiting. The MTD was 0.5 mg/m2 twice daily. No responses were observed. Pharmacokinetics showed a substantial variation of the area under the plasma concentration-time curve at time point "t" [AUC(t)] of topotecan and ring-opened product hydroxyacid. A significant correlation was observed between the percentage of decrease in WBC count versus the AUC(t) of topotecan (r = .75), which was modeled by a sigmoidal maximal effect concentration (Emax) function. CONCLUSION: The DLT in this phase I study for chronic oral topotecan for 21 days was diarrhea. The recommended dose for phase II studies is 0.5 mg/m2 twice daily.

Phase II and pharmacologic study of topotecan administered as a 21-day continuous infusion to patients with colorectal cancer.

PURPOSE: Topotecan is a specific inhibitor of topoisomerase I. Preclinical data have indicated that topoisomerase I inhibitors demonstrate more efficacy and have a greater therapeutic index with prolonged continuous exposure. The feasibility of this concept in humans using a 21-day continuous infusion of topotecan has been reported. We conducted a phase II study of this 21-day continuous topotecan administration schedule in patients with locally advanced, unresectable or metastatic colorectal cancer. PATIENTS AND METHODS: Topotecan, initially applied at a dose of 0.6 mg/m2/d, was administered as a continuous infusion via an ambulatory pump for 21 days repeated every 4 weeks. The starting dose was reduced to 0.5 mg/m2/d, because in five of the first 11 patients, the second course had to be delayed due to prolonged myelosuppression. Forty-two patients entered the study; one patient was ineligible and was excluded from further analyses. RESULTS: The overall response rate was 10%, with one complete and three partial responses. The median response duration was 7 months (range, 4 to 11). With this schedule, the major toxicity was prolonged cumulative myelosuppression, including a marked inhibition of erythropoiesis. A total transfusion of 250 U of erythrocytes was needed to maintain a hemoglobin level greater than 6.0 mmol/L. Other side effects were mild, and included alopecia (47%), periodic nausea (40%)/vomiting (22%), and fatigue (16%). Pharmacokinetic evaluation showed a mean steady-state plasma concentration (Css) of topotecan of 0.62 ng/mL (range, 0.33 to 1.1), with a significant relationship between the Css of topotecan and common cytotoxicity criteria (CTC) grade of leukocytopenia. CONCLUSION: Topotecan administered as a 21-day continuous infusion exerts minor activity as single-agent therapy in patients with metastatic colorectal cancer.

Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: results of a large European phase II study.

PURPOSE: Topotecan is a topoisomerase I inhibitor with preclinical activity against various tumor types. We conducted a large multicenter phase II study with topotecan in ovarian cancer in patients who had failed to respond to one prior cisplatin-based chemotherapeutic regimen. PATIENTS AND METHODS: Topotecan 1.5 mg/m2/d was administered intravenously by 30-minute infusion for 5 days repeated every 3 weeks. As the cisplatin-free interval relates to response in subsequent treatment, patients were stratified in subgroups, ie, cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive. RESULTS: One-hundred eleven patients entered the study. Nineteen patients were considered to be ineligible; 92 patients were assessable for response. A total of 552 courses were given (median, four per patient; range, one to 17). The major toxicities were leukocytopenia and neutropenia, which were grade 3 to 4 in 54.2% and 69.1% of courses, respectively, but with only 4.3% of these being grade 4 neutropenia plus fever or infectious complications. Prophylactic granulocyte colony-stimulating factor (G-CSF) was given in 20.5% of courses to maintain dose-intensity. Other relatively frequent side effects were alopecia (82%), nausea (36.4%), and vomiting (17.5%). The overall response rate was 16.3%, with one complete response (CR) and 14 partial responses (PRs). In the cisplatin-refractory, cisplatin-resistant, and cisplatin-sensitive strata, the response rates were 5.9%, 17.8%, and 26.7%, respectively. The median duration of time of documented response was 21.7 weeks (range, 4.6 to 41.9). CONCLUSION: Topotecan in a daily-times-five schedule is an effective regimen as second-line treatment in ovarian cancer. Further investigations of topotecan in ovarian cancer, including first-line use and combination with other active agents, are indicated.

Double-blind controlled trial of azathioprine in children with newly diagnosed type I diabetes.

A double-blind controlled trial of azathioprine (2 mg.kg-1.day-1) was conducted with 49 patients aged 2-20 yr (mean 10.8 yr) who had newly diagnosed type I (insulin-dependent) diabetes. Patients were randomly assigned to receive either azathioprine (n = 24) or placebo (n = 25) for 12 mo, beginning within the 20-day period after diagnosis. Baseline clinical and metabolic characteristics did not differ between the two groups. No patient experienced complete remission, defined as restoration of normal carbohydrate tolerance without other treatment. Partial remission, defined as good metabolic control (hemoglobin A1c less than or equal to 7.9%, preprandial blood glucose less than or equal to 8 mM with an insulin dose of less than 0.5 U.kg-1.day-1), occurred in 10 placebo (40%) and 7 azathioprine (29%) patients at 6 mo and in 4 placebo (16%) and 4 azathioprine (17%) patients at 12 mo (differences not significant). Fasting plasma C-peptide was significantly greater in the azathioprine-treated group at 3 and 6 mo, but this difference was not sustained. C-peptide responses to a standard meal and the frequency of islet cell and insulin antibodies did not differ between the two groups over the 12-mo period. Azathioprine caused no significant side effects. We conclude that in the dosage used, and despite early effects on endogenous insulin secretion, azathioprine alone does not influence the remission phase in children with newly diagnosed type I diabetes.

Oral topotecan given once or twice daily for ten days: a phase I pharmacology study in adult patients with solid tumors.

Prolonged exposure to topotecan (TPT) in in vitro experiments and in vivo studies in animals yielded the highest antitumor efficacy. An oral bioavailability of TPT of 32-44% enables convenient prolonged administration. Because of unpredictable diarrhea in the third week of the twice daily (b.i.d.) 21-day schedule of p.o. administered TPT and the finding of optimal down-regulation of topoisomerase I level after 10-14 days in mononuclear peripheral blood cells, a shorter period of administration (10 days) was chosen for Phase I and pharmacological studies of oral administration of TPT. Adult patients with malignant solid tumors that were refractory to standard forms of chemotherapy were entered. Two dose schedules were studied: once daily (o.d.) and b.i.d. administration for 10 days every 3 weeks. TPT o.d. for 10 days was studied at dose levels 1.0, 1.4, and 1.6 mg/m2/day, and dose levels were 0.5, 0.6, 0.7, and 0.8 mg/m2 with the 10-day b.i.d. schedule. Pharmacokinetics were performed on days 1 and 8 of the first course using a validated high-performance liquid chromatographic assay and noncompartmental pharmacokinetic methods. Nineteen patients were entered in the 10-day o.d. schedule, with a total of 48 courses given. Dose-limiting toxicity (DLT) was reached at 1.6 mg/m2/day and consisted of common toxicity criteria (CTC) grade IV thrombocytopenia and CTC grade III diarrhea. The maximum tolerated dose was 1.4 mg/m2/day. In the 10-day b.i.d. administration of TPT, a total of 64 courses were studied in 20 patients. DLT was reached at a dose of 0.8 mg/m2 b.i.d. and consisted of CTC grade IV myelosuppression and CTC grade IV diarrhea. The maximum tolerated dose was 0.7 mg/m2 b.i.d. Nonhematological toxicities with both schedules included mild nausea and vomiting, fatigue, and anorexia. Pharmacokinetics revealed a substantial variation of the area under the plasma concentration-time curve of TPT lactone in both schedules. Significant correlations were observed between the myelotoxicity parameters and the area under the plasma concentration-time curve at day 1 of TPT lactone o.d. and b.i.d. The DLT of 10 daily administrations of oral topotecan every 3 weeks consisted of a combination of myelosuppression and diarrhea for both schedules studied. The recommended doses for Phase II studies are 1.4 mg/m2/day for 10 days for the o.d. administration and 0.7 mg/m2 for the b.i.d. schedule.

A comparison of clinical pharmacodynamics of different administration schedules of oral topotecan (Hycamtin)

Prolonged exposure to topotecan in in vitro and in vivo experiments has yielded the highest antitumor efficacy. An oral formulation of topotecan with a bioavailability of 32-44% in humans enables convenient prolonged administration. Pharmacokinetic/pharmacodynamic relationships from four Phase I studies with different schedules of administration of oral topotecan in 99 adult patients with malignant solid tumors refractory to standard forms of chemotherapy were compared. Topotecan was administered as follows: (a) once daily (o.d.) for 5 days every 21 days (29 patients); (b) o.d. for 10 days every 21 days (19 patients); (c) twice daily (b.i.d.) for 10 days every 21 days (20 patients); and (d) b.i.d. for 21 days every 28 days (31 patients). Pharmacokinetic analysis was performed in 55 patients using a validated high-performance liquid chromatographic assay and noncompartmental pharmacokinetic methods. Totals of 109, 48, 64, and 59 courses were given, respectively. Dose-limiting toxicity consisted of granulocytopenia for the o.d. x 5-day dosage, a combination of myelosuppression and diarrhea in both of the 10-day schedules, and only diarrhea in the 21-day schedule. Pharmacokinetics revealed a substantial variation of the area under curve (AUC) of topotecan lactone in all of the dose schedules with a mean intrapatient variation of 25.4 +/- 31.0% (o.d. x 5), 34.5 +/- 25.0% (o.d. x 10), 96.5 +/- 70.1% (b.i.d. x 10), and 59.5 +/- 51.0% (b.i.d. x 21). Significant correlations were observed between myelotoxicity parameters and AUC(t) day 1 and AUC(t) per course of topotecan lactone. In all of the studies, similar sigmoidal relationships could be established between AUC(t) per course and the percentage decrease of WBCs. At maximum-tolerated dose level, no significant difference in AUC(t) per course was found [AUC(t) per course was 107.4 +/- 33.7 ng x h/ml (o.d. x 5), 145.3 +/- 23.8 ng x h/ml (o.d. x 10), 100.0 +/- 41.5 ng x h/ml (b.i.d. x 10), and 164.9 +/- 92.2 ng x h/ml (b.i.d. x 21), respectively.] For oral topotecan, the schedule rather than the AUC(t)-per-course seemed to be related to the type of toxicity. Prolonged oral administration resulted in intestinal side effects as a dose-limiting toxicity, and short-term administration resulted in granulocytopenia. On the basis of this pharmacokinetic study, no schedule preference could be expressed, but based on patient convenience, administration once daily for 5 days could be favored.

Serum inhibin concentrations rise throughout normal male and female puberty.

Using a newly developed, sensitive, and specific RIA, we measured the serum concentrations of inhibin, together with those of FSH, LH, and sex steroids, throughout puberty in 99 boys and 102 girls attending a suburban Melbourne school. Serum inhibin levels rose from a geometric mean level of 161 U/L (range, 87-310; 67% confidence interval) at stage I puberty in boys to 442 U/L (range, 300-626) at stage V, while corresponding values in girls were 97 U/L (range, 46-204) and 231 U/L (range, 187-372), respectively. Serum inhibin concentrations were strongly correlated with age and serum FSH, LH, testosterone, and estradiol; all hormones increased in parallel in both boys and girls. After adjustment for age, the partial correlation coefficients remained significant only for testosterone in the boys. We hypothesize that gonadal inhibin production is stimulated by rising gonadotropin levels during pubertal development.

Five days of oral topotecan (Hycamtin), a phase I and pharmacological study in adult patients with solid tumours.

Topotecan is a specific inhibitor to topoisomerase I. An oral formulation of topotecan is available with a bioavailability of 32-44% in humans. A phase I and pharmacological study of the oral formulation of topotecan administered daily for 5 days every 21 days was performed in adult patients with solid tumours to determine the maximum tolerated dose (MTD). Adult patients with a WHO performance status < or = 2 adequate haematological, hepatic and renal functions, with malignant solid tumours refractory to standard forms were entered into the study. Pharmacokinetics were performed on days 1 and 4 of the first course using a validated high performance liquid chromatographic assay. 29 patients entered the study, all patients were evaluable for toxicity and response. The doses studied in the 29 patients were 1.2, 1.8, 2.3, 2.7 mg/m2/day and a fixed dose of 4 mg/day without surface area adjustment. A total of 109 courses were given. Dose limiting toxicity (DLT) was reached at a dose of 2.7 mg/m2/day and consisted of CTC (NCI-Common Toxicity Criteria) grade IV granulocytopenia. The regimen was well tolerated. Non-haematological toxicities were mild, including fatigue, anorexia, nausea, vomiting and diarrhoea. A significant correlation was observed between the percentage decrease in white blood cells versus the area under the curve (AUC(t)) of topotecan lactone (R = 0.76 P < 0.01) which was modelled by a sigmoidal Emax function. The correlation coefficient between the absolute topotecan dose administered and the AUC(t) was R = 0.52 (P = 0.04). Pharmacokinetics of the fixed dose of 4 mg/day were comparable to the 2.3 mg/m2/day dose. DLT in this phase I study of five daily doses of oral topotecan every 21 days was granulocytopenia. The recommended dose for phase II studies is 2.3 mg/m2/day or alternatively, a fixed dose of 4 mg/day.

Automated system for capture and detection of nucleic acids.

A fully automated nucleic acid analysis system is described, which offers positive sample identification, improved sensitivity and reduced user interaction compared to conventional techniques. The system relies on the sequence-specific capture of DNA onto solid-phase particles, confirming product identity without the problems of interpretation and lack of sequence information inherent in gel-based analyses. The system can be used for sequence confirmation, mutation analysis and semiquantitative detection of PCR products.

Macrophages and mast cells in chronic cholecystitis and "normal" gall bladders.

An attempt was made to quantify mast cells using toluidine blue and macrophages, with alpha-1-antitrypsin as a marker, from adjacent sections in the mucosa of two groups of gall bladders showing either minimal inflammatory change or established chronic cholecystitis. The results were expressed as cells/mm2 of mucosa. Alpha-1-antitrypsin showed both macrophages and mast cells, and therefore an estimate of macrophage numbers was obtained by subtraction. Mast cells comprised more than 60% of the alpha-1-antitrypsin positive cells. There were significantly (p greater than 0.001) more mast cells and macrophages in minimal inflammatory gall bladder mucosa than in established chronic cholecystitis.

Aortic valve tumor causing acute myocardial infarction in a child.

A 10-year-old child presented with biventricular failure after an acute myocardial infarction. On investigation a large tumor arising from the aortic valve was diagnosed. The patient underwent successful aortic valve replacement for complete excision of the tumor mass, which was reported to be a papillary fibroelastoma. This case report highlights the unusual presentation of an aortic valve tumor in a child with myocardial infarction. The surgical dilemmas of the timing of the operation and the nature of the operation are discussed.

The efficacy of intranasal mupirocin in the prevention of staphylococcal infections: a review of recent experience.

Staphylococcal infections remain an important cause of morbidity and mortality. Methicillin-resistant Staphylococcus aureus (MRSA) present a particular problem because of the costs of treatment and containing outbreaks. The role of nasal carriage of staphylococci in the epidemiology of staphylococcal infection has been recognized for over 30 years. Until recently, eradication of nasal carriage of S. aureus has proved difficult, with a variety of topical and systemic agents yielding poor results with either little discernible effect on nasal carriage or rapid recolonization. Mupirocin is a novel topical antibiotic with excellent antibacterial activity against staphylococci, including MRSA. Intranasal administration of calcium mupirocin has achieved excellent results in the eradication of nasal carriage of S. aureus and producing an associated reduction in S. aureus infection in a variety of clinical settings, including MRSA outbreaks, neonatal nurseries, haemodialysis, cardiothoracic surgery and familial staphylococcal infections. This article reviews the efficacy and safety of intranasal mupirocin in the prevention of staphylococcal infections.

Factors predicting residual beta-cell function in the first year after diagnosis of childhood type 1 diabetes.

Twenty-five children aged 2-14 years (mean age 8.39 +/- 0.78 years) were studied prospectively during the first year after the diagnosis of type 1 diabetes. Of their clinical and metabolic features at diagnosis, only age showed a significant independent relationship with endogenous C-peptide production during the first year. Age was correlated with higher values for basal and stimulated plasma C-peptide at 7-14 days after diagnosis, at 6 months and at 12 months. At diagnosis, age was also associated with a higher value for HbA1c and a lower prevalence of insulin antibodies. C-peptide production peaked at 3 months and thereafter declined. Mean HbA1c and insulin requirement were both minimal at 6 months. At diagnosis, there were significant inverse relationships between basal C-peptide production and both insulin dose and HbA1c and between stimulated C-peptide production and HbA1c. Basal and stimulated C-peptide production were inversely related to insulin dose at 6 and 12 months. Stimulated C-peptide was higher at 12 months in children retaining islet cell antibodies. These findings confirm the importance of age as a predictor of residual beta-cell function in type 1 diabetes and indicate that older children present clinically following a slower course of beta cell destruction.

Are sex, age at diagnosis, or mode of presentation prognostic factors for cystic fibrosis?

Data on 622 patients with cystic fibrosis born in Victoria, Australia from 1955 to 1980 and on 344 surviving patients in the care of a specialist clinic on June 30, 1983 were analyzed for factors associated with better survival and a less rapid progress of lung disease. Presentation with predominantly gastrointestinal symptoms, other than meconium ileus, was associated with an improved prognosis, whereas presentation with predominantly respiratory symptoms was associated with a worse prognosis. While infants diagnosed before the age of 6 months as a result of routine testing because of a family history of the disease seemed to have less rapid progress of lung disease, their ultimate survival did not seem to be better than that of patients presenting symptomatically after the newborn period. The sex of the patients did not appear to have prognostic significance. Age at diagnosis did not affect rate of progress of lung disease or survival when infants dying within 6 months of birth were excluded. There was a close association between the extent of lung disease at diagnosis and current lung disease. Failure to reverse extensive disease at diagnosis or deterioration of lung disease in the first year after diagnosis was associated with a less favourable course.