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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 199 records · Page 11Linked to original sources

Degradation of the cyanobacterial toxin cylindrospermopsin, from Cylindrospermopsis raciborskii, by chlorination.

Cylindrospermopsin, a potent cyanobacterial toxin produced by Cylindrospermopsis raciborskii and other cyanobacteria, is regularly found in water supplies of Queensland, Australia. This study focussed on the effectiveness of chlorination as a water treatment procedure for cylindrospermopsin degradation. The results demonstrate that relatively low chlorine doses (<1 mg l(-1)) are sufficient for degradation of cylindrospermopsin, when the dissolved organic carbon content is low. However, if organic matter other than cylindrospermopsin is present in the solution, the effectiveness of chlorine for cylindrospermopsin degradation is reduced as other organic matter present consumes chlorine. Under the experimental conditions using samples with a solution pH of 6-9, a residual chlorine concentration of 0.5 mg l(-1)99% of cylindrospermopsin. Toxin degradation via chlorination occurs within the first minute and no difference was observable between degradation in an open system and in a closed system. With a decrease of the pH from 6 to 4 a reduction in the efficiency of chlorine for degradation of cylindrospermopsin was observable, a possible indication that cylindrospermopsin is more stable to chlorine degradation at lower pH. However, in normal water treatment this is not relevant since the pH is consistently higher than 6.

Alkaloids↗

Dopamine genes and ADHD.

Family, twin, and adoption studies have documented a strong genetic basis for ADHD/HKD, but these studies do not identify specific genes linked to the disorder. Molecular genetic studies can identify allelic variations of specific genes that are functionally associated with ADHD/HKD, and dopamine genes have been the initial candidates based on the site of action of the stimulants drugs, which for a half century have provided the primary pharmacological treatment for ADHD/HKD. Two candidate dopamine genes have been investigated and reported to be associated with ADHD/HKD: the dopamine transporter (DAT1) gene [Cook et al., American Journal of Human Genetics 1995;56:993-998, Gill et al., Molecular Psychiatry 1997;2:311-313] and the dopamine receptor D4 (DRD4) gene [LaHoste et al., Molecular Psychiatry 1996;1:121-124: Smalley et al., 1998;3:427-430; Swanson et al., Molecular Psychiatry 1998;3:38-41]. Speculative hypotheses [Swanson and Castellanos, NIH Consensus Development Conference: Diagnosis and Treatment of Attention Deficit Hyperactivity Disorder, November 1998. p. 37-42] have suggested that specific alleles of these dopamine genes may alter dopamine transmission in the neural networks implicated in ADHD/HKD (e.g. that the 10-repeat allele of the DAT1 gene may be associated with hyperactive re-uptake of dopamine or that the 7-repeat allele of the DRD4 gene may be associated with a subsensitive postsynaptic receptor). These and other variants of the dopamine hypothesis of ADHD will be discussed.

Alleles↗

Retention and changes of soy isoflavones and carotenoids in immature soybean seeds (Edamame) during processing.

Isoflavones and carotenoids in four experimental genotypes and Hutcheson cultivar soybeans were evaluated as a function of processing treatments and maturity. Total isoflavone and carotenoid contents were affected by genotypes and maturity stages (p < 0.0001). Total isoflavones ranged from 472 microg/g (in NTCPR93-40) to 2280 microg/g (in Hutcheson). Lutein contents ranged from 895 (in NTCPR93-286) to 2119 (in Honey Brown), and beta-carotene ranged from 291 (in Hutcheson) to 491 (in NICPR92-40) microg/100 g. Mean total isoflavone retention percentages in immature Hutcheson soybeans were 46% (boiling), 53% (freezing), and 40% (freeze-drying). Mean retentions of lutein and beta-carotene, respectively, were 92 and 73% in frozen, 62 and 62% in boiled, and 34 and 27% in freeze-dried soybeans. Boiling caused a substantial increase in daidzin, genistin, and genistein. The results show that post-harvest changes in total isoflavones and carotenoids in soybeans are influenced by processing methods, but genotype has an effect on isoflavone and carotenoid profiles during seed development.

Carotenoids↗

Behavioral treatment of insomnia: a clinical case series study.

There is substantial experimental evidence that behavioral treatment of insomnia produces significant clinical improvement and that treatment gains tend to be maintained over time. Less clear is whether behavioral treatment is effective as it is plied in clinical settings. In this clinical case series study, we evaluated 47 patients with primary insomnia. It was found that patients were, on average, 43% improved. This average corresponded to a 65% reduction in sleep latency, a 46% decrease in number of awakenings per night, a 48% reduction in wake time after sleep onset, and a 13% increase in total sleep time. These results suggest that behavioral treatment for insomnia is as effective in clinical settings as it is as under clinical trial conditions.

Adult↗

National data sources on the care and outcomes of patients with community acquired pneumonia.

Despite improved understanding and treatment of community acquired pneumonia (CAP), variations in clinical practice and patient outcomes still exists, resulting in excess healthcare dollars spent and decreased patient satisfaction. The use of treatment and outcomes research data can help providers improve their methods and standardize techniques to control costs and provide the best care for their patients. To better understand the utility and capabilities of this research, this article will compare several administrative and clinical databases. Two, data sources in particular, the EPI-Q Inc. CAP-Compare database and the University HealthSystem Consortium's (UHC) CAP Benchmarking Program contain clinical and utilization data specific to CAP. In addition there are several government and non-government sponsored data sources that include administrative data on many diagnosis including CAP. These include: Healthcare Benchmarking Systems International's EXPLORE database, the Center for Healthcare Industry Performance Studies database, the National Center for Health Statistics'--National Hospital Discharge Survey, and the Medicare Provider Analysis and Review data files.

Benchmarking↗

Assessing phytoestrogen exposure in epidemiologic studies: development of a database (United States).

BACKGROUND AND OBJECTIVE: Phytoestrogens (weak estrogens found in plants or derived from plant precursors by human metabolism) have been hypothesized to reduce the risk of a number of cancers. However, epidemiologic studies addressing this issue are hampered by the lack of a comprehensive phytoestrogen database for quantifying exposure. The purpose of this research was to develop such a database for use with food-frequency questionnaires in large epidemiologic studies. METHODS: The database is based on consumption patterns derived from semistructured interviews with 118 African-American, Latina, and white women residing in California's San Francisco Bay Area. HPLC-mass spectrometry was used to determine the content of seven specific phytoestrogenic compounds (i.e. the isoflavones: genistein, daidzein, biochanin A, and formononetin; the coumestan: coumestrol; and the plant lignans: matairesinol and secoisolariciresinol) in each of 112 food items/groups. RESULTS: Traditional soy-based foods were found to contain high levels of genistein and daidzein, as expected, as well as substantial amounts of coumestrol. A wide variety of "hidden" sources of soy (that is, soy protein isolate, soy concentrate, or soy flour added to foods) was observed. Several other foods (such as various types of sprouts and dried fruits, garbanzo beans, asparagus, garlic, and licorice) were also found to be substantial contributors of one or more of the phytoestrogens analyzed. CONCLUSIONS: Databases, such as the one described here, are important in assessing the relationship between phytoestrogen exposure and cancer risk in epidemiologic studies. Agencies, such as the United States Department of Agriculture (USDA), that routinely provide data on food composition, on which epidemiologic investigations into dietary health effects are based, should consider instituting programs for the analysis of phytochemicals, including the phytoestrogens.

Adult↗

Increased vascular expression of iNOS at day but not at night in asthmatic subjects with increased nocturnal airway obstruction.

Nitric oxide production by endothelial cells may have important consequences for the development of airway inflammation as well as for airway obstruction. The present study investigated whether the expression of vascular inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in human bronchi differs between asthmatic and healthy subjects, and whether it shows a circadian rhythm, especially in subjects with increased nocturnal airway obstruction. Bronchial biopsy samples were taken at 16:00 and 04:00 h from 13 healthy and 25 asthmatic subjects, 18-45 yrs. Biopsy samples were snap-frozen and double-immunostained for iNOS and eNOS in combination with a common vascular antigen (CD31). The degree of immunopositivity was expressed as a percentage of CD31-positive vessels encountered in complete biopsy sections. Asthmatic subjects showed greater iNOS expression than healthy controls: 23+/-15 versus 7+/-17% (mean+/-SD) at 16:00 h (p<0.001) and 19+/-15 versus 8+/-11% at 04:00 h (p<0.05). Asthmatic subjects with a fall in forced expiratory volume in one second of >10% of the predicted value between 16:00 and 04:00 h showed greater iNOS expression at 16:00 than at 04:00 h: 32+/-16 versus 20+/-13% (p<0.05). eNOS expression did not differ between healthy controls and asthmatic patients, nor did it differ between 16:00 and 04:00 h. It is suggested that asthmatic subjects with increased nocturnal airway obstruction demonstrate increased activation of inducible nitric oxide synthase during the day. The resulting nitric oxide production might protect against airway obstruction during the day. However, at night, nitric oxide production is probably insufficient to counterbalance the bronchoconstricting forces.

Adolescent↗

Malignant ovarian sex cord tumor with annular tubules in a patient with Peutz-Jeghers syndrome: a case report.

The majority of ovarian sex cord tumors with annular tubules (SCTAT) are benign neoplasms that arise sporadically. In patients who have Peutz-Jeghers syndrome (PJS), ovarian SCTAT is often an incidental finding. Malignant behavior in SCTAT has heretofore been reported only in sporadic cases. We report a case of bilateral, malignant SCTAT developing in a 47-year-old woman who had PJS, originally diagnosed as adenocarcinoma on cervicovaginal cytology. Cervicovaginal and peritoneal fluid cytologic preparations were characterized by pseudopapillary clusters and three-dimensional tubes of tumor cells with scanty cytoplasm and high nuclear: cytoplasmic ratio. Examination of surgical resection specimens revealed bilateral, solid ovarian tumors composed of simple and complex annular tubules with hyaline cores, typical of SCTAT. Tumor emboli were present within salpingeal lymphovascular spaces and in both right and left pelvic lymph nodes. Flow cytometry of tumor cells demonstrated a diploid phenotype. This case represents the first documented example of bilateral, malignant SCTAT arising in a patient who had PJS, presenting with an atypical cervicovaginal smear.

Female↗

The effects of ketoconazole on ziprasidone pharmacokinetics--a placebo-controlled crossover study in healthy volunteers.

AIMS: To assess the effects of multiple oral doses of ketoconazole on the single-dose pharmacokinetics of oral ziprasidone HCl. METHODS: This was a 14-day, open-label, randomized, crossover study in 14 healthy subjects aged 18-31 years. Group 1 received oral ketoconazole 400 mg once daily for 6 days, followed by a 2 day wash-out period and 6 days of placebo administration. Group 2 received placebo followed by ketoconazole. Single oral doses of ziprasidone HCl 40 mg were administered on days 5 and 13 in both groups. Ziprasidone pharmacokinetic parameters were compared between placebo and ketoconazole administration periods. RESULTS: Co-administration of ziprasidone with ketoconazole was associated with a modest increase in ziprasidone exposure; mean ziprasidone AUC(0,infinity) increased by 33%, from 899 ng ml(-1) h with placebo to 1199 ng ml(-1) h with ketoconazole. Mean Cmax increased by 34%, from 89 ng ml(-1) to 119 ng ml(-1), respectively. The treatment effect on both of these parameters was statistically significant (P<0.02). Most adverse events were of mild intensity. There were no serious adverse events, laboratory abnormalities, abnormal ECGs, or clinically significant alterations in vital signs throughout the study. CONCLUSIONS: The concurrent administration of ketoconazole and ziprasidone led to modest, statistically significant increases in ziprasidone exposure, although the changes seen were not considered clinically relevant. This suggests that other inhibitors of CYP3A4 are unlikely to significantly affect the pharmacokinetics of ziprasidone.

Adolescent↗

Salivary, but not serum or urinary levels of progesterone are elevated after topical application of progesterone cream to pre-and postmenopausal women.

OBJECTIVE: The use of topically applied micronised ('natural') progesterone as a substitute for synthetic oestrogens and progestogen preparations is controversial. The aim of this study was to examine the changes in blood and salivary concentrations of progesterone following a single topical application of a progesterone cream. PATIENTS AND MEASUREMENTS: We investigated six premenopausal women in the luteal phase and six postmenopausal women to determine the short-term changes in serum, urinary and salivary progesterone concentrations following a single 64 mg topical application of micronised progesterone. RESULTS: Serum progesterone concentrations did not increase during the first 3 hours after application of progesterone cream, however, salivary values rose significantly in both premenopausal and postmenopausal women, consistent with the view that progesterone is absorbed and transported through the body. Salivary progesterone concentrations were significantly elevated above basal levels by 30-60 minutes and reached peak levels at 1-4 h, with mean levels approximately fivefold higher in premenopausal, than in menopausal women. CONCLUSIONS: Salivary progesterone measurements confirm that topically applied progesterone is absorbed, despite the lack of change in serum progesterone concentrations. However, at the dose administered, serum progesterone levels do not reach those observed after oral or vaginally delivered progesterone preparations. Higher doses may be required to induce biological responses within the endometrium.

Absorption↗

Bell's palsy during interferon therapy for chronic hepatitis C infection in patients with haemorrhagic disorders.

Two adult patients with life-long severe haemorrhagic disorders commenced on interferon-alpha2b therapy for chronic hepatitis C infection. Both developed Bell's palsy several weeks after commencing therapy, They were started on steroids and, in addition, the first patient discontinued interferon-alpha2b therapy while the second patient elected to continue with therapy. In both cases facial paralysis improved over the ensuing weeks. Bell's palsy is often idiopathic but has been reported. in association with herpesviruses. It is not a recognised complication of chronic hepatitis B or C infection, or interferon-alpha2b therapy. However, the interferons are associated with numerous adverse reactions including various neuropsychiatric manifestations and neurological syndromes. There are several reports of nerve palsies, including optic tract neuropathy, occurring during interferon therapy, and immune-based mechanisms are thought to play a role in the aetiopathogenesis. No reports of Bell's palsy in association with interferon therapy were identified in our literature search, although one possible case has been reported to the Committee of Safety in Medicine. Although Bell's palsy in our patients may have occurred by chance, a neuropathic effect of interferon-alpha2b on the facial nerve cannot be excluded and we urge physicians using interferons to be aware of this potential side-effect.

Adult↗

The Ottawa Charter--from nursing theory to practice: insights from the area of alcohol and other drugs.

This article aims to assist nursing services to use the Ottawa Charter as a framework for nursing practice. Incorporation of the Ottawa Charter for Health Promotion into a nursing structure constitutes an innovation in nursing practice that was evaluated as a quality improvement exercise in a health-care organization responsible for providing services in the area of alcohol and other drugs. The evaluation consisted of two stages and sought to identify the degree to which the framework was effective in practice. This involved identifying issues surrounding the implementation of the Ottawa Charter as a framework for nursing practice as well as identifying the means by which quality improvements could occur. The evaluation involved an initial questionnaire to all nursing staff, followed by a series of focus groups. The data collected was both informative and enlightening and revealed a range of pertinent issues such as staff understanding and interpretation of the Ottawa Charter, expansion of the nurse's role and suggestions for organizational change. The Ottawa Charter strategies are discussed in relation to their relevance to the organization under evaluation and also expanded into recommendations to assist those contemplating using the Ottawa Charter as a framework for nursing practice. There was considerable agreement among the respondents that the Ottawa Charter provided a useful framework for nursing practice but was on occasions problematic.

Attitude of Health Personnel↗

Outcome analysis of chest pain patients discharged from the ED--a pilot study.

The objective of this pilot study was to determine clinical predictors of adverse outcome, defined as myocardial infarction, angioplasy or stent placement, coronary artery bypass graft, or death, within 60 days for patients discharged from the emergency department with a presenting complaint of chest pain. All patients presenting to the emergency department with a chief complaint of chest pain were eligible for the study. A chest pain risk analysis sheet was completed as part of the patient evaluation. Patients discharged from the emergency department, in whom a risk analysis sheet was completed, were contacted to determine their clinical course within 60 days of their discharge from the emergency department. During the 6-month study period, 129 eligible patients were enrolled. Of these 129 patients, four had an adverse outcome within 60 days of their discharge. All four patients had either a balloon angioplasty procedure, coronary artery bypass graft, or both. None of the study patients had a myocardial infarction or died. Statistically significant predictors of adverse outcome in our study population were an abnormal electrocardiogram (ECG), a history of myocardial infarction, and a history of hypertension. In conclusion, patients discharged from the emergency department with a presenting complaint of chest pain were at a low risk for having a myocardial infarction or dying within 60 days of their discharge. Several patients, however, did have significant coronary artery disease requiring angioplasty or bypass. These patients were more likely to have an abnormal ECG, a history of myocardial infarction, or have a history of hypertension. A prospective study with larger numbers of patients is needed to validate these findings.

Adult↗

A dose-finding study of raltitrexed (tomudex) with cisplatin and epirubicin in advanced gastro-oesophageal adenocarcinoma.

The standard treatment for advanced gastro-oesophageal cancer in the UK is epirubicin, cisplatin and continuous infusion 5-fluoruracil by an indwelling central venous catheter (ECF), which has significant morbidity. Raltitrexed (tomudex), a specific inhibitor of thymidylate synthase with a long plasma terminal half-life (50-100 h) has activity in gastro-intestinal tract malignancy. To reduce the Hickman line-associated morbidity of ECF; we have conducted a dose-finding study of tomudex combined with epirubicin and cisplatin. Twenty-four patients (22 males, two female), median age 63 years (range 21-75), ECOG performance status < or =2 with histologically proven, unresectable or metastatic gastric (14 patients), gastro-oesophageal junction (nine patients) or oesophageal (one patient) adenocarcinoma received treatment with 3-weekly cisplatin 60 mg m(-2), epirubicin 50 mg m(-2) and tomudex at doses of 2 mg m(-2), 2.5 mg m(-2) or 3 mg m(-2) in successive cohorts. Six patients were treated per dose level with no intra-patient dose escalation. Dose escalation occurred after six patients had completed at least one cycle of chemotherapy at the previous dose level. After defining the maximum tolerated dose a further six patients were treated at the preceding dose level to assess toxicity at the proposed phase II dose. A total of 102 cycles (50% completed 6 cycles) were administered. The dose-limiting toxicities are neutropenia and diarrhoea occurring in 2/6 patients at the 3 mg m(-2) dose level. Of those patients evaluable for response, there were eight partial and one complete response (overall response rate 38%). The median survival was 9.9 months. ECT is an active regimen in oesophagogastric adenocarcinoma. The recommended dose of tomudex for further study in combination with epirubicin and cisplatin is 2.5 mg m(-2).

Adenocarcinoma↗

A comparison of adult and teenage mother's self-esteem and satisfaction with social support.

OBJECTIVE: To investigate the similarities and differences between teenage and adult mothers and their level of self-esteem and satisfaction with social support at six weeks and six months postpartum. DESIGN: A two group comparative study. SETTING: Maternal child health, immunisation and midwives' clinics in New South Wales, Australia. PARTICIPANTS: 173 adult mothers and 72 adolescent mothers who had experienced a normal pregnancy, labour and delivery and delivered a healthy baby near term. MEASUREMENTS AND FINDINGS: Rosenberg's Self-esteem Scale, Brown's Support Behavior Inventory and a personal information form were used. Irrespective of age, breast-feeding rates and satisfaction with social support decreased significantly during the early months postpartum. Furthermore, a significant inverse relationship was noted between maternal age and satisfaction with support and a positive relationship was identified between maternal age and self-esteem. KEY CONCLUSIONS AND CLINICAL IMPLICATIONS: Maternal self-esteem may be challenged by the demands of motherhood and dissatisfaction with social support could contribute to the decline in breast-feeding practices. Developing a postnatal support plan, including fathers in education programmes and offering courses and workshops designed to enhance self-esteem and parentcraft may assist mothers to assume baby care responsibilities and increase their satisfaction with support.

Adolescent↗

Clinical value of real-time tertiary fetal ultrasound consultation by telemedicine: preliminary evaluation.

Congenital fetal abnormalities are major causes of perinatal mortality and morbidity. The performance of ultrasound in the diagnosis and assessment of fetal anomalies varies enormously between tertiary referral centers and general units. Telemedicine offers a chance for tertiary realtime ultrasound consultations using standard telephone lines for remote sites. Preliminary investigations by our group have shown that real-time transmission of fetal ultrasound images over long distances via telephone (integrated systems digital network [ISDN]) lines is technically feasible. A live link of up to 2 Mb/s was established between Mater Mothers Hospital in Brisbane and Kirwan Hospital for Women in Townsville, which are 1,500 km apart. The objective of the current study was to evaluate the clinical value of a tertiary teleultrasound consultation service. Patients requiring tertiary ultrasound consultations were recruited from North Queensland. Clinicians from the referral site established an initial diagnosis and management plan. Using standard ISDN lines, the real-time ultrasound images were transmitted to the maternal fetal medicine subspecialists in Brisbane. The ultrasound examination was completed under the direction of the subspecialist. The subspecialist explained the findings to the patient at the end of the session, and discussed the diagnosis and management plans with the clinicians involved. Any diagnosis and management variations were classified into minor and major upon agreement by the two teams of clinicians involved. The clinicians and patients in Townsville rated the value of the consultation, and the subspecialists rated the confidence of their diagnoses on five-point scales. Pregnancy outcomes were obtained and the data analyzed. Over a 3-month period, 24 teleultrasound consultations were carried out. The indications for referral were: assessment of growth restriction/fetal wellbeing in the third trimester (6); detailed assessment for high-risk patients (5); evaluation of markers for anomalies (5); isolated fetal anomalies (1); and complex fetal problems such as twin/twin transfusion, multiple anomalies, etc. (7). Overall, the consultations resulted in some modifications to the clinical diagnosis in 45.8% of the cases, and modifications to the management plan in 33.3% of the cases (about half of which were minor variations). The clinicians rated the teleconsultations highly (mean rating 4.7, SD 0.44). The patients also rated the consultations highly, and were comfortable that their privacy and confidentiality were maintained during the consultation. The subspecialists were confident in making their diagnoses by telemedicine (mean score for confidence 4.2, SD 0.43). All the pregnancies have now been completed, with all antenatal diagnoses confirmed to be correct postnatally. Tertiary real-time ultrasound consultation by telemedicine is not only technically feasible, it is welcomed by the clinicians and patients involved. It also contributes to diagnostic and management differences. Larger scale clinical trials are needed to evaluate the true benefits and costs involved. The social benefits in bridging the healthcare gap between the country and the city, and in enabling patients in remote areas to stay close to their family under times of stress is well recognized by all involved.

Congenital Abnormalities↗

Performance status assessment in home hospice patients using a modified form of the Karnofsky Performance Status Scale.

The Karnofsky Performance Status (KPS) scale is considered to be the gold standard for quantifying the physical functioning of patients with cancer. However, problems have been identified with the scoring system when the scale is used in the home hospice setting. The goal of this study was to compare assessments of performance status using two instruments, the KPS and a modified version, the Thorne-KPS (TKPS). The TKPS avoids reference to location of care and has new descriptors for assessing the frequency of professional visits and the proportion of time spent in bed. Comparisons were made on a sample of 78 home-hospice patients in Perth, Western Australia. The median score for both scales was 60. The scales agreed in 56% of ratings overall but after correcting for chance, agreement was reduced to 47%. However, 91% of the 34 discrepancies occurred within one or two levels of the 11-point scale. TKPS scores were consistently lower than KPS scores and were spread over a wider range of the scale. The strongest agreement occurred at the higher levels of performance and the weakest agreement was within the middle levels of the scales. Further studies are required to determine which of the two scales more accurately reflects performance status and survival time. However, the results to date suggest that the TKPS may be a more objective and sensitive measure of functional performance in home hospice patients.

Journal Article↗