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Biomedical subjects

R Hansen

Publications and source records attributed to R Hansen.

At least 55 records · Page 3Linked to original sources
PubMed1998

Psychopathology in pediatric complex partial and primary generalized epilepsy.

Structured psychiatric interviews were administered to 60 children with complex partial seizure disorder (CPS), 40 children with primary generalized epilepsy with absences (PGE), and 48 control children, aged 5 to 16 years. Significantly more patients with epilepsy had psychiatric diagnoses compared with the control children. There were no statistically significant differences, however, in the number of patients with CPS and PGE with psychiatric diagnoses. Other than a schizophrenia-like psychosis found only in the patients with CPS, the two groups of patients had similar psychiatric diagnoses. The presence of psychopathology was related to significantly lower IQ scores and socioeconomic status, but not to seizure-related factors. These findings suggest that the psychopathology of children with CPS and PGE reflects different subtle neuropsychological deficits.

Adolescent↗
PubMed1998

An audit of oestrogen implant hormone replacement therapy.

The aim of this review was to determine the factors that impact upon oestradiol levels in patients receiving oestradiol implants and to assess the relationship between symptom scores and oestradiol levels. In addition we sought to determine the incidence of tachyphylaxis (menopausal symptoms in spite of high oestradiol levels) among our patients, and to assess the degree of menstrual cycle control in the nonhysterectomized women receiving implant treatment. We undertook an audit of the medical records of 118 women who received 673 oestradiol implants (50 or 100 mg) over an 8-year period in the menopause clinics at Royal North Shore Hospital. Data on patient age, clinical diagnosis, symptom score, previous or subsequent hysterectomy, oestradiol implant dosage (50 mg or 100 mg), number of doses, oestradiol levels and concurrent testosterone implant insertion were recorded. We found that implant dosage (p<0.001) and implant number (p<0.001) were the factors that significantly impact upon oestradiol levels. Concomitant testosterone implant usage (p=0.74), patient age (p=0.14) and hysterectomy (p=0.57) did not have a statistically significant effect upon oestradiol levels. The incidence of tachyphylaxis was 1.7% (2 patients). There was no relationship between oestradiol levels and symptom scores (p=0.69). Oestradiol implant treatment, when administered on the basis of return of symptoms, without a strict target oestradiol level, results in a steady increase in baseline oestradiol levels. The dosage used and the number of implants received are important factors influencing oestradiol levels. The incidence of tachyphylaxis is low when patients are counselled regarding the lack of agreement between symptom scores and oestradiol levels.

Adult↗
PubMed1998

Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer.

PURPOSE: The administration of fluorouracil (5-FU) by continuous intravenous infusion (CI) is an alternative to the bolus administration of 5-FU in patients with advanced colorectal cancer. Although more than 1,200 patients have been enrolled onto randomized trials that compared these two treatment modalities, there is still no definitive evidence of an advantage of 5-FU CI, and the magnitude of this advantage, if any, is also controversial. A meta-analysis was performed to assess this benefit in terms of tumor response and survival, and to compare the toxicity profiles of these two modalities of administration of 5-FU. DESIGN: Individual data of 1,219 patients included in six randomized trials served as the basis for this meta-analysis, which was conducted by an independent secretariat in close collaboration with the investigators. RESULTS: Tumor response rate was significantly higher in patients assigned to 5-FU CI than in patients assigned to 5-FU bolus (22% v 14%; overall response odds ratio, 0.55; 95% confidence interval [95% CI], 0.41 to 0.75; P = .0002). Overall survival was also significantly higher in patients assigned to 5-FU CI (overall hazards ratio [HR], 0.88; 95% CI, 0.78 to 0.99; P = .04), although the median survival times were close. Multivariate analyses showed that randomized treatment and performance status were the only two significant predictors of tumor response, whereas the same plus primary tumor site were independent significant predictors of survival (patients with rectal cancer did somewhat better). Grade 3 or 4 hematologic toxicity was more frequent in patients assigned to 5-FU bolus (31% v 4%; P < 10(-16)), whereas hand-foot syndrome was more frequent in the 5-FU CI group (34% v 13%; P < 10(-7)). CONCLUSION: 5-FU CI is superior to 5-FU bolus in terms of tumor response and achieves a slight increase of overall survival. The hematologic toxicity is much less important in patients who receive 5-FU CI, but hand-foot syndrome is frequent in this group of patients.

Antimetabolites, Antineoplastic↗
PubMed1998

Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors.

PURPOSE: Fluorouracil (5-FU) continuous infusion is superior to 5-FU bolus in patients with advanced colorectal cancer, but the survival difference between the two treatments is small and, therefore, the difference in toxicity profile is crucial in choosing a treatment for individual patients. MATERIALS AND METHODS: We conducted a meta-analysis of all randomized trials that compared 5-FU bolus with 5-FU CI, based on individual data from 1,219 patients, to compare the toxicity of the two schedules of 5-FU administration and to identify predictive factors for toxicity. The toxicities considered were World Health Organization (WHO) grade 3 to 4 anemia, thrombopenia, leukopenia, neutropenia, nausea/vomiting, diarrhea, mucositis, and hand-foot syndrome. RESULTS: Hematologic toxicity, mainly neutropenia, was more frequent with 5-FU bolus than with 5-FU CI (31% and 4%, respectively; P < .0001). Hand-foot syndrome was less frequent with 5-FU bolus than with 5-FU CI (13% and 34%, respectively; P < .0001). There was no difference between the two treatment groups in terms of other nonhematologic toxicities. Independent prognostic factors were age, sex, and performance status for nonhematologic toxicities, performance status, and treatment for hematologic toxicities, and age, sex, and treatment for hand-foot syndrome. CONCLUSION: Based on a large data set, this study confirmed and quantified the toxicity profile of the two schedules of administration of 5-FU and allowed the identification of clinical predictors of toxicity.

Colorectal Neoplasms↗
PubMed1998

Internal calibration for a total body counter.

Whole body counting is used to monitor the ingestion of radioactivity by radiation workers when unsealed sources are used in biomedical or industrial applications. The whole body counter at Lucas Heights Research Laboratories has been running for four decades, and radiation workers are frequently monitored for radioactive contamination. In a retrospective study of total body potassium (TBK) values in radiation workers, it was found that the results varied markedly with time. In that TBK is a slowly varying quantity in healthy individuals, variation in TBK is therefore indicative of instability in the counting system. We conclude that TBK can be used as an internal calibration for the whole body counter. The activity of radioisotope contaminants can therefore be expressed relative to the value of the potassium activity in a given subject.

Humans↗
PubMed1998

Principal findings from the Washington State cognitive services demonstration project.

In addition to dispensing, pharmacists are ideally positioned to provide cognitive services that are targeted at optimizing drug therapy through identification and resolution of drug therapy problems. The Washington Cognitive Activities and Reimbursement Effectiveness project sought to determine: (1) if pharmacists would respond to a financial incentive by performing more cognitive services, and (2) the effect on drug cost of cognitive services they performed.

Attitude of Health Personnel↗
PubMed1997

Pharmacokinetics of zileuton and its metabolites in patients with renal impairment.

The pharmacokinetics of zileuton and its conjugated metabolites were evaluated in patients with chronic renal impairment. Five healthy volunteers (creatinine clearance > 90 mL/min), five patients with renal failure requiring hemodialysis, six with mild (creatinine clearance, 60-90 mL/min), eight with moderate (creatinine clearance, 30-59 mL/min), and six with severe (creatinine clearance < 30 mL/min) renal impairment participated in the study. Zileuton was well tolerated by all participants including those with severe renal impairment and those receiving hemodialysis. The pharmacokinetics of zileuton were similar in healthy volunteers; in patients with mild, moderate and severe renal impairment; and in patients with renal failure requiring hemodialysis. The mean metabolite/parent-area ratios for the pharmacologically inactive zileuton glucuronides progressively increased with the decline in renal function. A very small percentage of the administered zileuton dose (< 0.5%) was removed by hemodialysis. Therefore, adjustment in the dose regimen of zileuton does not appear to be necessary for patients with various degrees of renal impairment and patients with renal failure requiring hemodialysis.

Adult↗
PubMed1997

p53; from inductive signal to cellular effect.

During the past year, the story of how p53 suppresses carcinogenesis has increased in complexity. Further insight has been provided into the activation of latent p53, the biochemical mechanisms involved in growth arrest and apoptosis, and the influence of various signals on these cellular effects. Additionally, roles for p53 have been described in cell senescence, in suppressing teratogenesis, and in processes that may directly contribute to the maintenance of genomic stability.

Animals↗
PubMed1997

Auto-regulation of the estrogen receptor promoter.

The presence or absence of estrogen receptor (ER) plays a key role in the diagnosis and treatment of breast tumors. It is known that patients with breast tumors classified as ER-positive have a better prognosis. Observations such as this have led us to explore the question of what makes some breast tumors overexpress ER whereas others express either very low levels or none at all. To begin a study of ER regulation, we first chose to examine a 200 bp region of the ER promoter located immediately upstream from the transcribed sequence of the human ER gene. We found that this region of the ER promoter contained basal activity when transiently transfected into ER-negative HeLa cells. ER promoter activity was further increased by co-transfection of a wild-type ER expression vector, and this increased activity was hormone-dependent. Several ER deletion mutant constructs were also able to increase the activity of the ER promoter fragment, but none could support equivalent activity as was seen with the full-length ER. Therefore, we conclude that the ER can contribute to its own expression, and we hypothesize that this auto-regulation may contribute to its overexpression in some breast tumors.

Autocrine Communication↗
PubMed1997

Formal thought disorder and psychopathology in pediatric primary generalized and complex partial epilepsy.

OBJECTIVE: To examine whether formal thought disorder and psychopathology occurred in children with complex partial seizures (CPS) rather than children with primary generalized epilepsy with absences (PGE) or nonepileptic children. METHOD: Formal thought disorder was coded in 30 children with CPS, 24 children with PGE, and 61 nonepileptic children, and structured interview-based psychiatric diagnoses were obtained for the epileptic subjects. RESULTS: The CPS subjects had significantly more illogical thinking than the PGE and nonepileptic children. The severity of their illogical thinking was related to global cognitive dysfunction and a schizophrenia-like psychosis. Age of onset and seizure control, however, were significantly associated with the severity of illogical thinking in the PGE group. One or more psychiatric diagnoses were found in 63% of the CPS and 54% of the PGE patients, particularly if they had global cognitive deficits. CONCLUSION: Illogical thinking, associated with cognitive dysfunction or schizophrenia-like symptoms, might be a feature of pediatric CPS. Psychopathology might be related to global cognitive dysfunction in pediatric CPS and PGE.

Adolescent↗
PubMed1997

The physiological strain induced by a new low burden chemical protective ensemble.

The physiological responses of a group of nine subjects exercising at a metabolic rate of 510 W in a new low burden chemical protective ensemble, the Chemical/Biological Combat Suit (CBCS), have been determined under a warm, humid climatic condition, 30 degrees C and 60% relative humidity. The CBCS was significantly superior to a current NBC overgarment (MK4) in terms of induced physiological strain. Furthermore, there was no statistically significant difference between the normal combat uniform (DPCU) and the CBCS worn as a combat uniform (CS), without hood, mask and gloves, in terms of increase in rectal temperature and increase in heart rate. The major limitation on performance in the fully encapsulated CBCS was imposed by the combination of mask, permeable hood and impermeable gloves. It was concluded that there would be a significant improvement in soldier performance in the CBCS rather than in the current MK4 overgarment and that there would be no detriment to soldier performance when wearing the CS uniform in times of chemical threat.

Adult↗
PubMed1996

Phase II trial of prolonged continuous infusion of 5-fluorouracil and interferon-alpha in patients with advanced pancreatic cancer. Eastern Cooperative Oncology Group Protocol 3292.

Evidence suggests that interferon-alpha (IFN-alpha) augments the antineoplastic activity of 5-fluorouracil (5-FU) in human adenocarcinoma cell lines in vitro and may enhance the efficacy of 5-FU in patients with advanced colorectal carcinoma. In addition, 5-FU may be more effective when given as a prolonged, continuous i.v. infusion (PCI). The Eastern Cooperative Oncology Group performed a Phase II trial of PCI 5-FU plus IFN-alpha in patients with advanced pancreatic carcinoma. Twenty-six patients with advanced, surgically incurable adenocarcinoma of the pancreas received PCI 5-FU (250 mg/m2 daily for 28 days) in combination with IFN-alpha (5 x 10(6) IU/m2 s.c. thrice weekly). Treatment cycles were repeated 14 days or longer after completion of the previous cycle. Treatment was interrupted prior to day 28 if intolerable toxicity developed, and the dose of 5-FU was reduced in subsequent cycles. Partial response occurred in two of 24 evaluable patients (8%; 95% confidence interval, 0-19%). The majority of the study group (88%) had liver metastases. Patients whose serum lactate dehydrogenase (LDH) was more than twofold elevated developed 5-FU-related toxicity significantly sooner than patients with smaller elevations in serum LDH (9 vs. 22 days; p = 0.003). A similar trend was observed for patients with a more than twofold elevation in serum glutamic-oxaloacetic transaminase (SGOT; 9 vs. 15 days; p = 0.07). In conclusion, PCI 5-FU plus IFN-alpha has minimal activity in patients with advanced pancreatic carcinoma, and elevated serum LDH and/or SGOT may be useful for predicting greater toxicity from 5-FU-based therapy in patients with liver metastases.

Adenocarcinoma↗
PubMed1996

[Lithium poisoning].

A case of therapeutic overdosage in a 58-year-old woman is reported. Lithium plasma level was 3.7 mmol.l. All clinical and biological disturbances regressed in 3 days after controlled rehydration only. Aetiology, clinical picture, biological characteristics and treatment according to the severity of the lithium poisoning are discussed.

Bipolar Disorder↗
PubMed1995

The transforming oncoproteins determine the mechanism by which p53 suppresses cell transformation: pRb-mediated growth arrest or apoptosis.

To investigate the mechanisms by which p53 suppresses cell transformation, we used the simian virus 40 (SV40) large T antigen (LTag), the adenovirus E1a proteins, and an activated ras protein (EJ-ras), to examine different pathways of transformation for their susceptibility to suppression by p53: While p53 can suppress transformation by various oncoproteins, we have shown that it is unable to suppress the transformation of rat embryo fibroblasts (REFs) by LTag. Interestingly, the function of LTag which enables it to overcome the antiproliferative effects of p53 is not the binding and inactivation of p53, but the binding and inactivation of the pRb family of proteins. This observation indicates that pRb mediates a suppressive effect of p53 on cell transformation. We have also observed that in contrast to LTag, both E1a and EJ-ras cause transformation-related events which are susceptible to suppression by p53. Further studies have revealed that cells expressing E1a are susceptible to p53-mediated apoptosis, while cells expressing EJ-ras are susceptible to p53-induced growth inhibition. We therefore propose that p53 suppresses transformation either by arresting cell growth (mediated by pRb in late G1) or by inducing apoptosis, with the mechanism being determined by the transforming oncoprotein(s).

Adenovirus E1A Proteins↗
PubMed1995

Characterization of subcutaneous microvascular blood flow during tilt table-induced neurally mediated syncope.

OBJECTIVES: This study aimed to characterize subcutaneous blood flow changes during neurally mediated syncope and to determine whether microvasculature oscillation (vasomotion) is characteristically altered in conjunction with syncopal events. BACKGROUND: Marked pallor is commonly associated with neurally mediated syncope. However, little attention has been paid to the evaluation of subcutaneous blood flow and vasomotion in this setting. METHODS: This study utilized laser Doppler flowmetry to assess changes in subcutaneous microvascular blood flow during head-up tilt table testing in 13 patients with syncope and 6 control subjects. Blood flow and vasomotion frequency were measured continuously before, during and after completion of 80 degrees head-up tilt testing (< or = 25-min duration). RESULTS: Among the 13 patients with syncope, tilt testing reproduced syncopal symptoms in 9 (tilt-positive group) but not in 4 (tilt-negative group). None of the six control subjects developed symptoms during testing. Baseline mean subcutaneous blood flow did not differ significantly among the three groups. However, during upright tilt, blood flow gradually diminished in the tilt-positive group, reaching a nadir of 0.8 +/- 0.33 ml/min per 100 g of tissue (mean +/- SD), but remained relatively constant in the tilt-negative group and control subjects. The difference in mean blood flow response to tilt was statistically significant when the tilt-positive group was compared with either the tilt-negative group or control subjects (p < 0.001). Similarly, baseline blood flow oscillation frequency did not differ significantly in the three subgroups (tilt-positive group 0.2 +/- 0.11 Hz; tilt-negative group 0.2 +/- 0.02 Hz; control subjects 0.2 +/- 0.11 Hz). Subsequently, during tilt testing only the tilt-positive group exhibited increased oscillation frequency; oscillation frequency remained essentially constant throughout the tilt test in the tilt-negative group and control subjects (p < 0.001, tilt-positive group vs. either the tilt-negative group or control subjects). CONCLUSIONS: These findings document an expected diminution of subcutaneous blood flow in association with neurally mediated syncope and indicate that characteristic changes in microvasculature oscillation frequency occur in conjunction with syncopal symptoms. To the extent that microvasculature vasomotion is influenced by neural control, the changes in vasomotion frequency are consistent with relative diminution of peripheral sympathetic neural influence during neurally mediated syncopal episodes.

Adolescent↗