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Biomedical subjects

P Sargent

Publications and source records attributed to P Sargent.

15 recordsLinked to original sources
PubMed2004

Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis.

PURPOSE: The modulation of fluorouracil (FU) by folinic acid (leucovorin [LV]) has been shown to be effective in terms of tumor response rate in patients with advanced colorectal cancer, but a meta-analysis of nine trials previously published by our group failed to demonstrate a statistically significant survival difference between FU and FU-LV. We present an update of the meta-analysis, with a longer follow-up and the inclusion of 10 newer trials. PATIENTS AND METHODS: Analyses are based on individual data from 3,300 patients randomized in 19 trials on an intent-to-treat basis. Two trials had multiple comparisons, leading to a total of 21 pair-wise comparisons. FU doses were similar in both arms in 10 pair-wise comparisons, 15% to 33% higher in the FU-alone arm in six comparisons, and more than 66% higher in five comparisons. RESULTS: Overall analysis showed a two-fold increase in tumor response rates (11% for FU-LV v 21% for FU-LV v 11% for FU [corrected] alone; odds ratio, 0.53; 95% CI, 0.44 to 0.63; P <.0001) and a small but statistically significant overall survival benefit for FU-LV over FU alone (median survival, 11.7 v 10.5 months, respectively; hazards ratio, 0.90; 95% CI, 0.87 to 0.94; P =.004), which were primarily seen in the first year. We observed a significant interaction between treatment benefit and dose of FU, with tumor response and overall survival advantages of FU-LV over FU-alone being restricted to trials in which a similar dose of FU was prescribed in both arms. CONCLUSION: This updated analysis demonstrates, on a large data set, that FU-LV improves both response rate and overall survival compared with FU alone and that this benefit is consistent across various prognostic factors.

Aged↗
PubMed2004

Preliminary study of shunt related death in paediatric patients.

Hydrocephalus is a condition commonly encountered in paediatric and adult neurosurgery and cerebrospinal fluid (CSF) shunting remains the treatment of choice for many cases. Despite improvements in shunt technology and technique, morbidity and mortality remain. The incidence of early shunt obstruction is high with later failures seen less frequently. This review aims to examine mortality associated with mechanical failure of CSF shunts within Queensland. Neurosurgical and Intensive Care databases were reviewed for cases of mortality associated with shunt failure. Eight cases were identified between the years of 1992 and 2002 with the average age at death 7.7 years. Deaths occurred on average 2 years after last shunt revision. Seven of the eight patients lived outside the metropolitan area. Shunting remains an imperfect means of treating hydrocephalus. Mortality may be encountered at any time post surgery and delays to surgical intervention influence this. Alternative measures such as third ventriculostomy or the placement of a separate access device should be considered. In the event of emergency, a spinal needle could be used to access the ventricle along the course of the ventricular catheter.

Cerebrospinal Fluid Shunts↗
PubMed2001

Risk behaviours of young Indo-Chinese injecting drug users in Sydney and Melbourne.

OBJECTIVE: To investigate patterns of drug use and injection-related risk behaviours among young Indo-Chinese injecting drug users (IDUs). METHOD: Cross-sectional survey. A structured questionnaire was administered to 184 Indo-Chinese IDUs aged 15 to 24 in Sydney and Melbourne. Participants were recruited using snowball sampling techniques; measures included patterns of heroin and other drug use, injection-related risk behaviours, perceived susceptibility to HIV and HCV infection and access to services. RESULTS: Despite perceived high availability of sterile injecting equipment, 36% had ever shared a needle and syringe and 22% had done so in the preceding month. Lifetime sharing was significantly associated with duration of injecting, history of incarceration and residence in Sydney. Sharing of injecting paraphernalia other than needles and syringes was also common, with young women and Sydney residents significantly more likely to report sharing equipment in the preceding month. CONCLUSIONS: Young Indo-Chinese IDUs are at high risk of infection with hepatitis C and other blood-borne viruses. Results indicate an urgent need for culturally appropriate and sustainable risk reduction programs which specifically target this population. IMPLICATIONS: Health services must respond swiftly to implement effective blood-borne virus prevention programs for young Indo-Chinese IDUs. Failure to do so may sustain the current epidemic of hepatitis C among IDUs.

Adolescent↗
PubMed2000

Too many memories.

Explore the source record for details and available documents.

Alzheimer Disease↗
PubMed1998

Efficient construction of a large nonimmune phage antibody library: the production of high-affinity human single-chain antibodies to protein antigens.

A large library of phage-displayed human single-chain Fv antibodies (scFv), containing 6.7 x 10(9) members, was generated by improving the steps of library construction. Fourteen different protein antigens were used to affinity select antibodies from this library. A panel of specific antibodies was isolated with each antigen, and each panel contained an average of 8.7 different scFv. Measurements of antibody-antigen interactions revealed several affinities below 1 nM, comparable to affinities observed during the secondary murine immune response. In particular, four different scFv recognizing the ErbB2 protein had affinities ranging from 220 pM to 4 nM. Antibodies derived from the library proved to be useful reagents for immunoassays. For example, antibodies generated to the Chlamydia trachomatis elementary bodies stained Chlamydia-infected cells, but not uninfected cells. These results demonstrate that phage antibody libraries are ideally suited for the rapid production of panels of high-affinity mAbs to a wide variety of protein antigens. Such libraries should prove especially useful for generating reagents to study the function of gene products identified by genome projects.

Animals↗
PubMed1997

Effect of paroxetine and nefazodone on 5-HT1A receptor sensitivity.

Animal experimental studies suggest that the therapeutic effect of selective serotonin re-uptake inhibitors (SSRIs) may involve neuroadaptive changes in pre- and post-synaptic serotonin1A (5-HT1A) receptors. We used the endocrine and hypothermic responses to the 5-HT1A receptor agonist, gepirone (20 mg orally), to assess 5-HT1A receptor sensitivity in 37 healthy male volunteers who were studied before and following random double-blind, allocation to treatment with paroxetine, nefazodone or placebo for 17 days. Following antidepressant drug treatment, hypothermic responses to gepirone were markedly decreased by paroxetine but only slightly diminished by nefazodone. Paroxetine also lowered the growth hormone and cortisol responses to gepirone. There was no change in either hypothermic or endocrine response following placebo treatment. Our results suggest that paroxetine treatment produces a striking attenuation of measures of both pre- and post-synaptic 5-HT1A receptor function. Nefazodone appears to decrease the sensitivity of 5-HT1A autoreceptors to some extent and this effect may contribute to its antidepressant activity.

Adult↗
PubMed1996

Increased prolactin response to buspirone in chronic fatigue syndrome.

We studied the endocrine and subjective responses that followed acute administration of the 5-HT1A receptor agonist buspirone (0.5 mg/kg orally) in 11 male patients with chronic fatigue syndrome (CFS) and a group of matched healthy controls. Patients with CFS had significantly higher plasma prolactin concentrations and experienced more nausea in response to buspirone than did controls. However, the growth hormone response to buspirone did not distinguish CFS patients from controls. Our data question whether the enhancement of buspirone-induced prolactin release in CFS is a consequence of increased sensitivity of post-synaptic 5-HT1A receptors. It is possible that the increased prolactin response to buspirone in CFS could reflect changes in dopamine function.

Adolescent↗
PubMed1996

The effects of paroxetine and nefazodone on sleep: a placebo controlled trial.

We studied the effect of acute (1 day) and subacute (16 days) administration of the new antidepressant, nefazodone (400 mg daily), and the selective serotonin re-uptake inhibitor (SSRI), paroxetine (30 mg daily), on the sleep polysomnogram of 37 healthy volunteers using a random allocation, double-blind, placebo-controlled design. Compared to placebo, paroxetine lowered rapid eye movement (REM) sleep and increased REM latency. In addition, paroxetine increased awakenings and reduced Actual Sleep Time and Sleep Efficiency. In contrast, nefazodone did not alter REM sleep and had little effect on measures of sleep continuity. We conclude that in contrast to typical SSRIs, nefazodone administration has little effect on sleep architecture in healthy volunteers.

Adolescent↗
PubMed1995

Motor cortical activity in a context-recall task.

A monkey was trained to respond on the basis of the serial position of a test stimulus in a sequence. First, three stimuli were presented successively on a circle. Then one of them (except the last) changed color (test stimulus) and served as the go signal: The monkey was required to produce a motor response in the direction of the stimulus that followed the test stimulus. When the test stimulus was the second in the sequence, there was a change in motor cortical activity from a pattern reflecting the direction of this stimulus to the pattern associated with the direction of the motor response. This change was abrupt, occurred 100 to 150 milliseconds after the go signal, and was evident both in the activity of single cells and in the time-varying neuronal population vector. These findings identify the neural correlates of a switching process that is different from a mental rotation described previously.

Animals↗
PubMed1993

Cyclosporin therapy in steroid-dependent nephrotic syndrome.

Five children with multiple relapsing steroid-dependent nephrotic syndrome were treated with continuous cyclosporin for periods ranging from 18 to 48 months. Renal biopsy showed mild mesangial proliferation in three of the children and minimal change in two. All children previously had been treated with cyclophosphamide. Cyclosporin was started during remission at 5 mg/kg per day. If a relapse occurred the dose was increased until a trough blood level of 100-250 ng/mL (HPLC) was achieved. In the initial 12 months of treatment, the mean number of relapses decreased from 6.4 +/- 0.54 (s.d.) per annum to 1.6 +/- 1.3 per annum (P < 0.01). Cyclosporin was effective in maintaining long-term remission in four of the five patients. Side effects included hypertrichosis (5) and gum hyperplasia (1). The mean creatinine clearance decreased from 126 +/- 16 to 97 +/- 22 mL/min per 1.73 m2 (P = NS). A renal biopsy in all five patients after 12 months therapy showed no nephrotoxicity. A further biopsy in one patient after 4 years therapy showed interstitial fibrosis. Cyclosporin should be considered in children with steroid-dependent nephrotic syndrome who show signs of steroid toxicity and have only a short remission period after cyclophosphamide. Serial renal biopsies are recommended if prolonged therapy is used.

Adolescent↗
PubMed1979

Specific cellular defects in patients with Fanconi anemia.

Measurements of plating efficiency, accumulation of metaphases and generation times have shown that fibroblast from patients with Fanconi anemia (FA) have decreased probability of completing a further division after successful mitosis. Thus FA cells show decreased growth rates and increased generation times. We have also measured the survival of FA fibroblasts and lymphoblasts after treatment with a variety of mutagens. All FA cells show an increased sensitivity to drugs such as MMC and psoralen plus long wave length UV which cause DNA interstrand crosslinks. FA strains show varying degrees of sensitivity to these drugs and the extent of this sensitivity seems to be characteristic of each patient. FA cells are equal to controls in their sensitivity to other alkylating agents such as ethyl methane sulfonate, N-methyl-N1-nitro-N-nitrosoguanidine and actinomycin D. Both the decreased growth and increased drug sensitivity may result from defect in DNA replication or repair.

Adolescent↗