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J Webster

Publications and source records attributed to J Webster.

At least 109 records · Page 6Linked to original sources
PubMed1996

Use of G-CSF to Sustain Dose Intensity in Breast Cancer Patients Receiving Adjuvant Chemotherapy: A Pilot Study.

BACKGROUND: Adjuvant chemotherapy for breast cancer is frequently accompanied by neutropenia requiring dose reduction or treatment delay that can potentially compromise therapeutic effectiveness. Recombinant granulocyte-colony stimulating factor (G-CSF) reduces the duration and severity of neutropenia. METHODS: Nineteen patients with newly diagnosed breast cancer receiving adjuvant systemic chemotherapy met criteria for dose reduction or treatment delay due to neutropenia. All were treated with G-CSF. The mean duration of G-CSF therapy was five days. RESULTS: An increase in mean absolute neutrophil count was seen in cycles with G-CSF. Chemotherapy treatment was delayed less often following the use of G-CSF. CONCLUSIONS: Breast cancer patients receiving adjuvant chemotherapy who face treatment delays or dose reductions can continue on full-dose intensity therapy using supportive G-CSF. Prospective trials are needed to accurately measure the impact of G-CSF on dose intensity and long-term disease control.

Journal Article↗
PubMed1996

IGF-I receptor signalling: lessons from the somatotroph.

Insulin-like growth factor 1 (IGF-I) is a major feedback regulator of pituitary GH secretion, with defined actions occurring at both the hypothalamus and pituitary. The IGF-I gene is expressed in the anterior pituitary in a GH-dependent manner thus providing for both endocrine-as well as autocrine-mediated GH regulation. In turn, IGF-I selectively and specifically inhibits GH gene transcription and secretion, its attenuating effects on nascent GH mRNA synthesis being demonstrable within 1 h. Binding of IGF-I to its pituitary cell surface receptor is followed by rapid activation of the intrinsic tyrosine kinase activity of the receptor beta-subunit and phosphorylation of insulin receptor substrate 1 (IRS-1). Structure-function studies of the human IGF-I receptor were performed in stable, GH-secreting transfectants expressing either the cDNA encoding the wild-type (WT) human IGF receptor and exhibiting enhanced IGF-I responsiveness, or cDNAs encoding IGF-I receptor mutants and a truncated, kinase-deficient receptor (952STOP). 950Tyr situated on the submembrane receptor domain was found to be critical for transducing the IGF-I signal to the GH gene. IGF-I failed to suppress GH secretion by signalling endogenous rat IGF-I receptors when hybrid receptors were formed with kinase-deficient human receptors and rat hemi-receptors. This dominant negative effect on hormone secretion was also evidenced when mitogenic IGF-I signals were blocked in vitro and in vivo by these hybrid receptors. Using similar doses of IGF-I, the IGF-I receptor cell transfectants also demonstrated ligand-dependent activation of ERKs in pituitary cells. In conclusion, the pituitary IGF-I receptor mediates the negative feedback regulation of GH. Thus, IGF-I receptor mass may determine GH responses to malnutrition, pregnancy, and refeeding. IGF-I receptor mutations may also prove useful to abrogate the growth of IGF-I-dependent tumors. These structure-function studies of the human IGF-I receptor provide mechanistic insights into both metabolic control of the GH axis, as well as target tissue proliferative characteristics.

Animals↗
PubMed1996

Indomethacin does not attenuate the hypotensive effect of trandolapril.

This is a randomised, double-blind, placebo-controlled, four-way crossover study to determine if indomethacin attenuates the hypotensive effect of trandolapril. Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115) requiring NSAID were recruited. Seventeen completed the study. Three week treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril 2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5 mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98 mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin; 148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo; and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and placebo. There were no significant interactions between trandolapril and indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87). When trandolapril treatments (placebo or with indomethacin) were compared to treatments without trandolapril (placebo or indomethacin), trandolapril lowered clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo); 147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P = 0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered clinic SBP and ambulatory BP, but indomethacin did not attenuate this. Indomethacin had no significant effect on either clinic or ambulatory BP. The antihypertensive effects of trandolapril in this study were modest. Patient selection factors may have contributed to the observed responses, but it seems unlikely from these data that a clinically important drug interaction has occurred.

Adult↗
PubMed1995

Analysis of sevoflurane degradation products in vapor phase samples.

Sevoflurane degradation products were measured by GC-flame ionization detection in vapor phase samples using manual and automated injection methods. Sample handling techniques allowed the transfer and storage of samples for up to 72 h. Compound A, fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether, was the major vapor phase degradation product formed in simulated clinical conditions. Recoveries of 4-32 ppm (v/v) compound A concentrations using the manual method were in the range of 88-117% (n = 12, mean = 102%, R.S.D. = 9%).

Anesthetics↗
PubMed1995

Angiotensin II. Adrenergic sympathetic constrictor action in humans.

BACKGROUND: Angiotensin II (Ang II) facilitates adrenergic neurotransmission in normotensive and hypertensive subjects, whereas angiotensin-converting enzyme inhibitors have been shown to depress circulating catecholamine concentrations in some studies. We investigated the effect of local intra-arterial infusion of Ang II into the brachial artery of healthy volunteers during blockade of postsynaptic alpha-receptors with phentolamine. The response was compared with that seen with Ang II infused during nitroprusside administration at a dose designed to give a dilator response similar to that with phentolamine. METHODS AND RESULTS: Ang II (6.25, 25, and 100 pmol/min) was infused alone and then together with sodium nitroprusside (4 micrograms/min) and phentolamine (40 micrograms/min) in eight healthy volunteers. Forearm blood flow was measured by strain-gauge plethysmography. The percentage reduction in forearm blood flow produced by Ang II 100 pmol/min in the phentolamine-predilated vascular bed was significantly lower than that seen in the sodium nitroprusside-predilated forearm bed (28.1 +/- 2.9% versus 52.9 +/- 4.2%; P = .006). Comparison of the rate of change of blood flow in response to quadrupling doses of Ang II during blockade of alpha-receptors with phentolamine and during nitroprusside administration was calculated from the mean slope of the regression line of log-transformed blood flow versus dose of Ang II. The mean slope during nitroprusside administration (-0.16 +/- 0.025) was significantly greater than that during blockade with phentolamine (-0.098 +/- 0.020) (P = .046). CONCLUSIONS: We conclude that a significant part of the vasoconstrictive action of exogenous Ang II on forearm resistance vessels in humans is sympathetically mediated.

Adult↗
PubMed1995

Body heat transfer during hip surgery using active core warming.

The purpose of this study was to evaluate the effect of core warming on heat redistribution from the core to the periphery as manifested by changes in core, mean skin temperature and mean body heat, investigated in a group of 30 patients undergoing total hip replacement. The control group (n = 10) had no active warming. Core warming was achieved in the humidifier group (n = 10) by using humidified and warmed gases at 40 degrees C, whilst in the oesophageal group (n = 10), an oesophageal heat exchanger was used to achieve active warming. Operating room temperature and relative humidity was standardised. Aural canal and skin temperatures (15 sites) were measured before induction of anaesthesia, at the end of surgery and one hour of recovery after anaesthesia. Mean skin temperatures were calculated for a weighted four and unweighted 15 points, and mean body heat were calculated to quantify the distribution of body heat. Core temperature decreased in the control and the oesophageal groups, but not in the humidifier group at the end of surgery; by mean values +/- SD of 1.9 degrees C +/- 0.6, 1.2 degrees C +/- 0.6 and 0.4 degree C +/- 0.2 degree C, respectively (P < 0.01). Mean skin temperature (MST15) decreased in the control group by 1.0 degree C +/- 1.0, but not in the actively warmed groups where the mean increased by 0.1 degree C +/- 1.4 and 0.2 degree C +/- 0.2 in the oesophageal and humidifier groups, respectively (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Episiotomy at the Royal Women's Hospital, Brisbane: a comparison of practices in 1986 and 1992.

OBJECTIVE: to determine whether the incidence of perineal outcomes, including episiotomy, at the Royal Women's Hospital (RWH) Brisbane reflected trends reported in the literature. DESIGN: retrospective record review. SETTING: RWH Brisbane. PARTICIPANTS: 953 women who delivered vaginally at the RWH in 1986 and 1992. MEASUREMENTS AND FINDINGS: there was a decline in the episiotomy rate from 65% in 1986 to 36% in 1992. This was accompanied by an increase in the incidence of intact perinea and spontaneous perineal tears. There was no difference in the incidence of spontaneous third degree tears. The decline in the incidence of episiotomy was found when other factors, such as parity, were considered, with the exception of operative vaginal delivery, where no difference in the use of episiotomy was found. There was no significant increase in the number of babies with an Apgar score of < 7 at one minute of age, despite a significant reduction in the use of episiotomy when delivering these babies (55% in 1986 and 19% in 1992; P < 0.001). The second stage was significantly longer in 1992 (P < 0.01). KEY CONCLUSIONS: the findings reflect the decline in the incidence of episiotomy reported in the literature. This decline in rate was accompanied by an increase in the length of second stage and in the incidence of both intact perinea and perineal tears. Lowering the incidence of episiotomy did not result in a rise in the rate of babies with an Apgar score of < 7 at one minute.

Adolescent↗
PubMed1995

Alcohol intake and cardiovascular mortality in hypertensive patients: report from the Department of Health Hypertension Care Computing Project.

OBJECTIVE: To determine the benefits and risks of drinking alcohol in treated hypertensives. DESIGN: A prospective study of 6,369 hypertensives (3,161 men) attending primarily hospital clinics in the UK. METHODS: Relative risks both for drinkers compared with non-drinkers and for level of alcohol consumption were calculated for mortality from ischaemic heart disease, stroke, non-circulatory and all causes. RESULTS: At presentation 76% of the men and 48% of the women reported recent alcohol consumption. Compared with drinkers, non-drinkers were older, less likely to smoke and had a higher untreated blood pressure. After adjustment for confounding factors, male drinkers had a reduced risk of stroke mortality and possibly of ischaemic heart disease mortality. Similar results were observed in women for stroke mortality but not for ischaemic heart disease mortality. The trend remained after adjustment for previous cardiovascular disease. In men the lowest risk of ischaemic heart disease mortality occurred at intakes of > 21 units per week and stroke mortality was lowest at 1-10 units per week. Men consuming > 21 units per week had a twofold higher non-circulatory mortality. Total mortality was lowest in men who drank 1-10 units per week. Similar effects of alcohol on cardiovascular mortality were observed in women. CONCLUSIONS: Alcohol intake may reduce stroke mortality in treated hypertensives. Ischaemic heart disease mortality in men may also be reduced, especially at higher intakes ( > 21 units per week). The beneficial effects were offset by increasing incidence of non-circulatory causes of death. Alcohol consumption of 1-10 units per week was associated with the lowest mortality in men.

Adolescent↗
PubMed1995

Human and murine pituitary expression of leukemia inhibitory factor. Novel intrapituitary regulation of adrenocorticotropin hormone synthesis and secretion.

Leukemia inhibitory factor (LIF) gene expression was detected in human fetal pituitary tissue by expression of LIF mRNA transcripts, protein immunocytochemistry, and immunoelectron microscopy. Fetal LIF immunoreactivity colocalized with 30% of ACTH-expressing cells, approximately 20% of somatotrophs, and approximately 15% of non-hormone-expressing cells. LIF was also strongly expressed in normal adult pituitary and in four growth hormone-producing and two ACTH-producing adenomas, but not in eight nonfunctioning pituitary tumors. Culture of fetal cells expressing surface LIF-binding sites demonstrated predominance of in vitro ACTH secretion as compared with other pituitary hormones. In AtT-20 murine cells, LIF (ED50 10 pM) stimulated basal proopiomelanocortin mRNA levels by 40% and corticotropin-releasing hormone-induced ACTH secretion (two- to threefold), as did oncostatin M (ED50 30 pM), a related peptide. ACTH responses were not further enhanced by both cytokines together, which is consistent with their shared receptor. Anti-LIF antiserum neutralized basal and LIF-induced ACTH secretion, suggesting autocrine regulation of ACTH by LIF. The results show that human pituitary cells express the LIF gene and LIF-binding sites, predominantly in corticotrophs. Pituitary LIF expression and LIF regulation of proopiomelanocortin and ACTH reflect an intrapituitary role for LIF in modulating early embryonic determination of specific human pituitary cells and as a paracrine or autocrine regulator of mature ACTH.

Adenoma↗
PubMed1995

Breastfeeding outcomes for women with insulin dependent diabetes.

The incidence of breastfeeding among women with insulin dependent diabetes mellitus (IDDM) has received little attention. During a 17-month period, 19 pregnant women with IDDM attending the prenatal clinic of the Royal Women's Hospital (Brisbane) were recruited into a prospective study to compare their breastfeeding outcomes with a control group of 18 women who were not diabetic (non-IDDM). The incidence of breastfeeding was monitored. At discharge, 63 percent of IDDM and 78 percent of non-IDDM mothers were breastfeeding. At eight weeks, the proportion of each were nearly identical (58 percent and 56 percent respectively), and at three months of age, 47 percent of IDDM mothers and 33 percent of non-IDDM women continued to breastfeed. We conclude that women with IDDM breastfeed at least as commonly and for as long as women without diabetes, despite the fact that infants of the IDDM women were artificially fed more often and began breastfeeding later than infants in the control group. In addition, the IDDM women were more likely to be delivered by Caesarean section (p < 0.0005), to be delivered earlier (p < 0.0002), and their babies more likely to be admitted to the special care nursery (p < 0.0005).

Adult↗
PubMed1995

Tissue-specific, temporally regulated expression mediated by the proximal ovine beta-lactoglobulin promoter in transgenic mice.

The ovine beta-lactoglobulin gene is expressed abundantly in the mammary gland. This study determines whether the ovine beta-lactoglobulin promoter is sufficient for targeting tissue-specific expression in transgenic mice. To address this, the expression profile of an ovine beta-lactoglobulin promoter driven bacterial chloramphenicol acetyltransferase reporter construct was analysed. Comparison of the expression frequency of this hybrid transgene to that of a genomic beta-lactoglobulin transgene indicates that additional sequences, downstream of the promoter, are required for position-independent expression in transgenic mice. Nevertheless, the hybrid transgene was expressed specifically in the mammary gland. Furthermore, the hybrid transgene was expressed in the appropriate temporal pattern during pregnancy and lactation. Thus, the proximal promoter of the ovine beta-lactoglobulin gene contains sufficient sequence information to target expression to the mammary. This construct constitutes the basis for a compact mammary expression vector.

Animals↗
PubMed1995

Ventilator circuitry in neonatal intensive care: extending the period between changes from 4 to 7 days. A pilot study.

OBJECTIVE: To determine the effect of increasing the time span between changes of disposable ventilator tubing from 4 to 7 days. DESIGN: A prospective non-randomised study comparing levels of bacterial colonisation amongst babies who had ventilator circuits changed on either the 4th or 7th day. Data was collected sequentially with data collection from the '4-day group' preceding data collection from the '7-day group'. SETTING: A tertiary neonatal intensive care nursery. PATIENTS: All babies requiring ventilation at the time when data collection was possible. Ten babies were included in the first group (4 days) and 33 babies in the second group. INTERVENTIONS: Inspiratory and expiratory lines were swabbed and water from the humidifier trap sampled before the line was changed at either 4 or 7 days. Results of routine endotracheal aspirates, taken before and after the change of circuitry, were noted. MAIN OUTCOME MEASURE: The level of bacterial contamination of ventilator circuits. RESULTS AND CONCLUSIONS: In this small sample, no differences were found in terms of bacterial colonisation of ventilator lines. This has resulted in a change of practice in the hospital and a cost saving of over $15,000.

Equipment Contamination↗
PubMed1995

Decreased axial and peripheral bone density in patients taking long-term warfarin.

Impaired vitamin K metabolism is associated with under-carboxylation of the non-collagenous bone-matrix protein osteocalcin, which is required in its fully carboxylated state for normal bone formation. Post-menopausal women have under-carboxylation of osteocalcin which increases with age and is marked in the elderly. A similarly marked degree of impaired carboxylation occurs during coumarin therapy, and a key question is whether this may lead to accelerated loss of bone mass which is clinically important. We measured axial and peripheral bone mineral density (BMD) in 40 male patients on warfarin and 40 controls individually matched for age, disease and other drug therapy. A consistent trend for reduced BMD at all sites was observed in the warfarin-treated patients. This was particularly marked in the cancellous bone at the distal radius (9% reduction, p = 0.023) and at the cancellous rich lumbar spine site (10.4% reduction, p < 0.004). No significant relationship was observed between warfarin dose, International Normalized Ratio (INR) or duration of therapy and bone density. Because of the biochemical similarity, this study provides a new lead on post-menopausal osteoporosis, and supports the hypothesis that impaired carboxylation of osteocalcin plays a role in the pathogenesis of bone loss in the elderly through deficiency in vitamin K metabolism.

Absorptiometry, Photon↗
PubMed1995

Good grieving--an intervention program for grieving children.

PURPOSE/OBJECTIVES: To describe a program for grieving children including the agenda, activities, and logistics of organizing the program. DATA SOURCES: Clinical observations and evaluations from the program; literature review. DATA SYNTHESIS: A series of four seasonal programs were designed to promote a child's normal grieving process and enhance adjustment to the loss. Programs are cyclic, children are grouped by age, and activities are intended to promote expression of feelings, understanding of the loss, and good coping skills. A concurrent program for caregivers facilitates family communication and support. CONCLUSIONS: The program demonstrated positive behavioral changes in grieving children and provides a model for other nurses to use in organizing similar programs. IMPLICATIONS FOR NURSING PRACTICE: Nurses should be familiar with key elements of children's grief and incorporate this into their practice, especially when caring for terminally ill patients who have children.

Adaptation, Psychological↗
PubMed1995

Risk factors for ischaemic heart disease and stroke mortality in young and old hypertensive patients.

We investigated the predictors of cardiovascular mortality at different ages in a longitudinal study of 10186 hypertensive patients attending clinics in the UK. There were 7374 patients (51% were men) < 60 years of age and 2799 patients (44% men) were > or = 60 years. For IHD death the age-adjusted relative risks (RRs) and 95% confidence intervals (CI) for a 1 mmol/l increase in cholesterol were RR = 1.17 (1.07, 1.27) (men) and RR = 1.22 (1.12, 1.33) (women). The RRs for stroke were 0.99 (men) and 1.07 (women). In men and younger women, urea and smoking were important predictors of IHD and stroke death. Age differences were present in women for both urea and smoking. For IHD in women, smoking: RR = 2.65 (1.80, 3.89) (< 60 years) and RR = 1.38 (1.01, 1.88) (> or = 60 years). For stroke in women, smoking: RR = 2.03 (1.23, 3.35) (< 60 years) and RR = 1.06 (0.70, 1.61) (> or = 60 years). We conclude that urea and smoking are important risk factors for stroke and IHD death in hypertensive women aged < 60 years, but are less important in those aged over 60 years. Cholesterol predicted IHD death in all men and women, but did not predict stroke death.

Adult↗
PubMed1994

Domestic violence in pregnancy. A prevalence study.

OBJECTIVE: To determine the extent of physical and psychological abuse of pregnant women in an Australian population. DESIGN: All women attending the public prenatal clinic of the Royal Women's Hospital (Brisbane) between 23 November and 18 December 1992 were interviewed and asked to complete a self-report questionnaire on their history of abuse. RESULTS: Of 1014 women eligible to enter the study, 301 (29.7%) reported a history of abuse. Fifty-nine (5.8%) had been abused during the pregnancy. The proportion of women admitting to abuse rose over the duration of pregnancy to 8.9% at 36 weeks. Medical treatment was sought for injuries related to domestic violence by 31% of those who reported abuse during the pregnancy. Marital status and education were both significantly associated with the prevalence of abuse. CONCLUSION: Domestic violence towards women may continue or be initiated during pregnancy. RECOMMENDATION: Because most women will not reveal details about their experience of violence in the home unless asked, a relationship history should be included at the first visit along with medical, obstetric and other histories.

Adult↗
PubMed1994

A comparison of cabergoline and bromocriptine in the treatment of hyperprolactinemic amenorrhea. Cabergoline Comparative Study Group.

BACKGROUND: Cabergoline is a long-acting dopamine-agonist drug that suppresses prolactin secretion and restores gonadal function in women with hyperprolactinemic amenorrhea. We designed a study to compare its safety and efficacy with those of bromocriptine, which has been the standard therapy. METHODS: A total of 459 women with hyperprolactinemic amenorrhea were treated with either cabergoline (0.5 to 1.0 mg twice weekly) or bromocriptine (2.5 to 5.0 mg twice daily), administered in a double-blind fashion for 8 weeks and subsequently in an open fashion for 16 weeks, during which adjustments in the dose were made according to the response. Of the 459 women, 279 had microprolactinomas, 3 had macroprolactinomas, 1 had a craniopharyngioma, 167 had idiopathic hyperprolactinemia, and the remainder had an empty sella. Clinical and biochemical status was assessed at 2-week intervals for 8 weeks and monthly thereafter for a total of 6 months, with an additional assessment at 14 weeks. RESULTS: Stable normoprolactinemia was achieved in 186 of the 223 women treated with cabergoline (83 percent) and 138 of the 236 women treated with bromocriptine (59 percent, P < 0.001). Seventy-two percent of the women treated with cabergoline and 52 percent of those treated with bromocriptine had ovulatory cycles or became pregnant during treatment (P < 0.001). Amenorrhea persisted in 7 percent of the cabergoline-treated women and 16 percent of the bromocriptine-treated women. Adverse effects were recorded in 68 percent of the women taking cabergoline and 78 percent of those taking bromocriptine (P = 0.03); 3 percent discontinued taking cabergoline, and 12 percent stopped taking bromocriptine (P < 0.001) because of drug intolerance. Gastrointestinal symptoms were significantly less frequent, less severe, and shorter-lived in the women treated with cabergoline. CONCLUSIONS: Cabergoline is more effective and better tolerated than bromocriptine in women with hyperprolactinemic amenorrhea.

Adolescent↗