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Biomedical subjects

J Fawcett

Publications and source records attributed to J Fawcett.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effect of metabolic acidosis on the insulin-like growth factor-I system and cathepsins B and L gene expression in the kidney.

Prolonged acidemia causes growth retardation and muscle wasting, in part because of reduced food intake, depressed growth hormone secretion, and low serum insulin-like growth factor-I (IGF-I) levels. Paradoxically, in the rat kidney, protein synthesis increases, cathepsin B and L activities decline, protein degradation falls, and the kidneys enlarge. Because IGF-I has been implicated as a cause of renal hypertrophy in a variety of conditions, we examined whether IGF-I could be playing a role in the renal hypertrophy of acidosis. Rats were gavaged with NH4Cl or water for 4 days. Water-gavaged rats either were pair-fed with the NH4Cl-loaded rats (pH 7.15) or were given free access to food and served as controls. After 2 days, kidney weight and IGF-I mRNA levels did not differ between the groups, but kidney IGF-I protein levels were significantly higher in the acidotic rats. After 4 days the kidneys of the acidotic rats were significantly larger than the kidneys in both control groups but the renal IGF-I levels did not differ between the groups. It is notable that renal cathepsin B and L mRNA levels were reduced by 30% to 50% at both times. Thus the transient increase in renal IGF-I protein levels in acidosis, before the onset of hypertrophy, suggests that IGF-I may play a role in initiating kidney growth. Furthermore, it appears that reduced cathepsin B and L gene expression is a cause of the low renal cathepsin activity seen in acidosis. This likely contributes to the depressed renal proteolysis caused by acidosis.

Acid-Base Equilibrium↗
PubMed2000

The management challenges of chronic pain: the role of antidepressants.

Chronic pain is both difficult for patients to tolerate and for clinicians to treat effectively. It differs from other types of pain in etiology and impact, which in turn affects the duration and modalities of treatment options. Forty years of research have confirmed the efficacy of antidepressant agents in the management of chronic pain, yet these agents are used inadequately. A significant amount of evidence supports the use of the traditional tricyclic antidepressants (TCAs) in the management of chronic pain, but because of their acute synaptic effects on multiple, nontherapeutic receptor systems, they are associated with numerous undesirable side effects. The newer selective serotonin reuptake inhibitors (SSRIs) have, comparatively, only serotonin-receptor-mediated side effects. These agents have not been thoroughly studied in the treatment of chronic pain. Moreover, because SSRIs impact reuptake of only one monoamine system, it is plausible that they may be less efficacious than the TCAs in treating chronic pain. Venlafaxine, the first agent in the new class of serotonin (5-HT)-norepinephrine (NE) reuptake inhibitors, is unique because it inhibits reuptake of both 5-HT and NE (and to a lesser extent dopamine), as do some of the TCAs; however, it accomplishes this without affecting other nontherapeutic receptors. Venlafaxine is at least as effective as the TCAs, but is more tolerable, because it lacks the receptor-mediated side effects common to the TCAs. The unique characteristics of venlafaxine, including minimal cytochrome P-450 drug interaction, may make it a particularly useful antidepressant in the adjunctive treatment of chronic pain.

Antidepressive Agents↗
PubMed2000

Use of adjunctive therapy to heal a diabetic amputation site.

Diabetes can result in a range of complications, and is responsible for many lower limb amputations. This case report discusses a diabetic patient with a complex, non-healing wound following amputation of the foot. A number of adjunctive therapies were used to promote healing, and led to the complete healing of the wound.

Aged↗
PubMed2000

Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression.

BACKGROUND: The goal was to examine predictors of relapse during continuation/maintenance treatment of major depression that had remitted following 12 to 14 weeks of fluoxetine therapy. METHOD: The study utilizes data collected in a collaborative clinical trial including patients with DSM-III-R major depression at 5 university-affiliated outpatient psychiatry clinics. Three hundred ninety-five patients who remitted with fluoxetine therapy were randomly assigned to 1 of 4 treatments: fluoxetine for 14 weeks followed by placebo for 36 weeks, fluoxetine for 38 weeks followed by placebo for 12 weeks, fluoxetine for 50 weeks, or placebo for 50 weeks. Cox proportional hazard models were used to identify predictors of time to relapse. RESULTS: In addition to the previously reported longitudinal pattern of response during acute treatment, neurovegetative symptom pattern was a predictor of fluoxetine benefit compared with placebo. Greater chronicity predicted poorer survival, which was not differential by treatment. The most robust advantage of fluoxetine was seen for patients with endogenous vegetative symptoms, chronic depression, and acute treatment response characterized by onset in the third week or later and persistence of response once attained. CONCLUSION: Both nonspecific pattern of response and neurovegetative symptoms characteristic of atypical depression were predictive of lack of fluoxetine efficacy in continuation/ maintenance treatment. These findings have importance for both clinical management and analyses of future maintenance trials.

Adult↗
PubMed2000

Pharmacological treatments for alcoholism: revisiting lithium and considering buspirone.

OBJECTIVE: Previous research has suggested that both lithium and buspirone could lessen alcoholics' desire to drink as well as reduce the actual amounts of alcohol consumed. The purpose of this study was to compare lithium and buspirone monotherapy with placebo on outcomes of abstinence, alcohol quantity consumed, treatment retention and compliance, and medication side effects. METHODS: We conducted a randomized, double-blind, placebo-controlled, three-arm parallel group, clinical trial that compared lithium and buspirone with placebo in 156 alcohol-dependent men. RESULTS: Study retention rates for the three treatment groups at 3 and 6 months, respectively, were 61% and 46% for lithium, 44% and 27% for buspirone, and 52% and 38% for placebo (p = NS, for 3 and 6 months). Overall abstinence rates were 28% and 19% at 3 and 6 months, respectively. However, mean daily quantities of alcohol consumed and percentage of drinking days decreased significantly (p < 0.0001) over time in all treatment groups. Differential improvement was seen only for the decrement in quantity consumed in the buspirone group, compared with the placebo group, but only at a trend level (p = 0.07). According to pill counts, compliance did not differ significantly among the treatment groups. CONCLUSIONS: These results do not support the hypothesis that either lithium or buspirone, compared with placebo, produces differential reductions in alcohol consumption. The results suggest the need to enhance treatment retention to maximize outcomes.

Adult↗
PubMed1999

Reducing the risk of major elective surgery: randomised controlled trial of preoperative optimisation of oxygen delivery.

OBJECTIVES: To determine whether preoperative optimisation of oxygen delivery improves outcome after major elective surgery, and to determine whether the inotropes, adrenaline and dopexamine, used to enhance oxygen delivery influence outcome. DESIGN: Randomised controlled trial with double blinding between inotrope groups. SETTING: York District Hospital, England. SUBJECTS: 138 patients undergoing major elective surgery who were at risk of developing postoperative complications either because of the surgery or the presence of coexistent medical conditions. INTERVENTIONS: Patients were randomised into three groups. Two groups received invasive haemodynamic monitoring, fluid, and either adrenaline or dopexamine to increase oxygen delivery. Inotropic support was continued during surgery and for at least 12 hours afterwards. The third group (control) received routine perioperative care. MAIN OUTCOME MEASURES: Hospital mortality and morbidity. RESULTS: Overall, 3/92 (3%) preoptimised patients died compared with 8/46 controls (17%) (P=0.007). There were no differences in mortality between the treatment groups, but 14/46 (30%) patients in the dopexamine group developed complications compared with 24/46 (52%) patients in the adrenaline group (difference 22%, 95% confidence interval 2% to 41%) and 28 patients (61%) in the control group (31%, 11% to 50%). The use of dopexamine was associated with a decreased length of stay in hospital. CONCLUSION: Routine preoperative optimisation of patients undergoing major elective surgery would be a significant and cost effective improvement in perioperative care.

Aged↗
PubMed1999

Testing a theory for health-related quality of life in cancer patients: a structural equation approach.

The purpose of this study was to test a Roy Adaptation Model-based theory of health-related quality of life in patients with newly diagnosed cancer. Using a structural equation model, health-related quality of life (HRQOL) was regarded as a latent variable measured by 4 empirical indicators representing the 4 biopsychosocial response modes of the Roy Adaptation Model (RAM). The response modes are physiologic, self-concept, interdependence, and role function. These were empirically represented by physical symptoms, affective status, social support, and functional support, respectively. In this secondary analysis, 3 RAM propositions were tested in a sample of 375 newly diagnosed postsurgical cancer patients 60 years and over. These were: (a) that the 4 response modes are interrelated; (b) that environmental stimuli of gender, race, age, income, marital status, cancer treatment, and severity of illness influence the biopsychosocial response modes; and (c) that the biopsychosocial responses soon after diagnosis predict biopsychosocial responses 3 months later. The analyses did not support the proposition that all 4 response modes were interrelated. The results, however, revealed that severity of illness and adjuvant cancer treatment had the strongest association with the biopsychosocial responses and should be considered the focal environmental stimuli. The remaining environmental stimuli can be considered contextual. Also, the proposition that initial biopsychosocial responses predicted later responses was supported.

Adaptation, Psychological↗
PubMed1999

Differences in the cellular processing of AspB10 human insulin compared with human insulin and LysB28ProB29 human insulin.

Cellular metabolism studies were performed comparing human insulin with two rapid-acting analogs, LysB28ProB29 insulin (LysPro) and AspB10 insulin (B10-Asp). B10-Asp bound to isolated hepatocytes at 37 degrees C to a greater extent than LysPro or native insulin, which were equivalent. The rate of degradation was similar for the three materials, resulting in a significant reduction in the degraded/bound ratio for the B10 analog. The processing of membrane-bound material was examined by incubating cells with hormone at 4 degrees C, removing unbound insulin, and incubating the cells at 37 degrees C. Again, binding was greater for B10-Asp versus LysPro or native insulin, with a reduction in the degraded/bound ratio. Hormone internalization and processing was examined by an acid wash of cells incubated with 125I(A14)-labeled hormone to remove surface-bound materials. The processing rate was slower for B10-Asp versus LysPro or native insulin. Cell extraction and examination on molecular-sieve chromatography confirmed that B10-Asp was processed at a slower rate than either LysPro or native insulin. Intact B10-Asp was found in the cell after 4 hours, whereas all native insulin and LysPro were degraded by 90 to 120 minutes. B10-Asp also caused a greater incorporation of thymidine into DNA in cultured cells than LysPro or native insulin, which were similar. These data show that the cellular processing of LysPro is essentially identical to that of native insulin. However, B10-Asp has markedly different properties and is processed much more slowly. The prolonged cell residence time of B10-Asp could contribute to its greater effects on cell growth and mitogenesis.

Animals↗
PubMed1999

Fluoxetine efficacy in menopausal women with and without estrogen replacement.

UNLABELLED: A gradual decline in estrogen levels after the age of 40 may contribute to a higher rate of depression in women over 45 years of age. Estrogen replacement therapy (ERT) has been shown to produce cognitive and mood-enhancing effects in women and may facilitate antidepressant activity. METHODS: We examined the efficacy rates in women on ERT > or = 45 years (n = 40) compared to women > or = 45 years not on ERT (n = 132) and to women < 45 years (n = 396) and to men (n = 262) with major depression during fluoxetine 20 mg daily up to 8 weeks. Remitters with a HAM-D17 score < or = 7 from week 9 to 12 were then treated up to 1-year in a placebo-controlled, relapse-prevention trial. RESULTS: Efficacy rates were similar in women > or = 45 years on ERT when compared to women > or = 45 years taking fluoxetine alone, and when compared to women < 45 years and men taking fluoxetine. A Kaplan-Meier survival analysis in fluoxetine responders treated up to 26 weeks showed a somewhat greater relapse rate in women > or = 45 years taking ERT compared to other treatment groups (P < 0.06). LIMITATIONS: This study was retrospective nature and ERT was given in an uncontrolled fashion: 63% of women received estrogen alone while 37% also took intermittent progesterone. Other variables include the absence of hormonal documentation of menopausal status, no direct assessment of ERT compliance and the use of fixed-dose fluoxetine 20 mg daily. CONCLUSION: In contrast to prior reports suggesting that ERT may facilitate antidepressant activity, we observed similar efficacy in depressed women > or = 45 years taking fluoxetine plus ERT compared to those taking fluoxetine alone.

Antidepressive Agents, Second-Generation↗
PubMed1999

Blood pressure changes during short-term fluoxetine treatment.

Recent reports of sustained hypertension in some patients receiving venlafaxine have rekindled concerns about antidepressant-induced hypertension. This study examined sitting and standing systolic and diastolic blood pressure, pulse rate, and rate of sustained hypertension in 796 depressed patients (mean +/- SD age, 40 +/- 11 years) taking fluoxetine 20 mg daily for up to 12 weeks. A modest reduction in sitting and standing systolic (p < 0.001) and diastolic (p < 0.001) blood pressure measures were observed in the entire patient sample. Patients with pretreatment diastolic blood pressure < 60 mmHg (N = 32) showed a modest increase in mean diastolic blood pressure (p < 0.001), whereas patients with pretreatment diastolic blood pressure > or = 90 mmHg and < or = 95 mmHg (N = 57) had a modest reduction in mean diastolic blood pressure (p < 0.001). Patients with preexisting, stable cardiovascular disease (including hypertension) (N = 35) showed no significant blood pressure change (p = not significant). Of the patients receiving fluoxetine, 1.7% had sustained hypertension for > or = 3 consecutive clinic visits-a rate significantly lower than that previously reported with venlafaxine (4.8%) (chi2 = 13.3, p < 0.001) and similar to that previously seen with placebo (2.1%). In conclusion, these data demonstrate a low rate of sustained hypertension (1.7%) during short-term fluoxetine treatment.

Adolescent↗
PubMed1999

Treatment attrition among alcohol-dependent men: is it related to novelty seeking personality traits?

"Dropouts" are a major concern when monitoring treatment efficacy in clinical trials. Alcohol-dependent patients are especially prone to discontinuing treatment, perhaps because of impulsive behavior. The Tridimensional Personality Questionnaire (TPQ) measures a trait-like quality, novelty seeking, which may reflect impulsiveness. We tested the hypotheses that higher TPQ Novelty Seeking subscale scores would be associated with increased rates of treatment dropout and increased risk for dropping out earlier. A total of 170 alcohol-dependent men who participated in a double-blind, placebo-controlled pharmacotherapeutic trial for decreasing relapse drinking completed the TPQ and were monitored until treatment dropout. Logistic regression and Cox proportional hazards models were used to (1) describe the relationship between the TPQ Novelty Seeking score and the dichotomous outcome variable, treatment dropout; and (2) assess the effects of a number of potential confounding covariates on the relationship between the risk factor, novelty seeking, and the time to the outcome event. The mean Novelty Seeking score was significantly higher among study dropouts compared with nondropouts (p = 0.003). Higher Novelty Seeking scores were associated with a higher adjusted odds ratio for dropping out (adjusted odds ratio = 1.07, 95% confidence interval [CI] = 1.00-1.15) and a higher adjusted hazard rate for dropping out earlier (adjusted hazard rate = 1.05, 95% CI = 1.00-1.09). The TPQ Novelty Seeking subscale score may identify a subgroup of alcohol-dependent men who are at risk for dropping out of treatment. This information may be useful for developing treatment plans to encourage these high-risk patients to remain in treatment.

Adult↗
PubMed1999

Using CQI to prevent the placebo effect from causing failed clinical trials.

One of the greatest obstacles to bringing drugs to market is one of the most complex--the human mind. Despite the billions invested in R&D, a fundamental issue in drug development is that most patients' responses are enhanced or affected by the "placebo effect." An ongoing methodology for reducing the impact of placebo effect should be built into the clinical study design at the outset based on a continuous quality improvement model. A CQI program that requires continuous evaluation of study participant data and rater training is a way to improve study performance and, therefore, ensure more valid studies and reliable outcomes.

Controlled Clinical Trials as Topic↗
PubMed1999

A resource kit for women with breast cancer: development and evaluation.

PURPOSE/OBJECTIVES: To describe the development and evaluation of the Resource Kit for Women With Breast Cancer, designed to facilitate adaptation to diagnosis, treatment, and recovery. DATA SOURCES: Distributed to more than 200 women with newly diagnosed breast cancer. Derived from the Roy Adaptation Model of Nursing and the literature. DATA SYNTHESIS: The kit may be helpful, particularly for women who are too overwhelmed by their situations to retain the vast amount of new information to which they are exposed. CONCLUSIONS: The kit has the potential to assist women to adapt physically, emotionally, functionally, and interpersonally by concisely combining numerous relevant resources in one place, thereby facilitating the location and review of specific information. IMPLICATIONS FOR NURSING PRACTICE: The kit is a complete package that can be used independently of any professional support as a guide for women during individualized professional telephone support or as an adjunct to formal breast cancer support groups.

Adaptation, Psychological↗
PubMed1998

Amplification of DNA sequences from chromosome 19q13.1 in human pancreatic cell lines.

Conventional cytogenetics and comparative genomic hybridization (CGH) were utilized to identify recurrent chromosomal imbalances in 12 pancreatic adenocarcinoma cell lines. Multiple deletions and gains were observed in all cell lines. Losses affecting chromosomes or chromosome arms 9p, 13, 18q, 8p, 4, and 10p and gains involving chromosome arms or bands 19q13.1, 20q, 5p, 7p, 11q, 3q25-qter, 8q24, and 10q were commonly observed. Interestingly, 19 distinct sites of high-level amplification were found by CGH. Recurrent sites involved 19q13.1 (6 cases), 5p (3 cases), and 12p and 16p (2 cases). Amplification of KRAS2 was demonstrated in 2 cell lines and that of ERBB2 in another. To define the occurrence of chromosome 19 amplification further, two-dimensional analysis of NotI genomic restriction digests and fluorescence in situ hybridization using probes from band 19q13.1 were utilized. High-level amplification of overlapping sets of chromosome 19 NotI fragments was exhibited in 3 cell lines of which 2 showed amplification of both OZF and AKT2 genes and 1 that of AKT2 alone. In these 3 cell lines, amplification of chromosome 19 sequences was associated with the presence of a homogeneously staining region. Our results provide evidence of heterogeneity in the extent of chromosome 19 amplification and suggest the existence of yet unknown amplified genes that may play a role in pancreatic carcinogenesis.

Chromosome Aberrations↗