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Biomedical subjects

P Fitzgerald

Publications and source records attributed to P Fitzgerald.

At least 37 records · Page 2Linked to original sources
PubMed2000

An unusual cause of recurrent pancreatitis: duodenal duplication cyst.

Intestinal duplications are rare anomalies that usually present in childhood. Of these, duodenal duplications are among the most uncommon. Although these usually present with obstructive symptoms or bleeding, pancreatitis may occur. A case of duodenal duplication cyst causing recurrent pancreatitis in a 12-year-old girl is presented. The literature on duodenal duplications, and their epidemiology, embryology and pathophysiology is reviewed.

Child↗
PubMed2000

The effect of the position of the limb on venous impulse foot pumps.

Compression foot pumps are widely used for the prevention of postoperative venous thrombosis. We tested the efficiency of the pump in ten healthy subjects; the velocity of venous blood flow in the common femoral vein was measured in the horizontal, Trendelenberg (foot-up) and reverse-Trendelenberg (foot-down) positions. Application of the foot pump produced an increase in the venous velocity in all subjects. The mean increase in the horizontal position was 27.2% and in the Trendelenberg position 15.4%. In the reverse-Trendelenberg position, the foot pump produced a mean increase of 102.8%. The efficiency of the compression foot pump in increasing venous return is improved by adopting the reverse-Trendelenberg position. This may increase its thromboprophylactic effect.

Adult↗
PubMed2000

Pediatric laparoscopic splenectomy.

BACKGROUND: Lateral laparoscopic splenectomy in adults, first reported in 1991, was begun with children in 1993. METHODS: The authors reviewed records of 59 patients 2 to 17 years old who underwent laparoscopic splenectomy by the lateral approach between 1994 and 1998 at four medical centers. Patients received prophylactic penicillin or vaccinations preoperatively. RESULTS: Of the 59 patients, 51 required splenectomy for one of the following conditions: idiopathic thrombocytopenic purpura, hereditary spherocytosis, or sickle-cell disease. Splenomegaly was found in 86% of the patients, and ten accessory spleens were resected. No deaths or infection occurred, and only three patients had perioperative complications: acute chest crisis, small diaphragmatic injury, and intraoperative hemorrhage. One operation was converted to a minilaparatomy because of difficulty with specimen extraction. CONCLUSIONS: Pediatric laparoscopic splenectomy is safe and effective, resulting in little blood loss, rapid recovery, and a good cosmetic outcome.

Adolescent↗
PubMed2000

Efficacy of fish oil concentrate in the treatment of rheumatoid arthritis.

OBJECTIVE: To determine the efficacy of fish oil derived (n-3) fatty acid supplementation (3-6 capsules/day) in subjects with rheumatoid arthritis (RA) whose (n-6) fatty acid intake in the background diet was < 10 g/day, compared to olive/corn oil capsule supplement over a 15 week period. METHODS: A placebo controlled, double blind, randomized 15 week study to determine the effect of supplementation on clinical variables in 50 subjects with RA whose background diet was naturally low in (n-6) fatty acids. Fish oil containing 60% (n-3) fatty acids was supplemented at a rate of 40 mg/kg body weight. RESULTS: Analysis of 9 clinical variables indicated there was a significant difference (p < 0.02) between control and treatment groups. Five subjects in the treatment group and 3 in the control group met the American College of Rheumatology 20% improvement criteria. Dietary supplementation resulted in a significant increase in eicosapentaenoic acid in plasma and monocyte lipids in the supplemented group. CONCLUSION: The findings suggest that fish oil supplementation that delivers (n-3) fatty acids at a dose of 40 mg/kg body weight/day, with dietary (n-6) fatty acid intake < 10 g/day in the background diet, results in substantial cellular incorporation of (n-3) fatty acids and improvements in clinical status in patients with RA.

Arthritis, Rheumatoid↗
PubMed2000

A knowledge-based patient assessment system: conceptual and technical design.

This paper describes the design of an inpatient patient assessment application that captures nursing assessment data using a wireless laptop computer. The primary aim of this system is to capture structured information for facilitating decision support and quality monitoring. The system also aims to improve efficiency of recording patient assessments, reduce costs, and improve discharge planning and early identification of patient learning needs. Object-oriented methods were used to elicit functional requirements and to model the proposed system. A tools-based development approach is being used to facilitate rapid development and easy modification of assessment items and rules for decision support. Criteria for evaluation include perceived utility by clinician users, validity of decision support rules, time spent recording assessments, and perceived utility of aggregate reports for quality monitoring.

Artificial Intelligence↗
PubMed2000

A randomised controlled trial to evaluate the effectiveness and cost-effectiveness of counselling patients with chronic depression.

OBJECTIVES: To examine the effectiveness and cost-effectiveness of short-term counselling in general practice for patients with chronic depression or combined depression and anxiety, compared with general practitioner (GP) care alone. DESIGN: A randomised controlled trial and economic evaluation with an initial assessment at randomisation and follow-ups at 6 and 12 months. SETTING: Nine general practices that were well-established participants of the Derbyshire counselling in general practice scheme, and already had a counsellor in the practice team. SUBJECTS: Patients were screened at GP practices, and asked to participate if they scored >/= 14 on the Beck Depression Inventory (BDI), had suffered depression or depression/anxiety for 6 months or more, were aged 18-70 and had no history of drug or alcohol abuse, psychoses or suicidal tendencies. INTERVENTIONS: The experimental group received usual GP treatment and were also referred to an experienced, well-qualified counsellor attached to their general practice. Of the eight counsellors, two practiced cognitive behavioural therapy (CBT) and six had a psychodynamic approach. The controls were referred back to their GP for routine treatment. There were no restrictions regarding the treatment that could be used, except that GPs could not refer controls to practice counsellors. OUTCOME MEASURES: The main outcome measure was the BDI. Others included the Brief Symptom Inventory, the Inventory of Interpersonal Problems and the Social Adjustment Scale. All tests were given at initial, 6- and 12-month assessments. Comprehensive costs were also estimated, and combined with changes in outcomes to examine between-group differences and whether counselling was more cost-effective than standard GP care. RESULTS: The trial recruited 181 patients. There was an overall significant improvement in the actual scores over time but no difference between groups or between CBT and psychodynamic counselling approaches at either 6 or 12 months. However, fewer experimental group patients were still 'cases' on the BDI than controls. This difference was statistically significant at 12 months and neared significance at 6 months (using logistic regression with the initial score as a covariate). In addition, most patients were very positive about the counselling and considered it helpful. Visual inspection of the outcomes suggested that more patients with mild or moderate depression at study entry had improved and ceased to be cases, and that more of these patients had become 'non-cases' in the experimental than the control group. However, a multiple regression analysis indicated no significant interactions between group and initial severity of depression. This could be partly due to there being no difference in outcome between the experimental and control group patients who were initially severely depressed and few of these patients ceasing to be cases at follow-up. There were no significant differences in the mean total costs, aggregate costs of services, or any of the service-group costs, except for primary care, between the experimental and control groups over time. The cost-burden to GP practices was significantly higher in the experimental than the control group at 6 months. CONCLUSIONS: Although patients were generally appreciative of the counselling received, there was only limited evidence of improved outcomes in those referred to counselling. Stricter referral criteria to exclude the severely depressed may have yielded more conclusive results. It is also difficult to estimate the effect of recruitment by screening rather than GP referral, which may limit the applicability of the results to routine clinical practice, and may have interfered with the normal working alliance established between the GP, patient and counsellor. A patient preference trial may, therefore, have been more appropriate. The results indicated that there were similar improvements for both CBT and psychodynamic counselling, but a

Adolescent↗
PubMed1999

Growth inhibition by CDK-cyclin and PCNA binding domains of p21 occurs by distinct mechanisms and is regulated by ubiquitin-proteasome pathway.

The CDK inhibitor, p21WAF1/Cip1 blocks cell cycle progression. In vitro, the N-terminus of p21 binds and inhibits CDK-cyclin kinase activity, whereas the C-terminus binds and inhibits PCNA (proliferating cell nuclear antigen) function. PCNA is essential for processivity of both DNA polymerase delta and epsilon. We have performed a detailed analysis of growth inhibition by the N- and C-terminal regions of p21, and determined whether the N- and C-terminal regions mediate this effect by different mechanisms. Expression of either the N- or the C-terminal region of p21 inhibits DNA synthesis and cell growth, but not as efficiently as full length p21. The effectiveness of the two p21 domains is dependent on their stability which is determined by the ubiquitin-proteasome pathway. The stabilization of the N- and C-terminal region of p21 increases their effectiveness as inhibitors of DNA synthesis to levels comparable to full length p21. Inhibition of DNA synthesis by the N-terminal region of p21 involves suppression of E2F activity. In contrast, inhibition by the C-terminal region of p21 is not accompanied by suppression of E2F activity, but is mediated via PCNA binding. The C-terminal region of p21 therefore inhibits cell growth by a mechanism distinct from that of the N-terminal region containing the CDK-cyclin inhibitory domain.

3T3 Cells↗
PubMed1999

Growth inhibition by CDK-cyclin and PCNA binding domains of p21 occurs by distinct mechanisms and is regulated by ubiquitin-proteasome pathway.

The CDK inhibitor, p21(WAF1/Cip1) blocks cell cycle progression. In vitro, the N-terminus of p21 binds and inhibits CDK-cyclin kinase activity, whereas the C-terminus binds and inhibits PCNA (proliferating cell nuclear antigen) function. PCNA is essential for processivity of both DNA polymerase delta and epsilon. We have performed a detailed analysis of growth inhibition by the N- and C-terminal regions of p21, and determined whether the N- and C-terminal regions mediate this effect by different mechanisms. Expression of either the N- or the C-terminal region of p21 inhibits DNA synthesis and cell growth, but not as efficiently as full length p21. The effectiveness of the two p21 domains is dependent on their stability which is determined by the ubiquitin-proteasome pathway. The stabilization of the N- and C-terminal region of p21 increases their effectiveness as inhibitors of DNA synthesis to levels comparable to full length p21. Inhibition of DNA synthesis by the N-terminal region of p21 involves suppression of E2F activity. In contrast, inhibition by the C-terminal region of p21 is not accompanied by suppression of E2F activity, but is mediated via PCNA binding. The C-terminal region of p21 therefore inhibits cell growth by a mechanism distinct from that of the N-terminal region containing the CDK-cyclin inhibitory domain.

3T3 Cells↗
PubMed1999

Laparoscopic vs open splenectomy.

HYPOTHESIS: Laparoscopic splenectomy (LS) provides health benefits to patients compared with open splenectomy (OS) in terms of perioperative morbidity, complications, and patient recuperation. DESIGN: Prospective operative and outcome data of LS patients were compared with those of OS patients (historical controls). SETTING: Data were gathered, and patients were evaluated and treated at 2 McMaster University teaching hospitals in Hamilton, Ontario, and at the University of Kentucky Chandler Medical Center, Lexington, also a teaching hospital. PATIENTS: From January 1, 1994, through October 31, 1998, a total of 210 patients were studied. Of them, 147 patients from 3 university teaching hospitals underwent LS. These patients were matched with 63 OS patients according to age, sex, spleen weight, indication for splenectomy, and preoperative morbidity score. INTERVENTIONS: A total of 147 patients evaluated for elective splenectomy underwent LS. MAIN OUTCOME MEASURES: Spleen weight, operative time, intraoperative blood loss, postoperative hospital stay, perioperative complications, and cost. RESULTS: No significant difference in mean spleen weight was found between groups. Mean operative time was significantly longer for LS, but intraoperative blood loss was significantly lower. Mean postoperative hospital stay was significantly lower and perioperative complications significantly fewer for LS patients. Mean cost for LS with no complications was slightly lower than for OS. CONCLUSIONS: Compared with OS, the lateral approach to LS takes longer to perform but results in reduced blood loss, shorter postoperative stay, and fewer complications. Mean weighted cost of LS is lower than OS at the study institutions. A prospective, randomized, controlled trial comparing these techniques is planned.

Adolescent↗
PubMed1999

Novel nonsecosteroidal vitamin D mimics exert VDR-modulating activities with less calcium mobilization than 1,25-dihydroxyvitamin D3.

BACKGROUND: The secosteroid 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) acts through the vitamin D receptor (VDR) to elicit many activities that make it a promising drug candidate for the treatment of a number of diseases, including cancer and psoriasis. Clinical use of 1,25(OH)2D3 has been limited by hypercalcemia elicited by pharmacologically effective doses. We hypothesized that structurally distinct, nonsecosteroidal mimics of 1,25(OH)2D3 might have different activity profiles from vitamin D analogs, and set out to discover such compounds by screening small-molecule libraries. RESULTS: A bis-phenyl derivative was found to activate VDR in a transactivation screening assay. Additional related compounds were synthesized that mimicked various activities of 1,25(OH)2D3, including growth inhibition of cancer cells and keratinocytes, as well as induction of leukemic cell differentiation. In contrast to 1, 25(OH)2D3, these synthetic compounds did not demonstrate appreciable binding to serum vitamin D binding protein, a property that is correlated with fewer calcium effects in vivo. Two mimics tested in mice showed greater induction of a VDR target gene with less elevation of serum calcium than 1,25(OH)2D3. CONCLUSIONS: These novel VDR modulators may have potential as therapeutics for cancer, leukemia and psoriasis with less calcium mobilization side effects than are associated with secosteroidal 1,25(OH)2D3 analogs.

Animals↗
PubMed1999

Long-acting antipsychotic medication, restraint and treatment in the management of acute psychosis.

OBJECTIVE: Zuclopenthixol acetate (ZA) is the first parenteral antipsychotic medication introduced for clinical use in the treatment of aggression and agitation that has a relatively prolonged duration of action. The aim of this paper is to explore a number of important ethical and clinical issues that are raised by the use of this novel therapeutic formulation. METHOD: Relevant literature is explored and several issues are identified from which arguments for and against the use of medication of this type are raised. These issues are considered in general and with the use of a number of stylised clinical scenarios. RESULT: The use of long-acting antipsychotic medication is complicated by its impact upon patient autonomy, by considerations of informed consent and by the need to provide justice to all patients and staff in a psychiatric treatment setting. The use of ZA in the emergency treatment of psychotic patients may only be justified under specific clinical circumstances and its use is not appropriate as routine chemical restraint. CONCLUSIONS: Zuclopenthixol acetate is a novel and potentially useful treatment alternative in the acutely disturbed patient. Institutions in which ZA is used in emergency settings should develop protocols to guide clinicians in its appropriate use and provide monitoring.

Acute Disease↗
PubMed1999

Serum calcium and cardiovascular risk factors and diseases: the Tromsø study.

Total serum calcium levels were measured in 12 865 men and 14 293 women, between the ages of 25 and 97 years, in the Tromsø Study during 1994 and 1995. With the use of a sex-specific multiple linear regression model with age, calcium, body mass index, cholesterol, HDL cholesterol, triglycerides, systolic and diastolic blood pressure, and pulse as possible covariates, serum calcium was significantly (P<0.001) and positively associated with systolic and diastolic blood pressure, serum cholesterol, and HDL cholesterol in both sexes. A similar but weaker association was observed between serum calcium and triglycerides in men (P<0.01). In all age groups, serum calcium levels were higher in men with a history of myocardial infarction than in those without, and the difference was significant (P<0.0001) in a linear regression analysis adjusted for age. When all the other variables were also included in a logistic regression model, serum calcium was a highly significant (P<0.0001) predictor of myocardial infarction in men, with an odds ratio of 1.2 per 0.1 mmol/L increase in serum calcium. In women, a nonsignificant trend was again seen. Because the free or ionized form of calcium is the physiologically important form and serum calcium was not corrected for serum albumin in our study, the results must be interpreted with caution. However, it appears likely that serum calcium is a predictor of cardiovascular disease in men.

Adult↗
PubMed1999

Estrogen receptor beta activates the human retinoic acid receptor alpha-1 promoter in response to tamoxifen and other estrogen receptor antagonists, but not in response to estrogen.

Human estrogen receptor-alpha (hERalpha) or -beta (hERbeta) transfected into Hep G2 or COS1 cells each responded to estrogen to increase transcription from an estrogen-responsive element (ERE)-driven reporter vector with similar fold induction through a classical mechanism involving direct receptor binding to DNA. ER antagonists inhibited this estrogen induction through both hERalpha and hERbeta, although raloxifene was more potent through ERalpha than ERbeta, and tamoxifen was more potent via ERbeta than ERalpha. We have shown previously that estrogen stimulated the human retinoic acid receptor-alpha-1 (hRARalpha-1) promoter through nonclassical EREs by a mechanism that was ERalpha dependent, but that did not involve direct receptor binding to DNA. We show here that in contrast to hERalpha, hERbeta did not induce reporter activity driven by the hRARalpha-1 promoter in the presence of estrogen. While hERbeta did not confer estrogen responsiveness on this promoter, it did elicit transcriptional activation in the presence of 4-hydroxytamoxifen (4-OH-Tam). Additionally, this 4-OH-Tam agonist activity via ERbeta was completely blocked by estrogen. Like ERalpha, transcriptional activation of this promoter by ERbeta was not mediated by direct receptor binding to DNA. While hERalpha was shown to act through two estrogen-responsive sequences within the promoter, hERbeta acted only at the 3'-region, through two Sp1 sites, in response to 4-OH-Tam. Other ER antagonists including raloxifene, ICI-164,384 and ICI-182,780 also acted as agonists through ERbeta via the hRARalpha-1 promoter. Through the use of mutant and chimeric receptors, it was shown that the 4-OH-Tam activity via ERbeta from the hRARalpha-1 promoter in Hep G2 cells required the amino-terminal region of ERbeta, a region that was not necessary for estrogen-induced ERbeta activity from an ERE in Hep G2 cells. Additionally, the progesterone receptor (PR) antagonist RU486 acted as a weak (IC50 >1 microM) antagonist via hERalpha and as a fairly potent (IC50 approximately 200 nM) antagonist via hERbeta from an ERE-driven reporter in cells that do not express PR. Although RU486 bound only weakly to ERalpha or ERbeta in vitro, it did bind to ERbeta in whole-cell binding assays, and therefore, it is likely metabolized to an ERbeta-interacting compound in the cell. Interestingly, RU486 acted as an agonist through ERbeta to stimulate the hRARalpha-1 promoter in Hep G2 cells. These findings may have ramifications in breast cancer treatment regimens utilizing tamoxifen or other ER antagonists and may explain some of the known estrogenic or antiestrogenic biological actions of RU486.

Animals↗
PubMed1999

The association of Hb Khartoum [beta124(H2)Pro-->Arg] with gamma+-thalassemia is responsible for hemolytic disease in the newborn of a Sudanese family.

The unstable Hb Khartoum with a Pro-->Arg replacement at position beta124 was identified by isoelectrofocusing, high performance liquid chromatography, and peptide mapping in a mother and two male children of a Sudanese family. All three were heterozygous for the abnormal hemoglobin; the father and a third male child did not carry the mutation. The mother was also homozygous for two putative gamma+-thalassemia point mutations, one affecting both Agamma and Ggamma genes at IVS-II-115 (A-->G), and one affecting the Ggamma gene at the 3' untranslated region (-A) at position -6 from the polyadenylation site. The father had normal gamma genes. All three children were heterozygous for both the gamma+-thalassemia mutations. The two older children, who were compound heterozygotes for Hb Khartoum/gamma+-thalassemia, presented at birth with severe neonatal jaundice which necessitated exchange blood transfusions. Other causes of neonatal jaundice were excluded. The third male child, who did not carry the Hb Khartoum anomaly but was heterozygous for gamma+-thalassemia, did not develop neonatal jaundice. It is concluded that the instability of Hb Khartoum in combination with gamma+-thalassemia is responsible for neonatal hemolytic anemia in this family.

Adult↗
PubMed1999

Effect of dichotomising a continuous variable on the assessment of familial aggregation: an empirical study using body mass index data from the Busselton Health Study.

BACKGROUND: Continuous measures are often dichotomised according to some meaningful threshold. When measures of association are the study focus, such as in familial aggregation studies, we may use an odds-ratio (OR), instead of a Pearson correlation coefficient, to measure correlation between outcomes. In this paper, we examine the effect of using different threshold values on the resulting OR estimates and their statistical efficiency. METHODS: We use an example based on obesity data, in the form of BMI measurements on family members, to guide a study of the OR based on four-fold probabilities which result when a pair of normally distributed outcomes is dichotomised at a certain value. This leads to a study of outcomes from simulated nuclear family data. As a possible alternative, we also assess the performance use of a simple tetrachoric correlation coefficient, the dichotomous analogue of Pearson's correlation coefficient. RESULTS: The studies indicate that dichotomisation at values close to the mean leads to results more comparable to the continuous equivalent. The results show that, in our setting, there is a positive relationship between threshold value and resulting OR, and between threshold value and resulting standard errors. The value of the tetrachoric correlation coefficient decreases, relative to Pearson's correlation coefficient, as threshold values deviate from the mean. DISCUSSION: Familial OR that result from dichotomisation are influenced by the choice of threshold value. We discuss implications of this and related issues on the interpretation of results.

Adult↗