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Biomedical subjects

J A Davidson

Publications and source records attributed to J A Davidson.

At least 19 recordsLinked to original sources
PubMed2006

Addition of pioglitazone to stable insulin therapy in patients with poorly controlled type 2 diabetes: results of a double-blind, multicentre, randomized study.

AIM: To determine the effects of pioglitazone treatment combined with insulin on glucose and lipid metabolism in patients with type 2 diabetes. METHODS: In a multicentre, double-blind study, 690 patients [body mass index, 33.19 kg/m2 +/- 5.47; haemoglobin A1c (A1C), 9.78 +/- 1.51; mean duration, 12.9 years] with diabetes poorly controlled with a stable insulin dose (> 30 U/day for > or =30 days) were randomly allocated to pioglitazone 30 or 45 mg once daily for 24 weeks. RESULTS: In the pioglitazone 30- and 45-mg groups, respectively, 71 and 70% of patients completed the study. At 24 weeks, statistically significant, dose-dependent mean decreases from baseline were seen in the pioglitazone 30- and 45-mg groups for A1C (-1.17 and -1.46%, respectively) and fasting plasma glucose (-31.9 and -45.8 mg/dl, respectively). Insulin dosage also decreased significantly (-4.5 and -7.3 U, respectively; p < or = 0.05) from baseline. Decreases in triglycerides [pioglitazone 45 mg: -5.9% (p < or = 0.05)], very low-density lipoprotein cholesterol [pioglitazone 45 mg: -6.2% (p < or = 0.05)] and free fatty acids [-0.94 (p < or = 0.05) and -2.13 (p < 0.0001) mg/dl, respectively] and increases in high-density lipoprotein cholesterol (9.7 and 13.0%, respectively; p < 0.0001) also were observed from baseline. Small but significant increases in total and low-density lipoprotein cholesterol (p < 0.01) from baseline were observed. Mean weight gain was 2.9 and 3.4 kg in the respective groups; lower limb oedema was reported in 13 and 12% of patients, respectively. The incidences of oedema, weight gain and heart failure were not higher than anticipated in this population. No evidence of hepatotoxicity or clinically significant elevations in liver function test parameters was seen. CONCLUSIONS: In patients with poorly controlled type 2 diabetes, addition of pioglitazone to insulin significantly improved glycaemic control, had a positive effect on important components of the lipid profile in a dose-dependent manner and was generally well tolerated.

Blood Glucose↗
PubMed2005

An algorithm for the treatment of type 2 diabetes in Latin America.

Diabetes is a principal and growing health concern in Latin America, accounting for significant mortality and morbidities. Large, randomized, prospective trials of various interventional therapies in patients with both type 1 and type 2 diabetes have demonstrated that reductions in hyperglycaemia and management of diabetes-related risk factors can significantly reduce the micro- and macrovascular complications of diabetes. Therefore, patients with type 2 diabetes will benefit from more aggressive treatment regimens to help decrease the occurrence and rate of progression of diabetic complications. Given the many complexities of diabetes management, it is often difficult for general practice physicians to stay abreast of emerging treatment strategies and therapies. Owing to the high prevalence of type 2 diabetes in Latin America, the majority of patients with diabetes are treated by generalists rather than specialists. This article was intended to assist physicians and other healthcare professionals in developing and using effective treatment strategies to stem the growing epidemic of diabetes and its complications in Latin America.

Adult↗
PubMed2005

Sore throat in adults--does the introduction of a clinical scoring system improve the management of these patients in a secondary care setting?

OBJECTIVE: To audit sore throat management in adults, introduce proforma-based guidelines and to re-audit clinical practice. SETTING: Adult emergency department of an inner city teaching hospital. METHODS: A literature search was carried out to identify relevant guidelines. In stage one, patients presenting to the emergency department with sore throat were identified retrospectively from the emergency department attendance register. Proformas were completed retrospectively. In stage two, new guidelines were introduced and staff educated about the guidelines. In stage three, patients presenting with sore throat were identified at triage and proformas were completed at time of consultation. OUTCOME MEASURES: (1) appropriate clinical assessment of the likelihood of bacterial infection using the clinical scoring system, (2) appropriateness of antibiotic prescription, (3) recommendation of supportive treatments to patients. RESULTS: Introduction of a clinical scoring system reduced the inappropriate prescribing of antibiotics from 44 per cent to 11 per cent. Correct antibiotic prescription rose from 60 per cent to 100 per cent. Although the variety of advice given about supportive treatment increased, the actual number of patients receiving documented supportive advice fell from 67.8 per cent in stage one to 58 per cent in stage three. CONCLUSION: The introduction of clinically based guidelines for the diagnosis and management of sore throat in adults can reduce inappropriate antibiotic prescribing.

Adult↗
PubMed2003

A system to assess fitness of dairy cows responding to exercise training.

Objectives were to develop a system to administer exercise training to dairy cows, to measure potential physiological indicators of fitness, and to assess physical fitness. Nonlactating, nonpregnant multiparous Holstein cows (n = 19) were in one of three exercise training treatments: no exercise; 1-h exercise; or 2-h exercise by walking 3 km/h every other day for 60 d in a mechanical walker. Treadmill tests on d 15, 30, 45, and 60 consisted of walking (5 km/h) with 1.6% increases in slope at 3-min intervals until heart rates reached 180 beats per minute (experimentally specified maximum) or until cows refused to walk. Fitness indices analyzed in tests as single datum points at maximal heart rates were length of time of test, heart rate, and plasma L-lactate concentration at end of the test, and change in heart rate and lactate concentration during the test. Exercised (1 or 2 h) cows had longer times to end of tests than nonexercised cows. Maximal and change in heart rates or plasma lactate during tests did not indicate improved physical fitness. However, when all data were evaluated as repeated measures of day and minute of tests, reductions of heart rates and plasma lactate concentrations were greatest on d 60 between exercised and nonexercised cows indicating improved fitness. Acid-base measurements were not found useful in this study. Changes of heart rates and plasma lactate concentrations over time (repeated measures) of treadmill tests quantified the physical fitness of dairy cows and can be used to compare potential responses to different exercise training treatments in this system.

Acid-Base Equilibrium↗
PubMed2001

Short-form HLA-DP typing with 48 primer mixes using the polymerase chain reaction and sequence-specific primers.

We have developed a short-form SSP-based HLA-DP typing system for routine use adapted from a comprehensive HLA-DP typing method described by Gilchrist et at. (1998). Our short-form system detects 93 alleles, including the 18 most common HLA-DPB1 alleles and eight HLA-DPA1 alleles. The primer mixes described were tested using the PCR-SSP Manager (Bunce et al., 1998) database to confirm the specificity of selected primers, and to detect potentially ambiguous amplifications. This short-form HLA-DP typing system was validated using 50 fully typed samples obtained through the UCLA International DNA Exchange. All samples gave 100% concordance with the consensus type. Our laboratory routinely uses a PCR-SSP based system of 48 primer mixes for HLA-DRB and HLA-DQB typing. The advantage of the short-form HLA-DP typing system described here is that the additional 48 HLA-DP primer mixes required can be included on the second half of a 96-well format tray. This method now enables a full HLA class II typing at the level of allele group resolution in 2 1/2 h.

Alleles↗
PubMed2001

The differential regulation of CART gene expression in a pituitary cell line and primary cell cultures of ovine pars tuberalis cells.

The cocaine-amphetamine regulated transcript (CART) encodes for a protein which has an important role in the regulation of appetite and body weight. To date, no details of the molecular events and signal transduction pathways which regulate this gene are available. We report the identification of CART gene expression in the GH3 pituitary cell line. We have used activators of the cAMP or protein kinase C (PKC) signal transduction pathways to show that, in GH3 cells, CART is transcriptionally up-regulated by activators of the cAMP signal transduction pathway. We also identify CART gene expression in ovine pars tuberalis (PT) tissue and primary cell cultures. In PT cells in contrast to GH3 cells, CART gene expression is upregulated by activators of the PKC signal transduction pathway. Cultured cells have provided a valuable resource for the detailed analysis of specific regulatory mechanisms underlying transcriptional or translational regulation of genes, signal transduction events and many other cellular processes. GH3 and PT cells may therefore provide a resource for the further detailed molecular analysis of the events regulating CART gene expression and processing.

Animals↗
PubMed2000

Multiple mechanisms underlie HLA dysregulation in cervical cancer.

The consistent dysregulation of HLA expression in cervical neoplasia is likely to influence the natural history of the disease and prospects for cell-mediated vaccine therapies. We have studied the underlying mechanisms in eight new cervical cancer cell lines derived from primary tumour biopsies. At least five independent mechanisms leading to changes in HLA expression were seen: HLA class I allelic transcription but no protein; abnormal HLA class I allelic transcription; no HLA-B locus transcription; loss of heterozygosity (LOH); no gammaIFN-mediated upregulation of HLA class I expression, and/or no interferon-gamma (gammaIFN)-mediated HLA class II induction. These were evident in different combinations in 7/8 cell lines showing that multiple, mostly irreversible mechanisms not overridden by gammaIFN, are responsible for HLA dysregulation in cervical neoplasia. Point mutations were responsible for lack of HLA-A2 expression in two cases. In cell line 808, the mutation encodes a stop codon in exon 3; in cell line 778, mutation of the first intron acceptor site leads to use of an alternative AG site in exon 2, resulting in a frameshift and a stop codon after the translation of only 38 amino acids. Tumour cells showing specific HLA class I loss may have selective advantage in the face of tumour-specific cytotoxic T cells (CTL). Such immune escape mechanisms present a major obstacle for the success of CTL-mediated therapies in cervical cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Replication-restricted vaccinia as a cytokine gene therapy vector in cancer: persistent transgene expression despite antibody generation.

BACKGROUND: As antitumoral immunity requires the generation of local immunity directed against tissue proteins, we attempted to recreate within tumors the same environment found within tissues affected by autoimmune diseases (i.e., prolonged cytokine expression). Vaccinia virus (VV) has not been widely used as a cytokine gene therapy vector because of presumed high immunogenicity that would likely make repeated injections impossible; therefore, we modified it by inserting the cytokine gene into the thymidine kinase region, rendering it replication-restricted. The cytokine chosen was human interleukin-2 (IL-2); a molecule with powerful antitumoral effects. METHODS: Six patients with the treatment-resistant tumor malignant mesothelioma received intratumoral (i.t.) VV-IL-2 therapy for 12 weeks by injection of 10(7) plaque-forming units of VV-IL-2 per dose. Serial tumor biopsies, sputum, urine, and blood samples were tested for VV-IL-2 mRNA expression; VV culture and T-cell infiltrates were evaluated by immunohistochemistry. Patients and contacts of patients were monitored for changes in VV immunoglobulin G (IgG) levels and clinical evidence of VV infection. RESULTS: VV-IL-2 was not excreted and was only cultured in one patient from tumor biopsies. A T-cell infiltrate was detected in 50% of tumor biopsies. VV-IL-2 mRNA expression was highest on days 1-3 postinjection and was detected for up to 3 weeks after each injection even though VV IgG levels rose in all patients. No significant toxicities, infection of patient contacts, or tumor regressions were observed. CONCLUSIONS: I.t. VV-IL-2 administration is safe, is associated with minimal toxicity, and results in i.t. expression of VV-IL-2 for up to 3 weeks postinjection regardless of the level of anti-VV IgG titers generated. This suggests that VV may be a good vector for repeated cytokine gene therapy of solid human cancer.

Adult↗
PubMed1999

Cor pulmonale presenting in a patient with congenital kyphoscoliosis following intercontinental air travel.

We present the case of a 59-year-old man with congenital kyphoscoliosis who developed cor pulmonale for the first time following intercontinental air travel. Prolonged exposure to the low partial pressure of oxygen in the cabin of the aircraft led to pulmonary hypertension and right heart failure. The case highlights the potential for long-haul air travel to cause decompensation in patients with thoracic deformity and apparently stable cardiorespiratory function. It also emphasises the need for patients and their medical attendants to carefully consider the potential health implications of the hypoxic atmosphere in pressurised aircraft.

Aerospace Medicine↗
PubMed1999

Troponin I and myocardial injury in the ICU.

Cardiac troponin I (cTnI) is a protein that is specific to heart muscle. Increased concentrations appear in serum after myocardial cell injury. cTnI was compared with creatinine kinase MB (CK MB), myoglobin and the 12-lead ECG for detection of myocardial injury in an unselected series of 109 medical and surgical ICU patients. Clinical observations and daily 12-lead ECG were recorded prospectively. Samples for cTnI, myoglobin and CK MB serum analysis were collected each day. Increased serum cTnI concentrations (> 0.1 microgram litre-1) were observed in 70.6% (n = 77) of the ICU group. Tachycardia, arrhythmia, hypotension and treatment with inotropic drugs were associated with higher concentrations. The standardized mortality ratio by APACHE III for the ICU sample was 0.98. All subjects in an unmatched control group of 98 medical unit emergency admissions without a primary cardiac diagnosis had serum cTnI concentrations < 0.1 microgram litre-1. We conclude that increased serum cTnI concentrations occur frequently in the ICU suggesting that there is a high incidence of cardiac injury in these patients.

Aged↗
PubMed1999

Cisplatin and gemcitabine treatment for malignant mesothelioma: a phase II study.

PURPOSE: We performed a phase II study of combined cisplatin 100 mg/m2, given intravenously on day 1, and gemcitabine 1,000 mg/m2, given intravenously on days 1, 8, and 15 of a 28-day cycle for six cycles among patients with advanced measurable pleural mesothelioma. PATIENTS AND METHODS: Pleural tumor was measured at three levels on computed tomographic scans at study entry and before the second, fourth, and sixth cycles and every 2 months thereafter to disease progression. Of the 21 patients treated, 19 were male; the median age was 62 years (range, 46 to 74 years); 62% had epithelial tumors; and 18 were classified as tumor-node-metastasis system stage III or IV. Ninety-four cycles were given (median, six; mean, 4.5 per patient), with a mean relative dose intensity of cisplatin 96.7% and gemcitabine 82.5%. RESULTS: Best objective responses achieved were as follows: complete response, no patients; partial response, 10 patients (complete response + partial response, 47.6% [95% confidence interval, 26.2% to 69.0%]); no change, nine patients; and progressive disease, two patients. Median response duration was 25 weeks, progression-free survival was 25 weeks, and overall survival was 41 weeks. Nine of the 10 responders (90%) and three of nine patients with no change had significant symptom improvement. Serial measurements of vital capacity were performed on three of the responders; all showed a significant increase during the time of remission. Toxicity was mainly gastroenterologic and hematologic. Grade 3 nausea and vomiting occurred in 33% of patients, grade 3 leukopenia in 38%, grade 3 thrombocytopenia in 14%, and grade 4 thrombocytopenia in 19%. CONCLUSION: Combined cisplatin and gemcitabine is an active combination in malignant mesothelioma and produces symptomatic benefit in responding patients.

Aged↗
PubMed1998

Loss of heterozygosity on chromosome 2q: possibly a poor prognostic factor in head and neck cancer.

BACKGROUND: Loss of heterozygosity (LOH) correlates with inactivated tumor suppressor genes. The aim of this study was to see if LOH on chromosomes 2q, 3p, 5q, 9p, and 17p correlated with survival in early squamous cell carcinoma of the head and neck (SCCHN). METHODS: A case control study was performed. Ten patients with stage I or II tumors who ultimately died of their disease were identified and matched with suitable controls. None of the controls had a local recurrence and at time of last follow-up were alive with no evidence of disease or had died of an unrelated illness. The deoxyribonucleic acid (DNA) was extracted from paraffin blocks, and LOH studies were performed using microsatellite markers. RESULTS: The respective incidence of allelic loss for the index and control patients was as follows: chromosome 2q, 75% and 20% (p = .03); chromosome 3p, 71% and 57%, respectively (not significant); chromosome arm 5q, 30% and 25% (not significant); chromosome arm 9p, 71% and 73% (not significant); and chromosome arm 17p, 75% and 46% (not significant). Therefore, loss on chromosome 2q strongly correlated with poor survival (odds ratio = 10.4). CONCLUSION: Loss of heterozygosity on chromosome 2q may correlate with a poor prognosis in early-stage SCCHN.

Adult↗
PubMed1998

Intralesional cytokine therapy in cancer: a pilot study of GM-CSF infusion in mesothelioma.

Systemic cytokine therapy in cancer has major side effects, and we reasoned that the local infusion of cytokines into tumors could induce local immunologic responses with minimal toxicity and potentially strong systemic anticancer effects. This study investigated the toxicity and effectiveness of intralesional granulocyte/macrophage-colony-stimulating factor (GM-CSF) infusion in solid-tumor masses. We studied 14 patients (12 men, two women) with malignant mesothelioma (MM), aged 60 years (range, 46-70 years), with stage 2 disease, in whom the tumor was of sufficient size and accessibility for an intralesional catheter to be inserted. Recombinant human GM-CSF (Molgramostim; Schering Plough) was infused intralesionally for 8 weeks, by using a portable pump, at a dose of 2.5-10 micrograms/kg/day. One patient using GM-CSF developed histologically confirmed necrosis of tumor surrounding the distal catheter, one developed a marked lymphocytic infiltrate in the tumor and had a partial response measured by chest computed tomography (CT) scan, 10 progressed, and three had no response. Neutrophilia with morphologic evidence of neutrophil activation and clinical features suggestive of neutrophil plugging of blood vessels occurred at doses > 5 micrograms/kg/day. In vitro, GM-CSF doubled human neutrophil/CD11b/CD18 expression, suggesting that neutrophil clumping as seen in vivo might be due to integrin upregulation. Intralesional infusion of cytokines is feasible but can be associated with systemic toxicity and has considerable technical problems. It produces a localized immune reaction with tumor regression in a minority of patients.

Aged↗
PubMed1998

Tracheal intubating conditions after induction with propofol, remifentanil and lignocaine.

We have studied the intubating conditions in 60 ASA I or II patients, after induction of anaesthesia with propofol 2 mg kg-1, allocated to one of the following three groups: group 1, remifentanil 1 microgram kg-1; group 2, remifentanil 1 microgram kg-1 and lignocaine 1 mg kg-1; group 3, remifentanil 2 micrograms kg-1. No neuromuscular blocking agents were administered. Intubating conditions were assessed using a four-point scoring system based on ease of laryngoscopy, jaw relaxation, position of vocal cords, degree of coughing and limb movement. Overall intubating conditions were acceptable in 35% of patients in group 1, 100% of patients in group 2 and 85% of patients in group 3. There was a statistically significant drop in blood pressure after induction in groups 2 and 3, and two patients in each group required ephedrine 6 mg i.v. boluses, as dictated by the intervention criteria (mean arterial pressure fall > 25% from baseline). Similarly, there was a drop in heart rate in groups 2 and 3, but this did not reach statistical or clinical significance, and no patient required atropine.

Adolescent↗
PubMed1998

The effect of stimulus omission and interstimulus interval (ISI) on electrodermal habituation at short ISIs.

An experiment was conducted to examine the effects of complete stimulus omission and interstimulus interval (ISI) variability on habituation of the skin conductance response. A new scoring technique allowed shorter ISIs to be used (0.5-1.5 s) than in previous studies. It was found that both stimulus omission and variation of a previously constant ISI had a significant effect on the course of habituation at short ISIs. The results are consistent with comparator models of habituation and suggest that participants encode the ISI of a series of stimuli presented as short ISIs.

Electric Stimulation↗
PubMed1998

Long-term titrated-dose alpha-glucosidase inhibition in non-insulin-requiring Hispanic NIDDM patients.

OBJECTIVE: To assess the long-term safety and effectiveness of a titrated dose of the alpha-glucosidase inhibitor miglitol (BAY m 1099) in Hispanic NIDDM patients. RESEARCH DESIGN AND METHODS: A 1-year double-blind randomized placebo-controlled study in which diet-treated or diet plus sulfonylurea-treated Hispanic NIDDM patients received either placebo (n = 131) or miglitol in doses of 50, 100, 150, 200 mg t.i.d. (n = 254), up-titrated and down-titrated based on tolerability. Efficacy parameters included changes from baseline in HbA1c, fasting and 2-h postprandial plasma glucose and serum insulin, fasting serum lipids, and urinary albumin-to-creatinine ratio (ACR). Safety assessments consisted primarily of tabulation of adverse events and intercurrent illnesses, and of periodic laboratory determinations. RESULTS: Reductions from baseline in HbA1c levels at the 6-month (primary efficacy) endpoint were significantly greater by 0.83% in the miglitol group than in the placebo group. HbA1c reductions in the miglitol treatment group significantly exceeded those in the placebo group by 0.63, 0.73, and 0.92% at 3, 9, and 12 months of treatment, respectively. Reductions in 120-min postprandial glucose and insulin levels were significantly greater in the miglitol group than in the placebo group at all postbaseline visits. There was little difference between treatments for changes in fasting insulin or lipid levels. Miglitol-associated reductions versus placebo in fasting plasma glucose (P = 0.0587 at 6 months) and in ACR (P = 0.0541 at 1-year) were nearly statistically significant. These efficacy results were not notably different between the 6-month endpoint, at which time the mean miglitol dose was 100 mg t.i.d., and the 1-year visit, when the mean miglitol dose was 149 mg t.i.d. Notable adverse events seen significantly more often in the miglitol group than in the placebo group were flatulence and diarrhea (or soft stools). The incidence of these gastrointestinal adverse events appeared to be dose dependent. CONCLUSIONS: Miglitol treatment of non-insulin-requiring Hispanic NIDDM patients at doses from 50 to 200 mg t.i.d. produced statistically and clinically significant reductions of HbA1c, primarily associated with reduction of glucose and insulin levels in the postprandial period, which were sustained over a year of treatment. Adverse events related to the drug's mechanism of action were common, but generally well tolerated. Doses above 100 mg t.i.d. were not associated with notably enhanced efficacy in most patients.

1-Deoxynojirimycin↗