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P Ferguson

Publications and source records attributed to P Ferguson.

At least 19 recordsLinked to original sources

Estimate of the frequency of Wilson's disease in the US Caucasian population: a mutation analysis approach.

The frequency of Wilson's disease in many populations is thought to be about one in 40000 persons, based on case and autopsy studies. Although the Wilson's disease gene has been identified, there is such a large number of mutations already known that it is not currently feasible to determine disease gene frequency by mutation analysis of a population. We have used a novel approach to obtain an estimate of the number of cases of Wilson's disease expected at birth in the US Caucasian population. We used data from four studies to determine that approximately one-third of Wilson's disease mutations in US Caucasian Wilson's disease patients are due to His-->Gln at the 1069 position. We then determined the frequency of this mutation in random DNA samples from 2601 US Caucasian newborns to be 0.285%. Multiplying by three gives an expected Wilson's disease heterozygote frequency of 0.855% and an allele frequency of 0.428%, or 0.00428. These data translate into a Wilson's disease frequency of about one in 55000 births. The 95% confidence interval is rather broad, ranging from about one in 18000 to one in 700000 births, but will be reduced as more data are added.

DNA Primers↗

The effect of antithyroid drug pretreatment on acute changes in thyroid hormone levels after (131)I ablation for Graves' disease.

Acute changes in thyroid hormone levels before and after radioiodine therapy for Graves' disease were compared in 42 patients randomized to receive either antithyroid drug pretreatment or no pretreatment. Five patients (11.9%), including 3 in the pretreatment arm and 2 in the no pretreatment arm experienced a late exacerbation of thyrotoxicosis after radioiodine therapy. The majority (19 of 21, 90.5%) of pretreated patients experienced a transient increase in free T(4) and free T(3) after discontinuation of antithyroid drugs, with little further elevation after radioiodine therapy. After stopping antithyroid drugs and before radioiodine administration, mean serum free T(4) values rose from 14.7 +/- 6.9 to 21.6 +/- 12.1 pmol/L, representing a 46.9% increase, whereas serum free T(3) levels rose from 4.9 +/- 1.7 to 8.1 +/- 6.3 pmol/L, representing a 65.3% increase. The average pretreated patient experienced a 52.4% increase [95% confidence interval (CI), +26.4% to +78.5%] in free T(4) and a 61.8% increase (95% CI, +23.5% to +100.0%) in free T(3). Conversely, the majority (19 of 21, 90.5%) of nonpretreated patients experienced a rapid decline in thyroid hormone levels after radioiodine treatment. Over the 14 days after radioiodine therapy mean free T(4) values in nonpretreated patients fell from 85.8 +/- 60.4 to 58.0 +/- 76.5 pmol/L, representing a 32.4% decrease, whereas mean free T(3) levels fell from 16.1 +/- 8.0 to 10.8 +/- 11.1 pmol/L, representing a 32.9% decrease. The average nonpretreated patient experienced a 20.6% decrease (95% CI, -47.3% to +7.0%) in free T(4) and a 24.3% decrease (95% CI, -1.2% to -47.4%) in free T(3) during this time period. Excluding 2 patients with a late exacerbation after radioiodine, 19 nonpretreated patients experienced a decrease in mean free T(4) values from 76.8 +/- 46.6 to 36.6 +/- 19.8 pmol/L, representing a 52.3% decrease, whereas mean free T(3) levels fell from 15.5 +/- 7.7 to 7.8 +/- 3.6 pmol/L, representing a 49.7% decrease. The average decrease in free T(4) levels among this subgroup of patients was 30.1% (95% CI, -4.6% to -55.6%), whereas the average decrease in free T(3) was 34.4% (95% CI, -13.7% to -55.1%). High levels of TSH receptor autoantibodies at diagnosis were associated with an acute worsening of thyrotoxicosis after stopping antithyroid drug pretreatment. We conclude that pretreatment with antithyroid drugs does not protect against worsening thyrotoxicosis after radioiodine, but may allow such patients to start from a lower baseline level should an aggravation in thyrotoxicosis occur. The findings support the recommendation that most patients with Graves' disease do not require antithyroid drug pretreatment before receiving radioiodine.

Adult↗

Do researchers feel an LREC hinders research?

BACKGROUND: All medical professionals in the UK who wish to undertake clinical trials involving NHS patients must first obtain ethical approval. Although Local Research Ethics Committees (LRECs) play a crucial role, few studies have attempted to determine what researchers think about the effectiveness of their ethics committee. OBJECTIVE: To explore researchers' views as to the effectiveness or otherwise of their LREC. SUBJECTS: 78 experienced medical researchers. FINDINGS: While most researchers did not feel that the LREC made it more difficult to carry out their research, without good cause, a substantial minority was critical of the Committee, with many feeling that its approach was overly pedantic. CONCLUSION: There may be a need for greater dialogue between ethics committees and researchers, so that researchers understand why committees ask for certain information, and committees are aware of problems their requirements may cause.

Attitude↗

Possible relationship between birth weight and cancer incidence among young adults.

PURPOSE: Fetal and early life events have been associated with diseases that develop later in life. Low birth weight and the adult onset of hypertension, coronary heart disease, cerebrovascular disease, and non-insulin dependent diabetes have been identified. As well, associations with breast, ovarian, and prostate cancer to high birth weight have been found. An assessment of birth weight and cancer incidence was conducted in a cohort of black and white residents under the age of 46 years.METHODS: Cases were obtained from the Savannah River Region Health Information System cancer registry incident cases (1991-1995) and were limited to South Carolinians born in 1950 and later. Controls were obtained from birth certificate records by choosing the next two records after a cancer case record that matched on year of birth, race, and sex. Results were obtained for 117 cancer cases and 238 controls.RESULTS: After examining the birth distribution, the births were split into two groups based on mean birth weight among controls (3215 grams). Conditional logistic regression (CLR) showed that individuals with higher birth weights (> = 3215 g) were 1.65 (95% CI = 1.03-2.64) times more likely to be cancer cases than those with lower birth weights. When weights were categorized into 500 g increments, a CLR Score statistic showed there was a significant trend (p = 0.0006) of increasing proportion of cancer cases with increasing birth weight. Eight out of the eight cases of lymphoma had birth weights greater than 3579 g.CONCLUSIONS: The results of this preliminary study suggest that cancer incidence among the young may be associated with higher birth weights. One possible reason for this finding, which requires further investigation, might be that larger infants are exposed to higher levels of hormones and/or growth factor than smaller infants in utero that might increase the risk of certain cancers later in life. This may be suggestive of possible environmental factors affecting early growth. These findings support the need for additional study of this association.

Journal Article↗

Prospective evaluation of early versus delayed laparoscopic cholecystectomy for treatment of acute cholecystitis.

Although laparoscopic cholecystectomy (LC) is known to be safe in the treatment of acute cholecystitis (AC), the optimal timing of laparoscopic intervention remains controversial. The objective of this study is to prospectively compare the safety and cost effectiveness of early versus delayed LC in AC. Our study population consisted of 43 patients presenting with AC (localized tenderness, white blood cell count >10.0 or temperature >38.0 degrees C, and ultrasound confirmation) who were prospectively randomized to early versus delayed LC during their first admission. Exclusion criteria included a history of peptic ulcer disease or evidence of gallbladder perforation. All patients were treated with bowel rest and antibiotics (piperacillin 2 g intravenous piggyback every 6 hours). Early treatment patients underwent LC as soon as the operating schedule allowed. Delayed treatment patients received anti-inflammatory medication (indomethacin 50 mg per rectum every 12 hours) in addition to bowel rest and antibiotics and underwent operation after resolution of symptoms or within 5 days if symptoms failed to resolve. Early LC was performed in 21 patients, whereas 22 patients underwent delayed LC. There was no difference in age, temperature, or white blood cell count on admission between groups. Early LC slightly reduced operative time and conversion rate. There was no difference in complications. Estimated blood loss was significantly lower in those receiving early LC. There was also a significant reduction in total hospital stay and hospital charges with early LC. We conclude that delay in operation combined with anti-inflammatory medication showed no advantage with regard to operative time, conversion, or complication rate. Furthermore, early laparoscopic intervention significantly reduced operative blood loss, hospital days, and hospital charges.

Acute Disease↗

Linkage of a microsatellite marker to the canine copper toxicosis locus in Bedlington terriers.

OBJECTIVE: To identify a DNA marker for the copper toxicosis (CT) locus in Bedlington Terriers (BT). ANIMALS: 77 BT, of which 25 were affected. Diagnosis of affected or unaffected with CT was made in all cases by quantitative copper determinations on liver biopsy samples by use of established criteria. PROCEDURE: BT pedigrees segregating for CT were identified. Linkage studies were carried out using polymorphic microsatellite markers developed for the canine genome in these pedigrees. DNA was isolated from blood samples of pedigree members. Polymerase chain reaction was used to amplify and type alleles at 213 microsatellite loci in each dog, and findings were subjected to linkage analysis. RESULTS: One microsatellite marker was identified to be closely linked to CT with logarithm of odds score of 5.96 at a recombination fraction of zero. CONCLUSIONS: Using the linked marker, it has become possible to distinguish affected, homozygous normal, and carrier dogs in some BT pedigrees. CLINICAL RELEVANCE: In informative pedigrees where the marker is variable in the parents, it is possible to identify which dogs will require anticopper therapy and provide breeders with sound scientific advice about breeding strategies.

Alleles↗

Effects of theophylline and ipratropium on cognition in elderly patients with chronic obstructive pulmonary disease.

OBJECTIVES: To determine whether chronic therapy with theophylline or ipratropium has an adverse effect on cognition and psychomotor skills in geriatric patients with chronic obstructive pulmonary disease. DESIGN: The study design was a randomized, repeated measures, double-blind, double-dummy, placebo-controlled comparison of theophylline and ipratropium treatments. SETTING: Ambulatory patients were tested at the Clinical Trials Center of the University of California, San Diego, Medical Center. PATIENTS: Ambulatory patients with chronic obstructive pulmonary disease aged 65 years or more with FEV1 less than 60% predicted, FEV1/FVC less than 70%, and post bronchodilator FEV1 less than 70%. INTERVENTIONS: Patients received either theophylline or ipratropium for 2 weeks, followed by a 1-week placebo control period, then a 2-week treatment period of the alternative drug therapy. A standard therapy of albuterol MDI, 2 puffs (180 microg) qid was given throughout the study. MEASUREMENTS: The main response level was an 11-part battery of psychometric tests. Tests were administered at the end of each treatment period and at the end of the washout period. Covariates were sequence of treatment, pulmonary function tests, age, and baseline psychometric test scores. RESULTS: There was no difference in performance scores on the cognitive tests among the three treatment periods. CONCLUSIONS: We were unable to detect a harmful effect of treatment with either theophylline or ipratropium on the performance of elderly patients with chronic obstructive pulmonary disease on a battery of psychometric tests, suggesting that significant cognitive impairment in the elderly is not commonly associated with treatment with either theophylline or ipratropium.

Aged↗

Environmental and bronchoalveolar lavage Dermatophagoides pteronyssinus antigen levels in atopic asthmatics.

Overnight environmental home exposure to Dermatophagoides pteronyssinus in IgE-sensitized individuals is often clinically associated with increased morning symptoms of rhinitis and/or asthma. We have investigated whether household exposure to D. pteronyssinus is associated with the presence of immunoreactive D. pteronyssinus I antigen (Der p I) in bronchoalveolar lavage (BAL) fluid in nine atopic asthmatics sensitized to D. pteronyssinus. Significant environmental concentrations of D. pteronyssinus were noted by light microscopy and immunoassay in the subjects' bedroom carpets (13.4 +/- 3.8 micrograms immunoreactive Der p I/g dust), mattresses (27.3 +/- 7.2 micrograms immunoreactive Der p I/g dust), and living room carpets (5.9 +/- 1.5 micrograms immunoreactive Der p I/g dust). Immunoreactive Der p I was measurable in 20-fold concentrated BAL fluids (3.4 +/- 1.0 ng/ml concentrated BAL fluid) after overnight home exposure. A 24-h hospitalization in a D. pteronyssinus controlled environment (< 0.02 micrograms Der p I/g dust) resulted in a significant decrease in BAL Der p I concentrations (0.8 +/- 0.6 ng/ml). In vivo studies in nine asthmatics challenged endobronchially with D. pteronyssinus (5-60 ng Der p I) induced significant airway eosinophilia. These studies demonstrate that environmental exposure to microgram amounts of D. pteronyssinus is associated with airway recovery of small nanogram amounts of Der p I.

Adult↗

Words do matter.

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Female↗

Airway levels of mast cell-derived mediators in exercise-induced asthma.

In order to assess the role of mast cell-derived mediators in the pathogenesis of exercise-induced asthma (EIA), we completed pre- and postexercise bronchoalveolar lavage (BAL) in seven atopic subjects with EIA. The study subjects were defined as having EIA if they exhibited a greater than 15% decrease in FEV1 after completing 6 min of treadmill exercise. There were no significant differences between mean preexercise and mean postexercise mast cell-derived BAL histamine (186 +/- 67 versus 148 +/- 36 pg/ml), tryptase (4.5 +/- 2.0 versus 2.8 +/- 2.0 ng/ml), prostaglandin D2 (26 +/- 11 versus 32 +/- 25 pg/ml), or leukotriene C4 (less than 100 versus less than 100 pg/ml). In addition, mast cells present in BAL fluid after exercise contained similar amounts of cellular histamine compared with BAL mast cells obtained before exercise (preexercise BAL cellular histamine, 26.6 +/- 12.3 ng/10(6) BAL cells; postexercise BAL cellular histamine, 22.7 +/- 9.1 ng/10(6) BAL cells), indicating that depletion of preformed mast cell mediators are unlikely to account for the refractory period in EIA. This study suggests that the cellular pathogenesis of EIA (mast cell-independent) differs from current theories of the pathogenesis of extrinsic allergen-induced asthma (mast cell-dependent).

Adolescent↗