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Peter Campbell

Publications and source records attributed to Peter Campbell.

At least 19 recordsLinked to original sources
PubMed2025

Complex de novo structural variants are an underestimated cause of rare disorders.

Complex de novo structural variants (dnSVs) are crucial genetic factors in rare disorders, yet their prevalence and characteristics in rare disorders remain poorly understood. Here, we conduct a comprehensive analysis of whole-genome sequencing data of 12,568 families, including 13,698 offspring with rare diseases, obtained as part of the UK 100,000 Genomes Project. We identify 1,870 dnSVs, constituting the largest dnSV dataset reported to date. Complex dnSVs (n = 158; 8.4%) emerge as the third most common type of SV, following simple deletions and duplications. We classify 65% of these complex dnSVs into 11 subtypes. Among probands with dnSVs (n = 1,696), 9% exhibit exon-disrupting pathogenic dnSVs associated with the probands' phenotype. Notably, 12% of exon-disrupting pathogenic dnSVs and 22% of de novo deletions or duplications previously identified by array-based or whole-exome sequencing methods are found to be complex dnSVs. We also find distinct genomic properties of de novo deletions depending on the parent of origin. This study highlights the importance of complex dnSVs in the cause of rare disorders and demonstrates the necessity of specific genomic analysis to avoid overlooking these variants.

Humans↗
PubMed2005

Role of stereotactic radiosurgery as a primary treatment option in the management of newly diagnosed multiple (3-6) intracranial metastases.

OBJECTIVE: The objective of this study was to assess the role of stereotactic radiosurgery in the management of newly diagnosed multiple intracranial metastases from known primary cancer locations. METHODS: Fifty (29 women and 21 men) patients received radiosurgery for newly diagnosed 3 or more metastatic brain tumors. Their mean age was 53 years. Lung cancer was the most common primary cancer (66%). RESULTS: Arrest in the growth of irradiated tumors was achieved in 41 (82%) patients. Eight patients (16%) required further intervention for tumors in other brain locations. Mean survival after diagnosis of brain disease was 12 months and the brain disease-controlled period was 19 months. The period of brain disease control prolonged (P=.03) with decreasing tumor volumes (<10 mL). Control of treated tumors positively affected survival after diagnosis of brain disease (P=.0001). CONCLUSION: Radiosurgery as an adjuvant improves survival in patients with cancer who have newly diagnosed multiple intracranial metastases by arresting the growth of tumors.

Adult↗
PubMed2005

Effects of calcium and dairy on body composition and weight loss in African-American adults.

OBJECTIVE: Our objective was to determine the effects of dairy consumption on adiposity and body composition in obese African Americans. RESEARCH METHODS AND PROCEDURES: We performed two randomized trials in obese African-American adults. In the first (weight maintenance), 34 subjects were maintained on a low calcium (500 mg/d)/low dairy (<1 serving/d) or high dairy (1200 mg Ca/d diet including 3 servings of dairy) diet with no change in energy or macronutrient intake for 24 weeks. In the second trial (weight loss), 29 subjects were similarly randomized to the low or high dairy diets and placed on a caloric restriction regimen (-500 kcal/d). RESULTS: In the first trial, body weight remained stable for both groups throughout the maintenance study. The high dairy diet resulted in decreases in total body fat (2.16 kg, p < 0.01), trunk fat (1.03 kg, p < 0.01), insulin (18.7 pM, p < 0.04), and blood pressure (6.8 mm Hg systolic, p < 0.01; 4.25 mm Hg diastolic, p < 0.01) and an increase in lean mass (1.08 kg, p < 0.04), whereas there were no significant changes in the low dairy group. In the second trial, although both diets produced significant weight and fat loss, weight and fat loss on the high dairy diet were approximately 2-fold higher (p < 0.01), and loss of lean body mass was markedly reduced (p < 0.001) compared with the low dairy diet. DISCUSSION: Substitution of calcium-rich foods in isocaloric diets reduced adiposity and improved metabolic profiles in obese African Americans without energy restriction or weight loss and augmented weight and fat loss secondary to energy restriction.

Adipose Tissue↗
PubMed2005

Comparison of PCR-ELISA and galactomannan detection for the diagnosis of invasive aspergillosis.

AIM: To compare PCR with galactomannan antigen detection for the diagnosis of invasive aspergillosis (IA). METHODS: We prospectively collected serial blood samples from haematological patients at risk of IA, and analysed their samples retrospectively for galactomannan (GM) antigen using the Platelia test and for aspergillus DNA using an in-house PCR-ELISA assay. Matched GM and PCR analyses were performed on 263 samples from 25 patients. Patients were classified for potential IA according to international consensus criteria, with five patients classified as positive (four proven, one probable) and 20 classified as negative (seven possible, 13 no evidence IA). RESULTS: All five patients with IA were positive by PCR with positive results in 24 of 82 samples, whereas three of five patients were positive by GM with four of 82 samples being positive. Three of 20 patients without IA were positive by PCR in 18 of 181 samples, whereas corresponding results for GM detection were one of 20 and one of 181, respectively. Adjustment of ELISA cut-off values and/or the requirement for two consecutive samples to be positive generated different results; however, lowering the positivity index (PI) for GM detection to 0.5 did not improve the sensitivity of the assay. Optimal results for PCR detection and GM were: 100% and 60% sensitivity, 85% and 95% specificity, 0.625 and 0.75 positive predictive value, and 1.0 and 0.8 negative predictive value, with a false-positive sample rate of 8 and 0.4%, positive likelihood ratio of 6.66 and 11.99 and negative likelihood ratio of 0 and 0.42, respectively. CONCLUSIONS: This PCR method is very sensitive for the diagnosis of IA but is associated with a moderate rate of false positives; the GM assay exhibited poor sensitivity but high specificity. Further evaluation of PCR assays for the diagnosis of IA and other invasive fungal infections is warranted.

Adolescent↗
PubMed2005

Serum intact parathyroid hormone as a predictor of hypocalcaemia after total thyroidectomy.

BACKGROUND: Hypocalcaemia from hypoparathyroidism is a complication of total thyroidectomy. The aim of the present study was to determine whether an early postoperative level of serum parathyroid hormone (PTH) after total thyroidectomy predicts the development of significant hypocalcaemia and the need for treatment. METHODS: Patients undergoing total thyroidectomy had their serum level of intact PTH checked 1 h after removal of the thyroid gland. Serum calcium level was checked on the following morning. Oral calcium and/or calcitriol was commenced if the patient developed hypocalcaemic symptoms, or if the corrected serum calcium level was <2.0 mmol/L. RESULTS: Seventy-nine patients were included in the present study. Thirteen patients had symptoms of hypocalcaemia on postoperative days 1 or 2 and 66 patients remained asymptomatic. The postoperative intact PTH, day 1 calcium and day 2 calcium was 0.32 +/- 0.60 pmol/L, 2.01 +/- 0.11 mmol/L, and 2.02 +/- 0.16 mmol/L, respectively, for the symptomatic group and 1.98 +/- 1.25, 2.21 +/- 0.13, and 2.19 +/- 0.14, respectively, for the asymptomatic group. Calcium support was given to 25 patients, of whom 14 also required calcitriol. CONCLUSION: Serum PTH 1-h after total thyroidectomy is a reliable predictor of hypocalcaemia and can allow safe early discharge of patients from hospital.

Female↗
PubMed2004

Delays in open fracture management: where do they occur?

We audited the delays in the management of 29 patients presenting to our department with 30 open fractures over a 1-year-period to ascertain where the most lengthy delays were occurring. Gold standard treatment is the surgical debridement and stabilisation of the fracture within 6h of injury. In our series only 14 patients achieved this standard. The lengthiest delays were in getting a patient to the operating theatre following orthopaedic assessment. We have introduced an "open fracture proforma" to highlight the time-critical nature of the injury in an effort to speed-up the process.

Debridement↗
PubMed2004

Calcium and dairy acceleration of weight and fat loss during energy restriction in obese adults.

OBJECTIVE: Increasing 1,25-dihydroxyvitamin D in response to low-calcium diets stimulates adipocyte Ca2+ influx and, as a consequence, stimulates lipogenesis, suppresses lipolysis, and increases lipid accumulation, whereas increasing dietary calcium inhibits these effects and markedly accelerates fat loss in mice subjected to caloric restriction. Our objective was to determine the effects of increasing dietary calcium in the face of caloric restriction in humans. RESEARCH METHODS AND PROCEDURES: We performed a randomized, placebo-controlled trial in 32 obese adults. Patients were maintained for 24 weeks on balanced deficit diets (500 kcal/d deficit) and randomized to a standard diet (400 to 500 mg of dietary calcium/d supplemented with placebo), a high-calcium diet (standard diet supplemented with 800 mg of calcium/d), or high-dairy diet (1200 to 1300 mg of dietary calcium/d supplemented with placebo). RESULTS: Patients assigned to the standard diet lost 6.4 +/- 2.5% of their body weight, which was increased by 26% (to 8.6 +/- 1.1%) on the high-calcium diet and 70% (to 10.9 +/- 1.6% of body weight) on the high-dairy diet (p < 0.01). Fat loss was similarly augmented by the high-calcium and high-dairy diets, by 38% and 64%, respectively (p < 0.01). Moreover, fat loss from the trunk region represented 19.0 +/- 7.9% of total fat loss on the low-calcium diet, and this fraction was increased to 50.1 +/- 6.4% and 66.2 +/- 3.0% on the high-calcium and high-dairy diets, respectively (p < 0.001). DISCUSSION: Increasing dietary calcium significantly augmented weight and fat loss secondary to caloric restriction and increased the percentage of fat lost from the trunk region, whereas dairy products exerted a substantially greater effect.

Adipose Tissue↗
PubMed2003

Monoclonal antibody therapy for lymphoma.

Monoclonal antibodies are an exciting advance in the treatment of lymphoma. They are safe and well-tolerated, and exhibit little cross-resistance with conventional chemotherapeutic agents. In indolent lymphomas, antibody therapy has shown useful response rates, both as first-line therapy and in relapsed disease. Follicular lymphomas appear to be particularly sensitive to rituximab, and chronic lymphocytic leukaemia to alemtuzumab. In aggressive lymphomas, the addition of rituximab to CHOP chemotherapy significantly lengthens disease-free and overall survival compared to CHOP alone as first-line therapy. Newer agents, including radiolabelled antibodies, immunotoxin-linked antibodies and antibodies against novel target antigens are showing promise in phase I and II trials in a variety of clinical settings.

Alemtuzumab↗
PubMed2003

Clinical and molecular aspects of adrenocortical tumourigenesis.

Adrenal masses are a common problem affecting 3-7% of the population. The majority turn out to be benign adrenocortical adenomas, which may be functional or non-functional. Much more rarely, these masses represent a primary adrenal carcinoma. It is becoming increasingly recognized that of the benign functioning adenomas or hyperplasias, the majority will hypersecrete aldosterone and this will be more frequently detected when hypertensive populations are screened for this disease. In contrast, the incidence of primary adrenocortical carcinoma has remained steady and for this disease, surgery represents the mainstay of treatment. The advent of laparoscopic adrenal surgery has lowered the threshold size for recommending surgery for asymptomatic adrenal masses and as such, an increased proportion of adrenocortical cancers are being resected and detected at an earlier stage. Recent progress has been made in our understanding of the key genetic changes which underpin the biology of this disease. Progression from adrenal adenoma to carcinoma involves a monoclonal proliferation of cells which, among other defects, have undergone chromosomal duplication at the 11p15.5 locus leading to overexpression of the IGF2 gene and abrogation of expression of the CDKN1C and H19 genes. TP53 is involved in progression to carcinoma in a subset of patients and the frequency of ACTH receptor deletion needs to be more fully explored. Other key oncogenes and tumour suppressor genes remain to be identified although the chromosomal loci in which they lie can be identified at 17p, 1p, 2p16 and 11q13 for tumour suppressor genes and chromosomes 4, 5 and 12 for oncogenes.

Adrenal Cortex Neoplasms↗
PubMed2003

Randomised controlled trial of hip protectors for the prevention of second hip fractures.

OBJECTIVE: to assess whether the use of Safehip hip protectors would prevent second hip fractures among men and women living in the community. DESIGN: pragmatic randomised controlled trial. SETTING: people living in the community. PARTICIPANTS: men and women aged 70 years and over who had sustained one hip fracture and who were living in the community. RESULTS: 366 men and women who were either living outside residential care or were about to be discharged back home were randomised to receive three pairs of hip protectors or to act as controls. Approximately 34% of participants allocated to receive hip protectors wore them every day. After a median follow up of 14 months 8 participants had a second hip fracture with 6 in the intervention and 2 in the control group (Odds Ratio for second hip fracture=3.10, 95% confidence interval 0.62-15.58). Hip protectors had no effect on risk of other fractures or on falls. CONCLUSION: this trial does not suggest a benefit of the studied hip protector among people living outside residential accommodation.

Accidental Falls↗