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Biomedical subjects

C Pennington

Publications and source records attributed to C Pennington.

12 recordsLinked to original sources

A pilot study of brain tumour growth between radiotherapy planning and delivery.

AIMS: Delays between surgery and the delivery of radiotherapy may allow brain tumours to grow beyond the planned radiotherapy fields and therefore reduce the effectiveness of radiotherapy. This pilot study aimed to ascertain whether significant growth of brain tumours occurs between post-biopsy imaging and the start of radiotherapy. MATERIALS AND METHODS: Two estimates of tumour volume were obtained from contrast-enhanced magnetic resonance images obtained within 3 days of surgical debulking/biopsy (postoperative), and shortly before starting radiotherapy (pre-radiotherapy). The postoperative and pre-radiotherapy volumes were compared to assess tumour growth and expansion of the tumour margin. The enhancing tumour volume was measured on a workstation using two methods: tracing the area of the lesion on each slice on which it appeared and summing the volume in each slice, and by measuring the largest diameters in three planes. The ease of use and intra-operator variability of the two methods were compared. RESULTS: The median time between postoperative and pre-radiotherapy scans was 31.5 days (range 15-53 days). Both methods found that statistically significant tumour growth occurred between postoperative and pre-radiotherapy imaging. The tumour area method found median postoperative volume of 42,849 mm3 (range 4843-148,047 mm3), and median pre-radiotherapy volume of 49,382 mm3 (range 9327-150,850 mm3) and a median growth of 35.07% (range 0-105%). The enhancing tumour margin on the pre-radiotherapy scan overlapped the margin of the postoperative scan by a maximum of 20 mm. Our study found that the diameter method gave lower estimates of tumour growth than the area method. The diameter method was inaccurate when tumours were small or irregularly shaped. CONCLUSION: As a 2-3 cm margin is usually included around the tumour when planning radiotherapy, it seems unlikely that the visible tumour actually grew outwith the planned radiotherapy fields. However, cells beyond the tumour margin visible on imaging could be outside the planned radiotherapy field. This paper highlights difficulties in determining the most appropriate time for baseline radiotherapy planning imaging to be carried out.

Adult↗

Resistance to body fat gain in 'double-muscled' mice fed a high-fat diet.

OBJECTIVE: To determine if myostatin deficiency attenuates body fat gain with increased dietary fat intake. METHODS: Normal and myostatin-deficient mice were fed control (8-10 kcal %fat) and high-fat (HF) (45 kcal %fat) diets for a period of 8 weeks, starting at 2 months of age. Body composition, including percent body fat, lean mass, and fat mass, were measured using DXA. Serum adipokines were measured using a Beadlyte assay. RESULTS: Two-factor ANOVA revealed significant treatment x genotype interactions for body fat (g), percent body fat, and serum leptin. The HF diet significantly increased body fat, percent body fat, and serum leptin in normal mice but not in myostatin-deficient mice. CONCLUSION: Loss of myostatin function not only increases muscle mass in animal models but also attenuates the body fat accumulation that usually accompanies an HF diet.

Adiposity↗

Leptin deficiency produces contrasting phenotypes in bones of the limb and spine.

Leptin is a hormone secreted by adipocytes that can regulate bone mass through a central, neuroendocrine signaling pathway. We tested the hypothesis that the response of bone tissue to altered leptin signaling is not uniform throughout the skeleton, but may vary between different skeletal regions and between cortical and trabecular moieties. We investigated the effects of leptin deficiency on muscle mass and bone architecture in obese, leptin-deficient (ob/ob) mice, and in lean controls. Results indicate that the obese mice weigh approximately twice as much as the lean mice, but the quadriceps muscles of the ob/ob mice are 40% smaller than those of controls. Leptin-deficient mice have significantly shorter femora, lower femoral bone mineral content (BMC), bone mineral density (BMD), cortical thickness, and trabecular bone volume compared to lean mice. Marrow tissue from the femora of ob/ob mice also shows a marked increase in adipocyte number compared to that of normal mice. In contrast to the pattern observed in the femur, ob/ob mice have significantly increased vertebral length, lumbar BMC, lumbar BMD, and trabecular bone volume compared to lean controls. Few adipocytes are observed in bone marrow from lumbar vertebrae of ob/ob mice, despite being numerous in marrow of the femur. However, like the femur, significant cortical thinning is also observed in the spine. These results indicate that the effects of altered leptin signaling on bone differ significantly between axial and appendicular regions, and may be mediated in part by muscle mass. The muscle hypoplasia, increased marrow adipogenesis, and decreased bone mass observed in the hindlimbs of ob/ob mice are also observed with aging in humans, suggesting that the ob/ob mouse may be a new and useful animal model for studying the relationship between bone marrow adipogenesis and osteopenia.

Animals↗

Eight years' experience of gastrostomy tube management.

BACKGROUND AND STUDY AIMS: Increasingly, patients fed by gastrostomy tube are surviving the lifespan of the device. Data are scarce concerning the factors affecting the longevity and failure of gastrostomy tubes or the criteria for selection of replacement devices which leads to cost-effective patient management. The aims of the study were: to set criteria for selection of replacement gastrostomy tubes; to determine the causes of gastrostomy tube failure, and the factors affecting device longevity; and to examine the effect of initiating an educational programme for caregivers on resource utilization in long-term enteral nutrition patients. MATERIALS AND METHODS: We analyzed the clinical gastrostomy tube database compiled prospectively over 8 years by the nutrition team at Ninewells Hospital, Dundee. RESULTS: For 363 gastrostomy tubes inserted in 304 patients (160 women; median age 71), the median duration of gastrostomy tube use was 138 days. The total follow-up was 294 patient-years. Death occurred before the first gastrostomy tube replacement in 48 % of patients, but 20 % resumed oral nutrition. Tube failure mechanisms were: dislodgment, 28 %; perishing of tube material, 25 %; tube-related Candida albicans infection, 16 %; leakage, 7 %; and unspecified, 7 %. Of the balloon tubes and gastrostomy buttons, 8 % needed early replacement due to dislodgment and/or leakage. The cost per day for replacement percutaneous endoscopic gastrostomy (PEG) was Euro 2.12, for balloon tubes it was Euro 0.62, and for gastrostomy buttons Euro 1.80. Despite an increasing PEG insertion rate throughout the study period, yearly referrals for PEG-related problems dropped by 30 % between 1997 to 1999, coinciding with the initiation of an educational programme for caregivers. CONCLUSION: Tube longevity is mainly limited by the patient's diagnosis and prognosis. The choice of replacement device should be based on clinical factors. The use of more durable materials in the manufacture of gastrostomy tubes may prolong tube life and reduce cost. Education of patients and caregivers by a multidisciplinary nutrition support team promotes independence and limits demand on the service.

Adolescent↗

What's new at the point of care?

Preview the latest in near-patient specimen analysis technology, including blood glucose and occult blood tests, and ways to measure heparin's anti-coagulation.

Clinical Laboratory Techniques↗

Nuclear factor kappaB activation in acute appendicitis: a molecular marker for extent of disease?

Nuclear factor-kappaB (NF-kappaB) has been demonstrated to regulate the transcription of target genes and stimulate inflammatory cytokine responses in a variety of inflammatory diseases. Preliminary studies have demonstrated that NF-kappaB is activated early in acute inflammation and sepsis and may serve as an indicator of clinical severity. The present study was designed to evaluate the degree of activation of NF-kappaB in patients with acute appendicitis and correlate activation with clinical extent of disease. Ten patients with acute appendicitis and five control patients (elective inguinal hernia repair) were evaluated by assaying NF-kappaB activity preoperatively and 12 to 18 hours postoperatively. Assaying of NF-kappaB was determined by binding activity for consensus probes in nuclear extracts from peripheral mixed white blood cells obtained by venous puncture. The bands of NF-kappaB activity from gel electrophoresis were quantified with a phosphor imager and reported as units of integrated intensity. The preoperative NF-kappaB activity was increased in all patients with appendicitis versus the controls [mean 151 (range 97-189) vs mean 50.3 (range 13.7-77); P < 0.0001]. The increased NF-kappaB activity also correlated with length of time of symptoms before operation. The patients who were symptomatic for less than 24 hours had an average NF-kappaB value of 103 (range 97-105) versus 171.4 (range 152-189) (P < 0.0001) in those who were symptomatic 24 or more hours. The NF-kappaB activity did not correlate with the white blood cell count. Postoperative NF-kappaB binding activity in the appendicitis patients dropped to minimal levels (mean 50.3), even lower than the control patients' baseline values (mean 55.6). Control patients demonstrated low baseline values preoperatively and a slight rise postoperatively [mean 50.3 (range 13.7-77) vs mean 100 (range 45-186)]. We conclude the following: (1) NF-kappaB binding activity is elevated in patients with acute appendicitis and correlates with symptoms longer than 24 hours. (2) This increased activity returns to baseline values within 18 hours after appendectomy. (3) Molecular indicators of inflammation may have a role in both staging surgical inflammatory conditions and predicting ultimate outcome.

Acute Disease↗

Two-stage procedure for evaluating interassay carryover on random-access instruments.

A two-stage statistical procedure based on Dunnett's multiple comparison procedures with a control has been developed for detecting interassay carryover biases on the Abbott AxSYM(TM) System, a random- and continuous-access immunoanalyzer. With this procedure, every potential source of interassay carryover can be tested and estimated. In minimizing required sample sizes, the first stage is used primarily to detect and eliminate from further testing the assay reagent sources that do not cause carryover biases and the assay sources that cause very large carryover biases. Retested more extensively in the second testing stage are the cases where the data from the first testing stage are insufficient for judgment. An example data set from the Abbott AxSYM Free T4 assay is used to illustrate the methodology.

Autoanalysis↗

Histological observations on the effects of isoproterenol on regenerating submandibular glands of the rat.

The effect of isoproterenol (IPR) on acinar cell mitoses was studied in regenerating submandibular glands of the rat following partial extirpation. In controls, mitoses of acinar cells were markedly higher on the cut surface (reactive zone) than in the remainder of the gland through 10 ds post-operation. In experimental animals by 5 ds, a burst of mitoses of acinar cells was seen in all areas of the gland except the reactive zone. In the reactive zone, IPR appears to suppress or inhibit the induced mitoses seen in controls.

Animals↗

Hepatic oxygen supply and plasma lactate and glucose in endotoxic shock.

Hepatic oxygen supply and selected blood parameters were recorded in fasted male rates given 20--30 mg/kg Escherichia coli endotoxin intraperitoneally. Mortality was 70% within 24 hours. Measurements during the initial eight hours postendotoxin recorded no differences of hematocrit, systemic arterial pressure, or arterial pO2 between survivors and eventual nonsurvivors. However, by the sixth or eighth hour nonsurvivors showed significantly higher plasma lactate, lower plasma glucose and blood pH, and a greater degree of hypocapnea. In addition, a mean hepatic pO2 had decreased from 25.2 mm Hg during the control to 3.8 mm Hg after six hours. A decline of hepatic oxygen supply also occurred in surviving rats but was significantly less severe. Control rats showed a mild degree of respiratory alkalosis but were otherwise stable over eight hours. The relationship of hepatic oxygen supply to differences of plasma lactate and glucose is discussed. Failure of hepatic circulation is cited as the probable cause of extensive liver anoxia and related developments in nonsurviving endotoxic rats.

Acid-Base Equilibrium↗

Increased osteogenic response to exercise in metaphyseal versus diaphyseal cortical bone.

Recent experimental data suggest that the anabolic response of bone to changes in physical activity and mechanical loading may vary among different skeletal elements, and even within different regions of the same bone. In order to better understand site-specific variation in bone modeling we used an experimental protocol in which locomotor activity was increased in laboratory mice with regular treadmill exercise for only 30 min/day. We predicted that the regular muscle contractions that occur during exercise would significantly increase cortical bone formation in these animals, and that the increase in cortical bone mass would vary between metaphyseal and diaphyseal regions. Cortical bone mass, density, and bone geometry were compared between these two regions using pQCT technology. Results indicate that exercise increases bone mineral content (BMC) in the mid-diaphysis by approximately 20%, whereas bone mass in the metaphyseal region is increased by approximately 35%. Endosteal and periosteal circumference at the midshaft are increased with exercise, whereas increased periosteal circumference is accompanied by marked endosteal contraction at the metaphysis, resulting in an increase in cortical area of more than 50%. These findings suggest that the osteogenic response of cortical bone to exercise varies significantly along the length of a bone, and more distal regions appear most likely to exhibit morphologic changes when loading conditions are altered.

Animals↗