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Biomedical subjects

F Campbell

Publications and source records attributed to F Campbell.

At least 55 records · Page 3Linked to original sources

Posterior lumbar interbody fusion. Association between disability and psychological disturbance in noncompensation patients.

STUDY DESIGN: An observational study of the relation between disability and psychological distress in patients with no on-going compensation claim who underwent posterior lumbar interbody fusion for chronic low back pain. OBJECTIVES: To study the change in the relation between disability and psychological distress after surgical management for low back pain. SUMMARY OF BACKGROUND DATA: Patient-related factors such as an on-going compensation claim and patient psychology are thought to influence the outcome of low back pain management. METHODS: Of the 58 patients who underwent posterior lumbar interbody fusion for low back pain between 1990 and 1995, 53 were observed for a mean duration of 2.7 years after surgery. Oswestry Disability scores and Distress and Risk Assessment Method scores were collected before surgery and at the follow-up examination. RESULTS: Improvement of 10 points on the Oswestry Disability Score was observed in 52.8% of the patients. However, the results in patients who were distressed before surgery were similar to the results observed in healthy patients. The difference in the Oswestry Disability Scores was 3.1 (95% confidence intervals [-9.9, 16.2], P = 0.297). The change in Distress and Risk Assessment Method scores showed a significant relation to change in the Oswestry Disability Scores (P = 0.033). CONCLUSIONS: Postoperative improvement in disability was not found to be related to preoperative psychology as measured by the Distress and Risk Assessment Method score. Change in disability is significantly related to change in distress.

Adult↗

Laser doppler imaging--a new technique for quantifying microcirculatory flow in patients with primary Raynaud's phenomenon and systemic sclerosis.

This was a pilot study to investigate the new technique of laser Doppler imaging (scanning laser Doppler) as a tool to quantify microvascular blood flow in the digits of patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc), and to determine in the first instance whether the flux patterns obtained differ between patients with SSc, patients with PRP, and healthy control subjects. Laser Doppler images of the dorsum of the hand and fingers were acquired at 23 and 30 degrees C in 17 healthy control subjects, 7 patients with PRP, 9 patients with the diffuse cutaneous variant of SSc, and 24 patients with the limited cutaneous variant of SSc. Different flux parameters were compared between groups. Analysis of variance found significant differences between groups in two tests: maximum difference in flux between fingertips of the same hand at 23 degrees C (P = 0.001) and maximum gradient in flux along a finger ("distal-dorsal" flux difference) at 30 degrees C (P = 0. 019). Post hoc tests highlighted the differences between controls and patients with limited cutaneous SSc. This pilot study suggests that laser Doppler imaging may allow objective measurement of microvascular flow in patients with PRP and SSc. This new technique may overcome many of the problems inherent in single-channel laser Doppler equipment.

Adult↗

New classification of oesophageal and gastric carcinomas derived from changing patterns in epidemiology.

The current ICD-O classification of carcinomas of the oesophagus and stomach causes epidemiological and clinical confusion. This study compares the epidemiological and clinical features of each subtype and subsite of adenocarcinomas of the oesophagus and stomach, to assess requirements for a new classification of these carcinomas. Data were extracted with appropriate validity checks on all cases of oesophageal and gastric carcinomas identified throughout the period 1974-1993 by the Merseyside and Cheshire Cancer Registry, which covers a population of 2.5 million. The incidence of adenocarcinomas of the lower oesophagus and cardia trebled in males, and doubled in females, whereas adenocarcinoma of the subcardia region of the stomach declined in both sexes. Adenocarcinomas of the lower oesophagus and of the cardia were similar for median age at diagnosis, male to female ratio, percentage of patients who smoked and survival; both were significantly different from carcinomas of the subcardia in these respects. These data imply that adenocarcinomas of the lower oesophagus and cardia are the same disease. A new subsite classification of oesophageal and gastric carcinomas is proposed that includes the gastro-oesophageal junction as a distinct subsite, to facilitate surveillance, management and research.

Adenocarcinoma↗

Antibody response to accelerated Hib immunisation in preterm infants receiving dexamethasone for chronic lung disease.

AIM: To study the effect of dexamethasone on the routine immunisation of preterm infants with chronic lung disease. METHODS: Serum samples were obtained before and after immunisation from an unselected cohort of 59 preterm infants. Haemophilus influenzae antibodies were measured using an ELISA method and differences in the geometric mean values between the two groups of babies analysed. RESULTS: Sixteen infants received no dexamethasone. Before and after immunisation antibody titres for those receiving no dexamethasone were 0.16 and 4.63 mcg IgG/ml. Corresponding values for those receiving dexamethasone were 0.10 and 0.51 mcg IgG/ml, respectively. CONCLUSION: Dexamethasone used in the treatment of chronic lung disease seems to significantly affect the antibody response of preterm infants to immunisation against Haemophilus influenzae.

Anti-Inflammatory Agents↗

The "distal-dorsal difference" as a possible predictor of secondary Raynaud's phenomenon.

OBJECTIVE: To investigate the possibility that a hand distal-dorsal difference in temperature of greater than 1 degree C (fingers colder than the dorsum) at a room temperature of 30 degrees C is a good predictor of secondary Raynaud's phenomenon (RP). METHODS: We imaged the hands of patients with primary Raynaud's phenomenon (PRP) and systemic sclerosis (SSc) using a thermal camera at room temperatures of 23 and 30 degrees C. From these images we measured the distal-dorsal difference in temperature for all fingers excluding the thumbs. At a room temperature of 23 degrees C we also performed a cold challenge test using water at 15 degrees C for 1 min and thermally imaged the rewarming process for 15 min. Several variables were derived from the rewarming curve. The procedure was repeated within 3 days to assess reproducibility. RESULTS: The best discriminator between PRP and SSc was found to be a distal-dorsal difference of > 1 degree C at 30 degrees C (p = 0.005). There is reasonable reproducibility when considering groups of patients. However, the intra-subject standard deviations were large, indicating that measurements for the same patient on separate visits may vary considerably. CONCLUSION: Our results suggest that the finding of a distal-dorsal difference of > 1 degree C (cold fingers) at 30 degrees C in a patient with RP is specific for underlying connective tissue disease.

Adolescent↗

Systematic review of efficacy of cognitive behaviour therapies in childhood and adolescent depressive disorder.

OBJECTIVE: To determine whether cognitive behaviour therapy is an effective treatment for childhood and adolescent depressive disorder. DESIGN: Systematic review of six randomised trials comparing the efficacy of cognitive behaviour therapy with inactive interventions in subjects aged 8 to 19 years with depressive disorder. MAIN OUTCOME MEASURE: Remission from depressive disorder. RESULTS: The rate of remission from depressive disorder was higher in the therapy group (129/208; 62%) than in the comparison group (61/168; 36%). The pooled odds ratio was 3.2 (95% confidence interval 1.9 to 5.2), suggesting a significant benefit of active treatment. Most studies, however, were based on relatively mild cases of depression and were of only moderate quality. CONCLUSIONS: Cognitive behaviour therapy may be of benefit for depressive disorder of moderate severity in children and adolescents. It cannot, however, yet be recommended for severe depression. Definitive large trials will be required to determine whether the results of this systematic review are reliable.

Adolescent↗

Clonal overexpression of metallothionein is induced by somatic mutation in morphologically normal colonic mucosa.

Metallothionein (MT) overexpression occurs frequently in human tumours but the underlying mechanism is unknown. Morphologically normal-appearing mucosa from human colorectal carcinoma resection specimens and of the colons of ageing laboratory mice contains scattered single crypts whose cells show uniformly increased MT immunostaining, suggesting that MT overexpression arises directly from random crypt stem cell somatic mutation, followed by colonization of the clonal unit by the mutated progeny. This hypothesis has now been tested by quantifying the frequency of immunocytochemically detectable monocryptal colorectal MT overexpression, 5 and 30 days after injection of 8-week-old mice with a single dose of the mutagen dimethylhydrazine (DMH, 30 mg/kg subcutaneous). Otherwise normal-appearing MT-positive crypts were recorded as either wholly or partially involved by the overexpressing phenotype. Five days after DMH injection, the median frequency of partially involved MT-positive crypts was 11.7 x 10(-4), declining significantly to 1.8 x 10(-4) at 30 days (Mann-Whitney U, P < 0.01). In contrast, the median frequency of wholly involved crypts was 0.2 x 10(-4) at 5 days, increasing significantly (P < 0.005) to 12.9 x 10(-4) at 30 days. The frequency of MT-positive crypts and the time course of evolution of partially involved to wholly involved forms were similar to those described for mutation-induced crypt-restricted loss of glucose-6-phosphate dehydrogenase activity in mice treated with an identical DMH regimen. The findings indicate that cellular MT overexpression can occur as a direct consequence of somatic mutation, either cis-activating mutation(s) of the MT gene itself, or trans-activating mutation(s) of other genes involved in controlling MT expression. This is likely to be an important mechanism underlying MT overexpression in neoplasia. Such mutation-induced aberrant MT expression may be involved in the acquisition of selective cellular growth of survival advantage during tumour progression.

1,2-Dimethylhydrazine↗

No difference in stem cell somatic mutation between the background mucosa of right- and left-sided sporadic colorectal carcinomas.

Epidemiological, morphological, and molecular differences exist between carcinomas of the right and left sides of the large bowel. To investigate whether this is reflected in differences in somatic mutation frequency in the background mucosa, mutation of the neutral O-acetyltransferase gene (oat) was quantified in histologically normal resection margins from 20 informative (heterozygous) patients with caecal or ascending colon cancer (11 males, median age 75 years) and 20 with sigmoid colon or rectal cancer (10 males, median age 70 years). Mutant discordant crypts lacking O-acetyltransferase activity were visualized by mPAS staining and classified as wholly or partially involved by the mutant phenotype; median frequencies (x10(-4) were compared (Mann-Whitney U-test) after assessing a sample of more than 10,000 crypts per case. No significant difference was found between the frequencies of wholly involved mPAS-positive crypts in background mucosa of left- and right-sided cancers (p = 0.4569), indicating that tumours on both sides of the colon are associated with similar levels of lifetime-accumulated stem cell mutational load. However, partially involved mPAS-positive crypts were significantly more frequent in mucosa from left-sided cancers (p < 0.04), indicating increased mutational activity during the previous 12 months. Analysis of mucosa proximal and distal to left-sided cancers showed that this increase was due to a statistically higher frequency of partially involved crypts in proximal mucosa, which probably resulted from the obstructive effects of the tumour causing increased exposure of the proximal mucosa to luminal carcinogens and/or epithelial regeneration in response to low-grade inflammation or ischaemia. The findings indicate that although left-sided colonic cancer is commoner than right-sided cancer in the British population, carcinomas on both sides of the large bowel arise in a background of similar levels of stem cell mutational activity.

Acetyltransferases↗

Increased stem cell somatic mutation in the non-neoplastic colorectal mucosa of patients with familial adenomatous polyposis.

Colorectal tumorigenesis in familial adenomatous polyposis (FAP) results from somatic mutation of either the normal APC allele or another growth control gene in epithelial cells bearing a germline APC defect. The rate at which tumors develop is therefore dependent on the somatic mutation frequency; it is not known whether this is normal or elevated in FAP. We aimed to quantify stem cell somatic mutation in FAP, comparing it with hereditary nonpolyposis colorectal cancer (HNPCC) and Crohn's disease (CD). Stem cell somatic mutation frequency was studied in 47 FAP patients, 5 HNPCC patients, and 13 CD patients, all younger than 49 years, by quantifying crypt-restricted loss of O-acetyltransferase activity in sections of morphologically normal colonic mucosa from individuals heterozygous for this monogenically inherited polymorphism. Median stem cell somatic mutation frequency was significantly higher in FAP than HNPCC (4.2 x 10(-4) v 1.4 x 10(-4), Mann-Whitney U, P < .02). The level in CD (4.0 x 10(-4)) was similar to FAP. Mutated crypts occurred in groups more frequently in FAP (22%) than HNPCC (12%) or CD (10%), suggesting an increase in stem cell division associated with crypt fission in FAP. We conclude that stem cell somatic mutation frequency is raised in non-neoplastic colorectal mucosa in FAP. This is probably related to increased stem cell proliferation and contributes to the high rate of tumor formation in this condition.

Adenomatous Polyposis Coli↗

Bilateral femoral agenesis in femoral facial syndrome in a 19-week-old fetus.

Although the cause in most cases is unknown, there is a strong association of the femoral facial syndrome (FFS) with maternal diabetes mellitus. We describe an unusual presentation of FFS in the first pregnancy of a diabetic mother terminated at 19 weeks gestation because of bilateral femoral agenesis diagnosed on ultrasound scan. Autopsy confirmed the absence of the femora and acetabula and the presence of the facial traits of FFS in a female fetus.

Abnormalities, Multiple↗

Patients' assessment of sensory levels during epidural analgesia in labour.

Thirty women in established labour and with epidurals in situ were asked to assess the sensory level of the epidural using loss of light touch sensation with their own finger. This dermatomal level was then compared to the sensory level assessed by an anaesthetist using loss of cold sensation with ethyl chloride spray. A total of 88 assessments were made. The mean dermatomal difference was 0.20 and 95% of the differences lay between 3.5 and -3.1 dermatomes. This large variation in dermatomal differences between the two methods of sensory assessment means that patient light touch is not an acceptable method of assessing epidural sensory level when compared to ethyl chloride.

Journal Article↗

The influence of age, gender, Helicobacter pylori and smoking on gastric mucosal adaptation to non-steroidal anti-inflammatory drugs.

INTRODUCTION: Oral NSAIDs cause acute gastric injury that resolves, despite continued administration, by a process known as adaptation. Little is known about the factors that influence this process. METHODS: Sixty-two healthy volunteers were given a 28-day course of either etodolac 300 mg b.d. (13 subjects), naproxen 500 mg b.d. (23), enteric-coated diclofenac (10) or effervescent diclofenac 50 mg b.d. (16). All subjects were gastroscoped before and on days 1, 7 and 28 during drug administration, to assess gastric mucosal damage using a modified Lanza scale. Subjects were then divided into three categories: those who adapted completely, those who adapted incompletely and those who showed no adaptation. The proportion of subjects in each group was compared with respect to age, gender, smoking, the presence of Helicobacter pylori, and the NSAID prescribed. RESULTS: Fifty-nine subjects (median age 25.0 years, range 18-70) developed initial gastric injury to NSAIDs of whom 42 adapted completely, 13 adapted incompletely and four showed no evidence of adaptation. The mean age of subjects was lower in those who adapted (26.8 +/- 9.8 years) than those who adapted incompletely (32.5 +/- 10.3 years) and those who did not adapt (42.0 +/- 15.7 years, P = 0.01). There was no evidence of gender influencing adaptation. Of 17 H. pylori-positive subjects, a higher proportion had incomplete adaptation, with only nine subjects adapting completely (53% vs. 81%, P = 0.04). Sixteen subjects were smokers, of whom a greater proportion showed no evidence of adaptation (19% vs. 2%, P = 0.03). A smaller proportion of those who took naproxen (48%) adapted completely than those who took enteric-coated diclofenac (89%), effervescent diclofenac (75%) or etodolac (91%, P = 0.03). CONCLUSION: Some adaptation occurred in over 90% of subjects after 4 weeks dosing with an NSAID, but adaptation was less frequent in older subjects and in smokers. Complete adaptation occurred less frequently in H. pylori-positive subjects and in those who were given naproxen.

Adolescent↗

Reducing accident death rates in children and young adults: the contribution of hospital care. Steering Committee of the Major Trauma Outcome Study Group.

OBJECTIVE: To assess the contribution of trauma care to the recent decline in accident death rates among children and young people. DESIGN: Logistic regression modelling of temporal trends in the probability of death in patients admitted to hospital for the treatment of severe injury. SETTING: Hospitals participating the United Kingdom major trauma outcome study. SUBJECTS: 3230 patients with an injury severity score of 16 or more, who were admitted for more than three days, transferred or admitted to intensive care, or died from their injuries. MAIN OUTCOME MEASURES: Death or survival in hospital within three months of injury. RESULTS: Over the seven year period 1989-95 there was a substantial decline in the probability of death among children and young adults admitted to hospital after severe injury. The overall estimate of the reduction in the odds of death was 16% per year (odds ratio for the yearly trend 0.84; 95% confidence interval 0.79 to 0.89). This decline did not differ significantly between age groups. (0-4 years 0.79; 5-14 years 0.87; 15-24 years 0.83). CONCLUSIONS: Reductions in hospital case fatality have made an important contribution to reaching the Health of the Nation targets. The contribution of hospital care in the reduction of accident mortality should be taken into account in decisions about the allocation of resources to preventive and curative services.

Accidents↗

The urinary bladder angiotensin system: response to infusions of angiotensin I and angiotensin-converting enzyme inhibitors.

The circulating and urinary bladder tissue concentrations of angiotensin I (ANG I) and angiotensin II [ANG-(1-8)] were examined in anesthetized Sprague-Dawley male rats given an intravenous bolus infusion of either ANG I, the angiotensin-converting enzyme (ACE) inhibitors enalaprilat or ramiprilat, or saline. The mean concentrations of ANG I and ANG-(1-8) were markedly higher in the urinary bladder tissue than in whole blood. There was a significant increase in the concentration of ANG I and ANG-(1-8), both in the urinary bladder tissue and the circulation, after the ANG I infusion. Both ACE inhibitors were associated with an increase in the concentration of whole blood ANG I; however, tissue ANG I levels were significantly increased only following ACE inhibition with ramiprilat but not with enalaprilat. Both plasma and urinary bladder tissue ANG-(1-8) levels decreased significantly following ACE inhibition, but only with ramiprilat. The elevated urinary bladder tissue levels of ANG I and ANG-(1-8) at baseline, compared with circulating levels, and the maintenance of ANG-(1-8) in bladder tissue in the face of inhibition of the circulatory renin-angiotensin system with enalaprilat support the presence of an autocrine/paracrine renin-angiotensin system in the urinary bladder. Under the current experimental conditions, ramiprilat appears to have enhanced bladder activity compared with enalaprilat.

Anesthesia↗

Post-irradiation somatic mutation and clonal stabilisation time in the human colon.

BACKGROUND: Colorectal crypts are clonal units in which somatic mutation of marker genes in stem cells leads to crypt restricted phenotypic conversion initially involving part of the crypt, later the whole crypt. Studies in mice show that the time taken for the great majority of mutated crypts to be completely converted, the clonal stabilisation time, is four weeks in the colon and 21 weeks in the ileum. Differences in the clonal stabilisation time between tissues and species are thought to reflect differences in stem cell organisation and crypt kinetics. AIM: To study the clonal stabilisation time in the human colorectum. METHODS: Stem cell mutation can lead to crypt restricted loss of O-acetylation of sialomucins in subjects heterozygous for O-acetyltransferase gene activity. mPAS histochemistry was used to visualise and quantify crypts partially or wholly involved by the mutant phenotype in 21 informative cases who had undergone colectomy up to 34 years after radiotherapy. RESULTS: Radiotherapy was followed by a considerable increase in the discordant crypt frequency that remained significantly increased for many years. The proportion of discordant crypts showing partial involvement was initially high but fell to normal levels about 12 months after irradiation. CONCLUSIONS: Crypts wholly involved by a mutant phenotype are stable and persistent while partially involved crypts are transient. The clonal stabilisation time is approximately one year in the human colon compared with four weeks in the mouse. The most likely reason for this is a difference in the number of stem cells in a crypt stem cell niche, although differences in stem cell cycle time and crypt fission may also contribute. These findings are of relevance to colorectal gene therapy and carcinogenesis in stem cell systems.

Adult↗