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Biomedical subjects

W J Campbell

Publications and source records attributed to W J Campbell.

At least 19 recordsLinked to original sources

Screening for colorectal cancer.

Colorectal carcinoma represents a major cause of cancer deaths in the United Kingdom. Tumours detected at an early or even premalignant stage have a better prognosis. In this review we consider the argument for screening for colorectal carcinomas and discuss the means available and the implications of implementing screening programmes using some of these methods. A suggestion is made for the more rational use of limited resources to target those at greatest risk.

Colorectal Neoplasms

Familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant condition resulting in the development of more than 100 adenomatous polyps in the large bowel. In addition, a number of extracolonic manifestations of the condition may occur. Recently, increasing knowledge relating to the extracolonic abnormalities, and localization and sequencing of the gene for FAP, have had important implications for screening and long-term follow-up of those affected. In this review the natural history of the disease and the extracolonic manifestations associated with it are considered. Surgical management and advances in understanding at a molecular level are discussed, as well as the problems relating to screening for FAP and the implications of the new knowledge.

Adenomatous Polyposis Coli

The role of congenital hypertrophy of the retinal pigment epithelium in screening for familial adenomatous polyposis.

Retinal examination by indirect ophthalmoscopy was performed on seventy members from 20 kindreds demonstrating the clinical manifestations of familial adenomatous polyposis and forty controls. Thirty-four of 43 affected patients manifested CHRPE lesions compared with 2 of 27 at risk and 2 of 40 controls giving a sensitivity of 79% and specificity of 95% based on the control group. The difference between the affected and at risk groups was significant (Chi-squared = 34.098, 1 df, P = 0.001). The low sensitivity and variation in incidence of CHRPE in FAP patients and general population documented in the world literature prevent its use as a sole marker for the condition. With advances in knowledge of the disease at a molecular level it is now possible to alter risks for families by DNA analysis. There remain a number of patients in whom such techniques do not significantly alter risks. In these families by combining the results of DNA analysis, sigmoidoscopy and retinal examination it may be possible to alter risks by a significant degree. Retinal examination should be reserved for those families in whom risks cannot be altered sufficiently by DNA analysis alone.

Adenomatous Polyposis Coli

ASAP total knee arthroplasty instrumentation: all six, all precise?

Thirty consecutive cases requiring total knee replacement (TKR) were treated using the Richards Tricon Total Knee System with ASAP (All Six, All Precise) instrumentation (Richards Medical Company, Memphis, TN, USA). Preoperative and postoperative overall coronal alignment were measured using long-leg anteroposterior X-rays. The femoral and tibial bone cuts in this plane were assessed using intraoperative films. The aim was to achieve a postoperative coronal tibio-femoral alignment of 7 degrees valgus. The mean preoperative alignment was 1 degree valgus (SD = +/- 13.5 degrees). A mean postoperative alignment of 8 degrees valgus was obtained (SD = +/- 5.6 degrees). The results obtained in this series suggest that the ASAP system with careful use simplifies the technique of total knee replacement while maintaining accuracy.

Arthritis, Rheumatoid

Expression of fibroblast growth factor receptors by embryonal carcinoma cells and early mouse embryos.

We have previously shown that differentiation of embryonal carcinoma (EC) cells leads to both increased binding of FGF (fibroblast growth factor) and suppression of k-FGF expression. In the current study, we examined the expression of FGF receptors by EC cells, EC-derived differentiated cells and early mammalian embryos using the technique of reverse transcription-polymerase chain reaction (RT-PCR). We determined that both mouse, F9, and human, NT2/D1, EC cells as well as their differentiated counterparts express transcripts for two forms of FGF receptors, bek (bacterially expressed kinase) and flg (fms-like gene). In addition, we determined that mouse blastocysts express flg transcripts. The presence of FGF receptor transcripts in early embryos and the previous finding of FGF-related activity in medium conditioned by mouse blastocysts argue that the FGF family plays important roles during early mammalian development.

Animals

The surgical management of familial adenomatous polyposis in Northern Ireland.

Sixty-eight patients from 18 families have been identified as having familial adenomatous polyposis during the past 30 years in Northern Ireland (population 1.5 million). Six of the 18 probands (33%) had developed colonic carcinoma when first seen at mean age 34 years. Ten of the 44 patients identified by surgical screening (21%) at a significantly lower mean age of 23 years had colonic carcinoma. Surgical management has generally been by subtotal colectomy with ileorectal anastomosis, or by panproctocolectomy and ileostomy.

Adenomatous Polyposis Coli

Regulation and expression of transforming growth factor type-beta during early mammalian development.

We have examined the effect of differentiation on the expression of different members of the transforming growth factor type-beta (TGF-beta) family using embryonal carcinoma (EC) cells and early mammalian embryos. We determined that TGF-beta activity increases approximately 25-100% when the mouse EC cell line, F9, is induced to differentiate with retinoic acid (RA). Interestingly, the increased TGF-beta activity reflects the induction of TGF-beta 2 secretion following differentiation of both F9 EC cells and the human EC cell line, NT2/D1. Using the technique of reverse transcription-polymerase chain reaction (RT-PCR), we have verified that differentiation induces the expression of TGF-beta 2 as well as a distant member of the TGF-beta family, Vgr-1. Transcripts for TGF-beta 2 and Vgr-1 were readily detected in the differentiated cells of F9 and PC-13 but not in their undifferentiated counterparts. Moreover, TGF-beta 2 mRNA was readily detected in NT2/D1 cells following differentiation. In addition, transcripts for TGF-beta 2 were detected by RT-PCR in mouse morulae, preimplantation blastocysts and cultured blastocysts. Based on the data presented, it appears that the expression of both TGF-beta 2 and Vgr-1 is closely associated with the induction of differentiation during early development.

Animals

Expression of transforming growth factor-beta 3 by embryonal carcinoma cells, parietal endoderm-like cells and early mouse embryos.

Utilizing the technique of reverse transcription-polymerase chain reaction (RT-PCR), we have examined the expression of transforming growth factor-beta 3 (TGF-beta 3) by embryonal carcinoma (EC) cells, EC-derived differentiated cells and early mammalian embryos. Using a TGF-beta bioassay, we determined that PYS-2 cells express considerable TGF-beta activity that cannot be completely neutralized by antibodies specific for TGF-beta 1 and TGF-beta 2. We also have determined that PYS-2 cells, as well as F9 EC cells and their differentiated cells, express transcripts for TGF-beta 3. In addition, we have determined that blastocysts, cultured for three days in serum-containing medium, express TGF-beta 3 transcripts. Thus, our data suggest that expression of TGF-beta 3 is initiated during early stages of mammalian development.

Animals

Subungal melanoma.

Subungal melanoma is a rare condition accounting for 1-3% of all melanomas. It has been associated with a poor prognosis, with a 10-30% 5 year survival usually attributed to the delay in diagnosis. Early biopsy of suspicious lesions followed by amputation of the digit in those proving positive is the treatment of choice.

Aged

Effect of fructose consumption during lactation on sow and litter performance and sow plasma constituents.

The effects of dietary consumption of high-fructose corn syrup (HFCS) and dextrose during a 28-d lactation on sow and litter performance and sow plasma constituents were examined in 45 multiparous and 36 primiparous crossbred sows. Isocaloric and isonitrogenous corn-soybean meal diets were formulated to contain either 20% fructose or 20% glucose. Diets were fed on a metabolic BW basis from d 0 to d 28 of lactation. Litter and pig weights on d 28 were not affected (P greater than .05) by treatment. Litter size was greater (P less than .10) at weaning for primiparous sows fed HFCS, but multiparous sows weaned heavier (P less than .05) pigs. Sow weight change during lactation was not influenced by diet, but primiparous sows lost more (P less than .05) weight during lactation and had longer intervals to estrus than multiparous sows did. Milk yields on d 17 and 21 of lactation were not different (P greater than .05) for sows fed HFCS vs dextrose, but sows fed HFCS tended to have greater (P = .05) percentage of milk fat. Preprandial concentrations of fructose in plasma were low in sows fed HFCS and nondetectable in those fed dextrose but were elevated (P less than .05) after consumption of HFCS. Conversely, similar (P greater than .05) concentrations of glucose in plasma preprandially were followed by greater (P less than .05) postprandial glucose concentrations in sows fed dextrose. Although postprandial concentrations of insulin were not affected (P greater than .05) by diet, sows fed dextrose had greater (P less than .05) preprandial insulin concentrations in plasma. Concentrations of nonesterified fatty acids and growth hormone in plasma and response to a glucose challenge were not affected (P greater than .05) by feeding HFCS. However, concentrations of insulin in plasma following glucose infusion were less (P less than .05) during the glucose challenge period on d 25 than on d 13 of lactation.

Animals

Rigid endoscopy under general anaesthesia is safe for chronic injection sclerotherapy.

Injection sclerotherapy for acutely bleeding oesophageal varices has been used in Belfast since 1958. However, a chronic injection sclerotherapy programme with rigid oesophagoscopy under general anaesthesia commenced only in 1979. So far, 82 patients have entered the programme; 57 patients had already received 73 acute injections before commencing chronic sclerotherapy. Subsequently, the 82 patients received 221 chronic injections plus a further 29 acute injections for rebleeding episodes which occurred during the programme. There were 24 Child's grade A patients, 23 B and 35 C; 48 per cent had alcoholic cirrhosis. Forty-eight patients achieved variceal obliteration with a mean of four injections. During the programme 24 patients experienced 42 acute bleeds. There were only two bleeding episodes within 1 week of a chronic injection and eight within 4 weeks. In the 8-year period there have been four early deaths. One occurred 17 days after a chronic injection and three followed acute injections required for rebleeding during the programme. There were 21 late deaths, mostly due to progressive liver failure, and none from rebleeding. We conclude that chronic injection sclerotherapy using rigid oesophagoscopy under general anaesthesia is both safe and effective.

Adolescent

Ovarian inhibition of peripheral plasma concentration of follicle stimulating hormone in prepuberal Holstein heifers.

The objective of this study was to determine effects of age and castration on follicle stimulating hormone (FSH) secretion in prepuberal heifers. In experiment 1, twelve heifers were bilaterally ovariectomized at 3, 6, or 9 months of age (n = 4/group). Blood was collected at 10 min intervals for 8 hr at 1 week before ovariectomy and 1 and 4 weeks after ovariectomy. Frequency, amplitude and duration of FSH pulses were calculated. Mean plasma concentration of FSH (ng/ml), and frequency (pulses/8 hr), amplitude (ng/ml), and duration (min/pulse) of FSH pulses were not altered by age. Mean concentration of FSH increased (P less than .01) from 1 week before to 1 week and 4 weeks after ovariectomy, respectively, in all age groups. Pulse frequency increased (P less than .05) from 1 week before ovariectomy to 4 weeks after ovariectomy in 3 month old heifers, from 1 week before to 4 weeks after ovariectomy in 6 month old heifers, and from 1 week before to 1 week and 4 weeks after ovariectomy in 9 month old heifers. In experiment 2, twelve heifers were bilaterally ovariectomized at 3, 6 or 9 weeks of age (n = 4/group). Sample collection and measurement of mean concentration of FSH were the same as in experiment 1. Mean concentration of FSH increased (P less than .01) from 1 week before to 1 and 4 weeks after ovariectomy in heifers ovariectomized at 6 and 9 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging

Differential expression of placental lactogen-II and prolactin-like protein-A in the rat chorioallantoic placenta.

The rat chorioallantoic placenta is comprised of two morphologically distinct regions: the junctional zone and the labyrinth zone. The purpose of this investigation was to determine the relative contributions of trophoblast cells in each of these regions to the expression of placental lactogen-II (PL-II) and PRL-like protein-A (PLP-A) during development, mRNA expression was estimated by Northern blot analysis, whereas, protein expression was estimated by electrophoresis, immunoblotting, and immunocytochemical analyses. The immunochemical analyses used antipeptide antisera directed to amino acids 56-70 of PL-II and amino acids 152-164 of PLP-A. Northern and immunoblotting analyses indicated that both PL-II mRNA and protein expression were maximal in the junctional zone on day 13 of gestation and declined as gestation proceeded. In contrast, PL-II mRNA and protein expression in the labyrinth zone were low on day 13 and increased as gestation advanced. PL-II was specifically localized to giant cells. At midgestation, PL-II-positive giant cells were identified bordering the uterine decidua in the junctional zone and choriovitelline placenta. As gestation advanced. PL-II-positive cells were also localized to the labyrinth zone. Immunoreactivity was restricted to the cytoplasm of PL-II-positive cells. PLP-A mRNA and protein were predominantly expressed in the junctional zone of the chorioallantoic placenta. Expression of PLP-A increased as gestation advanced. PLP-A was specifically localized to giant and spongiotrophoblast cells of the junctional zone. Immunoreactivity was found in both cytoplasmic and nuclear compartments of PLP-A-positive cells. In summary, PL-II expression shifts from the junctional to the labyrinth zone during pregnancy, whereas PLP-A is predominantly expressed in the junctional zone during the latter third of pregnancy. Both hormones are produced by giant cells of the junctional zone, but only PL-II is expressed by choriovitelline and labyrinthine trophoblast cells. PLP-A is also expressed by spongiotrophoblast cells of the junctional zone. These findings provide insights into the process of placental morphogenesis.

Allantois