A frequent hMSH2 mutation in hereditary non-polyposis colon cancer syndrome.
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Base Sequence↗
Biomedical subjects
R Davies
Publications and source records attributed to R Davies.
Metastatic basal cell carcinoma of the eyelid. Report of a case.
A patient had metastatic basal cell carcinoma of the right upper eyelid and periorbital area. Initially treated with radiation, there were multiple, extensive local recurrences requiring wide surgical excision. Ten years after the first lesion appeared, a metastasis was found in the preauricular soft tissue. A literature search found 204 previously reported cases of metastatic basal cell carcinoma, but none in the Western or European ophthalmic literature. The pathogenesis and unique features of basal cell carcinoma behavior are discussed.
Aged↗
Documentation of abdominal exploration during laparoscopic cholecystectomy.
UNLABELLED: To assess the documentation of intraperitoneal exploration and events during laparoscopic cholecystectomy, we reviewed 200 dictated operative reports from eight different institutions. The 200 laparoscopic cholecystectomies were performed by 40 different surgeons on 158 female patients and 42 male patients. A description of the gallbladder was included in 134 (67%) reports and not mentioned in 66 (33%) reports. Fifty-four (27%) reports did not mention any intraperitoneal findings away from the gallbladder. Another 36 (18%) of the reports contained only a general comment indicating that no abnormalities were seen in the abdomen (excluding the gallbladder). The other 110 (55%) reports mentioned at least one specific site or finding in the abdomen other than the gallbladder. The most commonly mentioned sites were the liver, bowel, and stomach. Only 42 (21%) operative notes described what happened to the gallbladder contents: 30 described spillage of bile and/or gallstones and 12 stated that no spillage occurred. CONCLUSIONS: Laparoscopic cholecystectomy operative notes have often lacked a description of gallbladder appearance, documentation of abdominal exploration, and/or documentation of complete removal of the gallbladder and its contents.
Abdomen↗
Establishment of a colonic polyp registry in Rhode Island.
A colonic adenomatous polyp registry (PR) has been organized at the Roger Williams Medical Center whose main functions are to prevent the occurrence of colorectal cancer (CRC) in the enrollees, to provide a population of subjects for epidemiological and interventional studies, and to provide educational, including dietary, information to subjects and physicians. One hundred four and 202 patients with polyps, originally retrieved from the hospital pathology files, were enrolled in the 1984 and 1987 cohorts, respectively, of whom about 90% were followed for at least three years after polypectomy. Three carcinomas, all Dukes A, were found in the right colon in the follow-up period. New polyps identified in the first three years after polypectomy were generally small tubular adenomas with a greater predilection for the right colon than was found for the index polyps. Risk factors for new polyps included history of previous polyps and, probably, multiple index polyps. The use of colonoscopy for postpolypectomy surveillance increased between 1984 and 1987. About 25% of the subjects in each cohort were either lost to follow-up or received no endoscopic surveillance. On the other hand, some of those who were followed were probably subjected to excessive numbers of procedures. Defects in the PR include inadequacy of personal and family history data, and steady loss of patients during the three to six years after polypectomy. Despite the small size and limited resources of our hospital, its colonic polyp registry has already provided information that may help in the management of patients with this premalignant condition. The more widespread use of securely funded polyp registries would probably reduce the incidence of metachronous CRC in that population and would have significant epidemiological and educational functions.
Adenomatous Polyps↗
Time to arrhythmic, ischemic, and heart failure events: exploratory analyses to elucidate mechanisms of adverse drug effects in the Cardiac Arrhythmia Suppression Trial.
In this study we investigated the time to the first arrhythmic, ischemic, or failure event for encainide-flecainide and moricizine versus their respective placebo comparison groups in the Cardiac Arrhythmia Suppression Trial. The purpose was to explore possible mechanisms for the excessive deaths associated with active therapy that have been previously reported. Differences were noted between the active drugs. In particular, encainide-flecainide appeared to convert an ischemic event into death in more cases and more promptly than moricizine. However, the excessive deaths noted on encainide-flecainide were as likely to occur subsequent to a failure event as an ischemic event; for both encainide-flecainide and moricizine, the vast majority of excess deaths appeared to be the result of an increase in arrhythmia events without any protective effect of the drug. We were unable to identify any specific mechanism to explain the adverse effect of encainide and flecainide.
Anti-Arrhythmia Agents↗
An unusual case of deafness with speech impairment: lesson in diagnosis and management.
Hearing impairment can be the cause of significant disability and handicap. This medico-legal case demonstrates the need for accurate assessment of both the severity and type of hearing loss if the best clinical management is to be provided. In particular, the case identifies the critical role of additional, objective auditory testing when pure tone audiometry, which depends on the subjective response of the individual, is inconsistent or indicates severe hearing impairment.
Audiometry, Evoked Response↗
A prospective controlled crossover trial of a new heat-treated intravenous immunoglobulin.
Twenty-one patients with primary immunoglobulin deficiency were enrolled in a crossover study to test the efficacy and safety of Alphaglobin in comparison with the licensed preparations Sandoglobulin and Gamimune. There was no statistical difference in these parameters between Alphaglobin and Sandoglobulin/Gamimune. The level of total serum IgG and specific IgG to pneumococcal polysaccharides was similar in individual patients when they were receiving Alphaglobin or one of the other products. Transient increases in serum alanine transferase occurred in five patients on Sandoglobulin/Gamimune and two patients on Alphaglobin. Some patients showed a rise in total serum IgM afterwards, indicating a response to infection. However, serum hepatitis C virus (HCV) RNA was not found during the alanine transferase (ALT) rises, and IgM antibody to hepatitis A virus (HAV) was negative afterwards. We conclude that Alphaglobin is a safe, well tolerated and clinically efficacious treatment for patients with primary antibody deficiency.
Adult↗
Growth stimulating antibodies in endemic goitre: a reappraisal.
OBJECTIVE: Previous studies, using a variety of methods, have reported growth-promoting immunoglobulins (IGs) in a large proportion of patients with endemic goitre. We sought to determine whether thyroid growth-promoting immunoglobulins (TGI) are present in the serum of Indian patients with endemic goitre. DESIGN: IgG was prepared by protein G-Sepharose affinity purification and added to FRTL-5 thyroid cells in the presence of suboptimal concentrations of TSH. PATIENTS: We studied 30 sequential patients with endemic goitre and 16 euthyroid controls without a goitre from the same area. MEASUREMENTS: Two assays for thyroid cell growth were used: 3H-thymidine incorporation, and flow cytometric measurement of the proportion of cells in the S phase and G2/M phase of the cell cycle. RESULTS: Both assays were shown to detect growth produced by TSH and by thyroid stimulating antibodies in IgG preparations from 3 patients with Graves' disease. There was no significant increase in either 3H-thymidine incorporation or the distribution of cells in S or G2/M phase with IgGs from endemic goitre patients, and no difference between the effects of these IgGs and those from the normal subjects. CONCLUSIONS: Thyroid growth-promoting immunoglobulins cannot be detected in Indian patients with endemic goitre.
Adolescent↗
Molecular genetic analysis of exons 1 to 6 of the APC gene in non-polyposis familial colorectal cancer.
Familial adenomatous polyposis coli is caused by constitutional mutations in the APC gene. The hallmark of familial adenomatous polyposis coli is the presence of numerous (> 100) colorectal polyps, but mutations in the 5' end of the APC gene have been associated with familial colorectal cancer without florid polyposis. Although familial adenomatous polyposis coli accounts for only a minority of familial colorectal cancer cases, we hypothesised that APC mutations which were not associated with florid polyposis might make a significant contribution to nonpolyposis familial colorectal cancer. To investigate this possibility, we analysed 40 unrelated patients with familial colorectal cancer without classical familial adenomatous polyposis coli for mutations in exons 1 to 6 (codons 1 to 243) of the APC gene. No mutations were detected, but a C-->T polymorphism at nucleotide 333 (Arg-->Trp at codon 99) was identified. No 5' APC mutations were detected in two patients with desmoid tumours and a family history of colorectal cancer and polyps. We conclude that mutations in exons 1 to 6 of the APC gene are infrequent in patients with familial colorectal cancer who do not have many colorectal polyps.
Adult↗
Diffuse juvenile non-adenomatous polyposis: a rare cause of severe hypoalbuminaemia in childhood.
Hypoalbuminaemia is a well-recognized complication of juvenile polyposis, which is often not clinically apparent. We describe a child with diffuse colonic non-adenomatous polyposis who presented with generalized oedema and severe hypoalbuminaemia. The site of the protein loss was the polyps, and the problem resolved after colectomy. This is a case of unusually severe hypoalbuminaemia complicating juvenile polyposis.
Adenomatous Polyposis Coli↗
Genetic linkage analysis in hereditary non-polyposis colon cancer syndrome.
Hereditary Non-polyposis Colon Cancer Syndrome (HNPCC) is the most common cause of familial colorectal cancer. Molecular genetic studies of HNPCC have shown evidence of locus heterogeneity, and mutations in four genes (hMSH2, hMLH1, hPMS1, and hPMS2) which encode components of the mismatch enzyme repair system may cause HNPCC. To determine the extent and nature of locus heterogeneity in HNPCC, we performed genetic linkage studies in 14 HNPCC families from eastern and north-western England. Linkage to hMLH1 was excluded in six families, each of which were likely to be linked to hMSH2 (lod score > 1.0 in each family and total lod score for all six families = 7.64). Linkage to hMSH2 was excluded in three families, each of which were likely to be linked to hMLH1 (lod score > 1.0 in each family and total lod score at hMLH1 for all three families = 3.93). In the remaining five families linkage to hMSH2 or hMLH1 could not be excluded. These results confirm locus heterogeneity in HNPCC and suggest that, in the population studied, most large families with HNPCC will have mutations in hMSH2 or hMLH1. We did not detect any correlation between clinical phenotype and the genetic linkage results, but a Muir-Torre syndrome family excluded from linkage to hMLH1 was likely to be linked to hMSH2 and showed microsatellite instability in a tumour from an affected relative.
Adaptor Proteins, Signal Transducing↗
The dental phenotype in familial adenomatous polyposis: diagnostic application of a weighted scoring system for changes on dental panoramic radiographs.
A weighted scoring system (Dental Panoramic Radiograph Score) taking into consideration the nature, extent, and site of osseous and dental changes on dental panoramic radiographs in familial adenomatous polyposis is described. The weighting takes into consideration the incidence of the anomaly in the general population. The reliability of the system was tested by application to 85 people known to be affected by clinical or mutation analysis, 30 people lacking mutation in the adenomatous polyposis gene, and 19 people shown to be at low risk (< 1%) by linkage analysis. Using the highest thresholds, a specificity of 100% and sensitivity of approximately 68% was obtained. If all positive findings were considered as significant, sensitivity was increased to approximately 82% but the specificity was reduced to approximately 88%. Significant DPRS findings were observed at a significantly higher frequency in patients aged over 20 compared to the patients aged 20 and under. Overall, approximately 68% of the affected subjects had significant changes, and approximately 18% had normal appearance on DPR, with the remainder having changes classified as minimal or equivocal.
Adenomatous Polyposis Coli↗
Semi-quantitative analysis of interleukin-1 alpha, interleukin-6 and interleukin-8 mRNA expression by human thyrocytes.
It has been suggested that the thyroid itself may contribute to the inflammatory process observed in autoimmune thyroiditis by releasing the cytokines interleukin-1 alpha (IL-1 alpha), interleukin-6 (IL-6) and interleukin-8 (IL-8), but studies of cytokine gene expression in thyrocytes have been limited and conflicting. A semi-quantitative reverse transcription-PCR technique has been used to investigate the expression of IL-1 alpha, IL-6 and IL-8 mRNA in the human thyroid cell line HTori3 and in cultures of primary human thyroid follicular cells (TFCs). Cytokine mRNA levels were examined over a 24-h period, and the modulatory effects of exogenous IL-1 alpha, interferon-gamma (IFN-gamma) and TSH investigated. Basal expression of IL-1 alpha, IL-6 and IL-8 mRNA was detected in HTori3 and primary TFC cultures. Stimulation with IL-1 (10 U/ml) for 12 h produced an increase in the level of IL-1 alpha mRNA in both primary TFC and HTori3 cultures. IL-6 and IL-8 mRNA levels were increased by the addition of IL-1 in both cell types, and this effect was detected throughout the 24-h time-course. IFN-gamma (100 U/ml) had no significant effect on cytokine gene expression. A higher concentration of IFN-gamma (500 U/ml) had no significant effect on the expression of IL-1 alpha or IL-8 but produced an increase in the level of IL-6 mRNA in primary cultures and in HTori3 cells. Addition of TSH (1 mU/ml) produced an increase in the level of IL-1 alpha mRNA in primary TFC and HTori3 cells, at 12 and 24 h. TSH had no significant effect on the expression of IL-6 or IL-8 mRNA. These results demonstrate that human TFCs constitutively express IL-1 alpha, IL-6 and IL-8 mRNA and that this expression can be modulated by IL-1, IFN-gamma and TSH.
Base Sequence↗
Anticalculus efficacy of three dentifrices.
PURPOSE: To evaluate the anticalculus effect of three commercial dentifrices. MATERIALS AND METHODS: A 12-week independent and double-blind clinical study was conducted on a population of calculus-forming adult male and female subjects in Budapest, Hungary to directly compare the anticalculus efficacy of three commercially-available dentifrices, as compared to a placebo dentifrice. The three commercially-available anticalculus dentifrices compared in this clinical study to a 0.243% sodium fluoride/silica placebo dentifrice were as follows: (1) A dentifrice containing 1.3% soluble pyrophosphate and 1.5% of a PVM/MA copolymer in a 0.243% sodium fluoride/silica base. (2) A dentifrice containing 0.3% triclosan and 2% of a PVM/MA copolymer in a 0.243% sodium fluoride/silica base. (3) A dentifrice containing 0.3% triclosan and 0.75% zinc citrate in a 1.14% sodium monofluorophosphate/silica base. RESULTS: All three anticalculus dentifrices provided statistically significant reductions in supragingival calculus formation, as compared to a placebo dentifrice, after 12 weeks of use. The reductions in supragingival calculus formation ranged from 39% to 55%, as compared to a placebo dentifrice, for the three commercially-available anticalculus dentifrices. There was no statistically significant difference among the three commercially-available dentifrices with regard to anticalculus efficacy.
Adult↗
Localization of neutral endopeptidase (NEP) mRNA in human bronchi.
Neutral endopeptidase (NEP) may regulate peptide-induced inflammation in the respiratory tract. It is of interest to determine which respiratory resident cells express NEP. Trachea and bronchi from seven nonsmoking, nonasthmatic subjects were examined. NEP messenger ribonucleic acid (mRNA) was characterized by Northern blot hybridization of cultured human tracheobronchial epithelial and smooth muscle cells, and reverse transcriptase-polymerase chain reaction (RT-PCR) in trachea and bronchi. In situ hybridization with biotin- and 35S-labelled antisense complementary ribonucleic acid (cRNA) probes was used to determine the distribution of NEP mRNA in human bronchial mucosa. NEP-immunoreactive material was detected using MEK10 murine monoclonal antibodies and the immunogold method with silver enhancement. NEP mRNA was 4.5 kb in size in the cultured human smooth muscle and epithelial cells by Northern blot analysis. No evidence was found by RT-PCR for truncated, alternatively spliced NEP mRNAs, such as del exon 16 or del exons 5-18 in human bronchus. NEP mRNA was detected by in situ hybridization in epithelial cells, submucosal glands, bronchial smooth muscle and endothelium. NEP-immunoreactive material was identified in the epithelium, submucosal glands, bronchial smooth muscle, and endothelium, demonstrating an excellent correlation between the distribution of NEP mRNA and the cell surface protein. NEP mRNA and immunoreactive material were excluded from epithelial goblet cell and submucosal gland mucous cell vacuoles. We conclude that the various sites of NEP protein and mRNA expression correlate with the locations of peptide receptors and NEP enzyme function, and are consistent with the hypothesis that NEP may regulate peptide-induced inflammation in human bronchi.
Base Sequence↗
Clinical anticaries efficacy of NaF and SMFP dentifrices: overview and resolution of the scientific controversy.
Since the introduction of commercially marketed fluoride-containing dentifrices in the 1950s, the evolution of these products has seen a number of formulation changes, particularly with regard to the specific types of active fluoride agents they contain. Most currently marketed dentifrices contain one of two major fluoride compounds--sodium fluoride (NaF), or sodium monofluorophosphate (SMFP)--and much research effort has gone into continued investigations geared toward determining which, if either, of these two agents provides dentifrices with greater levels of anticaries efficacy. Historically, among clinical studies, most single-investigation attempts to resolve this issue have yielded equivocal results. During the past two years, however, renewed attempts on a larger scale have been made, including scientific symposia in Toronto, London, and Stockholm sponsored by major manufacturers of dentifrices. The conflicting conclusions derived from these undertakings have resulted in a scientific controversy as to which represents the most accurate resolution to the fluoride-comparison issue. The present paper considers processes for addressing this controversy, and identifies the key points of difference among those processes by which the three symposia arrived at their respective conclusions. An objective procedure for addressing the fluoride-comparison issue is offered, and applied to the clinical data which is currently available in the literature. The results of this analysis indicate that: 1) There is no statistically significant difference between the anticaries effectiveness of dentifrices containing fluoride as SMFP, and those containing fluoride as NaF; and 2) There is no clinically meaningful difference between the anticaries effectiveness of dentifrices containing fluoride as SMFP, and those containing fluoride as NaF.
Cariostatic Agents↗
Antibiotic prophylaxis.
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Anti-Bacterial Agents↗
HPV16 E7 oncoprotein deregulates B-myb expression: correlation with targeting of p107/E2F complexes.
HPV16 is a human tumour virus encoding two principal oncoproteins, E6 and E7. Expression of E7 can induce DNA synthesis in quiescent cells and this property coincides with its ability to bind to the cell proteins pRb and p107. As these cell proteins are regulators of the transcription factor E2F, we have investigated whether the interaction with E7 could result in induction of cell cycle regulated genes. We show that B-myb, whose induction at the G1/S boundary is regulated by release from E2F mediated transcriptional repression, is a target for transcriptional activation by E7 and is the first E7 responsive cell gene to be identified. E7 transactivation leads to both inappropriate transcription of B-myb during G1 and constitutive over-expression in cycling cells. B-Myb plays an essential role in cell cycle progression, and activation by E7 is likely to contribute to the mitogenic activity of the viral oncoprotein. Regulation of the B-myb promoter in NIH3T3 cells correlates with binding of distinct p107-containing complexes at the E2F binding site, and analysis of E7 mutants confirms that B-myb transcription in these cells is regulated through interactions with p107 rather than pRb. These results provide the first example of a potentially specific role for p107 in the regulation of the cell cycle.
3T3 Cells↗