Biomedical subjects
Publications and source records attributed to G Thomas.
Tuberculosis of the oral cavity is uncommon and poses a diagnostic challenge. We report three patients with primary tuberculosis of the tongue, all of whom responded well to treatment and were cured.
Primary intraosseous carcinoma (PIOC) is a rare malignant neoplasm of the jaw. These tumours are believed to arise from the odontogenic epithelium and hence are also referred to as odontogenic carcinoma. A detailed search was made for squamous cell PIOC of the jaw in English literature using Medline Cancer CD. The data obtained were transferred onto dBase software. Two detailed case reports of patients treated at Regional Cancer Centre, Trivandrum during 1996 and 1997 were also included. A pooled analysis was carried out. Survival analysis was carried out using Kaplan-Meier method and log-rank statistics were used for comparing survival. A total of 35 cases were analysed, of which 33 were from published literature. The mean age of the patients at the time of diagnosis was 52.3 years with male to female ratio being 2.5:1. Posterior mandible was the predominant site. The median follow-up time was 28 months. Overall survival at 5 years was 37.8% (95% CI; 14.8-61.0) while the corresponding disease free survival was 29.8% (95% CI; 9.2-54.1). Primary intraosseous carcinoma is a rare tumour of jawbones, characterized by progressive swelling of the jaw, pain and loosening of tooth. The tumour is locally aggressive and metastasizes to regional nodes. The overall and disease free survival is poor with almost 50% patients failing loco-regionally within the first 2 years of follow-up.
OBJECTIVE: In the era of a renewal of incomplete revascularization approaches, the controversy reappears as to whether the approach for complete revascularization is of prognostic value. The clear advantage of complete revascularization in elderly patients has recently been published. However, for the younger patient group, there is no conclusive information available so far. The aim of our study was to investigate the effect of complete vs. incomplete revascularization in patients up to 70 years of age. PATIENTS AND METHODS: 6531 patients underwent isolated CABG. 5003 of these patients were aged up to 70 years at the time of operation. RESULTS: Incomplete revascularization was performed in 534 (10.7 %) patients. The most common reasons for incomplete revascularization were small vessels and massive calcification. The differences in mortality up to the 180(th) day after CABG are statistically significant. By Kaplan-Meier analysis, the time relationship between incomplete revascularization and death affects predominantly the very early period after CABG. By logistical regression, incomplete revascularization was found to be an independent risk factor for death after CABG. CONCLUSION: Incomplete revascularization affects the early outcome after CABG in patients up to 70 years of age as an independent risk factor for death. In view of recent approaches for primarily incomplete CABG, our results indicate the necessity to reconsider the advantages of complete revascularization.
Although the largest effects of prison-based therapeutic community (TC) programs are associated with entry into aftercare, only a minority of prisoners volunteer for these aftercare programs. The study addresses the gap in our knowledge concerning these low rates of voluntary entry. A theoretical formulation of the TC process involving the effect of the interaction of clients' motivation and participation in the activities of the TC on entry into aftercare was tested on a sample of 110 volunteers in a prison-based TC for whom there were client and staff ratings of 3-month participation and 12-month follow-up data on relapse and recidivism. Path analyses support a model in which the interaction of motivation and 3-month participation ratings have a direct effect on the selection of aftercare, and aftercare has a direct effect on relapse and recidivism. The use of a combination of enhanced motivation and early program participation as a means of increasing the utilization and effectiveness of aftercare is discussed.
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Reactivation of cytomegalovirus (CMV) from latency is a frequent complication of organ transplantation, and the molecular mechanism by which this occurs is unknown. Previous studies have shown that allogeneic stimulation induces reactivation of human CMV (HCMV) in vitro (64). We find that transplantation of vascularized allogeneic kidneys induces murine CMV (MCMV) and HCMV immediate-early (ie) gene expression. This induction is accompanied by increased expression of transcripts encoding inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-2, and gamma interferon, and by activation of NF-kappaB. TNF alone can substitute for allogeneic transplantation in inducing HCMV and MCMV ie gene expression in some tissues. Our studies suggest that reactivation is a multistep process which is initiated by factors that induce ie gene expression, including TNF and NF-kappaB. Allogeneic transplantation combined with immunosuppression may be required to achieve complete reactivation in vivo.
INTRODUCTION: Germline mutations of the STK11/LKB1 tumour suppressor gene (19p13.3) are responsible for Peutz-Jeghers syndrome (PJS), a rare genetic disorder, which is dominantly inherited. In addition to the typical hamartomatous gastrointestinal polyps and perioral pigmented lesions, PJS is also associated with the development of tumours in various sites. No specific follow up has yet been evaluated for gene carriers. Furthermore, genetic heterogeneity has been reported, which makes genetic counselling difficult. METHODS: We report here the analysis of the STK11/LKB1 locus in a series of 34 PJS families, combining the search for mutations and rearrangements in the coding sequence, allele specific expression tests, and linkage studies. RESULTS: Germline deleterious mutation of the STK11/LKB1 gene were identified in 70% of cases. The hypothesis of a second PJS locus was reinforced and PJS families could be divided into two groups on the basis of the presence or absence of an identified STK11/LKB1 alteration. Analysis of clinical data indicates that the cancer associated risk is markedly different in the two groups. PJS patients with no identified STK11/LKB1 mutation are at major risk for proximal biliary adenocarcinoma, an infrequent tumour in the general population. CONCLUSION: Up to 30% of PJS patients are caused by mutation in an unidentified gene that confers high susceptibility to cancer development.
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The neurofibromatosis type 2 (NF2) tumor suppressor protein, known as schwannomin or merlin, is involved in linking membrane proteins to the cytoskeleton. Like the related ERM proteins, schwannomin has long been suspected of exhibiting a complex 3D organization caused by the association of different regions within the protein. Intramolecular interactions characterized to date are linking N-terminal sequences of the protein to C-terminal sequences. Here, we demonstrate, by a biochemical approach, the existence of a structured domain entirely contained within the N-terminal half of schwannomin. This structure, which is resistant to chymotryptic digestion, encompasses the FERM domain (residues 19-314), but excludes the 18 extreme N-terminal residues specific to schwannomin. The structure is disrupted by some, but not all, naturally occurring NF2 mutations. We investigated the significance of this structured domain in schwannomin cellular functions and found that normal schwannomin localization beneath the plasma membrane is directly dependent on proper folding of the N-terminal domain. In addition, folding of the N-terminal domain influences schwannomin interaction with actin through two novel actin-binding sites located in this region. These results suggest that loss of activity of several naturally occurring schwannomin mutants is due to disruption of the fold of the N-terminal domain, leading to loss of both membrane localization and actin association.
Osteoporosis is known to occur in patients with kidney transplants, but limited information is available about the prevalence and causes of this complication. We asked all 330 patients with kidney transplants in our unit to participate in this study of whom 165 (50%) agreed to do so. The characteristics of the participating patients were similar to the remaining 165 nonparticipants. Seventy of 165 (42%) of the participants were women of whom 40 were postmenopausal in contrast to the men of whom only one was hypogonadal. Bone mineral density (BMD) was significantly reduced at the radius (Z score, -1.5) and femoral neck (Z score, -0.7), but the lumbar spine was normal. BMD was lower in women than men at all skeletal sites. Osteoporosis was found in 10-44% and osteopenia was found in 35-50% of women depending on the site. BMD was related inversely to time since transplantation and cumulative prednisolone dose. Twenty-seven of the 165 (16%) patients had either vertebral deformities or a history of a low trauma fracture after transplantation. This fracture group consisted of 10/27 (37%) men and 17/27 (63%) women, of whom 14 were postmenopausal. Fracture patients tended to be older and have a longer duration of renal failure, dialysis, transplantation, greater cumulative steroid dose, and higher bone resorption markers than the nonfracture group. No differences were found for cumulative doses of cyclosporin or tacrolimus. Logistic regression showed that only duration of dialysis and time since transplantation significantly increased fracture risk, with odds ratio (OR) for each year of dialysis or transplantation being 1.21 (CI, 1.00-1.48) and 1.14 (CI, 1.05-1.23), respectively. These data show that low bone density and fractures are common in patients with kidney transplant and are determined by both pre- and posttransplant variables. Fracture risk was greatest in women, particularly if they were postmenopausal and we recommend that this subgroup is targeted for assessment and treatment.
BACKGROUND: Asthma is a major health care problem that affects all ages. It is uncertain whether asthma is a single clinical entity or a grouping of separate clinical syndromes that share a common set of treatment guidelines. AIM: To observe the symptoms, treatment step, and health service utilisation of a population of patients throughout the United Kingdom (UK) listed on an asthma register. DESIGN OF STUDY: A cross-sectional study and clinical assessment of asthma patients. SETTING: A total of 12,203 patients from 393 general practices throughout the UK. METHOD: A database was used to observe the symptoms, treatment step, and health service utilisation of the asthma patients. RESULTS: Children aged up to four years had a distinctive profile of symptoms, including night time cough. They also experienced increased health service utilisation including a high hospital admission rate. Symptoms in adults became more common with increasing age. The pattern of symptoms in patients aged 45 years and over suggest many patients on asthma registers may have chronic obstructive pulmonary disease. Patients aged 16 to 30 years showed a different pattern of health service usage to those aged 5 to 15 years and 31 to 45 years, relying more on unscheduled use of health services rather than a review-based management plan. Patients aged 16 to 30 years used less anti-asthma medication than those aged 5 to 15 years and 31 to 45 years. CONCLUSIONS: Databases may be a useful tool with which to study the natural history of asthma, but there are problems with bias. Several clinical subgroups exist within the broad diagnosis label of asthma. Knowledge of how these subgroups of doctor-diagnosed asthma use health services may help clinicians to create individual care plans for groups of patients.
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BACKGROUND: Human prostate cancers are initially androgen dependent but ultimately become androgen independent. Overexpression of the Her-2-neu receptor tyrosine kinase has been associated with the progression to androgen independence in prostate cancer cells. We examined the expression of Her-2-neu in normal and cancerous prostate tissues to assess its role in the progression to androgen independence. METHODS: Prostate cancer tissue sections were obtained from 67 patients treated by surgery alone (UNT tumors), 34 patients treated with total androgen ablation therapy before surgery (TAA tumors), and 18 patients in whom total androgen ablation therapy failed and who developed bone metastases (androgen-independent [AI] disease). The sections were immunostained for Her-2-neu, androgen receptor (AR), prostate-specific antigen (PSA), and Ki-67 (a marker of cell proliferation) protein expression. Messenger RNA (mRNA) levels and gene amplification of Her-2-neu were examined by RNA in situ hybridization and fluorescent in situ hybridization(FISH), respectively, in a subset of 27 tumors (nine UNT, 11 TAA, and seven AI). All statistical tests were two-sided. RESULTS: Her-2-neu protein expression was statistically significantly higher in TAA tumors than in UNT tumors with the use of two different scoring methods (P =.008 and P =.002). The proportion of Her-2-neu-positive tumors increased from the UNT group (17 of 67) to the TAA group (20 of 34) to the AI group (14 of 18) (P<.001). When compared with UNT tumors, tumor cell proliferation was higher in AI tumors (P =.014) and lower in TAA tumors (P<.001). All tumors expressed AR and PSA proteins. Although Her-2-neu mRNA expression was high in TAA and AI tumors, no Her-2-neu gene amplification was detected by FISH in any of the tumor types. CONCLUSIONS: Her-2-neu expression appears to increase with progression to androgen independence. Thus, therapeutic targeting of this tyrosine kinase in prostate cancer may be warranted.
The adaptation of growth in response to nutritional changes is essential for the proper development of all organisms. Here we describe the identification of the Drosophila homolog of the target of rapamycin (TOR), a candidate effector for nutritional sensing. Genetic and biochemical analyses indicate that dTOR impinges on the insulin signaling pathway by autonomously affecting growth through modulating the activity of dS6K. However, in contrast to other components in the insulin signaling pathway, partial loss of dTOR function preferentially reduces growth of the endoreplicating tissues. These results are consistent with dTOR residing on a parallel amino acid sensing pathway.
Studies of the frequencies of different alleles in young adults and aged individuals have implicated several genes, such as ApoE and ACE, in longevity. However such association studies can easily give rise to spurious results through unsuspected population subdivision, and an approach making use of genetic relationships among relatives is desirable. We have studied the effectiveness of non-parametric genetic analysis to detect different types of loci affecting longevity. The non-parametric method has high statistical power to detect infrequent recessive alleles that are required for, or significantly increase the probability of, survival to advanced age. Statistical power is reduced if a proportion of carriers of the alternative allele is allowed to survive. The method is least effective in detecting alleles that occur at low frequency in young individuals and that subsequently experience high mortality, as is the case for carriers of the epsilon4 allele of ApoE. Genotyping errors will also reduce the value of the NPL statistic in a linear fashion with the error rate and the number of loci genotyped. We have also used the method to analyse genotypes of seven highly polymorphic markers near the ApoE gene in a sample of 188 sibships of nonagenarians and centenarians (n=434) and their children (n=124), however no excess sharing of alleles was detected.
Although tobacco habits have been associated with the risk of oral leukoplakia, alcohol drinking and body mass index (BMI) as risk factors have not been well established. The purpose of this study is to evaluate the independent effects of drinking, BMI, tobacco chewing and smoking on the risk of oral leukoplakia. A case-control study was conducted, with data from an ongoing randomized oral cancer screening trial in Kerala, India. Trained health workers conducted interviews and performed oral visual inspections to identify oral premalignant lesions such as leukoplakia. The logistic regression model in SAS was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). A total of 927 leukoplakia cases and 47,773 controls were included in the analysis. Ever alcohol drinking was a significant risk factor for oral leukoplakia among nonsmokers (OR=2.1, 95%CI=1.3, 3.4) and non-chewers (OR=1.8, 95%CI=1. 3, 2.5) after adjusting for age, sex, education, BMI and tobacco habits. The association with alcohol drinking was stronger among women (OR=3.9, 95%CI=1.5, 10.4) than men (OR=1.5, 95%CI=1.3, 1.9). An inverse dose-response relationship was observed between BMI and the risk of oral leukoplakia (p for trend=0.0075). Tobacco chewing was a stronger risk factor for women (OR=37.7, 95%CI=24.2, 58.7) than for men (OR=3.4, 95%CI=2.8, 4.1). Smoking was a slightly stronger risk factor for men (OR=3.3, 95%CI=2.5, 4.3) than for women (OR=2.0, 95%CI=1.5, 2.9). In conclusion, alcohol drinking was found to be an independent risk factor while BMI might be inversely associated with the risk of oral leukoplakia in an Indian population.