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Biomedical subjects

G Thomas

Publications and source records attributed to G Thomas.

At least 37 records · Page 2Linked to original sources

[HNPCC syndrome (hereditary non polyposis colon cancer): identification and management].

BACKGROUND: The hereditary non-polyposis colon cancer (HNPCC) syndrome is an inherited condition defined by clinical and genealogical information, known as Amsterdam criteria. In about 70% of cases, HNPCC syndrome is caused by germline mutations in MMR genes, leading to microsatellite instability of tumor DNA (MSI phenotype). Patients affected by the disease are at high risk for colorectal and endometrial carcinomas, but also for other organs tumors. HNPCC syndrome is responsible for 5% of colorectal cancers. MAJOR ASPECTS: The lack of sensitivity of Amsterdam criteria in recognizing patients carrying a MMR germline mutation led to an enlargement of these criteria for the recruitment of possible HNPCC patients, and to a two-steps strategy, asking first for a tumor characterization according to MSI phenotype, especially in case of early-onset sporadic cases. FURTHER DEVELOPMENTS: The identification of germline MMR mutations has no major consequence on the cancer treatments, but influences markedly the long-term follow-up and the management of at-risk relatives. Gene carriers will enter a follow-up program regarding their colorectal and endometrial cancer risks; other organs being at low lifetime risk, no specific surveillance will be proposed.

Adolescent↗

A candidate gene approach to searching for low-penetrance breast and prostate cancer genes.

Most cases of breast and prostate cancer are not associated with mutations in known high-penetrance genes, indicating the involvement of multiple low-penetrance risk alleles. Studies that have attempted to identify these genes have met with limited success. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium--a pooled analysis of multiple large cohort studies with a total of more than 5,000 cases of breast cancer and 8,000 cases of prostate cancer--was therefore initiated. The goal of this consortium is to characterize variations in approximately 50 genes that mediate two pathways that are associated with these cancers--the steroid-hormone metabolism pathway and the insulin-like growth factor signalling pathway--and to associate these variations with cancer risk.

Breast Neoplasms↗

Hypertriglyceridemia as a possible risk factor for prostate cancer.

We retrospectively studied anthropometric and laboratory parameters (including serum triglycerides, cholesterol), as well as comedication in 504 patients diagnosed with prostate cancer between January 1997 and August 2002 at a single referral center, and compared these patients with 565 age-matched patients with benign prostatic hyperplasia. A positive correlation was found between serum triglycerides and prostate cancer (odds ratio: 1.148/mmol/l; 95% confidence interval (CI) 1.003-1.315; P<0.05) after correcting for age, body mass index, diabetes and comedication with statins. Hypertriglyceridemia may increase the risk of prostate cancer, and the prognostic relevancy of serum triglycerides should be studied prospectively.

Adult↗

Successful treatment of Acanthamoeba rhinosinusitis in a patient with AIDS.

Acanthamoeba infection is a rare, difficult-to-treat, and often fatal, opportunistic parasitic infection in immunocompromised hosts, such as patients infected with HIV. We describe an aggressive nasal and sinus infection by Acanthamoeba spp. in a person with AIDS. The resolution of this Acanthamoeba infection was secondary to a multidisciplinary treatment approach involving a combination of surgery as well as high-dose amphotericin B plus 5-fluorocytosine. In the era of the HIV/AIDS pandemic, the present report underscores the need for early identification and prompt aggressive treatment to ensure successful management of this rare but potentially fatal opportunistic infection.

AIDS-Related Opportunistic Infections↗

Renal clear-cell carcinoma: an ultrastructural study on the junctional complexes.

Junctional complexes such as tight junctions, adherens junctions, and desmosomes play crucial roles in the structure and function of epithelial cells. These junctions are involved in increasing cell-cell contact and as well serve as signaling centers regulating multiple functions in epithelial cells. Carcinoma cell lines cultured in the laboratory generally lack junctional complexes. However, studies directed towards understanding the distribution of junctional complexes in human cancer tissues are lacking. In this study, we analyzed by electron microscopy the distribution of junctional complexes in patients diagnosed with renal clear-cell carcinoma. We found that both tight junctions and adherens junctions were drastically reduced in patients with cancer compared to normal tissues. Desmosomes were not detected in normal proximal tubules while distinctly present in cancer tissues. These results suggest that analysis of junctional complexes in human tumors should provide valuable information that might have prognostic and diagnostic value.

Aged↗

Induction of biomolecules in mature leaves of Terminalia arjuna due to feeding of Antheraea mylitta Drury.

Terminalia arjuna is an important food plant of the tasar silkworm, Antheraea mylitta Drury. In this study, we investigated the induction of biomolecules in mature leaves of these plants subjected to insect feeding. Increase in total tannin content, lipid peroxidation, and trypsin inhibitor activity have been observed in mature leaves damaged by the insects. The growth rate of Vth instar larvae of A. mylitta fed on previously damaged foliage reduced by 87.1%. Induction of biomolecules for defense mechanisms in relation to herbivore damage has been discussed.

Animals↗

Comparing lecture and e-learning as pedagogies for new and experienced professionals in dentistry.

OBJECTIVE: To evaluate the relative effectiveness of e-learning versus lecture learning in VDPs and trainers. DESIGN: Experimental comparison of two groups' learning retention. SETTING: VDPs and trainers from two regions were assessed by independent researchers. METHOD: One region's VDPs and trainers received e-learning; another's received a traditional one hour lecture. Retention and understanding were tested and compared. Personal preference was assessed in group interviews. RESULTS: Significantly greater retention for the trainees occurred from lecturing rather than e-learning, and for the trainers e-learning was significantly more successful than lecturing. CONCLUSIONS: Small numbers in this study preclude wide generalisation. However, the results point to the benefits of face-to-face interaction for inexperienced staff, and the benefits of the speed and manageability of e-learning for busy, more experienced staff. The need for a discussion facility to be incorporated into ICT innovations to CPD (via, for example, online 'chatrooms') is also highlighted, with the potential of greatly enhancing e-learning efficacy.

CD-ROM↗

Isolate-specific and broad-spectrum QTLs are involved in the control of clubroot in Brassica oleracea.

Clubroot, caused by Plasmodiophora brassicae, is one of the most damaging diseases of vegetable Brassica crops in the world. In this study, genetic control and mapping of loci implied in quantitative resistance against five isolates of P. brassicae were studied in the F(1) and F(2/3 )progenies of the cross C10 (resistant kale)xHDEM (susceptible broccoli). A genetic map was constructed using RFLP, random and specific PCR-based markers. The 199 loci were assembled into nine linkage groups covering 1,226.3 cM. The F(3) families were assessed for resistance under controlled conditions with four single-spore isolates and one field isolate. A total of nine genomic regions were detected for clubroot resistance. Depending on the isolate, two to five QTLs were identified. The total phenotypic variation accounted for by QTLs ranged from 70% to 88% depending on the isolate. One of the QTLs ( Pb-Bo1) was detected in all isolates and explained 20.7-80.7% of the phenotypic variation. Pb-Bo1 had a major effect on three isolates but this effect was weaker for the last two. Five QTLs with minor effect were identified in only one isolate. To construct clubroot resistant varieties, the existence of both broad-spectrum and isolate-specific QTLs should be taken into account for the choice of genomic regions to use in a marker-assisted selection strategy.

Brassica↗

CompuCell, a multi-model framework for simulation of morphogenesis.

MOTIVATION: CompuCell is a multi-model software framework for simulation of the development of multicellular organisms known as morphogenesis. It models the interaction of the gene regulatory network with generic cellular mechanisms, such as cell adhesion, division, haptotaxis and chemotaxis. A combination of a state automaton with stochastic local rules and a set of differential equations, including subcellular ordinary differential equations and extracellular reaction-diffusion partial differential equations, model gene regulation. This automaton in turn controls the differentiation of the cells, and cell-cell and cell-extracellular matrix interactions that give rise to cell rearrangements and pattern formation, e.g. mesenchymal condensation. The cellular Potts model, a stochastic model that accurately reproduces cell movement and rearrangement, models cell dynamics. All these models couple in a controllable way, resulting in a powerful and flexible computational environment for morphogenesis, which allows for simultaneous incorporation of growth and spatial patterning. RESULTS: We use CompuCell to simulate the formation of the skeletal architecture in the avian limb bud. AVAILABILITY: Binaries and source code for Microsoft Windows, Linux and Solaris are available for download from http://sourceforge.net/projects/compucell/

Animals↗

mTOR: a mediator of intracellular homeostasis.

Earlier studies have shown that mTOR plays a key role in ribosome biogenesis. In bacteria, amino acids and ATP levels independently control ribosome biogenesis. Here, we describe recent findings demonstrating that homeostatic levels of amino acids, most notably branched-chain amino acids, and ATP, independently regulate the activity of mTOR. Unlike the effects of amino acids, the effects of ATP appear to be direct. Based on these findings we propose a model by which tumor cells existing in the anaerobic environment may have an advantage in growth by exploiting the rapid, although less efficient, production of ATP to drive growth via the mTOR signaling pathway.

Adenosine Triphosphate↗

Squamous cell cancer of the buccal mucosa in young adults.

BACKGROUND: Squamous cell carcinoma of the buccal mucosa is predominantly a cancer of elderly people and is seen rarely in young adults. Although many aetiological factors have been postulated, tobacco alone has been implicated as the main factor in the aetiology of such cancers at any age. PATIENTS AND METHODS: A retrospective analysis of 46 patients with cancer of the buccal mucosa who were under the age of 35 years at the time of presentation was made to evaluate their survival and predictors of survival. The details were extracted from the computerised records and case records of the Regional Cancer Centre, Trivandrum, India. These were analysed with particular emphasis on risk factors, clinical extent, and treatment. Survival was analysed by the Kaplan-Meier method, and differences in survival were compared using the log-rank test. RESULTS: The male:female ratio was 6.7:1. Almost all the patients (n = 42, 91%) used either tobacco or alcohol, with tobacco chewing being the most common. The 3 and 5 years disease-free survival were 72 and 61%, respectively. Non-smokers and patients with an advanced T stage at presentation had significantly worse prognoses.

Adult↗

Results of displaced subcapital fractures treated by primary total hip replacement.

We present morbidity, mortality and functional outcome in mobile, socially independent and alert patients with displaced subcapital hip fractures, treated by primary total hip replacement (THR). Fifty-one consecutive socially independent and mentally alert patients with displaced subcapital fractures were treated by primary THR, from April 1997 to March 2000, at a single hospital. Most patients were female (45/51) with an average age of 74 years. Patient hospital records were reviewed and patients interviewed by telephone. Functional outcome was assessed using Oxford hip score (OHS), short form 12 (SF12), and patient satisfaction. This study had a mean follow-up of 33 months (range 20-54). One patient with early dislocation went on to have recurrent dislocations. Two patients underwent revision surgery. Three patients died within 1 year of sustaining fracture. Function was comparable to elective THR in osteoarthritic patients. OHS correlated well with both SF12 and patient satisfaction. This study has the lowest reported dislocation rate (2%) and an acceptable 1-year mortality (6%) confirming the place of primary THR in treatment of these selected patients with a displaced hip fracture. The OHS proved a valuable instrument to assess function following THR in fracture patients.

Activities of Daily Living↗

Variation in the load of the horn fly, Haematobia irritans, in cattle herds is determined by the presence or absence of individual heifers.

The distribution of horn flies, Haematobia irritans (L.) (Diptera: Muscidae), in herds of Danish Holstein-Friesian cattle was investigated in two studies conducted during two field seasons. In the first study, highly significant differences in fly distribution between the most and the least fly-susceptible heifers were observed. In one herd, the mean difference between the most fly-susceptible and the most fly-resistant heifers was 268 Ha. irritans specimens. The highest ratio between upper and lower mean fly number was 64.1:1, whereas the lowest was 3.1:1. In the second year, it was demonstrated that the heifers kept their rank in fly attraction over time. The trial clearly demonstrated that some heifers were attracting flies, whereas others, even in the same herd, only carried a few. In the second study, heifers were moved in and out of herds in an attempt to manipulate fly loads in the herds. In year 1, one herd (herd A) received four fly-resistant heifers from another herd (herd B), resulting in a drop in the mean number of flies, whereas herd B received four fly-susceptible heifers from herd A, resulting in an elevation of the mean number of flies. In year 2, a similar pattern emerged using herds C and D, and when the cattle were later returned to their original herds, the fly loads returned to their original distribution. The data presented here show unequivocally that, for horn flies, there can be considerable differences in fly loads for individual heifers within the Holstein-Friesian breed. Furthermore, the overall fly load within herds can be manipulated, and can be reversed. Thus, the distribution in the number of flies within a herd appears to depend on the number of fly-resistant or fly-susceptible heifers. The possible role of chemical factors emitted by heifers, i.e. volatile semiochemicals, in determining differences in fly loads is discussed, whereby attractants are emitted by fly-susceptible heifers and enable flies to locate their host, and repellents are emitted by fly-resistant heifers such that the flies are actively repelled from the herd.

Animals↗

The role of volatile semiochemicals in mediating host location and selection by nuisance and disease-transmitting cattle flies.

The role of volatile semiochemicals in mediating the location and selection within herds of Holstein-Friesian heifers by nuisance and disease-transmitting cattle flies was investigated using coupled gas chromatography-electrophysiology (GC-EAG), coupled gas chromatography-mass spectrometry (GC-MS), electrophysiology (EAG), laboratory behaviour and field studies. Using volatile extracts collected by air entrainment from heifers in the Netherlands, a number of active peaks were located by coupled GC-EAG for Musca autumnalis (de Geer) (Diptera: Muscidae) and Haematobia irritans (L.) (Diptera: Muscidae). Volatile samples were also collected from two heifers in Denmark shown in previous counting experiments to differ significantly in their fly loads. Coupled GC-EAG using Ha. irritans antennae revealed differences in the EAG response to the samples, with additional EAG activity in the sample collected from the heifer with the lower fly load. To identify more EAG active compounds, volatiles were also collected from 48-h-old urine by air entrainment. In total, 23 compounds were located and identified by coupled GC-EAG and GC-MS. Further electrophysiological testing of these compounds with five fly species [M. autumnalis, Ha. irritans, Hydrotaea irritans (L.) (Diptera: Muscidae), Stomoxys calcitrans (L.) (Diptera: Musicidae) and Wohlfahrtia magnifica (Schiner) (Diptera: Sarcophagidae)] showed that only some of the compounds were physiologically active across the range of flies tested. These included 1-octen-3-ol, 6-methyl-5-hepten-2-one, (Z)-3-hexen-1-ol, naphthalene, and all EAG active compounds identified from urine. Compounds showing significant EAG activity were tested for behavioural activity using a wind-tunnel designed for measuring upwind flight behaviour. At certain concentrations, 1-octen-3-ol, 6-methyl-5-hepten-2-one and 3-octanol increased upwind flight, whereas naphthalene, propyl butanoate and linalool reduced upwind flight. In field studies using small herds of heifers ranked according to their fly load, individual slow-release formulations of 1-octen-3-ol and 6-methyl-5-hepten-2-one, when applied to low and high fly loading heifers, reduced fly loads on these individuals. This study provides evidence for the hypothesis that the natural differential attractiveness within herds of Holstein-Freisian heifers, i.e. a single host species, for cattle flies is partly due to differences in volatile semiochemicals emitted from the host. It is suggested that this phenomenon applies to other vertebrate host species and their associated insect pests.

Animals↗

Less IS less: a randomised controlled trial comparing cautious and rapid nalbuphine dosing regimens.

OBJECTIVE: This study aimed to determine which of two paramedic administered nalbuphine dosing regimens combined the greater analgesic effect with the minimum of adverse events. METHODS: Patients suffering from chest pain or trauma were randomised to receive either a rapid dosing regimen (10 mg over 30 seconds, repeated once after three minutes if pain score remained above three) or a cautious regimen (5 mg over two minutes, repeated at three minute intervals if pain score remained above three to a maximum dose of 20 mg). Data were collected on analgesic effectiveness, changes in vital signs, and patient reported side effects. RESULTS: The pain score fell by a mean of 4.29 and 3.49 in the rapid and cautious regimen groups respectively (difference = 0.79, 95% CI 0.09 to 1.5, p = 0.028). However, over half the patients in both groups continued to suffer significant pain on arrival at hospital. There were no significant changes in vital signs after nalbuphine, but there was a greater incidence of patient reported drowsiness in rapid regimen patients (42% compared with 21%, 95% CI = 6.96 to 34.12%, p = 0.003). CONCLUSION: A rapid dosing regimen of nalbuphine using 10 mg increments is more effective than and equally as safe as a cautious regimen using 5 mg increments. Further research is required to determine if a maximum dose exceeding 20 mg would result in fewer patients continuing to suffer significant pain before arrival at hospital.

Adult↗

Modified de Gramont with oxaliplatin in the first-line treatment of advanced colorectal cancer.

We previously reported high activity for oxaliplatin and a modified de Gramont regimen (OxMdG) in a single centre study of patients with metastatic colorectal cancer. We now report results with a further 56 patients treated at 14 centres. Low rates of grade 3 and 4 toxicity were seen, with no toxic deaths. Objective response rates were CR/PR=53%; NC=34.7%; PD=12.2%. Median time to progression was 8.3 months and overall survival was 14.5 months. This regimen is more convenient than those based around the conventional de Gramont regimen but is highly active and well tolerated; it forms part of a current UK MRC phase 3 trial.

Adult↗

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy--a prospective, randomised, double-blind trial.

BACKGROUND: Peristomal infection can sometimes complicate percutaneous endoscopic gastrostomy (PEG) placement. Antibiotic prophylaxis has, in some studies, been shown to reduce the incidence. However, the use of prophylaxis varies widely, possibly because the design and findings of the studies have differed, making their relevance to clinical practice difficult to interpret. AIM: To determine the efficacy of antibiotics, either prophylaxis or concurrent antibiotics at the time of the procedure, in reducing peristomal infection after PEG insertion in the context of a study designed to reflect current practice. METHODS: One hundred and forty-one patients undergoing PEG placement were randomised to group one to receive either a single dose of 750 mg of intravenous cefuroxime (n=50) or placebo (n=51) 30 min before PEG insertion. Forty patients who, for various reasons, were already receiving antibiotics were allocated to group two. The peristomal site was evaluated on day 3, 5 and 7 following insertion. Erythema and exudate were scored on a scale from 0 to 4; induration was scored on a scale of 0-3. A maximum combined score of 8 or higher or the presence of pus was criteria for infection. The primary outcome measure was the occurrence of a peristomal wound infection at any time within one week of PEG insertion. RESULTS: Peristomal wound infection was significantly reduced in patients who received antibiotics either as a single dose of cefuroxime [one of 33 (3%)], or in those on antibiotics for prior indications [one of 36 (3%)], compared with placebo [six of 33 (18%)], P=0.04 and 0.03, respectively. CONCLUSION: Antibiotics, either prophylaxis or concurrent, reduce the incidence of peristomal wound infection after PEG placement.

Adult↗