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T Guenther

Publications and source records attributed to T Guenther.

8 recordsLinked to original sources
PubMed2006

Genetic determinants modulate susceptibility to pregnancy-associated tumourigenesis in a recombinant line of Min mice.

Min mice provide a good model of human familial adenomatous polyposis. Recently, we have reported on two recombinant inbred lines (I and V) and the location of a modifier (Mom3) close to Apc, which altered polyp numbers in our mice possibly by modifying the frequency of wild-type (WT) allele loss at Apc; mice with severe disease (line V) showed elevated rates of loss. We now show that in line I only, a single pregnancy caused a significant increase in adenoma multiplicity compared with virgin controls (P<0.001) and that an additional pregnancy conferred a similar risk. Pregnancy was linked to both adenoma initiation and enhanced tumour growth in line I mice, and interline crosses indicated that susceptibility to pregnancy-associated adenomas was under genetic control. We found no evidence for the involvement of oestrodial metabolizing genes or the oestrogen receptors (Esr1 and 2) in tumour multiplicity. Importantly, a significantly elevated frequency of WT allele loss at Apc was observed in adenomas from parous mice (line and backcrossed) carrying the line I Min allele relative to equivalent virgin controls (P=0.015). Our results provide the first experimental evidence for genetic determinants controlling pregnancy-associated tumourigenesis; analogous genetic factors may exist in humans.

Adenomatous Polyposis Coli↗
PubMed2006

Disease severity and genetic pathways in attenuated familial adenomatous polyposis vary greatly but depend on the site of the germline mutation.

BACKGROUND: Attenuated familial adenomatous polyposis (AFAP) is associated with germline mutations in the 5', 3', and exon 9 of the adenomatous polyposis coli (APC) gene. These mutations probably encode a limited amount of functional APC protein. METHODS AND RESULTS: We found that colonic polyp number varied greatly among AFAP patients but members of the same family tended to have more similar disease severity. 5' Mutants generally had more polyps than other patients. We analysed somatic APC mutations/loss of heterozygosity (LOH) in 235 tumours from 35 patients (16 families) with a variety of AFAP associated germline mutations. In common with two previous studies of individual kindreds, we found biallelic changes ("third hits") in some polyps. We found that the "third hit" probably initiated tumorigenesis. Somatic mutation spectra were similar in 5' and 3' mutant patients, often resembling classical FAP. In exon 9 mutants, in contrast, "third hits" were more common. Most "third hits" left three 20 amino acid repeats (20AARs) on the germline mutant APC allele, with LOH (or proximal somatic mutation) of the wild-type allele; but some polyps had loss of the germline mutant with mutation leaving one 20AAR on the wild-type allele. CONCLUSIONS: We propose that mutations, such as nt4661insA, that leave three 20AARs are preferentially selected in cis with some AFAP mutations because the residual protein function is near optimal for tumorigenesis. Not all AFAP polyps appear to need "three hits" however. AFAP is phenotypically and genetically heterogeneous. In addition to effects of different germline mutations, modifier genes may be acting on the AFAP phenotype, perhaps influencing the quantity of functional protein produced by the germline mutant allele.

Adenomatous Polyposis Coli↗
PubMed2005

Primary cutaneous mucinous carcinoma of the eyelid in a young male.

Primary cutaneous mucinous carcinoma of the eyelid is an adenocarcinoma of the eccrine glands. It is rare and locally aggressive but the prognosis following local excision, confirmed with tumour-free margins, is good. This tumour is usually described in the elderly. We present the occurrence, clinical and histological features, and management of this tumour in a young male.A 36-year-old male presented with a small cystic right lower lid lesion, which had increased in size and pigmentation over two years. He underwent excision biopsy for diagnostic purposes followed by Moh's micrographic surgical removal. The defect was repaired with an upper eyelid skin graft. A full oncological screen including whole-body computed tomography scan excluded the presence of primary mucinous carcinoma elsewhere and any metastatic spread. There has been no recurrence of tumour 18 months following excision. Ophthalmologists should be aware of the occurrence of this tumour in a younger age group than previously described. Moh's micrographic surgery is the most suitable method of treatment following exclusion of both distant primaries and metastases.

Adenocarcinoma, Mucinous↗
PubMed2003

Assessing the benefit of biological valve prostheses: cumulative incidence (actual) vs. Kaplan-Meier (actuarial) analysis.

OBJECTIVE: The standard method of analysing structural valve degeneration (SVD) of biological prostheses is the Kaplan-Meier method. In order to assess SVD with regard to competing risks (e.g. death particularly in elderly patients) cumulative incidence (actual analysis) was compared to Kaplan-Meier (actuarial analysis). METHODS: We retrospectively analysed 257 patients older than 60 years, who underwent mitral valve replacement with different biological prostheses between 1974 and 2000. Reoperation-free survival was determined, both according to Kaplan-Meier and cumulative incidence analysis. RESULTS: For the total group of patients older than 60 years, the 10- and 15-year freedom from reoperation was 79+/-5 and 55+/-8%, respectively, according to Kaplan-Meier and 90+/-2 and 83+/-3% according to cumulative incidence analysis. For patients older than 65 years of age (n=170), Kaplan-Meier analysis revealed 85+/-7% freedom from reoperation at 10 years vs. 94+/-3% according to cumulative incidence analysis. For those between 60 and 65 years of age (n=87), Kaplan-Meier freedom from reoperation was 76+/-7% at 10 years and 48+/-9% at 15 years vs. 86+/-4 and 75+/-5% according to cumulative incidence analysis. CONCLUSIONS: Kaplan-Meier analysis overestimates the 10- and 15-year risk of SVD compared to cumulative incidence analysis, thus underestimating the benefit of biological valve replacement. Cumulative incidence analysis may lead to a more complete evaluation of risk and benefit and thus better patient management.

Aged↗
PubMed2001

Femtosecond near-field spectroscopy: carrier relaxation and transport in single quantum wires.

Quasi-two-colour femtosecond pump and probe spectroscopy and near-field scanning optical microscopy are combined to study the carrier dynamics in single semiconductor nanostructures. In temporally, spectrally and spatially resolved measurements with a time resolution of 200 fs and a spatial resolution of 200 nm, the non-linear change in reflectivity of a single quantum wire is mapped in real space and time. The experiments show that carrier relaxation into a single quantum wire occurs on a 100 fs time scale at room temperature. Evidence is given for a transient unipolar electron transport along the wire axis on a picosecond time and 100 nm length scale.

Journal Article↗
PubMed1998

Aortic valve replacement in children: are we on the right track?

OBJECTIVE: The choice of the ideal prosthesis for aortic valve replacement (AVR) in children is still controversial. Early degeneration of bioprostheses and the potential risks related to anticoagulation in the child have renewed the interest of many surgeons towards the Ross operation. This study concerns our 22-year experience with AVR in children. METHODS: Forty-six children, aged 4 months to 16 years (mean 11.6 years), had AVR between April 1974 and December 1996. Preoperative diagnosis revealed aortic regurgitation (AR) in 25 cases, aortic stenosis (AS) in ten, combined AS and AR in nine and LVOTO in two patients. Of the 46 patients, 26 had 37 previous procedures. Isolated AVR was performed in 19 cases, 27 children underwent 36 concomitant intracardiac procedures. Mechanical prostheses were implanted in 30 children, bioprostheses in eight, aortic homografts in three. Five patients underwent a Ross procedure. RESULTS: There was one hospital death in the latter group (2.1%). Six of seven late deaths occurred in patients who underwent complex intracardiac procedures (15.2%). Reoperation rate was 19.5% (n = 10), differentiating 16.6% for mechanical (5/30 patients) and 50% (4/8 patients) for bioprostheses. The mean follow-up period was 8.01 years, ranging from 0.45 to 21.66 years (304.04 patient-years). There was one hemorrhagic event (2.1%) due to anticoagulation, thrombosis of the mechanical valve occurred in two patients (4.2%). CONCLUSIONS: AVR can be performed with acceptable mortality rate and good long-term results in children. We perform the Ross operation only in selected cases. According to our experience, mechanical prostheses show excellent performances in children with a low incidence of complications related to anticoagulation.

Adolescent↗
PubMedDate not supplied

Oral magnesium intake reduces permanent hearing loss induced by noise exposure.

INTRODUCTION: Following animal experiments where correlations were observed between serum magnesium level and noise-induced permanent hearing threshold shifts (NIPTS), we tested the prophylactic effect of magnesium in human subjects exposed to hazardous noise. METHODS: Subjects were 300 young, healthy, and normal-hearing recruits who underwent 2 months of basic military training. This training necessarily included repeated exposures to high levels of impulse noises while using ear plugs. During this placebo-controlled, double-blind study, each subject received daily an additional drink containing either 6.7 mmol (167 mg) magnesium aspartate or a similar quantity of placebo (Na-aspartate). RESULTS: NIPTS was significantly more frequent and more severe in the placebo group than in the magnesium group, especially in bilateral damages. NIPTS was negatively correlated to the magnesium content of blood red cells but especially to the magnesium mononuclear cells. Long-term additional intake of a small dose of oral magnesium was not accompanied by any notable side effect. CONCLUSION: This study may introduce a significant natural agent for the reduction of hearing damages in noise-exposed population.

Administration, Oral↗