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M Thorne

Publications and source records attributed to M Thorne.

15 recordsLinked to original sources
PubMed2001

Faecal incontinence after lateral internal sphincterotomy is often associated with coexisting occult sphincter defects: a study using endoanal ultrasonography.

BACKGROUND: Troublesome faecal incontinence following a lateral internal sphincterotomy (LIS) is often attributed to faulty surgical techniques: division of excessive amount of internal sphincter or inadvertent injury to the external sphincter. The aim of the present paper was to assess the anatomic and physiological factors that may contribute to faecal incontinence following a technically satisfactory lateral internal sphincterotomy by a group of colorectal specialists. METHODS: Fourteen patients (nine women, five men; median age: 38 years; range: 23-52 years) who developed troublesome postoperative faecal incontinence were evaluated by clinical assessment, endoanal ultrasonography and anorectal physiological studies (manometry, pudendal nerve terminal motor latency) by two independent observers. The Cleveland Clinic continence score (0-20; 0, perfect continence; 20, complete incontinence) was used to quantify the severity of faecal incontinence. Fourteen continent subjects after a LIS (nine female patients, five male patients; median age: 36 years; range: 20-44 years) were also evaluated as 'continent' controls (continence score </= 4). RESULTS: In the incontinent group, the median postoperative Cleveland Clinic continence score was 9 (range: 6-13) compared with a preoperative score of 1 (range: 0-3). On assessment by endoanal ultrasonography the site of the internal sphincterotomy was clearly identified. There were additional coexisting defects, on endoanal ultrasonography, of the external anal sphincter in seven female patients, of the internal sphincter in two female and two male patients; and a defect of both the external and internal sphincters in a male patient who had had a prior fistulotomy. The pudendal nerve terminal motor latency (PNTML) was prolonged in two female patients on the side contralateral to the lateral internal sphincterotomy. In two of five male patients there was no evidence of any occult sphincter injuries. In the continent controls a defect of the distal portion of the external sphincter was noted in one female patient. None of the patients had a prolonged PNTML. The maximum voluntary contraction was significantly lower in the female subjects than in the female continent controls (92 mmHg vs 140 mmHg; P < 0.05), while the resting anal canal pressures and length of the high pressure zone were similar between the study subjects and the continent controls. CONCLUSION: Troublesome faecal incontinence after a satisfactorily performed lateral internal sphincterotomy is often associated with coexisting occult sphincter defects.

Adult↗
PubMed2000

A role for N-cadherin in the development of the differentiated osteoblastic phenotype.

Cadherins are a family of cell surface adhesion molecules that play an important role in tissue differentiation. A limited repertoire of cadherins has been identified in osteoblasts, and the role of these molecules in osteoblast function remains to be elucidated. We recently cloned an osteoblast-derived N-cadherin gene from a rat osteoblast complementary DNA library. After in situ hybridization of rat bone and immunohistochemistry of human osteophytes, N-cadherin expression was localized prominently in well-differentiated (lining) osteoblasts. Northern blot hybridization in primary cultures of fetal rat calvaria and in human SaOS-2 and rat ROS osteoblast-like cells showed a relationship between N-cadherin messenger RNA expression and cell-to-cell adhesion, morphological differentiation, and alkaline phosphatase and osteocalcin gene expression. Treatment with a synthetic peptide containing the His-Ala-Val (HAV) adhesion motif of N-cadherin significantly decreased bone nodule formation in primary cultures of fetal rat calvaria and inhibited cell-to-cell contact in rat osteoblastic TRAB-11 cells. HAV peptide also regulated the expression of specific genes such as alkaline phosphatase and the immediate early gene zif268 in SaOS-2 cells. Transient transfection of SaOS-2 cells with a dominant-negative N-cadherin mutant (NCADdeltaC) significantly inhibited their morphological differentiation. In addition, aggregation of NCTC cells derived from mouse connective tissue stably transfected with osteoblast-derived N-cadherin was inhibited by either treatment with HAV or transfection with NCADdeltaC. Together, these results strongly support a role for N-cadherin, in concert with other previously identified osteoblast cadherins, in the late stages of osteoblast differentiation.

Animals↗
PubMed1999

Cochlear fluid space dimensions for six species derived from reconstructions of three-dimensional magnetic resonance images.

OBJECTIVES: To establish the dimensions and volumes of the cochlear fluid spaces. STUDY DESIGN: Fluid space volumes, lengths, and cross-sectional areas were derived for the cochleas from six species: human, guinea pig, bat, rat, mouse, and gerbil. METHODS: Three-dimensional reconstructions of the fluid spaces were made from magnetic resonance microscopy (MRM) images. Consecutive serial slices composed of isotropic voxels (25 microm3) representing the entire volume of fixed, isolated cochleas were obtained. The boundaries delineating the fluid spaces, including Reissner's membrane, were resolved for all specimens, except for the human, in which Reissner's membrane was not consistently resolved. Three-dimensional reconstructions of the endolymphatic and perilymphatic fluid spaces were generated. Fluid space length and variation of cross-sectional area with distance were derived by an algorithm that followed the midpoint of the space along the length of the spiral. The total volume of each fluid space was derived from a voxel count for each specimen. RESULTS: Length, volume, and cross-sectional areas are provided for six species. In all cases, the length of the endolymphatic fluid space was consistently longer than that of either perilymphatic scala, primarily as a result of a greater radius of curvature. For guinea pig specimens, the measured volumes of the fluid spaces were considerably lower than those suggested by previous reports based on histological data. CONCLUSIONS: The quantification of cochlear fluid spaces provided by this study will enable the more accurate calculation of drug and other solute movements in fluids of the inner ear during experimental or clinical manipulations.

Animals↗
PubMed1998

An illustrative comparison of the event-size distributions for gamma-rays and alpha-particles in the whole mammalian cell nucleus.

PURPOSE: Recent laboratory studies of endpoints designated as due to radiation-induced genomic instability have cast doubt on the validity of the current theoretical framework. Under this framework extrapolations are made from directly determined risks of radiation-induced cancer to those circumstances for which no direct information exists, namely at low doses and dose rates at low LET and at low dose exposures to high LET radiations. Based upon an approach in which the 'state' of the genome, as exemplified by the pattern of gene expression, rather than the base sequence of the genomic DNA, is taken to be the origin of genomic stability, it is hypothesized that the critical factor determining the likelihood of destabilization by ionizing radiation is the dose to the whole cell nucleus. CALCULATIONS: The frequency distributions of event sizes from two qualities of radiation, low LET y-rays and 5 MeV alpha-particles, are compared with 60Co gamma-rays being taken to be a low LET reference radiation in determining the RBE of other radiation qualities. In the absence of measured event-size distributions for 60Co gamma-rays in spheres of similar size to the human cell nucleus, the 4.5 microm sphere has been chosen as illustrative. Frequency distributions for 5 MeV alpha-particles are derived, based on the idealized situation of a parallel beam of constant LET, with all particles traversing the sphere. RESULTS: When compared for a dose of 1 mGy the event-size (dose) distributions of the two qualities do not intersect. It is estimated that only 0.4% of the energy from the alpha-particles falls in the range of event sizes that can be produced by 60Co gamma-rays. CONCLUSIONS: Contrary to belief over the past 50 years, there is, in this low dose range, no 'continuum' based upon quantities such as LET or lineal energy that would provide a basis for extrapolation from measured RBE values. RBE is thus seen to be purely empirical. In addition, the potential to induce effects in bystander cells is not considered when deriving weighting factors for alpha-particles of the type that contribute significantly to public exposure to environmental radiation.

Alpha Particles↗
PubMed1997

Detection of metal binding to bovine inositol monophosphatase by changes in the near and far ultraviolet regions of the CD spectrum.

Mg2+ ions, essential for the catalytic activity of mammalian inositol monophosphatase, increase the ellipticity in the near-ultraviolet region of the CD spectrum of the enzyme. These spectral changes are not affected by the additional presence of substrate and are reversed if EDTA is added to the solution of enzyme and metal ions. Titration of the spectral perturbation at 275 nm shows that this binding occurs with a dissociation constant (Kd) around 275 microM, 292 microM and 302 microM for the wild-type, [Gln217]inositol monophosphatase and [Phe219]inositol monophosphatase enzymes respectively. The source of the spectroscopic change at 275 nm is not Trp219. The addition of Mg2+ also causes a decrease in ellipticity over most of the far-ultraviolet region of the spectrum (between 205-240 nm). The Kd values describing the binding of Mg2+ ions are 3.9 mM, 6.8 mM and 29.1 mM for the wild-type, [Gln217]inositol monophosphatase and [Phe219]inositol monophosphatase enzymes, respectively, each showing an approximate 12% change in ellipticity. In the additional presence of 10 mM Pi, there is a fourfold increase in the affinity of wild-type enzyme for Mg2+. It is concluded that CD spectral changes at wavelengths around 275 nm are indicative of metal ions interacting with a high-affinity metal-binding site (site 1). The spectral changes around 225 nm are associated with interactions at a lower-affinity site normally occupied by the Mg2+ ion which is reflected by the Km value for this metal ion. Other metal ions such as Ca2+ and Tb3+ (but not Mn2+ or Zn2+) also perturb the CD spectrum of the enzyme in both regions of the spectrum. The amplitudes of these signal changes are greater for Mg2+ or Tb3+ (25%) ions than for Ca2+ (8.5%), although two Ca2+-binding sites with Kd values of 20 microM and 100 microM have been identified. The uncompetitive inhibitor Li+ causes little change in the near-ultraviolet spectrum in the absence or presence of either substrate or Pi. However, in contrast to other metal ions, Li+ ions elicit a 10% increase in ellipticity at 220 nm with a Kd of 0.8 mM.

Animals↗
PubMed1996

Brush cytology for the diagnosis of rectal carcinoma.

The use of brush cytology as an aid in the preoperative diagnosis of rectal cancer was prospectively assessed at 328 examinations in 289 consecutive patients with rectal lesions suspicious of carcinoma. Forty-five patients were reported as having benign polyps. There was 97 per cent agreement between conventional biopsy and cytology brushings for this group. Some 249 patients underwent a subsequent resection allowing comparison with formal histology. Forceps biopsy produced a true-positive diagnosis of cancer in 218 patients (89.7 per cent) and cytology in 222 (91 per cent). The sensitivity for forceps biopsy and cytology was 81 and 83 per cent respectively, with a combined sensitivity of 98 per cent. It is concluded that the addition of cytology to forceps biopsy increases the diagnostic yield in a single examination, and may be a complementary method of establishing the diagnosis of rectal lesions.

Biopsy↗
PubMed1994

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