Practice parameters for the identification and testing of patients at risk for dominantly inherited colorectal cancer--supporting documentation.
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Biomedical subjects
Publications and source records attributed to A Lowry.
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It should be recognized that these guidelines should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all of the circumstances presented by the individual patient.
PURPOSE: In our clinical and research experience, persons with fecal incontinence anecdotally report altered diet intake to avoid incontinence. The purpose of this study was to compare the dietary intake of 39 persons with fecal incontinence living in the community with that of age- and gender-matched control subjects who had normal bowel function. The diets of both groups were compared with recommended dietary allowances (RDAs) for their constituent nutrients. METHODS: Subjects prospectively recorded the type, amount, and method of preparing all foods and beverages ingested for 8 consecutive days. Diet records were analyzed using the Nutritionist IV software program. MAIN OUTCOME MEASURES: The main outcome measures were the amounts and percentage of the RDAs of macronutrients and micronutrients in the subjects' diets. RESULTS: There were no significant differences in the intake of total kilocalories, protein, fat, dietary fiber, caffeine, or lactose by the fecal incontinence and control groups. The fecal incontinence group had a greater intake of carbohydrates, manganese, and vitamin B(1) compared with the control group. Diets of both groups exceeded 100% of the RDA for protein, phosphorus, iron, sodium, potassium, Vitamins B(1), B(2), B(3), B(12), and C and folate. Diets of both groups had less than 50% of the RDA for biotin, chromium, copper, and manganese but did not differ significantly. The percentages of the RDA for calcium and vitamin D were 84% +/- 6% and 56% +/- 8% for the fecal incontinence group and 90 +/- 8 (P =.6) and 69 +/- 11 for the control group (P =.4). CONCLUSIONS: The diets of persons with fecal incontinence were similar to those of control subjects with normal bowel function. Both the fecal incontinence and control groups may improve their nutritional patterns by lowering sodium and protein intake and increasing dietary fiber and monounsaturated fat intake. Calcium and vitamin D supplementation may improve dietary deficiencies and lower disease risks. Including a nutritional assessment and consultation in the care of persons with fecal incontinence to improve their general health and prevent disease is recommended, but consideration must be given to altered diet patterns perceived by the patient to prevent fecal incontinence.
AIM: The relationship between perineurial collagen IV content and fascicle size was determined in diabetic and control human peripheral nerve. METHODS AND RESULTS: Age-matched diabetic and control sural nerve samples were immunostained using antibodies to collagen IV. The number of cell layers and the perimeter of the fascicle were measured and the collagen IV content of the perineurium determined. Using this method, a comparison could be made of collagen IV content in the perineuria of fascicles of different size. A positive linear relationship was found between fascicle size and the amount of collagen IV per unit of perineurium. The number of perineurial cell layers and the collagen IV content of the diabetic nerve did not differ from control values. CONCLUSIONS: The linear relationship between fascicle size and perineurial collagen IV content per unit of perineurium underlines the importance of taking fascicle size into account when determining changes in basement membrane components associated with neuropathy. The results indicate that increased deposition of collagen IV is not involved in the early changes in the perineurial cell basement membrane and is thus not the primary factor involved in altered nerve function associated with diabetic neuropathy.
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OBJECTIVE: The purpose of this study was to compare the stool consistency categorizations made by 39 adults with fecal incontinence and the percentage of water in their stools determined by lyophilization. METHODS: Subjects collected all stools daily for 8 days during a baseline period and at the end of a fiber treatment period. Stool consistency was recorded as hard and formed, soft but formed, loose and unformed, or liquid. Aliquots of the stools were lyophilized to constant weight. MAIN OUTCOME MEASURES: The main outcome measures were the percentage of stool water among stools in each consistency category and the correlation between subjects' stool consistency categorizations and the percentage of stool water. RESULTS: The subjects were 8 men and 21 women, ranging in age from 30 to 89 years, who were participating in a study of the effectiveness of dietary fiber for treating fecal incontinence. A total of 1023 stool samples were analyzed. Significant differences in the mean percentage of water were found among the 4 stool consistency categories (hard and formed = 68% +/- 0.9%, soft but formed = 74% +/- 0.3%, loose and unformed = 80% +/- 0.4%, and liquid = 85% +/- 0.3%; P < .001). Ninety-six percent of the stools had a percentage of water within 2 SDs of the mean percentage of water of other stools in their consistency category. CONCLUSION: This classification system of stool consistency is a valid and practical measure for clinical studies. It may be useful for clinicians and patients to evaluate outcomes of treatments directed at improving stool consistency.
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Methods are described for the semiquantitative analysis of the connective tissue components of human peripheral nerve using light microscopy. General histological preservation was assessed using haematoxylin and eosin staining and the distribution of collagen type IV was investigated using immunohistochemistry. Several techniques were investigated to establish the one giving optimum structural preservation, immunobinding and greatest contrast for image analysis. Frozen sections were unsuitable for this tissue and paraffin wax sections were therefore used. Alcohol fixation was rejected due to poor preservation of the endoneurium, although immunobinding was excellent. Ice-cold formalin fixation for 24 h was found to be adequate for structural preservation and antibody binding, provided that a protease step was introduced. Trypsin was found to be superior to pepsin for exposing collagen type IV epitopes. Of the detection systems investigated indirect immunofluorescence was not suitable due to considerable autofluorescence of the nerve. The avidin-biotin method provided the greatest contrast, and was therefore the detection method of choice for image analysis. The optimum techniques for image analysis were then used on control human sural nerve to ascertain the best comparative method for collagen type IV in the perineurium. A method of semiquantitative analysis is described which takes into account the fact that there is a close linear relationship between collagen content per unit of perineurium and perineurial perimeter as fascicle size increases in peripheral nerve. This means that data from 2 different sample groups can easily be compared, provided that a range of fascicle sizes is analysed in each case.
While Ras proteins are activated by stimulated GDP release, which enables acquisition of the active GTP-bound state, little is known about how guanine nucleotide exchange factors (GEFs) interact with Ras to promote this exchange reaction. Here we report that mutations within the switch 2 domain of Ras (residues 62-69) inhibit activation of Ras by the mammalian GEFs, Sos1, and GRF/CDC25Mm. While mutations in the 62-69 region blocked upstream activation of Ras, they did not disrupt Ras effector functions, including transcriptional activation and transformation of NIH 3T3 cells. Biochemical analysis indicated that the loss of GEF responsiveness of a Ras(69N) mutant was due to a loss of GEF binding, with no change in intrinsic nucleotide exchange activity. Furthermore, structural analysis of Ras(69N) using NMR spectroscopy indicated that mutation of residue 69 had a very localized effect on Ras structure that was limited to alpha-helix 2 of the switch 2 domain. Together, these results suggest that the switch 2 domain of Ras forms a direct interaction with GEFs.
OBJECTIVE: We investigated interindividual differences in the shape, slope and setpoint of the pituitary-thyroid axis (PTA) in normal persons. Based on these physiological data we propose a novel bivariate concept for the interpretation of thyroid function tests which is less biased by interindividual differences in the PTA than the currently used univariate approach. DESIGN: In two separate trials (A and B), healthy volunteers were given small, increasing doses of T3 (7.5-45 micrograms/day orally) over 5 days. The regulation characteristics of the individual PTAs and the effects of age and gender were assessed by general linear regression models. In addition, serum samples were collected from normal persons to establish the proposed bivariate approach for the interpretation of thyroid function tests. SUBJECTS: The regulatory characteristics of the PTA were determined in a total of 21 normal volunteers (eight females, 13 males; age 24-49 years). Single blood samples were collected from 257 normal volunteers. The participants had no history of pituitary or thyroid disease. MEASUREMENTS: Free and total thyroid hormone and TSH concentrations were determined in the serum. All samples from one person were analysed in the same assay in duplicate. RESULTS: A log-linear relationship between T3 and TSH was found to describe best the individual PTA (multiple r = 0.96). However, significant differences in the setpoint (P < 0.001) and to a lesser degree in the slope (P < or = 0.05) of the PTA were detected; this variability was not dependent on age or gender. Since these findings invalidate the assumptions on which the current univariate interpretation of thyroid function tests is based, we propose a novel model for the evaluation of thyroid function tests derived from the experimentally determined shape and average slope of the PTA. CONCLUSIONS: The presence of significant age and gender-independent interindividual variations in the setpoint of the pituitary-thyroid axis raises conceptual problems with the current approach for interpreting thyroid function tests. An easy to use graphical bivariate representation of the normal ranges for thyroid function tests is presented and exemplified by the thyroid hormone and TSH measurements in a large reference population. This concept should improve the diagnostic accuracy in the borderline-normal, and particularly subclinical hypothyroid region of these hormone measurements.
A group of non goitrous, potential Gurkha army recruits were tested in Nepal for serum free triiodothyronine (fT3), free thyroxine (fT4) and thyrotropin (TSH) concentrations. Twenty-five percent of the men were recruited into the army and urine samples taken for analysis of iodine and creatinine. Twenty per cent of the recruits underwent thyrotropin releasing hormone (TRH) stimulation tests. After ten months basic training on a diet considered to be iodine sufficient, the tests were repeated on the same men. The results were also compared to army recruits in the UK. All the potential Gurkha recruits had higher serum levels of thyroid hormones than the UK recruits. Some regional differences were found with those men from the Western recruiting depot having lower fT4 and higher TSH concentrations. Urinary iodine and creatinine concentrations showed evidence of slight relative malnutrition and iodine deficiency which was more pronounced in the Western depot. TRH stimulation tests showed no evidence of thyroid dysfunction but highlighted the differences between the Eastern and Western groups. After ten months on an iodine sufficient diet the serum thyroid hormone concentrations became closer to those of the UK recruits, showing any differences to be reversible. The results from the two Gurkha groups became similar which was reflected in the urine analysis results.
Fifty-six patients in Europe were entered into a multi-centre study to compare the accuracy of technetium 99m methoxyisobutylisonitrile (99mTc-MIBI) for the detection of coronary artery disease (CAD) with thallium 201 (201Tl) chloride perfusion scanning. The results showed a high degree of concordance between the two radiopharmaceuticals. Some 81% (678/840) of myocardial segments showed the same result (normal, infarct or ischaemia), and 80% (45/56) of patients had the same diagnosis. Overall detection of CAD in patients was 98% for 201T1 and 96% for 99mTc-MIBI. Detection of CAD in total arteries was 68% for both agents. In this study 99mTc-MIBI was as accurate as 201Tl for the detection of coronary artery stenoses.
The white-ivory test is based upon the reversion of the X-linked, recessive eye-colour mutation white-ivory to wild-type. Somatic reversion of white-ivory results in clones of red facets in the white-ivory eyes of eclosing adult flies. 4 anti-cancer drugs, bleomycin, adriamycin, mitoxantrone and cyclophosphamide were found to significantly increase the white-ivory reversion frequency whereas cytosine arabinoside, methotrexate and vincristine did not give positive results.
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Conditions were developed to permit the extraction of branched-chain 2-oxoacid dehydrogenase from brain tissue in the state of phosphorylation in which it occurred in vivo. Tissue was cold clamped to prevent interconversion of the enzyme forms without rupturing mitochondrial membranes. Extraction was carried out in the presence of NaF to prevent dephosphorylation of the enzyme complex and in the presence of ADP to prevent phosphorylation. In adult male control rats, approximately 35% of the total enzyme from brain was present in the active form. In brains of diabetic rats, the active fraction was increased to 56%. Total activities did not differ in the two groups of rats.