Inclusion body myositis with cricopharyngeus muscle involvement and severe dysphagia.
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Deglutition Disorders↗
Biomedical subjects
M Friedman
Publications and source records attributed to M Friedman.
Fluoxetine treatment of slow eating.
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Adult↗
Cancer control and the older person. Issues in treatment.
The Committee on Treatment acknowledged the paucity of information related to the management of cancer in older patients and identified short-term and long-term efforts to study these issues. Short-term efforts should focus on effects of cancer and cancer treatment on survival and quality of life, efficacy and toxicity of antineoplastic therapy, barriers to adequate treatment, alternative settings of cancer care, and special supportive care needs. Long-term efforts should focus on unique features of cancer in older patients, long-term effects of cancer and cancer treatment, and prevention and detection of new primary malignancies. The Committee recognized that our recent advances in cancer treatment including palliative surgery, limited surgery, radiosurgery, and antidotes to drug toxicity may improve the tolerance of antineoplastic therapy by older patients and be beneficial in terms of survival and quality of life.
Aged↗
Use of sulfonated primers to detect and type papillomavirus in cell cultures and cervical biopsies.
Human papillomavirus (HPV) was detected by using two sets of deoxyribonucleotide primers for differentiating between 'low-risk' types (HPV11 and HPV6) and 'high-risk' (hri) types (HPV16, HPV18 and HPV33). A new application of the Chemiprobe method for labeling DNA was used to detect products of the polymerase chain reaction (PCR) from 36 cervical biopsies. This method, first demonstrated by Uchimura et al. (submitted), is based on the sulfonation of a polycytidylic acid tail of 5-20 monomers attached to the 5' end of either one or both of the PCR primers. This procedure can increase the sensitivity of detection of PCR products more than 100-fold with respect to ethidium bromide (EtdBr) staining. Various methods were used to detect hri HPV DNA in the 36 clinical samples. The number of positive results obtained was as follows, two by Southern-blot hybridization; five by PCR amplification followed by electrophoresis and detection of products by EtdBr staining; six by PCR amplification using one or two sulfonated C-tailed primers followed by electroblotting and immunoenzymatic visualization; and five by hybridization of sulfonated genomic viral recombinant with a PCR product immobilized on a membrane. The yield of the PCR product was significantly greater when one of the primers was C-tailed than when both or neither of the primers were C-tailed. PCR employing sulfonated C-tailed oligo primers is very specific and sensitive, and the entire procedure can be employed as a nonradioactive substitute for radioactive dot-blot or Southern-blot hybridization procedures, routinely used for detection of HPV in clinical samples.
Base Sequence↗
Variable histotoxicity of histoacryl when used in a subcutaneous site: an experimental study.
Histoacryl (butyl-2-cyanoacrylate) is one of the least histotoxic cyanoacrylate derivatives and is used as a tissue adhesive. Clinical applications primarily include skin closure (blepharoplasty incisions, etc.). In a recent study, we demonstrated that Histoacryl elicits minimal histotoxicity when used to glue bone grafts to rabbit-ear cartilage. Acute inflammation was limited to areas where Histoacryl escaped from between the bone graft and ear cartilage to contact well-vascularized soft tissue. In this study, Histoacryl was applied between bone graft and cartilage in one rabbit ear and adjacent to well-vascularized soft tissue with no graft in the opposite ear. Histologic analysis revealed minimal if any inflammation when small amounts of glue was used in the nonvascular region between bone graft and cartilage. However, subcutaneous implantation contacting well-vascularized soft tissue resulted in increased acute inflammation and prolonged foreign-body giant-cell response. Further studies are required to rule out any long-term problems associated with subcutaneous implantation of Histoacryl.
Administration, Cutaneous↗
Prevention of adverse effects of food browning.
Amino-carbonyl interactions of food constituents encompass those changes commonly termed browning reactions. Such reactions are responsible for deleterious post-harvest changes during processing and storage and may adversely affect the appearance, organoleptic properties, nutritional quality, and safety of a wide spectrum of foods. A growing area of concern is nutritional carcinogenesis, in which nutritionally linked cancer has been associated with amino-carbonyl reaction products. Specific practical and theoretical approaches to prevent adverse effects of food browning include: (1) modification and removal of primary reactants and endproducts in the browning reaction; (2) prevention of deleterious browning reactions through the use of antioxidants; (3) blocking of in vivo toxicant formation from browning products by means of dietary modulation; (4) accurate estimation of low levels of browning products in whole foods and their removal through antibody complexation; and (5) stimulation of inactivation in vivo toxicants from browning products by use of amino acids and sulfur-rich proteins.
Animals↗
ELISA analysis of soybean trypsin inhibitors in processed foods.
Soybean proteins are widely used in human foods in a variety of forms, including infant formulas, flour, protein concentrates, protein isolates, soy sauces, textured soy fibers, and tofu. The presence of inhibitors of digestive enzymes in soy proteins impairs the nutritional quality and possibly the safety of soybeans and other legumes. Processing, based on the use of heat or fractionation of protein isolates, does not completely inactivate or remove these inhibitors, so that residual amounts of inhibitors are consumed by animals and humans. New monoclonal antibody-based immunoassays can measure low levels of the soybean Kunitz trypsin inhibitor (KTI) and the Bowman-Birk trypsin and chymotrypsin inhibitor (BBI) and the Bowman-Birk foods. The enzyme-linked immunosorbent assay (ELISA) was used to measure the inhibitor content of soy concentrates, isolates, and flours, both heated and unheated; a commercial soy infant formula; KTI and BBI with rearranged disulfide bonds; browning products derived from heat-treatment of KTI with glucose and starch; and KTI exposed to high pH. The results indicate that even low inhibitor isolates contain significant amounts of specific inhibitors. Thus, infants on soy formula consume about 10 mg of KTI plus BBI per day. The immunoassays complement the established enzymatic assays of trypsin and chymotrypsin inhibitors, and have advantages in (a) measuring low levels of inhibitors in processed foods; and (b) differentiating between the Kunitz and Bowman-Birk inhibitors. The significance of our findings for food safety are discussed.
Alkalies↗
Effect of heat on the nutritional quality and safety of soybean cultivars.
To evaluate whether soybean strains with reduced levels of trypsin inhibitors have enhanced nutritional and safety characteristics, we measured protease inhibitor content of a standard cultivar (Williams 82) and an isoline (L81-4590) lacking the Kunitz trypsin inhibitor, using enzyme inhibition assays and enzyme-linked immunosorbent assays (ELISA). Less heat was needed to inactivate the remaining trypsin inhibitory activity of the isoline than that of the standard soybean cultivar. In fact, autoclaving (steam heating at 121 degrees C) of the isoline for 20 min resulted in a near zero level of trypsin inhibitor activity, while 20% remained in the Williams 82 sample. Feeding studies with rats showed that the raw soy flour prepared from the isoline was nutritionally superior to the raw flour prepared from the standard variety, as measured by PER and pancreatic weights. Since the content of amino and fatty acids of the flours from both strains was identical and the hemagglutinating activities were within a factor of 2, the increased PER was likely due to the lower level of trypsin inhibitory activity in the isoline. Steam heating the flours for up to 30 min at 121 degrees C progressively increased the PER for both strains. Preliminary screening of several accessions from the USDA Soybean Germplasm Collection showed considerable variation in the content of trypsin inhibitors, sulfur amino acids, and lectins. The BBI content of these cultivars, determined by chymotrypsin inhibition assays, was identical to that found by ELISA. The results indicate that further screening studies could lead to the discovery of soybeans which yield flour that is safe and nutritious, with minimal need for heating.
Amino Acids↗
Improvement in the nutritional quality of bread.
To assess whether the dipeptide N-epsilon-(gamma-L-glutamyl)-L-lysine (glutamyl-lysine) can serve as a nutritional source of lysine, we compared the growth of mice fed (a) an amino acid diet in which lysine was replaced by six dietary levels of glutamyl-lysine; (b) wheat gluten diets fortified with lysine; (c) a wheat bread-based diet (10% protein) supplemented before feeding with lysine or glutamyl-lysine (0, 0.75, 1.50, 2.25, and 3% lysine HCl-equivalent in the final diet), not co-baked and (d) bread diets co-baked with these levels of lysine or glutamyl-lysine. With the amino acid diet, the relative growth response to glutamyl-lysine was about half that of lysine. The effect of added lysine on the nutritional improvement of wheat gluten depended on both lysine and gluten concentrations in the diet. With 10 and 15% gluten, 0.37% lysine HCl produced a marked increase in weight gain. Further increase in lysine HCl to 0.75% proved detrimental to weight gain. Lysine HCl addition improved growth at 20 and 25% gluten in the diet and did not prove detrimental at 0.75%. For whole bread, glutamyl-lysine served nearly as well as lysine to improve weight gain. The nutritive value of bread crust fortified or not was markedly less than that of crumb or whole bread. Other data showed that lysine or glutamyl-lysine at the highest level of fortification, 0.3%, improved the protein quality (PER) of crumb over that of either crust or whole bread, indicating a possible greater availability of the second-limiting amino acid, threonine, in crumb. These data and additional metabolic studies with U-14-C glutamyl-lysine suggest that glutamyl-lysine, co-baked or not, is digested in the kidneys and utilized in vivo as a source of lysine; it and related peptides merit further study as a sources of lysine in low-lysine foods.
Amino Acids↗
Formation, nutritional value, and safety of D-amino acids.
The extent of racemization of L-amino acid residues to D-isomers in food proteins increases with pH, time, and temperature. The nutritional utilization of different D-amino acids vary widely, both in animals and humans. In addition, some D-amino acids may be deleterious. For example, although D-phenylalanine is nutritionally available as a source of L-phenylalanine, high concentrations of D-tyrosine inhibit the growth of mice. The antimetabolic effect of D-tyrosine can be minimized by increasing the L-phenylalanine content of the diet. Similarly, L-cysteine has a sparing effect on L-methionine when fed to mice; however, D-cysteine does not. The wide variation in the utilization of D-amino acids is exemplified by the fact that D-lysine is not utilized as a source of L-lysine, whereas the utilization of D-methionine as a source of the L-isomer for growth is dose-dependent, reaching 76% of the value obtained with L-methionine. Both D-serine and the mixture of L-L and L-D isomers of lysinoalanine induce histological changes in the rat kidneys. D-tyrosine, D-serine, and lysinoalanine are produced in significant amounts under the influence of even short periods of alkaline treatment. Unresolved is whether the biological effects of D-amino acids vary, depending on whether they are consumed in the free state or as part of a food protein. Possible, metabolic interaction, antagonism, or synergism among D-amino acids in vivo also merits further study. The described results with mice complement related studies with other species and contribute to the understanding of nutritional and toxicological consequences of ingesting D-amino acids. Such an understanding will make it possible to devise food processing conditions to minimize or prevent the formation of undesirable D-amino acids in food proteins and to prepare better and safer foods.
Amino Acids↗
Hepatic ornithine decarboxylase induction by potato glycoalkaloids in rats.
The induction of hepatic ornithine decarboxylase (ODC) activity in rat livers by the potato glycoalkaloids alpha-solanine, alpha-chaconine, and their aglycone solanidine, has been studied. Ip administration of alpha-solanine at 7.5, 15 and 30 mg/kg body weight produced markedly elevated enzyme activity at 4 hr after treatment, with a linear dose response. The increase was four-fold at the lowest dose administered to 12-fold at the highest. ODC activity was measured at 1, 2, 3, 4, 5, 6, 8, and 24hr after alpha-solanine was given. A statistically significant increase in enzyme activity was evident at 3 hr after treatment; maximal activity occurred at 5 hr and was approximately 12 times greater than the dimethylsulphoxide (DMSO) control level. Elevated activities persisted for several hours, decreasing to about one-third of the maximal level at 8 hr. The relative effects of alpha-solanine, alpha-chaconine and solanidine on ODC activities were studied at 4 hr using an equimolar dose of 17 mM/kg body weight. ODC activity induced by alpha-chaconine was higher than that induced by alpha-solanine; the latter activity was two-thirds that of the former. The aglycone solanidine did not induce any increase in activity compared with the DMSO control. ODC activity with dexamethasone, a glucocorticoid, at 4 mg/kg body weight, followed a pattern similar to that of alpha-solanine. However, maximal activity occurred slightly earlier at 4 hr after treatment. The results show that the extent of induced ODC activity depends on the structure of the potato alkaloid.
Animals↗
Developmental toxicology of potato alkaloids in the frog embryo teratogenesis assay--Xenopus (FETAX).
Potatoes frequently contain growth inhibitors and toxic compounds including digestive enzyme inhibitors, lectins and glycoalkaloids. The literature suggests that Solanum alkaloids have the ability to induce neurological damage such as spina bifida and other malformations. As part of a programme of improvement in the safety of potatoes using molecular plant genetics and parallel food safety evaluation, we evaluated the effect of several potato glycoalkaloids and aglycones in the frog embryo teratogenesis assay--Xenopus (FETAX) with and without metabolic activation by Aroclor 1254-induced rat liver microsomes. The data suggest that the glycoalkaloid alpha-chaconine is teratogenic and more embryotoxic than alpha-solanine, in terms of the median lethal concentration (LC50) after 96 hr of exposure, the concentration inducing gross terata in 50% of the surviving frog embryos (96-hr EC50, malformation), and the minimum concentration needed to inhibit the growth of the embryos. Since these two compounds differ only in the nature of the carbohydrate side chain attached to the 3-OH group of solanidine, the side chain appears to be an important factor in governing teratogenicity. The aglycones demissidine, solanidine and solasodine were less toxic than the glycosides alpha-chaconine and alpha-solanine. The in vitro teratogenesis assay should be useful for: (a) predicting the teratogenic potential of solanaceae alkaloids, glycoalkaloids and related natural products; and (b) facilitating experimental approaches to suppress plant genes and enzymes that control the biosynthesis of the most toxic compounds.
Abnormalities, Drug-Induced↗
Education for leadership in health development.
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Education, Medical, Undergraduate↗
Rethinking critical issues in performance assessment.
The recent interest of medical schools and licensure organizations in establishing performance assessment methods in medical education presents new challenges to medical educators. The problems encountered in establishing the reliability and validity properties of performance assessment necessitate rethinking the accepted definitions of reliability and validity. The authors examine the relationship between Classical Test Theory and job performance. They discuss several critical issues: the meanings of reliability and validity in performance assessment and the balance between them (including simple versus complex behaviors), stability of performance, specific versus generic abilities, and the role of experts in clinical performance assessment. The authors call for a critical appraisal of applying Classical Test Theory to the assessment of job-related behaviors.
Clinical Competence↗
The use of standardized patients to evaluate the spoken-English proficiency of foreign medical graduates.
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Clinical Competence↗
Assessment of emergency medicine: a comparison of an experimental objective structured clinical examination with a practical examination.
An emergency medicine and trauma programme was implemented at Ben Gurion University Medical School in Israel. Clinical performance assessment of the first-year course in emergency medicine and trauma was done using a practical examination (PE). In the continuous process of critically reviewing the course objectives and assessment methods the objective structured clinical examination (OSCE) was chosen, for the first time in our medical school, as a tool for course development as well as evaluation of the existing PE. Seven experimental OSCE stations were designed which covered some of the course and practical examination topics. Twenty-six first-year medical students have taken both examinations concurrently. Twenty-three students answered an attitude questionnaire regarding both examinations. Results have indicated that the OSCE provided additional and crucial information on students' deficiencies in clinical performance which were not available from the PE. Those differences were probably due to realistic OSCE station content, highly simulated set-ups, and the objectivity of the examiner, all of which have contributed to a more challenging examination, as compared to the PE. The OSCE in emergency medicine and trauma seemed to have a relatively high level of acceptance by both staff and students. In our opinion it seems that the OSCE is a better tool for first-year level final assessment in emergency medicine and trauma. is a better tool for first-year level final assessment
Clinical Competence↗
The effect of growth hormone on weight gain and pulmonary function in patients with chronic obstructive lung disease.
Thirty to 60 percent of patients with chronic obstructive pulmonary disease (COPD) are malnourished, and this affects ventilatory muscle function and prognosis for survival adversely. We studied the effect of growth hormone (GH) in malnourished patients with COPD (n = 7, mean FEV1 of 1.1 +/- 0.2 L, 45 +/- 7 percent of predicted values; less than 90 percent of ideal body weight). The subjects received a balanced diet of 35 kcal/kg with 1 g of protein/kg for 1 week (pre-GH). During the following three weeks, they received the same diet plus subcutaneous injections of recombinant methionyl human GH (0.05 mg/kg daily). The subjects had no significant weight gain during the week of diet alone (0.07 +/- 0.11 kg, p = NS) but they had substantial weight gain during the first week of GH treatment (1.37 +/- 0.23 kg, p less than 0.01). Nitrogen balance also improved during GH treatment (+1.6 +/- 0.7 g/day on diet alone vs +3.8 +/- 0.5 g/day on diet plus GH, p less than 0.02). Maximal inspiratory pressure improved by 27 +/- 8 percent after GH treatment (p less than 0.02). No significant adverse effects occurred. Further study of the potential usefulness of GH in COPD utilizing a placebo-controlled trial is warranted.
Aged↗
The use of sustained release delivery of chlorhexidine for the maintenance of periodontal pockets: 2-year clinical trial.
The release of chlorhexidine from an ethyl cellulose-based dosage form (SRD) has been shown to be effective in the reduction of the flora associated with periodontal pockets as well as in reducing probing depths. In this study, treatment with this dosage form was compared to routine maintenance therapy (RMT) in a 2-year, split mouth clinical trial. Ten patients with 84 pockets greater than or equal to 5 mm who had not received any periodontal therapy or systemic antibiotics over the last 6 months were included. The patients all received a full mouth scaling and root planing together with through oral hygiene instruction. Two months later (baseline) plaque index (P1I), bleeding on probing (BOP), pocket probing depth (PD), and attachment levels (AL) were assessed at all selected sites. Pockets on the control side then received RMT while the experimental pockets were treated with the SRD only. Treatment was repeated every 3 months for 2 years. The SRD treatment resulted in an improvement of greater than or equal to 3 mm in PD of at least 1 pocket in 8 of 10 patients, while RMT resulted in a similar improvement in only 1 of 10 patients (P = 0.012). Similarly a gain of attachment of greater than or equal to 3 mm was found in at least 1 SRD pocket in 8 of 10 patients. The RMT resulted in a similar improvement in only 2 patients (P = 0.012).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗