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Biomedical subjects

M K Robinson

Publications and source records attributed to M K Robinson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Feeding critically ill patients: current concepts.

Provision of nutritional support to critically ill patients can be challenging. Critical care nurses must be aware of which patients require specific nutritional support, when to initiate nutritional support, and by which route to provide nutritional support. Consultation with a dietitian or nutritional support service can help facilitate this process. The key points in addressing these questions are (1) the nutritional status of the patient or the length of time he or she has been without significant nutrient intake, (2) whether the patient has a hypermetabolic condition that warrants the early use of nutritional support, and (3) the function of the patient's gastrointestinal tract. What to feed depends on the physiological state of the patient. Adjusting the nutrient composition of the feeding solution may prevent metabolic complications and may improve the overall outcome for the patient.

Acute Kidney Injury↗
PubMed2000

Short bowel syndrome.

The short bowel syndrome is a symptom complex that occurs in adults who have less than 200 cm of jejunum-ileum remaining after intestinal resection. Similar symptoms are observed in infants and children following massive bowel resection or congenital anomalies and in individuals with longer segments of intestine with severe mucosal disease. Initial care should focus on a thorough excision of nonviable bowel, an exact measurement of the remaining viable bowel, placing all intestine in continuity at the initial or subsequent operation, and controlling initial food intake. With time, adaptation of the remnant intestine occurs, and absorptive function may be maximized by enhancing the enteral diet and minimizing parenteral nutrition. Growth factors and specialized nutrients may also enhance this process. Intestinal transplantation should be considered in selected individuals with the short bowel syndrome who fail intestinal rehabilitation protocols.

Enteral Nutrition↗
PubMed2000

Racial differences in acute and cumulative skin irritation responses between Caucasian and Asian populations.

Japanese, and Chinese subjects. In this 2nd study, no differences were seen in the acute or cumulative irritation responses between the Japanese and Caucasian subjects. The Chinese subjects showed a heightened response to 10% acetic acid (after 4 h of exposure), but otherwise displayed a similar response profile in the acute irritation test. They showed a slower and less severe response in the cumulative irritation test compared to the Caucasian or Japanese subjects. These divergent results underscore the difficulty in ascribing true population-based differences in skin reactivity based upon studies in limited subject populations. It may be possible to detect differences in individual studies, but repeat testing may fail to confirm a consistent trend. These findings may be indicative of the wide variation in skin responsiveness across human subjects in general.

Asian People↗
PubMed2000

The importance of exposure estimation in the assessment of skin sensitization risk.

The development of new ingredients and products for the consumer market requires a thorough assessment of their potential for skin sensitization and the possible clinical manifestation of allergic contact dermatitis. The process by which low molecular weight chemicals induce and elicit skin sensitization reactions is complex and dependent on many factors relevant to the ability of the chemical to penetrate the skin, react with protein, and trigger the cell-mediated immune response. These major factors include inherent potency, chemical dose, duration and frequency of exposure, vehicle or product matrix, and occlusion. The fact that a chemical is a contact allergen does not mean that it cannot be formulated into a consumer product at levels well tolerated by most individuals. Many common ingredients (e.g., fragrances, preservatives) are known skin allergens. However, all allergens show dose-response and threshold characteristics. Therefore, one should be able to incorporate these chemicals into products at levels that produce acceptably low incidences of skin sensitization under foreseeable conditions of exposure. The critical exposure determinant for evaluating skin sensitization risk is dose per unit area of skin exposed. Use of this parameter allows for comparative assessments from different types of skin sensitization tests (including cross-species comparisons), and, at least for known potent allergens, there is remarkable similarity in threshold dose/unit area determinations across species. The dose/unit area calculation enables a judgment of the sensitization risk for different product types. This is illustrated using the chemical preservative methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) as a case study.

Animals↗
PubMed2000

A skin sensitization risk assessment approach for evaluation of new ingredients and products.

Skin sensitization risk assessment of new ingredients or products is critical before their introduction into the marketplace. The risk assessment process described in this article involves evaluation of skin sensitization hazard, consideration of all potential human exposures, comparative ingredient/product benchmarking, and, when appropriate, the management of the risk. In this article, a risk assessment process is reviewed along with a description of the risk assessment tools that are employed for evaluating a new ingredient or product. The basic process we use for evaluating the skin sensitization risk of a new product or ingredient is considered a no effect/safety factor approach. The tools used for conducting a risk assessment include structure activity relationship analysis, exposure assessment, preclinical testing (e.g., local lymph node assay [LNNA]) and clinical testing (e.g., human repeat insult patch testing [HRIPT]). The skin sensitization risk assessment process described in this paper has been used successfully for many years for the safe introduction of new products into the marketplace. This process is dynamic--it can be applied to a diversity of product categories (e.g., shampoo, transdermal drug). In summary, the skin sensitization risk assessment process described in this article allows one to carefully assess the skin sensitization potential of a new ingredient or product so that it can be safely introduced into the marketplace.

Allergens↗
PubMed2000

Influence of MHC background on the antibody response to detergent enzymes in the mouse intranasal test.

The mouse intranasal test (MINT) was developed to assess the immunogenic potential of detergent enzymes. The BDF1 mouse (H-2(b/d)), a cross of C57Bl/6 (H-2(b)) x DBA/2 (H-2(d)) has been used for most of the development work. Preliminary data in the CB6F1(H-2(d/b)), a cross of Balb/c (H-2(d)) x C57Bl/6 showed that this strain was similar to the BDF1 in its response to enzymes. These data also showed that the parental strains responded differently to the enzymes. To understand better the influence the major histocompatibility complex (MHC) background has on immune responses to enzymes, 3 different enzymes were tested in 4 inbred strains (C57Bl/6, DBA/2, Balb/c, and C57Bl/10), 2 hybrid strains (BDF1 and CB6F1), and 2 congenic strains (Balb.B10 and B10.D2). BDF1 mice rank enzymes the same as the guinea pig, which in turn correlates with sensitization in occupationally exposed humans. The ranking is based upon the dose of enzyme needed to give one-half maximal IgG1 antibody response (ED(50)) where Termamyl is more potent than Alcalase, which is equipotent to Savinase. The H-2(d) strains ranked the enzymes the same as the BDF1 but generated ED(50)s for the proteases that were one order of magnitude greater than the BDF1 ED(50)s. The response to Termamyl was the same in the two F1 strains and the H-2(d) strains. The H-2(b) strains did not rank the enzymes the same as BDF1 but the ED(50)s for the proteases were similar to the ED(50)s in the F1 strains. The response to Termamyl in the H-2(b) strains was lower than the response in the F1 and H-2(d) strains. Initial data show that the inbred strains will make enzyme-specific IgE antibody to high doses of enzyme with DBA/2 > Balb/c > C57Bl/6 in terms of the robustness of the response. The IgG1 responses in the congenic strains were similar to the responses in the H-2 matched strains. In addition, the antibody response to enzymes was consistent regardless of the source of BDF1 mice. The responses to these enzymes are clearly MHC linked with a role for Class II I-E molecules indicated. The current data strongly support the use of the F1 hybrid as an appropriate strain for evaluating allergic responses to enzymes.

Administration, Intranasal↗
PubMed2000

In vitro and human testing strategies for skin irritation.

Prior to the manufacture, transport, and marketing of chemicals or products, it is critical to assess their potential for skin toxicity (corrosion or irritation), thereby protecting the worker and consumer from adverse skin effects due to intended or accidental skin exposure. Traditionally, animal testing procedures have provided the data needed to assess the more severe forms of skin toxicity, and current regulations may require animal test data before permission can be obtained to manufacture, transport, or market chemicals or the products that contain them. In recent years, the use of animals to assess skin safety has been opposed by some as inhumane and unnecessary. The conflicting needs of the industrial toxicologist to (1) protect human safety, (2) comply with regulations, and (3) reduce animal testing have led to major efforts to develop alternative, yet predictive, test methods. A variety of in vitro skin corrosion test methods have been developed and several have successfully passed initial international validation. These have included skin or epidermal equivalent assays that have been shown to distinguish corrosive from noncorrosive chemicals. These skin/epidermal equivalent assays have also been modified and used to assess skin irritation potential relative to existing human exposure test data. The data show a good correlation between in vitro assay data and different types of human skin irritation data for both chemicals and consumer products. The effort to eliminate animal tests has also led to the development of a novel human patch test for assessment of acute skin irritation potential. A case study shows the benefits of in vitro and human skin irritation tests compared to the animal tests they seek to replace, and strategies now exist to adequately assess human skin irritation potential without the need to rely on animal test methods.

Animals↗
PubMed2000

Expression of a soluble functional form of the integrin alpha4beta1 in mammalian cells.

The integrin alpha4beta1(VLA4) has been expressed as a soluble, active, heterodimeric immunoglobulin fusion protein. cDNAs encoding the extracellular domains of the human alpha4 and beta1 subunits were fused to the genomic DNA encoding the human gamma1 immunoglobulin Fc domain and functional integrin fusion protein was expressed as a secreted, soluble molecule from a range of mammalian cell lines. Specific mutations were introduced into the Fc region of the molecules to promote alpha4beta1 heterodimer formation. The soluble alpha4beta1-Fc fusion protein exhibited divalent cation dependent binding to VCAM-1, which was blocked by the appropriate function blocking antibodies. The apparent Kd for VCAM-1 binding were similar for both the soluble and native forms of alpha4beta1. In addition, the integrin-Fc fusion was shown to stain cells expressing VCAM-1 on their surface by FACs analysis. This approach for expressing soluble alpha4beta1 should be generally applicable to a range of integrins.

Animals↗
PubMed1999

Hindlimb ischemia-reperfusion increases complement deposition and glycolysis.

BACKGROUND: Hindlimb ischemia-reperfusion (HIR) impairs cellular energy metabolism and causes local muscle injury possibly through free radical or complement-mediated mechanisms. MATERIALS AND METHODS: To determine the relationship among myocellular energetics, histopathological injury, and mediator activity, male Wistar rats underwent 4 h of Sham (n = 8), Unilateral (n = 8), or Bilateral (n = 8) hindlimb ischemia followed by 4 h of reperfusion. All rats underwent 31P magnetic resonance spectroscopy of their right gastrocnemius muscle to determine various high-energy phosphate ratios including ATP to Pi (ATP/Pi, a measure of energy status) and phosphocreatine to Pi (PCr/Pi, a measure of thermodynamic capacity). Gastrocnemius muscles were then harvested to determine muscle damage and complement membrane attack complex (MAC) deposition by immunohistochemical staining [grade 0 (none) to 3 (very severe)] and to measure glutathione (GSH), DNA, and enzyme activities: beta-hydroxyacyl-CoA dehydrogenase, phosphofructokinase, and citrate synthetase. RESULTS: HIR was associated with significant declines in ATP/Pi and PCr/Pi (P < 0.001). Progressively more severe HIR (Sham, Unilateral, Bilateral) was associated with greater MAC deposition (0. 0 +/- 0.0, 1.0 +/- 0.3, 1.5 +/- 0.4, P = 0.06, mean +/- SEM) and histological damage (0.0 +/- 0.0, 0.9 +/- 0.3, 1.3 +/- 0.4, P < 0. 05). GSH levels, beta-hydroxyacyl-CoA dehydrogenase, and citrate synthetase activities were not affected by HIR, but phosphofructokinase activity increased (24.09 +/- 2.42, 35.16 +/- 5. 26, 59.29 +/- 9.82 mmol/mg of DNA/min, P < 0.05). Although GSH levels were not significantly altered, complement deposition was closely associated with skeletal muscle injury and compensatory changes in glycolysis. Alterations in myocellular bioenergetics after HIR closely paralleled complement deposition rather than GSH depletion. CONCLUSIONS: Therapeutic strategies aimed at controlling complement activity and assessment techniques based on bioenergetics may allow more precise determinations of the effects of HIR injury.

Adenosine Triphosphate↗
PubMed1999

A two-center study of the development of acute irritation responses to fatty acids.

BACKGROUND: A human 4-hour patch test has been developed for evaluating the acute irritation potential of chemicals. This method was developed for comparative irritation assessments. Although skin irritation responses in human subjects can be quite variable, this test method has proven robust in both intra- and interlaboratory tests. However, the previous interlaboratory studies were not optimal in that slightly differing protocols were used and the studies were not controlled for time of year or source of test chemicals. As a result, some variation in acute irritation responses were seen that might have been reduced somewhat had these variables been controlled to a greater extent. OBJECTIVE: The purpose of the current study was to examine interlaboratory reproducibility of the 4-hour patch test when conducted under as identical as set of test conditions as possible. METHODS: Two laboratories conducted a direct comparison study of the acute irritation potential of three structurally related, undiluted fatty acids (octanoic acid, decanoic acid, and dodecanoic acid) in comparison to a benchmark positive control chemical (20% sodium dodecyl sulfate [SDS]). The studies were run within a 4-month period using the same commercial source of test chemicals. Test subjects were treated with each chemical under occluded patch conditions for gradually increasing exposure duration up to 4 hours. The results were then evaluated in terms of total cumulative incidence of positive responses and time response patterns. RESULTS: Using statistical comparisons of the proportion of the subjects with a positive irritant reaction to each substance, the rank order of irritation potential was decanoic acid >/= octanoic acid > SDS >> and dodecanoic acid. The statistical comparisons and the time-response patterns for each chemical were nearly identical at the two laboratories. There were also very similar, and intriguing, variations in the interchemical response patterns seen in the two studies. CONCLUSION: When conducted under as controlled a set of test conditions as was reasonably possible, this acute irritation protocol shows remarkably high consistency across independent test laboratories, further supporting its continued development and acceptance as a valid and more predictive tool for assessing skin irritation potential.

Adult↗
PubMed1999

Overview of intestinal adaptation and its stimulation.

Total parenteral nutrition (TPN) can be life-saving for many patients with short-bowel syndrome (SBS). However, chronic TPN administration is associated with nutritional deficiencies, septic complications, high health care costs, and life-threatening organ failure. In an effort to rehabilitate SBS patients so they may achieve enteral autonomy, investigators have attempted to stimulate the adaptive response following extensive small-bowel resection. Intestinal adaptation may include: 1) morphological changes of the residual bowel which increase the absorptive surface area; 2) functional changes that increase the absorptive capacity of individual enterocytes and colonocytes; and 3) changes in colonic production and absorption of short-chain fatty acids which improve intestinal vitality and maximize efficiency of energy and fluid absorption. Several peptides, nutrients, cytokines, and other factors promote intestinal adaptation in animals. These "growth" factors may predominantly affect one aspect of the adaptive response while having little or no effect on other physiologic or morphologic parameters. In addition, combined administration of stimulatory agents may be necessary to enhance adaptation. Dietary constituents may have profound positive and negative effects on adaptation and must be considered in developing an overall plan for treatment of the SBS patients. Only a few clinical studies have been performed to evaluate therapeutic regimens for SBS beyond standard supportive care and TPN administration. The combined administration of growth hormone, glutamine and a modified diet to over 225 adults has been shown to eliminate or decrease TPN dependence in 80% of patients receiving this therapy. Further study is required to optimize the treatment of humans with intestinal failure and to determine which patients are most likely to benefit from medical therapy. The authors conclude that the intestinal length to body weight index may be one predictive factor useful for determining which SBS patients will benefit from a trial of pharmacologic manipulation before attempting alternative, potentially more invasive therapies.

Adaptation, Physiological↗
PubMed1999

Comparison of in vitro and in vivo human skin responses to consumer products and ingredients with a range of irritancy potential.

Human skin equivalent cultures were investigated as possible pre-clinical skin irritation screens to aid safety assessments for chemicals and product formulations, and to facilitate design of safe and efficient human studies. In vitro responses in human skin equivalent cultures were compared directly to in vivo human skin responses from historic or concurrent skin tests for representative chemicals and products, including surfactants, cosmetics, antiperspirants, and deodorants. The in vivo data consisted of visual scores (i.e., erythema and edema) from skin-patch tests and diary accounts of skin irritation from product-use studies. In the in vitro studies, cornified, air-interfaced human skin cultures (EpiDerm) were evaluated using methods designed to parallel human clinical protocols with topical dosing of neat or diluted test substances to the stratum corneum surface of the skin cultures. The in vitro endpoints have previously been shown to be relevant to human skin irritation in vivo, including the MTT metabolism assay of cell viability, enzyme release (lactate dehydrogenase and aspartate aminotransferase), and inflammatory cytokine expression (Interleukin-1alpha). For surfactants, dose-response curves of MTT cell-viability data clearly distinguished strongly-irritating from milder surfactants and rank-ordered irritancy potential in a manner similar to repeat-application (3x), patch-test results. For the antiperspirant and deodorant products, all the in vitro endpoints correlated well with consumer-reported irritation (r, 0.75-0.94), with Interleukin-1alpha (IL-1alpha) release, showing the greatest capacity to distinguish irritancy over a broad range. IL-1alpha release also showed the best prediction of human skin scores from 14-day cumulative irritancy tests of cosmetic products. These results confirm the potential value of cornified human skin cultures as in vitro pre-clinical screens for prediction of human skin irritation responses. A preliminary report of these results has been published.

Aspartate Aminotransferases↗