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1.
J Adv Nurs ; 78(1): 252-263, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34812517

ABSTRACT

AIMS: To (1) describe experiences of home from a well-being perspective, (2) describe participant characteristics and well-being measures in relation to housing type (3) and how the aforementioned aspects may affect well-being in very old persons. DESIGN: Cross-sectional, convergent parallel-results mixed method design with semi-structured interviews analysed by qualitative content analysis, in relation to descriptive statistics and specific well-being outcome measures related to home. METHODS: A total of 50 persons 80 years or older living in ordinary housing were interviewed (July 2017 to November 2018) about home in relation to well-being, along with collection of participant characteristics and well-being measures related to home. RESULTS: Participants described how home had become increasingly important as it provided autonomy and acted as a social and occupational hub. However, autonomy was not unconditional, and home could also be perceived as a place of inactive solitude. Results were interpreted as relating to being in the margins of home and had a major impact on well-being. Housing type seemed of importance with higher measures of well-being for participants in single-living housing compared with those living in apartment. CONCLUSION: Home is increasingly central to well-being in old age; however, very old persons also have to relate to being physically and mentally in the margins of being able to remain in the home. These aspects of home potentially have a major impact on well-being. IMPACT: As very old persons living in ordinary housing will constitute a larger segment of society in coming years, aspects of home can potentially have a considerable impact on well-being for this age-group. This study describes aspects of home that contribute to, or has adverse impact on well-being. These aspects need thorough consideration in policy-making and planning of health care that can affect experiences of home.


Subject(s)
Housing , Cross-Sectional Studies , Humans
2.
J Anim Sci ; 85(10): 2517-23, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17526659

ABSTRACT

Specific pig breeds with unique characteristics have been developed, and the current study sought to characterize some of these differences. Using modified Ussing chambers, electrophysiological mucosal transport of D-glucose, L-Gln, L-Pro, L-Arg, L-Thr, and glycylsarcosine was assessed in small intestinal tissues (duodenum, jejunum, ileum) taken from Yorkshire-based hybrid (BW = 142.4 +/- 2.0 kg; mean age = 8 mo) and Meishan (BW = 65.8 +/- 0.8 kg; mean age = 6 mo) female pigs after 4 h of lipopolysaccharide (LPS) exposure. Gilts were randomly assigned to control (saline infusion; n = 6 Yorkshires, n = 5 Meishans) or LPS (n = 7 Yorkshires, n = 5 Meishans) groups. Therefore, treatments were arranged in a 2 (breed) x 2 (LPS infusion) factorial. Four hours after infusions, pigs were euthanized, and intestinal segment samples were removed. Glucose transport in the ileum was decreased (P < 0.001) in Yorkshires with LPS but was increased (P < 0.001) by over 2-fold in Meishans with LPS. After LPS infusion, Pro transport was increased in duodenum (over 5-fold; P = 0.04) and ileum (over 10-fold; P < 0.001) of Meishans but was unaffected in Yorkshires. Arginine transport in the ileum of control Meishans was greater (P = 0.05) than Arg transport in control Yorkshires. Glycylsarcosine transport was greater (P = 0.02) in Meishans than Yorkshires (nearly 2-fold), regardless of LPS provision. Glycylsarcosine transport was increased (P = 0.003) over 2-fold by LPS, regardless of pig breed. Resistance (barrier function) was increased (P = 0.03) by LPS in Yorkshires but was unaffected in Meishans. The current study indicates that small intestinal function responded differently to LPS in Yorkshire and Meishan gilts and that these effects were nutrient- and segment-dependent.


Subject(s)
Amino Acid Transport Systems/drug effects , Amino Acids/metabolism , Intestine, Small/metabolism , Lipopolysaccharides/toxicity , Swine/metabolism , Amino Acid Transport Systems/metabolism , Animal Feed , Animal Nutritional Physiological Phenomena , Animals , Breeding , Female , Glucose/metabolism , Random Allocation
3.
J Hum Nutr Diet ; 19(6): 401-19, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17105538

ABSTRACT

AIM: To update dietetic guidelines based on systematic review evidence on dietary advice to prevent further events in people with existing cardiovascular disease (CVD) (secondary prevention). METHODS: The Cochrane Library, MEDLINE and EMBASE were comprehensively searched to January 2005 for systematic reviews on aspects of diet and heart health. Reviews were included if they searched systematically for randomized controlled trials relating to diet and secondary prevention of CVD. Each review was critically appraised by at least two members of the UK Heart Health and Thoracic Dietitians Group. The quality and results of each review were discussed and summarized at a group meeting. RESULTS: Evidence-based strategies that reduce cardiovascular events in those with CVD include reduction in saturated fat and substitution with unsaturated fats. Individuals who have suffered a myocardial infarction may also benefit from adopting a Mediterranean type diet and increasing intake of omega 3 fats, but it is not clear whether they are beneficial for all patients with CVD. There is no systematic review evidence to support the use of antioxidant vitamins supplements, low glycaemic index diets, or homocysteine lowering therapies in this group. CONCLUSION: There remains good evidence that reducing saturated fat reduces morbidity in patients with CVD. This advice is consistent for most manifestations of CVD, with the addition of Mediterranean dietary advice and increased omega 3 fats for those who have had a myocardial infarction.


Subject(s)
Cardiovascular Diseases/prevention & control , Dietetics/standards , Practice Guidelines as Topic , Antioxidants/administration & dosage , Antioxidants/therapeutic use , Cardiovascular Diseases/diet therapy , Dietary Fats, Unsaturated/administration & dosage , Dietary Fats, Unsaturated/therapeutic use , Evidence-Based Medicine , Glycemic Index , Homocysteine/blood , Humans , Randomized Controlled Trials as Topic , United Kingdom
4.
J Anim Sci ; 82(9): 2610-4, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15446477

ABSTRACT

A pig growth assay was conducted to determine the relative biological value (RBV) of lysine from L-lysine sulfate compared with feed-grade L-lysine HCl. One hundred nursery pigs with an average initial BW of 9.5 +/- 1.5 kg were blocked by BW and gender and allotted randomly to five dietary treatments in five replicates of four pigs per pen. A corn-peanut meal diet containing 0.6% total lysine (as-fed basis) was supplemented with two levels (0.1 and 0.2%) of lysine from L-lysine-HCl or L-lysine sulfate. The RBV of L-lysine sulfate was determined using multiple regression slope-ratio methodology, with ADG and G:F as the response criteria. At the tested levels, linear responses for gain and G:F were obtained from increments of lysine from the two lysine sources. When ADG was regressed on supplemental lysine intake, the RBV of lysine in L-lysine sulfate was 99% of the RBV of lysine in L-lysine HCl. When G:F was regressed on supplemental lysine intake, the RBV of lysine in L-lysine sulfate was 97% of the RBV of lysine in L-lysine-HCl. The t-test analysis revealed that the RBV of lysine in L-lysine sulfate was not significantly different from the RBV of lysine in L-lysine HCl, which was assumed to be 100% bioavailable. In conclusion, L-lysine sulfate can replace L-lysine HCl in diets for growing swine.


Subject(s)
Animal Feed , Animal Nutritional Physiological Phenomena , Eating/drug effects , Lysine/pharmacokinetics , Swine/growth & development , Weight Gain/drug effects , Animals , Biological Availability , Dose-Response Relationship, Drug , Female , Lysine/administration & dosage , Lysine/analogs & derivatives , Male , Nutritive Value , Random Allocation , Regression Analysis , Swine/metabolism
5.
J Anim Sci ; 81(12): 3035-45, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14677859

ABSTRACT

Cultivation-independent microbial molecular ecology approaches were used to examine the effects of antibiotic growth promoters on the pig ileal microbiota. Five-week-old barrows were fitted with a simple T-cannula at the distal ileum. Three diets meeting or exceeding the minimum nutrient requirements were fed for 5 wk and supplemented as follows: 1) negative control (no antibiotic; n = 5), 2) continuous tylosin administration (n = 5), and 3) an antibiotic rotation sequence (wk 1, chlorotetracycline sulfathiazole penicillin; wk 2, bacitracin and roxarsone; wk 3, lincomycin; wk 4, carbadox; wk 5, virginiamycin; n = 5). Ileal luminal contents were collected for DNA isolation at the end of each of the 5 wk of the testing period. The V3 region of 16S rDNA was amplified by PCR and analyzed via denaturing gradient gel electrophoresis (DGGE) and quantitative polymerase chain reaction (qPCR). Resulting PCR-DGGE band numbers (bacterial species) were counted, and the banding patterns analyzed by calculating Sorenson's pairwise similarity coefficients (C(S)), an index measuring bacterial species in common among samples. Band numbers and total bacterial DNA concentrations decreased (P < 0.05) temporally in antibiotic-treated pigs compared with controls. Comparisons between treatments yielded low intertreatment C(S) indices, indicating treatment-dependent alterations in banding patterns, whereas intratreatment comparisons revealed increased homogeneity in antibiotic-treated vs. control pigs. Sequence analysis of treatment-specific bands identified three Lactobacillus, one Streptococcus, and one Bacillus species that were diminished with antibiotic rotation treatment, whereas tylosin selected for the presence of L. gasseri. Lactobacillus-specific qPCR was performed and analyzed as a percentage of total bacteria to further evaluate the effects of antibiotic administration on this genus. Total bacteria were decreased (P < 0.05) by tylosin and rotation treatments, whereas the percentage of lactobacilli increased (P < 0.05) by d 14 and through d 28 in tylosin-treated pigs. The decrease in total bacteria by antibiotics may reduce host-related intestinal or immune responses, which would divert energy that could otherwise be used for growth. Conversely, the ability of tylosin to improve animal growth may relate to its apparent selection for lactobacilli, commensals known to competitively exclude potentially pathogenic species from colonizing the intestine.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacteria/genetics , DNA, Bacterial/analysis , Ileum/microbiology , Swine/growth & development , Animals , Bacteria/drug effects , DNA, Bacterial/genetics , DNA, Ribosomal/analysis , DNA, Ribosomal/genetics , Ecosystem , Electrophoresis, Agar Gel/methods , Electrophoresis, Agar Gel/veterinary , Ileum/drug effects , Male , Polymerase Chain Reaction/methods , Polymerase Chain Reaction/veterinary , RNA, Ribosomal, 16S/analysis , Random Allocation , Species Specificity , Swine/microbiology , Time Factors
6.
J Anim Sci ; 80(9): 2433-41, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12350021

ABSTRACT

Fourteen ileally cannulated pigs (BW = 35 +/- 2 kg) were randomly allotted to a replicated 7 x 7 Latin square design experiment to evaluate the influence of the soybean oligosaccharides (OS), raffinose and stachyose, on ileal nutrient digestibility and fecal consistency. Semipurified diets containing soy protein concentrate (SPC) or soybean meal (SBM) as the sole protein sources were fed. Soy solubles (SS), a by-product of SBM processing containing 3.5% raffinose and 11.5% stachyose, were used to increase dietary raffinose and stachyose concentrations. The seven dietary treatments were SPC, SPC + 9% SS, SBM, SBM + 9% SS, SBM + 18% SS, SBM + 24,000 U alpha-galactosidase enzyme preparation/kg diet, and a low-protein casein (LPC) diet used to calculate true digestibility. Diets, with the exception of the LPC diet, were formulated to contain 17% CP. All diets contained 0.5% chromic oxide as a marker for ileal digestibility determination. The experimental periods were divided into a 5-d diet adaptation followed by 2-d of ileal digesta collection. Diets and digesta were analyzed for DM, N, Cr, amino acids (AA), raffinose, and stachyose. Fecal consistency was determined on d 6 and 7 of each experimental period. The apparent and true ileal AA digestibilities were not different (P < 0.05) for the SPC and SBM control diets. When SS was added to the SPC diet, apparent and true N and AA digestibilities were depressed (P < 0.05) with the exception of Trp and Pro. The apparent and true ileal N and AA digestibilities were not different (P > 0.05) between the SBM control and SBM + 9% SS diets with the exception of Glu. There was a linear decrease (P < 0.05) in apparent and true DM, Val, Gly, and Tyr digestibilities when increasing levels of SS were added to the SBM diet. The addition of alpha-galactosidase did not improve apparent or true ileal N or AA digestibilities except for apparent and true Val and Tyr. Ileal raffinose digestibility was improved (P < 0.05) by addition of a-galactosidase, but was not affected by any other dietary treatment. Ileal stachyose digestibility was not affected (P > 0.58) by treatment. Fecal consistency likewise was not affected (P > 0.36) by dietary treatment. In conclusion, soy OS reduced nutrient digestibilities, but the reductions were small, ranging from approximately 1.1 to 7.4 percentage units. This suggests that other factors may be negatively impacting SBM digestibility.


Subject(s)
Amino Acids/metabolism , Digestion , Feces/chemistry , Ileum/metabolism , Oligosaccharides/administration & dosage , Swine/metabolism , Animal Feed , Animals , Chromium Compounds , Nutritive Value , Oligosaccharides/metabolism , Raffinose/metabolism , Random Allocation , Glycine max/chemistry , Glycine max/metabolism , alpha-Galactosidase/metabolism
7.
J Anim Sci ; 80(2): 429-39, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11883431

ABSTRACT

To assess differences in soybean meal quality related to region of production, researchers in Illinois, Kansas, North Carolina, The Netherlands, and Ohio collected four soybean meal samples processed locally at least 15 d apart. These samples were assayed for ileal amino acid digestibility by pigs using a common soybean meal and a soy protein concentrate as references, and a low-protein casein diet for determination of endogenous amino acid losses. Digestibility was determined at each university using seven barrows surgically fitted with ileal cannulas in a 7 x 7 Latin square design. The experimental diets contained 17% CP from the test material except for the low-protein casein diet. Animals were fed twice daily, 12 h apart, at a level of 45 g x kg(-0.75) BW for each meal. Following a 5-d adaptation period, ileal digesta were collected for two 12-h periods for 2 d to be used for determination of ileal digestibility. Variation in amino acid digestibility was very small among and within sites and was much smaller than variation in the concentration of amino acids. Among sites, samples from The Netherlands had less total and thus digestible lysine and methionine than the U.S. samples (P < 0.05). The soybean meals tested in this experiment were approximately 4% higher in amino acids than that reported in the NRC (1998). True (standardized) digestibilities, however, were very similar to NRC values except for cysteine and threonine, which were 5 and 3 percentage points lower in this experiment, respectively. In conclusion, soybeans grown in the United States and locally processed into soybean meal were very similar in nutritional composition. Soybean meals produced in The Netherlands were lower in lysine and methionine (P < 0.05) but had a digestibility similar to that produced in the United States.


Subject(s)
Amino Acids/metabolism , Animal Feed/standards , Glycine max/chemistry , Ileum/physiology , Swine/physiology , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Catheterization/veterinary , Digestion , Male , Netherlands , Nutritive Value , United States
8.
Contemp Top Lab Anim Sci ; 40(6): 27-31, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11703054

ABSTRACT

Inserting a device (cannula) into the ileum is a common technique for studying nutrient digestibility, determining the disappearance or synthesis of a component, live tissue sampling, and inserting compounds or therapeutic agents into a specific region of the gastrointestinal tract. The purpose of this study was to implement improved cannulation procedures and care and management practices for cannulated pigs. Using these improved procedures, we successfully cannulated and maintained 15 pigs, each with an initial body weight of 30 kg. The newly designed cannula afforded improved stability and ease of adjustment while providing increased comfort to the pigs. The cannula was exteriorized through the last two ribs, providing excellent stability and security. To increase pig comfort, the cannulation site was washed and dried thoroughly and ointment was applied to the skin twice daily throughout the 63-day experiment. These updated procedures and maintenance practices should be considered and implemented in future experiments involving intestinal cannulation in pigs.


Subject(s)
Catheterization/veterinary , Ileum/physiology , Animal Welfare , Animals , Body Weight , Catheterization/methods , Male , Swine
9.
Curr Opin Clin Nutr Metab Care ; 4(5): 351-4, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11568495

ABSTRACT

Malnutrition is a serious problem, and malabsorption of nutrients is believed to be partially responsible for its prevalence. A wide variety of innovative methods have been developed to study gastrointestinal transport function. Some of the first research into gastrointestinal function was conducted in the 1700's with animal and human models. Methodological advancements continue to allow scientists to innovatively assess gastrointestinal function in animal models, cellular preparations and clinical settings. For this update, the methods are divided into in vivo, ex vivo, isolated cells and membranes, and molecular biology approaches. The in vivo methods discussed include animal and human models to measure nutrient disappearance, catheterized animal models, models with isolated intestinal segments, and a new procedure for sampling luminal fluid from patients. The ex vivo approaches discussed obtain measurements with intact tissue, such as the everted sleeves method and Ussing chambers. The utility of novel cellular preparations, membrane fractionation procedures and various molecular biology techniques is included. Various aspects of these methods are evaluated to provide a detailed overview of recent methodological developments.


Subject(s)
Intestinal Mucosa/metabolism , Nutrition Disorders/etiology , Parenteral Nutrition , Animals , Biological Transport/physiology , Culture Techniques , Humans , Intestinal Absorption , Models, Animal , Models, Biological , Nutrition Disorders/epidemiology
12.
J Anim Sci ; 79(5): 1223-9, 2001 May.
Article in English | MEDLINE | ID: mdl-11374542

ABSTRACT

Six experiments were conducted to determine the true digestible valine requirement of 5- to 20-kg pigs. In Exp. 1, a valine-deficient diet for 5- to 10-kg pigs was developed and validated in terms of growth performance in response to supplemental L-valine. A different basal diet was validated for 10- to 20-kg pigs in Exp. 2. Both diets were demonstrated to be deficient in valine and to support performance equivalent to typical nursery diets when fortified with L-valine. In Exp. 3, true ileal digestibility of valine in the two basal diets was determined in eight pigs fitted with a simple T-cannula at the terminal ileum. Another four pigs received an enzymatically hydrolyzed casein-based diet to determine endogenous contributions to collected ileal digesta. The two diets were found to have true valine digestibilities of 82% (5- to 10-kg pigs) and 86% (10- to 20-kg pigs). In Exp. 4, 80 weaned pigs (5.8 kg) were offered the basal diet fortified with five incremental doses (0.08%) of L-valine. Weight gain increased quadratically (P < 0.05) with increasing levels of valine. Broken-line analysis revealed a true digestible valine requirement of 0.86 +/- 0.03%. In Exp. 5, the true digestible valine requirement of 10- to 20-kg pigs was estimated with 120 pigs (10.9 kg) using the second basal diet fortified with six incremental doses (0.05%) of L-valine. The data suggested a digestible valine requirement level of about 0.775%, which was reevaluated in Exp. 6, wherein pigs did not respond to levels of digestible valine higher than 0.775%. In conclusion, requirement estimates were 2.50 and 2.22 g of true digestible valine per megacalorie of ME for 5- to 10- and 10- to 20-kg pigs, respectively. These empirical estimates are in close agreement with recent estimates of the National Research Council Subcommittee on Swine Nutrition of 2.48 and 2.11 g of true digestible valine per megacalorie of ME, respectively.


Subject(s)
Animal Nutritional Physiological Phenomena , Swine/physiology , Valine/physiology , Weaning , Animals , Diet/veterinary , Dietary Proteins/administration & dosage , Digestion , Female , Ileum/metabolism , Male
13.
J Anim Sci ; 79(5): 1250-8, 2001 May.
Article in English | MEDLINE | ID: mdl-11374545

ABSTRACT

The apparent ileal digestibilities of amino acids and rate of passage were evaluated in pigs (BW = 78.3 +/- 7.4 kg) fed a semipurified diet. The pigs were fed 1.82, 2.73, or 3.65 kg DMI/d. The highest level of feed intake was considered to be ad libitum feeding. The pigs were fed according to a 3 x 3 Latin square design and were allowed to adapt to each experimental diet for 5 d. This was followed by 1 d of continuous collection of ileal digesta and a 2nd d of continuous collection separated into six 2-h postprandial time blocks. Ytterbium chloride hexahydrate was used to determine rate of passage. The ileal digestibilities of amino acids and rate of passage were unaffected (P > 0.05) by level of feed intake. The use of correction factors to more accurately express amino acid concentrations in the diet and digesta affected (P < 0.05) the apparent ileal digestibility coefficients of some amino acids.


Subject(s)
Amino Acids/metabolism , Diet/veterinary , Digestion , Energy Intake , Ileum/metabolism , Swine/metabolism , Animals , Chlorides/metabolism , Female , Male , Postprandial Period , Ytterbium/metabolism
14.
J Agric Food Chem ; 48(5): 1684-91, 2000 May.
Article in English | MEDLINE | ID: mdl-10820079

ABSTRACT

Accurate determination of amino acid levels in soy products facilitates optimum diet formulation and amino acid supplementation. A study was carried out to investigate the effect of hydrolysis time and method of amino acid measurement on amino acid levels. Correction factors to standardize amino acid levels to 24 h of hydrolysis were also determined. Six different soybean products were evaluated. Hydrolysis was carried out for 10 different periods of time. Amino acids were analyzed by both ion-exchange chromatography and precolumn derivatization with phenyl isothiocyanate. Both hydrolysis time and measurement method affected (P < 0.05) amino acid levels. Standard hydrolysis conditions (hydrolysis in 6 M HCl at 110 degrees C for 24 h) rarely provide the maximal amino acid values. Therefore, sequential hydrolyses curves were very useful and should be used.


Subject(s)
Amino Acids/analysis , Chromatography, Ion Exchange/methods , Glycine max/chemistry , Thiocyanates/chemistry , Hydrolysis , Indicators and Reagents , Isothiocyanates , Kinetics
15.
J Pediatr ; 128(4): 479-84, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8618180

ABSTRACT

BACKGROUND: The exact amount of drug deposited in the respiratory and gastrointestinal tract in children with airway obstruction, when delivered from a metered-dose inhaler (MDI) via a spacer with mask, and its distribution in children with airway obstruction, are unknown. METHODS: We studied 15 children, using salbutamol labeled with technetium 99m. Each patient was imaged with a gamma-camera immediately after one puff of labeled salbutamol was administered via a spacer with mask. Drug deposition was then analyzed to measure the distribution of the labeled spray in the oropharynx, the lungs, the stomach, and the spacer with mask (Aerochamber) itself. RESULTS: Fifteen infants and children (mean age, 21 months (range, 3 months to 5 years); mean weight, 9.3 kg (range, 3.2 to 15 kg)) were studied. Mean aerosol deposition was 1.97% +/- 1.4% in the lungs, 1.28% +/- 0.77% in the oropharynx, and 1.11% +/- 2.4% in the stomach. The remainder was trapped in the spacer. Lung imaging after inhalation from an MDI via a spacer showed widespread deposition of the drug in central and peripheral intrapulmonary airways. In two adult volunteers the deposition after one puff of the same radiolabeled drug, inhaled from an MDI via a spacer with a mouthpiece, was 19% in the lungs and 2% in the stomach. CONCLUSIONS: Infants and toddlers with obstructive lung disease can be reliably and safely treated with inhaled medication administered with an MDI via a spacer with mask. The doses of a drug given from an MDI to infants and toddlers when a spacer with mask is used are not yet well defined but should be higher than the currently recommended doses, perhaps as much as an adult dose.


Subject(s)
Adrenergic beta-Agonists/administration & dosage , Albuterol/administration & dosage , Drug Delivery Systems , Lung Diseases/drug therapy , Nebulizers and Vaporizers , Administration, Inhalation , Adrenergic beta-Agonists/therapeutic use , Adult , Albuterol/therapeutic use , Child, Preschool , Female , Humans , Infant , Male , Radionuclide Imaging , Sodium Pertechnetate Tc 99m , Treatment Outcome
16.
J Med Chem ; 33(2): 614-26, 1990 Feb.
Article in English | MEDLINE | ID: mdl-1967650

ABSTRACT

Lofexidine, an alpha 2-agonist, has central hypotensive activity and peripheral intestinal antisecretory activity. Analogues were synthesized with increased polarity in an attempt to prevent penetration of the blood-brain barrier. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber with a rabbit ileum preparation. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The 2,6-dimethyl derivative of lofexidine, 4a, was as active as lofexidine in vivo, but derivatives with 2,6-substituents larger than ethyl were inactive. (Aryloxy)alkyl derivatives which have an imidazoline and a methyl or larger group as part of the alkyl exhibited the best antisecretory activity. Compounds with substituents in the para position of the phenyl ring were generally inactive. 3-Amino-2,6-dimethyl derivative 21 was twice as active as 4a. A 2-methyl substituent is required in the 3-amino series to retain good activity. 2-Methyl derivative 12a had activity comparable to that of 4a, while 6-methyl derivative 12f was inactive. Substituents on the 3-amino group did not affect the activity, but substituting a hydroxyl for the amino group produced an inactive compound. Replacing the phenyl moiety with a 4-indole resulted in retention of activity, but other heterocycles were inactive. Compound 12a was resolved and d isomer 32 was five times more potent than l isomer 33. The more active compounds in the rat cholera toxin assay (RCTA), when evaluated in the dog, exhibited antisecretory activity but also exhibited central nervous system (CNS) effects, sedation and ataxia, at 10 mg/kg, and in spontaneously hypertensive rats at 50 mg/kg. A measure of polarity, log P, was calculated for the (aryloxy)alkyl groups. Regression analysis showed no correlation of antisecretory ED50 to the calculated log P. The active compounds did not show a separation of the central CNS effects from the peripheral antisecretory activity by increasing the polarity.


Subject(s)
Adrenergic alpha-Agonists/chemical synthesis , Antidiarrheals/chemical synthesis , Gastrointestinal Motility/drug effects , Imidazoles/chemical synthesis , Receptors, Adrenergic, alpha/drug effects , Adrenergic alpha-Agonists/pharmacology , Animals , Blood Pressure/drug effects , Blood-Brain Barrier , Chemical Phenomena , Chemistry , Cholera Toxin/pharmacology , Dogs , Imidazoles/pharmacology , In Vitro Techniques , Intestinal Absorption/drug effects , Rats , Rats, Inbred SHR , Structure-Activity Relationship , Thermodynamics
18.
J Med Chem ; 31(1): 138-44, 1988 Jan.
Article in English | MEDLINE | ID: mdl-2891854

ABSTRACT

Guanabenz, a centrally acting antihypertensive agent, has been shown to have intestinal antisecretory properties. A series of aromatic aminoguanidine hydrazones was made in an effort to separate the antisecretory and cardiovascular activities. Benzaldehyde, naphthaldehyde, and tetralone derivatives were synthesized. The compounds were evaluated in the cholera toxin treated ligated jejunum of the rat and in the Ussing chamber using a rabbit ileum preparation. A number of compounds, including members of each structural class, were active upon subcutaneous administration in the rat. Active compounds were determined to be alpha 2-adrenergic agonists by yohimbine reversals of their Ussing chamber activities. The compound displaying the best separation of activities was the aminoguanidine hydrazone of 2,6-dimethyl-4-hydroxybenzaldehyde (20).


Subject(s)
Adrenergic alpha-Agonists/chemical synthesis , Antidiarrheals/chemical synthesis , Guanidines/chemical synthesis , Hydrazones/chemical synthesis , Adrenergic alpha-Agonists/pharmacology , Animals , Cholera Toxin/toxicity , Female , Guanidines/pharmacology , Hydrazones/pharmacology , Ileum/drug effects , Ileum/metabolism , In Vitro Techniques , Indicators and Reagents , Jejunum/drug effects , Jejunum/metabolism , Male , Rabbits , Rats , Structure-Activity Relationship
19.
Ann Surg ; 205(3): 322-3, 1987 Mar.
Article in English | MEDLINE | ID: mdl-3827366

ABSTRACT

Recent experience with a twin who had esophageal atresia and tracheoesophageal fistula revealed complex anatomy not suspected before operation. The experience in patients with esophageal atresia and tracheoesophageal fistula who were twins was reviewed at the Children's Hospital of Los Angeles. Of 245 patients seen in the past 23 years, 16 were twins (only two of whom were siblings). Six of the 16 patients (38%) had other than the most frequent anatomy, i.e., proximal atresia of the esophagus and distal fistula. Two of these patients had extremely complex anatomy. Twenty-five per cent of the patients had a right aortic arch compared with 5% of all patients with tracheoesophageal fistula. The surgeon who encounters a twin with esophageal atresia or tracheoesophageal fistula is appropriately cautioned that significant anatomic complexity may be encountered.


Subject(s)
Abnormalities, Multiple/surgery , Diseases in Twins , Esophageal Atresia/surgery , Tracheoesophageal Fistula/surgery , Abnormalities, Multiple/pathology , Esophageal Atresia/pathology , Humans , Infant , Pediatrics/methods , Tracheoesophageal Fistula/pathology
20.
J Trauma ; 25(3): 238-46, 1985 Mar.
Article in English | MEDLINE | ID: mdl-3981677

ABSTRACT

Selective management of 110 patients with bullet wounds to the neck resulted in 31 explored and 79 observed. There was an overall mortality rate of 2.7%, well within that reported in the literature, which ranges from 2 to 6%. At our institution, it is believed that a substantial number of patients can be selectively managed, depending on the signs and symptoms, the site and direction of the trajectory, and whether the interval of time between injury and entrance to the hospital is longer than 6 hours. Patients who are stable and lack physical signs of obvious major neck injury are evaluated by diagnostic radiologic and endoscopic techniques. If no significant injury is found, they are admitted for observation. The efficacy of this mode of management is strengthened by savings in the costs of hospitalization, risks of undergoing an additional operation, overall negative exploration rate in the mandatory exploration studies, and our own results of selective management. We do not recommend this form of management for all institutions. It has been found that in this well-staffed teaching hospital with an extensive trauma service, experienced personnel doing careful and repeated physical examinations, in addition to 24-hour availability of radiologic and endoscopic modalities, the policy of selective management of bullet wounds to the neck can be adhered to. Further studies need to be done into the various mechanisms of penetrating neck trauma, separating each mechanism into morbidity, mortality, and treatment.


Subject(s)
Neck Injuries , Wounds, Gunshot , Adolescent , Adult , Anti-Bacterial Agents/therapeutic use , Critical Care , Esophagoscopy , Female , Hemothorax/etiology , Humans , Laryngoscopy , Male , Neck/diagnostic imaging , Neck/surgery , Pneumothorax/etiology , Premedication , Radiography , Retrospective Studies , Tracheotomy , Wounds, Gunshot/diagnosis , Wounds, Gunshot/mortality , Wounds, Gunshot/surgery , Wounds, Gunshot/therapy
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