Biomedical subjects

R B Lu

Publications and source records attributed to R B Lu.

At least 19 recordsLinked to original sources

PubMed2001

Assaultive behavior by psychiatric in-patients and its related factors.

The purpose of this article is to explore assaultive behavior of psychiatric in-patients in a hospital and to examine the interplay of patient, environmental, and staff factors related to assault. The present study was carried out prospectively using standardized instruments applied in four acute wards in one hospital. A log system was used to record the occurrence of assaults. The results showed 595 episodes of assault from 238 patients in 7 months. Forty one nurses participated in the study. To further examine the differences between assaultive and non-assaultive patients, and assaulted and non-assaulted nurses, a logistic regression analysis was used. The results indicated that patient factors (diagnosis, history of assault, time since admission, and history of smoking), environmental factors (patient/nurse ratio and spatial density), and staff factors (age, length of work experience, training program received in prevention and management of assaults) are contributing variables to assaultive behavior. The present study examined a wider range of variables than have been included in many previous studies. This reinforces the necessary complexity of models likely to prove useful in predicting assaults among psychiatric inpatients.

Adolescent↗

PubMed2001

Dopamine D2 receptor gene (DRD2) is associated with alcoholism with conduct disorder.

This study examined whether there is evidence for an association between alcoholism with conduct disorder and alleles of the TaqI A and TaqI B polymorphisms, both individually and as haplotypes, at the dopamine D2 receptor gene (DRD2). We studied 182 Han Chinese subjects, including 34 alcoholics with conduct disorder, 63 alcoholics without conduct disorder, and 85 nonalcoholics. Alcohol dependence and conduct disorder were defined according to DSM-III-R criteria. Significant associations were observed between TaqI A and TaqI B at the DRD2 locus, tested individually and as haplotypes, and alcoholism with conduct disorder. Our results suggested that DRD2 might be associated with conduct disorder or a predisposition to both conduct disorder and alcoholism. However, this needs to be further investigated by examining the differences among conduct disorder with alcoholism, conduct disorder only, and controls for the TaqI A and B system at DRD2.

Adult↗

PubMed2000

Short tandem-repeat polymorphism/alu haplotype variation at the PLAT locus: implications for modern human origins.

Two dinucleotide short tandem-repeat polymorphisms (STRPs) and a polymorphic Alu element spanning a 22-kb region of the PLAT locus on chromosome 8p12-q11.2 were typed in 1,287-1,420 individuals originating from 30 geographically diverse human populations, as well as in 29 great apes. These data were analyzed as haplotypes consisting of each of the dinucleotide repeats and the flanking Alu insertion/deletion polymorphism. The global pattern of STRP/Alu haplotype variation and linkage disequilibrium (LD) is informative for the reconstruction of human evolutionary history. Sub-Saharan African populations have high levels of haplotype diversity within and between populations, relative to non-Africans, and have highly divergent patterns of LD. Non-African populations have both a subset of the haplotype diversity present in Africa and a distinct pattern of LD. The pattern of haplotype variation and LD observed at the PLAT locus suggests a recent common ancestry of non-African populations, from a small population originating in eastern Africa. These data indicate that, throughout much of modern human history, sub-Saharan Africa has maintained both a large effective population size and a high level of population substructure. Additionally, Papua New Guinean and Micronesian populations have rare haplotypes observed otherwise only in African populations, suggesting ancient gene flow from Africa into Papua New Guinea, as well as gene flow between Melanesian and Micronesian populations.

Africa South of the Sahara↗

PubMed2000

Haplotypes and linkage disequilibrium at the phenylalanine hydroxylase locus, PAH, in a global representation of populations.

Because defects in the phenylalanine hydroxylase gene (PAH) cause phenylketonuria (PKU), PAH was studied for normal polymorphisms and linkage disequilibrium soon after the gene was cloned. Studies in the 1980s concentrated on European populations in which PKU was common and showed that haplotype-frequency variation exists between some regions of the world. In European populations, linkage disequilibrium generally was found not to exist between RFLPs at opposite ends of the gene but was found to exist among the RFLPs clustered at each end. We have now undertaken the first global survey of normal variation and disequilibrium across the PAH gene. Four well-mapped single-nucleotide polymorphisms (SNPs) spanning approximately 75 kb, two near each end of the gene, were selected to allow linkage disequilibrium across most of the gene to be examined. These SNPs were studied as PCR-RFLP markers in samples of, on average, 50 individuals for each of 29 populations, including, for the first time, multiple populations from Africa and from the Americas. All four sites are polymorphic in all 29 populations. Although all but 5 of the 16 possible haplotypes reach frequencies >5% somewhere in the world, no haplotype was seen in all populations. Overall linkage disequilibrium is highly significant in all populations, but disequilibrium between the opposite ends is significant only in Native American populations and in one African population. This study demonstrates that the physical extent of linkage disequilibrium can differ substantially among populations from different regions of the world, because of both ancient genetic drift in the ancestor common to a large regional group of modern populations and recent genetic drift affecting individual populations.

Africa↗

PubMed1999

Linkage disequilibrium at the ADH2 and ADH3 loci and risk of alcoholism.

Two of the three class I alcohol dehydrogenase (ADH) genes (ADH2 and ADH3) encode known functional variants that act on alcohol with different efficiencies. Variants at both these genes have been implicated in alcoholism in some populations because allele frequencies differ between alcoholics and controls. Specifically, controls have higher frequencies of the variants with higher Vmax (ADH2*2 and ADH3*1). In samples both of alcoholics and of controls from three Taiwanese populations (Chinese, Ami, and Atayal) we found significant pairwise disequilibrium for all comparisons of the two functional polymorphisms and a third, presumably neutral, intronic polymorphism in ADH2. The class I ADH genes all lie within 80 kb on chromosome 4; thus, variants are not inherited independently, and haplotypes must be analyzed when evaluating the risk of alcoholism. In the Taiwanese Chinese we found that, only among those chromosomes containing the ADH3*1 variant (high Vmax), the proportions of chromosomes with ADH2*1 (low Vmax) and those with ADH2*2 (high Vmax) are significantly different between alcoholics and controls (P<10-5). The proportions of chromosomes with ADH3*1 and those with ADH3*2 are not significantly different between alcoholics and controls, on a constant ADH2 background (with ADH2*1, P=.83; with ADH2*2, P=.53). Thus, the observed differences in the frequency of the functional polymorphism at ADH3, between alcoholics and controls, can be accounted for by the disequilibrium with ADH2 in this population.

Alcohol Dehydrogenase↗

PubMed1999

Interaction between the functional polymorphisms of the alcohol-metabolism genes in protection against alcoholism.

The genes that encode the major enzymes of alcohol metabolism, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), exhibit functional polymorphism. The variant alleles ADH2*2 and ADH3*1, which encode high-activity ADH isoforms, and the ALDH2*2 allele, which encodes the low-activity form of ALDH2, protect against alcoholism in East Asians. To investigate possible interactions among these protective genes, we genotyped 340 alcoholic and 545 control Han Chinese living in Taiwan at the ADH2, ADH3, and ALDH2 loci. After the influence of ALDH2*2 was controlled for, multiple logistic regression analysis indicated that allelic variation at ADH3 exerts no significant effect on the risk of alcoholism. This can be accounted for by linkage disequlibrium between ADH3*1 and ADH2*2 ALDH2*2 homozygosity, regardless of the ADH2 genotypes, was fully protective against alcoholism; no individual showing such homozygosity was found among the alcoholics. Logistic regression analyses of the remaining six combinatorial genotypes of the polymorphic ADH2 and ALDH2 loci indicated that individuals carrying one or two copies of ADH2*2 and a single copy of ALDH2*2 had the lowest risk (ORs 0.04-0.05) for alcoholism, as compared with the ADH2*1/*1 and ALDH2*1/*1 genotype. The disease risk associated with the ADH2*2/*2-ALDH2*1/*1 genotype appeared to be about half of that associated with the ADH2*1/*2-ALDH2*1/*1 genotype. The results suggest that protection afforded by the ADH2*2 allele may be independent of that afforded by ALDH2*2.

Adult↗

PubMed1999

No association between DRD2 locus and alcoholism after controlling the ADH and ALDH genotypes in Chinese Han population.

BACKGROUND: Recent studies on the genetics of alcoholism have examined the association between alcoholism and the dopamine D2 receptor locus (DRD2); our study of Chinese Han gave negative results (Lu et al., 1996). The different genotypes at the genes encoding the enzymes involved in alcohol metabolism, class one alcohol dehydrogenase (ADH2 and ADH3) and mitochondrial aldehyde dehydrogenase (ALDH2), have previously been shown to confer different predispositions to the development of alcoholism in Chinese Han males (Thomasson et al., 1991; Chen WJ et al., 1996; Chen CC et al., unpublished data). Therefore, association studies of alcoholism in Chinese Han might be more sensitive if controlled for the genotypes of ADH2,ADH3, and ALDH2, when other loci, such as DRD2, are examined. This study employs such controls to evaluate the evidence for an association between alcoholism and TaqI-A and TaqI-B genotypes and haplotypes at DRD2 in the Chinese Han population. METHODS: We studied 213 Chinese Han subjects (128 alcoholics and 85 nonalcoholics) with alcohol dependence defined according to DSM-III-R criteria. RESULTS: Significant linkage disequilibrium was observed between the TaqI-A and TaqI-B sites at the DRD2 locus, as previously seen in smaller samples, but no significant association was observed between these genetic variants at the DRD2 locus and alcoholism in Chinese Han. Several different stratifications by ADH and ALDH2 genotypes were examined; no genotypes or haplotypes at DRD2 differ between alcoholics and nonalcoholics except for a small number of nominally significant p-values which do not constitute significant results given the many tests done, some of which are not independent of one another due to linkage disequilibrium. These tests included considering the high risk (ADH2*1/*1; *1/*2; ADH3*1/*2; *2/*2; and ALDH2*1/*1) and the low risk (ADH2*2/*2; ADH3*1/*1; and ALDH2*1/*2; *2/*2) groups of alcoholics, as well as nonalcoholic controls. CONCLUSIONS: After stratification by the relevant genotypes of ADH2, ADH3, and ALDH2 no significant association exists between the genetic variants at the DRD2 locus and alcoholism in the Chinese Han population.

Alcohol Dehydrogenase↗

PubMed1999

Alcohol metabolism and cardiovascular response in an alcoholic patient homozygous for the ALDH2*2 variant gene allele.

BACKGROUND: Alcohol metabolism is one of the biological determinants that can influence drinking behavior. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the principal enzymes involved in ethanol metabolism. Allelic variation of the ADH and ALDH genes can significantly affect vulnerability for the development of alcoholism. Homozygosity of the variant ALDH2*2 allele previously was believed to fully protect East Asian populations against the development of alcoholism. METHODS: Eighty Han Chinese alcoholics who met DSM-III-R criteria for alcohol dependence and 144 nonalcohol-dependent subjects were recruited and their data combined with data from 340 alcohol-dependent and 545 nonalcohol-dependent subjects described in an earlier report (Chen et al., 1999) to assess risk for alcoholism by logistic regression analysis. Genotypes of ADH2, ADH3, and ALDH2 were determined by polymerase chain reaction and restriction fragment length polymorphism. The ALDH2 genotype was confirmed by direct nucleotide sequencing. Blood ethanol concentration was determined by headspace gas chromatography and acetaldehyde concentration by high-performance liquid chromatography with fluorescence detection of the derivatized product. Cardiovascular hemodynamic parameters were measured by two-dimensional Doppler echocardiography and sphygmomanometry. Extracranial arterial blood flow was measured by Doppler ultrasonography. RESULTS: An alcohol-dependent patient was identified to be ALDH2*2/*2, ADH2*2/*2, and ADH3*1/*2. Following challenge with a moderate oral dose of ethanol (0.5 g/kg of body weight), the patient exhibited peak concentrations for ethanol (55.7 mg/dl) and acetaldehyde (125 microM). During 130 min postingestion, the patient generally displayed similar or even less intense cardiovascular hemodynamic alterations when compared to a previously published study of nonalcoholic individuals with ALDH2*2/*2 who had received a lower dose of ethanol (0.2 g/kg). Logistic regression analysis of the combinatorial genotypes of ADH2 and ALDH2 in 420 alcohol-dependent and 689 nonalcohol-dependent subjects indicated that risk for alcoholism was 100-fold lower for the ADH2*2/*2-ALDH2*2/*2 individuals than the ADH2*1/*1-ALDH2*1/*1 individuals. CONCLUSIONS: The gene status of ALDH2*2/*2 alone can tremendously but not completely (as thought previously) protect against development of alcohol dependence. Individuals carrying the combinatorial genotype of ADH2*2/*2-ALDH2*2/*2 are at the least risk for the disease in East Asians. Physiological tolerance or innate insensitivity to the accumulation of blood acetaldehyde following alcohol ingestion may be crucial for the development of alcoholism in individuals homozygous for ALDH2*2.

Adolescent↗

PubMed1998

The lower limits of dexamethasone window in Chinese depressives.

BACKGROUND: Previous studies have shown wide variation in plasma dexamethasone (DEX) concentrations following a standard 1-mg dexamethasone suppression test (DST), and significantly lower DEX concentrations in DST nonsuppressors compared with suppressors, suggesting that DEX pharmacokinetics/bioavailability is an important variable associated with DST nonsuppression. METHODS: To determine the effect of plasma DEX levels on the DST in Chinese depressives, we measured plasma DEX and post-DEX cortisol levels at 4:00 PM in a group of 50 depressed outpatients, 28 anxiety outpatients, and 33 normal subjects during the course of 1-mg oral overnight DST. RESULTS: We found a significant difference in the plasma DEX levels between DST nonsuppressors and suppressors in the depression group and overall subject population, and a significant negative correlation between the plasma DEX and cortisol levels in the depression, anxiety, and total groups. Within a DEX "window", the DST performance was enhanced, whereas the relationships between plasma DEX and post-DEX cortisol levels remained equally strong. CONCLUSIONS: Our findings support a relationship between plasma DEX and post-DEX cortisol levels, a relationship that might be superimposed on the hypothalamic-pituitary-adrenal axis. Comparing our "window" range with those of previous studies, we suggest that Chinese depressives may have lower limits of plasma DEX window, and that ethnicity may be an intervening variable in both DST response and pharmacokinetics of DEX.

Adult↗

PubMed1998

A global survey of haplotype frequencies and linkage disequilibrium at the DRD2 locus.

A four-site haplotype system at the dopamine D2 receptor locus (DRD2) has been studied in a global sample of 28 distinct populations. The haplotype system spans about 25 kb, encompassing the coding region of the gene. The four individual markers include three TaqI restriction site polymorphisms (RSPs) -- TaqI "A", "B", and "D" sites -- and one dinucleotide short tandem repeat polymorphism (STRP). All four of the marker systems are polymorphic in all regions of the world and in most individual populations. The haplotype system shows the highest average heterozygosity in Africa, a slightly lower average heterozygosity in Europe, and the lowest average heterozygosities in East Asia and the Americas. Across all populations, 20 of the 48 possible haplotypes reached a frequency of at least 5% in at least one population sample. However, no single population had more than six haplotypes reaching that frequency. In general, African populations had more haplotypes present in each population and more haplotypes occurring at a frequency of at least 5% in that population. Permutation tests for significance of overall disequilibrium (all sites considered simultaneously) were highly significant (P<0.001) in all 28 populations. Except for three African samples, the pairwise disequilibrium between the outermost RSP markers, TaqI "B" and "A", was highly significant with D' values greater than 0.8; in two of those exceptions the RSP marker was not polymorphic. Except for those same two African populations, the 16-repeat allele at the STRP also showed highly significant disequilibrium with the TaqI "B" site in all populations, with D' values usually greater than 0.7. Only four haplotypes account for more than 70% of all chromosomes in virtually all non-African populations, and two of those haplotypes account for more than 70% of all chromosomes in most East Asian and Amerindian populations. A new measure of the amount of overall disequilibrium shows least disequilibrium in African populations, somewhat more in European populations, and the greatest amount in East Asian and Amerindian populations. This pattern seems best explained by random genetic drift with low levels of recombination, a low mutation rate at the STRP, and essentially no recurrent mutation at the RSP sites, all in conjunction with an "Out of Africa" model for recent human evolution.

Alleles↗

PubMed1997

Plasma free 3-methoxy-4-hydroxyphenylglycol predicts response to fluoxetine.

This study was designed to investigate the relationship between platelet serotonin (5-HT) and plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG) measures in depressed outpatients obtained from the same patient with unipolar depression during the pretreatment period and subsequent response to 6 weeks of treatment with either fluoxetine or maprotiline. Compared to the nonresponder group, the fluoxetine responders showed significantly higher pretreatment levels of MHPG, but no difference in pretreatment 5-HT levels. There were no significant differences in either 5-HT or MHPG levels between maprotiline responders and nonresponders. As to posttreatment levels, there were no between-group differences in 5-HT or MHPG between responders and nonresponders to either fluoxetine or maprotiline. When the relationships between changes in 5-HT or MHPG levels and treatment response were examined, 5-HT values showed a marked decrease in both fluoxetine responders and nonresponders, but no significant changes were found in the maprotiline treatment groups. On the other hand, MHPG levels in the fluoxetine nonresponders tended to increase (borderline significance), whereas the MHPG levels for fluoxetine responders and maprotiline responders and nonresponders were unaffected from pre- to posttreatment. Pretreatment levels of plasma free MHPG appear to predict response to fluoxetine.

Adult↗

PubMed1997

The dopamine D4 receptor gene (DRD4) is not associated with alcoholism in three Taiwanese populations: six polymorphisms tested separately and as haplotypes.

The dopaminergic system has been implicated in alcoholism but studies at the dopamine D2 receptor gene (DRD2), one of the five dopamine receptors, have not given a consistent picture of an association with alcoholism. We have now studied the dopamine D4 receptor gene (DRD4) using six polymorphisms, both separately and as haplotypes. Three groups of alcoholics from Taiwan (Atayal, Ami, and Han) diagnosed as having severe alcohol dependence using DSM-III-R criteria, together with nonalcoholics matched for gender, ethnic group, and geographic origin, were typed by polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymorphism (RFLP) for all six polymorphisms. Three out of six markers are polymorphic in all three Taiwanese populations. Although the prevalence rates of alcoholism are remarkably different, no highly significant association of this locus with alcoholism was observed in any of the three groups whether the analysis considered genotype distributions or allele frequencies at the three polymorphic markers considered individually and as haplotypes. Neither is there any obvious pattern in the data that covaries with or hints at a relationship with the very different prevalences of alcoholism in the groups studied. Especially because the powerful, multi-site haplotype analysis was not statistically significant in any of the population samples, we conclude that there is no association of the DRD4 locus with alcoholism in Taiwanese populations.

Alcoholism↗

PubMed1997

Construction of a screening inventory for major mental disorder in the Army.

The development of a 29-item self-report inventory to screen for non-adaptiveness with an episode or a history of major mental disorder in the army is described. Initially, a 58-item inventory was constructed. However, through a pilot study 46 items remained. The reliability and validity test of the 46-item inventory was then carried out on 357 patients and 126 controls. Firstly, item analyses were performed which showed 12 items that distinguished between schizophrenic patients and controls, 9 items that distinguished between depressive patients and controls and 8 items that distinguished between manic patients and controls. A final 29-item inventory was found to have satisfactory reliability, sensitivity and specificity. The analyses of the best cut-off scores using the receiver-operating-characteristic curve suggested a score of 3 for the Schizophrenia Scale, 2 for the Depression Scale, and 3 for the Mania Scale. The inventory can be completed in about 5 to 10 minutes and has a simple method of scoring. The use of this screening inventory in the army is discussed.

Adult↗

PubMed1996

No association between alcoholism and multiple polymorphisms at the dopamine D2 receptor gene (DRD2) in three distinct Taiwanese populations.

This study examined whether there is evidence for an association between alcoholism and the alleles of the TaqI A, TaqI B, and short tandem repeat polymorphisms (STRP), both individually and as haplotypes, at the dopamine D2 receptor gene (DRD2) in males of three populations from Taiwan. We studied 46 Chinese Han (21 alcoholics and 25 nonalcoholics), 42 Atayal (21 alcoholics and 21 nonalcoholics), and 40 Ami (20 alcoholics and 20 nonalcoholics). Alcoholism was diagnosed according to DSM-III-R criteria and all individuals in the alcoholic groups were severely affected. Significant linkage disequilibrium occurs for the three polymorphic sites in all three populations. No significant association was observed between any of the three polymorphisms at the DRD2 locus, tested individually and as haplotypes, and alcoholism in the three subject groups. We conclude that no association exists between genetic variation at the DRD2 locus and alcoholism in Chinese Han, Atayal, and Ami males.

Adult↗

PubMed1996

DRD2 haplotypes containing the TaqI A1 allele: implications for alcoholism research.

In recent years, a possible role of the dopamine D2 receptor (DRD2) locus in the etiology of alcoholism has been the focus of considerable attention. The literature now contains a mix of association studies with positive and negative conclusions. Various methodological flaws undermine the claims in many of the studies that conclude a positive association exists between alcoholism and the DRD2*A1 allele at the Taql "A" site. Although the studies with negative findings have more often come from studies using better analytic methodology, satisfactory resolution of whether or not genetic variation at the DRD2 locus plays some role in the etiology of alcoholism is unlikely to come from additional studies of the kind conducted thus far; an approach enlightened by a more thorough understanding of the population genetics of DRD2 and the phylogenetic origins of the DRD2 alleles is one alternative. If genetic variation at the DRD2 locus affects susceptibility to alcoholism, then such variation has a mutational and evolutionary history that can be traced with the aid of the various genetic polymorphisms that have been identified at the DRD2 locus. In this study, a third Taql restriction fragment-length polymorphism at DRD2, the Taql "D" site, has been converted to polymerase chain reaction-based typing and its frequencies determined in 22 populations from around the world. Haplotypes defined by the polymorphisms at the Taql "B" and "A" sites, and the short tandem repeat polymorphism in intron 2 have been constructed and the diversity of haplotypes containing the DRD2*A1 allele examined for all 22 populations. The ancestral origins of the three Taql polymorphisms have also been determined by sequencing the homologous regions in other higher primates. Because A1-containing haplotypes in populations of European, Middle Eastern, and African origin show considerable diversity within and among populations, properly designed association studies in populations descended from those areas of the world need to use haplotypes, not a single allelic system, and need to use appropriate methods to compensate for the near impossibility of genetically matching unrelated control samples.

Alcoholism↗

PubMed1996

[Preparation of diclofenac sodium controlled release pellets and multiple-dose evaluation in healthy volunteers].

The yield of pellets obtained in preparing diclofenac sodium (DC-Na) controlled release pellets was affected by the lactose/starch ratio of the feed granules, viscosity of the binding solution and residence time in the rolling pot. The pellet shape was found to be correlated with surface tension of the binding solution. The concentration and composition of the coating solution and pellet size distribution were responsible for the agglutination in coating. The controlled release pellets (CRP) and commercial tablets (CT) of DC-Na were administrated orally to healthy volunteers by multiple-dose. The steady-state condition, based on trough plasma concentration on day 3-5, was achieved on day 3. A great difference in plasma drug concentration fluctuation index (FI) between CRP (0.476 +/- 0.0484) and CT (0.935 +/- 0.092) was observed (P < 0.05) during steady-state. The area under the plasma drug concentration-time curve for a 0-12 h interval (AUC) on day 5 of CRP (6.493 +/- 0.4169 micrograms.h.ml-1) and CT (7.551 +/- 0.4745 micrograms.h.ml-1) was shown to be not significantly different (P > 0.05). The relative bioavailability in the human was about 86%.

Adult↗

PubMed1994

Short-term effect of epidermal growth factor (EGF) on sodium and glucose cotransport of isolated jejunal epithelial cells.

This study was undertaken to assess the short-term effects of EGF on sodium and glucose uptake, glucose metabolism and Na+/K(+)-ATPase activity in isolated enterocytes of rats. Jejunal cells exposed to EGF had a significantly greater total uptake of sodium compared to controls after 6 min. Kinetic analysis of glucose transport across BBMV's demonstrated similar Km values but a significant increase of the Vmax in vesicles prepared from cells first exposed to EGF as compared to controls. EGF was also associated with a significant increase in glucose metabolism of jejunal enterocytes after 15 min. The activity of Na+/K(+)-ATPase increased in jejunal enterocytes exposed to EGF. The increase in Na+/K(+)-ATPase activity of the cells following EGF exposure was not accompanied by an increase in immunodetectable total or assembled Na+/K(+)-ATPase protein. EGF's effect on enzyme activity was abolished by removing NaCl from the incubation solution, and by preincubating the enterocytes with phlorizin prior to addition of EGF. Preincubation with amiloride did not inhibit the effect of EGF on Na+/K(+)-ATPase. The results confirm that EGF promotes uptake of both sodium and glucose by the jejunal mucosal cells, and suggest the effect of EGF on glucose and sodium is mediated through the brush-border membrane glucose-sodium transporter. The increase in Na+/K(+)-ATPase activity that occurs with EGF appears to be secondary to a rise in intracellular Na+ concentration. The short-term effects of EGF on glucose and sodium transport by the small intestine may have potential therapeutic implications.

Amiloride↗

PubMed1994

Small intestinal glucoamylase deficiency and starch malabsorption: a newly recognized alpha-glucosidase deficiency in children.

To determine the prevalence of short polymers of glucose and starch malabsorption caused by small intestinal glucoamylase deficiency in children with chronic diarrhea, we studied small bowel biopsy specimens from 511 children (aged 1 month to 9 years) with chronic diarrhea evaluated at 54 medical centers. Glucoamylase and disaccharidase (lactase, sucrase, maltase, and palatinase) enzyme assays were performed. Of the 511 children, 15 had glucoamylase deficiency. Six who had significant small intestinal mucosal injury and disaccharidase deficiencies were defined as having secondary glucoamylase deficiency; the other nine patients with normal mucosal morphologic features were defined as having primary glucoamylase deficiency. Secretin tests showed normal pancreatic amylase values for age in all seven children tested. Four of them had abnormal findings on tolerance tests for starch and short polymers of glucose (rise in blood glucose concentration: < 20 mg/dl) and reducing substances in stools, and three of these four had symptoms of intolerance (abdominal distention, flatulence, and diarrhea). All seven patients responded to a starch elimination diet. After reintroduction of a starch diet, diarrhea recurred in four patients; this was alleviated 48 hours after reelimination of starch. We conclude that intestinal glucoamylase deficiency is present in some patients with chronic diarrhea.

Carbohydrate Metabolism, Inborn Errors↗