Diving deeper into individual foraging specializations of a large marine predator, the southern sea lion.

Despite global declines in the abundance of marine predators, knowledge of foraging ecology, necessary to predict the ecological consequences of large changes in marine predator abundance, remains enigmatic for many species. Given that populations suffering severe declines are of conservation concern, we examined the foraging ecology of southern sea lions (SSL) (Otaria flavescens)-one of the least studied otariids (fur seal and sea lions)-which have declined by over 90% at the Falkland Islands since the 1930s. Using a combination of biologging devices and stable isotope analysis of vibrissae, we redress major gaps in the knowledge of SSL ecology and quantify patterns of individual specialization. Specifically, we revealed two discrete foraging strategies, these being inshore (coastal) and offshore (outer Patagonian Shelf). The majority of adult female SSL (72% or n = 21 of 29 SSL) foraged offshore. Adult female SSL that foraged offshore travelled further (92 ± 20 vs. 10 ± 4 km) and dived deeper (75 ± 23 vs. 21 ± 8 m) when compared to those that foraged inshore. Stable isotope analysis revealed long-term fidelity (years) to these discrete foraging habitats. In addition, we found further specialization within the offshore group, with adult female SSL separated into two clusters on the basis of benthic or mixed (benthic and pelagic) dive behavior (benthic dive proportion was 76 ± 9 vs. 51 ± 8%, respectively). We suggest that foraging specialization in depleted populations such as SSL breeding at the Falkland Islands, are influenced by foraging site fidelity, and could be independent of intraspecific competition. Finally, the behavioral differences we describe are crucial to understanding population-level dynamics, impediments to population recovery, and threats to population persistence.

Targeting histone deacetylase 6 mediates a dual anti-melanoma effect: Enhanced antitumor immunity and impaired cell proliferation.

The median survival for metastatic melanoma is in the realm of 8-16 months and there are few therapies that offer significant improvement in overall survival. One of the recent advances in cancer treatment focuses on epigenetic modifiers to alter the survivability and immunogenicity of cancer cells. Our group and others have previously demonstrated that pan-HDAC inhibitors induce apoptosis, cell cycle arrest and changes in the immunogenicity of melanoma cells. Here we interrogated specific HDACs which may be responsible for this effect. We found that both genetic abrogation and pharmacologic inhibition of HDAC6 decreases in vitro proliferation and induces G1 arrest of melanoma cell lines without inducing apoptosis. Moreover, targeting this molecule led to an important upregulation in the expression of tumor associated antigens and MHC class I, suggesting a potential improvement in the immunogenicity of these cells. Of note, this anti-melanoma activity was operative regardless of mutational status of the cells. These effects translated into a pronounced delay of in vivo melanoma tumor growth which was, at least in part, dependent on intact immunity as evidenced by the restoration of tumor growth after CD4+ and CD8+ depletion. Given our findings, we provide the initial rationale for the further development of selective HDAC6 inhibitors as potential therapeutic anti-melanoma agents.

The association of HIV viral load with indirect markers of liver injury.

This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV)-coinfected and 68 HIV-infected participants without hepatitis C or B co-infection (mono-infected). In unadjusted analyses, detectable HIV viral load (vs undetectable, <400 copies/mL) was associated with a 40% greater odds (OR 1.4, 95% CI: 1.1-1.9, P = 0.016) of FIB-4 > 1.45 in the HIV/HCV-coinfected group and 70% greater odds of FIB-4 > 1.45 (OR 1.7, 95% CI: 1.0-2.8; P = 0.046) in the HIV-mono-infected group. In multivariable analyses, a 1 log(10) increase in HIV RNA was associated with a median increase in FIB-4 of 12% in the HIV/HCV-coinfected group and 11% in the HIV-mono-infected group (P < 0.0001). Among the HIV/HCV-coinfected group, the elevating effect of HIV RNA on FIB-4 was strongest at low CD4 counts (P = 0.0037). Among the HIV-mono-infected group, the association between HIV RNA and FIB-4 was independent of CD4 cell counts. HIV RNA was associated with alterations in both liver enzymes and platelet counts. HIV antiretroviral therapy was not associated with any measure of liver injury examined. This study suggests that HIV may have direct, injurious effects on the liver and that HIV viral load should be considered when these indirect markers are used to assess liver function.

Role of acquired immune deficiency syndrome-defining conditions in human immunodeficiency virus-associated wasting.

To evaluate the contribution of acquired immune deficiency syndrome-defining conditions (ADCs) in human immunodeficiency virus (HIV)-associated wasting, we analyzed longitudinal data from 671 participants in a nutrition and HIV cohort study. Data on ADCs, height, and weight were collected at baseline and during 6 monthly study visits. The frequency of ADCs decreased over time, but the relative risk (RR) of wasting (decrease in body mass index [BMI] to <20 kg/m(2)) increased with a history of >1 ADC; the RR of wasting increased 1.3-fold with each additional historical ADC. Any ADC during the 6 months prior to a study visit was associated with a decrease in BMI to <20 kg/m(2). The risk of wasting increased 2.7-fold with each additional recent ADC. These risks were not altered when adjusted for socioeconomic status, CD4 cell count, energy intake, or baseline BMI. Although ADCs contribute to the development of wasting, their contribution is relatively small.

Enhanced vector competence of Aedes aegypti (Diptera: Culicidae) from the Torres Strait compared with mainland Australia for dengue 2 and 4 viruses.

Australian Aedes aegypti (L.) mosquitoes colonized from the Torres Strait and three mainland localities (Charters Towers, Townsville, and Cairns) were fed on blood suspensions containing dengue virus type 2 (DEN-2) or dengue virus type 4 (DEN-4). Variation was found in oral susceptibility to DEN-2 (59 -99% infection) and DEN-4 (28-79% infection) among Ae. aegypti assayed for virus at 8, 12, 16, or 20 d after ingestion of infected blood. Torres Strait Ae. aegypti were the most susceptible to DEN-2 and were significantly more efficient in transmission to capillary tube at 16 d (76% transmission) than mainland Ae. aegypti populations (20-28% transmission). Torres Strait Ae. aegypti were also the most susceptible to DEN-4, although transmission did not vary significantly from mainland populations at 16 d (12% compared with 0-4%) or 20 d (16% compared with 4-16%). Disseminated infection (i.e., leg infection) with either DEN-2 or DEN-4 was not an accurate predictor of transmission potential. This study demonstrates differences among Australian Ae. aegypti populations in vector competence for DEN-2 and DEN-4. Torres Strait Ae. aegypti were more frequently infected and able to transmit DEN-2 at higher rates than mainland populations. These data indicate that the Torres Strait region is potentially more receptive to dengue transmission than mainland localities, a finding discussed with respect to past outbreaks.

Changes in lean body mass and total body weight are weakly associated with physical functioning in patients with HIV infection.

CONTEXT: For clinicians managing weight loss in patients with HIV, it would be useful to understand how changes in lean body mass (LBM) effect physical functioning, and whether LBM is more strongly related to physical functioning than total body weight (TBW). OBJECTIVE: To determine the relationship of changes in LBM and changes in total body weight (TBW) to changes in self-reported physical functioning in men and women with HIV infection. METHODS: Study design was longitudinal analysis of 1474 patient-intervals (each interval was approximately 6 months long) in 486 persons. Patients were participants in Nutrition for Healthy Living, a cohort study of HIV positive persons in Massachusetts and Rhode Island. The main outcome measure was change in self-reported physical functioning. RESULTS: Of the 1,474 intervals, 1,165 were contributed by men and 309 by women. The mean CD4 count for the 1,474 intervals was 383 cells/ micro L. In men, 5 kg changes in LBM and TBW were associated with 2.2 (95% confidence interval, 0.9, 3.4, P= 0.001) and 2.6 (95% confidence interval, 1.3, 3.9, P= 0.0002) point changes in physical functioning (on a 100-point scale), respectively, after adjusting for covariates. The relationships of changes in LBM and TBW to changes in physical functioning were linear. In women, there were no significant relationships between changes in LBM or TBW to changes in physical functioning. CONCLUSIONS: In this longitudinal analysis of relatively healthy persons with HIV infection, changes in LBM and TBW were significantly related to changes in physical functioning in men, but the magnitude of the relationship was small. In women, changes in LBM and TBW were not related to changes in physical functioning. Our data suggest that it is not necessary to measure body composition (lean and fat compartments) to understand the impact of changes in weight on physical functioning - it is sufficient to follow total body weight.

Effect of highly active antiretroviral therapy on fat, lean, and bone mass in HIV-seropositive men and women.

BACKGROUND: Alterations in body composition have been reported in HIV-positive adults receiving highly active antiretroviral therapy (HAART), but the magnitude and potential determinants of these changes are unclear. OBJECTIVE: We compared total and regional body composition, as measured by dual-energy X-ray absorptiometry, in 203 HIV-positive men and 62 HIV-positive women according to HAART. DESIGN: This was a cross-sectional analysis of a cohort study of nutrition and HIV infection. RESULTS: After adjustment for age, weight, race, and exercise habits, total weight and fat mass did not differ significantly in men or women by HAART. Trunk fat was greater in men (1.0 kg; P < 0.001) and women (1.4 kg; P = 0.005) and leg fat was lower in men (-1.0 kg; P < 0.001) and women (-1.5 kg, P = 0.005) receiving HAART than in those not. This corresponded to a greater percentage of total fat mass located in the trunk (men: 7.5%, P < 0.001; women: 5.1%, P = 0.02). Lean mass was also greater with longer duration of HAART in men (P < 0.002). In men receiving HAART, total and regional bone mineral content were less than in the men not receiving HAART (P < 0.001). These effects increased with longer duration of HAART. Protease inhibitors were associated with the largest differences in regional fat. CONCLUSIONS: HAART is associated with redistribution of fat mass from the legs to the trunk, despite no significant differences in total fat mass or weight. In men, HAART is also associated with a reduction in bone mineral content, suggesting that HAART increases the risk of central obesity and osteoporosis.

Colonic mucosal concentrations of folate are accurately predicted by blood measurements of folate status among individuals ingesting physiologic quantities of folate.

Folate status is inversely related to the risk of colorectal cancer. Whether conventional blood measurements of folate status accurately reflect folate concentrations in the colorectal mucosa has been a controversial topic. This is an important issue because accurate measures of folate status in the colorectal mucosa are important for ascertaining the risk of colorectal cancer in epidemiological studies and for determining the effects of folate supplementation in clinical trials. We examined whether conventional blood measurements of folate and a more sensitive, inverse indicator of systemic folate status, serum homocysteine, accurately reflect folate concentrations in human colonic mucosa obtained by endoscopic biopsy. Study subjects (n = 20) were participants in a randomized trial that investigated the effect of folate supplementation (5 mg daily for 1 year) on provisional molecular markers of colon cancer. Blood samples and biopsies of normal rectosigmoid mucosa were obtained at baseline, at 6 months, and at 1 year. Serum, RBC, and colonic mucosal folate and serum homocysteine concentrations were determined. Colonic mucosal folate concentrations correlated directly with serum folate concentrators at each time point (r = 0.572-0.845; P < 0.015) and with RBC folate concentrations at 6 months and 1 year (r = 0.747-0.771; P < 0.001). Colonic mucosal folate concentrations correlated inversely with serum homocysteine concentrations at each time point (r = -0.622-0.666; P < 0.008). Systemic measures of folate status did not correlate with colonic mucosal folate concentrations among individuals receiving supplemental folate. Our observations indicate that colonic mucosal concentrations of folate may be predicted accurately by blood measurements of folate status only among individuals not ingesting supraphysiological quantities of folate.

Weight and body composition in a cohort of HIV-positive men and women.

OBJECTIVE: At issue is whether weight loss in HIV infection is a cachectic process, characterised by loss of lean body mass with conservation of fat, or a process of starvation. We present data on body composition from 516 persons at different stages of HIV infection as determined by CD4 counts. DESIGN: Cross-sectional analyses of body composition in relation to CD4 count. SETTING: The baseline data from a prospective cohort study of outcomes in HIV/AIDS in relation to nutritional status in Boston, Massachusetts, USA. SUBJECTS: : The first 516 subjects with HIV/AIDS to enroll in the study. RESULTS: Differences in weight in relation to CD4 counts were present only at CD4 counts of 600 or less (slope below : 1.9 kg per 100 CD4 cells, On average, 68% of the difference in weight over CD4 counts was fat (slope: 1.3 kg fat per 100 CD4 cells, CONCLUSIONS: This cross-sectional analysis suggests that weight loss consists principally of fat loss in those persons with adequate fat stores. This observation will need to be confirmed in longitudinal analyses.

Nutrition in the era of highly active antiretroviral therapy.

Despite tremendous advances in treatment, persons with human immunodeficiency virus (HIV) infection commonly experience a variety of nutritional problems, such as weight loss, fat redistribution, and obesity. We discuss basic dietary and metabolic problems as they pertain to persons with HIV infection and provide practical suggestions for their management. In all persons, changes in weight are caused by disruptions of energy balance, which can be disturbed by alterations in energy intake (effective ingestion of calories), energy expenditure (use of calories), or both. Factors that contribute to the disturbance of energy balance are discussed in the context of HIV infection. Management of weight loss and weight gain may then be directed at the affected components of energy balance. This information is intended to raise health care providers' attention to nutrition in their patients, including monitoring of weight, dietary issues, and relevant symptoms, and to encourage liaisons with experienced dietitians and exercise trainers.

Aspartic peptide hydrolases in Salmonella enterica serovar typhimurium.

Two well-characterized enzymes in Salmonella enterica serovar Typhimurium and Escherichia coli are able to hydrolyze N-terminal aspartyl (Asp) dipeptides: peptidase B, a broad-specificity aminopeptidase, and peptidase E, an Asp-specific dipeptidase. A serovar Typhimurium strain lacking both of these enzymes, however, can still utilize most N-terminal Asp dipeptides as sources of amino acids, and extracts of such a strain contain additional enzymatic activities able to hydrolyze Asp dipeptides. Here we report two such activities from extracts of pepB pepE mutant strains of serovar Typhimurium identified by their ability to hydrolyze Asp-Leu. Although each of these activities hydrolyzes Asp-Leu at a measurable rate, the preferred substrates for both are N-terminal isoAsp peptides. One of the activities is a previously characterized isoAsp dipeptidase from E. coli, the product of the iadA gene. The other is the product of the serovar Typhimurium homolog of E. coli ybiK, a gene of previously unknown function. This gene product is a member of the N-terminal nucleophile structural family of amidohydrolases. Like most other members of this family, the mature enzyme is generated from a precursor protein by proteolytic cleavage and the active enzyme is a heterotetramer. Based on its ability to hydrolyze an N-terminal isoAsp tripeptide as well as isoAsp dipeptides, the enzyme appears to be an isoAsp aminopeptidase, and we propose that the gene encoding it be designated iaaA (isoAsp aminopeptidase). A strain lacking both IadA and IaaA in addition to peptidase B and peptidase E has been constructed. This strain utilizes Asp-Leu as a leucine source, and extracts of this strain contain at least one additional, as-yet-uncharacterized, peptidase able to cleave Asp dipeptides.

Effects of folate supplementation on two provisional molecular markers of colon cancer: a prospective, randomized trial.

OBJECTIVES: Dietary folate intake is inversely associated with the risk of colorectal cancer. This study investigated the effect of folate supplementation on genomic DNA methylation and DNA strand breaks in exons 5-8 of the p53 gene of the colonic mucosa, two provisional biomarkers of colon cancer. METHODS: Twenty subjects with adenomas were randomized to receive either folate (5 mg/day) or placebo for 1 yr after polypectomy. At baseline, 6 months and 1 yr, systemic and colonic measures of folate status were determined, as were the biomarkers mentioned earlier. RESULTS: Folate supplementation increased serum, red blood cell and colonic mucosal folate concentrations (p < 0.02). Folate supplementation also increased the extent of genomic DNA methylation at 6 months and 1 yr (p = 0.001), whereas placebo administration was associated with an increase in the extent of genomic DNA methylation only at 1 yr. Similarly, folate supplementation decreased the extent of p53 strand breaks in exons 5-8 at 6 months and 1 yr (p < 0.02), whereas placebo administration was associated with a decrease in the extent of p53 strand breaks only at 1 yr. CONCLUSIONS: Both of these provisional biomarkers of colon cancer underwent accelerated improvement at 6 months with folate supplementation. However, these markers also improved with placebo at 1 yr. Therefore, potential confounding factors that seem to modulate these biomarkers need to be identified and corrected in order for these markers to serve as suitable surrogate endpoints in folate chemoprevention trials.

Endoscopic ultrasound of the upper gastrointestinal tract.

Endoscopic ultrasound (EUS) is an evolving technique used by gastroenterologists to examine lesions that are located either within or adjacent to the walls of the upper gastrointestinal (GI) tract; this topic is relatively unknown to most radiologists. Proper use of this modality is benefited by a cooperative effort between gastroenterologists and radiologists specializing in ultrasound and cross-sectional imaging. This article informs radiologists of the applications of this procedure. Most patients are examined with EUS after a biopsy of a mucosal tumor has been performed. A smaller number are performed to evaluate submucosal masses or when pancreatic disease is suspected but not diagnosed. The examinations can be performed either with dedicated flexible echoendoscopes or with catheter-based probes passed through a conventional endoscope. The exact location of abnormalities associated with the upper GI tract can be observed. Known anatomic landmarks are sought. Abnormalities of structures outside the upper GI tract will occasionally be found during these examinations. The specific layers of the walls of the gut are examined, and the T and N-classification of upper GI tumors can be determined accurately. The performance of an EUS examination requires advanced skills, and in many medical centers, it is the imaging modality of choice to stage cancers, to evaluate submucosal masses, and to investigate both malignant and benign pancreaticobiliary disease. Endoscopic ultrasound is sensitive but not specific, and biopsy is necessary to establish a diagnosis. Therapeutic applications of EUS are evolving. Specialized applications with catheter-based probes are also being developed.

Body composition and dietary intake in relation to drug abuse in a cohort of HIV-positive persons.

We examined the relationships between drug abuse, weight, body composition, and dietary intake in persons infected with HIV in a cross-sectional analysis of baseline data from a longitudinal study of nutritional status and HIV. Body composition was measured by bioelectrical impedance analysis. Dietary data were collected by 3-day food records or 24-hour recalls. We analyzed data from 39 current intravenous drug users (IVDU), 103 past intravenous drug users (past-IVDU), 239 users of nonintravenous drugs (users-NIVD), and 61 nonusers (reference category). In the men, there were no differences in weight, body mass index (BMI), or body composition among the drug-use groups. In the women, there was a trend to lower weight and BMI across the drug use categories: IVDU women had lower average weight (-13.7 kg; p = .006), BMI (-5.6 units; p = .003) and less fat mass than non-users (-9.8 kg; p = .0001). In women, drug users had higher weight-adjusted energy intakes than nonusers, whereas in the men both drug using groups, NIVD and IVDU, had higher energy intakes than nonusers. These data suggest that intravenous drug-abuse is associated with lower weight and fat mass in women with HIV infection despite adequate self-reported energy intake.

Current Views on Hepatitis C Virus Infection.

Hepatitis C virus infection affects more than 4 million people in the United States and is a leading cause of liver failure necessitating transplantation. Effective combination therapies are now available for subgroups of patients at risk for progression to cirrhosis. The benefits of therapy in immunosuppressed hosts, such as HIV-infected patients and liver transplant recipients, are less well established.

Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy.

It has been postulated that the use of highly active antiretroviral therapy (HAART) would reduce the occurrence of human immunodeficiency virus (HIV)-associated weight loss and wasting. To test this assumption, we evaluated, by means of longitudinal analysis, a prospective cohort of 469 HIV-infected individuals enrolled in a study of the impact of HIV on nutrition. Overall, 156 individuals in the cohort (33.5%) met at least 1 of these definitions of wasting. Furthermore, 58% of the cohort (289 patients) lost >1.5 kg of weight in a 6-month period between any 2 study visits. More than 50% of the cohort was receiving HAART at the time that they met 1 of the definitions of wasting; with regard to the occurrence of wasting; no differences were related to therapy.

Relation of lean body mass to health-related quality of life in persons with HIV.

OBJECTIVE: To determine the nature and strength of the relation between lean body mass and measures of health-related quality-of-living (HRQL) including physical functioning in men and women with HIV. DESIGN: Cross-sectional analysis using 619 patients with HIV infection from two cities in the northeastern United States. MAIN OUTCOME MEASURES: Lean body mass (LBM) was assessed by bioimpedance analysis (BIA). Physical functioning, general health perceptions, energy/fatigue, and number of days spent in bed in the last month were determined by patient self-report. RESULTS: Data from 450 men and 169 women were analyzed. Mean age was 39 years, 37.6% were nonwhite, and mean CD4 counts were 352 cells/ml. In multivariable models, higher LBM was significantly associated with better physical functioning in men but not in women. In men, a 10-kg increment in LBM was associated with a 3.7 point (95% confidence interval [CI], 0.19-7.2) increment in physical functioning (0-100 scale). In similar analyses, higher LBM was significantly associated with better general health perceptions (10-kg increment in LBM associated with a 4.8 point [95% CI, 1.4-8.1] increment in general health perceptions), and fewer days in bed in the last month (10-kg increment in LBM associated with 0.9 [95% CI, -1.8-0] fewer days in bed). Lean body mass was not independently associated with energy/fatigue. CONCLUSIONS: In this diverse population of persons with HIV, LBM was significantly related to physical functioning and other measures of HQRL in men, but not in women. In men, the relation was linear but relatively weak. These data have potential implications for assessing the clinical impact of interventions aimed at increasing LBM. Even in men, increases in LBM in the ranges that are currently achievable may produce relatively small improvements in physical functioning and other measures of HRQL.

Salmonella enterica serovar typhimurium peptidase B is a leucyl aminopeptidase with specificity for acidic amino acids.

Peptidase B (PepB) of Salmonella enterica serovar Typhimurium is one of three broad-specificity aminopeptidases found in this organism. We have sequenced the pepB gene and found that it encodes a 427-amino-acid (46.36-kDa) protein, which can be unambiguously assigned to the leucyl aminopeptidase (LAP) structural family. PepB has been overexpressed and purified. The active enzyme shows many similarities to other members of the LAP family: it is a heat-stable (70 degrees C; 20 min) hexameric ( approximately 270-kDa) metallopeptidase with a pH optimum of 8.5 to 9.5. A detailed study of the substrate specificity of the purified protein shows that it differs from other members of the family in its ability to hydrolyze peptides with N-terminal acidic residues. The preferred substrates for PepB are peptides with N-terminal Asp or Glu residues. Comparison of the amino acid sequence of PepB with those of other LAPs leads to the conclusion that PepB is the prototype of a new LAP subfamily with representatives in several other eubacterial species and to the prediction that the members of this family share the ability to hydrolyze peptides with N-terminal acidic residues. Site-directed mutagenesis has been used to show that this specificity appears to be determined by a single Lys residue present in a sequence motif conserved in all members of the subfamily.

Diarrhea and abnormalities of gastrointestinal function in a cohort of men and women with HIV infection.

OBJECTIVE: The aim of this study was to determine the prevalence of gastrointestinal dysfunction in the era of improved treatment of HIV infection. METHODS: Gastrointestinal function was studied cross-sectionally in 671 persons with HIV. Absorptive function was measured by a 25-g D-xylose test, a Sudan-III stain for fecal fat on a 100-g fat diet, and serum levels of micronutrients. RESULTS: Eighty-eight percent had at least one abnormality of gastrointestinal function: 47.7% had low D-xylose absorption; 40.3% had a history of liver disease; 38.9% had diarrhea; 28.3% had chronic diarrhea; 22.5% had borderline or low serum vitamin B12 levels; 12.2% had stool pathogens; and 7.2% were hypoalbuminemic. Men were more likely to have low D-xylose absorption, diarrhea, and stool pathogens than women. Intravenous drug users (IVDUs) were more likely to have a history of liver disease and hypoalbuminemia. However, borderline or low vitamin B12 levels were less frequent in IVDUs; they tended to have less diarrhea and a lower prevalence of stool pathogens. Despite less history of liver disease, 14.1% of women were hypoalbuminemic. Differences in patterns of gastrointestinal dysfunction are unlikely to be due to severity of immunosuppression as abnormalities were seen in all risk groups with CD4 >200 cells/mm3. D-xylose absorption below 30 mg/dl, current diarrhea, and borderline levels of vitamin B12 were associated with advanced immunosuppression. CONCLUSIONS: Abnormalities of gastrointestinal function are common in the current era of HIV treatment, appear early in the course of HIV infection, and in the absence of diarrhea. Gender and IVDU are important determinants of the type and frequency of gastrointestinal abnormalities.