Persisting abdominal symptoms after travelers' diarrhea: Is there a genetic predisposition?

Functional gastrointestinal disorders (FGIDs) are defined as ailments of the mid or lower gastrointestinal tract which are not attributable to any discernable anatomic or biochemical defects.1 FGIDs include functional bowel disorders, also known as persisting abdominal symptoms (PAS). Irritable bowel syndrome (IBS) is one of the most common illnesses classified under PAS.2,3 This is the first prospective study that looks at the etiology and pathogenesis of post-infectious PAS in the context of environmental exposure and genetic susceptibility in a cohort of US travelers to Mexico. Our objective was to identify infectious, genetic and environmental factors that predispose to post infectious PAS. ^ Methods. This is a secondary data analysis of a prospective study on a cohort of 704 healthy North American tourists to Cuernavaca, Morelos and Guadalajara, Jalisco in Mexico. The subjects at risk for Travelers' diarrhea were assessed for chronic abdominal symptoms on enrollment and six months after the return to the US. ^ Outcomes. PAS was defined as disturbances of mid and lower gastrointestinal system without any known pathological or radiological abnormalities, or infectious, or metabolic causes. It refers to functional bowel disease, category C of functional gastrointestinal diseases as defined by the Rome II criterion. PAS was sub classified into Irritable bowel syndrome (IBS) and functional abdominal disease (FAD). ^ IBS is defined as recurrent abdominal pain or discomfort present at least 25% and associated with improvement with defecation, change in frequency and form of stool. FAD encompasses other abdominal symptoms of chronic nature that do not meet the criteria for IBS. It includes functional diarrhea, functional constipation, functional bloating: and unspecified bowel symptoms. ^ Results. Among the 704 travelers studied, there were 202 cases of PAS. The PAS cases included 175 cases of FAD and 27 cases of IBS. PAS was more frequent among subjects who developed traveler's diarrhea in Mexico compared to travelers who remained healthy during the short term visit to Mexico (52 vs. 38; OR = 1.8; CI, 1.3–2.5, P < 0.001). A statistically significant difference was noted in the mean age of subjects with PAS compared to healthy controls (28 vs. 34 yrs; OR = 0.97, CI, 0.95–0.98; P < 0.001). Travelers who experienced multiple episodes, a later onset of diarrhea in Mexico and passed greater numbers of unformed stools were more likely to be identified in PAS group at six months. Participants who developed TD caused by enterotoxigenic E.coli in Mexico showed a 2.6 times higher risk of developing FAD (P = 0.003). Infection with Providencia ssp. also demonstrated a greater risk to developing PAS. Subjects who sought treatment for diarrhea while in Mexico also displayed a significantly lower frequency of IBS at six months follow up (OR = 0.30; CI, 0.10–0.80; P = 0.02). ^ Forty six SNPs belonging to 14 genes were studied. Seven SNPs were associated with PAS at 6 months. These included four SNPs from the Caspase Recruitment Domain-Containing Protein 15 gene (CARD15), two SNPs from Surfactant Pulmonary-Associated Protein D gene (SFTPD) and one from Decay-Accelerating Factor For Complement gene (CD55). A genetic risk score (GRS) was composed based on the 7 SNPs that showed significant association with PAS. A 20% greater risk for PAS was noted for every unit increase in GRS. The risk increased by 30% for IBS. The mean GRS was high for IBS (2.2) and PAS (1.1) compared to healthy controls (0.51). These data suggests a role for these genetic polymorphisms in defining the susceptibility to PAS. ^ Conclusions. The study allows us to identify individuals at risk for developing post infectious IBS (PI-IBS) and persisting abdominal symptoms after an episode of TD. The observations in this study will be of use in developing measures to prevent and treat post-infectious irritable bowel syndrome among travelers including pre-travel counseling, the use of vaccines, antibiotic prophylaxis or the initiation of early antimicrobial therapy. This study also provides insights into the pathogenesis of post infectious PAS and IBS. (Abstract shortened by UMI.)^

Long-term gastrointestinal complications of Clostridium difficile associated diarrhea (CDAD)

Background. The incidence of Clostridium difficile -associated diarrhea (CDAD) is increasing worldwide likely because of increased use of broad spectrum antibiotics and the introduction of a clonal hyper-virulent strain called the BI strain. Short-term complications of CDAD include recurrent disease, requirement for colectomy, and persistent disease. However, data on the long-term consequences of CDAD are scarce. Among other infectious diseases (Shigella, Salmonella, and Campylobacter), long-term consequences such as irritable bowel syndrome (IBS), chronic dyspepsia/diarrhea, and other GI effects have been noted. Since the mechanism of action of these agents is similar to C.difficile, we hypothesized that patients with CDAD have greater likelihood of developing IBS and other functional gastrointestinal disorders (FGIDs) in the long-term as compared to a general sample of recently hospitalized patients. ^ Objective. To evaluate the long-term gastrointestinal complications of CDAD, (IBS, functional diarrhea, functional abdominal bloating, functional constipation and functional abdominal pain syndrome). ^ Methods. The current study was a secondary analysis of a previously completed observational case-control outcome study. Adult CDAD patients at St. Luke's Episcopal Hospital, Houston (SLEH) were followed up and interviewed by telephone six months after the initial diagnosis thereafter evaluated for the development of IBS and other FGIDs. A total of 46 patients with CDAD infection were recruited at SLEH between May-November 2007. The comparators were patients hospitalized in SLEH within one month before or after the admission of the reference case, hospital length of stay within one week longer or shorter than reference case, and age within 10 years more or less than the reference case. Cases and comparators were compared using Fisher's exact test. A p<0.05 was considered significant. ^ Results. Thirty CDAD patients responded to the questionnaires and were compared to 40 comparators. No comparator developed a FGID, while 3 (10%) CDAD patients developed new onset IBS (p=0.07), 4 (13.3%) developed new onset Functional Diarrhea (p=0.03), and 3 (10%) developed new onset Functional Constipation (p=0.07). No patient developed Functional Abdominal Bloating and Functional Abdominal Pain Syndrome. ^ Conclusion. In this study, new onset functional diarrhea was significantly more common in patients CDAD within six months after initial infection compared to matched controls.^

Diffusely adherent Escherichia coli (DAEC) as a cause of acute diarrhea

Acute diarrhea is the most common medical problem in the developing countries. Infectious agents are responsible for a majority of cases of acute diarrhea. Knowing the cause of acute diarrhea is important to developing plans for disease prevention, control and therapy. Acute diarrhea is caused by many viruses, bacteria and parasites. ^ Travelers to developing countries of the world commonly develop diarrhea as a result of eating contaminated food or drinking contaminated water. About 30-50% of travelers who travel from industrialized countries like United States to the developing countries are at risk of developing diarrhea. High risk areas for travelers' diarrhea are Mexico, Latin America and Southeast Asia. Public restaurants are the common sites for exposure to this type of food-borne infectious disease in travelers. Food becomes contaminated when they are handled by people with fecal content on their hands. ^ The importance of Diffusely Adherent Escherichia Coli (DAEC) in travelers to these areas has not been well studied. Some of the studies looking at DAEC have shown the organism to be present in children without symptoms. Other studies have shown a relationship between DAEC infection and presence of symptoms. I have selected this topic because the patho-physiological processes in DAEC infection that allow intestinal and extra-intestinal infections to develop are not fully understood. DAEC related acute diarrhea is a relatively new topic of public health significance. There is a limited number of studies regarding the virulence and pathogenic mechanisms of DAEC. The presumed virulence factor of the organism is diffuse attachment to the intestinal lining of the infected host. However more research needs to be done to identify the pathogenic mechanisms and virulence factors associated with DAEC infection for better treatment planning and diarrhea prevention. ^

Identification of diabetic retinopathy genes through a genome-wide association study among Mexican-Americans from Starr County, Texas

To identify genetic susceptibility loci for severe diabetic retinopathy, 286 Mexican-Americans with type 2 diabetes from Starr County, Texas completed detailed physical and ophthalmologic examinations including fundus photography for diabetic retinopathy grading. 103 individuals with moderate-to-severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy were defined as cases for this study. DNA samples extracted from study subjects were genotyped using the Affymetrix GeneChip® Human Mapping 100K Set, which includes 116,204 single nucleotide polymorphisms (SNPs) across the whole genome. Single-marker allelic tests and 2- to 8-SNP sliding-window Haplotype Trend Regression implemented in HelixTreeTM were first performed with these direct genotypes to identify genes/regions contributing to the risk of severe diabetic retinopathy. An additional 1,885,781 HapMap Phase II SNPs were imputed from the direct genotypes to expand the genomic coverage for a more detailed exploration of genetic susceptibility to diabetic retinopathy. The average estimated allelic dosage and imputed genotypes with the highest posterior probabilities were subsequently analyzed for associations using logistic regression and Fisher's Exact allelic tests, respectively. To move beyond these SNP-based approaches, 104,572 directly genotyped and 333,375 well-imputed SNPs were used to construct genetic distance matrices based on 262 retinopathy candidate genes and their 112 related biological pathways. Multivariate distance matrix regression was then used to test hypotheses with genes and pathways as the units of inference in the context of susceptibility to diabetic retinopathy. This study provides a framework for genome-wide association analyses, and implicated several genes involved in the regulation of oxidative stress, inflammatory processes, histidine metabolism, and pancreatic cancer pathways associated with severe diabetic retinopathy. Many of these loci have not previously been implicated in either diabetic retinopathy or diabetes. In summary, CDC73, IL12RB2, and SULF1 had the best evidence as candidates to influence diabetic retinopathy, possibly through novel biological mechanisms related to VEGF-mediated signaling pathway or inflammatory processes. While this study uncovered some genes for diabetic retinopathy, a comprehensive picture of the genetic architecture of diabetic retinopathy has not yet been achieved. Once fully understood, the genetics and biology of diabetic retinopathy will contribute to better strategies for diagnosis, treatment and prevention of this disease.^

The impact of antibiotic associated diarrhea on health related quality of life in hospitalized patients

Objective. To determine the impact of antibiotic associated diarrhea (AAD) on health related quality of life (HRQOL) in hospitalized patients compared to matched controls without diarrhea. ^ Methods. This is a hospital-based, matched case-control study using secondary data from a prospective cohort trial of patients receiving broad-spectrum antibiotics. One hundred and seventy-eight patients were recruited of whom 18 (10%) reported having antibiotic associated diarrhea. Two non-diarrhea controls were selected for each case with diarrhea giving a final sample of 18 cases and 36 controls. Responses from Short Form (SF) 36 questionnaire were aggregated into eight domains including physical functioning (PF), role-functioning physical (RP), bodily pain (BP), general health (GH), social functioning (SF), vitality (VT), role-functioning emotional (RE), and mental health (MH). The eight domains were compared between cases and controls. A GI targeted HRQOL measure was administered to 13 patients with AAD. Responses from the disease-specific instrument were combined in eight subscale scores: dysphoria, interference with activity, body image, health worry, food avoidance, social reaction, sex, and relationships. ^ Results. The sample consisted of 41 females (75.9%) and 13 males (24.1%) aged 53.5 ± 14.4 years (range: 21-76 years). Twenty five patients (46%) were Caucasian, 15 (27%) were African American, 13(24%) were Hispanic and 1(2%) was Asian. In univariate analysis, no significant differences in quality of life outcomes were observed in each of the SF36 domains between the case patients and matched controls. There were trends for decreased scores on the role-functioning physical, bodily pain, general health, social functioning, mental health, and mental summary domains. In total, 7 of 8 domain scores were lower in patients with AAD and 5 of 8 domain scores were lower by more than 5 points (considered clinically significant). Controlling for age, patients with antibiotic associated diarrhea had significantly lower general health, vitality, and mental health scale scores (p<0.05 each). The disease-specific scores were significantly lower in patients with AAD than those in published norms for irritable bowel syndrome patients. ^ Conclusion. In this small sample, several areas of decreased QOL in patients with AAD compared to matched controls were noted. A larger sample size to validate these results is necessary.^

Susceptibility to travelers' diarrhea and histo-blood group antigens

Histo-blood group antigens (HBGAs) have been associated with susceptibility to enteric pathogens including noroviruses (NoVs), enterotoxigenic Escherichia coli (ETEC), Campylobacter jejuni, and Vibrio cholerae. We performed a retrospective cohort study to evaluate the relationship between traveler HBGA phenotypes and susceptibility to travelers' diarrhea (TD) and post-infectious complications. 364 travelers to Guadalajara, Mexico were followed prospectively from June 1 - September 30, 2007 and from June 7–July 28, 2008 for the development of TD and at 6 months for post-infectious irritable bowel syndrome (PIIBS). Noroviruses were detected from illness stool specimens with RT-PCR. Diarrheal stool samples were also assayed for enterotoxigenic and enteroaggregative E. coli, Salmonella species, Shigella species, Vibrio species, Campylobacter jejuni, Yersinia enterocolitica, Aeromonas species, and Plesiomonas species. Diarrheal stools were evaluated for inflammation with fecal leukocytes, mucus, and occult blood. Phenotyping for ABO and Lewis antigens with an ELISA assay and FUT2 gene PCR genotyping for secretor status were performed with saliva. 171 of 364 (47%) subjects developed TD. HBGA typing for the travelers revealed O (62.9%), A (34.6%), B (1.6%), and AB (0.8%) phenotypes. There were 7% nonsecretors and 93% secretors among the travelers. AB phenotypes were more commonly associated with Cryptosporidium species (P=0.04) and ETEC ( P=0.08) as causes of TD. AB and B phenotype individuals were more likely to experience inflammatory diarrhea, particularly mucoid diarrhea ( P=0.02). However, there were relatively few individuals with AB and B phenotypes. GI and GII NoV and Cryptosporidium species infections and PI-IBS were identified only in secretors, but these differences were not statistically significant, (P=1.00), (P=1.00), and (P=0.60), respectively. Additional studies are needed to evaluate whether AB phenotype individuals may be more susceptible to developing TD associated with Cryptosporidium species or ETEC, and whether AB and B phenotype individuals may be more likely to develop inflammatory TD. Further studies are needed to investigate whether nonsecretor travelers may be at less risk for developing infections with NoVs and Cryptosporidium species and PI-IBS.^

A systematic review of selected birth outcomes in diabetic women who received preconception care and/or used multivitamins prior to pregnancy

Objective. To conduct a systematic review of published literature on preconception care in pre-existing diabetic women looking at the effect of glycemic control and multivitamin usage on the frequency of spontaneous abortion and birth defects.^ Methods. Articles were retrieved from Medline (1950–Dec 2007), Cochrane Library (1800–Dec 2007), Academic Search Complete (Ebsco) (Jan 1800–Dec 2007) and Maternal and Child Health Library (1965–Dec 2007). Studies included women with pre-existing, non-gestational diabetes and a comparison group. Participants must have either received preconception care and/or consumed a multivitamin as part of the study.^ Results. Overall, seven studies met the study criteria and applicability to the study objectives. Four of these reported the frequency of spontaneous abortion. Only one found a statistically significant increased risk of spontaneous abortion among pregnant women who did not receive preconception care compared with those who did receive care, odds ratio 4.32; 95% CI 1.34 to 13.9. Of the seven studies, six reported the frequency of birth defects. Five of these six studies found a significantly increased rate of birth defects among pregnant women who did not receive preconception care compared with those who did receive care, with odds ratios ranging from 1.53 to 10.16. All seven studies based their preconception care intervention on glycemic control. One study also used multivitamins as part of the preconception care.^ Conclusion. Glycemic control was shown to be useful in reducing the prevalence of birth defects, but not as useful in reducing the prevalence of spontaneous abortion. Insulin regimen options vary widely for the diabetic woman. No author excluded or controlled for women who may have been taking a multivitamin on their own. Due to the small amount of literature available, it is still not known which preconception care option, glucose control and/or multivitamin usage, provides better protection from birth defects and spontaneous abortion for the diabetic woman. An area for future investigation would be glycemic control and the use of folic acid started before pregnancy and the effects on birth defects and spontaneous abortion.^

Evaluation of environmental contamination of Clostridium difficile associated diarrhea in hospital rooms at St. Luke's Episcopal Hospital (SLEH) and review of literature on environmental sampling

The study was carried out at St. Luke's Episcopal Hospital to evaluate environmental contamination of Clostridium difficile in the infected patient rooms. Samples were collected from the high risk areas and were immediately cultured for the presence of Clostridium difficile . Lack of microbial typing prevented the study of molecular characterization of the Clostridium difficile isolates obtained led to a change in the study hypothesis. The study found a positivity of 10% among 50 Hospital rooms sampled for the presence of Clostridium difficile. The study provided data that led to recommendations that routine environmental sampling be carried in the hospital rooms in which patients with CDAD are housed and that effective environmental disinfection methods are used. The study also recommended molecular typing methods to allow characterization of the CD strains isolated from patients and environmental sampling to determine their type, similarity and origin.^

Diabetic nephropathy in African-Americans with type 1 diabetes: The new Jersey 725 study

Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in the United States. African-Americans and patients with type 1 diabetes (T1D) are at increased risk. We studied the rate and factors that influenced progression of glomerular filtration rate (GFR) in 401 African-American T1D patients who were followed for 6 years through the observational cohort New Jersey 725 study. Patients with ESRD and/or GFR<20 ml/min were excluded. The mean (SD) baseline GFR was 106.8 (27.04) ml/min and it decreased by 13.8 (mean, SD 32.2) ml/min during the 6-year period (2.3 ml/min/year). In patients with baseline macroproteinuria, GFR decreased by 31.8 (39.0) ml/min (5.3 ml/min/year) compared to 8.2 (mean, SD 27.6) ml/min (1.3 ml/min/year) in patients without it (p<0.00001). Six-year GFR fell to <20 ml/min in 5.25% of all patients, but in 16.8% of macroproteinuric patients.^ A model including baseline GFR, proteinuria category and hypertension category, explained 35% of the 6-year GFR variability (p<0.0001). After adjustment for other variables in the model, 6-year GFR was 24.9 ml/min lower in macroproteinuric patients than in those without proteinuria (p=0.0001), and 12.6 ml/min lower in patients with treated but uncontrolled hypertension compared to normotensive patients (p=0.003). In this sample of patients, with an elevated mean glycosylated hemoglobin of 12.4%, glycemic control did not independently influence GFR deterioration, nor did BMI, cholesterol, gender, age at diabetes onset or socioeconomic level.^ Taken together, our findings suggest that proteinuria and hypertension are the most important factors associated with GFR deterioration in African-American T1D patients.^

A systematic review of the evidence for use of herbal medicine for the treatment of acute diarrhea

Background. Acute diarrhea (AD) is an important cause of morbidity and mortality among both children and adults. An ideal antidiarrheal treatment should be safe, effective, compatible with Oral Rehydration Solution, and inexpensive. Herbal medicines, if effective, should fit these criteria as well or better than standard treatment. ^ Objective. The objective of the present study was to assess the effectiveness of plant preparations in patients with AD in reports of randomized and non-randomized controlled trials. ^ Aims. The aims of the present study were to identify effective antidiarrheal herbs and to identify potential antidiarrheal herbs for future studies of efficacy through well designed clinical trials in human populations. ^ Methods. Nineteen published studies of herbal management of AD were examined to identify effective plant preparations. Ten plant preparations including Berberine (Berberis aristata), tormentil root ( Potentialla tormentilla), baohauhau (from the baobaosan plant), carob (Ceratonia siliqua), pectin (Malus domestica), wood creosote (Creosote bush), guava (Psidium guajava L.), belladonna (Atropa belladonna), white bean (Phaseolis vulgaris), and wheat (Triticum aestivum) were identified. ^ Results. Qualitative data analysis of nineteen clinical trials indicated berberine’s potentially valuable antisecretory effects against diarrhea caused by Vibrio cholerae and enterotoxigenic Escherichia coli. Tormentil root showed significant efficacy against rotavirus-induced diarrhea; carob exhibited antidiarrheal properties not only by acting to detoxify and constipate but by providing a rich source of calories; guava and belladonna are antispasmodics and have been shown to relieve the symptoms of AD. Finally, white bean and wheat yielded favorable clinical and dietary outcomes in children with diarrhea. ^ Conclusion. The present study is the first to review the evidence for use of herbal compounds for treatment of AD. Future randomized controlled trials are needed to evaluate their efficacy and safety.^

Retrospective cohort study to determine the effect of metformin on survival of diabetic patients with pancreatic adenocarcinoma

Background: Pancreatic cancer is the fourth most common cause of cancer death in the United States. Despite advances in cancer treatment, prognosis of pancreatic cancer remains extremely poor with survival rates of 24% and 5% in 1 and 5 years, respectively. Many patients with pancreatic cancer have a history of diabetes and are treated with various antidiabetic regimens including metformin. In multiple retrospective studies, metformin has been associated with decreased risk of cancer and cancer-related mortality. Metformin has also been reported to inhibit the growth of cancer cells, both in vitro and in vivo.^ Methods: We conducted a retrospective cohort study to examine the survival benefit of metformin in diabetic patients with pancreatic cancer at MD Anderson Cancer Center (MDACC). A dataset of 397 patients who carried the diagnosis of "Diabetes Mellitus" and "Pancreatic Cancer" at MD Anderson were screened for this study. ^ Results: Mean age of patients at diagnosis of cancer was 64.0 ± 8.7 years (range 37-84). The majority of the patients were male (65.6%) and of Caucasian race (78.5%). The most common antidiabetic regimen used were insulin and metformin (in 39.1% and 38.7%, respectively). Patients' cancer were staged as resectable in 34.1%, locally advanced unresectable in 29.1%, and disseminated disease in 36.7% of cases. Overall 1-year and 3-year survival rates for all stages combined were 51.8% and 7.6%, respectively. Earlier stage, metformin use, low CA19-9 level, better ECOG performance status, surgical intervention, negative surgical margins, and smaller tumor size were associated with longer survival. Metformin use was associated with a 33% decrease in risk of death (HR: 0.67; 95% CI: 0.51-0.88). Multivariate Cox proportional hazard regression showed hazard ratio of 1.77 (95% CI 1.49-2.10) for cancer stage, 0.65 (95% CI 0.49-0.86) for metformin use, and 1.68 (95% CI 1.26-2.23) for CA 19-9 level above population median. ^ Conclusion: Our study suggests that metformin may improve the outcome in diabetic patients with pancreatic cancer independently of other known prognostic factors. Pancreatic cancer carries extremely poor prognosis; metformin may provide a suitable adjunct therapeutic option for pancreatic cancer in patients with and without diabetes mellitus.^

Community diagnosis: A working tool for developing culturally appropriate diarrhea intervention programs

Most studies related to diarrhea have been focused narrowly on the etiological and pathophysiological factors involved in inducing the disease. Such studies have often failed to consider other facets contributing to and possibly prolonging the problem, namely: socio-economic conditions, educational opportunities and attainments, cultural characteristics and beliefs, and the political administration and its commitment towards fulfilling its moral and ethical obligations in responding to and fostering human development.^ This study utilized the diagnostic approach of the PRECEDE model. The acronym stands for the predisposing reinforcing, and enabling constructs in educational diagnosis and evaluation. The constituents of this model were identified by utilizing participant observation field methods, traditionally applied by ethnographers to collect data describing the multiple facets of a culture, and linguistic anthropology used to capture and define characteristic semantics and viewpoints. The household study sample was randomly selected from a defined list of households known to have at least one child less than five years of age. An open-ended questionnaire format was used to interview the 115 mothers in the selected households sample.^ Kalama, the study community, is characteristically an agricultural village, situated in the Governorate of Kaliobia and located approximately 25 Km (about 15.5 miles) from the capital, Cairo, Egypt. The 1986 census indicates a population size of 13,328 people in 4,818 households. There were 65 deaths occurring among children less than five years in 1986. The causes of death were primarily related to diarrhea, followed by upper respiratory infections, congenital anomalies and birth injuries.^ This study outlines (a) practices related to the management of diarrhea, including the administration of foods and drinks during such episodes; (b) influences of governmental policies; and (c) recommended strategies for overcoming barriers and promoting effective diarrhea intervention programs. ^

Cardiovascular disease risk factors in Hispanic children identified through a diabetic proband

Prevalence and mortality rates for non-insulin dependent (Type II) diabetes mellitus are two to five times greater in the Mexican-American population than in the general U.S. population. Diabetes has been associated with risk factors which increases the likelihood of developing atherosclerosis. Relatives of noninsulin dependent diabetic probands are at increased risk of developing diabetes; and offspring of diabetic parents are at greater risk. Elevation in risk factor levels clearly began to develop prior to adulthood. Therefore an excess of these risk factors are expected among offspring and relatives of diabetics.^ The purposes of this study were to describe levels of risk factors within a group of Mexican American children who were identified through a diabetic proband, and to determine if there was a relationship between risk factor levels and heritability. Data from three hundred and seventy-six children and adolescents between the ages of 7 and 13 years, inclusively, were analyzed. These children were identified through a diabetic proband who participated in the Diabetes Alert Study. This study group was compared to a representative sample of Mexican American children, who participated in the Hispanic Health and Nutrition Examination Survey.^ For females, there were statistically significant associations between upper body fat distribution and increased systolic and diastolic blood pressure after adjusting for age and measures of fatness. Body mass index was positively related to and explained a significant portion of the variability in systolic blood pressure, total cholesterol, and HDL-cholesterol, for males only. No relationship was found between degree of relationship to the diabetic proband and risk factor levels. The most likely explanations for this were insufficient sample size to detect differences, and/or incomplete ascertainment of pedigree information.^ Although there was evidence that these Mexican American children are fatter and have more central fat distribution than non-Hispanic children, there is no evidence of increased risk for diabetes and/or cardiovascular disease at these ages. ^

Feeding practices and their associations with diarrhea incidence in a cohort of rural Egyptian infants

A study was conducted in 4 villages in Bilbeis, Egypt, to document the infant feeding practices and identify their determinants, and examine the associations between feeding practices and diarrhea incidence in infants. A cohort of 152 infants were followed from birth with twice-weekly home visits to record feeding practices and diarrheal illness. Cross-sectional information was obtained about child birth; early neonatal feeding practices; and the socioeconomic, demographic, and water and sanitation characteristics of study families.^ Prelacteal fees were given to 60% of the infants. Nineteen percent of the infants were wet nursed at least once during the first week of life. Breast-feeding prevalence declined from 100% among infants aged less than 12 weeks to 84% among those aged 44-47 weeks. The prevalence of exclusive breast-feeding among breast-fed infants was 38% in those aged less than 4 weeks, increased to 54% in age period 4-7 weeks, and then declined rapidly to 4% in age period 24-27 weeks. The patterns and determinants of consumption by breast-fed infants of specific supplements were examined in detail.^ Between birth and age 47 weeks, the diarrhea incidence rate per person-year among breast-fed infants (6.84 episodes) was identical to the rate among all infants (6.89 episodes). In age period 0-11 weeks, the diarrhea incidence rate among breast-fed infants receiving supplements was 1.3 times (95% confidence interval: 0.9-2.0) higher than the rate among those exclusively breast-fed. In other age periods, diarrhea incidence was generally nonsignificantly higher among exclusively breast-fed infants than among those partially breast-fed and those completely weaned.^ Both univariate and multivariate analyses were done to examine the associations between diarrhea incidence and the consumption by breast-fed infants of specific supplements. After multivariate adjustment, supplements that showed significant, borderline, or suggestive positive associations with diarrhea incidence were cereal-water, cheese, raw vegetables, and 'other' foods. Significant, borderline, or suggestive negative associations were observed between diarrhea incidence and the intake of fresh animal milk, and potatoes.^ To reduce the risk of diarrhea, indiscriminate use of supplements among Bilbeis infants aged less than 12 weeks should be strongly discouraged. While mothers in this area should be educated about methods of safer preparation, handling, storage, and administration of all weaning foods, their attention should be particularly drawn to the 4 foods that were found to be positively associated with diarrhea incidence among infants in this study. ^

Natural history of placebo treatment in adults acquiring travelers' diarrhea in Mexico

The natural history of placebo treated travelers' diarrhea and the prognostic factors of recovery from diarrhea were evaluated using 9 groups of placebo treated subjects from 9 clinical trial studies conducted since 1975, for use as a historical control in the future clinical trial of antidiarrheal agents. All of these studies were done by the same group of investigators in one site (Guadalajara, Mexico). The studies are similar in terms of population, measured parameters, microbiologic identification of enteropathogens and definitions of parameters. The studies had two different durations of followup. In some studies, subjects were followed for two days, and in some they were followed for five days.^ Using definitions established by the Infectious Diseases society of America and the Food and Drug Administration, the following efficacy parameters were evaluated: Time to last unformed stool (TLUS), number of unformed stools post-initiation of placebo treatment for five consecutive days of followup, microbiologic cure, and improvement of diarrhea. Among the groups that were followed for five days, the mean TLUS ranged from 59.1 to 83.5 hours. Fifty percent to 78% had diarrhea lasting more than 48 hours and 25% had diarrhea more than five days. The mean number of unformed stools passed on the first day post-initiation of therapy ranged from 3.6 to 5.8 and, for the fifth day ranged from 0.5 to 1.5. By the end of followup, diarrhea improved in 82.6% to 90% of the subjects. Subjects with enterotoxigenic E. coli had 21.6% to 90.0% microbiologic cure; and subjects with shigella species experienced 14.3% to 60.0% microbiologic cure.^ In evaluating the prognostic factors of recovery from diarrhea (primary efficacy parameter in evaluating the efficacy of antidiarrheal agents against travelers' diarrhea). The subjects from five studies were pooled and the Cox proportional hazard model was used to evaluate the predictors of prolonged diarrhea. After adjusting for design characteristics of each trial, fever with a rate ratio (RR) of 0.40, presence of invasive pathogens with a RR of 0.41, presence of severe abdominal pain and cramps with a RR of 0.50, number of watery stools more than five with a RR of 0.60, and presence of non-invasive pathogens with a RR of 0.84 predicted a longer duration of diarrhea. Severe vomiting with a RR of 2.53 predicted a shorter duration of diarrhea. The number of soft stools, presence of fecal leukocytes, presence of nausea, and duration of diarrhea before enrollment were not associated with duration of diarrhea. ^