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Biomedical subjects

H L DuPont

Publications and source records attributed to H L DuPont.

At least 37 records · Page 2Linked to original sources

Virulence of three distinct Cryptosporidium parvum isolates for healthy adults.

The infectivity of three Cryptosporidium parvum isolates (Iowa [calf], UCP [calf], and TAMU [horse]) of the C genotype was investigated in healthy adults. After exposure, volunteers recorded the number and form of stools passed and symptoms experienced. Oocyst excretion was assessed by immunofluorescence. The ID50 differed among isolates: Iowa, 87 (SE, 19; 95% confidence interval [CI], 48.67-126); UCP, 1042 (SE, 1000; 95% CI, 0-3004); and TAMU, 9 oocysts (SE, 2.34; 95% CI, 4.46-13.65); TAMU versus Iowa, P=.002 or UCP, P=.019. Isolates also differed significantly (P=.045) in attack rate between TAMU (86%) and Iowa (52%) or UCP (59%). A trend toward a longer duration of diarrhea was seen for the TAMU (94.5 h) versus UCP (81.6 h) and Iowa (64.2 h) isolates. C. parvum isolates of the C genotype differ in their infectivity for humans.

Adult↗

Improved detection of enterotoxigenic Escherichia coli among patients with travelers' diarrhea, by use of the polymerase chain reaction technique.

This study sought to determine whether a specific polymerase chain reaction (PCR) for enterotoxigenic Escherichia coli (ETEC) toxins after chaotropic extraction of DNA from stool would increase the detection of ETEC over that of conventional oligonucleotide probe hybridization of 5 E. coli colonies per stool sample (a standard method). By DNA hybridization, 29 (21%) of 140 patients were positive for ETEC, and 59 (42%) of 140 were positive for ETEC when PCR was used. Sensitivity of the PCR assay was confirmed through spiked stool experiments to be approximately 100-1000 ETEC colonies per sample. Specificity of the assay was determined by showing an absence of ETEC by the PCR technique in a subgroup of 48 subjects and by confirming the presence of ETEC DNA of positive samples by dot blot procedure. PCR technique detected significantly more ETEC infections in these subjects than did the hybridization method (P<.0001).

Bacterial Toxins↗

Oral rehydration therapy plus loperamide versus loperamide alone in the treatment of traveler's diarrhea.

Eighty United States students in Mexico received either loperamide (an initial dose of 4 mg, followed by 2 mg after passage of each unformed stool, up to 8 mg/d; 40 patients) or loperamide (at the same dosage schedule) plus an oral rehydration therapy (ORT) preparation (500 mL initially, followed by 250 mL after each subsequently passed unformed stool, up to 1,000 mL per 24 hours; 40 patients). The ORT preparation was a modification of the World Health Organization-recommended solution, adjusted to a sodium concentration of 60 mEq/L. All treatments were given for 48 hours. The study demonstrated equivalent clinical responses with regard to diminishment of diarrhea or subjective findings such as abdominal pain/cramps, headache, dry mouth, dizziness, or thirst. Stool number (by form) and specific gravity of urine postenrollment were similar in the groups. Administration of loperamide plus ORT for the management of traveler's diarrhea, in cases in which subjects were encouraged to drink ad libitum, offered no benefit over administration of loperamide alone.

Administration, Oral↗

Enteroaggregative Escherichia coli as a cause of traveler's diarrhea: clinical response to ciprofloxacin.

The purpose of this study was to determine the role of enteroaggregative Escherichia coli (EAEC) in the development of traveler's diarrhea and the clinical response of patients with EAEC diarrhea following treatment with ciprofloxacin. Sixty-four travelers with diarrhea and no other recognized enteropathogen were enrolled in treatment studies in Jamaica and Mexico from July 1997 to July 1998. EAEC was isolated from 29 travelers (45.3%). There was a significant reduction in the duration of posttreatment diarrhea in the 16 patients treated with ciprofloxacin, as compared with that in the 13 patients who received placebo (mean of 35.3 versus 55.5 hours; P = .049). There was a nonsignificant reduction in the mean number of unformed stools passed during the 72 hours after enrollment in the ciprofloxacin-treated group (5.6), as compared with that in the placebo group (7.5) (P = .128). This study provides additional evidence that EAEC should be considered as a cause of antibiotic-responsive traveler's diarrhea.

Adult↗

A multicenter randomized controlled trial of a liquid loperamide product versus placebo in the treatment of acute diarrhea in children.

This randomized, double-blind, placebo-controlled trial of 48 hours' duration conducted in 13 primary care ambulatory practices in the United States and Mexico was used to compare the efficacy and safety of loperamide with placebo for the treatment of acute diarrhea in children aged 2 through 11 years. Two hundred fifty-eight children with acute nonspecific diarrhea were enrolled. Children were randomly assigned to treatment with loperamide HCl 0.5 mg/5 mL (n = 130) or placebo (n = 128). The first dose of loperamide consisted of either 1.0 mg (children 2 through 5 years of age) or 2.0 mg (children 6 through 11 years of age) of study medication under the observation of study personnel. This was followed by 1 mg after each unformed stool, with a total daily dose of up to 3.0 mg in the children 2-5 years of age, 4.0 mg in the children 6-8 years of age, and 6.0 mg in the children 9-11 years of age. The primary outcome measures were time to last unformed stool, time to first unformed stool, number of unformed stools during six consecutive 8-hour periods, and overall rating of efficacy/acceptability. Secondary outcomes included abdominal pain/cramping, vomiting, and fever. Children who received loperamide had significantly shorter time to last unformed stool (p = 0.0017) and fewer numbers of unformed stools (p = 0.0237) than children who received placebo. The end-of-study overall efficacy/acceptability rating of loperamide was significantly better than for placebo (p = 0.0107). All other clinically important outcome measures related to diarrhea relief favored loperamide. There was no significant difference in the incidence of drug-related adverse events between treatment groups, although total adverse events were reported more frequently (p = 0.048) by the loperamide group (15%) compared with the placebo group (7%). In conclusion, this controlled study provides data demonstrating that at recommend doses, loperamide is well tolerated and significantly shortens the duration and severity of symptoms of acute nonspecific diarrhea in children 2 through 11 years of age.

Acute Disease↗

The antibody response to 27-, 17-, and 15-kDa Cryptosporidium antigens following experimental infection in humans.

Previous studies have suggested that persons infected with Cryptosporidium parvum develop antibody responses to 27-, 17-, and 15-kDa C. parvum antigens. Studies of volunteers infected with Cryptosporidium species provided an opportunity to evaluate the relationship between antibody reactivity to these antigens and infection outcome. As monitored by immunoblot, increases in specific antibody reactivity were more prevalent among volunteers who developed signs and symptoms of cryptosporidiosis (n = 11) than among asymptomatic infected (n = 7; P = .05) or oocyst-negative volunteers (n = 11; P = .02). Volunteers with preexisting IgG antibody to the 27-kDa antigen excreted fewer oocysts than volunteers without this antibody (P = .003). IgG reactivity to the 17-kDa antigens and IgM reactivity to the 27-kDa antigens were higher at day 0 for asymptomatic infected persons than for those who developed symptoms (P = .03 and P = .04, respectively). These results suggest that characteristic antibody responses develop following C. parvum infection and that persons with preexisting antibodies may be less likely to develop illness.

Animals↗

Prophylactic effect of bovine anti-Cryptosporidium hyperimmune colostrum immunoglobulin in healthy volunteers challenged with Cryptosporidium parvum.

Bovine hyperimmune anti-Cryptosporidium colostrum immunoglobulin (BACI) decreases the intensity of Cryptosporidium parvum infection in vitro. We investigated the prophylactic effect of BACI in healthy adults challenged with C. parvum. After we established an oocyst dose that resulted in 100% infection in four volunteers (baseline group), 16 volunteers were randomized to receive (1) BACI prior to C. parvum challenge (BACI group) and a nonfat milk placebo 30 minutes later, (2) BACI prior to and 30 minutes after challenge (reinforced BACI group), or (3) nonfat milk placebo prior to and 30 minutes after challenge. Subjects received BACI (10 g) or nonfat milk placebo three times a day for a total of 5 days and were followed for clinical symptoms and oocyst excretion for 30 days. A trend toward less diarrhea (P = .08) was observed for subjects receiving BACI in comparison with occurrences in placebo recipients. Subjects receiving BACI or nonfat milk placebo had a 100-fold reduction in oocyst excretion as compared with excretion in the baseline group.

Administration, Oral↗

HEp-2 cell-adherent Escherichia coli and intestinal secretory immune response to human immunodeficiency virus (HIV) in outpatients with HIV-associated diarrhea.

HEp-2 cell-adherent Escherichia coli and the human immunodeficiency virus (HIV) itself have recently been incriminated as causes of chronic HIV-associated diarrhea. This study sought to determine the prevalence of these two agents among HIV-infected patients with diarrhea in an outpatient setting in the United States and to compare their prevalence to that of other commonly recognized enteropathogens known to be present in this population. HEp-2 cell-adherent E. coli was found in 20 of 83 (24.1%) patients with diarrhea. A diffuse pattern of adherence was the most common, found in 14 of 20 (70%) patients, followed by a localized adherence pattern (6 of 20; 30%). An intestinal secretory immune response against the p24 antigen of HIV was found in 9 of 34 (27.5%) patients with HIV-associated diarrhea. The following pathogens or products were also detected in lower frequencies: Cryptosporidium spp. (10.8%), Clostridium difficile toxin (8.8%), microsporidia (6%), Isospora belli (3.6%), Blastocystis hominis (2.4%), Giardia spp. (1.2%), Salmonella spp. (1.2%), and Mycobacterium spp. (1.2%). The role of HEp-2 cell-adherent E. coli and HIV enteric infections in patients with HIV-associated diarrhea deserves further study.

Bacterial Adhesion↗

Susceptibility and serologic response of healthy adults to reinfection with Cryptosporidium parvum.

Healthy adults are susceptible to infection with small numbers of Cryptosporidium parvum oocysts, resulting in self-limited infection. We investigated if infection of humans with C. parvum is protective 1 year after primary exposure. At 1 year after a primary challenge with 30 to 10(6) oocysts, 19 healthy immunocompetent adults were rechallenged with 500 oocysts and monitored for the development of infection and/or illness. Oocyst excretion was quantitated by direct immunofluorescence with a C. parvum-specific monoclonal antibody, and anti-C. parvum antibodies in serum were detected by an enzyme-linked immunosorbent assay. Fewer subjects shed oocysts after the second exposure (3 of 19; 16%) than after the first exposure (12 of 19; 63%) (P < 0.005). Although the rates of diarrhea were comparable after each of the two exposures, the clinical severity as determined by the mean number of unformed stools passed was lower after reexposure (11.25 versus 8.62; P < 0.05). The number of anti-Cryptosporidium immunoglobulin G and A seroconversions increased after secondary exposure. However, the C. parvum serum antibody response did not correlate with the presence or absence of infection.

Adult↗

Management of travellers' diarrhoea.

The most common health problem encountered in international travellers to topical and subtropical areas is diarrhoea. Even though it is not a life-threatening condition, it may influence deeply the quality of a vacation or the success of a business trip. The majority of cases of travellers' diarrhoea are due to bacterial pathogens, but viruses have also been implicated in a minority of patients. It is advocated that travellers with diarrhoea provide themselves with sources of salt (crackers or soup) and mineral water, to prevent and treat dehydration. Otherwise, treatment recommendations follow illness severity. For mild cases, symptomatic relief alone can be recommended. Loperamide is an effective agent improving diarrhoea and associated symptoms. For moderate diarrhoea (requiring a forced change in itinerary) combination therapy is advised using a fluoroquinolone together with loperamide. Severe diarrhoea [fever > 38 degrees C, dysentery (bloody stools) or incapacitating symptoms] should prompt the voyager to take an antibiotic alone for 3 to 5 days. Loperamide is relatively contraindicated in these cases. For the minority of patients receiving chemoprophylaxis to prevent travellers' diarrhoea, fluoroquinolones taken once a day while in the area at risk produce the highest protection rate (up to 95%). However, most authorities do not recommend routine prophylaxis for travellers.

Aged↗

Guidelines on acute infectious diarrhea in adults. The Practice Parameters Committee of the American College of Gastroenterology.

Guidelines for clinical practice are intended to suggest preferable approaches to particular medical problems as established by the interpretation and collation of scientifically valid research, derived from an extensive review of published literature. When data are not available that will withstand objective scrutiny, a recommendation may be made based on a consensus of experts. Guidelines are intended to apply to the clinical situation for all physicians without regard to specialty. Guidelines are intended to be flexible, not necessarily indicating the only acceptable approach, and should be distinguished from standards of care that are inflexible and rarely violated. Given the wide range of choices in any health care problem, the physician should select the course best suited to the individual patient and the clinical situation presented. These guidelines are developed under the auspices of the American College of Gastroenterology and its Practice Parameters Committee. These guidelines are also approved by the governing boards of the American Gastroenterology Association and the American Society of Gastrointestinal Endoscopy. Expert opinion is solicited from the outset for the document. Guidelines are reviewed in depth by the Committee, with participation from experienced clinicians and others in related fields. The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time. The following guidelines are intended for adults and not for pediatric patients.

Acute Disease↗

Persistent diarrhea in travelers.

Most patients with traveler's diarrhea can be efficiently treated with available pharmacological agents. A more difficult problem is the persistent diarrhea (lasting > or = 14 days) that occurs in approximately 3% of travelers who have acute diarrhea. In the initial evaluation of these patients, ideally three stool samples should be obtained for examination for pathogens. If an agent is not identified or the patient has not responded to specific therapy, he or she may be empirically treated with an antimicrobial drug directed toward common bacterial enteropathogens, if such treatment has not already been administered. For those patients whose conditions do not respond, antiprotozoal therapy may be employed empirically. If diarrhea continues, then an endoscopic evaluation is indicated, and specific treatment can be given if an agent or condition is identified. A proportion of patients will continue to have diarrhea following empirical therapy and a gastroenterologic workup. These individuals are best given symptomatic treatment and reassured that the prognosis is good.

Chronic Disease↗

Major differences in the spectrum of gastrointestinal infections associated with AIDS in India versus the west: an autopsy study.

The spectrum of bowel infections in patients with AIDS in India is not well characterized. To examine this spectrum of infections, an autopsy study of 49 subjects was carried out. Multiple sections were obtained from the gastrointestinal tract. A pathogenic organism was detected in 25 (71%) of 35 patients with diarrhea vs. 4 (29%) of 14 patients without diarrhea (P < .01). The most frequent pathogen was cytomegalovirus (in 13; 27%), followed by parasites (9; 18%), fungi (8; 16%) and Mycobacterium tuberculosis (7; 14%). This is the first autopsy study of patients with AIDS in the Indian subcontinent and shows important differences in the profile of their opportunistic infections compared with those of such patients in the West. These findings will help define the optimal diagnostic and therapeutic approaches to patients with AIDS, which, in view of the considerable budgetary restrictions in developing countries, should be targeted toward the pathogens most frequently identified in such areas.

AIDS-Related Opportunistic Infections↗

Cryptosporidium parvum: intensity of infection and oocyst excretion patterns in healthy volunteers.

Data about human Cryptosporidium parvum infection have originated from travelers, community and day care center outbreaks, and persons infected with the human immunodeficiency virus. In addition, experimental infection in 29 antibody-negative, healthy, adult volunteers generated information on the dose-infection response of C. parvum (Iowa strain). In that report, low inocula were sufficient to cause infection in 18 and illness in 7 persons. To further define the duration and intensity of infection in this population, oocyst shedding patterns were investigated in the 18 subjects infected with C. parvum. Oocyst quantitation revealed that volunteers with diarrheal illness (n = 7) excreted more oocysts over the course of the infection than did volunteers without diarrhea (n = 11; P < .05). Symptomatic subjects were more likely to shed oocysts on consecutive days. Further, a statistical nonsignificant inverse trend (r2 = .330, P = .136) was seen between challenge dose and total excreted oocysts. This paradox may relate to receptor saturation or a toxic effect on cells, parasites, or both afforded by a high inoculum.

Animals↗