Immune response, ciprofloxacin activity, and gender differences after human experimental challenge by two strains of enterotoxigenic Escherichia coli.

In order to test vaccines against enterotoxigenic Escherichia coli (ETEC)-induced diarrhea, challenge models are needed. In this study we compared clinical and immunological responses after North American volunteers were orally challenged by two ETEC strains. Groups of approximately eight volunteers received 10(9) or 10(10) CFU of E. coli B7A (LT+ ST+ CS6+) or 10(8) or 10(9) CFU of E. coli H10407 (LT+ ST+ CFA/I+). About 75% of the volunteers developed diarrhea after challenge with 10(10) CFU B7A or either dose of H10407. B7A had a shorter incubation period than H10407 (P = 0.001) and caused milder illness; the mean diarrheal output after H10407 challenge was nearly twice that after B7A challenge (P = 0.01). Females had more abdominal complaints, and males had a higher incidence of fever. Ciprofloxacin generally diminished or stopped symptoms and shedding by the second day of antibiotic treatment, but four subjects shed for one to four additional days. The immune responses to colonization factors CS6 and colonization factor antigen I (CFA/I) and to heat-labile toxin (LT) were measured. The responses to CFA/I were the most robust responses; all volunteers who received H10407 had serum immunoglobulin A (IgA) and IgG responses, and all but one volunteer had antibody-secreting cell (ASC) responses. One-half the volunteers who received B7A had an ASC response to CS6, and about one-third had serum IgA or IgG responses. Despite the differences in clinical illness and immune responses to colonization factors, the immune responses to LT were similar in all groups and were intermediate between the CFA/I and CS6 responses. These results provide standards for immune responses after ETEC vaccination.

Use of azithromycin for the treatment of Campylobacter enteritis in travelers to Thailand, an area where ciprofloxacin resistance is prevalent.

We evaluated the use of azithromycin (500 mg) or ciprofloxacin (500 mg) daily for 3 days for the treatment of acute diarrhea among United States military personnel in Thailand. Stool cultures were obtained and symptoms were recorded on study days 0, 1, 2, 3, and 10. Campylobacter species were the most common pathogen isolated (44 isolates from 42 patients). All Campylobacter isolates were susceptible to azithromycin; 22 were resistant to ciprofloxacin. Among the 42 patients with campylobacter infection, there were 2 clinical and 6 bacteriologic treatment failures in the ciprofloxacin group and no treatment failures in the azithromycin group (P = .021 for bacteriologic failures). Overall, azithromycin was as effective as ciprofloxacin in decreasing the duration of illness (36.9 hours vs. 38.2 hours, respectively) and the number of stools (6.4 vs. 7.8, respectively). Among those not infected with Campylobacter species (n = 30), the duration of illness was 32.9 hours vs. 20.7 hours (P = .03) for the azithromycin and ciprofloxacin groups, respectively. Azithromycin is superior to ciprofloxacin in decreasing the excretion of Campylobacter species and as effective as ciprofloxacin in shortening the duration of illness. Azithromycin therapy may be an effective alternative to ciprofloxacin therapy in areas where ciprofloxacin-resistant Campylobacter species are prevalent.

Effects of a behavioral stress-management program on anxiety, mood, self-esteem, and T-cell count in HIV positive men.

This study evaluated the effects of a behavioral stress-management program on anxiety, mood, self-esteem, and T-cell count in a group of HIV-positive men who were asymptomatic except for T-cell counts below 400. The program consisted of 20 biweekly sessions of progressive muscle relaxation and electromyograph biofeedback-assisted relaxation training, meditation, and hypnosis. Ten subjects were randomly assigned to either a treatment group of a no-treatment control group, and the 2 groups were compared on pre- to posttreatment changes in the dependent measures. Analysis showed that, compared with the no-treatment group, the treatment group showed significant improvement on all the dependent measures, which was maintained at a 1-mo. follow-up. Since stress is known to compromise the immune system, these results suggest that stress management to reduce arousal of the nervous system and anxiety would be an appropriate component of a treatment regimen for HIV infection.

Clinical and experimental evaluation of cranial TENS in the U.S.: a review.

A review of studies evaluating therapeutic applications of cranial TENS in clinical populations reveals frequent use of unreliable self-report outcome measures, insufficient description of treatment protocol, invalid double-blind and placebo conditions and often a lack of adequate description of the electrical parameters used. A review of the experimental literature indicates that cranial TENS is capable of modulating central nervous system activity. It is suggested that the inconclusiveness of the clinical literature may be due to incomplete research design rather than to the questionable nature of the treatment, and that cranial TENS merits continued research.

Sine-wave auricular TENS produces frequency-dependent hypesthesia in the trigeminal nerve.

OBJECTIVE: To evaluate the effects of different frequencies of auricular (ear-to-ear) sine-wave transcutaneous electrical nerve stimulation (TENS), administered at subliminal intensity, on trigeminal nerve sensitivity. DESIGN: In a double-blind protocol, healthy volunteer subjects were administered one of three different frequencies of active TENS (5, 100, or 2,000 Hz) or placebo TENS (no current was passed) for 30 min. SETTING: Department of Psychology, City University of New York. SUBJECTS: 72 healthy undergraduate volunteers with no preexisting pain problems (16 men and 56 women), from the Department of Psychology, City University of New York. OUTCOME MEASURE: Pretreatment to posttreatment changes were measured in sensation threshold for a 250-Hz electrical stimulus applied transcutaneously to an area 1 cm anterior to the tragus of the ear (mandibular division of the trigeminal nerve). RESULTS: Analysis of variance indicated no group differences in baseline trigeminal sensation threshold, but there were significant group differences in pretreatment to posttreatment changes in sensation threshold (p < 0.001). A postiori analysis showed significant increases in trigeminal sensation threshold after active TENS as compared to placebo TENS (p < 0.05), with 5- and 100-Hz TENS producing significantly greater hypesthesia than 2,000-Hz TENS (p < 0.05). CONCLUSIONS: Sine-wave auricular TENS produces frequency-dependent trigeminal hypesthesia that is not a placebo effect.

Frequency-dependent effects of sine-wave cranial transcutaneous electrical nerve stimulation in human subjects.

In a double-blind protocol, ninety healthy volunteer subjects received 30 minutes of constant current sine-wave cranial transcutaneous electrical nerve stimulation (TENS) of 5 Hertz (Hz), 100 Hz, or 2000 Hz frequency (current maintained below .5 mA for safety), placebo TENS, or no treatment. The five groups were compared on pre- to posttreatment changes in blood pressure, heart rate, peripheral temperature, and anxiety. Analysis showed significant reductions in systolic and diastolic blood pressure and heart rate after 100 Hz cranial TENS as compared to the other groups. No other differences achieved significance.

Treatment of traveler's diarrhea with ciprofloxacin and loperamide.

To determine the efficacy of loperamide given with long- and short-course quinolone therapy for treating traveler's diarrhea, 142 US military personnel were randomized to receive a single 750-mg dose of ciprofloxacin with placebo, 750 mg of ciprofloxacin with loperamide, or a 3-day course of 500 mg of ciprofloxacin twice daily with loperamide. Culture of pretreatment stool specimens revealed campylobacters (41%), salmonellae (18%), enterotoxigenic Escherichia coli (ETEC, 6%), and shigellae (4%). Of the participants, 87% completely recovered within 72 h of entry. Total duration of illness did not differ significantly among the three treatment groups, but patients in the 3-day ciprofloxacin plus loperamide group reported a lower cumulative number of liquid bowel movements at 48 and 72 h after enrollment compared with patients in the single-dose ciprofloxacin plus placebo group (1.8 vs. 3.6, P = .01; 2.0 vs. 3.9, P = .01). While not delivering a remarkable therapeutic advantage, loperamide appears to be safe for treatment of non-ETEC causes of traveler's diarrhea. Two of 54 patients with Campylobacter enteritis had a clinical relapse after treatment that was associated with development of ciprofloxacin resistance.

Perception of different frequencies of cranial transcutaneous electrical nerve stimulation in normal and HIV-positive individuals.

Sine-wave transcutaneous electrical nerve stimulation (TENS) of varying frequencies applied across the cranium (ear to ear) has been demonstrated to evoke three different noncutaneous sensations in three discrete, nonoverlapping frequency bands in normal, healthy subjects. This report describes two studies which evaluate perception of these cranial TENS-evoked, frequency-dependent sensations in normal and HIV-positive individuals. In Exp. I, all of 50 normal, healthy subjects reported perceiving the same three noncutaneous sensations in the same three nonoverlapping frequency bands as long as stimulated and over repeated trials. In Exp. II, 34 HIV-positive individuals (14 asymptomatic, 9 ARC, 11 AIDS) who were free of neurological symptoms differed significantly from 10 normal, healthy controls, and from the norms observed in Exp. I, on perception of the three different TENS-evoked sensations. Also, inability to maintain perception of the stimulus over repeated trials, observed only in the HIV-positive individuals, increased significantly with severity of HIV infection.

Sensory perception in uremic patients.

Peripheral (PNS) and central (CNS) sensory nervous system function was quantitatively assessed using neuroselective transcutaneous electrical nerve stimulation (TENS) in a population of 19 chronic hemodialysis patients (ages 17-77, median 47 years; duration 1-14, median 3 years). Cutaneous current perception threshold (CPT) provided an index of PNS integrity, and a new technique involving cranial TENS to characterize cephalic evoked noncutaneous sensations (CENS) was used to assess CNS sensory function. Patients showed both CPT (32%) and CENS (89%) abnormalities as compared with previously tested healthy subjects. No significant correlation was observed between age, duration of dialysis, PNS, and CNS abnormalities. The CPT examination provides a sensitive and easy to administer test of PNS sensory function for the purpose of assessing the adequacy of dialysis in chronic hemodialysis patients; the CENS examination also may prove useful in this regard.

Lack of correlation between frontalis electromyography and self-ratings of either frontalis tension or state anxiety.

Since training in deep muscular relaxation is common to most behavioral treatments for anxiety and tension-related disorders, muscle tension measures, such as electromyography (EMG), would provide valuable information as to the efficacy of these treatments. In the past, however, the majority of clinical reports on behavioral treatments employing muscular relaxation have based results primarily on self-rated outcome measures, despite evidence in the literature of a lack of correspondence between self-ratings and physiological measures of muscle tension. An experiment was performed on 20 normal subjects comparing self-ratings of anxiety and frontalis muscle tension with frontalis EMG before and after a 15-min. relaxation period accompanied by frontalis EMG biofeedback. Analysis showed that the self-ratings of anxiety and frontalis tension correlated significantly both before and after the relaxation period. However, no correlation was observed between self-rated anxiety or frontalis tension and frontalis EMG either before or after the relaxation period. The relaxation period had no significant effect on the dependent measures. It is suggested that, if people are unable to report accurately on their somatic states, then physiological outcome measures, such as EMG, would be preferable to self-rated measures in assessments of relaxation training procedures.

Treatment of travelers' diarrhea: ciprofloxacin plus loperamide compared with ciprofloxacin alone. A placebo-controlled, randomized trial.

OBJECTIVE: To compare the safety and efficacy of loperamide used in combination with ciprofloxacin or ciprofloxacin alone for the treatment of travelers' diarrhea. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: United States Army hospital in Egypt. PARTICIPANTS: United States military personnel with travelers' diarrhea (n = 104) during a military exercise in November 1989. Persons who were noncompliant, had bloody diarrhea, or had received antidiarrheal medications before entry into the study were excluded. INTERVENTIONS: All participants with travelers' diarrhea were treated with ciprofloxacin, 500 mg twice daily for 3 days. Fifty of these patients were randomly assigned to receive loperamide, a 4-mg first dose and 2 mg for every loose stool (as much as 16 mg/d), and 54 were randomly assigned to receive placebo. MEASUREMENTS: Enterotoxigenic Escherichia coli was isolated from 57% of patients; Shigella and Salmonella, seen in 4% and 2% of patients, respectively, were not common. MAIN RESULTS: After 24 hours, the symptoms of 82% of patients in the ciprofloxacin and loperamide group compared with 67% in the ciprofloxacin and placebo group had improved or fully recovered (odds ratio, 2.3; 95% CI, 0.8 to 6.3; P = 0.08). After 48 hours, the symptoms of 90% of both groups had improved or fully recovered. The mean number of stools for those receiving loperamide was not much lower than those who did not receive loperamide after 24 hours (1.9 +/- 0.2 [SE] compared with 2.6 +/- 0.2) or 48 hours (3.1 +/- 0.3 compared with 4.0 +/- 0.3) of treatment (P = 0.19). CONCLUSIONS: In a region where enterotoxigenic E. coli was the predominant cause of travelers' diarrhea, loperamide combined with ciprofloxacin was not better than treatment with ciprofloxacin alone. Loperamide appeared to have some benefit in the first 24 hours of treatment in patients infected with enterotoxigenic E. coli. Both regimens were safe.

Effects of cranial transcutaneous electrical nerve stimulation in normal subjects at rest and during psychological stress.

Some effects of sub-threshold sine-wave transcutaneous electrical nerve stimulation (TENS), passed between earlobe electrodes at a constant alternating current (AC) frequency of 100 Hertz (Hz), were investigated in 90 normal subjects after 30 minutes of treatment, and after 3 minutes of standardized mental stress (mental arithmetic) which immediately followed the 30 minute treatment. In a double-blind protocol, five groups received 1) active TENS during treatment and active TENS during stress; 2) active TENS during treatment and placebo TENS during stress; 3) placebo TENS during treatment and placebo TENS during stress; 4) placebo TENS during treatment and active TENS during stress; and 5) no treatment during both treatment and stress. Results showed significant reductions in systolic blood pressure, pulse rate and anxiety, but not in diastolic blood pressure or peripheral vascular tension, after 30 minutes of active TENS as compared to no treatment. No placebo TENS effect was observed. No significant differences were observed between active TENS; placebo TENS and no treatment in physiological or psychological response to the stress procedure. Results are discussed in terms of the applicability of this technique to the management of stress.

The effects of cranial TENS on measures of autonomic somatic and cognitive activity.

Peripheral and central nervous system effects of the cranial application of sub-threshold transcutaneous electrical nerve stimulation (TENS), of sinusoid waveform passed between earlobe electrodes at an AC frequency of 100 Hertz, were investigated. In a single-blind study, each of thirty healthy volunteer subjects was administered one 30 minute treatment of either active TENS, placebo TENS or no treatment. Pretreatment to post-treatment changes in measures of autonomic activity (blood pressure, pulse rate, peripheral vasomotor activity), somatic activity (skeletal muscle tension), and anxiety were evaluated. Significant reductions in systolic blood pressure (p less than .05), diastolic blood pressure (p less than .01), pulse rate (p less than .05), peripheral vasomotor activity (marginally significant: p less than .07) and anxiety (p less than .05) were observed subsequent to active. TENS as compared to both placebo TENS and no TENS. No significant placebo TENS effect was observed. Possible mechanisms of action of this form of cranial TENS on the peripheral and central nervous system are discussed.

Evaluation of 500- and 1,000-mg doses of ciprofloxacin for the treatment of chancroid.

A randomized, double-blind study was performed comparing ciprofloxacin in a 500-mg single dose with 1,000 mg (500-mg doses given 12 h apart) for the treatment of chancroid in Thailand. Haemophilus ducreyi was isolated from 87 (48%) of 180 men with a clinical diagnosis of chancroid. For men with ulcers that were culture positive for H. ducreyi, rates of cure were 100% in the 500-mg group and 98% in the 1,000-mg group. For men with ulcers that were culture negative for H. ducreyi, rates of cure were 93% in the 500-mg group and 96% in the 1,000-mg group. The MIC of ciprofloxacin for 50% of isolates among 85 isolates of H. ducreyi was 0.007 micrograms/ml (range, 0.002 to 0.03 micrograms/ml). No significant adverse effects were detected in either group. These data indicate that both of these treatment regimens are equally effective therapies for chancroid in Thailand.

Erythromycin-resistant Campylobacter infections in Thailand.

Erythromycin therapy was compared with no treatment in a prospective trial of acute diarrheal disease among 100 infants in an orphanage in Bangkok. Within 24 h of the onset of diarrhea, 50 children received erythromycin ethylsuccinate (40 mg/kg per day) in four divided doses for 5 days. Campylobacter jejuni isolated from 31, Campylobacter coli isolated from 21, and Shigella spp. isolated from 21 of 100 children were the most commonly recognized pathogens; use of a sensitive, nonselective method substantially increased Campylobacter isolation. Treatment with erythromycin had no effect on the duration of diarrhea caused by Campylobacter spp., Shigella spp., or other agents; 37% of the treatment group and 35% of the control group had diarrhea for 1 week. Of 23 Campylobacter strains isolated from the treatment group before treatment, 15 (65%) were resistant (MIC, greater than or equal to 8 micrograms/ml) to erythromycin. Among orphanage-acquired strains, 53% of 43 C. jejuni strains and 91% of 23 C. coli strains were resistant to erythromycin compared with 11% of 114 C. jejuni strains and 46% of 35 C. coli strains that were community acquired. Erythromycin resistance is common among Campylobacter strains in Bangkok, especially in an institutional setting, which may account for the lack of efficacy of erythromycin for treatment of acute diarrheal illnesses.

Application of different counting systems in measuring localised retention the entero-hepatic circulation.

The use of labelled bile salt retention is likely to be a major new technique in assessing the function of the terminal ileum. Papers to date have described two techniques to measure both the 100% and the seven-day retention values. These use whole body counters or uncollimated gamma cameras. We have compared the use of simple probe systems with an uncollimated gamma camera for the retention measurements. There was no significant difference in the results obtained with any of these systems. It is concluded that simple probe measurements can provide a precise and highly reproducible assessment of bile salt retention which greatly increases the availability of this test.