Efficacy, safety and immunological actions of butanol-extracted Food Allergy Herbal Formula-2 on peanut anaphylaxis.

BACKGROUND: Therapies for peanut allergy (PNA) are urgently needed. Food Allergy Herbal Formula-2 (FAHF-2) has profound therapeutic effects in a murine PNA model and is safe for food-allergic adults in clinical trials. However, the large FAHF-2 pill-load is not conducive to clinical studies in children. Thus, refining FAHF-2 to decrease pill-load is essential for the inclusion of children in clinical trials and to facilitate studying FAHF-2 as a clinically useful botanical drug. OBJECTIVES: Testing long-term efficacy and safety of a butanol-purified extract of FAHF-2 (B-FAHF-2) in a murine model of PNA, and to explore its immunological mechanisms of action. METHODS: FAHF-2 was purified by butanol extraction. C3H/HeJ mice with established PNA received the first course of B-FAHF-2 at 6 mg, twice daily for 7 weeks (PNA/B-FAHF-2) or water (PNA/sham) and were then challenged immediately after completing the treatment and six more times every 1-2 months post-treatment up to week 50. Mice then received a second course of B-FAHF-2 treatment at week 52 and were challenged at week 65. In vivo and in vitro immunological effects on T, B and mast cells were also determined. RESULTS: Butanol purification reduced the volume of the effective dose ∼5-fold. All PNA/B-FAHF-2 mice were completely protected from PN anaphylaxis until the fifth challenge after the first course of treatment, as compared with PNA/sham mice. Partial protection persisted up to 50 weeks. A second treatment course restored complete protection. B-FAHF-2 significantly suppressed Th2 cytokine, IgE and histamine levels in vivo, and showed direct inhibition of Th2, IgE-producing B cells and mast cell activation in vitro. B-FAHF-2 had a high margin of safety. CONCLUSION AND CLINICAL RELEVANCE: B-FAHF-2 produced long-lasting protection against PN anaphylaxis for approximately half of the murine life span without side-effects. B-FAHF-2 exhibited direct effects on multiple food allergy effector cells.

Evidence of 'genuine empty follicles' in follicular aspirate: a case report.

Failure to retrieve oocytes after normal ovarian stimulation has been labeled 'empty follicle syndrome' (EFS). The existence of genuine EFS has been questioned and is still controversial. Here, we report an unusual case in which an extraordinary number of empty follicle-like structures were identified in the ovarian aspirate at the time of retrieval. A 31-year-old woman presented with a 4-year history of primary infertility and underwent ovulation induction. The patient was given hCG and oocyte retrieval was performed 36 h later. During the oocyte retrieval, more than 200 tiny structures resembling pre-antral follicles were noted in the ovarian aspirate. They exhibited two to three layers of granulosa cells and appeared to enclose an immature oocyte. They showed a great variation in size ranging between 40 and 80 microm. These structures were further characterized by electron microscopy and cultivated in vitro to assess hormone secretion. The follicles were found to be devoid of oocytes, but each had a readily identifiable zona. Hormone assays revealed that these follicles were secreting increasing levels of estradiol. A second in vitro fertilization attempt gave similar results. These data are suggestive of some failure in the oocyte maturation process. We speculate that this may be the first actual evidence to support the existence of true empty follicles, which if left to grow in vivo might lead to empty graffian follicles and genuine EFS.

Non-isotopic polymerase chain reaction methods for the detection of HIV-1 in Ugandan mothers and infants.

Two non-isotopic polymerase chain reaction (PCR) methods were evaluated by testing blood from 41 HIV-1-seropositive and 16 HIV-1-seronegative Ugandan mothers and 56 of their children (aged 0.5-15.0 months). Amplification of HIV-1 sequences was performed in duplicate using a biotinylated primer pair to the gag region (SK 462-431) and nested primer pairs (JA 17-20) to the pol region of HIV-1. gag sequences were hybridized using a microtiter plate coated with the SK 102 probe followed by colorimetric detection using an avidin-horseradish peroxidase conjugate and tetramethylbenzidine/peroxide substrate. pol sequences were detected on agarose gel stained with ethidium bromide. Results of HIV-1 PCR analysis showed that 40 out of 41 (98%) seropositive mothers and 10 out of 29 (34%) seropositive children had detectable HIV-1 gag and pol sequences. None of the 16 seronegative mothers nor 27 seronegative or Western blot-indeterminate children had detectable HIV-1 sequences. Our results suggest that non-isotopic PCR methods are sensitive, specific, and potentially useful in the early diagnosis of HIV-1 infection in developed and developing countries.

Electrophysiologic studies of serotonin receptor activation. Answered and unanswered questions.

Cellular electrophysiologic responses to serotonin and serotonin agonists in vertebrate neurons and cell cultures derived from neuronal or neuroblastoma x glioma hybrids are reviewed. Emphasis is on local rather than systemic drug administration, and on intracellular and patch clamp recording. Activation of serotonin receptors can open and close potassium channels, reduce voltage-dependent calcium currents and calcium-activated potassium currents, enhance hyperpolarization-activated cation currents, and open ligand-gated cation channels. The pharmacology of these responses is described and the assignment of serotonin receptor subtypes discussed. The review is selective rather than inclusive and was concluded in November 1989.

Kinetics of response and drug action.

Vascular smooth muscle tone is modulated in vivo by the functional interaction of a variety of vasoconstrictor and vasodilator stimuli. Endogenous substances (e.g., epinephrine) acting on smooth muscle, simultaneously activate alpha-adrenergic receptors (alpha-AR) eliciting contraction and beta-adrenergic receptors (beta-AR) which relax the muscle. This study characterizes the beta-adrenergic response in the isolated rabbit aorta precontracted with phenylephrine (PE) or serotonin (5-hydroxytryptamine [5-HT]). The beta-adrenergic agonist isoproterenol (ISO) produces a biphasic response that is composed of a rapid relaxation followed by a slower regaining of tension identified as desensitization. An exploratory kinetic model that describes both relaxation and desensitization as first order processes provides a good description of the experimental data. The five parameters used to describe the ISO response are: the observed rate constants for relaxation and desensitization (krel and kdes), the fractional magnitudes of the changes in tension for the two processes (R/C) and D/R), and the observed delay in the onset of the desensitization response, td. The krel and R/C were dependent on concentration of ISO in a saturable manner in rings precontracted with either 1 mumol/L PE or 1 mumol/L 5-HT and inversely related to the concentration of the contractile agonist. Yet, although the degree of fractional relaxation in the presence of PE covered the full range, that of 5-HT extended over a range of 20%. This behavior leads to the conclusion that the functional interaction between the contractile and relaxing stimuli is non additive. No dependence on the concentration of ISO was observed for D/R, kdes, and td.(ABSTRACT TRUNCATED AT 250 WORDS)

Ciprofloxacin monotherapy for acute pulmonary exacerbations of cystic fibrosis.

Ciprofloxacin has potent in vitro activity against Pseudomonas aeruginosa and Pseudomonas cepacia strains isolated from cystic fibrosis patients. Our previous single-dose pharmacokinetic and pharmacodynamic studies identified important differences between cystic fibrosis patients and age- and sex-matched controls. Based on these data, 30 acutely ill cystic fibrosis patients (aged 18 to 44 years) received 750 mg of ciprofloxacin orally every eight hours for 21 days. Multiple timed serum, urine, and sputum samples for pharmacokinetic analysis were obtained on Days 3, 12, 14, and 21 of the study. Estimates of steady-state pharmacokinetic parameters averaged (+/- SD): t1/2 beta, 3.8 (1) hours; Vd/F, 4.4 (2) liters/kg; Cl/F, 772.9 (301) ml/minute/1.73 m2; Fe, 46 percent; peak, 5.4 (2) mg/liter; and trough, 1.8 (0.8) mg/liter. Serum ciprofloxacin concentrations and pharmacokinetic estimates remained unchanged throughout the study. Sputum ciprofloxacin concentrations exceeded those observed in serum. Sputum cultures revealed 43 P. aeruginosa (MIC90 = 2 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml) strains. Sputum ciprofloxacin concentrations exceeded the MIC90 for P. aeruginosa approximately fivefold, yet only eight isolates were fully suppressed. Posttreatment sputum cultures revealed 35 P. aeruginosa (MIC90 = 16 micrograms/ml) and 15 P. cepacia (MIC90 = 16 micrograms/ml). All patients showed clinical improvement based upon the results of pulmonary function tests and an acute clinical efficacy score (median pre 49/post 60). No patients experienced drug-related toxicity. Ciprofloxacin monotherapy is effective for the acute treatment of cystic fibrosis patients. The development of pathogen resistance during oral therapy may limit its utility in ambulatory patients.

The penetration of gentamicin into the vitreous humor in man.

Twenty-two patients received gentamicin intramuscularly or subconjunctivally 35-220 min prior to undergoing ocular surgery. There were no detectable gentamicin levels in the vitreous humor of patients who received the drug systemically. Of the patients who received gentamicin subconjunctivally, three quarters had no detectable gentamicin levels, only three of these patients had therapeutic concentrations in their vitreous humor. These results confirm kinetic drug studies performed in animals in which low or absent vitreal gentamicin levels were observed following systemic and subconjunctival administrations. It is suggested that intravitreal injection of aminoglycosides is required in the treatment of bacterial endophthalmitis.

HIV vertical transmission rate determinations are subject to differing definitions and therefore different rates. The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection Study Group.

The HIV infection status of a cohort of 600 prospectively followed children born to HIV infected mothers was determined using HIV peripheral blood culture tests at 0, 3, and 6 months of age, HIV serology at > or = 15 months, and CDC AIDS criteria. We estimated transmission rates using five methods which differed in how HIV indeterminates are handled. These methods were applied at two points in time to illustrate effects of length of follow-up of the cohort on results. In January 1997, 30 months after the last birth, transmission rate estimates ranged from 15.5% (known positives/known positives x known negatives) to 18.1% (known positives x those with one positive culture x deaths/entire cohort minus those lacking negative cultures at age > or = 5 months). Estimates ranged from 14.8% to 20.7% using the subcohort of 284 children followed > or = 12 months as of May 1993. These results indicate that methods for assigning HIV infection status and for handling HIV indeterminates should be carefully defined when estimating transmission rates.

Comparison study of the immunogenicity and safety of 5- and 10-microgram dosages of a recombinant hepatitis B vaccine in healthy children.

OBJECTIVE: To compare the immunogenicity and safety of 5 micrograms with 10 micrograms of Engerix-B recombinant hepatitis B vaccine when given to healthy children, 2 to 6 years of age. METHODS: Randomized multicenter study of serongative children 2 to 6 years of age who received Engerix-B hepatitis B vaccine either 5 micrograms/0.25 ml or 10 micrograms/0.5 ml (the current Food and Drug Administration-approved dosage of Engerix-B in children) at 0, 1 and 6 months. Serum was obtained at 1, 3, 6 and 8 months after the first vaccine dose was given for antibody measurement. RESULTS: A total of 223 subjects were screened and received the first dose of vaccine. Of these subjects 193 continued in the study. Both dosages proved to be highly immunogenic, producing high seroconversion and seroprotection rates and geometric mean antibody to hepatitis B surface antigen concentrations after 3 doses. The geometric mean concentrations of seroconverters at Months 6 and 8 were significantly greater for the 10-micrograms group compared with the 5-micrograms group. Both dosages were well-tolerated and no serious adverse events were reported. CONCLUSIONS: There was a significant reduction in geometric mean concentrations on lowering the dosage of Engerix-B from 10 to 5 micrograms in children 2 to 6 years of age. Although a high seroprotection rate was elicited by the 5-micrograms dose, the lower antibody concentrations achieved may make this lower dosage less desirable in the long term. Further studies are required to examine the need for booster doses of vaccine with both dosing schedules.

Ceftibuten vs. penicillin V in group A beta-hemolytic streptococcal pharyngitis. Members of the Ceftibuten Pharyngitis International Study Group.

The efficacy and safety of a 10-day course of ceftibuten oral suspension (9 mg/kg once daily) were compared with those of penicillin V (25 mg/kg/day in 3 divided doses) in children 3 to 18 years old treated for symptomatic pharyngitis and scarlet fever caused by group A beta-hemolytic streptococci (Streptococcus pyogenes). The study was prospective, randomized, multicenter and investigator-blinded; patients were randomized in a 2:1 ratio (ceftibuten:penicillin V). Overall clinical success (cure/improvement) at the primary end point of treatment (5 to 7 days posttherapy) was achieved in 97% (285 of 294) of ceftibuten-treated patients vs. 89% (117 of 132) of penicillin V-treated patients (P < 0.01). Elimination of infecting streptococci 5 to 7 days posttherapy was achieved in 91% (267 of 294) of ceftibuten-treated patients vs 80% (105 of 132) of penicillin V-treated patients (P < 0.01). A significant rise in anti-streptolysin O or anti-DNase B was observed in approximately 30% of patients in both treatment groups. No patient developed rheumatic fever or nephritis. Treatment-related adverse events were similar between the two groups; mild vomiting (2%) was most frequently reported. These data suggest that once daily ceftibuten is as safe as and more effective than three times daily penicillin V for the treatment of group A beta-hemolytic streptococcal pharyngitis.

Comparison study of the immunogenicity and safety of 5- and 10-microgram dosages of a recombinant hepatitis B vaccine in healthy infants.

BACKGROUND: It has been suggested that lower dosages of hepatitis B vaccine may be adequate for vaccinating infants and would be less costly. OBJECTIVES: To compare the immunogenicity and safety of 5 and 10 micrograms of Engerix-B recombinant hepatitis B vaccine given to healthy infants. METHODS: A prospective randomized comparison of 5- and 10-micrograms doses of Engerix-B recombinant hepatitis B vaccine given to infants at 2, 4 and 6 months of age. Seroconversion (antihepatitis B surface antigen (anti-HBs) > or = 1 mIU/ ml) and seroprotection (anti-HBs > or = 10 mIU/ml) rates as well as geometric mean antibody titers were compared at 4, 6 and 8 months. RESULTS: A total of 190 healthy infants were screened and received the first dose of vaccine. Of these infants 153 were eligible to continue in the study. Both dosages proved to be highly immunogenic, producing high seroconversion and seroprotection rates and geometric mean anti-HBs concentrations after 3 doses. Although 10 micrograms induced significantly greater geometric mean concentrations (1641 mIU/ml compared 880 mIU/ml at 8 months of age), the seroprotection rates were identical (98.5%). CONCLUSIONS: Both dosages were well-tolerated and no serious adverse experiences were reported. However, the 5 micrograms of Engerix-B administered at 2, 4 and 6 months of age did not induce as great an anti-Hbs concentration as did 10 micrograms. Long term studies are required to determine whether using the lower dosage would sacrifice long term efficacy.

Comparative study of the immunogenicity and safety of two dosing schedules of Engerix-B hepatitis B vaccine in neonates.

A randomized multicenter study compared the routine hepatitis B vaccine schedule of 0, 1, 6 months with an accelerated schedule of 0, 1, 2 months in newborns. Two hundred ninety-nine infants whose mothers were seronegative for hepatitis B were enrolled in the study and randomized to either the routine or accelerated schedule. All infants had blood drawn for antibody titers to hepatitis B at 2, 3, 6 and 7 months of age. For 222 infants data were evaluable, at least for safety; 193 of these 22 had antibody titers that were evaluable. The infants vaccinated on the accelerated schedule developed seroprotective concentrations of antibody more quickly than the infants vaccinated on the routine schedule; 92.6% vs. 66.1% had seroprotective concentrations (> or = 10 mIU/ml) at 3 months of age (P < 0.001). However, infants in the accelerated schedule had lower geometric mean antibody titers at 7 months, 420.0 vs. 3141.8. We conclude that the accelerated vaccination schedule resulted in the more rapid development of seroprotective concentrations of antibody, but levels of antibodies were not as high as in the routinely vaccinated infants at 7 months. These data suggest that an accelerated vaccine schedule can be used in the newborn period. The effectiveness of the accelerated schedule in preventing perinatal infections compared to the standard schedule and the necessity for booster doses of vaccine remain to be studied.

The effect of echothiophate on the biphasic response of rabbit ocular pressure to dipivefrin.

A time-course study was performed on the intraocular pressure response of pigmented rabbit eyes. Dipivefrin administration produced in initial hypertensive phase lasting less than two hours followed by a prolonged hypotensive phase. Echothiophate iodide therapy produced a more pronounced and prolonged hypertensive response; there was no hypotensive phase. Administration of echothiophate plus dipivefrin resulted in a hypertensive phase similar to that from echothiophate alone; as previously reported, this combination was not followed by a hypotensive phase. The alpha-blocker phentolamine mesylate prevented the echothiophate-induced hypertension. When dipivefrin was administered with echothiophate plus phentolamine, there was an immediate hypotensive effect. It was concluded that the hypertensive effect of echothiophate in pigmented rabbit eyes may mask the hypotensive action of dipivefrin. This, rather than an echothiophate-induced inhibition of esterases, may explain why combination therapy with these drugs seemed ineffective.

Pleiotropic behavior of 5-HT2A and 5-HT2C receptor agonists.

There is now considerable evidence that a single receptor subtype can couple to multiple effector pathways within a cell. Recently, Kenakin proposed a new concept, termed "agonist-directed trafficking of receptor stimulus", that suggests that agonists may be able to selectively activate a subset of multiple signaling pathways coupled to a single receptor subtype. 5-HT2A and 5-HT2C receptors couple to phospholipase C-(PLC) mediated inositol phosphate (IP) accumulation and PLA2-mediated arachidonic acid (AA) release. Relative efficacies of agonists (referenced to 5-HT) differed depending upon whether IP accumulation or AA release was measured. For the 5-HT2C receptor system, some agonists (e.g. TFMPP) preferentially activated the PLC-IP pathway, whereas others (e.g. LSD) favored PLA2-AA. As expected, EC50's of agonists did not differ between pathways. For the 5-HT2A receptor system, all agonists tested had greater relative efficacy for PLA2-AA than for PLC-IP. In contrast, relative efficacies were not different for 5-HT2A agonists when sequential effects in a pathway were measured (IP accumulation vs. calcium mobilization). These data strongly support the agonist-directed trafficking hypothesis.

Evaluation of immune survival factors in pediatric HIV-1 infection.

Peripheral blood CD4+ and CD8+ T cells, CD19+/20+ B cells, and serum immunoglobulins (Igs) have been implicated as survival factors for pediatric HIV-1 infection. To determine which of these immune factors might be important in predicting survival, we studied HIV-1 vertically infected (HIV-1+) children over a 5-year period. Peripheral blood lymphocytes and Igs were measured in 298 HIV-1+ children, who were classified as survivors or nonsurvivors, and in 463 HIV-1 vertically exposed and noninfected (HIV-1-) children. Measurements of other possible survival factors were included in this study: albumin, hemoglobin, lactic dehydrogenase (LDH), and HIV-1 RNA levels. Survivors had significantly higher CD4+ T-cell, CD8+ T-cell, and CD19+/CD20+ B-cell counts and serum IgG levels, but lower serum IgA and IgM levels than nonsurvivors. Serum albumin and blood hemoglobin levels were higher, but serum LDH and HIV-1 RNA levels were lower in the survivors compared to nonsurvivors. In univariable analysis, factors affecting survival were baseline CD4+ T-cell and CD8+ T-cell counts, IgG, albumin, hemoglobin, LDH, and HIV-1 RNA (all p < 0.001). In multivariable analysis, high baseline CD4+ T-cell count, IgG and albumin levels, and low baseline HIV-1 RNA load remained important factors for survival. Serum IgG level has been identified as an immune factor that independently predicts survival, in addition to the already established CD4+ T-cell count. The HIV-1 RNA and serum albumin levels also predicted survival.

Cost-effectiveness of in vitro fertilization.

OBJECTIVE: To estimate the cost per woman delivered of pregnancies from an in vitro fertilization (IVF) program, and to assess what factors contribute to the cost. METHODS: The cost during 2 years' experience of a single IVF program was analyzed retrospectively. Cost analysis included cost of the IVF procedure itself as well as costs incurred because of maternal and neonatal complications. RESULTS: The major contributor to the total cost of IVF was high-order multiple pregnancies. The cost per woman delivered of singleton or twin pregnancies was approximately $39,000, whereas the cost per woman delivered of triplet and quadruplet pregnancies was approximately $340,000. CONCLUSION: In vitro fertilization can be cost-effective if steps are taken to minimize high-order multiple (triplet or more) pregnancies.

Salt therapy in pregnancy complicated by chronic renal disease.

A case is presented of a woman with severe chronic renal disease who developed evidence of salt wasting during pregnancy. Restoration of renal function and a successful pregnancy outcome were achieved through the use of large quantities of oral and intravenous salt supplementation, together with oral bicarbonate.

Cost analysis of shared oocyte in vitro fertilization.

OBJECTIVE: To estimate the cost per woman delivered of a shared oocyte in an in vitro fertilization (IVF) program, and to compare these costs with those of a routine IVF program. METHODS: The cost of 23 shared oocyte cycles was analyzed retrospectively and compared with the cost of routine IVF. RESULTS: The cost per woman delivered in the shared oocyte program was approximately $22,000, compared with $66,000 in the routine IVF program. CONCLUSION: Shared IVF is a very cost-effective program and others donors and recipients an otherwise unavailable opportunity.

Elevated interleukin-6 levels in the ovarian hyperstimulation syndrome: ovarian immunohistochemical localization of interleukin-6 signal.

OBJECTIVE: To examine the production and immunolocalization of interleukin-6 (IL-6) in patients with the ovarian hyperstimulation syndrome. METHODS: The study group consisted of patients with ovarian hyperstimulation syndrome (n = 9) from whom serum and ascites samples were obtained. The control samples used were serum (n = 10) and peritoneal (n = 16) and follicular fluids (n = 8) from healthy individuals. Follicular fluid (n = 40) and serial serum samples were also obtained from patients undergoing menotropin stimulation for in vitro fertilization (IVF) before (n = 10) and after ovulation (n = 34). Interleukin-6 measurements were performed with a sensitive immunoassay and confirmed with a bioassay. Immunohistochemical localization of IL-6 was performed with a mouse monoclonal antibody in normal premenopausal (n = 5) and postmenopausal ovaries (n = 5), as well as with cells from stimulated follicular fluid aspirates (n = 3). RESULTS: We found significantly higher serum and ascites IL-6 levels in ovarian hyperstimulation syndrome (mean 18.8 +/- 1.1 and 810.8 +/- 60.7 pg/mL, respectively) compared with postovulatory serum and peritoneal fluid from normal controls (mean 4.4 +/- .69 and 44.7 +/- 7.5 pg/mL, respectively) (P < .001) or serum after menotropin stimulation (13.1 +/- 1.1 pg/mL) (P < .001). At the time of ovulation, follicular fluid IL-6 levels (normal controls, mean 9 +/- 2.1 pg/mL; menotropin stimulation, mean 10.1 +/- 4 pg/mL) were higher than in preovulatory serum (normal controls, mean 4.5 +/- .8 pg/mL; menotropin stimulation, mean 6.3 +/- 1.4 pg/mL) (P < .001). Immunohistochemical localization of IL-6 revealed intense staining in corpora lutea and theca cells from large antral follicles and luteinized granulosa cells in follicular aspirates after menotropin stimulation. CONCLUSION: Interleukin-6 levels are markedly elevated in the ovarian hyperstimulation syndrome when compared with controls. The higher follicular fluid IL-6 levels seen suggest local secretion of this cytokine. Immunohistochemical correlation demonstrated IL-6 within ovarian theca cells. These findings suggest a local role for IL-6 both in normal and stimulated ovarian function. Whether IL-6 is directly responsible for the clinical manifestations of this syndrome is unclear. However, when produced in massive amounts, the pro-inflammatory effects of IL-6 may contribute to its pathogenesis and perhaps serve as a marker for the disease.

Single-dose pharmacokinetics of oral ciprofloxacin in patients with cystic fibrosis.

The single-dose pharmacokinetics of oral ciprofloxacin were studied in ten patients with cystic fibrosis aged 18 to 34 years. Each patient received three different drug doses (500 mg, 750 mg, and 1,000 mg) at successive one-week intervals. Dosing and drug assays were double blinded. Blood and urine were assayed over the 48 hours following each dose. Ciprofloxacin was absorbed from the gastrointestinal tract. Peak serum concentrations averaged 2.8, 4.5, and 4.6 micrograms/mL respectively at the three doses, well above the mean inhibitory concentrations of most isolates of Pseudomonas aeruginosa. Time to peak concentration was approximately two hours. The range of sputum levels in three patients was 1.1-2.1 micrograms/mL at four hours after the three doses. The serum elimination half-life was 3.7 hours and was independent of dose. Urinary recovery was 26%; greater than 90% of urinary excretion occurred within the first 12 hours. The results of this study indicate that ciprofloxacin has potential for use in the treatment of P aeruginosa infections in patients with cystic fibrosis.