Combined use of ciprofloxacin and sucralfate.

The effect of sucralfate on the bioavailability of ciprofloxacin hydrochloride was assessed in 12 healthy male volunteers. The study was a four-period crossover design where subjects were randomized to one of four treatment sequences at entry. Treatments A, B, and C included sucralfate 2 g q12h for five doses. For treatment A, the fifth dose sucralfate was administered concurrently with ciprofloxacin 750 mg. For treatment B, 750 mg of ciprofloxacin was administered two hours before the fifth dose of sucralfate. Treatment C consisted of ciprofloxacin 750 mg six hours before the fifth dose of sucralfate. A 750-mg dose of ciprofloxacin was administered alone for treatment D. Blood and urine samples were collected at predetermined time intervals for 24 hours. Ciprofloxacin concentrations were determined by HPLC. The area under the concentration versus time curve from zero to infinity and the urinary recovery of ciprofloxacin were used for determining relative bioavailability. Concurrent administration of ciprofloxacin and sucralfate (treatment A) resulted in a significant decrease (p less than 0.05) in ciprofloxacin absorption. The relative bioavailabilities for treatments A, B, and C were 0.0429 +/- 0.0202, 0.829 + 0.21, and 0.965 + 0.32, respectively, relative to ciprofloxacin alone. In normal volunteers, ciprofloxacin may be administered between two and six hours before sucralfate, allowing sufficient time for ciprofloxacin absorption prior to the sucralfate dose and thereby minimizing the chance of a significant interaction. In patients with decreased gastric emptying the interaction may be more difficult to avoid.

The effect of sucralfate pretreatment on the pharmacokinetics of ciprofloxacin.

Based on the results of our study of norfloxacin-sucralfate coadministration, we suspected that sucralfate would interact also with ciprofloxacin if the drugs were administered concurrently. Therefore, we decided to give a 1-g dose of sucralfate at 6 and 2 hours before a single 750-mg dose of ciprofloxacin and evaluate its effect on the bioavailability of ciprofloxacin. Twelve healthy, male volunteers received ciprofloxacin alone and with sucralfate pretreatment in a randomized, balanced, crossover design. Blood and urine samples were collected over 24 hours after ciprofloxacin administration, and drug concentrations were assayed by high-performance liquid chromatography. When sucralfate was given at 6 and 2 hours before ciprofloxacin, an average 30% decrease in ciprofloxacin's bioavailability was noted (p less than 0.05). Four of the 12 subjects, however, had decreases in the agent's area under the curve of more than 50% with sucralfate pretreatment. The results of this study suggest that ciprofloxacin and sucralfate should not be administered concurrently until a dosing interval is found that will avoid this potential interaction.

Sucralfate reduces the gastrointestinal absorption of norfloxacin.

The effect of sucralfate on the bioavailability of norfloxacin after single 400-mg doses of norfloxacin was evaluated in eight healthy males. Subjects received each of the following treatments in random sequence: (i), norfloxacin, 400 mg alone; (ii) sucralfate, 1 g, concurrently with norfloxacin, 400 mg; and (iii) sucralfate, 1 g, followed by norfloxacin, 400 mg, 2 h later. One day before administration of treatments 2 and 3, 1 g of sucralfate was given at 7 a.m., 11 a.m., 5 p.m., and 10 p.m. Blood samples were collected immediately before the norfloxacin dose and at 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 6, 8, 12, and 24 h postdose. Urine was collected in divided intervals: from 0 to 12, from 12 to 24, and from 24 to 48 h. Norfloxacin concentrations in plasma and urine were determined by high-performance liquid chromatography. Mean area under the plasma concentration-versus-time curve extrapolated to infinity decreased significantly (P less than 0.001) after norfloxacin was given with and 2 h after sucralfate. The relative bioavailabilities were 1.8% when norfloxacin was taken with sucralfate and 56.6% when it was taken 2 h after sucralfate. After norfloxacin was given alone, the mean norfloxacin concentrations in urine collected during intervals of 0 to 12, 12 to 24, and 24 to 28 h were 118.9 +/- 72.3, 18.8 +/- 12.5, and 2.4 +/- 2.2 micrograms/ml, respectively. After norfloxacin was given with sucralfate, however, the mean norfloxacin concentrations in urine collected during the same time intervals were 6.8 +/- 4.7, 1.8 +/- 1.4, and 0 +/- 0 microgram/ml, respectively. Because of low pH and relatively high magnesium concentration in urine, susceptibilities of bacteria in urine are 8- to 32-fold lower than in broth. This fact, in combination with the reduced bioavailability of norfloxacin in the presence of sucralfate or antacids, is likely to result in treatment failure. The effect of sucralfate given after norfloxacin was not examined, nor was the effect of sucralfate given more than 2 h before norfloxacin. Administration or norfloxacin with sucralfate should therefore by avoided.

Reconstruction of penile agenesis by a posterior sagittal approach.

Penile agenesis is a rare condition requiring gender reassignment and staged perineal reconstruction. This report describes two children reconstructed by taking advantage of the posterior sagittal approach. This approach allows a precise anatomic dissection, construction of a neovagina and accurate positioning of all perineal orifices. We think that this is the preferred approach for this rare condition.

Long-term functional results of urinary tract reconstruction in childhood.

When reviewing the important long-term parameters of urinary tract reconstruction in childhood, one must consider the protection of renal function, maintenance of social continence and freedom from urinary tract infection as paramount. The 3-year assessment of 25 patients who underwent urinary tract reconstruction for a variety of underlying conditions is presented in terms of renal function, social continence and urinary tract sterility. The underlying pathological condition in our patients was weighted toward children with obstructive uropathy rather than neurogenic vesical dysfunction, and the most common form of diversion was an ileal conduit. Maintenance of renal function was achieved in 21 of our 25 patients (84 per cent). All 8 children (100 per cent) who underwent reconstruction for neurogenic vesical dysfunction have maintained preoperative renal function, while only 12 of the 17 children originally diverted for obstructive uropathy (75 per cent) have done well with reconstruction. Social continence with or without intermittent catheterization has been achieved in 23 of the 25 patients (92 per cent) and sterile urine has been maintained in 22 of the 25 patients (88 per cent). Factors involved in the success or failure of reconstruction are discussed, and observations toward future selection are made from this data base.

An apparent small cluster of choroidal melanoma cases.

Three choroidal melanomas were detected in a 2.5-year period in a small community of 3,592 persons. This small cluster represented an incidence about 20 times that expected (P = .0006). The community has an isolated water supply and very little industry. We determined the incidence of cancer in this and two adjacent communities and found no other unexpectedly high incidence. The three patients had no common exposures. Analyses of air and water from the involved community by mass spectroscopy, chromatography, and Ames (mutagenicity) tests were noncontributory. Nine of 60 mice given community water after weaning developed lens opacities eight to 16 months later; electron microscopy showed an abnormal monolayer of cells on the outer surface of the anterior lens capsule. The genesis of this monolayer was not clear. None of the 30 controls showed such lesions.

Urinary undiversion in adults.

At our medical center 7 adult patients with various types of urinary diversion have undergone total reconstruction during a 3-year period. Followup has ranged from 12 to 36 months. Initial pathological conditions included 3 patients with obstruction, 3 with myelodysplasia and associated incontinence, and 1 with massive vesicoureteral reflux. Thorough radiologic, endoscopic and urodynamic evaluation, as well as physiologic testing after vesical hydrodistension, allows careful preoperative selection of reconstruction candidates. Followup studies, including excretory urography and voiding cystourethrography at 3 and 12 months, as well as monthly urine cultures during the first year, have shown that 5 of the 7 patients (71 per cent) are free of vesicoureteral reflux. Two patients have persistent reflux after reconstruction and sterile urine cultures on antibiotic suppression. Renal function has been maintained in 5 of the 7 reconstructed patients (71 per cent) and social continence has been achieved in all 7, including 3 who have achieved social continence by means of clean intermittent catheterization.

The ureteral "J" sign: radiographic demonstration of iatrogenic distal ureteral obstruction after ureteral reimplantation.

Progressive caliceal and ureteral dilatation in postoperative patients is assumed to be secondary to either postoperative distal ureteral stricture or ureteral atony. Any study used to differentiate obstruction from atony must be done with an awareness of the effect of a full bladder on the upper tracts, since it can by itself produce varying degrees of ureteral dilatation. We describe 2 patients who had virtually complete distal ureteral obstruction on anterograde pyelography with a "J" shaped distal ureteral segment. The striking observation was that the deformity and associated distal ureteral obstruction could be made to appear and disappear at will, merely by distending or emptying the bladder. We believe that this is an important factor in the progressive dilatation, as well as in the observed deterioration of renal function, and it is properly regarded as an iatrogenic complication.

Visual urethrotomy in management of male urethral duplication.

Anatomically, three types of urethral duplication have been described: Type I or complete urethral duplication, Type II which includes multiple variations of bifid urethra, and Type III, those urethral duplications with a perineal opening. A new, simplified approach to the management of some Type II urethral duplications is described, using the pediatric cold-knife visual urethrotome. This technique provides a maximally patent urethra, while removing the site of chronic refractory infection, and minimizing both morbidity and patient hospitalization. Alternatives for treatment of Type I and Type III urethral duplications also are discussed.

Carcinoma of gallbladder simulating metastatic prostatic cancer.

This is a case of carcinoma of the gallbladder, which clinically, chemically, and radiographically simulated metastatic prostate cancer. Other causes of elevated serum and bone marrow acid phosphatase and axial skeletal osteoblastic metastases are reviewed.