Effects of ofloxacin administration on the reliability of urine glucose testing.

OBJECTIVE: To study the effects of ofloxacin on the reliability of urine glucose testing. DESIGN: Open-label, nonrandomized. SETTING: A university-affiliated tertiary care hospital, ambulatory clinic. PARTICIPANTS: Ten healthy volunteers (8 men and 2 women) aged 22-39 years. MAIN OUTCOME MEASURES: Phase I (in vitro) involved the addition of selected amounts of ofloxacin to a set of standard 50-mL urine samples prepared to simulate glycosuria. Phase II (in vivo) involved the oral administration of ofloxacin 400 mg to 10 subjects. Urine was collected: (1) immediately predose, (2) pooled 0-4 hours postdose, and (3) pooled 4-8 hours postdose. Known glucose concentrations were then added to these samples. Clinitest and Diastix tests were performed on all samples. The accuracy of these tests in determining glucose concentrations was compared among urine samples taken before and after ofloxacin dosing. RESULTS: None of the ofloxacin concentrations in phase I (0, 25, 50, 100, 200, 400, and 800 micrograms/mL) influenced these testing methods at the urine glucose concentrations of 0.0%, 0.5%, 1%, and 2%. Likewise, the accuracy of these two tests was unaffected by ofloxacin administration in phase II. CONCLUSIONS: In single-dose administration, ofloxacin does not interfere with Clinitest or Diastix for determining urine glucose concentrations.

A fluorimetric liquid chromatographic method for the determination of propranolol in human serum/plasma.

A simple, rapid, and sensitive fluorimetric-high-performance liquid chromatographic method for the determination of propranolol in human serum/plasma has been developed, without the need for solvent extraction. The procedure required 200 microliters of serum/plasma, and the addition of 1 ml of acetonitrile for protein precipitation followed by vortexing and centrifugation at 10 000 g. The clear supernatant was evaporated to dryness under a stream of nitrogen at 50-60 degrees C, the residue was reconstituted in 100 microliters of methanol, and a 90 microliters portion was injected onto the high-performance liquid chromatograph for propranolol quantitation. Chromatography was accomplished using a Hypersil cyano column, a mobile phase of acetonitrile-aqueous acetic acid (1%) containing 0.2% triethylamine (35:65, v/v) (pH 3.6), a flow rate of 1.5 ml min-1, a fluorescence detector set at an excitation wavelength of 230 nm and an emission wavelength of 340 nm, and using pronethalol as the internal standard. Retention times for pronethalol and propranolol were 7.5 min and 9.5 min, respectively. Standard curves were linear in the range 5-200 ng ml-1. Relative standard deviations for both inter-day and intra-day precision analysis were less than 7% for serum. No interference was observed from endogenous serum/plasma components. Specificity was shown for some, but not all, commonly coadministered drugs tested. The advantages of this method include good precision, low sample volume, good reproducibility and recovery, and high sensitivity.

Crossover comparison of drug information online database vendors: Dialog and MEDLARS.

OBJECTIVE: To compare Dialog EMBASE with the National Library of Medicine's (NLM's) MEDLARS MEDLINE, TOXLINE, and TOXLIT to evaluate differences among the databases and vendors in a method consistent with routine drug information practice. DESIGN: Crossover comparison. METHODS: NLM MEDLARS databases MEDLINE, TOXLINE, and TOXLIT were searched directly. EMBASE was searched via Dialog Information Services. MEDLINE was searched back to 1980; TOXLINE and TOXLIT were searched back to 1981, reflecting the different database structures. EMBASE was searched back to 1980. To control bias, searches were randomized; identical strategies were used during the same session and were performed by the same trained searcher. RESULTS: Twenty-six drug information requests were compared. The MEDLARS and Dialog databases were generally similar, with no significant differences in the number of potentially relevant references, English references, clinically relevant references, available abstracts, unique citations, time online, and number of questions answered. EMBASE searches were more costly (p = 0.0005). TOXLIT was costlier than TOXLINE and MEDLINE (p = 0.0018). CONCLUSIONS: NLM MEDLARS databases were comparable to Dialog EMBASE. Although MEDLARS provided more total and English-language citations, the differences were small and did not influence the proportion of questions answered. The greatest difference between the vendors was the significantly lower cost of searching on MEDLARS. Although this difference may be partially offset by the significantly shorter search times on EMBASE, the mean 1.9 minutes saved would not recoup the mean $7.89 difference in cost. MEDLARS databases are less expensive for routine drug information requests.

Stability of cyclosporine with magnesium sulfate in 5% dextrose injection.

The compatibility and stability of cyclosporine with magnesium sulfate in 5% dextrose injection was studied. Cyclosporine solution 50 mg/mL was added to each of three glass bottles containing magnesium sulfate injection and 5% dextrose injection; final theoretical concentrations of cyclosporine and magnesium sulfate were 2.0 mg/mL and 30 mg/mL, respectively. The samples were stored under fluorescent lighting at controlled room temperature (24 +/- 2.4 degrees C). At 6, 12, 24, and 36 hours each solution was visually inspected under normal lighting against a white and black background for color change, haze, or precipitation. Samples were assayed in duplicate for cyclosporine concentration by using a stability-indicating high-performance liquid chromatographic method. Turbidity occurred immediately after mixing but resolved in approximately 30 seconds. No other changes in clarity or color were noted. The admixtures retained > 90% of initial cyclosporine concentration for six hours, and there were no significant differences in mean cyclosporine concentrations among the individual samples. Cyclosporine 2.0 mg/mL added to magnesium sulfate 30 mg/mL in 5% dextrose injection was stable for six hours when stored in glass bottles at 24 degrees C under fluorescent lighting.

Seizure after lidocaine for bronchoscopy: case report and review of the use of lidocaine in airway anesthesia.

Lidocaine-induced seizures have been reported after topical administration. A 30-year-old, 48-kg women with acquired immunodeficiency syndrome, chronic end-stage renal failure, anemia, congestive heart failure (CHF), cardiomyopathy, and increased liver function tests was admitted to the hospital with fever, chills, and dry cough. Bronchoscopy was performed to rule out Pneumocystis carinii pneumonitis; the patient experienced seizure activity after administration of a total dose of topical lidocaine 300 mg. Plasma drug concentration measured shortly after seizure, and at 4 and 22 hours after seizure were 12.0, 7.6, and 1.4 mg/L, respectively. A direct correlation exists between clinical symptoms and blood level of lidocaine; as the level increases to 8-12 mg/L the probability of seizure increases. The extent of absorption and bioavailability after airway administration depends on tissue vascularity, sites and techniques of application, patient's disease state, and, most important, the dose/unit body weight. The lidocaine dose should be titrated slowly and patients monitored for altered mental status. The dose often has to be decreased empirically in patients with liver disease or CHF. Efforts should be made to deliver minimum amounts of the drug to the lower respiratory tract, since its pharmacokinetics at that site are similar to those with intravenous administration.

The effect of vasoactive intestinal polypeptide on the lower esophageal sphincter in achalasia.

Vasoactive intestinal polypeptide (VIP) is one of the main neurotransmitters implicated in the relaxation of the lower esophageal sphincter (LES). The effect of exogenous VIP on LES motor activity was determined by esophageal manometry. LES pressure (LESP) and LES relaxation were compared in four healthy volunteers and in six patients with achalasia. The effects of intravenous doses of 1.5, 3, and 5 pmol.kg-1.min-1 of VIP were compared with placebo. Neither placebo nor 3 and 5 pmol.kg-1.min-1 of VIP produced any effect on esophageal motility in healthy volunteers. In achalasia the three doses of VIP caused a dose-dependent decrease in LESP with a significant improvement in LES relaxation. A dose of 5 pmol.kg-1.min-1 produced a maximal decrease of 51% in LESP. A beta-adrenergic agonist, isoproterenol, caused a decrease in LESP both in healthy volunteers and in patients with achalasia without improving LES relaxation. In summary, intravenous VIP improved LES relaxation and caused a decrease in LESP in patients with achalasia without affecting LESP in healthy volunteers, indicating that the LES muscle in achalasia is supersensitive to VIP. The current study suggests that a selective damage in the noncholinergic nonadrenergic innervation of the esophagus is in part responsible for the motor alteration seen in these patients. The findings and the inability of isoproterenol to improve LES relaxation despite decreasing LESP support a role in VIP as a indicator of LES relaxation.

DUE of ciprofloxacin in the treatment of urinary tract infections in hospitalized patients.

In this retrospective study of 30 patients with urinary tract infections, a drug usage evaluation indicated that 60% of the patient population sampled were appropriately switched to ciprofloxacin from IV antimicrobial agents; inappropriate use was identified in 40%. The drug's safety profile indicates that patients can be safely removed from IV antimicrobial therapy and continue treatment on ciprofloxacin, a measure which reduces treatment costs. These costs also can be lowered when inappropriate ciprofloxacin use is ruled out in patients with organisms sensitive to less costly oral antimicrobials. Identifying which patients should be removed from parenteral therapy maximizes the economic benefit of ciprofloxacin therapy and optimizes the impact of pharmacy intervention on patient care.

Therapeutic alternatives for subacute peripheral arterial occlusion. Comparison by outcome, length of stay, and hospital charges.

Thrombolytic therapy using streptokinase or urokinase has been shown to be a viable alternative to surgical thrombectomy in patients with subacute peripheral arterial occlusion. Urokinase is associated with higher success and lower complication rates than streptokinase, but the cost of urokinase is at least seven times higher. To address questions of utility and effectiveness in the treatment of subacute peripheral arterial occlusions, the authors designed a retrospective study of patients treated either by surgical thrombectomy (n = 70), thrombolysis with streptokinase (n = 19), or thrombolysis with urokinase (n = 22). Outcome of therapy, length of hospital stay, and total hospital charges in the three groups were examined. Treatment successes in the three groups, defined as complete clearing of the occluded segment with patency maintained for 60 days, were 76% for thrombectomy, 32% for streptokinase, and 64% for urokinase. Total duration of hospitalization was 21.1, 21.3, and 11.5 days (P less than .05), respectively. Mean charges for thrombolytic agents were $690 for streptokinase and $6429 for urokinase. Mean total hospital charges, however, were $25,978 for streptokinase, $22,203 for urokinase, and $25,336 for thrombectomy (P = NS). The higher cost of urokinase, then, accounted for the similar total charges, despite the shortened length of stay. These results suggest that urokinase is cost-effective compared to streptokinase for subacute peripheral arterial occlusion. Compared to thrombectomy, thrombolysis with urokinase has a marginally lower patency rate at 60 days, but a significantly shorter length of hospital stay.

Transcutaneous electrical nerve stimulation decreases lower esophageal sphincter pressure in patients with achalasia.

Vasoactive intestinal peptide (VIP) is believed to be an inhibitory neurotransmitter responsible for lower esophageal sphincter (LES) relaxation. In patients with achalasia the concentration of VIP and the number of VIP-containing nerve fibers are reduced or absent. It has been suggested that the response to low-frequency transcutaneous electrical nerve stimulation (TENS) may be mediated by a nonadrenergic noncholinergic pathway in which the release of VIP is responsible for the smooth muscle relaxation. The present study was designed to evaluate the effect of TENS on LES pressure and on VIP plasma concentrations in six patients with achalasia (five female, one male). TENS was performed daily during one week for 45-min sessions with a pocket stimulator that delivered low-frequency pulses (6.5 Hz), at 10 pulses/sec of 0.1-msec duration at intensities of 10-20 mA until rhythmic flexion of the fingers was obtained without producing pain. LES pressure and VIP levels were obtained before TENS, after the first 45-min session, and after a week of daily stimulation. After 45-min, TENS produced a significant reduction (P less than 0.01) in LES resting pressure from the mean value 56 +/- 6.4 mm Hg to 42.3 +/- 6.4 mm Hg; with LES relaxation improvement from 50.6 +/- 3% to 63.1 +/- 3.2% (P less than 0.01). After one week of daily TENS, an additional reduction in LES resting pressure (40.3 +/- 4 mm Hg) was observed (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of local instillation of alcohol on sphincter of Oddi motor activity: combined ERCP and manometry study.

The effect of local instillation of alcohol on sphincter of Oddi motor activity was determined by endoscopic manometry. Sphincter of Oddi pressures and motor function were compared in eight cholecystectomized subjects with normal sphincter of Oddi motor function and in four patients with chronic alcoholic pancreatitis. The effect of local instillation of 3 ml of 40% alcohol was compared with water instillation. In cholecystectomized subjects, alcohol produced a significant increase of basal sphincter of Oddi pressure from 21.0 +/- 2.8 mm Hg to 95.8 +/- 83 mm Hg (p less than 0.01) without significant changes in the amplitude, duration, and frequency of phasic contractions. In patients with alcoholic chronic pancreatitis, alcohol instillation resulted in a significant increase of basal sphincter of Oddi pressure from 32.5 +/- 4.8 mm Hg to 225.1 +/- 105 mm Hg without changes in amplitude, duration, and frequency of phasic contractions. Two patients with chronic alcoholic pancreatitis had a tonic contraction of the sphincter of Oddi with transitory and mild epigastric pain. Local instillation of alcohol increases sphincter of Oddi motor activity which may play a role in the pathogenesis of alcoholic pancreatitis.

The effect of transcutaneous nerve stimulation on sphincter of Oddi pressure in patients with biliary dyskinesia.

Vasoactive intestinal polypeptide (VIP) has been postulated as a neuropeptide with inhibitory neurotransmitter activity in nonadrenergic noncholinergic pathways. Transcutaneous electric nerve stimulation (TENS) relaxes the lower esophageal sphincter in patients with achalasia. Such response is accompanied by a 30% increase in VIP concentrations in the systemic circulation. Since the sphincter of Oddi (SO) receives a very dense VIP nerve supply, we evaluate the effect of TENS on SO motor activity and on VIP plasma concentrations in patients with biliary dyskinesia and in healthy volunteers. TENS was performed with a pocket stimulator for 45 min. SO pressure and VIP levels were obtained before and after 45 min of TENS. In patients with SO dyskinesia, TENS produced a significant decrease in SO pressure from 80.1 +/- 11.9 mm Hg to 58.3 +/- 9.7 mm Hg p less than 0.01); this was accompanied by a significant increase in VIP plasma levels from 21.1 +/- 0.5 pg/ml to 32.6 +/- 1.5 pg/ml (p less than 0.01). In healthy volunteers, TENS did not produce significant changes in SO pressure. However, a significant increase in VIP plasma values was observed (p less than 0.01). No significant changes in amplitude, duration and frequency of SO phasic contractions were observed in either of the two groups evaluated. We conclude that, in patients with SO dyskinesia, TENS decreases SO basal pressure, possibly by a direct action of the released VIP in the systemic circulation. In healthy volunteers, TENS increases VIP plasma values without significant effect on SO basal pressure. These findings suggest that the response to TENS may be mediated by VIP. It is also possible that the alterations seen in patients with biliary dyskinesia may be due to impairment of the VIP nerve supply at the level of the SO.

High vasoactive intestinal polypeptide plasma levels in patients with Barrett's esophagus.

We have evaluated the correlation between vasoactive intestinal polypeptide (VIP) plasma concentration and severity of gastroesophageal reflux in patients with Barrett's esophagus and the possible differences in the VIP values of these patients compared with healthy volunteers. We also evaluated the relation between VIP plasma concentration and lower esophageal sphincter (LES) pressure in 24 patients with Barrett's esophagus. The mean VIP plasma concentration in 14 patients with severe gastroesophageal reflux was 25.6 +/- 0.75 pg/ml, significantly higher than the mean value observed in 10 patients with moderate reflux (18.9 +/- 0.67 pg/ml) (p less than 0.01). The mean LES resting pressure was significantly lower in the group of patients with severe gastroesophageal reflux than that observed in patients with moderate reflux (3 +/- 0.64 and 10.3 +/- 0.69 mm Hg, respectively; p less than 0.01). The mean VIP plasma concentration in 11 healthy volunteers (20.6 +/- 0.65 pg/ml) was significantly lower than the mean value observed in the subgroup of patients with severe gastroesophageal reflux (p less than 0.01). VIP values in patients with moderate reflux were not significantly different from those observed in our volunteers. There was a significant correlation between LES pressure and VIP plasma level (r = -0.9253; p less than 0.01). In conclusion, it is possible that the decreased LES resting pressure observed in patients with Barrett's esophagus and severe gastroesophageal reflux may be due to impairment of the VIPergic innervation, resulting in an increased local VIP release with possible overflow to peripheral plasma.