Comparison of Bayer Advia Centaur immunoassay results obtained on samples collected in four different Becton Dickinson Vacutainer tubes.

BACKGROUND: Medicines and Healthcare products Regulatory Agency's (MHRA's) Medical Device Alert MDA/2004/048 described bias in some endocrine test results obtained on a few immunoassay platforms, particularly the Bayer Advia Centaur instrument, when using blood specimens collected into Becton Dickinson (BD) Vacutainer SSTII Advance tubes. As users of BD tubes and the Advia Centaur instrument, we addressed our concerns about the quality of the results that we had previously reported by undertaking an independent study. METHOD: We compared the results of 15 immunoassays performed on Bayer Advia Centaur using blood specimens collected into four different BD Vacutainer tubes (plain, old and newly released BD SSTII Advance, and BD PSTII). RESULTS: Compared with plain tubes, old SSTII Advance tube results showed no bias for testosterone, CA15-3, follicle-stimulating hormone and folate assays, but gave a positive bias for cortisol and a negative bias for vitamin-B12. Compared with plain tubes, BD PSTII tubes gave no significant bias for thyroid function tests, prolactin, parathyroid hormone, and CA125, but gave a negative bias for steroid assays, and a positive bias for gonadotrophins. The results obtained using new BD SSTII Advance tubes were generally comparable with those on plain tubes. CONCLUSIONS: Only for cortisol did our findings support the bias described by MHRA. Based on our results, apart from vitamin-B12 and possibly cortisol, there may have been no significant influence on clinical decisions as a result of using the old BD SSTII Advance specimen tubes. New BD SSTII Advance tubes and plain tubes give generally comparable results. BD PSTII tubes should not be used for steroid hormone measurements on the Bayer Advia Centaur instrument.

Sorbitol compared with xylitol in prevention of dental caries.

OBJECTIVE: To summarize published data on the comparative efficacy of sorbitol and xylitol for prevention of dental caries. DATA SOURCES: Published double-blind comparative trials, using sorbitol and xylitol products, identified by MEDLINE (January 1966-December 1998) and International Pharmaceutical Abstracts (January 1970-December 1998) searches. DATA SYNTHESIS: Clinical trials generally used sorbitol and xylitol gums, which patients chewed three to five times daily for 20-40 months. Xylitol was superior to sorbitol in two longer, secondary dentition trials (30-63% reductions), but not in two primary dentition trials. CONCLUSIONS: The data suggest that xylitol-containing gums may provide superior efficacy in reducing caries rates in high-risk populations.

Is rectally administered cisapride an effective prokinetic agent?

OBJECTIVE: To summarize the published data on the efficacy of rectally administered cisapride. DATA SOURCES: Published double-blind, placebo-controlled trials on rectally administered cisapride identified by MEDLINE (January 1966-December 1998) and International Pharmaceutical Abstracts (January 1970-December 1998) searches. DATA SYNTHESIS: Cisapride is an oral prokinetic agent that increases lower esophageal sphincter tone, accelerates gastric emptying, and increases small-bowel motility. Clinical trials of rectal cisapride have used both single- and multiple-dosing regimens. Typically, patients received one or two 30-mg suppositories (provided by the manufacturer). Rectal cisapride was effective in enhancing gastric emptying of solid or semisolid meals in healthy patients or patients with chronic gastric emptying disorders. Rectal cisapride was not effective in antagonizing the gastrointestinal effects of narcotic analgesics or promoting the return of small-bowel activity in adults with postoperative ileus. Mixed results were seen when rectal cisapride was used to promote enteral feedings in patients with persistent ileus. CONCLUSIONS: The use of rectal cisapride cannot be recommended at this time. Rectal cisapride was effective only in patients who could have otherwise taken either cisapride tablets or suspension but it was not effective in patients who are physically unable to swallow or restricted from ingesting anything orally following surgical procedures. Considering the varied patient populations and evaluation methods used in these studies, the lack of a commercially available cisapride suppository, and absence of studies involving extemporaneously prepared cisapride suppositories, the use of suppositories should be limited to investigational trials.

Octreotide or vasopressin for bleeding esophageal varices.

Acute bleeding due to esophageal varices continues to be a life-threatening complication of liver disease. Despite the availability of improved therapy, mortality continues to be high. Octreotide has been shown to be at least as effective as vasopressin in the treatment of bleeding varices, with fewer and less severe systemic adverse effects. In addition, octreotide has also been consistently associated with a decreased need for transfusions. Octreotide has been used safely in patients without serious cardiovascular disease when administered as a continuous intravenous infusion of 25 micrograms/h for 24 hours with or without an initial 100-micrograms bolus dose. Since these trials have used small numbers of patients, the ability to detect small but clinically important differences has been limited. Additional controlled trials comparing octreotide with the combination of vasopressin and nitroglycerin are needed to more clearly determine the efficacy and cost-effectiveness of therapy. Furthermore, the optimal dosage, duration, and route of administration of octreotide in the treatment of bleeding esophageal varices has yet to be determined.

Drug-induced pure red cell aplasia.

Pure red cell aplasia (PRCA) is an uncommon hematologic disorder characterized by the absence of erythroblasts in otherwise normal bone marrow. It is commonly an autoimmune disorder sometimes associated with a congenital error. It may also be acquired in association with thymomas, hematologic malignancies, human parvovirus B19 infection, drugs, and other disease states. Thirty drugs have been implicated as causative in PRCA, but most literature reports describe only one or two patients. Data evaluating possible mechanisms of drug-induced PRCA are extremely limited, with conflicting results from different investigators. The criteria we used were at least five patients reported, reports from at least three separate investigators, and a minimum of one case of probable causality or better using a published assessment scale. With these criteria, phenytoin, azathioprine, and isoniazid had sufficient evidence of causality. All three are documented causes of PRCA and should be considered in any case of selective erythrocyte aplasia.

Rapid infusion of amphotericin B in dextrose.

OBJECTIVE: To review the data examining the use of rapid infusion of amphotericin B in dextrose infusions. DATA SOURCES: A MEDLINE search of the English-language literature and review of pertinent references' bibliographies was used to identify articles evaluating the effect of amphotericin B infusion rates on the incidence of adverse reactions. STUDY SELECTION AND DATA EXTRACTION: Controlled and uncontrolled studies involving humans are reviewed; emphasis is placed on recent comparative trials. Pertinent information, as judged by the authors, was selected for discussion. DATA SYNTHESIS: Amphotericin B, a polyene antifungal agent with significant toxicity, remains the agent of choice for many serious fungal infections. The potential benefits of rapid administration of amphotericin B in reducing the incidence and/or severity of adverse reactions were noted soon after its introduction. Recent studies have examined the tolerability of rapid (0.75-1 h) amphotericin B infusions. Results of studies assessing the tolerability of rapid amphotericin B infusions suggest that tolerance to infusion-related reactions develops during therapy. Comparative trials have obtained variable results. The comparative trials supporting rapid amphotericin B infusion have generally used crossover designs, enrolled small numbers of patients, and excluded patients with significant renal or cardiovascular dysfunction. CONCLUSIONS: Rapid amphotericin B infusions should be avoided during initiation of therapy when infusion-related reactions tend to be most problematic, and in patients with cardiovascular disease, renal dysfunction, and potassium disorders because of the potential risk for cardiac arrhythmias. The literature currently available is conflicting and insufficient to support the routine use of rapid amphotericin B infusion.

Oral antihypertensives for hypertensive urgencies.

OBJECTIVE: To review the data describing the use of oral antihypertensive agents in the treatment of hypertensive urgencies (HU). DATA SOURCES: A MEDLINE search of the English-language literature and fan searches of papers evaluating oral antihypertensives in HUs and emergencies were conducted. STUDY SELECTION: Controlled and uncontrolled studies in humans are reviewed. Emphasis was placed on recent trials evaluating individual agents and comparative trials. DATA SYNTHESIS: Comparative trials have demonstrated that four currently available oral agents can lower blood pressure rapidly and predictably. Nifedipine, the most extensively studied, and clonidine have served traditionally as the oral agents of choice for the treatment of HUs. All the agents can lower blood pressure effectively within the first few hours after dosing, but their use also has been associated with adverse effects. Nifedipine and captopril are the two agents with the most rapid onset, within 0.5-1 hour, and may treat hypertensive emergencies as well as urgencies. Clonidine and labetalol have maximal blood pressure lowering effects at 2-4 hours. CONCLUSIONS: Captopril, clonidine, labetalol, and nifedipine are all effective agents for the treatment of HUs. Agent selection should be based on the perceived need for urgent blood pressure control, the cause of HU, and concomitant conditions. A definite benefit from acute blood pressure lowering in HUs has yet to be demonstrated, especially in asymptomatic patients. More controlled trials with less aggressive dosing regimens and placebo controls need to be performed to assess the most appropriate treatment for HUs with the fewest adverse effects.

Granulocyte-colony stimulating factor for sulfasalazine-induced agranulocytosis.

OBJECTIVE: To report a case of sulfasalazine-induced agranulocytosis that was successfully treated with granulocyte-colony stimulating factor (G-CSF). CASE SUMMARY: An 82-year-old woman developed agranulocytosis within two months of initiating sulfasalazine therapy. She was hospitalized, empiric antibiotic and antifungal agents were prescribed, and sulfasalazine therapy was stopped. The patient received G-CSF 600 micrograms/d subcutaneously for six consecutive days, starting on hospital day 5. Agranulocytosis resolved on day 5 and leukopenia on day 6 of G-CSF therapy. No adverse reactions were attributed to administration of this agent and the patient was discharged on hospital day 13. DISCUSSION: Numerous agents, including sulfasalazine, have been associated with agranulocytosis. Agranulocytic patients frequently experience life-threatening bacterial and fungal infections. Administration of colony stimulating factors may reduce the duration of agranulocytosis and incidence of life-threatening infections. CONCLUSIONS: G-CSF administration appears to have decreased the duration of this elderly patient's agranulocytosis and hospitalization.

A double-blind controlled cross-over trial of cyproterone acetate in females with hidradenitis suppurativa.

In order to examine whether anti-androgen therapy was effective in hidradenitis suppurativa (HS), ethinyloestradiol 50 micrograms/cyproterone acetate 50 mg in a reverse sequential regimen was compared with ethinyloestradiol 50 micrograms/norgestrel 500 micrograms (Eugynon 50) in 24 female patients. Both treatments produced substantial improvement in disease activity. Seven patients cleared and have remained free of disease for 18 months, five patients improved, four remained unchanged, while two deteriorated. Cyproterone acetate was not clinically significantly more effective than E50, and both gave a similar reduction in free androgen index. Anti-androgen therapy appears to be beneficial in the treatment of hidradenitis suppurativa.

Mediation of hidradenitis suppurativa by androgens.

Forty two women with hidradenitis suppurativa were assessed clinically and biochemically for evidence of androgen excess. Thirteen had irregular menses; 22 of 36 experienced exacerbation of hidradenitis suppurativa premenstrually; 19 had or had had acne vulgaris; and seven were hirsute. Comedones (blackheads) were found in apocrine sites in 37, but also in retroauricular sites in 18 and were considered to be an important physical sign for early diagnosis. Eight had evidence of pilonidal (postanal) sinus. The patients had a higher concentration of total testosterone (p less than 0.01) and free androgen index (testosterone to sex hormone binding globulin concentrations) (p less than 0.01) than normal controls. Patients with hidradenitis suppurativa appear to have endocrine abnormalities sufficient to suggest an androgenic basis for the disease.