O’Marcaigh, Aengus

A variety of drugs including certain antibiotics have been implicated in causing acute pancreatitis.1 So far, there have been three reported cases in adults in which erythromycin was identified as a possible cause of acute pancreatitis.2-4 We report the first case of erythromycin-induced acute pancreatitis in childhood. We suggest a possible pathophysiological mechanism based on the known motilin agonist properties of erythromycin. CASE REPORT A 12-year-old girl was brought to the Emergency and Trauma Unit, with acute, crampy abdominal pain and vomiting. These symptoms had started 1 hour earlier, approximately 30 minutes after the deliberate ingestion of 20 tablets of erythromycin (Erythromycin Base Filmtab, 250 mg, Abbot Laboratories, Pharmaceutical Products Division, North Chicago, IL) after an argument with her parents and her boyfriend.

Objective. Tilt-table testing is useful for investigating unexplained syncope in pediatric patients. No data are available on the use of intravenous metoprolol during testing to identify children who might respond to subsequent oral β-adrenergic blockade or on the efficacy and safety of such oral therapy. Design. To provide these data, we obtained follow-up information on 27 consecutive pediatric patients who had tilt-table testing for unexplained syncope. Results. Nineteen patients (70%) had positive test results with or without isoproterenol infusion. All these patients had negative test results after intravenous infusion of metoprolol and subsequently were treated with oral metoprolol. Taking oral metoprolol therapy alone, 9 (47%) of the 19 patients were asymptomatic, 8 (42%) reported a decreased frequency of syncopal episodes, and 2 (11%) had unchanged or more frequent episodes. The mean dosage of metoprolol required to prevent symptoms was 1.5 mg/kg per day. Mild side effects were reported by 6 (32%) of the 19 patients. Six patients (32%) required additional medications. Conclusions. We conclude that metoprolol is safe and effective for the treatment of most cases of neurocardiogenic syncope in children and that this response cannot be predicted accurately by the use of intravenous metoprolol during testing.

The structural abnormalities and functional characteristics of dysfunctional prothrombin variants in two new kindreds have been determined. Prothrombin Corpus Christi (family 1) was purified and found to have markedly reduced fibrinogen clotting activity, yet normal amidolytic and near-normal platelet aggregating activity. A transition (C to T) at nucleotide position 8885, present in the heterozygous form in affected family members, resulted in the substitution of Cys for Arg 382. This substitution results in the loss of a positive charge within the fibrinogen-binding exosite of thrombin, thus accounting for the observed functional defect. A heterozygous C to T transition was also present at position 19994 in other family members with a hypoprothrombinemic phenotype. This mutation results in the replacement of Gln 541 (CAA) by a premature stop codon (TAA). Prothrombin Dhahran (family 2) was found to have markedly reduced fibrinogen clotting activity, but normal amidolytic activity. Affected family members were found to have a G to A transition at nucleotide position 7312 resulting in the substitution of His for Arg 271. This substitution results in the abolition of a factor Xa cleavage site, yielding meizothrombin rather than thrombin, on activation of prothrombin Dhahran by factor Xa. All but one of the above mutations occur at CpG dinucleotides, thus further supporting the observation of a high incidence of CpG transitions in hereditary dysprothrombinemia. The significant bleeding tendencies of individuals homozygous for prothrombin Dhahran (prothrombin clotting activity 5% to 7%) contrast sharply with the absence of significant chronic bleeding in the proband expressing prothrombin Corpus Christi (prothrombin clotting activity 2%). Our findings underscore the capacity of thrombin to contribute to clinical hemostasis by mechanisms other than its fibrinogen clotting activity.

The diagnostic process consists of a series of steps in which the estimated probability of particular disease is increased or decreased until either treatment can be instituted or the diagnosis excluded. The history and physical exam play an important role. If a therapeutic decision cannot confidently be made on clinical grounds alone, a diagnostic test may confirm or exclude a diagnosis or clearly indicate the need for further testing. An inappropriately chosen test or misinterpreted test result, however, may mislead the clinician and possibly harm the patient or simply be wasteful. Estimating the predictive values of a diagnostic test will help to avoid these pitfalls. This article shows the clinician a simplified way to do this.