EDITORIAL SYNOPSIS This paper indicates the need for close clinical and biochemical observation of the patient during treatment with carbenoxolone.In 1962, Doll, Hill, Hutton, and Underwood reported the results of a clinical trial of a triterpenoid liquorice compound, carbenoxolone sodium (Biogastrone), in the treatment of gastric and duodenal ulcer. They suggested that carbenoxolone sodium promotes the healing of gastric ulcers. The results in patients with duodenal ulcer were not significantly different from those receiving placebo tablets. Of 58 patients who were given the active drug in a dose of 100 mg. three times daily for four weeks, 10 (17 %) developed oedema. In 1965, Doll, Hill, and Hutton, in a further series, re-affirmed the value of carbenoxolone sodium in promoting the reduction in size of gastric ulcers. Twenty-four patients were treated as out-patients using doses of 75 to 100 mg. three times daily of carbenoxolone sodium. In this series, a liability to fluid retention was again noted: 21 % of patients developed oedema of the ankles and showed a rapid gain in weight. During the later stages of the second trial the blood pressure was recorded weekly and in a number of patients significant elevation of the systolic and diastolic blood pressure was noted. The mean maximum increase of pressure over the pretreatment reading was 20 mm.Hg systolic and 12 mm.Hg diastolic for the carbenoxolone sodium group. In one patient the increase in diastolic pressure was 30 mm.Hg.This communication describes our experience using carbenoxolone sodium in doses of 100 mg. three times daily and 50 mg. three times daily in the treatment of patients with gastric ulcer. Special attention was paid to the incidence of side-effects. METHODA double-blind pilot trial of carbenoxolone sodium was carried out in 12 patients with gastric ulcer. Only patients in whom the profile of the gastric ulcer niche was greater than 10 sq.mm. in area (Doll et al., 1962) were included in the trial. Six patients received the active drug in a dose of 100 mg. three times daily and six received inert placebo tablets. A further four patients were given carbenoxolone sodium in a dose of 100 mg. three times daily. All subjects were in-patients and the drug therapy was given for a maximum period of one month. Patients were allowed up to go to the lavatory, took a light ward diet, and were encouraged to take freely milk and antacid (colloidal aluminium hydroxide) whenever dyspeptic symptoms occurred. They were advised to stop smoking cigarettes. Progress was recorded at weekly intervals, by full clinical examination, by barium meal examination, and in many by fibroscopy. Also at weekly intervals serum electrolytes and urea were measured; liver function tests were carried out and routine blood examinations were made (haemoglobin, packed cell volume, and white blood count). There were weekly electrocardiograms and chemical analyses of the urine. The weight was recorded at least once weekly, and more frequently if indicated. The blood pressure was recorde...

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Objective: To determine the effect of neonatal and maternal blood group on the mortality risk from necrotizing enterocolitis (NEC).Study Design: Retrospective chart review of all neonates admitted to the neonatal intensive care unit over 24 years. Data on birth date, gestational age, maternal/neonatal blood group, number of transfusions, and survival time (defined as date of birth to date of death/discharge) were collected on those with NEC.Result: 276 neonates with Bell stage II-III NEC were analyzed. AB neonates had a significantly higher risk of mortality from NEC compared with other blood groups (HR 2.87; 95% CI 1.40 to 5.89; P ¼ 0.003). Multivariate analysis showed AB blood group to be an independent risk factor for mortality from NEC. Conclusion:Neonatal and maternal blood groups are significantly associated with a neonate's survival from NEC. The increased mortality of AB neonates may be related to factors such as neonatal blood group antigens and/or transplacental transfer of isoagglutinins.

electrical cardioversion without a suitable period of withdrawal of digoxin (Gilbert and Cuddy, 1965). It seems likely that many patients with atrial fibrillation have latent digoxin toxicity which can readily become manifest without any increase in plasma concentration of the drug.In view of the wide variations in dose requirements needed to achieve control of the heart rate in atrial fibrillation, and the fact that many patients with atrial fibrillation may have slow heart rates with or without digoxin, the poor correlation between ventricular rate and plasma levels was to be expected. The extent to which plasma levels reflect myocardial concentrations in chronically digitalized patients, however, remains to be defined. Daily Dose and Plasma LevelsThe relationship between the size of the daily dose and the plasma levels of digoxin was investigated. Because most of the drug is excreted unchanged by the kidneys (Marcus et al., 1964), renal function is as important as dose in determining blood levels. We therefore restricted the analysis to those patients who had normal or near-normal renal function indicated by blood urea concentrations of less than 40 mg./100 ml. The data presented in Fig. 3 show a significant relationship between oral dose and plasma levels. Several factors must have militated against more uniform blood levels. The patients were of different heights and weights; blood urea provides only a rough index of glomerular filtration rate; the potency of some commercially available digoxin tablets may vary widely (Feinberg, 1969); and blood samples were taken at intervals after the previous dose ranging from about 8 to 24 hours. Clearly, however, 0.5 mg. of digoxin daily will usually provide plasma levels in a satisfactory therapeutic range of 1 to 2 ng./ml. in the presence of normal renal function. Larger doses, or moderate doses in the presence of considerably impaired renal function, are associated with levels which fall within the toxic range.Di,oxin toxicity is particularly common in the elderlv (Soffer, 1961), and the suggestion has been made that this may be due in part to increased sensitivity to the drug (Feibush, 1959). We found, however, that blood levels in patients aged 60 and over with controlled atrial fibrillation were closely similar to the levels in younger patients (Fig. 4). The blood levels in the older age group were attained with a smaller mean dose, and the blood urea of these patients tended to be higher than those found in the under-60 group. This observation is consistent with the findings of Ewy, Kapadia, Yao, Lullin, and Marcus (1969), who used tritiated digoxin to show that a given dose of the drug resulted in higher blood concentrations in the elderly compared with younger subjects, and that the difference was associated with smaller body size and diminished urinary excretion of digoxin.The present findings indicate that the ventricular response to atrial fibrillation is not well correlated with plasma concentration of digoxin. Patients receiving more than 0.5 mg. daily o...

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Background Necrotizing enterocolitis (NEC) affects up to 10% of extremely-low-birthweight infants, with a 30% mortality rate. Currently, no biomarker reliably facilitates early diagnosis/prevention. Since thrombocytopenia and bowel ischemia are consistent findings in advanced NEC, we prospectively investigated the impact of two potential biomarkers: reticulated platelets (RP) and intestinal alkaline phosphatase (iAP). Methods Infants born ≤32 weeks and/or ≤1500g were prospectively enrolled from 2009–2012. Starting within 72 hours of birth, 5 weekly whole blood specimens were collected to measure RP and serum iAP. Additional specimens were obtained at NEC onset (Bell stage II or III) and 24 hours later. Dichotomous cut-points for both biomarkers sought to maximize sensitivity. The Mann-Whitney U test highlighted differences in median biomarker levels between NEC and non-NEC infants. Chi-square or Fisher’s exact test highlighted categorical differences. The Kaplan-Meier method and Logrank test estimated the probability of developing NEC. The Cox proportional hazards model estimated hazard ratios. Results Of 177 infants, 8.5% developed NEC. Of these, 40% required surgery, 20% expired before discharge, 93% had “low” RP (≤2.3%), and 60% had high iAP (>0 U/L). Infants with “low” RP were significantly more likely to develop NEC [HR=11.0 (1.4–83); p=0.02], while those with “high” iAP showed a similar trend [HR=5.2 (0.7–42); p=0.12]. Median iAP levels were significantly higher at week 4 (p=0.02), preceding the average time to NEC onset by one week (35.7 ± 17.3 days). Conclusion Decreased RP serves as a sensitive marker for NEC onset, thereby enabling early preventative strategies. iAP overexpression may signal NEC development.

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