An exploratory analysis of the epidemiology and surgical management of perforated diverticular disease over a two-year period at a referral centre in the Caribbean.

OBJECTIVE: We present an exploratory analysis of data collected on perforated diverticular disease (PDD) in Barbados and suggest possible areas for further study. SUBJECTS AND METHODS: All cases of perforated diverticular disease treated at the Queen Elizabeth Hospital (QEH) Barbados, between January 1, 2005 and December 31, 2006 were reviewed. The patient's age, gender location of disease, Hinchey stage, operative procedure, rate of colostomy reversal, length of hospitalization, incidence of peri-operative morbidity and postoperative mortality were analysed using principal components analysis (PCA). RESULTS: Fourteen cases of PDD were treated at the QEH during this period. Six (43%) of the patients had perforated right-sided diverticulitis (PRSD). In the PCA, Dimensions 1 and 2 were the two dimensions examined, as they both had Eigenvalues over 1. Dimension 1 can be taken as an indicator of the intensity of the disease. On dimension 2, length of hospitalization had the highest component loading (0.875). The mean hospital stay was 10.6 days in PRSD, 9.5 in left-sided perforations with primary anastomosis, and 16.2 days for those with a Hartmann's procedure. The overall peri-operative morbidity was 28% and there was no mortality in the series. CONCLUSION: This preliminary study seems to show a relatively high incidence of PRSD in a predominantly Afro-Caribbean population. More research is needed to determine the exact aetiology of this disease. In our experience, primary anastomosis in carefully selected patients with either PRSD or perforated left-sided diverticulitis (PLSD) may result in shorter hospitalization.

Inhibition of pyruvate carboxylase by sequestration of coenzyme A with sodium benzoate.

Pyruvate-dependent CO2 fixation by isolated mitochondria was strongly inhibited by sodium benzoate. Pyruvate carboxylase was identified as a site of inhibition by limiting flux measurements to assays of pyruvate carboxylase coupled with malate dehydrogenase. Benzoate reduced pyruvate-dependent incorporation of [14C]KHCO3 into malate and pyruvate-dependent malate accumulation by 74 and 72%, respectively. Aspartate-dependent malate accumulation was insensitive to benzoate, ruling out malate dehydrogenase as a site of action. Inhibition by benzoate was antagonized by glycine, which sharply accelerated conversion of benzoate to hippurate. Assays of coenzyme A and its acyl derivatives revealed inhibition to correlate with depletion of acetyl CoA and accumulation of benzoyl CoA. Depletion of acetyl CoA was sufficient to account for greater than 50% reduction in pyruvate carboxylase activity. Competition between acetyl CoA and benzoyl CoA for the activator site on pyruvate carboxylase was insignificant. Results support the interpretation that the observed inhibition of pyruvate carboxylase occurred primarily by depletion of the activator, acetyl CoA, through sequestration of coenzyme A during benzoate metabolism.

The effect of sodium benzoate on ammonia toxicity in rats.

At 9.5 mmoles/kg body weight, sodium benzoate sharply increased mortality in rats subsequently challenged with ammonia. Fasted animals were less sensitive to potentiation of ammonia toxicity by benzoate than were fed animals. At 2.5 mmoles/kg body weight, benzoate was observed to protect fasted animals against ammonia toxicity. Measurements of ammonia disappearance, urea formation, and hippurate synthesis in suspensions of isolated hepatocytes indicate that benzoate potentiates ammonia toxicity by inhibiting the urea cycle.