In organophosphate intoxication the assessment of both the degree of severity of poisoning and the initial dose of pralidoxime and atropine are as yet based only on clinical symptoms. We present three patients with clinically severe organophosphate poisoning in whom a prompt recovery from central nervous symptoms occurred after the administration of low doses of atropine and pralidoxime. It is suggested that the true severity of organophosphate intoxication as well as the initial therapy should be determined by the amount ingested, the propensity for aging, and the pharmacodynamic properties of the organophosphorus compound, as well as by the time interval between exposure and initiation of appropriate treatment, as far as these data can be verified in the individual patient.

BackgroundThe intra-patient variability in tacrolimus exposure (TAC-IPV) after paediatric liver transplantation and its impact on patient outcomes has been poorly studied. The present study aims to investigate whether there is a trend in TAC-IPV during the first 5 years post transplantation, which variables influence IPV and wheth-er the IPV during the first year is associated with liver transplantation outcomes in paediatric patients.MethodsWe conducted a single centre retrospective study including 41 living paediatric patients transplanted between January 2003 and September 2016 at the Ghent University Hospital. The intra-patient variability in the dose-adjusted tacrolimus pre-dose concentrations was calculated yearly during the first five years following trans-plantation, expressed as coefficient of variation (CV%1–5) The difference in CV% in the years following transplanta-tion was analysed using the Friedman test. A linear uni-variate and multivariate regression analysis was applied to identify factors associated with TAC-IPV. The following parameters were tested: age, gender, origin, the number of missed clinic appointments as a surrogate marker for ther-apy adherence, the total number of medications, concom-itant medications potentially interfering with TAC metabo-lism-CYP3A4/A5 inductors or inhibitors and biochemical parameters. Logistic and linear regression models were fit-ted to test an association of TAC-IPV with patient outcomes: need for biopsy during year 1, 3 and 5; hypertension and renal function at 1, 3 and 5 years; acute rejection and CMV/EBV viremia during year 1 post-transplantation.ResultsWe identified a significant decrease in TAC-IPV during the first 3 years after transplantation with the me-dian CV%1=39,4%; CV%2=30,9%; CV%3=28,5% (p=0,004), after which the CV% reaches a plateau (CV%4=23,6% en CV%5=28,9%). Multivariate analysis showed that serum albumin in the first year (p=0,029), haematocrit in the third year (p=0,019) and the number of missed clin-ic appointments in the fifth year after transplantation (p=0,009) were associated with TAC-IPV.in the 1 st, 3rd and 5th year, respectively. Univariate analysis showed that CV%1 was significantly associated with the need for bi-opsy during the first year post-transplantation (p=0.036) and the occurrence of one or more episodes of acute al-lograft rejection during the first year post-transplantation (p=0.031). In univariate analysis a trend was observed for association with hypertension one year after transplan-tation (p=0,085). Multivariate logistic regression analysis confirmed that CV%1 was an independent factor associ-ated with the need for liver biopsy in the first year follow-ing liver transplantation. (p=0.05; Exp(B)=1.045).ConclusionAs expected, tacrolimus intra-patient vari-ability is higher during the first two years after transplantation. Our results suggest that while albumin and hae-matocrit are associated with TAC-IPV in the first 3 years, therapy adherence expressed as the number of missed clinic appointments is associated with TAC...

The gravimetric plethysmograph measures blood flow in the limb in terms of the increase in weight which follows temporary venous occlusion. Following validation of the device, blood flow in the leg was evaluated in normal subjects and in patients with intermittent claudication. Measurement of the immediate hyperaemic response to a three-minute period of arterial occlusion proved to be very reproducible in patients with occlusive arterial disease of the legs.

The gravimetric plethysmograph is a simple, robust and inexpensive device which measures bloodflow in the limb in terms of the increase in weight which follows temporary venous occlusion. Validation of the instrument using an artificial circuit shows that it is accurate and gives reproducible results. The mean resting bloodflow in the legs of f 8 healthy volunteers was 3.95 ml100 ml-' tissue min-and this measurement was not reproducible. A 3-min period of arterial occlusion resulted in an immediate hyperaemic responseofamean43,5 m1100 ml-lmin-',andthisresult was much more reproducible (r = 0.78). The mean resting blood flow of 45 patients with occlusive arterial disease of the legs was 2.7 mlI00 mlmin-', and this flow rate was variable(r = 0.71). Their immediate hyperaemic response of 5. I8 ml100 ml-min-' was much less than that in normal volunteers, but was quite reproducible (r = 0.93). Following arterial reconstruction, their mean immediate hyperaemic response rose to 10.35 mlI00 ml-' min -' ,