Shai Luria

Inherited and acquired interactions between ACHE and PON1 polymorphisms modulate plasma acetylcholinesterase and paraoxonase activities

The 5.5 Mb chromosome 7q21–22 ACHE/PON1 locus harbours the ACHE gene encoding the acetylcholine hydrolyzing, organophosphate (OP)‐inhibitable acetylcholinesterase protein and the paraoxonase gene PON1, yielding the OP‐hydrolyzing PON1 enzyme which also displays arylesterase activity. In search of inherited and acquired ACHE–PON1 interactions we genotyped seven polymorphic sites and determined the hydrolytic activities of the corresponding plasma enzymes and of the AChE‐homologous butyrylcholinesetrase (BChE) in 157 healthy Israelis. AChE, arylesterase, BChE and paraoxonase activities in plasma displayed 5.4‐, 6.5‐, 7.2‐ and 15.5‐fold variability, respectively, with genotype‐specific differences between carriers of distinct compound polymorphisms. AChE, BChE and arylesterase but not paraoxonase activity increased with age, depending on leucine at PON1 position 55. In contrast, carriers of PON1 M55 displayed decreased arylesterase activity independent of the − 108 promoter polymorphism. Predicted structural consequences of the PON1 L55M substitution demonstrated spatial shifts in adjacent residues. Molecular modelling showed substrate interactions with the enzyme variants, explaining the changes in substrate specificity induced by the Q192R substitution. Intriguingly, PON1, but not BChE or arylesterase, activities displayed inverse association with AChE activity. Our findings demonstrate that polymorphism(s) in the adjacent PON1 and ACHE genes affect each others expression, predicting for carriers of biochemically debilitating ACHE/PON1 polymorphisms adverse genome–environment interactions.

Hand Surgery for Dystrophic Epidermolysis Bullosa

Background: Epidermolysis bullosa (EB) is a group of inherited, mechanobullous disorders caused by mutations in various structural proteins in the skin. The manifestation of these disorders in the hand is of digital contractures and pseudosyndactyly or “cocoon hands,” causing significant functional impairment. Our preferred surgical treatment of these patients involves separation of the digits from the palm by releasing the finger flexion contractures and separating them, primarily the adducted thumb. However, recurrence is common. Our hypothesis was that functional improvement is gained irrespective of recurrence of contractures. Methods: We retrospectively evaluated 4 patients, 2 male and 2 female, whose average age was 11 years, treated surgically by the separation of all their digits and by coverage with skin grafts. The follow-up period was between 1 and 3½ years. Results: Partial recurrence of the deformity was observed in all patients. Recurrence was more pronounced in the nondominant hand, especially between the digits and of flexion contractures, but did not preclude the use of precision or oppositional pinch at final follow-up. The patient with the longest follow-up has been referred for revision surgery to gain further release of contractures. Significant rehabilitation goals were achieved in all 4 patients after surgery. After 6 months, both of the younger patients were measured for finger dexterity, which showed lower scores than the norm, although this was felt to be dependent on which daily manual activities they were more familiar with. These tests could not have been performed before surgery. Conclusions: All patients and families felt the effort was worthy. Separating the thumb and straightening the digits was found to be significant, yet the indication for separating all the digits is debatable. The need for revision surgery, to maintain the digit function, is clear. Level of evidence: Level 4, case series.

Safety of Biological/Chemical Respiratory Protection Filter for Patients in Need of Oxygen Supplementation

BACKGROUND During the 2003 war in Iraq, Israel faced the problem of supplying biological/chemical respiratory protection for a population in need of ventilator support. The devices in use were insufficient in terms of protective value, costs, and availability. An adaptor was developed to allow connection between respirators and the standard biological/chemical filter canister. OBJECTIVE As part of the safety protocol for such a device, an investigation was made to determine the possibility of combustion of the biological/chemical filter canister, because of a possible exothermic reaction between the inspired oxygen-enriched air flow passing through the canister and the activated charcoal component of the filter. METHODS A mechanical ventilator generated airflow with a frequency of 24 breaths per minute and a 500-mL tidal volume, for 90 minutes, through 14 standard filter canisters in a sealed chamber at a temperature of 25 degrees C and through seven canisters at a temperature of 30 degrees C. Incremental levels of oxygen (21-100%) were used for each set of canisters. The temperature of each filter was recorded throughout the examination. RESULTS There was no elevation in the final temperature of the filters after 90 minutes of airflow with high oxygen levels. There were no signs of ignition. CONCLUSION High oxygen levels passing through the activated carbon in the filter canister placed between the mechanical ventilator and the patient do not cause a combustion reaction, making it a safe means for respiratory protection for patients undergoing mechanical ventilation.