The effect of noradrenaline on the toad skin potential

1. The electrical response of isolated toad skins to the presence of 4 x 10(-5)M noradrenaline in the inner medium has been studied.2. When skins were bathed in Ringer solution, noradrenaline initiated a partial depolarization of the skin potential (inside surface becoming less positive) followed by a hyperpolarization; however, noradrenaline depolarized skins in sulphate Ringer.3. The origin of the hyperpolarizing phase of the response to noradrenaline was studied by comparing the size of perturbations in the skin potential, produced by identical changes in external sodium, external chloride or internal potassium concentrations, before and during the response to noradrenaline.4. Measurements of skin conductance were made in different sulphate media in order to estimate the magnitudes of the conductance of the shunt pathway through the skin and the conductance of the pathway for actively transported sodium ions.5. Interpretation of both the variations in the perturbations of skin potential and the skin conductance measurements led to the conclusion that the hyperpolarizing phase of the response to noradrenaline was generated by an increase in the sodium to chloride permeability ratio for the outer barrier. It was considered that other evidence was compatible with this view.6. Similar experimental methods were employed to study the action of antidiuretic hormone (ADH) and an elevated external concentration of calcium on the outer barrier. It was found that ADH increased the sodium to chloride permeability ratio whereas calcium decreased it. The separate actions of ADH and calcium on the sodium permeability of the outer barrier did not interfere apparently with the subsequent ability of noradrenaline to increase the sodium to chloride permeability ratio for this barrier in the skin.     

Surgeon experience contributes to improved outcomes in pancreatoduodenectomies at high risk for fistula development

BackgroundPancreatoduodenectomies at high risk for clinically relevant pancreatic fistula are uncommon, yet intimidating, situations. In such scenarios, the impact of individual surgeon experience on outcomes is poorly understood.MethodsThe fistula risk score was applied to identify high-risk patients (fistula risk score 7–10) from 7,706 pancreatoduodenectomies performed at 18 international institutions (2003–2020). For each case, surgeon pancreatoduodenectomy career volume and years of practice were linked to intraoperative fistula mitigation strategy adoption and outcomes. Consequently, best operative approaches for clinically relevant pancreatic fistula prevention and best performer profiles were identified through multivariable analysis models.ResultsEight hundred and thirty high-risk pancreatoduodenectomies, performed by 64 surgeons, displayed an overall clinically relevant pancreatic fistula rate of 33.7%. Clinically relevant pancreatic fistula rates decreased with escalating surgeon career pancreatoduodenectomy (–49.7%) and career length (–41.2%; both P < .001), as did transfusion and reoperation rates, postoperative morbidity index, and duration of stay. Great experience (≥400 pancreatoduodenectomies performed or ≥21-year-long career) was a significant predictor of clinically relevant pancreatic fistula prevention (odds ratio 0.52, 95% confidence interval 0.35–0.76) and was more often associated with pancreatojejunostomy reconstruction and prophylactic octreotide omission, which were both independently associated with clinically relevant pancreatic fistula reduction. A risk-adjusted performance analysis also correlated with experience. Moreover, minimizing blood loss (≤400 mL) significantly contributed to clinically relevant pancreatic fistula prevention (odds ratio 0.40, 95% confidence interval 0.22–0.74).ConclusionSurgeon experience is a key contributor to achieve better outcomes after high-risk pancreatoduodenectomy. Surgeons can improve their performance in these challenging situations by employing pancreatojejunostomy reconstruction, omitting prophylactic octreotide, and minimizing blood loss.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Biochemical Changes after Vertical Banded Gastroplasty for Morbid Obesity

A prospective study of biochemical changes after vertical banded gastroplasty for morbid obesity, in 94 patients (10 males and 84 females, ages ranging from 18 to 59 years) has been carried out. Liver function tests and electrolyte estimations were performed preoperatively, during hospitalisation for surgery, at 6 weeks and at 6 months postoperatively, and demonstrated no significant changes in liver function in these patients 6 months after surgery. The study concludes that there is no increase in the risk of liver damage or electrolyte disturbance after vertical gastroplasty, but that there may be subtle hepatic changes present as gall bladder disease developed in 18 patients postoperation (19%).     

Postoperative deposits on the Acrysof intraocular lens

PURPOSE: To report a commonly occurring change on the anterior surface of the Acrysof intraocular lens which is presumed to be due to the proliferation of lens epithelial cells from the capsulo-rhexis margin. METHOD: Forty-one consecutive cases (31 patients) of Acrysof intraocular lens implantation were followed prospectively. Clinical charts were reviewed for changes on or within the lens and visual acuity and refractive changes recorded. All cases were dilated at 3-5 weeks postoperatively to facilitate observation of changes. Representative slit lamp photos were taken. RESULTS: Deposits on the intraocular lens surface were noted on 18 of 41 lenses at 3-5 weeks post surgery. Deposits were not found on examinations conducted during the first postoperative week. All changes had fully resolved by 3 months. CONCLUSIONS: The changes recorded had no impact on visual acuity. The deposits noted do not represent clinically important pathology. They may be an unusual marker of biocompatibility with this lens. Surgeons using this lens should be aware of these changes.