The reverse sural flap: modifications to improve efficacy in foot and ankle reconstruction

The aim of this work is to evaluate the efficacy of the reverse sural flap in covering defects in the foot and ankle region when certain technical modifications are employed. We provide a retrospective review of 32 consecutive reverse sural flaps for foot and ankle defects, and compare the technique and results with other reports. There were 23 fasciocutaneous flaps, 7 fascial flaps, and 2 tissue-expanded flaps. Four flaps (12.5%) suffered significant flap loss, and 4 patients had delayed healing.Several modifications are suggested to increase the versatility of the sural flap in covering foot and ankle defects, including preserving the mesentery connecting the sural nerve to the deep fascia, inclusion of skin of the upper third of the leg, limiting pedicle width to 2 cm with preservation of a tongue-like skin process all along its length, and generous release of the fascia over the peroneal compartment. In addition, we describe the use of tissue expanded sural flaps.     

Ouabain binds with high affinity to the Na,K-ATPase in human polycystic kidney cells and induces extracellular signal-regulated kinase activation and cell proliferation

In autosomal dominant polycystic kidney disease (ADPKD), cyst formation and enlargement require proliferation of mural renal epithelial cells and the transepithelial secretion of fluid into the cyst cavity. Na,K-ATPase is essential for solute and water transport in ADPKD cells, and ouabain blocks fluid secretion in these cells. By binding to the Na,K-ATPase, ouabain also induces proliferation in some cell types. Surprisingly, it was found that nanomolar concentrations of ouabain, similar to those circulating in blood, induced ADPKD cell proliferation but had no statistically significant effect on normal human kidney (NHK) cells. Ouabain, acting from the basolateral side of the cells, also caused an increase in the level of phosphorylated extracellular signal-regulated kinases (ERK). Mitogen-activated protein kinase kinase (MEK) inhibitor U0126 blocked ouabain-induced ERK activation and cell proliferation, suggesting that ouabain effect is mediated through the MEK-ERK pathway. In contrast to NHK cells, the dose-response curve for ouabain inhibition of Na,K-ATPase activity indicated that approximately 20% of the enzyme in ADPKD cells exhibits a higher affinity for ouabain. The increased ouabain affinity of ADPKD cells was not due to differences in Na,K-ATPase isoform expression because these cells, like NHK cells, possess only the alpha1 and beta1 subunits. The gamma variants of the Na,K-ATPase also are expressed in the cells but are elevated in ADPKD cells. Currently, the basis for the differences in ouabain sensitivity of NHK and ADPKD cells is unknown. It is concluded that ouabain stimulates proliferation in ADPKD cells by binding to the Na,K-ATPase with high affinity and via activation of the MEK-ERK pathway.     

Allografts in knee surgery

The use of musculoskeletal allograffs in knee surgery is expanding as outcome studies continue to delineate roles for ligament, meniscal, and osteochondral allouraffs.     

The lateral atlanto-axial joint as a source of headache in congenital atlanto-occipital fusion

A 47-yr-old woman presented with severe right-sided neck pain and headache, predominantly in the right-occipital region, for 3 yrs. The symptoms persisted despite using nonsteroidal antiinflammatory medications and undergoing physical therapy. The patient's examination was unremarkable except for reduced neck motion and prominent right-occipital tenderness. Imaging showed congenital fusion of the atlanto-occipital joints bilaterally. A fluoroscopically guided diagnostic right-lateral atlanto-axial joint injection was positive. We are reporting the first case of clinically proven lateral atlanto-axial joint arthropathy with neck pain and headache in a patient with congenital atlanto-occipital joint fusion. Subsequently, the patient received a set of two therapeutic lateral atlanto-axial joint injections. She had remarkable improvement of her headache and neck pain. At 1-yr follow-up, the patient continued to have significant improvement of the right-sided neck pain and headache.     

Alcohol assessment using wireless handheld computers: a pilot study

The present study sought to test the feasibility of measuring quantity and frequency of self-reported alcohol consumption among college students using the Handheld Assisted Network Diary (HAND) by comparing results to a retrospective Timeline Followback (TLFB). A total of 40 undergraduate college students completed a HAND assessment during the two-week study period and completed a TLFB at follow-up. The HAND recorded similar levels of alcohol consumption compared to the TLFB. There were no significant differences in overall alcohol consumption, drinks per drinking day, or heavy drinking days between the two methods of assessment. Handheld computers may represent a useful tool for assessing daily alcohol use among college students.     

Pharmacokinetic considerations in clinical toxicology: clinical applications

Pharmacokinetic and pharmacodynamic principles should be regarded in the assessment and proper management of patients exposed to a poison. Clinicians must apply these principles to make rational clinical decisions regarding the significance of the poisoning (risk assessment) and to formulate an appropriate management plan. However, pharmacokinetic processes and parameters may be changed in the patient with acute poisoning. This may result from saturation of the capacity of a number of physiological processes due to the high dose, or the toxic effects of the poison may change these processes directly. For example, absorption kinetics may be altered because of increased gastrointestinal transit time (e.g. cholinergic receptor antagonists) or saturable absorption (e.g. methotrexate). Saturation of protein binding may increase the volume of distribution and thereby increase the elimination half-life (e.g. salicylates). Alteration of the acid-base balance (poison-induced or iatrogenic) may also increase or decrease the distribution of a poison. Saturation of metabolism at high doses can prolong toxicity (e.g. phenytoin) or lead to other routes of metabolism that lead to increased toxicity (e.g. paracetamol [acetaminophen]). Excretion may be reduced by saturation of active transporters or decreased renal blood flow.A better understanding of pharmacokinetic principles should improve the clinical care of patients. It should lead to more accurate interpretation of blood concentrations or biomarkers (e.g. ECG intervals or acetylcholinesterase activity) and how these relate to the time course for that poison, and better prediction of prognosis. This in turn, indicates the appropriate duration of observation and the requirement for some specific treatments. Many specific poisoning treatments aim to favourably alter the pharmacokinetics of the poison. These include activated charcoal, whole bowel irrigation, extracorporeal elimination, chelating agents, antitoxins and urinary alkalinisation. The evidence supporting them, their indications and limitations can only be understood using pharmacokinetic principles. These principles also underpin the appropriate choice within the flexible dosage regimen for many antidotes. In particular, naloxone, flumazenil, methylene blue, atropine and pralidoxime all use variable doses and have an elimination half-life that is much shorter than many (but not all) of the poisons treated by these agents. A firm grounding in pharmacokinetics/toxicokinetics should be regarded as a core competency for all professionals involved in clinical care or undertaking research in clinical toxicology.     

Evolution of cell-based reagent provision

Cell-based screening is now part of all stages of drug discovery, and therefore, cell supply is a rate-limiting step. Reagent provision groups have responded by exploiting automation and new concepts such as frozen cells to ease the constraint and increase quality and flexibility of cell supply. With increasing numbers of projects to support, reagent development is now perceived as a new bottleneck. In this review, we describe a new operating model that has emerged at Pfizer UK addressing reagent development and cell supply issues without growing headcount, by complementing the application of internal expertise with use of contract research organisations.