Failure of diltiazem to prevent 1:1 conduction of atrial flutter: a case report.

BACKGROUND: Atrial flutter with 1:1 conduction to the ventricles is a dangerous cardiac arrhythmia. Contemporary guidelines recommend atrioventricular nodal blocking agents should be co-administered with class 1C anti-arrhythmics, as prophylaxis against 1:1 flutter. No guidance is provided on the type or strength of atrioventricular nodal blockade required, and in practice, these agents are frequently prescribed at low dose, or even omitted, due to their side effect profile. CASE PRESENTATION: A 62 year old Caucasian man with a history of paroxysmal atrial fibrillation treated with flecainide, presented with atrial flutter with 1:1 conduction to the ventricles and was cardioverted. Diltiazem was added to prevent this complication and he again presented with atrial flutter with 1:1 conduction to the ventricles, despite prophylaxis with coadministration of diltiazem. CONCLUSIONS: This case report demonstrates failure of diltiazem to prevent 1:1 flutter in a patient chronically treated with flecainide for paroxysmal atrial fibrillation.

Assisted lipid deposition by reductive electrochemical aryldiazonium grafting and insertion of the antiport NhaA protein in this stable biomimetic membrane.

Quartz crystal microbalance studies have been carried out to monitor the fusion of lipid vesicles (pure 1,2-dimyristoyl-sn-glycero-3-phosphocholine, DMPC) and mixed vesicles (DMPC and 4-decylaniline). In order to increase the stability of the lipid deposits onto the electrodes, we have developed an original approach involving electrografting of adsorbed mixed vesicles. Aryldiazonium salts generated in situ from 4-decylaniline (4DA) present in adsorbed and fused mixed vesicles at the electrode surface allow their cathodic reduction and subsequent grafting. The stability of the supported lipid deposit has been shown to significantly increase from less than one day for pure DMPC to about two weeks with the lipid deposition assisted by electrochemical grafting. In this stable lipid deposit, the insertion of the sodium/proton antiporter membrane protein (NhaA) or its inactive mutant has been carried out by fusion of proteoliposomes. This has been followed by characterization of the inserted protein activity by cyclic voltammetry onto an electrode previously modified by an adsorbed pH sensor (2-anthraquinone sulfonate). Activation of the protein function by sodium ions leads to a shift of the interfacial pH and confirms the integrity of the immobilized NhaA.

Laccase-based biocathodes: Comparison of chitosan and Nafion.

Chitosan and Nafion(®) are both reported as interesting polymers to be integrated into the structure of 3D electrodes for biofuel cells. Their advantage is mainly related to their chemical properties, which have a positive impact on the stability of electrodes such as the laccase-based biocathode. For optimal function in implantable applications the biocathode requires coating with a biocompatible semi-permeable membrane that is designed to prevent the loss of enzyme activity and to protect the structure of the biocathode. Since such membranes are integrated into the electrodes ultimately implanted, they must be fully characterized to demonstrate that there is no interference with the performance of the electrode. In the present study, we demonstrate that chitosan provides superior stability compared with Nafion(®) and should be considered as an optimum solution to enhance the biocompatibility and the stability of 3D bioelectrodes.

Are current thrombo-embolic prophylaxis guidelines applicable to unicompartmental knee replacement?

Symptomatic and asymptomatic deep-vein thrombosis (DVT) is a common complication of knee replacement, with an incidence of up to 85% in the absence of prophylaxis. National guidelines for thromboprophylaxis in knee replacement are derived from total knee replacement (TKR) data. No guidelines exist specific to unicompartmental knee replacement (UKR). We investigated whether the type of knee arthroplasty (TKR or UKR) was related to the incidence of DVT and discuss the applicability of existing national guidelines for prophylaxis following UKR. Data were collected prospectively on 3449 knee replacements, including procedure type, tourniquet time, surgeon, patient age, use of drains and gender. These variables were related to the incidence of symptomatic DVT. The overall DVT rate was 1.6%. The only variable that had an association with DVT was operation type, with TKR having a higher incidence than UKR (2.2% versus 0.3%, p < 0.001). These data show that the incidence of DVT after UKR is both clinically and statistically significantly lower than that after TKR. TKR and UKR patients have different risk profiles for symptomatic DVT. The risk-benefit ratio for TKR that has been used to produce national guidelines may not be applicable to UKR. Further research is required to establish the most appropriate form of prophylaxis for UKR.

Spinal anaesthesia for ambulatory arthroscopic surgery of the knee: a comparison of low-dose prilocaine and fentanyl with bupivacaine and fentanyl.

BACKGROUND: Prospective data on the use of prilocaine for ambulatory spinal anaesthesia remain limited. We compared the behaviour and characteristics of subarachnoid block using prilocaine and fentanyl with that of bupivacaine and fentanyl. METHODS: In a prospective, double-blind, randomized controlled trial, 50 patients undergoing elective ambulatory arthroscopic knee surgery received subarachnoid anaesthesia, with either prilocaine 20 mg and fentanyl 20 µg (Group P) or plain bupivacaine 7.5 mg and fentanyl 20 µg (Group B). Primary endpoints included times for onset of maximum sensory block level and regression of sensory block to L4, and also motor block at 1 and 2 h, and levels of haemodynamic stability. Comparisons between the groups were made by χ² test for proportions and the Mann-Whitney test for ordinal data. Time-to-event data were analysed by the Mann-Whitney test for uncensored data or the logrank test for censored data. RESULTS: At 2 h, motor block in Group P had fully resolved in 86% of patients, compared with 27% in Group B (P<0.001). Median time to regression of sensory block to L4 was significantly shorter in Group P (97 min) than in Group B (280 min) (P<0.001). A clinically significant decrease in arterial pressure was more common in Group B (73%) than in Group P (32%) (P=0.004). Two patients in Group P required conversion to general anaesthesia, but for reasons unrelated to prilocaine itself. CONCLUSIONS: The combination of prilocaine and fentanyl is a better alternative to that of low-dose bupivacaine and fentanyl, for spinal anaesthesia in ambulatory arthroscopic knee surgery.

Terminating polyelectrolyte in multilayer films influences growth and morphology of adhering cells.

Polyelectrolyte films of anionic poly(sodium 4-styrenesulphonate) (PSS) and cationic poly (allylamine hydrochloride) (PAH) were constructed using layer-by-layer assembly. The authors examined the cytocompatibility of these films for future use in nanobiotechnology applications. Cell lines HEK-293 and 3T3-L1 were cultured on these films and the initial attachment, adhesion, proliferation and cytotoxicity of the cells were measured using a propidium iodide assay. The morphology and spread of the cells were measured by phase-contrast microscopy. The actin cytoskeleton was observed using fluorescent microscopy. Neither the PAH-terminated nor the PSS-terminated polyelectrolyte films were cytotoxic. The PAH-terminated polyelectrolyte films improved the initial attachment and subsequent adhesion of the cells, in addition to enhancing the production of extracellular matrix and the modelling of the actin filaments. The PSS-terminated film enhanced the proliferation of the cells compared to the PAH-terminated film. That was despite the cell cycle, the spreading or the cytotoxicity of both cell types being similar for either the PSS-terminated surfaces or the PAH-terminated surfaces. Cell behaviour can be modulated by the final surface charge of the polyelectrolyte film and the results are useful in guiding the choice of substrates and/or coatings for potential biomedical applications (e.g. implants) as well as cell biology research.

Factors affecting the incidence of infection in hip and knee replacement: an analysis of 5277 cases.

Infection remains a significant and common complication after joint replacement and there is debate about which contributing factors are important. Few studies have investigated the effect of the operating time on infection. We collected data prospectively from 5277 hip and knee replacements which included the type of procedure, the operating time, the use of drains, the operating theatre, surgeon, age and gender. In a subgroup of 3449 knee replacements further analysis was carried out using the tourniquet time in place of the operating time. These variables were assessed by the use of generalised linear modelling against superficial, deep or joint-space post-operative infection as defined by the Australian Surgical-Site Infection criteria. The overall infection rate was 0.98%. In the replacement data set both male gender (z = 3.097, p = 0.00195) and prolonged operating time (z = 4.325, p < 0.001) were predictive of infection. In the knee subgroup male gender (z = 2.250, p = 0.02447), a longer tourniquet time (z = 2.867, p = 0.00414) and total knee replacement (versus unicompartmental knee replacement) (z = -2.052, p = 0.0420) were predictive of infection. These findings support the view that a prolonged operating time and male gender are associated with an increased incidence of infection. Steps to minimise intra-operative delay should be instigated, and care should be exercised when introducing measures which prolong the duration of joint replacement.

Does peri-operative pregnancy alter the outcome of anterior cruciate ligament reconstruction? A report of four cases.

Transient laxity in association with pregnancy of the native anterior cruciate ligament has been previously documented. This phenomenon has only been previously reported in one case of ACL reconstruction, but it has been recommended that patients that become pregnant soon after surgery should be closely observed. We report three cases of pregnancy in relation to primary ACL reconstruction with no obvious adverse outcomes observed on objective assessments. We also report one case of revision ACL reconstruction during pregnancy with a good clinical outcome. We suggest that any hormonal effects on ACL reconstruction during pregnancy, if they do occur, are likely to be very transient and of doubtful clinical impact. In addition, we feel that pregnancy should not be regarded as an orthopaedic contraindication to ACL reconstruction surgery.

Contractility of retinal pericytes grown on silicone elastomer substrates is through a protein kinase A-mediated intracellular pathway in response to vasoactive peptides.

The normal function of retinal capillaries to distribute blood within the retina depends on appropriate contractility of retinal pericytes, which is thought to be modulated by agents that alter intracellular cyclic adenosine-3'-monophosphate (cAMP) levels. We examined the hypothesis that the vasoactive peptides Vasoactive Intestinal Peptide (VIP) and Pituitary Adenylate Cyclase Activating Peptide (PACAP) reduce pericyte contractility via a protein kinase A (PKA)-mediated intracellular pathway that utilises cAMP. We utilised a single-call assay of contractility that is based on visualising the contractile force exerted by the pericytes on a silicone elastomer substrate and quantified, as a contractility index, from the number and length of wrinkles induced in the silicone elastomer by the pericytes. Pericytes were cultured from the retinas of freshly killed abattoir cattle, and identified in culture using immunohistochemical techniques. The pericytes contracted in response to norepinephrine (EC(50)=8 microM) and relaxed in response to both VIP (EC(50)=48 nM) and PACAP (EC(50)=3 nM). The relaxation induced by PACAP was inhibited by Rp-cAMPS (EC(50)=26 microM), which is an agent that inhibits cAMP binding at PKA. We confirmed the activation of PKA by PACAP in experiments where H89 also inhibited the PACAP-induced relaxation. U71322, which inhibits phospholipase C-linked events, was also able to inhibit the PACAP-induced pericyte relaxation. Our results support the hypothesis that PACAP leads to the relaxation of pericytes via a PKA-mediated intracellular pathway and a phospholipase C-mediated pathway, which probably relies on hyperpolarisation because of activation of Ca(2+)-dependent potassium channels. This single-cell assay has proved useful as the basis for the development of a diagnostic procedure for diabetic retinopathy, which is an eye disease caused by abnormal regulation of blood flow in the retinal capillaries.

Intra-articular fibrous band of the ankle: an uncommon cause of post-traumatic ankle pain.

A case of an intra-articular fibrous band of the ankle is presented with emphasis on the MR imaging appearances. This entity is an important but uncommon cause of post-traumatic ankle pain and is well recognized within the arthroscopy literature, but there is little if any documentation of this condition in the imaging literature.

Access to intensive care unit beds for neurosurgery patients: a qualitative case study.

OBJECTIVES: The purpose of this study was to describe the process used to decide which patients are admitted to the intensive care unit (ICU) at a hospital with special focus on access for neurosurgery patients, and evaluate it using "accountability for reasonableness". METHODS: Qualitative case study methodology was used. Data were collected from documents, interviews with key informants, and observations. The data were subjected to thematic analysis and evaluated using the four conditions of "accountability for reasonableness" (relevance, publicity, appeals, enforcement) to identify good practices and opportunities for improvement. RESULTS: ICU admissions were based on the referring physician's assessment of the medical need of the patient for an ICU bed. Non-medical criteria (for example, family wishes) also influenced admission decisions. Although there was an ICU bed allocation policy, patient need always superceded the bed allocation policy. ICU admission guidelines were not used. Admission decisions and reasons were disseminated to the ICU charge nurse, the bed coordinator, the ICU resident, the intensivist, and the requesting physician/surgeon by word of mouth and by written documentation in the patient's chart, but not to the patient or family. Appeals occurred informally, through negotiations between clinicians. Enforcement of relevance, publicity, and appeals was felt to be either non-existent or deficient. CONCLUSIONS: Conducting a case study of priority setting decisions for patients requiring ICU beds, with a special focus on neurosurgical patients, and applying the ethical framework "accountability for reasonableness" can help critical care units improve the fairness of their priority setting.

Priority-setting decisions for new cancer drugs: a qualitative case study.

BACKGROUND: Frameworks for legitimate and fair priority setting emphasise the importance of the rationales for priority setting decisions. However, priority setting rationales, in particular for new cancer drugs, are not well described. We describe the rationales used by a committee making funding decisions for new cancer drugs. METHODS: We did a qualitative case study of a priority setting committee (Cancer Care Ontario Policy Advisory Committee for the New Drug Funding Program) by analysing documents, interviewing committee members, and observing committee meetings. FINDINGS: We identified and described decisions and rationales related to 14 drugs in eight disease conditions over 3 years. Our main findings were that: priority setting existed in relation to resource mobilisation; clinical benefit was the primary factor in decisions; in the context of an expanding budget, rationales changed; rationales could change as costs for individual treatments increased; when all options were reasonable, groups funded a range of options and let patients decide; and priority setting rationales involve clusters of factors, not simple trade-offs. INTERPRETATION: Observing priority-setting decisions and their rationales in actual practice reveals lessons not contained in theoretical accounts.

Comparison of torsional strengths of bioabsorbable screws for anterior cruciate ligament reconstruction.

The goals of this study were to evaluate torsional strength and modes of failure in commercially available bioabsorbable interference screws and to test the effect of screw diameter on torsional strength when screws become jammed during insertion. We tested the Arthrex, BioScrew, Endo-Fix, Phantom, and Sysorb screws, all 20 mm in length. Four major modes of failure were encountered. Analysis of variance revealed that both screw type and diameter had a significant effect on failure torque. The Endo-Fix 7-mm screw had the lowest failure torque (1.07 +/- 0.18 N x m) and the Sysorb 8-mm screw had the highest (5.23 +/- 0.24 N x m). The Sysorb was significantly stronger than all the other screws. The failure torques were within the range that has been reported for manual screw insertion. We concluded that technical factors, which can affect insertion torque, assume particular importance with the use of bioabsorbable interference screws.

Waiting lists for radiation therapy: a case study.

BACKGROUND: Why waiting lists arise and how to address them remains unclear, and an improved understanding of these waiting list "dynamics" could lead to better management. The purpose of this study is to understand how the current shortage in radiation therapy in Ontario developed; the implications of prolonged waits; who is held accountable for managing such delays; and short, intermediate, and long-term solutions. METHODS: A case study of the radiation therapy shortage in 1998-99 at Princess Margaret Hospital, Toronto, Ontario, Canada. Relevant documents were collected; semi-structured, face-to-face interviews with ten administrators, health care workers, and patients were conducted, audio-taped and transcribed; and relevant meetings were observed. RESULTS: The radiation therapy shortage arose from a complex interplay of factors including: rising cancer incidence rates; broadening indications for radiation therapy; human resources management issues; government funding decisions; and responsiveness to previous planning recommendations. Implications of delays include poorer cancer control rates; patient suffering; and strained doctor-patient relationships. An incompatible relationship exists between moral responsibility, borne by government, and legal liability, borne by physicians. Short-term solutions include re-referral to centers with available resources; long-term solutions include training and recruiting health care workers, improving workload standards, increasing compensation, and making changes to the funding formula. CONCLUSION: Human resource planning plays a critical role in the causes and solutions of waiting lists. Waiting lists have harsh implications for patients. Accountability relationships require realignment.

Priority setting for new technologies in medicine: qualitative case study.

OBJECTIVE: To describe priority setting for new technologies in medicine. DESIGN: Qualitative study using case studies and grounded theory. SETTING: Two committees advising on priorities for new technologies in cancer and cardiac care in Ontario, Canada. PARTICIPANTS: The two committees and their 26 members. MAIN OUTCOME MEASURES: Accounts of priority setting decision making gathered by reviewing documents, interviewing members, and observing meetings. RESULTS: Six interrelated domains were identified for priority setting for new technologies in medicine: the institutions in which the decision are made, the people who make the decisions, the factors they consider, the reasons for the decisions, the process of decision making, and the appeals mechanism for challenging the decisions. CONCLUSION: These domains constitute a model of priority setting for new technologies in medicine. The next step will be to harmonise this description of how priority setting decisions are made with ethical accounts of how they should be made.

An entrustment model of consent for surgical treatment of life-threatening illness: perspective of patients requiring esophagectomy.

OBJECTIVE: Consent to treatment has been extensively discussed and prescribed from the viewpoint of law, ethics, and policy experts; the viewpoint of patients is less well represented. The purpose of this study was to describe the process of decision making and consent to surgical treatment from the patients' perspective, in the context of life-threatening illness. METHODS: Face-to-face interviews with 36 patients who had recovered from esophagectomy for cancer at university hospitals in Toronto, Ontario, were analyzed by means of a qualitative analytic approach. RESULTS: Instead of the accepted model of informed consent and shared decision making, patients identified 6 concepts that describe their experience: (1) cultural belief in surgical cure, (2) enhancement of trust through the referral process, (3) idealization of the specialist surgeon, (4) belief in expertise rather than medical information, (5) resignation to risks of treatment, and (6) acceptance of an expert recommendation as consent to treatment. These concepts were developed into a model of entrustment that unites the narratives of all our patients. CONCLUSIONS: There is a gap between accepted legal and ethical theories concerning consent and the patients' account of their experiences with surgical treatment of esophageal cancer. Although our findings should not be used to circumvent the ethical and legal requirements of the consent process and are limited to survivors of treatment of life-threatening disease, they support a careful reassessment of informed consent that includes the perspective of patients.

Sensitive and selective gas chromatographic methods for the quantitation of camphor, menthol and methyl salicylate from human plasma.

Analytical methods using gas chromatography-flame ionization detection (GC-FID) for the quantitation of camphor and menthol and GC-MS for the quantitation of methyl salicylate have been developed for measurement of low concentrations from human plasma. Anethole serves as the internal standard for camphor and menthol and ethyl salicylate serves as the internal standard for methyl salicylate. Plasma samples undergo multiple, sequential extractions with hexane in order to provide optimal recovery. For menthol and camphor, the extracting solvent is reduced in volume and directly injected onto a capillary column (Simplicity-WAX). Extracted methyl salicylate is derivatized with BSTFA prior to injection onto a capillary column (Simplicity-5). Between-day variation (% RSD) at 5 ng/ml varies from 6.2% for methyl salicylate to 13.5% for camphor. The limit of detection for each analyte is 1 ng/ml and the limit of quantitation is 5 ng/ml. These analytical methods have been used in a clinical study to assess exposure from dermally applied patches containing the three compounds.