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PubMedDate not supplied

Clinical vignette in antiretroviral therapy: jaundice.

HIV caregivers face many challenges following initiation of ART. The development of jaundice is uncommon but worrisome. In this case, two distinct and contrasting episodes of jaundice were observed. In the first instance, isolated elevation of the indirect bilirubin without elevation of the alkaline phosphatase was noted. The normal PT and serum aminotransferase levels indicate the absence of intrinsic liver dysfunction. Elevations in the indirect bilirubin may result from either impaired uptake/conjugation or excess production. The latter, usually from acquired hemolysis, may be a complication of an occult NHL. A work-up for this AIDS-related malignancy was not initiated since the caregivers recognized jaundice as a complication of IDV, which inhibits UDP-glucuronyl transferase and produces a Gilbert's-like syndrome. Physicians can expect to encounter this syndrome even more frequently with ATV. Experienced patients given RTV-boosted ATV have experienced elevations of unconjugated hyper-bilirubinemia in up to 45 percent of cases in clinical trials. However, such elevations do not reflect liver dysfunction and symptomatic jaundice requiring dosage reduction that occurred infrequently (7 to 8 percent of study patients). Counseling patients about this syndrome may promote adherence and prevent self-directed interruptions of ATV that compromise efficacy. The second case of jaundice provides a more formidable diagnostic challenge. The triad of LFT abnormalities (mild elevation of aminotransferases, normal PT, and marked cholestatic jaundice) implies an acute process that is mildly toxic to hepatocytes without affecting their synthetic function. The subacute nature of the patient's cholestatic jaundice suggests either intrahepatic infiltrative disease of the liver or extrahepatic obstruction of the biliary tree, most likely due to the patient's relatively modest level of pain and lack of fever. Despite LFT abnormalities occurring 17 months after a switch in his ART, cumulative drug-related toxicities must still be considered. Ritonavir can produce significant elevations in the AST/ALT, especially with pre-existing chronic liver disease as with hepatitis C virus coinfection. The NRTIs can produce hepatic steatosis, a result of mitochondrial toxicity and impaired fatty acid oxidation. However, jaundice and cholestasis are not typical of the latter syndrome. With a negative contrast CT that excludes parenchymal liver disease, investigation of the biliary tree to assess the presence of AIDS-related cholangitis was the next step. Performing a sphincterotomy or stent placement, and obtaining brushings or biopsy specimens to determine the extent of extrahepatic obstruction may help define a pathogen and be life-saving. The negative results of the ERCP justify the final diagnostic step, a liver biopsy to evaluate microscopic infiltrative disease that might not have been detected on contrast abdominal CT. Examples might include granulomatous disease (MAC), fungal etiologies (histoplasmosis), carcinomatosis (lymphoma, hepatoma, cholangiocarcinoma), and microvascular disease (bacillary angiomatosis). The failure to observe granulomatous inflammation in the liver does not exclude MAC infection, as MAC may involve other peri-aortic or mesenteric lymph nodes. This form of IRIS is unlikely given the abdominal CT findings, lack of systemic complaints, and extended persistence of liver aminotransferases. The nonspecific results of the liver biopsy are a common outcome in advanced AIDS patients with elevated alkaline phosphatase levels. Despite not having identified a pathogen, the biopsy establishes chronic liver disease and prompts re-evaluation and change of treatment to NFV. The subsequent normalization of the patient's aminotransferase levels suggests a prior adverse effect of LPV/r in the setting of unexplained, chronic liver disease. Most importantly, this case highlights the importance of HIV caregivers to review ART for safety when noting chronic liver dysfunction. Patients need to be counseled to minimize acetaminophen use, to consume alcohol in moderation, and to avoid behavior with risk for hepatitis C. Finally, all HIV patients should receive appropriate vaccination against hepatitis A and B if serology shows lack of protective immunity.

Acquired Immunodeficiency Syndrome↗

PubMed2004

Does the use of the Advanced Medical Priority Dispatch System affect cardiac arrest detection?

BACKGROUND: Cardiac arrest is the most widely recognised prehospital event that early intervention can directly affect. Chance of survival from this event decreases every minute that passes without treatment. To deliver a rapid ambulance response to these patients the early detection of cardiac arrest by control room staff is crucial. To achieve this, the London Ambulance Service (LAS) uses the Advanced Medical Priority Dispatch System. What impact has AMPDS had on identifying patients in cardiac arrest? Does compliance with AMPDS protocol influence the identification of patients in cardiac arrest? METHODS: A two stage study was undertaken. The first, compared cases coded as "cardiac arrest" and found by the responding ambulance to be in cardiac arrest before the implementation of AMPDS. This was compared with cases triaged as "cardiac arrest" and found to be in cardiac arrest across three years after AMPDS implementation. The second stage compared AMPDS compliance, over a 32 month period against the percentage of cardiac arrest calls that were found to be cardiac arrest upon the ambulance arrival. The correlation coefficient was calculated and analysed for statistical significance. FINDINGS: AMPDS resulted in a 200% rise in the number of patients accurately identified as suffering from cardiac arrest. A relation was identified between identification and AMPDS compliance (r(2) = 0.65, p = 0.001). DISCUSSION: The implementation of AMPDS increased accurate identification of patients in cardiac arrest. Additionally, the relation between factors identified suggests compliance with protocol is an important factor in the accurate recognition of patient conditions.

Ambulances↗

PubMed1997

"En-bloc" removal of small- to medium-sized acoustic neuromas with retrosigmoid-transmeatal approach.

Surgery of acoustic neuroma (AN) has significantly refined over the past years due to a series of advances in diagnostics and surgical technique. Electrophysiologic investigation performed during surgery has greatly contributed to this progress, increasing the surgeon's understanding of the mechanism of damage and suggesting various changes in his or her surgical strategy.In this context, the advantages of the retrosigmoid "en-bloc" removal of small to medium size ANs have been examined in the present study. At the ENT Department of the University of Verona, 103 subjects with AN were operated on, from January 1990 to December 1995, with a retrosigmoid-transmeatal approach. Eighteen subjects (17.4%) presented pure a intracanalar (IC) tumor and 85 (82.6%) had both IC and extracanalar (EC) involvement. All the IC tumors (n = 18) and 70 of the IC-EC neuromas with an EC size less than 25 mm are reported in this paper for a total of 88 patients. The first 48 patients were operated on via the classic procedures described in the literature, characterized by removal of the tumor after "debulking" and limited exposure of the internal auditory canal (IAC). The following 40 subjects were operated on according to the technique of "en-bloc" removal of the tumor and wide exposure of the IAC.In the "en-bloc" group the tumor was first detached from the cerebellar flocculus and the pons, when necessary. The tumor was not debulked to preserve the anatomic relationship with the nerves and to facilitate identification, cleavage and dissection of the tumor from the neural structures. Thereafter, the posterior wall of the IAC was drilled out and opened in a circumferential range from 180 to 270 degrees . The IAC dura was subsequently opened, and the distal end of the AN along with the vestibular nerves were identified. The vestibular nerves were sectioned in the distal portion of the IAC and dissected with the tumor from the underlying facial and cochlear nerves. Dissection continued medially to the IAC porus. The AN was progressively dissected from the cochlear and facial nerves in the cerebellopontine angle (CPA) with multiple direction maneuvers, as required by the characteristics and degree of adherence to the neural structures.The anatomic and functional results obtained with this new procedure ("en-bloc" removal) were compared with the classic "debulking" technique. The statistical analysis shows an improvement in postoperative outcome for both auditory and facial nerve function. The "en-bloc" removal procedure along with the wide exposure of the content of the IAC and electrophysiologic monitoring of the seventh and eighth cranial nerves are, in our experience, the recommended strategies for improving outcomes in small to medium size ANs.

Journal Article↗

PubMed1997

Inhaled nitric oxide does not prevent endotoxin-induced lung injury in rabbits.

BACKGROUND: Neutrophils, platelets, and cytokines are thought to play a pivotal role in the pathogenesis of endotoxin-induced lung injury which resembles features of acute respiratory distress syndrome (ARDS). For initiation of this pathological process, neutrophils and platelets are activated and adhere to pulmonary endothelium. Nitric oxide (NO) inhibits adhesion and activation of these cells and decreases the cytokine level in bronchoalveolar lavage (BAL) fluid obtained from patients with ARDS. Limited data are available on the effect of NO treatment before and after endotoxin on the development and advance of ARDS. The aim of the current study was to determine whether NO inhalation prevents acute lung injury. METHODS: Thirty-two male anaesthetized rabbits were randomly assigned to receive one of four treatments (n = 8 each); Group S-N received saline with nitrogen (N2), Group S-NO received saline infusion with NO (20 p.p.m.) inhalation, Group E-N received an infusion of Escherichia coli endotoxin 100 micrograms/ kg over 60 min with inhalation of N2, and Group E-NO received endotoxin with NO (20 p.p.m.) inhalation. The lungs of the rabbits were ventilated with 40% oxygen until 6 h after the start of endotoxin or saline administration. Haemodynamics and PaO2 were recorded during the ventilation period. After observation, the lung wet-to dry-(W/D) weight ratio, lung mechanics, and cell fraction, activated complements, cytokines, arachidonic acid metabolites, and albumin concentrations in the BAL fluid were measured and analysed. Light microscopic findings were compared among the four groups. RESULTS: Pulmonary hypertension and deterioration of oxygenation by endotoxin were less pronounced in rabbits receiving NO. The lung compliance after endotoxin was similar in Groups E-NO and E-N. The W/D weight ratio and neutrophils and albumin concentrations in the BAL fluid increased in Groups E-NO and E-N. The BAL fluid concentrations of interleukin-8, thromboxane A2, and prostacyclin were similar in the two endotoxin-treated groups. Endotoxin caused extensive morphologic lung damage regardless of NO inhalation. CONCLUSIONS: The increase in pulmonary arterial pressure and deterioration of oxygenation were less in endotoxin-exposed rabbits receiving NO inhalation compared with those receiving N2. Accumulation of neutrophils and platelets in the lung, morphological lung damage, and the release of cytokines and prostanoids were observed in the E-NO group. However, we are unable to extrapolate these results directly to the human clinical setting because of the short observation period, the use of only one dose of NO, and the species difference.

Administration, Inhalation↗

PubMed2000

Current, new and future treatments in dyslipidaemia and atherosclerosis.

The new therapeutic options available to clinicians treating dyslipidaemia in the last decade have enabled effective treatment for many patients. The development of the HMG-CoA reductase inhibitors (statins) have been a major advance in that they possess multiple pharmacological effects (pleiotropic effects) resulting in potent reductions of low density lipoproteins (LDL) and prevention of the atherosclerotic process. More recently, the newer fibric acid derivatives have also reduced LDL to levels comparable to those achieved with statins, have reduced triglycerides, and gemfibrozil has been shown to increase high density lipoprotein (HDL) levels. Nicotinic acid has been made tolerable with sustained-release formulations, and is still considered an excellent choice in elevating HDL cholesterol and is potentially effective in reducing lipoprotein(a) [Lp(a)] levels, an emerging risk factor for coronary heart disease (CHD). Furthermore, recent studies have reported positive lipid-lowering effects from estrogen and/or progestogen in postmenopausal women but there are still conflicting reports on the use of these agents in dyslipidaemia and in females at risk for CHD. In addition to lowering lipid levels, these antihyperlipidaemic agents may have directly or indirectly targeted thrombogenic, fibrinolytic and atherosclerotic processes which may have been unaccounted for in their overall success in clinical trials. Although LDL cholesterol is still the major target for therapy, it is likely that over the next several years other lipid/lipoprotein and nonlipid parameters will become more generally accepted targets for specific therapeutic interventions. Some important emerging lipid/lipoprotein parameters that have been associated with CHD include elevated triglyceride, oxidised LDL cholesterol and Lp(a) levels, and low HDL levels. The nonlipid parameters include elevated homocysteine and fibrinogen, and decreased endothelial-derived nitric oxide production. Among the new investigational agents are inhibitors of squalene synthetase, acylCoA: cholesterol acyltransferase, cholesteryl ester transfer protein, monocyte-macrophages and LDL cholesterol oxidation. Future applications may include thyromimetic therapy, cholesterol vaccination, somatic gene therapy, and recombinant proteins, in particular, apolipoproteins A-I and E. Non-LDL-related targets such as peroxisome proliferator-activating receptors, matrix metalloproteinases and scavenger receptor class B type I may also have clinical significance in the treatment of atherosclerosis in the near future. Before lipid-lowering therapy, dietary and lifestyle modification is and should be the first therapeutic intervention in the management of dyslipidaemia. Although current recommendations from the US and Europe are slightly different, adherence to these recommendations is essential to lower the risk of atherosclerotic vascular disease, more specifically CHD. New guidelines that are expected in the near future will encompass global opinions from the expert scientific community addressing the issue of target LDL goal (aggressive versus moderate lowering) and the application of therapy for newer emerging CHD risk factors.

Anticholesteremic Agents↗

PubMed2005

An observational examination of the literature in diagnostic anatomic pathology.

Original research published in the medical literature confronts the reader with three very basic and closely linked questions--are the authors' conclusions true in the contextual setting in which the work was performed (internally valid); if so, are the conclusions also applicable in other practice settings (externally valid); and, if the conclusions of the study are bona fide, do they represent an important contribution to medical practice or are they true-but-insignificant? Most publications attempt to convince readers that the researchers' conclusions are both internally valid and important, and occasionally papers also directly address external validity. Developing standardized methods to facilitate the prospective determination of research importance would be useful to both journals and their readers, but has proven difficult. In contrast, the evidence-based medicine (EBM) movement has had more success with understanding and codifying factors thought to promote research validity. Of the many variables that can influence research validity, research design is the one that has received the most attention. The present paper reviews the contributions of EBM to understanding research validity, looking for areas where EBM's body of knowledge is applicable to the anatomic pathology (AP) literature. As part of this project, the authors performed a pilot observational analysis of a representative sample of the current pertinent literature on diagnostic tissue pathology. The results of that review showed that most of the latter publications employ one of the four categories of "observational" research design that have been delineated by the EBM movement, and that the most common of these observational designs is a "cross-sectional" comparison. Pathologists do not presently use the "experimental" research designs so admired by advocates of EBM. Slightly > 50% of AP observational studies employed statistical evaluations to support their final conclusions. Comparison of the current AP literature with a selected group of papers published in 1977 shows a discernible change over that period that has affected not just technological procedures, but also research design and use of statistics. Although we feel that advocates of EBM deserve credit for bringing attention to the close link between research design and research validity, much of the EBM effort has centered on refining "experimental" methodology, and the complexities of observational research have often been treated in an inappropriately dismissive manner. For advocates of EBM, an observational study is what you are relegated to as a second choice when you are unable to do an experimental study. The latter viewpoint may be true for evaluating new chemotherapeutic agents, but is unacceptable to pathologists, whose research advances are currently completely dependent on well-conducted observational research. Rather than succumb to randomization envy and accept EBM's assertion that observational research is second best, the challenge to AP is to develop and adhere to standards for observational research that will allow our patients to benefit from the full potential of this time tested approach to developing valid insights into disease.

Anatomy↗

PubMed1997

Expression of the PAF receptor in human monocyte-derived macrophages is downregulated by oxidized LDL: relevance to the inflammatory phase of atherogenesis.

Human monocyte-derived macrophages play a major role in the initiation and progression of atherosclerotic lesions as a result of the production of a wide spectrum of proinflammatory and prothrombotic factors. Among such factors is a potent inflammatory phospholipid, platelet-activating factor (PAF), which is produced after macrophage activation. Because the cells involved in PAF biosynthesis are typically targets for the bioactions of PAF via specific cell surface receptors, we evaluated the expression of the PAF receptor in human monocyte-derived macrophages. Oxidized LDL (oxLDL) exerts multiple cellular effects that enhance lesion progression; we therefore investigated the potential modulation of expression of the macrophage PAF receptor by oxLDL. [3H]PAF bound to adherent human macrophages with a K(d) of 2.1 nmol/L and a B(max) of 19 fmol/10(6) cells; approximately 5300 binding sites per cell were detected. OxLDL (100 microg protein per milliliter) induced a twofold decrease in cellular PAF binding after 3 hours at 37 degrees C. Analysis of macrophage mRNA by reverse transcription-polymerase chain reaction (RT-PCR) revealed two forms corresponding to the PAF receptor, of which the leukocyte type (type 1 promoter) predominated. Expression of PAF receptor mRNA, evaluated by quantitative RT-PCR using an actin or a GAPDH mimic, was progressively reduced (up to 70%) by oxLDL up to 6 hours and remained low for at least 24 hours. Such downregulation was reversible after incubation of the cells for 24 hours in oxLDL-free medium. Addition of forskolin (3 micromol/L) or dibutyryl cAMP (1 mmol/L) to macrophage cultures reproduced the oxLDL-mediated inhibition of PAF receptor expression; carbamyl PAF reduced PAF binding and PAF mRNA to a similar degree (approximately 50%). These data demonstrate that atherogenic oxLDL downregulates the expression of both cellular PAF receptors and PAF receptor mRNA in macrophages, consistent with both a diminished bioresponse to PAF and decreased cell motility. Such diminished bioresponse to a powerful antacoid reflects the suppression of an acute inflammatory reaction, thereby leading to chronic, low-level inflammation, such as that characteristic of fatty streaks and more advanced atherosclerotic plaques.

Cyclic AMP↗

PubMedDate not supplied

A statewide study of EMS oversight: medical director characteristics and involvement compared with national guidelines.

INTRODUCTION: From their inception, advanced life support (ALS) programs have had oversight by emergency medical services (EMS) medical directors. Position statements about medical direction have been published in the medical literature, initially by the American College of Emergency Physicians (ACEP). Most recently, the National Association of EMS Physicians (NAEMSP) published a position paper to serve as a guideline for the medical directors' tasks, describing qualifications and areas of involvement. OBJECTIVE: To study the baseline status of EMS oversight in Maryland as the position paper was disseminated, to view how local directors meet the published guidelines. METHODS: Twenty-two of the 23 (96%) jurisdictional EMS medical directors (JMDs) in Maryland were interviewed in face-to-face meetings. Information was collected about their qualifications and their regular involvement in activities within various EMS subsystems. RESULTS: Sixteen (73%) JMDs are members of ACEP and four (18%) are members of NAEMSP. Six (27%) received EMS medical director training. Three (14%) went through a formal application process for their positions. Activities of relatively high involvement were investigations of variance from protocols (100% of JMDs involved), runsheet review (15 [68%]), liaison duties (20 [91%]), and disaster drills (15 [68%]). Most other subsystems, including dispatch, public health, administration, system evaluation, and quality programs, showed relatively low regular involvement (0-59%). CONCLUSION: In Maryland, significant increases in active physician involvement in EMS are necessary to meet the national job description. These data provide supportive evidence of the need for further commitment by state and local agencies, as well as trained EMS physicians in national societies, to enable all JMDs to reach the goals set forth for their important roles in EMS systems.

Clinical Protocols↗

PubMed2026

Health Literacy and Capecitabine Adherence in a Remote Monitoring Pilot Trial for Breast Cancer: Post Hoc Exploratory Analysis.

BACKGROUND: Oral anticancer therapy enables convenient, home-based cancer care but can introduce adherence challenges, particularly with complex dosing schedules. Capecitabine is commonly used in breast cancer, often as adjuvant therapy or in advanced disease, and typically requires twice-daily dosing on cyclical schedules, increasing the risk of missed or incorrect doses. Low health literacy may exacerbate these difficulties, and emerging remote monitoring tools may help close this gap. OBJECTIVE: In this post hoc exploratory analysis, we evaluated whether health literacy (1) was associated with capecitabine adherence and (2) modified a remote monitoring intervention's effectiveness. METHODS: We conducted post hoc analyses of a 2-arm pilot trial that randomized women with breast cancer treated with capecitabine to enhanced usual care (EUC) or remote patient monitoring (RPM). Adherence was captured with a smart pill bottle, Nomi by SMRxT, that recorded dose timing and quantity. Participants in the RPM group received messages for missed or incorrect doses and weekly symptom assessments. Incorrect or missed doses and severe symptoms triggered alerts to the oncologist. Health literacy was assessed at enrollment. To evaluate moderation, we used linear regression with an interaction term (health literacy × intervention arm) predicting adherence (proportion of days). Marginal effects quantified differences in adherence by study arm and health literacy. RESULTS: Among 28 participants (EUC, n=15 and RPM, n=13), 9 (32.1%) had lower health literacy, 16 (57.1%) identified as Black, 10 (35.7%) identified as White, and 15 (53.6%) had income below 200% of the federal poverty level. In the regression model, the health literacy × randomized group interaction did not reach statistical significance (-16.3 percentage points, 95% CI -35.5 to 2.9; P=.09). Predicted adherence among lower health literacy participants was 87.5% in the RPM group and 65.5% in the EUC group (difference: +22.1 percentage points, 95% CI 6.2-37.9; P=.008). Among participants with higher health literacy, adherence was 89.9% in the RPM group and 84.1% in the EUC group (difference: +5.7 percentage points, 95% CI -5.2 to 16.7; P=.29). Within the EUC group, predicted adherence was 18.6 percentage points lower among those with lower versus higher health literacy (95% CI -32.4 to -4.9; P=.01); within the RPM group, this difference was 2.3 percentage points lower among those with lower versus higher health literacy (95% CI -15.8 to 11.1; P=.73). CONCLUSIONS: In this post hoc exploratory analysis, the estimated difference in capecitabine adherence between the RPM and EUC groups was larger among participants with lower health literacy. Although the formal interaction test was not statistically significant, the magnitude and direction of the observed difference support further investigation of RPM as a potential approach to improve adherence among patients facing health literacy-related adherence barriers. Larger, prospectively powered studies are needed to confirm these findings and evaluate downstream clinical outcomes.

Humans↗

PubMed2006

Performance of department staff in the window between discovery of collapse to cardiac arrest team arrival.

INTRODUCTION: Guideline-directed therapy during the first minutes of resuscitation may be life saving. This study assessed the performance of American Heart Association (AHA) guidelines by trained departmental staff in the period between discovery of collapse and emergency team arrival. METHODS: Over a period of 24 months, departmental performance prior to the arrival of the emergency team (median 180 s) was assessed by debriefings conducted within 24h of each event in a 740-bed tertiary hospital with a dedicated certified resuscitation team. Outcome measures were failure to meet AHA treatment recommendations (primary) and return of spontaneous circulation (ROSC)/survival to hospital discharge (secondary). RESULTS: Two hundred and forty four events were included (216 patients). Mean age was 69+/-17 years; 45% were women. The underlying causes of collapse were mainly cardiac (39%) or respiratory (32%). Residents conducted most of the resuscitations (69%) prior to the arrival of the emergency team. Basic diagnostic measures such as assessments of pulse and rhythm were not performed in 19 and 33% of events. Therapeutic measures such as positive pressure ventilation, chest compressions and defibrillation were not provided according to the guidelines in 17, 12 and 44% of the events. ROSC occurred in 62% of events; 54% of VF/VT, 30% of asystole, 22% of PEA and 76% of bradyarrhythmias/severe bradycardias. Survival to hospital discharge was 37% overall and 41% for patients found in VF/VT (n=33). CONCLUSIONS: Trained departmental staff performed poorly in the moments between patient discovery and arrival of the emergency team. Since patient outcomes were comparable to those described in the literature, poor resuscitation performance may be commonplace in hospitals where ward personnel are expected to deliver advanced life support prior to arrival of the emergency team.

Adult↗

PubMed2003

Issues related to monitoring the safety of over-the-counter (OTC) medicines.

Pharmaceutical advances over the past 50 years have benefited many people in terms of disease prevention and management. However, probably without exception, most pharmaceutical products can cause adverse consequences of varying severity and frequency. In the last 10 years, many medicines that were originally prescription only have now become available over the counter (OTC), either from pharmacies or other general retail outlets. The volume and value of OTC medicine sales have increased accordingly. These switches have been well regulated and based on clear criteria and evidence of safety. Benefits of the changes include increased convenience to patients, greater self-management of minor ailments and a reduction in government drug expenditure.However, there are important differences between medicines supplied OTC and on medical prescription. With OTC medicines there is generally less healthcare professional input into the recommendation or ongoing monitoring of use. There is an absence of records per se, or linkage to other medication records elsewhere, and most countries allow direct-to-consumer advertising of the product. Taken together these differences can result in inappropriate expectations, demand and use of the OTC medicines, with limited opportunity for ongoing patient follow-up and monitoring of safety. Methodologies for pharmacy-based epidemiological studies of OTC medicines need to be developed. Studies should be large enough to detect associations that might exist, and to consider other explanations for associations such as chance, bias or confounding. There have already been some pilot studies with encouraging results with respect to follow-up rates. Outcome data however have usually been self-reported and the studies have lacked a suitable comparison group. Purchasers and suppliers of OTC medicines should also be made aware of, and encouraged to use, existing systems for spontaneous reporting of suspected adverse events, such as the Yellow Card Scheme in the UK. While available OTC medicines are perceived to be generally safe, problems have occasionally arisen with some earlier switched products (e.g. terfenadine). There have also been concerns about some traditional herbal and homeopathic remedies such as St John's wort. While such adverse events are rare, they emphasise the need for healthcare professionals and the public to understand and manage such risks. Many doctors are unaware of the range of OTC preparations available, and therefore do not consider them as a possible cause of presenting symptoms. Neither do they take them into account when making a new prescribing decision. The public need to be aware that OTC medicines should be treated with the same care as prescribed medicines, and that advice on recommended dose, contraindications and interactions should be adhered to.

Humans↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗