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Asymptomatic common bile duct stones are different to depression quick fix cheap wellbutrin 300 mg without prescription asymptomatic gallbladder stones depression definition yahoo purchase wellbutrin 300mg on-line. The group agreed that an appropriate trial would be one that screened a large population to depression in the bible buy wellbutrin online now identify sufficient people with asymptomatic gallbladder stones cns depression symptoms generic wellbutrin 300 mg with visa, who would then need to be followed up for many years. This is because once people are aware they have asymptomatic gallbladder stones they may report symptoms they would not have otherwise have noticed, or seek medical attention for symptoms that they would not have normally sought attention for. Internal Clinical Guidelines, 2014 51 Gallstone disease Managing asymptomatic gallbladder stones 4. Of the 47 included references, 15 references relating to 9 randomised controlled trials met the inclusion criteria for this review question (see study flow chart in appendix E. In this approach, randomised controlled trials are started with a ‘high’ quality rating and are further downgraded as appropriate. Laparoscopic Conservative Patients with complicated and Under 18 or over 80 years of Conservative 2011a; Schmidt cholecystectomy management non-complicated gallbladder age, severe concomitant management carries a risk et al. October 1991 and May 1994 bile duct stones, acalculous events, but escalation of 2002; Vetrhus et cholecystitis, patients with disease severity or al. There cholecystectomy adequate motivation levels was no advantage in cost N=150 savings compared with inpatient management. Day-case N= 80 suspicion of bile duct stones, procedures are preferable acute cholecystitis, and because it is less calcified gallbladder expensive. As no existing health economic studies were found that addressed all the comparisons in questions 4 and 5, an original economic model was constructed. A single Markov structure with 2-week cycles was used to assess all comparisons (see Figure 1). Not all states and transitions were used in each comparison (see Appendix J for descriptions of the states and transitions available for each comparison). The quality of life impact of interventional procedures reflects length of stay, but is assumed to return to normal within 2 weeks, unless a bile duct injury occurred (assumed to have lifelong impact). The utility impact of living with asymptomatic gallbladder stones were taken from a study of urinary stones (Penniston and Nakada 2007). A number of key parameters are based on the included clinical evidence that has wide confidence intervals; zero event rates in 1 arm are common. Interventions Internal Clinical Guidelines, 2014 57 Gallstone disease Managing symptomatic gallbladder stones are costed using average costs – micro-costing of interventions may help identify differences between options, but may limit the generalisability of the model. This result is driven by the increased costs of higher laparoscopic to open cholecystectomy conversion rates and uncertain rates of bile duct injury and bile leak in the intraoperative cholangiography arm neither of the latter were statistically significant. The increased costs are driven by the additional length of stay in the inpatient arm. Readmission rates were lower in the laparoscopic cholecystectomy group than the conservative management group, and 44% of people in the conservative management group also required cholecystectomy Three studies provided moderate to low quality evidence about laparoscopic cholecystectomy in comparison with laparoscopic cholecystectomy with intraoperative cholangiography and there was uncertainty about whether the addition of intraoperative cholangiography was beneficial or not since there were no significant differences between the groups on any of the outcomes. Five studies providing moderate to low quality evidence compared day-case laparoscopic cholecystectomy with planned inpatient laparoscopic cholecystectomy. A directly applicable original health economic model analysis with minor limitations suggests laparoscopic cholecystectomy is cost effective compared with conservative management. Trade off between benefits and Laparoscopic cholecystectomy compared with conservative harms management the evidence comparing conservative management to laparoscopic cholecystectomy was limited. The evidence showed that disease progression was statistically significantly lower in patients offered cholecystectomy compared with conservative management, but there were no statistically significant differences between the groups in terms of Internal Clinical Guidelines, 2014 59 Gallstone disease Managing symptomatic gallbladder stones readmission, or mortality. Of course all surgeries carry some risks, particularly for people with complex, multiple conditions and for these patients the risk of surgery may well outweigh the risk of disease progression. This was attributed to the fact that patients presenting with symptomatic gallbladder stones will usually be admitted to a surgeon, and when surgery is identified as not being an appropriate treatment option, the patient is then considered for percutaneous cholecystostomy. This is because improved visualisation improves the surgeon’s ability to plan and progress with laparoscopic cholecystectomy, making it safer for the patient. Although some surgeons are appropriately trained for performing endoscopies, the majority of surgeons trained to perform laparoscopic cholecystectomy are not, and surgical lists are not usually planned with both a surgeon and an endoscopist in attendance. For example, patients require adult Internal Clinical Guidelines, 2014 62 Gallstone disease Managing symptomatic gallbladder stones supervision for 24hours after cholecystectomy and people who do not have someone at home to supervise them will require an inpatient stay. Consideration of For laparoscopic cholecystectomy compared with conservative Health Benefits management, the economic model suggests the costs and health and Resource benefits of surgery outweigh the health detriment of leaving the Use gallbladder in situ and having recurrent biliary events. For laparoscopic cholecystectomy versus laparoscopic cholecystectomy with intra-operative cholangiography, the economic model suggests laparoscopic cholecystectomy is a more cost-effective option. Increased costs of inpatient laparoscopic cholecystectomy were driven by higher lengths of stay. Internal Clinical Guidelines, 2014 63 Gallstone disease Managing symptomatic gallbladder stones 8. Journal of Evaluation in Clinical Practice 14: 577-84 Department of Health (2012) National Schedule of Reference Costs 2011-2012. Hollington P (1999) A prospective randomized trial of day-stay only versus overnight-stay laparoscopic cholecystectomy. The Australian and New Zealand Journal of Surgery 69: 8413 Johansson M, Thune A, Nelvin L et al. British Journal of Surgery 98: 362-7 National Institute for Health and Care Excellence (2013) Guide to Methods of Technology Appraisal. For example, some studies didn’t report randomisation procedures and those that did sometimes used inappropriate methods (patient identifying numbers – Hong, 2006), or had methods that led to differences in baseline characteristics of the groups (for example, Hui, 2002) which could bias results. Data from multiple studies were available for most of the comparisons; therefore, metaanalysis was performed wherever possible (see appendix H. However, since the network of evidence for this review question was relatively small, very few of the additional criteria actually applied. Preoperative Surgical bile duct Patients aged 16 to 70 years, Active acute pancreatitis. After cholangiography hospital stay in patients patients with common bile duct treated by surgical bile stones were randomised to bile duct exploration. Alternative management options are only considered for patients for whom surgery/endoscopy is not appropriate, such as those who have complex, comorbid conditions, or those who make an informed choice not to opt for surgery/endoscopy. There were no significant differences in any of the critical or important outcomes and this was attributed to lack of statistical power in the evidence. This was usually when an outcome was possible in one arm of the comparison but not in the other (for example, requirement for cholecystectomy isn’t possible in people who have already had cholecystectomy, but is possible in those waiting for cholecystectomy). Since zero event data cannot be meaningfully analysed, only evidence from studies where deaths were observed were compared. Thus, the range of clinical scenarios that the evidence covered does not reflect reality. Furthermore, the patient would be exposed to the risks of anaesthesia/sedation twice, and there is a risk that their clinical condition could deteriorate in the time between the two procedures. Conversely, laparoscopic cholecystectomy performed after bile duct stones have been removed does not require a surgeon trained in bile duct exploration, and can be performed by any surgeon trained to perform laparoscopic cholecystectomy. The study was underpowered and so no clear conclusions could be drawn about the efficacy and safety of biliary stenting in comparison with ductal clearance. Although the evidence was inconclusive since the single study it was based on was underpowered, the point estimates showed that risk of death and disease progression were higher in the stent group than in the cleared duct group. However, there are various patient and clinical factors that need to be taken into consideration. For example, patients require adult supervision for 24hours after sedation and people who do not have someone at home to supervise them will require an inpatient stay. Similarly, some patients with comorbidities may need admitting to hospital before or after the operation to manage their other conditions. Internal Clinical Guidelines, 2014 82 Gallstone disease Managing common bile duct stones 12. Archives of Surgery 145: 28-33 Sgourakis G, Karaliotas K (2002) Laparoscopic common bile duct exploration and cholecystectomy versus endoscopic stone extraction and laparoscopic cholecystectomy for choledocholithiasis. Hepato-Gastroenterology 59: 51-3 Internal Clinical Guidelines, 2014 84 Gallstone disease Timing of laparoscopic cholecystectomy 4. Of the 8 included studies, 7 related to acute cholecystitis (Gul, 2013; Johansson, 2003; Kolla, 2004; Lai, 1998; Lo, 1998; Macafee, 2009; Yadav, 2009) and one related to common bile duct stones (Reinders, 2010). All studies were assessed for methodological quality using randomised controlled trial checklists, and meta-analysis was performed wherever possible (see appendix H. Overall, the individual studies had good methodological quality, with adequate randomisation and appropriate study conduct.
Step Time Temperature Cycles Enzyme activation 10 minutes 95oC 1 Denaturation 15 seconds 95oC 40 Annealing and extension 1 minute 60oC 40 2 depression symptoms after breakup wellbutrin 300mg amex. Step Time Temperature (oc) Cycles Enzyme activation 15 minutes 95 1 Denaturation 15 seconds 94 Annealing 30 seconds 55 40 Extension 30 seconds 70 15 seconds 95 Melt curve 15 seconds 60 1 15 seconds 95 2 depression support groups order 300 mg wellbutrin mastercard. The group size for the adrenal tissue study was dictated by the availability of suitable clinical samples depression symptoms yawning buy 300mg wellbutrin visa. We initially received 4 control samples (normal adrenal) and were able to bipolar depression in adolescents discount wellbutrin 300 mg with visa subsequently match these with 4 aldosterone-producing adenoma samples. The four non-diseased control samples were more difficult to obtain and determined our sample size. The chip was scanned using a GenePiz 4000B laser scanner and analysed using ArrayPro image software. The raw data were subtracted to background and 107 underwent data adjustment including data filtering, log2 transformation, gene centering and normalisation. The need for such a threshold arises from the non-specific, background fluorescence, which is an unavoidable feature of this method, and requires the imposition of an arbitrary cut-off point for all measurements. The database is derived from peerreviewed scientific literature (Ingenuity Expert Finding, Ingenuity ExpertAssist Finding), miRecords, Tarbase and TargetScan Human. Firstly, terminate any further investigation or secondly choose the most significant hits from the microarray analysis. For in vitro experiments, at least 3 biological samples were performed with a minimum of 3 technical replicate were performed, unless stated otherwise. None of the results were significant, so we proceeded to analyse the most significant hits of the microarray results using unadjusted p-value. We were unable to access to the clinical data for these samples for reasons of ethics and privacy. Microarray allows the analysis of thousands of genes simultaneously in one experiment: a timeand cost-efficient investigation. Similarly, no expression of the remaining cluster members, let-7a-3p and let-7f-1-3p, was detected from the microarray. This is due to its function as a limiting enzyme for cholesterol synthesis, and the fact that cholesterol is the main substrate for steroidogenesis. However in another study, miR-29 was found to be upregulated in aortic dilation (Boon, Seeger et al. It is correlated with significant downregulation of many extracellular matrix 147 components (Boon, Seeger et al. One study suggests that anti miR-29 could improve vascular integrity during aneurysm (Boon, Seeger et al. These genes and proteins can lead to cardiac, liver, renal and pulmonary fibrosis. It is suggested that anti miR-29 could be used as a therapeutic method for aneurysm, vulnerable plaque and pro-elastin/pro-collagen therapies (Van Rooij and Olson 2012). This study proposed miR-29b as a therapeutic tool for antifibrotic therapy (Ogawa, Iizuka et al. Increased miR-29a/b/c might cause insulin resistance by repressing insulin-stimulated glucose uptake (He, Zhu et al. In other tumours, members of let-7 family were significantly suppressed in primary malignant melanoma compared to the control (benign melanocytic nevi). In the urinary system, the expression of miR-125b was significantly decreased in bladder cancer tissue and bladder cancer cell lines. This in vitro experiment showed that miR-125b inhibits the formation of cancer colonies and suppresses bladder tumour in mice. Among miR-125b targets are E2F3 and Cyclin A2, both essential for cell cycle transition (G1/ S phase). This experiment suggested that miR-125b may be involved in cell cycle regulation via the E2F3Cyclin A2 signalling pathway and that downregulation of miR-125b may be a contributing factor to tumorigenesis (Huang, Luo et al. These data suggest that miR125a-5p might be a metastasis suppressor (Wang, Mao et al. In another study, miR-125b was significantly suppressed in malignant melanoma cell lines and downregulates c-Jun protein. Statin is a potent cholesterol lowering drug that lowers cardiovascular mortality in hypercholesterolemia patients (Gould, Rossouw et al. Furthermore, in breast cancer, miR-335 supresses tumour reinitiation and metastasis (Png, Yoshida et al. However, it was first necessary to optimise the selected in vitro cell model, and this is described in Chapter 4. However, this original strain grew very slowly and only loosely attached to surfaces. Therefore, new subtypes were developed by flushing out floating cells and culturing the remaining attached cells. The different subtypes and their culturing conditions are as described in Chapter 2. This chapter describes a series of studies conducted to characterise and compare the different cell strains in order to choose the most suitable model for my subsequent studies. However, the proliferation of H295R was significant using the BrdU assay (Figure 4-5 B) at time points from 24 to 72 hours poststimulation. However the cells were developed further for monolayer cultures (Rainey, Bird et al. This resulted in different strains, each with different serum supplementation required for cell growth (Wang, Rowland et al. In this chapter, a series of studies was conducted to characterise and compare the different strains in order to choose the most suitable model for subsequent in vitro studies. The finding is supported by several studies indicating that the cell line is an effective model for steroidogenesis (Bird, Hanley et al. The cells determine the reliability and reproducibility result; if impaired, these will introduce great variability into the experiment. This is consistent with a de-differentiation of the cells from their steroidogenic phenotype as passage number increases. Transfection is defined as the process of deliberately introducing nucleic acid. The cationic state of the complex will overcome the electrostatic repulsion of the cell membrane and permit entry to the cell. In conclusion, my optimisation studies established H295R strain 1 at lower passage numbers as the best cell line to be used for validation of microarray data. This 164 suggests that changes in the expression of miR-125a-5p are a statistically significant phenomenon related to changes in aldosterone regulation. A miR-125a expression B miR-125a expression (Lipofectamine transfection) (Lipofectamine transfection) 10 * * 10 8 8 6 6 4 4 2 2 0 0 pre-Neg pre-miR-125a anti-Neg anti-miR-125a Figure 5-2: miR-125a-5p expression in H295R cells following transfection with (A) pre-miR125a-5p or (B) anti-miR-125a-5p transfection (n=6 in each group). This effect was tested in vitro by transfecting H295R cells with pre-miR-125a to significantly increase miR-125a-5p levels (see above). To investigate this further, H295R Strain 1 cell was this time transfected with pre-miR-335 and anti-miR-335. A B miR-335 expression miR-335 expression (Lipofectamine transfection) (Lipofectamine transfection) * 0. However, the same significant effect was also observed following anti-miR-335 transfection (Figure 5-6 B); this result contradicts the hypothesis, which predicted that anti-miR-335 should upregulate the miR-335-5p expression. Therefore, stimulated cells from the H295R Strain 1 adrenocortical cell line were used instead. In another recent study, suppression of miR-125a-5p expression in colon cancer cell lines and colon cancer tissue inhibited their proliferation. In addition, to find the cell line that is a precise model for the tissue of interest is challenging. Quantitative data relating to the differentially-expressed miRs mentioned above are provided in Figure 6-5, Figure 6-6 and Figure 6-7, below. Furthermore, miR-106a-5p, miR-19b-3p, miR-20b-5p have similar patterns of expression while mir-92a-3p exhibits an opposite trend, being upregulated by the 3 stimulations. The filter is based on 3 levels of confidence (experimentally observed, highly predicted and moderately predicted), as shown above. Examples are: hsa-miR-1185-1-3p, hsa-miR-136-3p, hsa-miR-1393p, hsa-miR-16-2-3p, hsa-miR-20a-3p, hsa-miR-218-1-3p, hsa-miR-335-3p, hsamiR-3617-3p, hsa-miR-376b-5p, hsa-miR-376c-5p, hsa-miR-493-5p, hsa-miR-5100, hsa-miR-5190, hsa-miR-539-3p, hsa-miR-6076, hsa-miR-7-1-3p, hsa-miR-937-5p.
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Start from birth and review the date when each was given anxiety breathing exercises purchase wellbutrin 300 mg with amex, as well as what was given depression symptoms early morning discount 300mg wellbutrin with visa. Past medical history In this part of the history you will need to bipolar depression xkcd buy wellbutrin 300mg nd out about past visits to bipolar depression checklist cheap wellbutrin 300mg visa the doctor and any admissions to hospital that the child has had. The following list of questions can be used for further review, although it is not exhaustive. Some of these questions will have been covered in your assessment of the presenting problem, so there is no point repeating them. However, it is important that you tailor this part of the history to issues you think relevant to the child’s condition—particularly when you suspect multisystem disease. Heart • Is there a history of heart murmur or rheumatic fever in the patient or family Practice point Draw a family tree to assist your note-taking, and identication of key family and social history information Examining a child: introduction the physical examination of a child is one of the hardest parts of the doctor–patient interaction. You will need to have gained the condence of the family and the child if you are to get the information that you require. How you approach the family (and how you communicate with them) throughout the interaction will be picked up by the child. In fact, a child may decide very early into the interview whether you’ve gained their condence, and whether or not they will let you examine them. No amount of coercing will improve the situation—the parent will often be your advocate and do the convincing for you. It is therefore very worthwhile investing in the art of communication—how to talk with toddlers to teenagers and how to speak effectively with parents of sick children. There is much overlap between the different systems and you will have to decide on when, and in what order, you do things. In a growth clinic, length or height measurements are best done by the auxologist. Practice point • In those under 2yrs old, obtain a length measurement using a table stadiometer. Different units use different methods: • an electronic thermometer in the axilla; • a chemical dot thermometer in the axilla; or • an infrared tympanic thermometer b p. In the infant, count abdominal movements over 1min, if you nd it is easier to see diaphragmatic, rather than chest wall movement. It is important that the size and width of the cuff is appropriate for the size of limb in which pressure is being measured. A single measurement is required in most cases, but if heart disease is suspected, 4-limb measurements are needed. Is there nasal aring, intercostals, subcostal, and sternal recession, use of accessory muscles, forced expiration, grunting, or tracheal tug It is often easier to have the child sitting on the mother’s lap; one of her arms should be held around the upper body, and with the other arm she should place her hand against the side of the child’s head so that it is held rm against her. Is there a rash in the post-auricular area (a feature of dermatitis, measles, and rubella) In young children (<7yrs) it will be in the 4th intercostal space, to the left of the mid-clavicular line, on the left. Listen over the whole precordium—the apex, the 2nd intercostal space to the left of the sternum (pulmonary valve area), the 2nd intercostal space to the right of the sternum (aortic valve area), and the 4th intercostal space over the sternum (tricuspid valve area). Abdomen the child needs to be relaxed and positioned supine, with the knees bent and hands by the sides. First auscultate for bowel sounds, and then percuss in your assessment of hepatomegaly and ascites. In the right mid-clavicular line an enlarged liver extends more than 2cm below the costal margin. The normal span of the liver—between its upper and lower margins—is shown in Table 3. Rectum and anus In most instances you will only need to observe the patency of the anus and to look for ssures and rectal prolapse. However, if the child has abdominal symptoms, a digital examination may be required to check for sphincter tone, masses, and tenderness. For hands, mouth, tongue, abdomen, and eyes see b Respiratory system, Cardiovascular system, and Gastrointestinal system. The external genitalia are examined for any evidence of ambiguity, congenital abnormality, and size. In the older child you must ensure privacy and preserve the child’s dignity with the appropriate use of covers and gowns. Is there evidence of fused labia, enlarged clitoris, or infection with discharge or bleeding Inspect the full length of the spine looking for tufts of hair, dimples, masses, or cysts at the base. Observe for any abnormal curvature or posture with the child standing and bending over touching their toes. The outcome of out-of-hospital arrest is poor, but respiratory arrest alone is associated with a rate of survival of 80%. In hospital, even though unexpected cardiac arrest is now a rare event (1 per 5000 paediatric admissions), it is important that events or signs that may lead to arrest are recognized early. Rapid cardiopulmonary assessment the rapid cardiopulmonary assessment should take less than 1min. Is there recession, nasal aring, grunting, use of accessory muscles, stridor, or wheeze Check pulse volume, capillary rell, skin temperature, level of consciousness, and urine output. Paediatric basic life support algorithm 1 First things • Assess the safety of the situation. Useful formulae in children • Estimation of weight • 0–12 months—Weight (kg) = (0. Sinus tachycardia • Heart rate can be as high as 220/min in an infant, but not higher. Supraventricular tachycardia • the most common primary arrhythmia in infancy and childhood. Ventricular tachycardia • Rare in children; caused by primary cardiac problem or overdose. Most parents will want to see and hold their dead child and they should be offered this opportunity. Follow-up • Arrangements should be made for the family to discuss the results of the coroner’s post-mortem. Practising paediatrics under these conditions means that you will need to anticipate what could happen next, which can be very difcult. Then, we shall cover most of what is needed next for acute care—knowledge, assessments, and treatments. A—establish an airway Provide oxygen Use fractional inspired oxygen (FiO2) 100%; use the optimum method for patient size and monitor. Maintain airway and air movement • Support airway when needed with jaw lift: suction nasopharynx and mouth as needed. B—use respiratory support for breathing • Identify the level of respiratory involvement: treat specic problems appropriately. Respiratory failure • Hypoxaemia despite high FiO2: arterial oxygen tension (PaO2) <8kPa in previously well child. Neuromuscular weakness • Clinical: bulbar dysfunction with poor or absent cough, gag, swallow, or chest wall weakness of neurological or muscular origin. Investigations • Non-invasive: pulse oximetry measurement of oxyhaemoglobin saturation, pulse oximetry measurement of oxyhaemoglobin saturation (SpO2). Therapy There are specic therapies for each condition listed in the ‘Differential diagnoses’ on b p. With regard to uid therapy, we generally restrict total volume to 80% maintenance for the following reasons. After initial symptoms, there may be an asymptomatic period followed by features of pneumonia (see b p. Diagnosis • A monophonic wheeze or absent breath sounds on one side of the chest may be noted on examination. When water has been aspirated into the lungs it is usually a small amount (<22mL/kg).
The risk of photoxicity increases if high concentrations of phototoxic essential oils are used or a blend contains several phototoxic essential oils or if used by fair-skinned people depression line order wellbutrin in india. Orange essential oil can be used in a vapouriser or massage to depression symptoms numbness wellbutrin 300 mg amex aid focus and concentration and facilitate communication anxiety bible verses purchase wellbutrin 300 mg online. There is some evidence that the oil may be an effective treatment for treatment-resistant fungal skin infections depression symptoms without sadness 300mg wellbutrin with mastercard. When the oil or oil products are applied topically to fungal infections, results may be seen within 1–2 weeks; however, 3–4 weeks of treatment may be required. Used internally, bitter orange peel products should provide dyspeptic symptom relief quickly. Use in recommended doses and do not use more than 15% of orange essential oil in a blend. Oral use of bitter orange peel products is not recommended in pregnancy and Seville orange juice can Citrus aurantium 276 induce multiple drug interactions. Antiobesity and cardiovascular toxic effects of Citrus aurantium extracts in the rat: a preliminary report. Quantification and determination of chemical composition of the essential oil extracted from natural orange blossom water (Citrus aurantium L. Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furanocoumarins. Determination of adrenergic agonists from extracts and herbal products of Citrus aurantium L. Citrus aurantium as a thermogenic, weight-reduction replacement for ephedra: an overview. Antioxidant effect of citrus essential oil components on human low-density lipoprotein in vitro. Citrus aurantium 277 © 2007 Elsevier Australia Cloves Historical note Spices such as cloves have been used as food preservatives, disinfectants and antiseptics for centuries (De et al 1999). Modern research has confirmed that cloves are an effective preservative that inhibit the growth of many food-poisoning and food-spoiling bacteria. Eugenol acts on contact to depress nociceptors, the sensory receptors involved in pain perception (Brodin & Roed 1984). Eugenol also inhibits prostaglandin biosynthesis through potent cyclo-oxygenase-1 and -2 inhibitory activity (Huss et al 2002, Kelm et al 2000). Although eugenol is chiefly responsible, other constituents are also involved (Ghelardini et al 2001a). Beta-caryophyllene, another key component of clove oil, exhibits significant anti-inflammatory and rapid Cloves 278 local anaesthetic activity in several animal models (Ghelardini et al 2001b, © 2007 Elsevier Australia Muruganandan et al 2001). Local anesthetic effects develop within 5 minutes of application and diminish after about 15 minutes. Antibacterial activity has been demonstrated against Gram-negative anaerobic periodontal oral pathogens, including Porphyromonas gingivalis and Prevotella intermedia (Cai & Wu 1996). Activity has also been demonstrated against Bacillus subtilis, Listeria monocytogenes, Salmonella enterica, Escherichia coli and Saccharomyces cerevisiae (De et al 1999, Dorman & Deans 2000, Friedman et al 2002). In vitro assays have identified inhibitory effects on hepatitis C virus protease (Hussein et al 2000) and human cytomegalovirus (Shiraki et al 1998, Yukawa et al 1996). An animal model confirmed significant activity against herpes simplex virus type 1 (Kurokawa et al 1998). Cloves are also effective against species belonging to the Eurotium, Aspergillus and Penicillium genera in vitro (Guynot et al 2003). It was more potent than aspirin in several experimental models and equivalent to indomethacin in one (Srivastava 1993). Based on the evidence available, Commission E has approved cloves for use as a local anaesthetic and antiseptic (Blumental et al 2000). The combination significantly reduced the development of skin lesion and/or prolonged survival times of infected mice and reduced viral loads. It is generally used to relieve the symptoms of sore muscles, but a randomised double-blind study found that it is also as effective as paracetamol in reducing headache severity (Schattner & Randerson 1996). Although encouraging, the role of cloves in this combination is difficult to assess from the study. Oral use of the oil Cloves 280 can cause nervous system depression, seizures, hepatic dysfunction and irritation to mucosal tissues. Clove flower buds and clove oil have antiseptic, anti-inflammatory, analgesic, and local anaesthetic properties that are useful in the treatment of toothache, dry socket and common mouth infections. Massaging one drop of the oil into the temples may relieve the symptoms of headache. Clove buds and clove oil should not be taken internally, and only applied externally. Compounds from Syzygium aromaticum possessing growth inhibitory activity against oral pathogens. Antifungal activity of volatile compounds generated by essential oils against fungi commonly causing deterioration of bakery products. Efficacy of traditional herbal medicines in combination with acyclovir against herpes simplex virus type 1 infection in vitro and in vivo. Purification and characterization of eugeniin as an anti-herpesvirus compound from Geum japonicum and Syzygium aromaticum. Tiger Balm as a treatment of tension headache: A clinical trial in general practice. Inhibitory effect of spices on in vitro histamine production and histidine decarboxylase activity of Morganella morganii and on the biogenic amine formation in mackerel stored at 30 degrees C. Antiplatelet principles from a food spice clove (Syzygium aromaticum L) [corrected]. Cloves 282 © 2007 Elsevier Australia Cocoa Historical note Cocoa originates from Mexico where the Mayas, Incas, and Aztecs considered it the food of the gods. Chocolate, mixed with vanilla and sugar, was first introduced as a beverage to Europe by Colombus and was considered an aphrodisiac and a symbol of wealth and power. The phenolics in chocolate prevent the fat becoming rancid, decreasing the need for added preservatives. The beans are dried, roasted, and crushed to produce high-fat, unsweetened chocolate, which is also called baking chocolate. This intermediate is pressed and alkalised to form cocoa powder, which is then homogenised with sugar and cocoa butter, and sometimes milk, to ultimately form chocolate. Dark chocolate generally contains more than 50% cocoa, whereas massproduced milk chocolate only contains around 10% cocoa. White chocolate is based on cocoa butter (or theobroma oil) without the cocoa solids. Although many different types of cocoa beans grow throughout the world, three varieties of cocoa beans are mainly used to make chocolate products: (a) criollo (meaning ‘native’), distributed to the north and west of the Andes, (b) forastero (meaning ‘foreign’), found mainly in the Amazon basin, and (c) trinitario (meaning ‘sent from heaven’) (Bruinsma & Taren 1999). Chocolate also contains additional flavonoids not found in tea, with high concentrations of Cocoa 283 oligomeric procyanidins (Lazarus et al 1999). Post-harvesting and processing pro© 2007 Elsevier Australia cedures can have a striking influence on the flavanol content of chocolate and cocoa (Hollenberg et al 2004). White chocolate primarily contains cocoa butter with minimal levels of polyphenols. Cocoa also contains the methylxanthines, caffeine and theobromine, the biogenic amines phenylethylamine, phenylalanine and tyrosine (Bruinsma & Taren 1999) and the cannabinoid-like fatty acid anandanine analogs, Noleoylethanolamine and N-linoleoylethanolamine (Di Tomaso et al 1996). Chocolate is also a rich source of minerals, including magnesium, calcium, iron, copper, phosphorus, potassium and zinc (Steinberg et al 2003). There is, however, tremendous variability in cocoa processing, flavonoid content and measurement of flavonoids, and questions remain around bioavailability and dosing frequency (Fisher & Hollenberg 2005). A feeding study demonstrated that procyanidins were remarkably stable in the stomach environment and thus most ingested procyanidins reach the small intestine intact and are available for absorption or metabolism (Rios et al 2002). Epicatechin and its metabolites reach maximal levels 2 hours after either chocolate or cocoa intake, with rapid excretion in the urine (Baba et al 2000) and dimeric procyanidins have been detected in human plasma as early as 30–60 minutes after the consumption of flavanol-rich beverages providing 0. It has been suggested that the antioxidant capacity of cocoa polyphenols is greater than synthetic antioxidants and that they have the potential to complement or replace synthetic antioxidants in aqueous and oil-based food applications (Osman et al 2004). Human studies have confirmed that the polyphenols in chocolate are indeed bioavailable and able to increase the antioxidant capacity of plasma, with one study reporting that ingestion of 80 g of procyanidin-rich chocolate increased plasma epicatechin concentrations 12-fold, significantly increased plasma total antioxidant capacity by 31% and significantly decreased 2-thiobarbituric acid reactive substances Cocoa 284 © 2007 Elsevier Australia by 40% after 2 hours, with levels returning to normal within 6 hours (Rein et al 2000a). Similar results were seen in a randomised, double-blind crossover trial that found that a high-flavanol cocoa drink providing 187 mg flavan-3-ols/100 mL significantly reduced lipid peroxidation, compared with a low-flavanol cocoa drink providing only 14 mg/100 mL (Wiswedel et al 2004). In addition to reducing lipid oxidation, consumption of a flavanol-rich cocoa beverage has been shown to reduce susceptibility of erythrocytes to haemolysis and to increase their ability to buffer free radicals (Zhu et al 2005).