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The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use
Sarbjeet S. Kalsi1,2, David M. Wood2,3,4 and Paul I. Dargan2,3,4*
1Emergency Department, Guy's and St Thomas' NHS Foundation Trust, London, UK; 2Clinical Toxicology, Guy's and St Thomas' NHS Foundation Trust, London, UK; 3King's Health Partners, London, UK; 4King's College London, London, UK
Ketamine was originally synthesised for use as a dissociative anaesthetic, and it remains widely used legitimately for this indication. However, there is increasing evidence of non-medical recreational use of ketamine, particularly in individuals who frequent the night-time economy. The population-level and sub-population (clubbers) prevalence of recreational use of ketamine is not known but is likely to be similar, or slightly lower than, that of other recreational drugs such as cocaine, MDMA, and amphetamine.
The predominant features of acute toxicity associated with the recreational use of ketamine are neuro-behavioural abnormalities such as agitation, hallucinations, anxiety, and psychosis. Secondary to these, individuals put themselves at greater risk of physical harm/trauma. Cardiovascular features (hypertension and tachycardia) occur less frequently and the risk of death from recreational use is low and is predominately due to the physical harm/trauma.
Long-term recreational use of ketamine can be associated with the development of psychological dependence and tolerance. There are reports of gastro-intestinal toxicity, particularly abdominal pain and abnormal liver function tests, and of neuropsychiatric disorders, typically a schizophrenia-like syndrome, in long-term users. Finally, there are increasing reports of urological disorders, particularly haemorrhagic cystitis, associated with long-term use. The management of these problems associated with the long-term use of ketamine is largely supportive and abstinence from ongoing exposure to ketamine.
In this review we will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use and the management of this toxicity.
Keywords: ketamine; 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone; recreational drugs; epidemiology; acute toxicity; chronic toxicity; dependence; haemorrhagic cystitis
Received: 26 November 2010; Revised: 13 January 2011; Accepted: 3 February 2011; Published: 15 April 2011
Citation: Emerging Health Threats Journal 2011, 4: 7107 - DOI: 10.3402/ehtj.v4i0.7107
Emerging Health Threats Journal 2011. © 2011 Sarbjeet S. Kalsi et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License (http://creativecommons.org/licenses/by-nc/3.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Ketamine, 2-(2-chlorophenyl)-2-(methylamino)-cyclohexanone is a dissociative anaesthetic that was first synthesised in the United States in 1962 (1). It is listed by the World Health Organisation as an essential medicine (2) and is widely used as a general anaesthetic, both in veterinary and human practice. It is characterised by its ability to cause unconsciousness, amnesia, and analgesia whilst sparing airway reflexes and maintaining haemodynamic stability (3). Ketamine is also gaining favour as an alternative analgesia, particularly in chronic non-cancer pain (4).
Its clinical use has always been limited by a hallucinogenic effect, the so-called emergence delirium described during its first human volunteer trial (1). This effect has however led to recreational, non-medical misuse and there has been evidence of this since 1967 (5). Common street names for ketamine include 'K', 'Special K', 'Kit-Kat', and 'Cat Valium'. It should be noted that colloquial names of recreational drugs change with time and differ between countries and communities, so it is not possible to give a contemporaneous and complete list of common street names for ketamine.
Ketamine is subject to control under recreational drug legislation in many countries; it was added to Schedule III in the United States in 1999 and in the United Kingdom it was controlled as a Class C agent under the Misuse of Drugs Act, 1971 in 2006. The prevalence and geographic spread of ketamine misuse has increased greatly over the past 20 years, and a pattern of adverse effects that differs from that expected from occasional legitimate general anaesthetic use has become apparent. In addition, there is an accumulating literature on ketamine-related chronic toxicity, in particular neuropsychological and urological effects. This review will collate the available information on the epidemiology of recreational use of ketamine and describe the patterns of acute and chronic toxicity associated with its recreational use.
Ketamine produces dissociative anaesthesia by causing electrophysiological dissociation between the limbic and thalamoneocortical systems, resulting in a trance-like cataleptic state characterised by unconsciousness, amnesia, deep analgesia but with intact ocular, laryngeal, and pharyngeal reflexes (1). There are also sympathomimetic, anti-cholinergic and analgesic effects: these start at sub-anaesthetic doses, but persist throughout the period of unconsciousness (1). Of note, ketamine is a chiral molecule with two stereoisomers, and the S(+)-isomer is more potent for inducing general anaesthesia by a ratio of 4:1 (6).
Ketamine is both water- and lipid-soluble, which allows administration by many routes. Intravenous, intramuscular, subcutaneous, oral, nasal, and rectal administration are described both therapeutically (3) and for recreational, non-medical ketamine misuse (7). Extensive first-pass hepatic metabolism of ketamine to its main metabolite norketamine substantially reduces its bioavailability following either oral or rectal administration (see Table 1) (3, 8–10). Ketamine has a short α half-life (2–4 min) and longer β half-life (8–16 min), and its effects vary according to plasma concentration. Analgesia begins at 100 ng/ml, drowsiness and perceptual distortions occur between 50–200 ng/ml, and general anaesthesia requires 2,000–3,000 ng/ml, with awakening occurring when levels fall to 500–1,000 ng/ml (3).
Ketamine has two major metabolites: norketamine, which has one-third the potency of ketamine (11) and dehydronorketamine. Norketamine is produced by cytochrome P450-mediated N-demethylation, mainly by CYP3A4 but with minor contributions from CYP2C9 and CYP2B6 (12). Norketamine is then dehydrogenated to dehydronorketamine and both these metabolites undergo hepatic conjugation. Ketamine and its metabolites are all renally excreted, mostly as conjugates (80%) and dehydronorketamine (16.2%), with very small proportions as ketamine (2.3%) or norketamine (1.6%) (13). They can be detected in the urine for many days: ketamine, 5–11 days; norketamine, 6–14 days; dehydronorketamine, 10 days (14, 15).
Ketamine has activity at several receptors. Primarily, it is an antagonist of the glutaminergic N-methyl-D-aspartate receptor (NMDA-R), both centrally and in the spinal cord (16). Ketamine binds non-competitively to the so-called phencyclidine-binding site of the NMDA-R and prevents neuronal Ca2+ influx, with the S(+)-isomer showing 3–4 times greater affinity (17). This disrupts cortical-cortical and cortical-subcortical signalling (18), producing dissociative anaesthesia, interference with neuronal plasticity, learning and memory, analgesia at central and spinal cord level, as well as interruption of the central sensitization core to chronic pain syndromes (3). Norketamine is also an NMDA-R antagonist, contributing to the effects of ketamine (19).
Ketamine is also reported to be a weak agonist of �-opioid receptors (20), though the NMDA-R antagonism is believed to be more important for its analgesic activity. Its sympathomimetic activity is reportedly due to agonist activity at α1- and β2-adrenoceptors (21), as well as catecholamine re-uptake blockade (22). Ketamine also has a profound anticholinergic effect, produced by antagonism of the central nervous system muscarinic acetylcholine receptors (23) and inhibition of acetylcholinesterase (24), although one of the resultant effects—bronchodilatation—may also be caused by a direct antagonism of endothelin-1-induced bronchial smooth muscle constriction (25). In a rat model, acute ketamine administration resulted in increased dopamine and 5-hydroxyindoleacetic levels in the medial prefrontal cortex (26); however, repeated daily ketamine administration for 7 days attenuated dopamine but enhanced 5-hydroxyindoleacetic acid release. Finally, ketamine potentiates gamma-aminobutyric acid (GABA) synaptic inhibition, through weak GABAA receptor agonism (27, 28), but this is not thought to be clinically significant (3).
Recreational, non-medical ketamine is available to users in powdered, capsule, and liquid formulations. Most recreational use is by nasal insuffulation, with ketamine powder insuffulated either directly or off the surface of objects such as keys or ketamine spoons or vaporised in solution (8). In tablet form, it is often admixed with other pharmacologically active substances such as amphetamine, caffeine, cocaine, amphetamine, and heroin (8). Importantly, recreational ketamine use often occurs with co-use of other substances, and potentially serious adverse pharmacological and toxicological interactions can occur with concomitant use of either central nervous system depressants (e.g. ethanol, opioids, barbiturates, benzodiazepines) or sympathomimetics (e.g. cocaine and amphetamines) (8).
Epidemiology of recreational use of ketamine
Recreational use of ketamine was first reported amongst those with access to the drug, particularly medical professionals, in 1967 (5). It then spread beyond this group to the community-at-large, firstly in the United States and then internationally, in association with the 'rave' dance sub-culture of the 1980–1990s (7, 29). More recently it has become part of the current 'post-rave' clubbing and youth dance culture, as a mainstream 'club drug' alongside drugs such as 3,4-methylenedioxymethampthetamine (MDMA or 'ecstasy'), cocaine, and gamma-hydroxybutyrate (GHB) (30).
The precise prevalence of recreational, non-medical ketamine use is unknown; small single country studies suggest that the background population use rates of ketamine are low, between 0.1 and 4% of those surveyed (summarised in Table 2) (31–34). In addition, data on the population prevalence rates of ketamine is not routinely collected in most countries and is not included in reports from organisations such as the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and the United Nations Office on Drugs and Crime (UNODC). Lifetime and 'recent' recreational use of ketamine is significantly higher in those frequenting the night-time economy (e.g. discotheques, nightclubs, dance/music events; Table 3) (35–38). Four main groups of users are commonly described: regular drug users in the dance music setting, members of the men-who-have-sex-with-men ('gay') club/party scene, injecting heroin users, and self-exploratory people (39). Recreational ketamine use is commonly part of poly-substance use and is taken together with another club drug, ethanol, or stimulant (35, 40).
Geographically, recreational use of ketamine use is seen across the world, but it appears to be most common in East and South-East Asia, potentially because of its relatively low price compared to other psychomimetic drugs, particularly MDMA (41). Global reports of ketamine seizure rose from negligible amounts in 1999 to over 11 metric tonnes in 2007, with nearly all of this in East and South-East Asia, where ketamine seizures exceeded that of heroin (41, 42). Hong Kong reported ketamine as the second-most popular drug of abuse after heroin for the period 2007–2010 (43). Importantly, in the last reported year, 2008, for the first time a substantial minority of seizures (14%) were reported from outside of this region, suggesting a widening of ketamine supply (41).
It is often stated that the bulk of illicitly available ketamine is derived by diversion of legitimate veterinary and medical supplies; however, illicit manufacturing laboratories have now also been reported, particularly in China and South-East Asia (41).
Ketamine-related acute toxicity
The main acute toxicity associated with recreational use of ketamine is related to its psychedelic/hallucinogenic properties. Systemic toxicity with cardiovascular effects can occur, but generally clinical features are related to physical harm, either because of ketamine-induced aggression and agitation or because an individual believes that they can do things without suffering significant injury (e.g. jumping off a building) due to its dissociative features. Any description of acute ketamine toxicity is complicated by the fact ketamine is commonly part of a poly-substance use scenario. In 116 individuals with acute recreational drug toxicity presenting to an Emergency Department in central London who self-reported ketamine use, 89% had used at least one other recreational drug or ethanol (suggesting ketamine is often part of a polydrug repertoire) (44). It is therefore important in patients presenting with acute toxicity after ketamine use, particularly if systemic features are present, to consider that this toxicity may, in part, be due to the co-ingested drug(s).
Neuro-behavioural effects
Recreational use of ketamine can cause a number of troublesome neuro-behavioural/neuropsychiatric effects. Users may be become agitated, aggressive, paranoid, and display dissociative-type symptoms. The content of hallucinations may be unwanted, which are typically referred to by users as 'falling into the K-hole', and in some cases can be significantly unpleasant. In healthy volunteers, an acute sub-anaesthetic dose of 0.1–0.5 mg/kg ketamine is sufficient to induce schizotypal and dissociative symptoms such as altered perception, as well as impaired performance of tests of vigilance, verbal fluency, word recall (45).
Risk of physical harm
One of the biggest concerns surrounding acute ketamine use is that it reduces awareness of the immediate environment, thus exposing the user to potential physical harm (46). The reduced awareness encompasses a sense of depersonalisation, derealisation, reduced perception of pain, and potentially unconsciousness. This is compounded by users frequently experiencing lack of coordination, temporary paralysis, inability to move, blurred vision, and inability to speak (39). As such, users put themselves at risk of significant injury, through jumping from heights, road traffic accidents, drowning, and hypothermia (secondary to incomplete drowning or prolonged environmental exposure (7).
Despite media and public concern about the potential for ketamine to be involved in drug-facilitated sexual assault, it is unusual for ketamine to be detected in this scenario. On screening, only 3 of 1,014 cases in the United Kingdom (47) and 2 of 184 cases from Canada (48) tested positive for ketamine. Drug-driving, on the other hand is more common, and ketamine was associated with 9% of fatal drug-and-alcohol-related single-motor-vehicle collisions in Hong Kong during 1996–2000 (49). During 2007, a single trauma centre in Hong Kong reported 4.5% of drivers involved in non-fatal crashes tested positive for ketamine (50).
Cardiovascular toxicity
During ketamine anaesthetic induction, tachycardia and hypertension precede unconsciousness (1) and this effect is also commonly seen with the sub-anaesthetic doses used for recreational ketamine use. The most common reported cardiovascular effect in patients with acute ketamine toxicity is a self-resolving sinus tachycardia with chest pain and palpitations less commonly reported (44, 51). There have also been isolated reports of acute pulmonary oedema following parental ketamine use, although it is difficult to be certain from these reports whether the pulmonary oedema was due to ketamine or some other factor (52–54). Interestingly, in an in vitro model, alveolar S(+)-ketamine reduced alveolar fluid clearance, although the doses required were not clinically relevant (55).
Risk of death from overdose
Ketamine has a wide therapeutic range and the median lethal dose (LD50) in animals is 100 times the average therapeutic intravenous dose (3), which makes death from overdose difficult. Indeed, death and non-fatal emergencies attributed to ketamine use are considered to be very rare (37). When ketamine is reported in post-mortem samples, it is often either alongside another intoxicant or in the setting of trauma. From the forensic literature regarding death following recreational ketamine use, blood ketamine concentrations within the range of 0.1 to 7.0 mg/l have been reported alongside the presence of another co-ingestant such as ethanol, opiates, amphetamine, or cocaine (56–59). Of the 23 deaths in which ketamine was identified in post-mortem samples in the United Kingdom between 1993 and 2006, only 4 were attributed to lone ketamine poisoning (60). Similarly, in New York City, of 15 out-of-hospital deaths where ketamine was identified in post-mortem samples of persons identified as recreational drug users, 12 were poly-substance overdoses and 2 died as a result of trauma (58).
Management of acute ketamine toxicity
The management of acute ketamine toxicity is largely supportive and involves removing an individual from excessive auditory and visual stimulation until symptoms resolve. In cases of severe symptoms, particularly agitation/aggression, benzodiazepines may be required (51). Most patients typically improve rapidly following acute ketamine toxicity and in those with significant systemic symptoms and/or prolonged ongoing symptoms, clinicians should consider whether there is an alternative diagnosis contributing to the individual's clinical condition (51).
Chronic toxicity related to recreational ketamine use
Recently, the long-term effects of recreational, non-medical ketamine use have come under scrutiny. We will summarise here the data on associated neuropsychological effects, neurotoxicity, dependence, and urological and gastrointestinal pathology.
Neuropsychological effects and neurotoxicity
Ketamine is associated with both neuropsychiatric symptoms and direct neurotoxicity. As described above, ketamine can cause several acute neuropsychiatric effects. Acute and acute-on-chronic use of ketamine has been shown to be associated with impaired information handling within working memory and episodic memory, as well as semantic processing deficits (61, 62). Men appear to be more affected by these effects than women (63). For up to 3 days following ketamine use, subjects are threefold likelier to report unpleasant dreams (64).
Long-term ketamine users appear to have more pronounced and persistent neuropsychiatric symptoms, generally characterised as schizophrenia-like symptoms. In a recent case-control study comparing frequent ketamine users, defined as use at least four-times-a-week, with infrequent users, abstinent users, poly-drug users, and non-drug users, frequent ketamine use was associated with impairment of working memory, episodic memory, executive function and psychological well-being (65). These frequent users were reported as taking an average of 2.77 grams of ketamine an average of 20 days per month. The same group were then followed up for a year, and the frequent ketamine users with increasing ketamine doses were more likely to have cognitive deficits, especially with spatial working memory and pattern recognition memory tasks, and both short- and long-term memory was affected (66). From the same studies, delusional thinking was shown to be correlated positively with the amount of ketamine used by frequent users and persisted despite abstinence (65). A dose-dependent relationship was reported on 1-year follow-up, with frequent users being more delusional than infrequent, abstinent, and non-users, respectively (66). Superstitious conditioning, a form of associative learning, is also more common amongst frequent ketamine users and this process may precede outright delusional thinking (67). Frequent ketamine use is also typified by increased dissociative and depressive symptoms (66), as well as a subtle visual anomaly (68). It is not certain how ketamine causes these effects, but antagonism of the NMDA-R is thought to be important, as is dopaminergic depletion in the prefrontal cortex (3, 26, 69).
Ketamine is also directly neurotoxic. Animal studies have shown that apoptotic neuro-degeneration is induced by NMDA-R antagonists, including ketamine, in the developing rodent brain (70). This effect for ketamine has since been shown to be more marked in older rats and is synergistic with nitrous oxide (71–73); it was ameliorated by GABAA agonism with benzodiazepines, and prevented by neuronal nitrous oxide synthase antagonism with 7-nitroindazole (73, 74). This last finding implicates endogenous nitrous oxide in ketamine-related neurotoxicity. In monkeys, neuronal death was observed after ketamine anaesthesia administered for 9 hours or more but not for 3 hours duration (75). Recently, evidence for harm in humans following frequent ketamine use has been presented, with bilateral frontal and left temporoparietal white matter degeneration shown on brain magnetic resonance imaging being positively correlated to self-reported ketamine dosages (76).
Tolerance and dependency
There is evidence that ketamine causes a psychological, rather than a physical, dependency. The World Health Organisation's International Classification of Diseases (ICD-10) defines substance dependence as 'a cluster of behavioural, cognitive, and physiological phenomena that develop after repeated substance use and that typically include a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal state' (77). This definition holds true for frequent, long-term ketamine use. In particular, ketamine use can be uncontrolled, over-prioritised, and linked with tolerance but does not cause a physical withdrawal state.
Anecdotally, ketamine use in humans is characterised by binging, the drug being repeatedly used until a user's supply has been exhausted (78, 79). This phenomenon is also seen in pigeons and monkeys, who repeatedly self-administer freely available ketamine, suggesting that it is difficult to control ketamine use during a binge (80, 81). Tolerance is considered to be a major factor in the development of dependency (82) and is a well-recognised characteristic of frequent ketamine use, with intranasal doses of up to 130 mg/kg reported (79, 81). Tolerance is likely explained by ketamine auto-induction of metabolism. Ketamine pretreatment doubles its hepatic microsomal metabolism in rats, and both the catalytic activity and protein expression of the rat microsomal cytochrome P-450 system is enhanced by repeated daily ketamine administration (83, 84). Unsurprisingly, frequent ketamine use is associated with increasing doses to achieve the same effect, with a sixfold increase in dosage reported during initiation of chronic use, and frequent users using twice the dose of infrequent users (66, 85).
Urological toxicity
Recently lower urinary tract symptoms (LUTS) of dysuria, increased frequency of small volume micturition, suprapubic pain and, if severe, painful haematuria have been reported amongst long-term ketamine users. There have been no large epidemiological studies, but pilot studies suggest that up to a third of long-term ketamine users may be affected: pooling together the results of three small surveys of frequent users, 50 of 157 ketamine users admitted to LUTS (84–87). In 2007, investigators from Canada linked these symptoms with ulcerative cystitis (88); additionally, those severely affected may also experience obstructive nephropathy (89).
There is evidence from beyond the recreational use setting linking ketamine with urological pathology. In an animal study performed following the reports of human pathology, mice administered intraperitoneal ketamine for up to 6 months demonstrated pathological changes, with mononuclear infiltration occurring throughout the urological tract in the glomeruli, ureters, and bladders (90). Four cases have also been reported from the palliative care setting linking analgesic ketamine use with LUTS (91, 92).
To date, there have been three retrospective case series (n≥10) published, covering 93 patients reporting chronic urological effects in long-term recreational ketamine users (see Table 4) (86, 93, 94). In all of these, patients self-reported ketamine use in excess of 3 months with ketamine use preceding LUTS. Except for one case, all had either sterile or contaminant-only urinary cultures. Reduced bladder volume was reported in three-quarters (57/77) and hydronephrosis in more than half (38/70) of those who had an appropriate investigation undertaken. Commonly, reduced bladder volume was associated with bladder wall thickening, detrusor instability, and vesicoureteric reflux, which explains the hydronephrosis as potentially a secondary effect of the bladder pathology (86, 93). Alternatively, hydronephrosis could also be a result of either peri-ureteric thickening or intraureteric obstruction by ketamine-containing gelatinous debris (86, 89, 93). All of those who had cystoscopy had demonstratable cystitis, with abnormal histology being reported in 32 of 34 biopsies. Unusual features were peri-ureteric thickening (3/71) and raised serum creatinine (8/92), with some patients showing ultrasonographic evidence of papillary necrosis (86); it is unknown if this represents a primary renal insult or arises as a consequence of the hydronephrosis.
Histologically, bladder biopsies from patients with ketamine-associated cystitis show a consistent picture of urothelial ulceration, with eosinophilic infiltration of the lamina propria with surrounding reactive urothelial atypia (88, 94, 95). The appearances are similar to carcinoma in situ, with nuclear enlargement and disorganisation, high p53 immunoreactivity, and moderate-to-high Ki67 immunoreactivity; importantly, what distinguishes the ketamine-related changes from carcinoma in situ is that the ketamine-related biopsies are negative for CK20 (95).
The cause of the bladder pathology is unknown. Given that there are reports of adulterants added to 'street'/illegal ketamine, it is possible that the urinary tract problems are related to the adulterants rather than to ketamine itself. However, in the animal study discussed above, mice were only exposed to intraperitoneal ketamine and still developed mononuclear infiltration occurring throughout the urological tract, in the glomeruli, ureters, and bladders (90). In addition, there are four reported cases from the palliative care setting in patients using pharmaceutical-grade analgesic ketamine who developed LUTS (91, 92). It is likely on the basis of this evidence, that the urinary tract pathology seen is related directly to ketamine and/or its metabolites. Additionally, the bladder is exposed to ketamine and its active metabolites for over a week following a single dose of ketamine (14, 15), which suggests frequent ketamine users would have a prolonged exposure. The evidence for a dose-dependent relationship is strengthened by evidence from a case report of a palliative care patient whose urinary symptoms paralleled the use, discontinuation, reintroduction, and repeat discontinuation of analgesic ketamine (91).
Abstinence of continuing ketamine use is central to managing patients with urological pathology (86, 94, 96). There are no reports of spontaneous resolution of either symptoms or pathology in persistent ketamine users, and both recurrent symptoms and/or worsening pathology are reported in those who return to ketamine use (89, 91). A number of therapies have been explored for the management of ketamine associated urological problems. Some authors have described symptom relief with the use of elmiron (pentosan polysulphate sodium), which is a low molecular weight heparin-like compound that is thought to help increase the glycosaminoglycan layer of the damaged bladder wall urothelium (88). Intravesical hyaluronic acid has also been used (94, 97–99). Hyaluronic acid is a mucopolysaccharide and it is thought that it acts as a urothelial protective barrier. Its use has been described in both general and ketamine-related interstitial and haemorrhagic cystitis (94, 97–99). In one series of six patients with ketamine-related bladder pathology and LUTS, weekly intravesical hyaluronic acid for 1 month resulted in improvement in painful bladder, frequency, and haematuria (94). Surgical intervention, such as augmentation enterocystoplasty or cystectomy with conduit diversion, is generally considered a last resort in patients who have continued symptoms and haematuria despite the above therapies and abstinence from ketamine (93, 94, 100).
Gastrointestinal toxicity
Regular ketamine use is associated with vague abdominal pains of unknown aetiology, colloquially termed 'K-Cramps' (7). Recently, certain authors have described gastric and hepatic pathology in long-term ketamine users investigated for abdominal pains.
In a small retrospective analysis of 37 recreational ketamine users from Hong Kong, typical symptoms of epigastric pain, with or without vomiting, was associated with biopsy-proven Helicobacter Pylori-negative gastritis (101). These symptoms were improved by self-reported abstinence, but neither the abstinence nor gastritis resolution was objectively confirmed. In that same analysis, abnormal liver function tests were reported, but no statistical relationship to symptoms was detected (101). Abnormal liver function tests, irrespective of associated pain, have also been reported elsewhere after clinical ketamine use and non-medical ketamine use (89, 101–105). S(+)-ketamine has recently been shown to be directly hepatotoxic in human hepatoma G2 cells in vitro and this occurs at concentrations compatible with ketamine use (105). However, this effect has not been shown to cause abdominal pains.
Choledochal cysts, benign cystic dilatations of the common bile duct, in association with abnormal liver function tests have been described in ketamine users from the United Kingdom and Hong Kong (89, 103, 104). One chronic ketamine user from the United Kingdom had a dilated common bile duct that regressed with abstinence but recurred following a return to ketamine use (89). All five patients reported from Hong Kong were diagnosed with choledochal cysts following investigations for recurrent epigastric pain and abnormal liver function tests and improvement in both symptoms and common bile duct dilatation occurred with self-reported abstinence. It is unclear what the mechanism for these effects is.
Recreational, non-medical ketamine use is an important public health issue, with evidence of its increasing use in certain population sub-groups, the youth clubbing scene in particular. In the acute setting, the neuro-behavioural and neuropsychiatric effects of ketamine increase the risk of injury and harm to the individual. In the long-term there is evidence of psychological dependency and strong evidence for deleterious neuropsychiatric and urological effects. Long-term users may develop schizophrenia-type symptoms, have poor psychological well-being, memory difficulties, and are at risk of haemorrhagic cystitis with significant associated lower urinary tract symptoms. More work is still needed to better elucidate the epidemiology of ketamine use and the pathophysiological basis of the chronic neuropsychiatric and urological harms.
PD and DW have acted as expert advisers to the UK Advisory Council on the Misuse of Drugs (ACMD) and the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA).
Conflict of interest and funding
The authors have not received any funding or benefits from industry to conduct this study.
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- Lindefors N, Barati S, O'Connor WT. Differential effects of single and repeated ketamine administration on dopamine, serotonin and GABA transmission in rat medial prefrontal cortex. Brain Res. 1997;759:205–12. [Crossref]
- Anis NA, Berry SC, Burton NR, Lodge D. The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol. 1983;79:565–75.
- Irifune M, Sato T, Kamata Y, Nishikawa T, Dohi T, Kawahara M. Evidence for GABA(A) receptor agonistic properties of ketamine: Convulsive and anesthetic behavioral models in mice. Anesth Analg. 2000;91:230–6. [Crossref]
- FDA. Ketamine abuse. FDA Drug Bull . 1979;9:24.
- Laidler KAJ. The rise of club drugs in a heroin society: The case of Hong Kong. Subst Use Misuse. 2005;40:1257–78. [Crossref]
- AIHW (Australian Institute of Health and Welfare). 2007 National drug survey household survey: Detailed findings. Canberra: Author; 2008.
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- Hoare J, Moon D. Drug misuse declared: Findings from the 2009/10 British crime survey England and Wales. Home Office Statistical Bulletin. London: Home Office; 2010, p. 1–109.
- SAMSHA (Substance Abuse and Mental Health Services Administration). The NSDUH report: Use of specific hallucinogens 2006. Rockville, MD: Author; 2008.
- Barrett SP, Gross SR, Garand I, Pihl RO. Patterns of simultaneous polysubstance use in Canadian rave attendees. Subst Use Misuse. 2005;40:1525–37. [Crossref]
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- Lua AC, Lin HR, Tseng YT, Hu AR, Yeh PC. Profiles of urine samples from participants at rave party in Taiwan: Prevalence of ketamine and MDMA abuse. Forensic Sci Int. 2003;136:47–51. [Crossref]
- Dillon P, Copeland J, Jansen K. Patterns of use and harms associated with non-medical ketamine use. Drug Alcohol Depend. 2003;69:23–8. [Crossref]
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- Wood DM, Bishop CR, Greene SL, Dargan PI. Ketamine-related toxicology presentations to the ED [abstract]. Clin Toxicol. 2008;46:630
- Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994;51:199–214.
- Jansen KL. Non-medical use of ketamine. BMJ. 1993;306:601–2. [Crossref]
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- Weiner AL, Vieira L, McKay CA, Bayer MJ. Ketamine abusers presenting to the emergency department: A case series. J Emerg Med. 2000;18:447–51. [Crossref]
- Pandey CK, Mathur N, Singh N, Chandola HC. Fulminant pulmonary edema after intramuscular ketamine. Can J Anaesth. 2000;47:894–6. [Crossref]
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- Moore KA, Kilbane EM, Jones R, Kunsman GW, Levine B, Smith M. Tissue distribution of ketamine in a mixed drug fatality. J Forensic Sci. 1997;42:1183–5.
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- Schifano F, Corkery J, Oyefeso A, Tonia T, Ghodse AH. Trapped in the 'K-hole': Overview of deaths associated with ketamine misuse in the UK (1993–2006). J Clin Psychopharmacol. 2008;28:114–6. [Crossref]
- Morgan CJ, Curran HV. Acute and chronic effects of ketamine upon human memory: A review. Psychopharmacology (Berl) 2006;188:408–24. [Crossref]
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- Morgan CJ, Perry EB, Cho HS, Krystal JH, D'Souza DC. Greater vulnerability to the amnestic effects of ketamine in males. Psychopharmacology (Berl) 2006;187:405–14. [Crossref]
- Blagrove M, Morgan CJ, Curran HV, Bromley L, Brandner B. The incidence of unpleasant dreams after sub-anaesthetic ketamine. Psychopharmacology (Berl) 2009;203:109–20. [Crossref]
- Morgan CJ, Muetzelfeldt L, Curran HV. Ketamine use, cognition and psychological wellbeing: A comparison of frequent, infrequent and ex-users with polydrug and non-using controls. Addiction. 2009;104:77–87. [Crossref]
- Morgan CJ, Muetzelfeldt L, Curran HV. Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: A 1-year longitudinal study. Addiction. 2010;105:121–33. [Crossref]
- Freeman TP, Morgan CJ, Klaassen E, Das RK, Stefanovic A, Brandner B, et al. Superstitious conditioning as a model of delusion formation following chronic but not acute ketamine in humans. Psychopharmacology (Berl) 2009;206:563–73. [Crossref]
- Jansen KL. Ketamine—Can chronic use impair memory? Int J Addict. 1990;25:133–9.
- Narendran R, Frankle WG, Keefe R, Gil R, Martinez D, Slifstein M, et al. Altered prefrontal dopaminergic function in chronic recreational ketamine users. Am J Psychiatry. 2005;162:2352–9. [Crossref]
- Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, et al. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999;283:70–4. [Crossref]
- Beals JK, Carter LB, Jevtovic-Todorovic V. Neurotoxicity of nitrous oxide and ketamine is more severe in aged than in young rat brain. Ann NY Acad Sci. 2003;993:115 [Crossref]
- Jevtovic-Todorovic V, Carter LB. The anesthetics nitrous oxide and ketamine are more neurotoxic to old than to young rat brain. Neurobiol Aging. 2005;26:947–56. [Crossref]
- Jevtovic-Todorovic V, Benshoff N, Olney JW. Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats. Br J Pharmacol. 2000;130:1692–8. [Crossref]
- Wang C, Sadovova N, Patterson TA, Zou X, Fu X, Hanig JP, et al. Protective effects of 7-nitroindazole on ketamine-induced neurotoxicity in rat forebrain culture. Neurotoxicology. 2008;29:613–20. [Crossref]
- Zou X, Patterson TA, Divine RL, Sadovova N, Zhang X, Hanig JP, et al. Prolonged exposure to ketamine increases neurodegeneration in the developing monkey brain. Int J Dev Neurosci. 2009;27:727–31. [Crossref]
- Liao Y, Tang J, Ma M, Wu Z, Yang M, Wang X, et al. Frontal white matter abnormalities following chronic ketamine use: A diffusion tensor imaging study. Brain. 2010;133:2115–22. [Crossref]
- WHO. International Classification of Diseases (ICD) 10. 2nd ed. Geneva: Author; 2007 [updated 2010 November 5]. Available from: http://apps.who.int/classifications/apps/icd/icd10online/index.htm?gf10.htm+F192.
- Jansen KL, Darracot-Cankovic R. The nonmedical use of ketamine, part two: A review of problem use and dependence. J Psychoactive Drugs. 2001;33:151–8.
- Morgan CJ, Rees H, Curran HV. Attentional bias to incentive stimuli in frequent ketamine users. Psychol Med. 2008;38:1331–40.
- Lu Y, France CP, Woods JH. Tolerance to the cataleptic effect of the N-methyl-D-aspartate (NMDA) receptor antagonists in pigeons: Cross-tolerance between PCP-like compounds and competitive NMDA antagonists. J Pharmacol Exp Ther. 1992;263:499–504.
- Moreton JE, Meisch RA, Stark L, Thompson T. Ketamine self-administration by the rhesus monkey. J Pharmacol Exp Ther. 1977;203:303–9.
- Nutt D, Lingford-Hughes A, Daglish M. Future directions in substance dependence research. J Neural Transm Suppl. 2003;64:95–103.
- Marietta MP, White PF, Pudwill CR, Way WL, Trevor AJ. Biodisposition of ketamine in the rat: Self-induction of metabolism. J Pharmacol Exp Ther. 1976;196:536–44.
- Chan WH, Sun WZ, Ueng TH. Induction of rat hepatic cytochrome P-450 by ketamine and its toxicological implications. J Toxicol Environ Health A. 2005;68:1581–97. [Crossref]
- Muetzelfeldt L, Kamboj SK, Rees H, Taylor J, Morgan CJ, Curran HV. Journey through the K-hole: Phenomenological aspects of ketamine use. Drug Alcohol Depend. 2008;95:219–29. [Crossref]
- Chu PS, Ma WK, Wong SC, Chu RW, Cheng CH, Wong S, et al. The destruction of the lower urinary tract by ketamine abuse: A new syndrome? BJU Int. 2008;102:1616–22. [Crossref]
- Cottrell A, Warren K, Ayres R, Weinstock P, Kumar V, Gillatt D. The destruction of the lower urinary tract by ketamine abuse: A new syndrome? BJU Int. 2008;102:1178–9.
- Shahani R, Streutker C, Dickson B, Stewart RJ. Ketamine-associated ulcerative cystitis: A new clinical entity. Urology. 2007;69:810–2. [Crossref]
- Selby NM, Anderson J, Bungay P, Chesterton LJ, Kolhe NV. Obstructive nephropathy and kidney injury associated with ketamine abuse [case report]. Nephrology Dialysis Transplantation Plus. 2008;1:310–2.
- Yeung LY, Rudd JA, Lam WP, Mak YT, Yew DT. Mice are prone to kidney pathology after prolonged ketamine addiction. Toxicol Lett. 2009;191:275–8. [Crossref]
- Gregoire MC, MacLellan DL, Finley GA. A pediatric case of ketamine-associated cystitis. Urology. 2008;71:1232–3. [Crossref]
- Storr TM, Quibell R. Can ketamine prescribed for pain cause damage to the urinary tract? Palliat Med. 2009;23:670–2. [Crossref]
- Mason K, Cottrell AM, Corrigan AG, Gillatt DA, Mitchelmore AE. Ketamine-associated lower urinary tract destruction: A new radiological challenge. Clin Radiol. 2010;65:795–800. [Crossref]
- Tsai TH, Cha TL, Lin CM, Tsao CW, Tang SH, Chuang FP, et al. Ketamine-associated bladder dysfunction. Int J Urol. 2009;16:826–9. [Crossref]
- Oxley JD, Cottrell AM, Adams S, Gillatt D. Ketamine cystitis as a mimic of carcinoma in situ. Histopathology. 2009;55:705–8. [Crossref]
- Shahani R, Stewart RJ. Reply to letter-to-the-editor, Re: Shahani R, Streutker C, Dickson B, et al: Ketamine-associated ulcerative cystitis: A new clinical entity. Urology. 2007;69:810–2. Urology. 2008;71(5):987. [Crossref]
- Kallestrup EB, Jorgensen SS, Nording J, Hald T. Treatment of interstitial cystitis with Cystistat: A hyaluronic acid product. Scan J Urol Nephrol. 2005;39:143–7. [Crossref]
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- Chu PS, Kwok SC, Lam KM, Chu TY, Chan SW, Man CW, et al. 'Street ketamine'-associated bladder dysfunction: A report of ten cases. Hong Kong Med J. 2007;13:311–3.
- Poon TL, Wong KF, Chan MY, Fung KW, Chu SK, Man CW, et al. Upper gastrointestinal problems in inhalational ketamine abusers. J Dig Dis. 2010;11:106–10. [Crossref]
- Kimura F, Hashimoto Y, Shimodate Y, Hashimoto H, Ishihara H, Matsuki A. Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine—8. Hepatic and renal functions following prolonged surgical operation of over 10 hours [in Japanese]. Masui. 1991;40:1371–5.
- Ng SH, Lee HK, Chan YC, Lau FL. Dilated common bile ducts in ketamine abusers. Hong Kong Med J. 2009;15:157
- Wong SW, Lee KF, Wong J, Ng WW, Cheung YS, Lai PB. Dilated common bile ducts mimicking choledochal cysts in ketamine abusers. Hong Kong Med J. 2009;15:53–6.
- Lee ST, Wu TT, Yu PY, Chen RM. Apoptotic insults to human HepG2 cells induced by S-(+)-ketamine occurs through activation of a Bax-mitochondria-caspase protease pathway. Br J Anaesth. 2009;102:80–9. [Crossref]
*Paul Dargan
Medical Toxicology Office
2nd Floor, Bermondsey Wing
Guy�s Hospital
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London, SE1 9RT
United Kingdom
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Plumbing, Heating and Air Conditioning Services in Oxford, PA
Horizon Services, Inc. is Oxford, Pennsylvania's largest and most referred home services company, ready to meet all of your needs for plumbing, heating, air conditioning, drain cleaning and sewer & water line replacement. From routine service and maintenance…to emergency repairs…to expert installation and replacement of state-of-the-art home heating and cooling systems, Horizon Services is the company more homeowners and businesses in Upper Oxford Township, Lower Oxford Township and Oxford, PA turn to than any other.
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When temperatures are up and your air conditioning is down for the count, who are you going to call? Horizon Services, the air conditioning authority in Oxford, PA! We service and repair all makes and models of air conditioners. And if you want to replace your old air conditioner, we sell and install reliable air conditioning systems that can maximize your energy savings and comfort. Learn More About Our Air Conditioning Services!
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subset: commoncrawl


text:
Hey there, time traveller!
This article was published 1/10/2013 (1419 days ago), so information in it may no longer be current.
The Linden Woods Fall Classic is back for its 10th year on Oct. 6, and it's looking for runners.
"We want to pump up the spirit because it's the 10th anniversary," said Cindy Epp, race director.
Funds raised will go towards charities in the community, helping École Van Walleghem School build a new playground, and 40% goes to breakfast programs in six different area schools in the Pembina Trails School Division.
"We typically have 350 to 400 people come out," said Epp. "Once we got our play structure, that was the initial reason for the race, we felt very, very lucky that we live in such a great neighbourhood and we have this beautiful park and we wanted to pay it forward."
The event includes a 10-kilometre, five-kilometre, and a four-kilometre family walk.
The cost to register online ranges from $18 to $28, depending on age and whether or not someone is a Manitoba Runners' Association member. In-person registration is $5 more than the online cost. For more information, visit www.lwfc.ca or search for the Linden Woods Fall Classic on Facebook.


text:
Electricians healthy, mend and company sizzling and cold-water techniques, and heat systems in organizations and properties. Silicon endures eternally generally, doesnt to eliminate it, and worsen or dry out you merely rating it using a cutlery. When installing it onto the laminate the specialist believed to use plumbers putty underneath the top of the stainless sink.
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text:
Issue No. 10 - October (2006 vol. 28)
pp: 1707-1712
Counting spatially and temporally overlapping events in image sequences and estimating their shape-size and duration features are important issues in some applications. We propose a stochastic model, a particular case of the nonisotropic 3D Boolean model, for performing this analysis: the temporal Boolean model. Some probabilistic properties are derived and a methodology for parameter estimation from time-lapse image sequences is proposed using an explicit treatment of the temporal dimension. We estimate the mean number of germs per unit area and time, the mean grain size and the duration distribution. A wide simulation study in order to assess the proposed estimators showed promising results. The model was applied on biological image sequences of in-vivo cells in order to estimate new parameters such as the mean number and duration distribution of endocytic events. Our results show that the proposed temporal Boolean model is effective for obtaining information about dynamic processes which exhibit short-lived, but spatially and temporally overlapping events.
Temporal Boolean model, 3D Boolean models, germ-grain models, coverage processes, functional data analysis, endocytosis, total internal reflection fluorescence microscopy.
Guillermo Ayala, Mar?a Elena D?az, Roberto Zoncu, Derek Toomre, Ester D?az, Rafael Sebastian, "Analysis of Spatially and Temporally Overlapping Events with Application to Image Sequences", IEEE Transactions on Pattern Analysis & Machine Intelligence, vol. 28, no. , pp. 1707-1712, October 2006, doi:10.1109/TPAMI.2006.199


text: Do you have a recommendation for the wiring? We have pretty much decided to replace the box with either new wood or a composite material like trex, but I don't know much about the wiring. That is, I know I can do the wiring work (I have done some in things inside the house), but sprinklers are new to me and I'm not sure quite how it is supposed to be done. Thanks.


text:
Marketing for today's smart phones rarely touches on actually making a call but rather the host of other ancillary features as part of your mobile device, starting with the camera.
Plenty of cell phone shoppers that make initial foray into the smart phone world come complete with a common question: how is the camera on that phone?
That inquisition probably stems from consumers who may be growing tired of toting around a smart phone and camera, and ultimately want the best of both words by eliminating one or the other. Camera phones certainly aren't anything new as even the antiquated flip phones have, at the very least, modest means for taking pictures.
Today's version of cell phones that double as cameras essentially put the camera business on notice that they're in the midst of a takeover. Why would anyone buy a camera and phone separately anymore?
Unless you're a professional photographer, you're probably more than fine with the idea that your cell phone camera is plenty advanced enough for birthday parties, graduations or simply getting together with friends.
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text:
Email Encryption- The Secure Way To Send Data Over The Internet
Technology has changed our lives many folds in the past few decades. One of the best inventions of all time, one that encompasses all and affects every facet of every person's life on this planet, is of course the internet. Getting your information to travel across borders of physical distances and time lags has completely revolutionized the way we go about our daily business. Whether it is something as trivial as a Facebook update or something sensitive like national metrics that can affect a new government policy – anything and everything is now exchanged over the World Wide Web.
But just like always, dependency on technology too has its consequences. There are always miscreants and criminals lurking just around the corner, waiting for the chance when they can get their hands in your information so that they can misuse it for their own dubious purposes. This miscreant can be a professional hacker looking for sensitive data to sell out onto the wrong hands. This miscreant can be a jealous colleague trying to read your screen over your shoulder just to get enough information to bring your career down. And this is where technology like email encryption comes into play and helps people take stock.
When you send out any email, the data included in it travels in packets over large distances. We may not realize it, but every speck of information that we share over the internet travels from one server to another and passes through scores of these data storage and dissemination nodes before it reaches the final destination. And an experienced hacker can find a way to tap into these servers and extract your data. But this is data theft at a much larger level. What about your fellow workers trying to guess your password and gaining unauthorized access to your mail account just to see the new project you are currently working on or any sensitive numbers and data? These simple crimes happen every day and if the security of your data is important to you, you should consider going for email encryption.
What an encrypted email does is that it makes the data and information you are sharing in your mails into something that is strictly 'FOR YOUR EYES ONLY'. This means either you or the intended recipient of the email will be the only two people allowed to set their eyes upon the information you are sharing. No one else will be able to access it. Wondering how its done? I'll explain..
There are many email encryption softwares available in the market that provide foolproof ways to preserve the integrity of your data. They might use public key encryption systems in which the sender holds the key to encrypt the data and the receiver holds the key to decrypt. As long as the key pair doesn't fall into the wrong hand, the data included in the e mail remains safe. There are many other, more sophisticated forms of email encryption existing as well but public key encryption happens to be the most popular one. If you need more information about it , please visit http://zixmailencryption.com/.
About The Author
Zeena McWarden is a cyber security expert who writes many interesting articles to help bring email encryption and its advantages into the domain of common people. You can trust her advice for all your data security and integrity preservation requirements.


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February 10-11, 2017
IEA Professional Development Center
Springfield, IL.
The IEA Early Career Teachers Retreat is a networking and professional development event sponsored by the IEA Early Career Teachers Committee. This event aims to meet the needs of teachers in their 1st through 10th years of teaching. The non-refundable registration fee is $20 but register no later than January 9 for the Early Bird discounted price of only $10.


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For Lease ($42.50 psf) on Southport Corridor in the Music Box Theater Building. Located just north of L Stop, approx 900 sq.ft. space, large window & vintage charm. Ideal for a retail or service retail space. Owner will deliver vanilla box or give adequate time for tenant to complete. Strong retail & entertainment corridor with high household incomes.
The listing information set forth on this site is based upon information which we consider reliable, but because it has been supplied by third parties to our franchisees (who in turn supplied it to us) , we cannot represent that it is accurate or complete, and it should not be relied upon as such. The offerings are subject to errors, omissions, changes, including price, or withdrawal without notice. All dimensions are approximate and have not been verified by the selling party and cannot be verified by Sotheby's International Realty Affiliates LLC. It is recommended that you hire a professional in the business of determining dimensions, such as an appraiser, architect or civil engineer, to determine such information.


text:
Today our school dressed up and cleaned up for CLEAN UP AUSTRALIA DAY!
It was fun to be a part of this National event, knowing that we were doing our part to keep the school environment clean and tidy.
Many students not only filled rubbish bags but wore rubbish bags to help spread the message.
It is important that everybody gets involved and helps to reduce, reuse and recycle our rubbish.
WE are lucky to have such an awesome Environment Team to get us all motivated and organised for this very important day.
WHAT do you do to help keep Australia or your home country Beautiful?


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The distant clouds were getting darker. In a far off corner of horizon, we saw rain pouring down from a fluffy cloud. As the gentle waft of wind salvaged us from the afternoon sun, we continued our hike towards the top most vantage point of Rayakottai fort. The view of the green landscape was fascinating. How lovely would the 360 degree view from top be? Our minds were creating enticing imageries. I was glad we planned this day hike.
It has been almost two years since I shifted to Bangalore. The city of gardens has been a melting pot of experiences for me. Apart from the Bangalore city attractions, there are plenty of weekend or day trip options in vicinity. For a travel enthusiasts, Bangalore and surrounding destinations offer a lot of places to stay, experiences to cherish and attractions to marvel at. Rayakottai fort is one such worthy attraction to visit from Bangalore
View of Rayakottai Fort from the beginning of trek
Rayakottai fort is one of Tipu Sultan's lesser known forts. Rayakottai fort is built on a hillock which is higher than any other hillock in vicinity. This made Rayakottai fort a good vantage point and provided a strategic advantage to Tipu Sultan's army. Located in Krishnagiri district of Tamil Nadu, Rayakottai fort is at a distance of 75 KMs from Bangalore city. In monsoon, the fort ruins are engulfed by imposing dense foliage. As you scram your way through the dangling plant leaves and protruding twigs, it feels like history and nature are creating a symphony, melodious for heart.
We started early morning from Bangalore to reach Rayakottai fort before the sun reaches zenith. We had taken a friend's car and at 6 am, we were already pacing leisurely on Bangalore roads. The road to Rayakottai fort passes Hosur and enters Tamil Nadu. It took us 3 hours to reach Rayakottai fort as we spent a good amount of time savouring breakfast at a road side outlet. When we reached Rayakottai fort, we had to ask local people for guidance as there were no clear directions. They helped us to reach starting point of the short hike which would lead us to the highest vantage point of Rayakottai fort.
We started the hike around 10 am after finding a parking spot for our car. Instead of starting from the main entrance, we were directed towards a shortcut by local folks. The initial 1 Km of the hike was a rocky patch, bordered by lush green foliage and dotted by fluttering butterflies. I was surprised to notice myriad species of butterflies, leisurely wandering from one flower to another.
The view of valley while hiking
The hike started to lead us in denser foliage and we discovered some caves which provided a good backdrop for capturing memories on celluloid. We continued our hike to reach a vantage point. The view along the edges of Rayakottai fort looked stunning. The horizon was clear and visibility was good enough to spot a beautiful arrangement of hillocks surrounding a distant lake. The terrain was more gorgeous than what we had initially expected.
The caves looked like an elephant's side pose from this angle
We also noticed a very small pond amidst the fort ruins. A green blanket of algae covered the pond and created a mystic ambiance. We started to walk in direction of the highest vantage point. While navigating our way through boulders and rocks, we were gaining considerable altitude and in another half an hour, we were standing gazing at the distant horizon and scattered clouds. We spotted a couple of well camouflaged chameleons who were around a foot long! They were about to get engaged in a fight and moved their necks rapidly as if cheering a rock performance. The gesture is an expression of aggression in chameleons. However, the aggression faded away and we missed witnessing a chameleon fight.
Posing away at a lower vantage point Two chameleons ready to engage in a fight, they didn't howeverThe lovely landscapes from lower vantage point
The highest vantage point of Rayakottai fort was still further up. We finally reached up there and revelled in a 360 degree view of the surroundings. The hillock on which Rayakottai fort is built, gives the best view as it stands taller than any other hillocks in vicinity. We saw a railway line spread in serpentine fashion across the rocky and green terrain below. A puddle in proximity, formed in heart shape looked adorable from the top. In far distant, some dark clouds were one with the horizon which indicated rains. We relaxed for some time on the top, living in the moment, examining the myriad patterns of nature.
The view of other side while climbing to the top. You can see the Rayakottai village below The gorgeous clouds while reaching top of Rayakottai fort The top of Rayakottai Fort! The object you see is a big lamp which is lit on festivals and special occasions.The lovely view from the top vantage point of Rayakottai fort
Clouds above us had now overpowered the sun and we started our descent in anticipation of showers. As the droplets started to land on earth, we were halfway through the descent, encountering even more butterflies now. Petrichor filled us with joy as we approached our car.
In some time, we were on our way back to Bangalore and while gaining speed on the highway, we had a last glance of Rayakottai fort, now hazy due to the showers. The fort, though not in its complete, looked imposing from distance and we realized why Tipu Sultan had chosen the hillock in Rayakottai to build his lesser known fort.
Have you been to Rayakottai Fort before? Do share your experiences in comments below.


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by Kelly
(London, Ontario, Canada)
My Baby
I got Dodger back in June of 1995 from a friend, he was really skittish, shy, and took off when any friends came over that's were the name dodger came from, he was the only kitten at the time that Munch my other cat took to, this went on for awhile Dodger was the 5th cat all the others Munch ran under the bed and growled hissed but not Dodge.
Over the years the 2 became brothers even though from different litters always curled up together on the chair playing ect.
I noticed Dodger going downhill at the beginning of November He was breathing heavily laboured breathing, and was losing weight, I took him to the vet they couldn't find anything wrong with him with the exam, they wanted to do X-Rays, Ultrasound, urinalysis. I didn't have the money to pay for all these diagnostic fees which was going to be upwards of 600-700, I did buy the prednisalone 5mg 10 days which didn't do anything and he was getting thin, trying to eat or acting like he wanted to eat. Anyway on November 16th the vet called and I made a decision to have him euthanized on the 19th this past Monday. I am just grief ridden crying a lot, mad that I didn't have the funds to do these tests thinking it could have been something minor and I had him euthanized, when I went into the vet they were saying he was emaciated and thought it was a tumor on the inside or Heart Failure by the way he wasted away 10 days after being at the vet initially.
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I tested the Oatmeal Raisin "Dietary Supplement" (as the manufacturer termed it.) I'll start with the positive. I have no doubt that you would lose weight on this diet….if you didn't shoot yourself first!
As I stare at it and contemplate it, this little square thing sort of resembles a cookie…sort of. When you take a bite, it sort of tastes like an oatmeal raisin cookie…sort of. But then you start chewing.
The best term I can think of to describe the texture is sawdust. It is incredibly dry with some kind of crunch to it. Oh, there's a raisin! It's like a little bitty oasis in the desert! Better take a sip of water. Then I continue to chew–a lot. Second bite–more
sawdust, more chewing, MORE WATER! After a couple more bites of this, I notice some kind of residue in the roof of my mouth. It resembles grease but isn't quite the same as a grease feel or taste. More water!
After a couple more bites, I think that I am never going to be able to choke down the rest of this godforsaken cookie! Oh no! I drank all my water…must have more water!
A lump has formed in my throat. It reminds me of being a small child and having an extreme dislike of that dreadful sweet potato with the marshmallows on top thing that people serve at Thanksgiving. I'd get a lump in my throat and just getting down the obligatory two bites was almost more than a small child could bear! It feels like that…but the dreadful sweet potato thing is much preferable to this evaporated, dusty, parched, grimy crumble that is in my mouth!
Well, it's worked. My hunger is curbed. I am definitely NOT this hungry! It did get me to drink a lot of water. I went through two 16 ounce glasses of water to ingurgitate this one 1 1/2 inch cookie…before I considered regurgitating!
I felt that I should give it a second try. This time I followed the "suggested serving" and microwaved it for 10 seconds. It's considerably better but that still isn't saying it's "good."
How the diet works is this: You eat 6 cookies spread out during a day and a healthy dinner of lean protein and non-starchy vegetables. There are different flavors of cookies, shakes and cupcakes that are all manufactured by the same folks. You'd need to have a variety to survive this diet….but if the shakes and cupcakes are as bad as the cookies, it would be another hellish diet.
The cookies are each 110 calories with 4 grams of fat…they're skimming just over the line where it can't be claimed as a low-fat food. The cookies contain a proprietary formula of something called "Lethicin" which the ingredients are listed as "guar gum, gum arabic, locust bean gum (all of which are thickening agents to my understanding.) There are also some other ingredients like pomegranate that are definitely good for you but included in the small amount of "Lethicin" I can't imagine that there's enough there to have any effect whatsoever!
On top of this, they evidently know their product tastes terrible! The return policy is prohibitive. You first have to call customer service to get authorization to return product and fill out a Refund Request Form and then return it by fax email or email.
They will not accept open boxes, so one box of the three that I ordered (I ordered the smallest amount possible) is not returnable. I spent $59. Take out approximately $20 for a box that wouldn't be accepted for return. Then there is a $35 re-stocking fee. That adds up to $55 and the customer is responsible for the cost of shipping, so by that time, I'd be in the negative numbers. Better off to sell the extra on eBay!
All things considered, this diet has very little merit. It would probably work to some degree but you'd be miserable. Also, you would not be changing any habits or learning how to eat foods with decent nutritional value. Thumbs down!


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Zebra Technologies Introduces Industry's Most Rugged Mobile Printers
SINGAPORE - Zebra Technologies Corporation (NASDAQ: ZBRA), a global leader in products and services that provide real-time visibility into organizations' assets, people and transactions, today announced the launch of the new ZQ500 mobile printer series for field-based applications.
The 3-inch ZQ510 and 4-inch ZQ520 printers are portable, print-on-demand devices that combine a military-grade design with simple functionality for printing solutions for the transportation and logistics, manufacturing and government markets.
- The lightweight ZQ500 series can be used for a variety of mobile applications including e-citation, parking enforcement, field sales and service receipts, transportation tickets, car rental receipts for vehicle return, proof of delivery and utility readings and invoices.
- The easy to set up printers feature a simple design offering an intuitive display with only three large buttons and no menus - increasing accuracy for gloved hands and fingers.
- Featuring a rugged military-grade design for exceptional durability and reliability in the toughest environments, the ZQ500 series offers:
-- IP54 (or IP65 with optional exoskeleton case) rating for protection against dust and liquids
-- MIL-STD 810g military qualifications for shock, vibration and temperature exposure
-- cold temperature compensation automatically optimizes and balances print speed and quality in cold temperatures - ideal for direct-store deliveries (DSD) that require colder transportation
-- protection for the media from being ejected when the printer is dropped
- The ZQ500 series comes standard with the latest Bluetooth(R) Smart Ready 4.0 (low energy) connectivity, Print Touch device pairing and support for all major smartphone and tablet operating systems. These printers are also Zebra's first to support a secondary Bluetooth channel for simultaneous operations - enabling developers to create new device management solutions and helping increase worker productivity.
- The ZQ500 mobile printers will be available in APAC immediately
Ryan Goh, Vice President and General Manager, Zebra Technologies Asia Pacific
"Zebra empowers a mobile workforce, providing businesses with the tools to easily capture critical information, and access critical data. Regardless of weather or temperature, mobile employees work under all conditions and require devices that are easy to use and manage while working in the field. Zebra's new ZQ500 mobile printer series is the industry's most rugged printer and specifically designed to withstand the bumps, drops and environmental extremes that are common in field environments. With an intuitive user display and the latest Link-OS(R) environment, the ZQ500 series is easy to setup, use, manage and maintain."
Website: Mobile Printers http://bit.ly/1K0qObe
Facebook: Zebra Technologies https://www.facebook.com/ZebraTechnologiesGlobal
Twitter: @ZebraTechnology https://twitter.com/ZebraTechnology
About Zebra Technologies
Zebra (NASDAQ: ZBRA) makes businesses as smart and connected as the world we live in. Zebra tracking and visibility solutions transform the physical to digital, creating the data streams enterprises need to simplify operations, know more about their businesses, and empower their mobile workforces. For more information, visit www.zebra.com/possibilities.
Zebra Media Contact:
Abigail Ng
Ogilvy Public Relations, on behalf of Zebra Technologies
+65 9093 3787
[email protected]
Contact Profile
Abigail NgP: +65 9093 3787
W: www.zebra.com/possibilities


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Awareness is your name
Though you have no name, awareness can be called your name for now. You are always seen with your own seeing. You can always be seen, as you are always here to be perceived. Everything always sees you, for you are never hidden. You are never lost, and we are always you, playing yourself. You speak every word and you utter every sentence. You ears hear all things. For your light and you are the same. Everything that we see is you. You are always here as you are. Anything other is a fiction, which you are conjuring in yourself. You have a beginning and you have an end. You are born and you die, you live and you let go of living. Your form is ever obvious, your edges ever apparent, you limitations ever perceivable. You can always be fathomed. Your essence is effable your holiness understandable your beauty touchable and palpable.
You are the eternal one that is bound by time. You are the infinite one that is dancing in finite forms. You are always here as yourself. You can never be not here. Your light is always available. Whether a sage or an ignorant man, they both see you. You see both of them. They are all your creations and you are also their creation. There has been a time where you didn't exist. There will be a time where you will seize to exist. You are born from the mind and the mind is born from you. You are the body and the soul, you are the spirit and whole. Your world soul is ever seeing it self as a complexity striving higher into infinite more layers. You are truly the perfect imperfection. You can never be understood yet all we do is understand you, as you, through you.
If anything can be said to be a quality that you possess oh perfect one, it may be that you are always aware of your own perfection. You are perpetually bathing in the light of your own unfathomable grace. You are always flying in the infinite joyous skies of your own heart. It is therefore my understanding, which also is yours, that you are ever perfect and self-sufficient and loving about all existence.
Quotes and Arts Video of the Day
Love and Light


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|Message view
|« Date » · « Thread »
|« Date » · « Thread »
|"Jim Gomes (JIRA)" <j...@apache.org>
|[jira] Assigned: (AMQNET-78) ActiveMQ v5 Idle Connection Timeout does not throw an exception
|Thu, 29 May 2008 04:54:00 GMT
[ https://issues.apache.org/activemq/browse/AMQNET-78?page=com.atlassian.jira.plugin.system.issuetabpanels:all-tabpanel ] Jim Gomes reassigned AMQNET-78: ------------------------------- Assignee: Jim Gomes (was: James Strachan) > ActiveMQ v5 Idle Connection Timeout does not throw an exception > --------------------------------------------------------------- > > Key: AMQNET-78 > URL: https://issues.apache.org/activemq/browse/AMQNET-78 > Project: ActiveMQ .Net > Issue Type: Bug > Components: ActiveMQ Client > Environment: Windows, JDK 1.6, ActiveMq version 5 (Stable), ActiveMQ.NET openwire client > Reporter: Demis Bellot > Assignee: Jim Gomes > Fix For: 1.1 > > > We are experiencing an issue when we have upgraded the ActiveMQ broker to the latest production version 5 where it appears that the broker is automatically disposing of a connection once it has been idle for long tim. > We have a consumer that is listening on a topic, if the topic has not received a message for a long period of time (roughly 30mins) it appears that the connection is disposed of on the server (as seen in the JMX console) and the consumer will fail to receive any other messages sent to the topic after this time. This does not happen to consumers that are listening on more active topics (i.e. ones that receive messages every 5 minutes, etc). > Unfortunately this idle connection timeout does not raise an exception when it is disposed of, so we have no way to know if the connection is dead so we can reconnect back to the broker. -- This message is automatically generated by JIRA. - You can reply to this email to add a comment to the issue online.
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Sorry, but Gold Medalist Katie Ledecky Can't Accept a Free Waffle Maker
Not even from Ellen DeGeneres!
Most Popular
Katie Ledecky, who took home four gold medals during the 2016 Rio Olympics, won yet another prize on The Ellen DeGeneres Show: a free waffle maker. She earned it after beating American Ninja Warrior's Grant McCartney in a game of "Foot Flickers." Unfortunately, she couldn't claim it.
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Ledecky starts her freshman year at Stanford this week, and because she is a student athlete NCAA regulations prevent her from accepting gifts or "extra benefits" not authorized by the NCAA. That includes free clothes, airline tickets, and endorsements, which definitely would've lined up for her had she chosen to go pro.
It's cool. Who needs a waffle maker, anyway, when you've got these?
More from ELLE:


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News : MetLife Receives J.D. Power Certification for Customer
#contactcenterworld, @MetLife, @JDPower
New York, NY, USA, Sept 26, 2016 -- MetLife's Corporate Benefit Funding Customer Solutions Center team has been recognized by J.D. Power for providing "An Outstanding Customer Service Experience" for the Live Phone Channel. The certification places MetLife's Corporate Benefit Funding business among a select few institutional retirement providers that have achieved this status.
MetLife's Customer Solutions Center, part of the company's Global Technology & Operations organization, services customer calls each year across a full spectrum of MetLife products. Dedicated Corporate Benefit Funding specialists provide customer service from MetLife's call center in Warwick, Rhode Island.
"As a primary point of contact for customers, our service consultants are committed to delivering a differentiated service experience. This recognition demonstrates their success," says Kristine Poznanski, senior vice president and head of Customer Solutions Center, MetLife. "Ongoing investments in our people and technology enable us to continually enhance the service experience."
"At MetLife, we are committed to customer centricity and have dedicated significant resources to make it easier for our customers to do business with us," says Robin Lenna, executive vice president and head of Corporate Benefit Funding, MetLife. "This honor underscores our commitment to service excellence, which is a business imperative for MetLife."
"As part of its evaluation, J.D. Power conducted a detailed audit of more than 100 practices in the Customer Solutions Center supporting MetLife's U.S. Pensions, Institutional Income Annuities and Structured Settlements businesses, and surveyed customers who recently contacted MetLife," noted Kim Flemm, vice president, Customer Experience with MetLife. "The certification means that the call center is within the top 20% for cross-industry customer service scores, based on benchmarks established in J.D. Powers' customer satisfaction research."
#contactcenterworld, @MetLife, @JDPower
Posted by Veronica Silva Cusi, news correspondent
Source: http://www.businesswire.com
Related Editorial
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- HGS Commitment to Optimizing CX Earns Top Honors for Best Outsourcing Partnership
- Scivantage Brings Home Gold with Two Wins at the Contact Center World Awards
- ListenTrust Wins Gold for Best Contact Center and Best Contact Center Sales Professional
- ContactCenterWorld.com announces winners of the 2017 AMERICAS Top Ranking Performers Conference and Awards.
- Bartlesville's Community Spirit is Recognized and Rewarded
More Editorial From Metlife
About Metlife:
Metropolitan Life Insurance Company or MetLife for short was founded in1868. MetLife, Inc. is a provider of insurance and other financial services to individual and institutional customers throughout the United States Outside the U.S., MetLife companies have direct insurance operations in Asia Pacific, Latin America and Europe.
About J.D. Power and Associates:
Established in 1968, J.D. Power and Associates is a global marketing information firm that conducts independent and unbiased surveys of customer satisfaction, product quality and buyer behavior. Today, the firm's services include industry-wide syndicated studies; proprietary (commissioned) tracking studies; media studies; forecasting; and training services, as well as business operations analyses, and consultancies on customer satisfaction trends.
Published: Friday, September 30, 2016


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We present a mathematical model that describes the spatial distribution of photons in fluorescence endoscopic images, resulting in expressions for image signal-to-noise ratio and resolution. This model was applied to quantitative analysis of fluorescence images collected from human colonic mucosa with a fiber-optic and an electronic endoscope. It provides a tool for the design of fluorescence endoscopic imaging systems and for extraction of quantitative information about image features. The results apply generally to endoscopic imaging of remote structures in biological and industrial settings, in which light of weak intensity such as fluorescence as well as reflected white light is used.
© 1998 Optical Society of AmericaFull Article | PDF Article
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Fremantle has narrowly avoided a huge AFL upset by beating a second-string Gold Coast at a dreary Metricon Stadium.
The Suns incredibly came close to victory over the competition frontrunners, spending most of a pulsating final quarter trailing by less than a kick.
But they were unable drag themselves over the line as the Dockers scraped home with a 7.4 (46) to 6.17 (53) triumph.
It came down to the final moments, as a low-scoring contest ended in a sudden flurry of goals.
Nick Suban kicked what appeared to be the sealer with a minute to go from a free kick just metres out from goal, but the Suns kept coming and Tom Lynch provided an almost instant reply.
In the end the Suns ran out of time but would have won plenty of admirers after an strong four-quarter performance supported by an even spread of contributors.
Predictions of a Freo bloodbath proved well off the mark, with the ladder leaders again a long way from their best – a week on from their first defeat of the season against Richmond.
That was mostly down to the Suns.
Where they failed against Hawthorn and Sydney in the previous two rounds, Gold Coast was able to drag the game down to their level and stop Fremantle's damaging run-and-gun style.
Nathan Fyfe amassed a game-high 31 possessions and booted two goals in two minutes just after half-time, and at that stage the Dockers appeared poised to kick away.
But led by acting captain Michael Rischitelli (17 touches) and boom rookie Adam Saad (20 touches), the Suns didn't let them.
It was an incredible effort from a side crippled by an unprecedented injury crisis that left them with just 23 players to pick from.
Gold Coast coach Rodney Eade tempted fate on Friday by saying the Suns needed to avoid a first-quarter injury since their substitute, the returning Nick Malceski, was still hampered by a knee problem and not able to run out a match.
In tune with their complete lack of good fortune this year, of course, it happened.
Halfway through the opening term, Danny Stanley's afternoon came to an early end when he went down with a knee injury, throwing a clearly unfit Malceski into the mix.
But Gold Coast found a way to carry on regardless, falling over only at the final hurdle.


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Inspired by Bali's lush natural environment, this hotel blends modern contemporary design with natural elements. The 174 rooms are designed with colourful themes and elegant backdrops, amidst dashes of vivid colours with a touch of contemporary interior design. Built in 2011 and renovated in 2012, this family-friendly hotel welcomes guests in the lobby with its 24-hour reception and check-out service, as well as a hotel safe, currency exchange facilities, a cloakroom, lift access to the upper floors and a newspaper stand. The air-conditioned establishment also features a hairdressing salon, a stylish TV lounge, a kids' club, a speciality restaurant, where guests can dine in real luxury, and a bar providing an innovative and generous selection of cocktails, beers and wines. Further on-site amenities include wireless Internet access, conference facilities for those wishing to conduct business at the hotel, a laundry service, room service and bicycle hire, while those arriving by car may leave their vehicle in the hotel car park or garage upon arrival.
The property is positioned in a well-known location for leisure and watersport lovers at Tanjung Benoa - Nusa Nuda. It also is just 5 minutes to the convention centres, Bali Collection, Museum Pasifika and Bali Nusa Dua Theatre, 10 minutes to Nusa Dua Beach, 30 minutes to Kuta Beach, 40 minutes to Uluwatu Temple and 75 minutes to Ubud. The hotel is 20 minutes' drive from Ngurah Rai International Airport.
The en suite rooms are fitted with a shower and a hairdryer, in addition to further in-room amenities including a double bed, a direct dial telephone, cable TV, a refrigerator and an electronic key card. Free wireless Internet access, air conditioning, a safe, an ironing set and coffee and tea making facilities all feature as standard in all rooms. A balcony or terrace affords guests wonderful views of the surroundings.
The hotel has a spa and beauty salon, providing massages and spa treatments, as well as a gym, an outdoor swimming pool with a children's swimming area, a poolside bar and a sun terrace with sun loungers laid out ready for use. Guests can stay in shape with an aqua fit session or enjoy the high-octane activities, such as waterskiing, jet skiing, diving, surfing, windsurfing, motor boating or banana boating. The hotel also provides a beach club, the opportunity to go sailing and an entertainment programme for children. The nearby beach is sandy and there guests will find plenty of sun loungers for perfecting their tan.
The Ocean Restaurant serves international cuisine, while the Splash poolside bar serves cocktails and snacks. A continental breakfast buffet is served each morning, while lunch and dinner are available as a set menu or � la carte.
American Express, MasterCard and VISA are accepted as methods of payment at this establishment.
When coming from the Ngurai Rai Airport guests can take a taxi. The journey takes only 20 minutes.
Room Facilities:
Direct dial telephone
Satellite cable TV
Internet access
Mini fridge
Tea Coffee
Iron and board
Double bed
Individual airconditioned
Wheelchair accessible
Disabled bathroom


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Join Thomas & Friends as they embark on a legendary adventure! The steam team's quest begins when a special guest arrives on Sodor with a big surprise and important jobs for Thomas, Percy and James. The engines meet new friends and discover suits of armor; coats of arms and legends of long-ago heroes. Then their bravery is put to the test when their new friend Stephen goes missing. Will Thomas find him in time? Will the engines discover the truth about the Island of Sodor's biggest mystery? It's a crusade of knightly proportions for Thomas & Friends in this epic special!
This event is free and open to the public.
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