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Biomedical subjects

J A Henry

Publications and source records attributed to J A Henry.

At least 19 recordsLinked to original sources
PubMed2006

Acute toxic effects of 'Ecstasy' (MDMA) and related compounds: overview of pathophysiology and clinical management.

Since the late 1980s 'Ecstasy' (3,4-methylenedioxymethamphetamine, MDMA) has become established as a popular recreational drug in western Europe. The UK National Criminal Intelligence Service estimates that 0.5-2 million tablets are consumed weekly in Britain. It has been reported that 4.5% of young adults (15-34 yr) in the UK have used MDMA in the previous 12 months. Clinically important toxic effects have been reported, including fatalities. While the phenomenon of hyperpyrexia and multi-organ failure is now relatively well known, other serious effects have become apparent more recently. Patients with acute MDMA toxicity may present to doctors working in Anaesthesia, Intensive Care and Emergency Medicine. A broad knowledge of these pathologies and their treatment is necessary for anyone working in an acute medical speciality. An overview of MDMA pharmacology and acute toxicity will be given followed by a plan for clinical management.

Adolescent↗
PubMed2006

The in utero passage of meconium by very low birth weight infants: a marker for adverse outcomes.

OBJECTIVES: To determine the incidence of in utero meconium passage and the rate of associated complications among VLBW infants. STUDY DESIGN: Retrospective review of medical records and prospective evaluation of placental samples from 431 VLBW infants who survived >24 h. Cases with histologic evidence of meconium were re-examined and hemosiderin excluded by a negative iron stain. Statistical analysis included chi2, logistic regression, Student's t-test and Kruskal-Wallis. RESULTS: The 70 infants (16.2%) who had placental evidence of in utero meconium passage were younger, weighed less, and more likely to be delivered by C-section (P = 0.006), intubated in the delivery room (P = 0.02), receive chest compressions (P = 0.003), require volume resuscitation (P = 0.001) and develop grade III-IV intraventricular hemorrhages (P = 0.011) than were control infants. CONCLUSION: Microscopic evaluation of the placental membranes reveals that the in utero passage of meconium occurs in about 16% of premature infants and is associated with adverse perinatal outcomes, including the need for resuscitation at delivery and an increased risk for grade III-IV intraventricular hemorrhages.

Amniotic Fluid↗
PubMed2006

New instrumentation for automated tinnitus psychoacoustic assessment.

CONCLUSION: Although tinnitus is a major health problem, techniques to quantify its perceptual aspects are not standardized. This study represents a key step in our efforts to develop clinical methodology to accurately and reliably quantify the sensation of tinnitus, using a uniform method for obtaining a battery of tinnitus measures. OBJECTIVES: The purpose of this study was to evaluate the performance of the automated system, which was redesigned to reduce time of testing and to add new testing capabilities. The primary difference in function was the use of a 'knob' device that enabled patient control of auditory stimuli. The new tests included assessment of minimum masking level (MML) and residual inhibition (RI). MATERIALS AND METHODS: As with previous iterations of the system, a computer program ran all testing and subjects read instructions and provided responses via a computer touch-screen. Three separate studies were conducted. Study 1 evaluated within- and between-session test-retest response reliability of tinnitus loudness matches (LMs) and pitch matches (PMs). Study 2 was conducted to evaluate differences in LMs and PMs between subjects with and without tinnitus - to obtain pilot data to assist in the development of a test for 'tinnitus malingering.' Study 3 evaluated the system's capability of obtaining MMLs and RI as well as the between-session reliability of these measures. RESULTS: Study 1 documented that the new system could obtain LMs and PMs within approximately 20 min, while maintaining clinically acceptable reliability. Study 2 revealed characteristic differences in LM and PM test results for individuals who did not experience tinnitus. Study 3 documented the system's ability to obtain measures of MML and RI that were reliable across sessions.

Auditory Threshold↗
PubMed2006

Clinical trial to compare tinnitus masking and tinnitus retraining therapy.

CONCLUSION: Both tinnitus masking (TM) and tinnitus retraining therapy (TRT) can be effective therapies for amelioration of tinnitus. TM may be more effective for patients in the short term, but with continued treatment TRT may produce the greatest effects. OBJECTIVES: Although TM and TRT have been used for many years, research has not documented definitively the efficacy of these methods. The present study was a controlled clinical trial to prospectively evaluate the clinical efficacy of these two methods for US military veterans with severe tinnitus. SUBJECTS AND METHODS: Over 800 veterans were screened to ensure that enrolled patients had tinnitus of sufficient severity to justify 18 months of individualized treatment. Qualifying patients (n=123) were placed quasi-randomly (alternating placement) into treatment with either TM or TRT. Treatment was administered at 0, 3, 6, 12, and 18 months. Outcomes of treatment were evaluated primarily using three self-administered tinnitus questionnaires (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity Index). RESULTS: Findings are presented from the three written questionnaires with respect to three categories of patients: describing tinnitus as a 'moderate,' 'big,' and 'very big' problem at baseline. Based on effect sizes, both groups showed considerable improvement overall. In general, TM effects remained fairly constant over time while TRT effects improved incrementally. For the patients with a 'moderate' and 'big' problem, TM provided the greatest benefit at 3 and 6 months; benefit to these TRT patients was slightly greater at 12 months, and much greater at 18 months. For patients with a 'very big' problem, TM provided the greatest benefit at 3 months. For these latter patients, results were about the same between groups at 6 months, and improvement for TRT was much greater at 12 months, with further gains at 18 months.

Acoustic Stimulation↗
PubMed2006

Does meta-chlorophenylpiperazine (mCPP) activate human platelets?

mCPP (meta-chlorophenylpiperazine), an agonist at serotonin (5-hydroxytryptamine, 5-HT) 5-HT2 receptors, has been used as a probe of serotonergic function. We assessed its effect on platelet activation by measuring median platelet volume (MPV), the Sonoclot (SCT) pattern and plasma and intraplatelet serotonin. (a) In vitro study: MPV was measured (n = 7) using a high-resolution channelyzer: Saline (median and range (5.23 fl; 5.10-6.18) vs. mCPP (5.36; 5.10-6.44) P = 0.03; ADP (5.42; 5.29-6.44) vs. ADP + mCPP (5.67; 5.42-6.63) P = 0.02; mCPP (5.36; 5.10-6.44) vs. ADP + mCPP (5.67; 5.42-6.63) P = 0.02. Therefore, mCPP increases the MPV and enhances the effect of ADP. (b) In vivo study: The SCT time to inflection (TI) and time to peak (TP) were measured following the oral administration of mCPP (0.5 mg/kg) or aspirin (300 mg) (n = 10). Ingestion of mCPP significantly shortened TI and TP indicating platelet activation. TI: 0 h (mean +/- SD: 10.2 +/- 2.0 min) vs. 6 h (9.3 +/- 1.5) P = 0.03; TP: 0 h (31.9 +/- 7.6) vs. 6 h (23.1 +/- 2.9) P = 0.01. Aspirin had no effect on TI or TP. There were no significant changes in plasma and intraplatelet 5-HT. It is concluded that mCPP activates human platelets via 5-HT receptors.

Adenosine Diphosphate↗
PubMed2006

Treatment of poisoning induced cardiac impairment using cardiopulmonary bypass: a review.

Severe poisoning can cause potentially fatal cardiac depression. Cardiopulmonary bypass (CPB) can support the depressed myocardium, but there are no clear indications or guidelines available on its use in severe poisoning. A review was conducted of relevant papers in the available literature (seven single case reports of both deliberate and accidental ingestion of cardiotoxic drugs and two animal studies). Although CPB is rarely used in the management of poisoning, it may have potential benefits for haemodynamic instability not responding to conventional measures. At present there is insufficient evidence concerning the use of CPB as a treatment for severe cardiac impairment due to poisoning (grade C). This review suggests that in patients with severe and potentially prolonged reversible cardiotoxicity there is potential for full survival with CPB, provided that the patient has not already sustained hypoxic cerebral damage due to resistant hypotension prior to its use.

Adult↗
PubMed2005

Assessment of a point-of-care test for paracetamol and salicylate in blood.

BACKGROUND: Paracetamol and salicylate are commonly taken in acute overdose. Clinicians have a low threshold for excluding the presence of these two drugs, by ordering laboratory tests in any patient suspected of ingesting an overdose or with an altered mental state. AIM: To test the effectiveness of a new point of care test that qualitatively detects paracetamol and salicylate in blood and to examine the potential time saved by its use. DESIGN: Prospective multicentre trial. METHODS: The new test was compared with laboratory analysis in a routine blood sample taken from patients presenting to emergency departments with suspected overdose. RESULTS: The test had sensitivities of 98.5% and 88.5%, and specificities of 74.7% and 92%, for paracetamol and salicylate, respectively, at cut-off levels of 25 mg/l and 100 mg/l, respectively The point of care test results were available 2 h before the laboratory result. DISCUSSION: This point-of-care test could be used to rule out an overdose with either of these two drugs, and could thus lead to earlier clinical decisions for suspected overdose patients. Recommendations have been made following this trial that the cut-off value for paracetamol should be reduced from 25 mg/l to 12.5 mg/l in order to increase its usefulness. To prevent the test being misread, we also suggest that each device should be embossed to remind users that the presence of a line indicates there is no drug present.

Acetaminophen↗
PubMed2005

Screening for Type 2 diabetes in the accident and emergency department.

AIM: To assess the proportion of patients, aged 40 years and over, attending an inner city accident and emergency department that have Type 2 diabetes, and the proportion previously undiagnosed, and to assess whether the identification of undiagnosed Type 2 diabetes is feasible in this setting. METHODS: Five hundred unselected people participated. All completed a demographic questionnaire regarding risk factors for diabetes. In those without known diabetes, random capillary blood glucose (CBG) was measured. If this was greater than 7.0 mmol/l, patients were asked to return for two fasting blood glucose tests. Diagnosis of diabetes was based on World Health Organization criteria. RESULTS: Of the 500 participating subjects, 73 were already known to have Type 2 diabetes. Of the remaining 427 subjects, 36 had CBG>7.0 mmol/l. All 36 returned for fasting blood tests: 13 fulfilled the diagnostic criteria for Type 2 diabetes, eight for impaired fasting glucose (IFG), and 15 had normal fasting glucose values. The prevalence of Type 2 diabetes was therefore 17.2%, including 2.6% with a new diagnosis, and 14.6% with pre-existing disease; 1.6% were found to have IFG. Body mass index was greater in those with Type 2 diabetes (previously and newly diagnosed) [27.1 (5.15) (mean+/-standard deviation)] vs. 25.8 (4.70) kg/m2; unpaired t-test P=0.0213), and those with Type 2 diabetes were more likely to be of black and minority ethnic origin (57 vs. 28%; chi2 P<0.001) and to have a first-degree family history of diabetes (45 vs. 23%; chi2 P<0.001). CONCLUSIONS: It can be estimated from this survey that, annually, this case-finding methodology could identify 539 (95% CI 249-828) people aged 40 years and over attending our accident and emergency department with previously undiagnosed Type 2 diabetes.

Adult↗
PubMed2002

The effect of lofepramine and other related agents on the motility of Tetrahymena pyriformis.

Tricyclic antidepressants (TCAs) were introduced almost 50 years ago. Whilst there is no doubt that TCAs are effective in treating depression, they are also more cardiotoxic when taken in overdose than other antidepressant groups. Lofepramine is a more recently introduced modified TCA, which in animals and man has low toxicity when compared to older TCAs. Paradoxically, lofepramine is extensively metabolised to desipramine, which has considerable toxicity, both experimentally and in overdose. The toxicity of such compounds is attributed, in part, to a membrane stabilising effect (MSA) on cell membranes. This MSA causes gross effects to the cell structure and in turn, normal cell activity. The aim of this study was to compare the MSA of lofepramine with that of desipramine and amitriptyline in order to see if this might help to explain the low toxicity of lofepramine. The local anaesthetic agent lignocaine was also studied for comparison. Each compound was enclosed in a beta-cyclodextrin to increase its solubility in aqueous medium. The extent of MSA was determined as a measure of the effect on the swimming speed of the protozoan Tetrahymena pyriformis using a video image analysis system. The IC50s for the various drugs were then correlated with their respective octanol-water partition coefficient values (Pow). Amitriptyline had an IC50 of 1.26+/-0.29 mM, desipramine 75.99+/-14.40 mM, while lofepramine had an IC50 of 357.40+/-25.00 mM. Lignocaine had an IC50 of 85.73+/-18.30 mM. There was also a significant correlation between the IC50 values and the Pow values.

Amitriptyline↗
PubMed2002

Hyponatraemic states following 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') ingestion.

BACKGROUND: Life-threatening and fatal hyponatraemic complications following ecstasy use have previously been documented. AIM: To define clinical features of hyponatraemia following the ingestion of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). DESIGN: Retrospective case series. METHODS: All enquiries to the London centre of the National Poisons Information Service (NPIS) between December 1993 and March 1996 were screened for cases of MDMA use associated with hyponatraemia (serum sodium <130 mmol/l). History of fluid consumption, presenting features and subsequent clinical course were recorded. RESULTS: Seventeen patients, aged 15-26 years, were identified. Serum sodium levels ranged between 107 mmol/l and 128 mmol/l. In six patients, biochemical results were consistent with inappropriate secretion of antidiuretic hormone (SIADH). Analytical confirmation of MDMA ingestion was obtained in 10 patients. Ten patients were known to have ingested a large amount of non-alcoholic or alcoholic fluid. The clinical pattern was remarkably uniform, with initial vomiting and disturbed behaviour, followed in 11 patients by seizures. Drowsiness, a mute state and disorientation were observed for up to 3 days. Two patients died; 14 made a complete recovery. DISCUSSION: MDMA can cause life-threatening hyponatraemic encephalopathy when accompanied by excessive fluid ingestion. The mechanism involves inappropriate secretion of antidiuretic hormone.

Adolescent↗
PubMed2002

Action of MDMA (ecstasy) and its metabolites on arginine vasopressin release.

3,4-Methylenedioxymethamphetamine (MDMA) has been reported to cause hyponatraemia, which appears to result from inappropriate secretion of the antidiuretic hormone arginine vasopressin (AVP). After administration of a low dose of (R,S)-MDMA (40 mg) to eight healthy drug-free male volunteers, concentrations of AVP in plasma increased significantly at 1, 2, and 4 hours. Although no relation between plasma MDMA and AVP was found on an examination of the entire data set over the 24-hour study period, a statistically significant negative correlation was observed at 1 hour. As this occurred at a time when both AVP and MDMA concentrations were rising, it was postulated that a metabolite, or metabolites, could primarily be responsible for the increase in AVP. To test this hypothesis we examined the effect of MDMA and five of its metabolites, in the dose range 0.1-1,000 nM, on AVP release from the isolated rat hypothalamus. All compounds tested were found to increase AVP release (using 10 nM and 1,000 nM concentrations), with 4-hydroxy-3-methoxymethamphetamine (HMMA), the major metabolite of MDMA, being the most potent, and 3,4-dihydroxymethamphetamine (DHMA) the least potent. Each compound (1,000 nM), with the exception of DHMA, also enhanced the response to 40-mM potassium stimulation. Our findings confirm that metabolites of MDMA, in addition to the parent drug, contribute to AVP secretion in vitro. Further work will demonstrate whether this is also true in vivo.

Animals↗
PubMed2002

Increase in alcohol related deaths: is hepatitis C a factor?

AIM: To evaluate recent trends in alcohol related deaths in the UK and to consider possible causative factors. DESIGN: Observational retrospective study of the database of the Office for National Statistics, alcohol consumption data reported by the General Household Survey, and other published data. SETTING: England, 1993-9. RESULTS: Deaths for each million of the population from alcohol related illness increased by 59% in men and 40% in women over the years 1993 to 1999. One subgroup of alcohol related deaths, ICD 571.3 (alcoholic liver damage unspecified), showed a 243% increase in men aged 40 to 49 years over the same period. Figures for younger men, and women in all age groups, showed less pronounced increases. There has been no associated rise in alcohol intake. There has been an increase in the incidence of hepatitis C virus (HCV) infection in recent years, and alcohol consumption in HCV positive individuals accelerates the progression to cirrhosis. Circumstantial evidence links the rise in HCV infection to the use of illicit drugs in the 1970s and 1980s, among those currently aged 40 to 59 years. CONCLUSIONS: The recent increase in alcohol related deaths cannot be solely explained by a change in drinking habits. It is suggested that this probably results from the rapid progression of alcoholic cirrhosis in people who have acquired HCV infection through intravenous drug use. Alcohol consumption in HCV positive individuals is firmly linked with a poor outcome.

Adult↗
PubMed2002

The acute effects of tetrahydrocannabinol on auditory threshold and frequency resolution in human subjects.

AIMS: The study was designed to investigate the acute effects of ingested tetrahydrocannabinol (THC) on auditory function. METHODS: Eight male subjects (aged 22-30 years), who had previous experience of cannabis use, took part in this study. They performed air conduction pure tone audiometry in both ears over 0.5-8 kHz. A simple test of frequency selectivity by detecting a 4-kHz tone under two masking noise conditions was also carried out in one ear. Three test sessions at weekly intervals were carried out, at the start of which they ingested a capsule containing either placebo, or 7.5 or 15 mg of THC. These were administered in a randomized cross-over, double-blind manner. Auditory testing as described above was carried out 2 hours after ingestion. Blood samples were also obtained at this time point and assayed for delta 9- and 11-OH-THC levels. RESULTS: No significant changes in threshold or frequency resolution were seen with the dosages employed in this study. CONCLUSIONS: This suggests that THC at the plasma levels attained in this study does not have profound effect on the processing of elementary stimuli by the auditory pathway.

Administration, Oral↗
PubMed2001

The antidotal effect of alpha(1)-acid glycoprotein on amitriptyline toxicity in cardiac myocytes.

Tricyclic antidepressants in overdose cause toxicity marked by prolongation of the QRS interval of the electrocardiogram. These drugs are bound to alpha(1)-acid glycoprotein (AAG) with high affinity in plasma. Animal studies have shown that the administration of AAG shortens the QRS prolongation induced by tricyclic antidepressants. In order to clarify the pharmacological mechanism involved and to obtain clinically relevant evidence at the cellular level, whole-cell patch clamp techniques were performed in single guinea-pig ventricular myocytes to elicit the time and voltage-dependent fast sodium currents using both normal and modified physiological solutions. Cells stayed viable for much longer when they were placed in normal physiological solutions, providing sufficient recording time for consistently reproducible, clinically relevant toxicological results to be obtained. Amitriptyline (AMI) produced a concentration-dependent blockade of sodium currents with an approximate IC(50) of 0.69 microM. AAG reversed this blockade in a concentration-dependent fashion at concentrations ranging from 3.2 to 12.8 microM. Using the same experimental conditions, AAG also reversed the blockade of sodium current by quinidine, a class I antiarrythmic drug. Albumin did not reverse the blockade of sodium channels by AMI. The results indicate that AAG is a potential antidote for tricyclic antidepressant overdose.

Algorithms↗
PubMed2001

Assessment and management of acute poisoning by petroleum products.

Petroleum products are highly complex chemical mixtures consisting predominantly of hydrocarbons. Their composition varies with source and intended use of the product. Virtually all are blended products that come into contact with man in a wide range of circumstances. Their toxicity for man is generally low and the use of additives rarely affects the toxicity of the final product. Because products are blended to meet performance, and not chemical specifications, their composition varies significantly. Management of toxicity benefits from simplified guidelines that consider the product by its type. Management in most cases is symptomatic, but the doctor needs to be aware of the potential for development of sequelae such as aspiration pneumonia and central nervous system (CNS) depression. Local and systemic effects of exposure to hydrocarbons are reviewed, as are immediate assessment and recommended management of acute exposure to petroleum products. Because of the large scope of this subject, this paper limits itself to acute toxicity of petroleum products encountered inthe public domain. It does not address topics such as chronic toxicity, solvent abuse, petrochemicals, or pesticides.

Animals↗
PubMed2001

Arginine vasopressin release in response to the administration of 3,4-methylenedioxymethamphetamine ("ecstasy"): is metabolism a contributory factor?

The aim of this investigation was to examine the effect of 3,4-methylenedioxymethamphetamine (MDMA) administration on arginine vasopressin (AVP) release. (R,S)-MDMA (40 mg) was administered to eight normally hydrated healthy male volunteers (22-32 years) and blood samples were collected up to 24 h. Plasma was assayed for AVP and cortisol by radioimmunoassays, and for MDMA and the N-demethylated metabolite, MDA, by gas chromatography-mass spectrometry. Sodium concentrations and osmolality were also determined. Plasma AVP increased in all subjects after MDMA administration and a significant negative correlation was observed between concentrations of AVP and both single and total enantiomer MDMA at 1 h (r < -0.91, P < 0.01). This had disappeared by 2 h (P > 0.7). Compared with basal values, no significant change was observed for osmolality or cortisol at 1 h after drug administration. In conclusion, plasma AVP concentrations increase after MDMA administration, but the increase is not part of a generalized stress response since cortisol did not increase concurrently. A significant negative correlation between plasma MDMA and AVP was observed soon after administration. The possibility that a pharmacological effect of MDMA is primarily mediated via one or more metabolites, rather than by the parent drug, should be considered.

Adult↗