Search PubMed⌕ Search

Biomedical subjects

J A Henry

Publications and source records attributed to J A Henry.

At least 37 records · Page 2Linked to original sources

Delayed sodium thiosulfate as an otoprotectant against carboplatin-induced hearing loss in patients with malignant brain tumors.

Carboplatin is effective in the treatment of malignant brain tumors. However, when administered in conjunction with osmotic opening of the blood-brain barrier (BBB), carboplatin is ototoxic. The purpose of this study was to determine whether delayed administration of sodium thiosulfate (STS), given after BBB closure, provided protection against carboplatin ototoxicity. Patients underwent monthly treatment with intra-arterial carboplatin (200 mg/m2/day x 2) in conjunction with osmotic opening of the BBB, for up to 1 year. Audiological assessment was conducted at baseline and within 24 h before each monthly treatment. STS was administered i.v. as one (20 g/m2) or two (20 g/m2 and 16 g/m2) 15-min doses, depending on baseline hearing status. The initial group received the first STS dose 2 h (or 2 and 6 h) after carboplatin (STS2) and a subsequent group received STS 4 h (or 4 and 8 h) after carboplatin (STS4). Audiological data were compared with a historical comparison group (HCG) treated with carboplatin without STS. Spearman correlation coefficients comparing STS 2 (n = 24), STS4 (n = 17), and HCG (n = 19) indicated significantly lower rates of ototoxicity with increased delay in STS (P = 0.0006). On the basis of the analysis of hearing levels, there were significant differences among the two STS groups and HCG at 8000 Hz (P = 0.0010) and at 4000 Hz (P = 0.0075). The log-rank test for time to ototoxicity indicated a significant difference between STS4 and HCG (P = 0.0018). Delayed STS was effective in protecting against carboplatin-induced hearing loss. STS delayed to 4 h after carboplatin significantly decreased time to development of ototoxicity and rate of ototoxicity when compared with HCG.

Adolescent↗

Ecstasy ingestion and fulminant hepatic failure: liver transplantation to be considered as a last therapeutic option.

Severe adverse effects due to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are reported with increasing frequency in the medical literature. The signs of acute toxicity most often seen are fulminant hyperthermia, hyperexcitatory states, acute renal failure and hyponatraemia. In 1992, hepatotoxicity was also described with unexplained jaundice and hepatomegaly after ingestion of MDMA. We report a case of severe toxic hepatitis following ingestion of MDMA with fulminant hepatic failure which required auxiliary liver transplantation. The diagnosis was necrotic toxic hepatitis following ecstasy ingestion. The outcome was successful, and the patient was discharged from ICU 20 d after surgery. Hepatotoxic effects of MDMA seem infrequent, but may be lethal; liver transplantation is the ultimate therapeutic option in some cases.

Adult↗

Computer-automated clinical technique for tinnitus quantification.

This study addresses the need for uniformity in techniques for clinical quantification of tinnitus. Because automation can be an effective means to achieve standardization, this laboratory is developing techniques to perform computer-automated tinnitus testing. The present study was conducted to demonstrate the feasibility of obtaining reliable tinnitus measures using a fully automated system. A computer-controlled psychoacoustical system was developed to quantify tinnitus loudness and pitch using a tone-matching technique. Hearing thresholds were also obtained as part of the procedure. The system generated test stimuli and simultaneously controlled a notebook computer positioned in the sound chamber facing the patient. The notebook computer displayed instructions for responding and relayed response choices through on-screen "buttons" that the patient touched with a pen device. Twenty individuals with tinnitus were evaluated with the technique over two sessions, and responses were analyzed for test-retest reliability. Analyses revealed good reliability of thresholds, loudness matches, and pitch matches. These results demonstrate that use of a fully automated system to obtain reliable measurements of tinnitus loudness and pitch is feasible for clinical application.

Adult↗

Substance abuse and the kidney.

Substance abuse has been increasing steadily in the UK and some other countries. Recent evidence suggests more than 40% of young people have tried illicit drugs at some time. There are numerous medical consequences to recreational drug use, and a physician should always consider substance abuse in any unexplained illness. The renal complications of drug abuse are also becoming more frequent, and may encompass a spectrum of glomerular, interstitial and vascular diseases. Although some substances are directly nephrotoxic, a number of other mechanisms are also involved. These effects are often chronic and irreversible, but occasionally acute with possible recovery. The rapid growth of illicit drug use is clearly a major public health problem. We review the commonly used substances of abuse and their associations with renal disease.

Adolescent↗

Twenty-stimulus train for rapid acquisition of auditory brainstem responses in humans.

This study addressed the clinical need to obtain frequency-specific auditory brainstem responses (ABRs) more rapidly than is currently possible. ABRs were obtained from 20 subjects using two different methods: a conventional method with tone bursts presented singly and a multiple-stimulus method using a train of 20 tone bursts. For both methods, tone bursts were presented at frequencies 1, 2, 4, and 8 kHz, shaped with a Blackman-Harris window and having intensity levels up to 105 dB peak equivalent sound pressure level (peSPL). The single tone bursts were presented at a 17.2/sec repetition rate. The 20 tone-burst train used the four frequencies at five intensities each and a repetition rate of 3.7/sec (separations between tone bursts of 9-12 msec, with 77 msec off-time between trains). Mean latencies and mean amplitudes for wave V were compared using t-tests for each of 12 conditions (four frequencies, each at the three highest output levels). For latency, only one comparison was significantly different (2 kHz, 77 dB peSPL). Similarly, only one comparison was significant for amplitude (2 kHz, 97 dB peSPL). There was, however, a trend for the tone bursts presented in trains to have longer latencies and reduced amplitudes compared to the respective responses for the single tone-burst condition. These results indicate the presence of some response adaptation when tone bursts are presented in a train. The use of a properly designed stimulus train can result in a significant time savings for obtaining frequency-specific ABRs as compared with single tone-burst presentations.

Adult↗

Psychoacoustic measures of tinnitus.

This report reviews research from the 1930s to the present that has extended our understanding by investigating the characteristics of tinnitus that can be studied using psychoacoustic techniques. Studies of tinnitus masking and residual inhibition began in the 1970s, leading to the therapeutic use of tinnitus masking and a consequent increase in research devoted to tinnitus measurement. In 1981, the CIBA Foundation symposium on tinnitus advocated general adoption of four tinnitus measures: (1) pitch, (2) loudness, (3) maskability, and (4) residual inhibition. Since then, psychoacoustic research into all four topics has proliferated, yielding many valuable insights and controversies concerning the details of measurement techniques. A consensus has emerged that neither the loudness nor other psychoacoustic measures of tinnitus bear a consistent relation to the severity or perceived loudness of tinnitus. Nevertheless, quantification is needed in clinical trials of proposed treatments and in a variety of other types of tinnitus research. Standardization of techniques for specifying the acoustic parameters of tinnitus thus continues to be an important research goal.

Humans↗

Pulse oximetry: evolution and directions.

Pulse oximetry monitoring is a relatively recent technique that has been embraced enthusiastically by medical, nursing and paramedical personnel in many clinical situations. Few people, however, have any idea of how it provides the reading of arterial blood saturation. This review performs several functions: it discusses the haemoglobin molecular structure and explains its relation to spectrophotometry, describes the history and principles of pulse oximetry and the nature of the equipment used, and reviews its common uses. It also explores the principles and proposed uses of its lesser known corollary, photoplethysmography.

Hemoglobins↗

An individualized, sensitive frequency range for early detection of ototoxicity.

OBJECTIVE: The aim of this study was to identify auditory frequencies at which serial threshold testing would provide the greatest sensitivity for early detection of ototoxicity. The overall objective is to develop a more time-efficient ototoxicity monitoring protocol. DESIGN: Threshold data were analyzed from 370 hospitalized patients treated with aminoglycoside antibiotics (AMGs) or cisplatin (CDDP) who received serial auditory monitoring before, during, and after treatment at conventional (0.25 to 8 kHz) and high (9 to 20 kHz) frequencies. RESULTS: For patients showing hearing changes due to ototoxicity, a frequency range was identified for its apparent high sensitivity to initial ototoxicity. This sensitive range is identified according to an individual's hearing threshold configuration, and is, therefore, unique for each patient. The range consists of five frequencies, generally separated by 1/6 octave, e.g., 8, 9, 10, 11.2, and 12.5 kHz. To determine frequencies and combinations of frequencies that were most often involved in ototoxicity detection, threshold data in the sensitive range were analyzed in detail. This analysis suggests that patients receiving treatment with AMG or CDDP can be monitored for hearing thresholds at only five frequencies, resulting in an 84% detection rate for AMG and 94% for CDDP compared with monitoring at all conventional and high frequencies. CONCLUSIONS: This comprehensive analysis supports earlier observations that a sensitive, limited frequency range exists in which serial threshold monitoring will provide early warning of ototoxicity before effects in the speech frequency range. This finding is now being evaluated in a prospective investigation.

Aminoglycosides↗

Clinical lead poisoning in England: an analysis of routine sources of data.

OBJECTIVE: To examine the occurrence of clinical lead poisoning in England based on routine sources of data. METHODS: Three routine data sources were examined, over different periods according to availability of data: (a) mortality for England, 1981-96; (b) hospital episode statistics data for England, for the 3 years 1 April 1992-31 March 1995; (c) statutory returns to the Health and Safety Executive under the reporting of injuries, diseases, and dangerous occurrences regulations (RIDDOR), also for the period 1 April 1992-31 March 1995. Also, analyses of blood lead concentrations carried out by the Medical Toxicology Unit, Guy's and St Thomas' Hospital Trust in London during the period 1 January 1991-31 December 1997 were examined. The analyses were performed both for industrial screening purposes and in response to clinicians' requests where lead poisoning was suspected. This is one of several laboratories carrying out such analyses in the United Kingdom. RESULTS: One death, of a 2 year old girl, was coded to lead poisoning in England during 1981-96. Analysis of hospital episode statistics data identified 83 hospital cases (124 admissions) over 3 years with any mention of lead poisoning, excluding two with admissions dating from 1965 and 1969. For these 83 cases the median hospital stay per admission was 3 days (range 0-115 days). Five were coded as having received intravenous treatment. Further clinical details of these cases beyond what is routinely recorded on the hospital episode statistics database were not available, except for blood lead concentrations in cases also identified on the Medical Toxicology Unit database. Eighteen cases (22%) were below 5 years of age of whom 10 (56%) came from the most deprived quintile of electoral wards. There was evidence to suggest spatial clustering of cases (p = 0.02). Six occupational cases were reported under RIDDOR in England during the period of study, two of whom were identified on the hospital episode statistics database. One further occupational case was identified on hospital episode statistics. Blood lead analyses for 4424 people carried out by the Medical Toxicology Unit (estimated at about 5% of such analyses in England over 7 years) found that among 547 children aged 0-4, 45 (8.2%) had a blood lead concentration in excess of 25 micrograms/dl, the action level in the United Kingdom for investigation, or removal of environmental sources of lead. At all ages, there were 419 (9.5%) such people, including 106 adults with no mention of industrial exposure. CONCLUSIONS: Both mortality and hospital admission ascribed to lead poisoning in England are rare, but cases continue to occur and some, at least, seem to be associated with considerable morbidity. Lead poisoning was confirmed as a probable cause of clinical signs and symptoms in only a small proportion of those in whom a blood lead concentration was requested. Where indicated, appropriate remedial action for the safe removal of environmental sources of lead should be taken.

Adolescent↗

Methadone: where are we now?

Methadone is now widely used as opioid replacement therapy because it reduces crime and prevents spread of disease by the intravenous route. However, it is potentially toxic, especially to drug naive patients, and requires careful prescribing.

Drug Overdose↗

Gene-environment interaction in the determination of levels of haemostatic variables involved in thrombosis and fibrinolysis.

Although a specific genotype may be associated in healthy subjects with modest differences in levels of a risk factor for thrombosis, this effect may be larger or smaller in subgroups of subjects. Documenting such gene-environment interactions is important if genotype information is ever to be used in a clinical or diagnostic setting, and understanding the molecular mechanisms of such interactions is vital to be able to use the information to develop novel therapeutic approaches for reducing the risk of myocardial infarction. This review focuses on gene-environment interactions detected to date for the G-455A beta fibrinogen gene promoter polymorphism. Carriers of the A allele, representing roughly 20% of the population, consistently have on average 7-10% higher fibrinogen levels than those with the genotype GG. Data will be presented to demonstrate interaction between gender, smoking habit, age, presence of ischaemic disease and level of physical exercise, in the determination of the magnitude of this A-raising effect and thus on an individual's plasma fibrinogen levels.

Adult↗

Pulsed versus continuous tones for evaluating the loudness of tinnitus.

Loudness balance techniques are commonly employed to match the loudness of tinnitus using either pulsed or continuous tones; however, it is not known whether the tone duration affects the observed loudness matches. In this study, hearing thresholds and tinnitus loudness matches were measured in 26 subjects with chronic tinnitus using both pulsed and continuous tones. Subjects' thresholds and loudness matches were determined at 11 frequencies between 0.5 and 10 kHz. No significant differences were found between pulsed versus continuous measures, either for thresholds or for loudness matches. There were, however, nine subjects (34.5% of the group) who showed relatively large differences (> or =10 dB) at one or more test frequencies. These "outlier" values did not show systematic trends; some were positive, some negative. In conclusion, studies employing group data appear to be comparable if group sizes are sufficiently large (e.g., > or =25 subjects). Studies employing smaller numbers of subjects may, however, be vulnerable to potential positive or negative biases introduced by one or more outliers.

Adult↗

Stereospecific analysis and enantiomeric disposition of 3, 4-methylenedioxymethamphetamine (Ecstasy) in humans.

BACKGROUND: Little is known concerning the enantioselective disposition of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) in humans. In addition, the potential of utilizing the stereochemical composition of an analyte in biological media for forensic purposes requires investigation. METHODS: The enantiomers of MDMA and its demethylated metabolite, 3,4-methylenedioxyamphetamine (MDA), present in plasma and urine extracts were derivatized with (-)-(R)-alpha-methoxy-alpha-trifluoromethylphenylacetyl chloride and analyzed by gas chromatography-mass spectrometry and gas chromatography, respectively. The enantioselective disposition of MDMA and MDA was determined following oral administration of racemic MDMA (40 mg) to eight male volunteers. RESULTS: The plasma concentrations of (R)-MDMA exceeded those of the S-enantiomer [ratio R:S of the area under the curve (AUC), 2.4 +/- 0.3], and the plasma half-life of (R)-MDMA (5.8 +/- 2.2 h) was significantly longer than that of the S-enantiomer (3.6 +/- 0.9 h). The majority of the recovered material in urine was excreted within 24 h after dosing, with the recovery of (R)-MDMA (21.4% +/- 11.6%) being significantly greater than that of (S)-MDMA (9.3% +/- 4.9%), and with (S)- and (R)-MDA accounting for 1.4% +/- 0.5% and 1.0% +/- 0.3% of the dose, respectively. Mathematical modeling of plasma enantiomeric composition vs sampling time demonstrated the applicability of using stereochemical data for the prediction of time elapsed after drug administration. CONCLUSIONS: Analytical methods for determining the enantiomeric composition of MDMA and MDA in plasma and urine were developed. The disposition of MDMA in humans is stereoselective, with the more active S-enantiomer having a reduced AUC and shorter half-life than (R)-MDMA. The determination of stereochemical composition may be applicable for forensic purposes.

Administration, Oral↗

Reliability of tinnitus loudness matches under procedural variation.

Repeated tinnitus loudness matches (LMs) were obtained to determine response reliability using a computer-automated technique with two procedural variations, fixed or random step sizes, to increase output level during the initial ascending series of tones at each frequency. Twenty subjects with stable, tonal tinnitus were evaluated with both methods during each of two sessions. Response instructions were displayed on a portable computer, and a pen device was used to make response choices that appeared on the touch-sensitive video monitor. For each method, hearing thresholds and LMs were obtained, with 1-dB resolution, at 1/3-octave frequencies from 1 to 16 kHz. Analyses revealed reliability of LMs to be equivalent between methods. LM data are reported in both dB SPL and dB SL, with the SPL values providing greater reliability both within and between sessions (all r's > or = .889, p's < or = .0001).

Acoustic Impedance Tests↗