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1.
J Voice ; 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38556379

ABSTRACT

OBJECTIVE: To verify breathiness in the cisgender and transgender men and women's voices, compare values of acoustic and perceptual indicators of breathiness and fundamental frequency (f0) between groups, and compare them between the voices attributed as female and male. STUDY DESIGN: Cross sectional retrospective study. METHODS: The study was approved by the Research Ethics Committee (4,937,140). Sustained vowel /a/ and continuous speech recordings of 21 cisgender men (CISM), 31 transgender men (TM), 32 cisgender women (CISW), and 31 transgender women (TW) were analyzed. Three judges conducted a perceptive-auditory analysis regarding the degree breathiness, using a visual analog scale, and attributed gender (female or male). The ABI (Acoustic Breathiness Index) was extracted using the PRAAT software (6.1.16). The f0, Harmonic-Noise Ratio (HNR), Voice Turbulence Index (VTI), and Soft Phonation Index (SPI) were analyzed using the Multi-Dimensional Voice Program (KayPentax). RESULTS: The ABI value for CISM was lower than for TM and CISW. CISW had a higher f0 than; TM had a higher f0 than CISM; and TW had a higher f0 than CISM. The groups did not differ for HNR and VTI. Regarding the SPI, CISM had higher values than CISW. Regarding the auditory perception, TM presented more intense breathiness than CISM in the vowel. Regarding gender attribution by voice, the voices CISM and CISW were 100% identified as male and female. On the other hand, in the vowel analysis, 45.2% of the TM voices were perceived as female, and 59.4% of TW voices as male. CONCLUSION: Breathiness occurs differently between groups and the voices perceived as male and female. Even when TM is submitted to the use of testosterone and undergoes vocal changes, the transglottal airflow remains, which is a female characteristic of phonation.

2.
Postgrad Med J ; 87(1031): 596-600, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21659451

ABSTRACT

INTRODUCTION Anaemia is common in rheumatoid arthritis (RA). Clinicians may focus on rheumatological issues and assume anaemia of chronic disease (ACD). This study challenged this assumption and investigated the causes of anaemia in a large cohort of RA patients to assess its implications. METHODS The hospital where the study was conducted monitors regular full blood count and erythrocyte sedimentation rate (ESR) monthly in all RA patients on disease modifying drugs to assess efficacy and safety. A computerised system identifies and records abnormal results. The database for 2009 was interrogated to find all patients with two consecutive haemoglobin values <11 g/dl. Using a proforma, patients were defined as having iron deficiency anaemia (IDA), ACD, macrocytic anaemia (MCA) or another cause. All results of further tests investigating the anaemia were recorded. RESULTS Among 2000 RA patients on the system, 199 (10%) were identified as having anaemia over a year. Of these, 90 had IDA, 78 had ACD, 25 had MCA, and 6 had postoperative anaemia. Among 90 patients with IDA, investigations were performed in 53, with 23 normal. An explanation for IDA was found in 30: gastrointestinal bleeding in 25, gynaecological blood loss in 3, and urinary bleeding in 2. Among 78 patients with ACD, response to intensification of RA treatment occurred in 45, but erythropoietin therapy was required in 9. Within the 25 patients with MCA, 12 had unrecognised vitamin B(12) deficiency, 4 drug induced changes, 3 myeloid malignancy, 2 hypothyroidism, and 2 alcoholism. CONCLUSIONS Anaemia in RA is common, multifactorial, and potentially both serious and correctable. Established malignancy was present in 10 patients and premalignancy in a further 10 (10% of total). Treatable causes were commonly identified. Clinicians need to investigate the nature and cause of persistent anaemia, and must not assume it to be simply ACD without evidence.


Subject(s)
Anemia/diagnosis , Anemia/etiology , Arthritis, Rheumatoid/complications , Anemia/therapy , Anemia, Iron-Deficiency/diagnosis , Anemia, Iron-Deficiency/etiology , Anemia, Iron-Deficiency/therapy , Anemia, Macrocytic/diagnosis , Anemia, Macrocytic/etiology , Anemia, Macrocytic/therapy , Chronic Disease , Cohort Studies , Costs and Cost Analysis , Ferritins/blood , Humans , Neoplasms/complications
3.
Diabet Med ; 27(6): 650-4, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20546282

ABSTRACT

AIMS: To review postpartum glucose tolerance in women with gestational diabetes and evaluate the role of formal 75 g oral glucose tolerance testing vs. fasting plasma glucose in screening for persistent abnormalities. METHODS: Retrospective study of 985 pregnancies over a 10 year period in a mixed ethnic cohort of women who underwent follow-up glucose tolerance testing at 6 weeks postpartum. Diagnosis obtained by oral glucose tolerance test was tested against that from the fasting plasma glucose value. RESULTS: There were 272 abnormal postpartum oral glucose tolerance test results (27.6%), with 109 women identified as having frank diabetes. Eleven of these (10%) had fasting plasma glucose < or =6.0 mmol/l, as did 62 of 114 cases of impaired glucose tolerance. A fasting plasma glucose concentration of > or =6.1 mmol/l correctly identified abnormal glucose tolerance in 199 of 272 cases (sensitivity 0.73). South Asian women were much more likely to have persistent abnormalities of glucose tolerance than were Europeans (32 vs. 15%, chi(2)P < 0.0001). CONCLUSIONS: A postpartum fasting plasma glucose measurement alone is not sensitive enough in our population to classify glucose tolerance status accurately. A formal postpartum oral glucose tolerance test is therefore needed to facilitate early detection and treatment.


Subject(s)
Diabetes Mellitus/diagnosis , Diabetes, Gestational/diagnosis , Postpartum Period/physiology , Adult , Blood Glucose/analysis , Ethnicity , Female , Glucose Tolerance Test/methods , Humans , Postpartum Period/blood , Predictive Value of Tests , Pregnancy , Retrospective Studies , Risk Factors , Time Factors
4.
Clin Med (Lond) ; 10(4): 326-9, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20849003

ABSTRACT

Morbidity and mortality from pneumonia is increased in patients with rheumatoid arthritis. Factors contributing to this have been recently identified and a number of recommendations have been implemented in an attempt to reverse this trend. The present paper shows that these measures have combined to produce a fourfold reduction in both admissions and case fatality rates. In the study population, immunisation rates against influenza and pneumococcus have improved to 86% and 65%, oral steroid consumption has halved and disease modifying drugs were usually appropriately suspended during acute infection. These measures may now merit more widespread adoption.


Subject(s)
Arthritis, Rheumatoid/complications , Clinical Protocols , Respiratory Tract Infections/complications , Respiratory Tract Infections/mortality , Aged , Antirheumatic Agents/adverse effects , Arthritis, Rheumatoid/drug therapy , Female , Glucocorticoids/adverse effects , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Influenza Vaccines , Leucovorin/therapeutic use , Leukocyte Count , Male , Middle Aged , Neutropenia/complications , Neutropenia/drug therapy , Patient Admission/trends , Pneumococcal Vaccines , Prednisone/adverse effects , Risk Factors , United Kingdom/epidemiology , Vaccination/statistics & numerical data , Vitamin B Complex/therapeutic use
5.
Science ; 240(4858): 1515-7, 1988 Jun 10.
Article in English | MEDLINE | ID: mdl-17798981

ABSTRACT

Experimental acidification of two small soft-water lakes caused nitrification to cease at pH values of 5.4 to 5.7. The resulting blockage of the nitrogen cycle caused a progressive accumulation of amnonium. When the epermental acidification of one of the lakes was ended and the pH was raised to 5.4, nitrification resumed after a time lag of 1 year.

6.
Sci Total Environ ; 642: 1340-1352, 2018 Nov 15.
Article in English | MEDLINE | ID: mdl-30045514

ABSTRACT

Fifty years ago, the Penobscot Estuary was contaminated by mercury discharged from the chlor-alkali plant located in Orrington, Maine, USA. Almost all of the mercury was discharged from the plant during the late 1960s and early 1970s. Despite the much lower mercury discharges in recent decades, present-day concentrations in surface sediment remain high (averaging 350-1100 ng/g dw) and are still high in blood of marsh birds (up to 10.5 µg/g), black duck muscle (0.8 µg/g), and lobster muscle (0.4 µg/g). Methyl mercury (MeHg) concentrations in marsh birds exceed levels that impair reproduction. There are health advisories for duck hunters and closures of shellfish fisheries. These continuing high mercury concentrations are caused by the trapping of legacy mercury in a mobile pool of sediment that is retained in the upper estuary above a tidally forced salinity front, which travels up and down the estuary each tidal cycle - slowing the transport of particulate mercury to Penobscot Bay. The trapped legacy mercury continues to be available for methylation 50 years after it first entered the estuary. This is demonstrated by the fact that rates of MeHg production are positively related to the inorganic mercury concentration in parts of the estuary with elevated concentrations of legacy mercury. Thus, remediation measures that would lower the THg concentration in surface sediment would lower the MeHg in birds, fish and shellfish. All of this new information leads us to recommend two remediation options. Addition of mercury binding agents may lower mercury concentrations in birds in some wetland areas. System-wide, we also recommend Enhanced Natural Recovery (ENR), a novel approach that involves the partial removal of the contaminated mobile sediment pool followed by replacement with clean-clay particulates to dilute inorganic mercury concentrations, which would lower methylation rates and mercury concentrations in biota.

7.
Brain Stimul ; 11(6): 1218-1224, 2018.
Article in English | MEDLINE | ID: mdl-30037658

ABSTRACT

BACKGROUND: Repeatedly pairing a brief train of vagus nerve stimulation (VNS) with an external event can reorganize the sensory or motor cortex. A 30 Hz train of sixteen VNS pulses paired with a tone significantly increases the number of neurons in primary auditory cortex (A1) that respond to tones near the paired tone frequency. The effective range of VNS pulse rates for driving cortical map plasticity has not been defined. OBJECTIVE/HYPOTHESIS: This project investigated the effects of VNS rate on cortical plasticity. We expected that VNS pulse rate would affect the degree of plasticity caused by VNS-tone pairing. METHODS: Rats received sixteen pulses of VNS delivered at a low (7.5 Hz), moderate (30 Hz), or high (120 Hz) rate paired with 9 kHz tones 300 times per day over a 20 day period. RESULTS: More A1 neurons responded to the paired tone frequency in rats from the moderate rate VNS group compared to naïve controls. The response strength was also increased in these rats. In contrast, rats that received high or low rate VNS failed to exhibit a significant increase in the number of neurons tuned to sounds near 9 kHz. CONCLUSION: Our results demonstrate that the degree of cortical plasticity caused by VNS-tone pairing is an inverted-U function of VNS pulse rate. The apparent high temporal precision of VNS-tone pairing helps identify optimal VNS parameters to achieve the beneficial effects from restoration of sensory or motor function.


Subject(s)
Auditory Cortex/physiology , Brain Mapping/methods , Neuronal Plasticity/physiology , Vagus Nerve Stimulation/methods , Vagus Nerve/physiology , Animals , Female , Rats , Rats, Sprague-Dawley
8.
J Clin Pathol ; 60(10): 1144-7, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17259296

ABSTRACT

AIMS: To develop an objective and easy to complete standardised questionnaire for documentation of synovial fluid (SF) gross appearance and use it in the assessment of patients presenting to the rheumatology service with a joint effusion. METHODS: A standardised questionnaire to record the gross appearance of SF was developed. Interobserver error in recorded observations and direct gross analysis of synovial fluid between four observers was calculated in a pilot study. In a prospective study over 8 months, SF gross analysis and cell count were documented in all patients presenting with a joint effusion. Fusch Rosenthal manual counting chamber was used for calculating SF cell counts. RESULTS: There was good interobserver agreement on direct gross analysis and between questionnaire assessors (mean kappa 0.889). 80 SF samples were collected. Gross analysis was performed in all samples and cell count in 72. Of the specimens thought to be inflammatory on gross analysis, 31% were found to be non-inflammatory based on cell count; however, 12 of these patients had an established inflammatory arthritis. Gross analysis had a sensitivity of 94% and specificity of 58% when used to determine whether SF is inflammatory or non-inflammatory. The positive and negative predictive values were 0.69 and 0.91 respectively. CONCLUSIONS: SF cell count did not add any information when SF gross analysis suggested a non-inflammatory process. Gross analysis was better than cell count to determine a potentially septic joint fluid. Further work needs to be done on the value of SF cell counts if gross analysis suggests the fluid to be inflammatory.


Subject(s)
Arthritis/diagnosis , Synovial Fluid/cytology , Adult , Aged , Aged, 80 and over , Arthritis/metabolism , Arthritis, Infectious/diagnosis , Arthritis, Infectious/metabolism , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/metabolism , Cell Count , Crystallization , Diagnosis, Differential , Humans , Middle Aged , Observer Variation , Osteoarthritis/diagnosis , Osteoarthritis/metabolism , Practice Guidelines as Topic , Prospective Studies , Synovial Fluid/chemistry , Synovial Fluid/microbiology
9.
J Mol Biol ; 221(2): 383-5, 1991 Sep 20.
Article in English | MEDLINE | ID: mdl-1920425

ABSTRACT

Malate dehydrogenase from mutant strain F428 of the thermophilic bacterium Thermus flavus has now been crystallized from polyethylene glycol 8000 in a form suitable for diffraction studies. The protein crystallizes in the orthorhombic P2(1)2(1)2(1) space group with unit cell dimensions a = 71.8 A, b = 88.6 A, c = 119.0 A. The asymmetric unit consists of one homodimer of molecular mass 67,000 Da. The X-ray diffraction extends beyond 1.7 A and a full data set to 1.9 A has been collected.


Subject(s)
Malate Dehydrogenase/genetics , Mutagenesis , Thermus/genetics , Crystallization , Malate Dehydrogenase/chemistry , Protein Conformation , Thermus/enzymology , X-Ray Diffraction
10.
Acta Diabetol ; 42(2): 82-6, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15944841

ABSTRACT

The aims of the study were to (1) compare peripheral bone mineral density (BMD) in men with diabetes to peripheral BMD in non-diabetic men, and (2) explore factors which may predict BMD in diabetic men. Ninety men with type 2 diabetes and 35 men with type 1 diabetes were randomly selected for participation via a computerised database. Fifty healthy males were also recruited. All patients had peripheral BMD measured by dual energy Xray absorptiometry (DEXA) at the non-dominant distal radius. Information on a number of clinical parameters was obtained by direct questioning, and from patient case notes. The mean age (95% confidence interval (CI)) of the type 1 diabetic group, type 2 diabetic group and control group were, respectively: 49.3 years (44.6-53.9), 62.8 years (60.7-64.8) and 38.5 (34.9-42.1) years. Median (95% CI) Z-scores for the three groups were: -0.18 (-0.68 to +0.32), +0.19 (-0.14 to +0.49) and -0.02 (-0.4 to +0.31), respectively (p=not significant). Only body mass index (BMI) was correlated with BMD in the type 1 diabetic group, and only BMI and age were correlated with BMD in type 2 diabetics. There was no correlation between BMD and glycosylated haemoglobin concentration (HbA(1)c), disease duration or presence of microvascular or macrovascular complications in either of the diabetic groups. We did not find any significant difference in peripheral BMD between patients with type 1 diabetes, type 2 diabetes and controls.


Subject(s)
Bone Density/physiology , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Absorptiometry, Photon , Adolescent , Adult , Confidence Intervals , Humans , Male , Middle Aged , Reference Values
11.
Int J Radiat Oncol Biol Phys ; 34(3): 727-32, 1996 Feb 01.
Article in English | MEDLINE | ID: mdl-8621298

ABSTRACT

PURPOSE: Contralateral breast dose from primary breast irradiation has been implicated in the risk of second breast malignancies. It has been previously shown that the use of half-beam blocking can increase the opposite breast dose by a factor of five. This study evaluates four different breast treatment techniques to compare the radiation dose to the contralateral breast. METHODS AND MATERIALS: Dose measurements were made using thermoluminescent dosimeters (TLD) capsules, which were placed in the Rando phantom in the following locations in the contralateral breast: seven along the central axis plane, on at 5 cm superior to, and one 5 cm inferior to the central axis plane. One TLD capsule was placed in the midcenter of the treated breast. The following radiation techniques were used: (a) half-beam with a custom block (HB+CB), (b) half-beam using asymmetric collimator jaw (HB/AJ), (c) half-beam using asymmetric collimator jaw with custom block (H/AJ+CB), and (d) isocentric technique with nondivergent posterior borders [Joint Center for Radiation Therapy (JCRT) techique]. For each technique, isodose distributions for the Rando phantom were optimized using (a) 15 degree medial and lateral compensating wedges, and (b) a single 30 degree lateral compensating wedge. The phantom was treated with 6 MV photons. Each technique was repeated six times, and the TLD readings were averaged. RESULTS: The custom cerrobend half-beam block technique gives the highest contralateral breast dose, regardless of wedge. The remaining techniques give results in a similar range, with the asymmetric jaw with no medial wedge technique giving the lowest total dose (p = not significant). The use of a medial wedge increases the opposite breast dose for all techniques. The asymmetric half-beam technique gives significantly less dose than the cerrobend half-beam technique, due to decreased transmission through the asymmetric collimators. The asymmetric jaw vs JCRT technique results in similar contralateral breast dose. CONCLUSIONS: As expected, dose to the contralateral breast increases with the use of a medial wedge. Cerrobend half-beam blocking gives the highest opposite breast dose. The lowest contralateral breast dose is with the asymmetric jaw with no medial wedge and no block. The asymmetric jaw technique with block yields equivalent contralateral breast doses to the JCRT technique.


Subject(s)
Breast Neoplasms/radiotherapy , Breast/radiation effects , Radiotherapy Planning, Computer-Assisted , Breast Neoplasms/etiology , Evaluation Studies as Topic , Female , Humans , Neoplasms, Radiation-Induced/etiology , Radiation Dosage , Radiation Protection , Radiotherapy/adverse effects , Radiotherapy/methods
12.
Autoimmunity ; 12(3): 207-14, 1992.
Article in English | MEDLINE | ID: mdl-1285317

ABSTRACT

Levels of CD5+ B lymphocytes were assayed in a large family study of Primary Sjögren's syndrome. There was no significant difference in CD5 expression by index cases or their relatives when compared to controls. No association between CD5 expression, serological abnormalities or HLA haplotype was found and, furthermore, no evidence of linkage with HLA was observed. There was, however, variation in the expression of CD5+ B cells between the families. Levels in spouses were lower and reached statistical significance. The role for genetic and environmental factors influencing CD5 expression is discussed. Any genetic influence does not appear to involve the HLA region or genes in linkage disequilibrium.


Subject(s)
Antigens, CD/analysis , B-Lymphocytes/immunology , Sjogren's Syndrome/immunology , Adult , Aged , CD5 Antigens , Female , HLA-DR Antigens/genetics , Haplotypes , Humans , Linkage Disequilibrium , Male , Middle Aged , Sjogren's Syndrome/genetics
13.
Infect Control Hosp Epidemiol ; 21(7): 455-8, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10926395

ABSTRACT

OBJECTIVE: To study the association of antibiotic-utilization measures and control of multidrug-resistant (MDR) Klebsiella pneumoniae after emergence in two hospitals in our medical center. DESIGN AND SETTING: Rates of MDR K. pneumoniae at two hospitals were compared before and after acute interventions, including emphasis on Contact Precautions and education in antibiotic utilization. Antipseudomonal beta-lactam antibiotic use was measured before and after the interventions at both hospitals. Pulsed-field gel electrophoresis of whole cell DNA was used as a marker of strain identity. RESULTS: Clonal strain dissemination was the major mechanism of emergence at hospital A; emergence was polyclonal at hospital B. Antibiotic-utilization interventions at both institutions included physician education regarding the association of ceftazidime use and MDR K. pneumoniae. At hospital A, ceftazidime use decreased from 4,301 g in the preintervention period, to 1,248 g in the postintervention period. Piperacillin-tazobactam use increased from 12,455 g to 17,464 g. Ceftazidime resistance in K. pneumoniae decreased from 110 (22%) of 503 isolates to 61 (15%) of 407 isolates (P<.05); piperacillin-tazobactam resistance decreased from 181 (36%) of 503 to 77 (19%) of 407 isolates (P<.05). At hospital B, ceftazidime use decreased from 6,533 g in the preintervention period to 4,792 g in the postintervention period. Piperacillin-tazobactam use increased from 58,691 g to 67,027 g. Ceftazidime resistance in K. pneumoniae decreased from 42 (10%) of 415 isolates to 19 (5%) of 383 isolates (P<.05). Piperacillin-tazobactam resistance decreased from 91 (22%) of 415 isolates to 54 (14%) of 383 isolates (P<.05). Follow-up data showed continued decrease in piperacillin-tazobactam resistance despite increased use at both hospitals. CONCLUSIONS: Antibiotic-use measures may be particularly important for control of MDR K. pneumoniae, whether emergence is clonal or polyclonal.


Subject(s)
Anti-Bacterial Agents/pharmacology , Drug Resistance, Multiple , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Anti-Bacterial Agents/therapeutic use , Cross Infection , DNA, Bacterial/analysis , Electrophoresis, Gel, Pulsed-Field , Humans , Infection Control/methods , Klebsiella Infections/transmission , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/pathogenicity , Lactams
14.
Clin Chim Acta ; 184(3): 251-8, 1989 Oct 16.
Article in English | MEDLINE | ID: mdl-2611998

ABSTRACT

The fucosylation of haptoglobins is altered in rheumatoid arthritis. In order to investigate the clinical usefulness of this finding, serum levels of abnormally-fucosylated haptoglobins (FHp) have been assessed in defined and matched groups of patients with different inflammatory joint diseases. FHp was elevated in 16/17 patients with active rheumatoid arthritis (RA); 1/20 patients with inactive rheumatoid arthritis; 1/11 patients with osteoarthritis; and 4/10 patients with seronegative polyarthritis. Raised FHp levels, therefore, are not disease-specific. There was no relationship between the duration of RA and the FHp level. The FHp expression in RA was also compared with other biochemical indices of disease activity. The degree of correlation between FHp and articular index, joint score and early-morning stiffness was very similar to that obtained for C reactive protein (CRP), and better than that obtained for erythrocyte sedimentation rate and haemoglobin. FHp, however, gives fewer false-positives than CRP in cases of inactive disease. until FHp can be measured more easily and cheaply, CRP estimation is still the biochemical test of choice in RA.


Subject(s)
Arthritis, Rheumatoid/blood , Fucose , Haptoglobins/analysis , Adult , Aged , Electrophoresis/methods , Female , Glycosylation , Haptoglobins/metabolism , Humans , Male , Middle Aged
15.
J Psychopharmacol ; 12(4): 396-400, 1998.
Article in English | MEDLINE | ID: mdl-10065915

ABSTRACT

The association between selective serotonin reuptake inhibitors (SSRIs) and hyponatraemia has been well documented, the elderly appearing to be at greatest risk. An analysis of data of hyponatraemia in the elderly using SSRIs from all published cases and from the Committee on Safety of Medicines found that the mean time to detection was about 3 weeks after commencing SSRIs. A wide range of time to detection (1-253 days) and non-specific symptoms suggest hyponatraemia is detected by chance rather than being specifically looked for. In the elderly there are physiological changes, a high prevalence of medical illnesses and concomitant drug use, which may precipitate hyponatraemia. Together with a risk of altered water regulation in psychiatric illness this may account for the particular susceptibility of the elderly to hyponatraemia whilst using SSRIs.


Subject(s)
Hyponatremia/chemically induced , Selective Serotonin Reuptake Inhibitors/adverse effects , Aged , Humans , Middle Aged , Retrospective Studies , Risk Factors
16.
Cochrane Database Syst Rev ; (3): CD000464, 2001.
Article in English | MEDLINE | ID: mdl-11686961

ABSTRACT

BACKGROUND: Neuroleptic drugs are controversial treatments in dementia, with evidence accumulating that they may hasten clinical decline. Despite these concerns, they are commonly prescribed for elderly and demented patients. Thioridazine, a phenothiazine neuroleptic, has been commonly prescribed because it was thought to produce relatively less frequent motor side effects. The drug has significant sedative effect, and it is thought that this is the main mechanism of action in calming and controlling the patient. However, pharmacologically, it also has marked anticholinergic properties that could potentially have a detrimental effect on cognitive function. OBJECTIVES: To evaluate the efficacy of thioridazine in dementia in terms of: 1) efficacy in controlling symptoms 2) cognitive outcome for the patient 3) safety SEARCH STRATEGY: The Cochrane Controlled Trials Register and other electronic databases were searched using the terms 'thioridazine', 'melleril', 'dementia' and 'old age'. In addition, Novartis, the pharmaceutical company that developed and markets thioridazine, was approached and asked to release any published or unpublished data they had on file. SELECTION CRITERIA: Unconfounded, single-blind or double-blind, randomised trials were identified in which treatment with thioridazine was administered for more than one dose and compared to an alternative intervention in patients with dementia of any aetiology. Trials in which allocation to treatment or comparator were not truly random, or in which treatment allocation was not concealed, were reviewed but are not included in the data analysis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers (VK, CAK and RJH). For continuous and ordinal variables, the main outcome measures of interest were the final assessment score and the change in score from baseline to the final assessment. The assessment scores were provided by behavioural rating scales, clinical global impression scales, functional assessment scales, psychometric test scores, and frequency and severity of adverse events. Data were pooled where appropriate or possible, and the Peto odds ratio (95%CI) or the weighted mean difference (95%CI) estimated. Where possible, intention to treat data were used. MAIN RESULTS: The meta-analysis showed that, compared with placebo, thioridazine reduced anxiety symptoms as evidenced by changes on the Hamilton Anxiety Scale. However, there was no significant effect on clinical global change, and a non-significant trend for higher adverse effects with thioridazine. Compared to diazepam, thioridazine was superior in terms of some anxiety symptoms, with similar adverse effects. Global clinical evaluation scales did not favour either treatment. Compared to chlormethiazole, thioridazine was significantly inferior when assessed on some items of the CAPE and the Crichton Geriatric Behavioural Rating Scales. Thioridazine was also associated with significantly more dizziness. No superiority for thioridazine was shown in comparisons with etoperidone, loxapine or zuclopenthixol, except to produce fewer side effects than loxapine. REVIEWER'S CONCLUSIONS: Very limited data are available to support the use of thioridazine in the treatment of dementia. If thioridazine were not currently in widespread clinical use, there would be inadequate evidence to support its introduction. The only positive effect of thioridazine when compared to placebo is the reduction of anxiety. When compared to placebo, other neuroleptics, and other sedatives, it has equal or higher rates of adverse effects. Clinicians should be aware that there is no evidence to support the use of thioridazine in dementia, and its use may expose patients to excess side effects.


Subject(s)
Antipsychotic Agents/therapeutic use , Dementia/drug therapy , Thioridazine/therapeutic use , Antipsychotic Agents/adverse effects , Humans , Thioridazine/adverse effects
17.
Cochrane Database Syst Rev ; (2): CD000464, 2000.
Article in English | MEDLINE | ID: mdl-10796547

ABSTRACT

BACKGROUND: Neuroleptic drugs are controversial treatments in dementia, with evidence accumulating that they may hasten clinical decline. Despite these concerns, they are commonly prescribed for elderly and demented patients. Thioridazine, a phenothiazine neuroleptic, is one of the most commonly prescribed. It has often been a preferred agent because it is thought to produce relatively less frequent motor side effects. The drug has significant sedative effects, and it is thought that these are the main mechanism of action in calming and controlling the patient. However, pharmacologically, it also has marked anticholinergic properties that could potentially have a detrimental effect on cognitive function. OBJECTIVES: To determine the evidence on which the use of thioridazine in dementia is based in terms of: 1) efficacy in controlling symptoms 2) cognitive outcome for the patient 3) safety SEARCH STRATEGY: The Cochrane Controlled Trials Register and other electronic databases were searched using the terms 'thioridazine', 'melleril', 'dementia' and 'old age'. In addition, Novartis, the pharmaceutical company that developed and markets thioridazine, was approached and asked to release any published or unpublished data they had on file. SELECTION CRITERIA: Unconfounded, single-blind or double-blind, randomised trials were identified in which treatment with thioridazine was administered for more than one dose and compared to an alternative intervention in patients with dementia of any aetiology. Trials in which allocation to treatment or comparator were not truly random, or in which treatment allocation was not concealed were reviewed but are not included in the data analysis. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the reviewers (VC, CAK and RJH). For continuous and ordinal variables, the main outcome measures of interest were the final assessment score and the change in score from baseline to the final assessment. The assessment scores were provided by behavioural rating scales, clinical global impression scales, functional assessment scales, psychometric test scores, and frequency and severity of adverse events. Data were pooled where appropriate or possible, and the Peto odds ratio (95%CI) or the weighted mean difference (95%CI) estimated. Where possible, intention to treat data were used. MAIN RESULTS: The meta-analysis showed that, compared with placebo, thioridazine reduced anxiety symptoms as evidenced by changes on the Hamilton Anxiety Scale. However, there was no significant effect on clinical global change, and a non-significant trend for higher adverse effects with thioridazine. Compared to diazepam, thioridazine was superior in terms of some anxiety symptoms, with similar adverse effects. Global clinical evaluation scales mostly did not favour either treatment. Compared to chlormethiazole, thioridazine was significantly inferior when assessed on some items of the CAPE and the Crichton Geriatric Behavioural Rating Scales. Thioridazine was also associated with significantly more dizziness. No superiority for thioridazine was shown in comparisons with etoperidone, loxapine or zuclopenthixol. REVIEWER'S CONCLUSIONS: Very limited data are available to support the use of thioridazine in the treatment of dementia. If thioridazine were not currently in widespread clinical use, there would be inadequate evidence to support its introduction. The only positive effect of thioridazine when compared to placebo is the reduction of anxiety. When compared to placebo, other neuroleptics, and other sedatives it has equal or higher rates of adverse effects. Clinicians should be aware that there is no evidence to support the use of thioridazine in dementia, and its use may expose patients to excess side effects.


Subject(s)
Antipsychotic Agents/therapeutic use , Dementia/drug therapy , Thioridazine/therapeutic use , Humans
18.
Hum Exp Toxicol ; 22(2): 103-5, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12693836

ABSTRACT

A 45-year-old man ingested 3000 mg of citalopram hydrobromide (2400 mg citalopram). He presented to the Emergency Department 2 hours post-ingestion with a pulse of 100 beats/min and blood pressure of 120/80 mmHg. His electrocardiogram (ECG) was normal. Chest X-ray showed bilateral shadowing, with no evidence of aspiration of gastric contents. Shortly after, he had three tonic-clonic seizures, requiring intravenous diazepam. Eight hours post-ingestion he became oliguric with deteriorating renal function, despite normal arterial and central venous pressures. He became increasingly hypoxic, with chest X-ray changes compatible with adult respiratory distress syndrome (ARDS). Despite treatment with 100% oxygen and continuous positive airway pressure, his gas exchange continued to deteriorate, requiring intubation and ventilation. His renal function also deteriorated with a peak creatinine of 492 micromol/L on day 4 in the absence of rhabdomyolysis. There was complete spontaneous recovery of renal function after 2 weeks. A peak plasma total citalopram (R+S enantiomers) concentration of 1.92 mg/L was recorded 2 hours post-ingestion. Total norcitalopram concentrations continued to rise up to 24 hours post-ingestion. Citalopram has been associated with seizures, ECG abnormalities, rhabdomyolysis and coma after overdose. The renal and respiratory complications seen in this patient have not been reported previously.


Subject(s)
Citalopram/poisoning , Poisoning/etiology , Respiratory Distress Syndrome/chemically induced , Selective Serotonin Reuptake Inhibitors/poisoning , Suicide, Attempted , Citalopram/blood , Drug Overdose , Humans , Male , Middle Aged , Poisoning/physiopathology , Poisoning/therapy , Renal Insufficiency/etiology , Renal Insufficiency/physiopathology , Respiratory Distress Syndrome/pathology , Selective Serotonin Reuptake Inhibitors/blood , Treatment Outcome
19.
Mar Pollut Bull ; 44(9): 903-11, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12405215

ABSTRACT

Concentrations of polycyclic aromatic hydrocarbons have been determined in sediments, mussels and crustacea in the vicinity of a former gasworks site by Shoreham Harbour, UK. Very high concentrations of PAH were found in the substrate, an ash-like material deposited on the former gasworks site, which exhibited a profile consistent with the major source of contamination being coal or coke tar produced during the period of gas production at the site. Elevated PAH concentrations were also found in mussels both from the beach below the former gasworks site, and from sites further to the east in Portslade and Hove. The significance of these concentrations were assessed using an approach which involved the calculation of benzo[a]pyrene equivalent conoentrations (BaPEs), summing concentrations of individual PAH on the basis of their comparative potency as carcinogens. BaPE ranged from values of, or close to, zero for crustacea, to 336 microg kg(-1) wet weight in mussels from Southwick Beach. The contaminated mussels are not exploited commercially but may be taken by casual gatherers, and notices have been posted to warn potential consumers.


Subject(s)
Bivalvia/metabolism , Crustacea/metabolism , Geologic Sediments/analysis , Polycyclic Aromatic Hydrocarbons/analysis , Water Pollutants, Chemical/analysis , Animals , England , Environmental Monitoring/methods , Gasoline , Industry , Oceans and Seas
20.
Med Dosim ; 19(3): 169-73, 1994.
Article in English | MEDLINE | ID: mdl-7818757

ABSTRACT

The treatment of abutting fields presents multiple difficulties, including problems of field overlaps or gaps, complexity of simulation, and the difficulties of daily setup and variation. Multiple techniques have been described for the treatment of the breast/chest wall and supraclavicular nodes using tangents and a matched supraclavicular field. The techniques described have used collimator angles, couch angles, and/or corner blocks in an attempt to match these fields with no overlap or gap. Some of these techniques required complex calculations or treatment devices to achieve a geometric match between fields. We describe a technique for treatment of breast and supraclavicular nodes that uses a single isocenter and requires asymmetric collimator jaws to give half-blocked fields. The simulation and setup are done empirically, with no complex calculations required. The daily setup and treatment can be done rapidly and reliably, with no extra equipment required. Custom blocks may be used to conform to the chest wall contour and decrease the amount of lung in the treatment fields.


Subject(s)
Breast Neoplasms/radiotherapy , Female , Humans , Lymphatic Metastasis , Models, Structural , Radiotherapy/instrumentation , Radiotherapy/methods
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