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Biomedical subjects

D Richardson

Publications and source records attributed to D Richardson.

At least 19 recordsLinked to original sources

Use of botanicals in food supplements. Regulatory scope, scientific risk assessment and claim substantiation. 2005.

BACKGROUND/AIMS: In the European Union, an elaborate legal framework regulates botanical products both under food and medicinal law. The decision as to which legal framework applies to an individual product may differ between the Member States. In the case of botanical food supplements, all food law provisions apply to their manufacturing, composition and marketing, including the new claims legislation. METHODS: Elements from EU and national law, scientific and other publications are brought together to investigate how to clarify the differentiation between the use of botanicals for medicinal and health-promoting purposes on a scientific basis. RESULTS: Guidance on the safety assessment and quality evaluation of botanicals is proposed in light of the different approaches described in the scientific literature with particular attention to the concept of long-term use as an integral part of safety evaluation. Guidance on claims substantiation is also included, taking into consideration the proposed legislation, the concept of long-term experience and grading of evidence. CONCLUSIONS: A model for safety and efficacy assessment of botanical food supplements in the EU is proposed, and should be taken into consideration in the development of legislation and scientific research on botanicals.

Animals↗

Predictors of recurrent stroke in African Americans.

BACKGROUND: Stroke incidence and mortality are disproportionately higher among African Americans than among whites. OBJECTIVE: To describe the recurrent stroke characteristics and determine the predictability of known vascular risk factors for stroke recurrence in African Americans. METHODS: The authors followed 1,809 African Americans in the African-American Antiplatelet Stroke Prevention Study with recent noncardioembolic ischemic stroke for recurrent stroke, recurrent stroke subtype, and disability. RESULTS: Of the subjects, 10.6% experienced a recurrent stroke during follow-up. The mean interval between eligibility and recurrent stroke was 325 days (median 287 days, SD = 224 days). Stroke recurrence resulted in an average 1.5-point increase in the National Institute of Health Stroke Scale (p < 0.001) and a 3.5-point decrease in modified Barthel Index (p < 0.001). Of previously nondisabled subjects, 48% became disabled or died after stroke recurrence (p < 0.0001). Longitudinal analysis resulted in a hazard for recurrent stroke for each 10-mm Hg increase in systolic blood pressure of 1.103 (95% CI: 1.031 to 1.179, p = 0.004), pulse pressure 1.123 (95% CI: 1.041 to 1.213, p = 0.003), and mean arterial pressure 1.123 (95% CI: 1.001 to 1.260, p = 0.048). Multivariate analysis revealed increases in the recurrent stroke hazard for increases in baseline Glasgow Outcome Score (1.449, 95% CI: 1.071 to 1.961, p = 0.016) and increases in longitudinal pulse pressure (1.009, 95% CI: 1.001 to 1.017, p = 0.029). CONCLUSION: Recurrent stroke leads to disability and disability predicts recurrent stroke. Hypertension is the most predictive modifiable stroke risk factor.

Activities of Daily Living↗

Craniofacial surgery for orbital malformations.

Paediatric craniofacial surgery is a highly specialised field requiring a multidisciplinary team input. Orbital and ocular involvement is relatively common in craniofacial patients. This is more in syndromic patients. In nonsyndromic patients, orbital involvement is common in frontal plagiocephaly and trigonocephaly. The management of these conditions requires close working between the craniofacial surgeon and ophthalmologist. An outline of the management of these deformities is discussed.

Abnormalities, Multiple↗

A randomized clinical trial of activated charcoal for the routine management of oral drug overdose.

BACKGROUND: Activated charcoal (AC) is commonly used for the routine management of oral drug overdose. AIM: To determine whether the routine use of activated charcoal has an effect on patient outcomes. DESIGN: Randomized controlled unblinded trial. METHODS: We recruited all adult patients presenting with an oral overdose at The Canberra Hospital, excluding only transfers, late presenters, those who had ingested drugs not adsorbed by activated charcoal or where administration was contraindicated, and very serious ingestions (at the discretion of the admitting physician). Patients were randomized to either activated charcoal or no decontamination. RESULTS: The trial recruited 327 patients over 16 months. Of 411 presentations, four refused consent, 27 were protocol violations and 53 were excluded from the trial. Only seven were excluded due to the severity of their ingestion. The most common substances ingested were benzodiazepines, paracetamol and selective serotonin reuptake inhibitor antidepressants. More than 80% of patients presented within 4 h following ingestion. There were no differences between AC and no decontamination in terms of length of stay (AC 6.75 h, IQR 4-14 vs. controls 5.5 h, IQR 3-12; p=0.11) or secondary outcomes including vomiting, mortality and intensive care admission. DISCUSSION: Routine administration of charcoal following oral overdose did not significantly influence length of stay or other patient outcomes following oral drug overdose. There were few adverse events. This does not exclude a role in patients who present shortly after ingestion of highly lethal drugs.

Acetaminophen↗

Cyclooxygenase-2 protein levels are independent of epidermal growth factor receptor expression or activation in operable non-small cell lung cancer.

UNLABELLED: Both cyclooxygenase (COX)-2 and epidermal growth factor receptor (EGFR) are thought to play important roles in the pathogenesis of non-small cell lung cancer (NSCLC). A number of in vitro studies have postulated a link between EGFR activation and subsequent COX-2 upregulation. The relationship between these factors has not been established in patients with NSCLC. COX-2 and EGFR expression were studied in 172 NSCLC specimens using standard immunohistochemical techniques. Western blotting was used to determine COX-2 and EGFR levels in five NSCLC cell lines. The effect of treatment with EGF on COX-2 expression in A549 cells was assessed. RESULTS: Both EGFR and COX-2 are overexpressed in NSCLC. The predominant pattern of COX-2 and EGFR staining was cytoplasmic. Membranous EGFR staining was seen in 23.3% of cases. There was no relationship between COX-2 and EGFR expression and survival or any clinicopathological features. No correlation was seen between EGFR expression and COX-2 expression in the immunohistochemical series or in the cell lines. Treatment with EGF did not upregulate COX-2 levels in A549 cells, either in serum free or serum-supplemented conditions. CONCLUSIONS: Although COX-2 and EGFR are over-expressed in NSCLC neither was of prognostic significance in this series of cases. There is no correlation between these two factors in either tumour samples or cell lines. Although these factors show no correlation in NSCLC, they remain potential, though independent targets for treatment.

Aged↗

Investigation of human contacts: a Mycobacterium bovis outbreak among cattle at a California dairy.

BACKGROUND: In May 2002, a Mycobacterium bovis outbreak occurred among cattle at a California dairy. We investigated to determine whether persons were infected after working with the cattle or drinking their raw milk. METHODS: We identified persons with potential contact with infected cattle, including dairy workers, their family members, and slaughterhouse workers. Persons were given a tuberculin skin test (TST), and their occupational and milk-drinking habits were recorded. RESULTS: Of 88 potential contacts, 78 (90%) were given a TST; 33 (43%) had positive TST results, of whom 32 were Mexican-born (RR 15.8, 95%CI 2.3-108.8). No persons had active tuberculosis. Eighteen (72%) dairy workers, 11 (27%) family members, and four (33%) slaughterhouse workers had positive TST results. After adjusting for Mexican-birth and age, dairy workers were no more likely to have positive TST results than others (adjusted RR 1.2, 95%CI 0.6-2.1). Forty-one (62%) dairy staff and their family members drank raw milk from the dairy; 21 (51%) had positive TST results and were Mexican-born. All 13 US-born raw milk drinkers had negative TST results. CONCLUSION: A high prevalence of positive TST results was documented among workers at the affected dairy, although results were not independently associated with contact with infected cattle or milk products. Further assessment of California dairy workers should be considered.

Agricultural Workers' Diseases↗

Adiponectin receptors gene expression and insulin sensitivity in non-diabetic Mexican Americans with or without a family history of Type 2 diabetes.

AIMS/HYPOTHESIS: The recent discovery of two adiponectin receptors (AdipoR1 and AdipoR2) will improve our understanding of the molecular mechanisms underlying the insulin-sensitising effect of adiponectin. The aim of this study was to determine for the first time whether skeletal muscle AdipoR1 and/or AdipoR2 gene expression levels are associated with insulin resistance. METHODS: Using RT-PCR and northern analysis we measured AdipoR1 and AdipoR2 gene expression in skeletal muscle from healthy Mexican Americans with normal glucose tolerance who had (n=8) or did not have (n=10) a family history of Type 2 diabetes. RESULTS: Gene expression profiling indicated that the AdipoR1 and AdipoR2 isoforms are highly expressed in human skeletal muscle, unlike in mice where AdipoR2 expression was highest in the liver, and AdipoR1 was highest in skeletal muscle. In the study subjects, the expression levels of AdipoR1 (p=0.004) and AdipoR2 (p=0.04), as well as plasma adiponectin concentration (p=0.03) were lower in people with a family history of Type 2 diabetes than in those with no family history of the disease. Importantly, the expression levels of both receptors correlated positively with insulin sensitivity (r=0.64, p=0.004 and r=0.47, p=0.048 respectively). CONCLUSIONS/INTERPRETATION: Collectively, these data indicate that both isoforms of the adiponectin receptor play a role in the insulin-sensitising effect of adiponectin.

Adiponectin↗

Evidence for differential modulation of conditioned aversion and fear-conditioned analgesia by CB1 receptors.

Fear-conditioned analgesia is an important survival response mediated by substrates controlling nociception and aversion. Cannabinoid(1) (CB(1)) receptors play an important role in nociception and aversion. However, their role in fear-conditioned analgesia has not been investigated. This study investigated the effects of systemic administration of the CB(1) receptor antagonist, SR141716A (1 mg/kg, i.p.), on fear-conditioned analgesia and conditioned aversion in rats. Twenty-four hours after receiving footshock, rats exhibited reduced formalin-evoked nociceptive behaviour, increased freezing and increased defecation when tested in the footshock apparatus, compared with non-footshocked formalin-injected rats. SR141716A attenuated fear-conditioned analgesia, freezing and defecation. Importantly, SR141716A had no effect on formalin-evoked nociceptive behaviour over an equivalent time period in rats not receiving footshock. SR141716A had no effect on contextually induced freezing during the first half of the test trial in rats receiving intra-plantar injection of saline. Administration of SR1417176A did, however, attenuate short-term extinction of contextually induced freezing and ultrasound emission in rats receiving intra-plantar saline, compared with vehicle-treated saline controls. These data suggest an important role for the CB(1) receptor in mediating fear-conditioned analgesia and provide evidence for differential modulation of conditioned aversive behaviour by CB(1) receptors during tonic, persistent pain.

Analgesia↗

Emergency surgery in patients in extremis from blunt torso injury: heroic surgery or futile care?

BACKGROUND: Trauma strikes unexpectedly, frequently in the young and fit. When trauma victims arrive in the emergency room all possible steps, including surgery, are often undertaken in an attempt to achieve a successful outcome. However, for patients presenting in extremis, with cardiac arrest or exsanguinating blunt chest injury, the results of resuscitation and emergency surgery are extremely poor. PATIENTS AND SETTING: Eight patients in extremis with a mean injury severity score of 36, presented to the resuscitation room of Queens Medical Centre during 2001. On arrival all were in extremis or cardiac arrest after significant blunt injury to the torso, and during resuscitation had a brief loss of cardiac output. They underwent emergency surgery to control haemorrhage and correct injuries in an attempt to preserve life. Seven patients died within hours of their initial presentation either in theatre or the intensive care unit and one patient survived. CONCLUSIONS: Futile care in the management of severely injured patients is a controversial concept although the literature defines four concepts of futility within surgery. At present, while there remains even the remotest possibility of survival, there remains a strong incentive to act and reports of isolated survivors from studies of trauma patients in extremis or cardiac arrest continue to emerge. This may be seen as justification for either an aggressive surgical approach or an indication that surgery is futile. In an emerging culture of guidelines regarding effectiveness of treatment, is this an area in which such guidelines can or should be applied?

Accidents, Traffic↗

Prospective comparison of methods of closure of the coronal flap after craniofacial surgery in children.

The coronal flap in children may be closed with clips or sutures. The results of closure with clips in patients treated during 1 year at the paediatric craniofacial unit, Liverpool, UK, were audited. Eight of 43 required a further general anaesthetic for removal of clips. A prospective audit the following year of patients whose wounds were closed with a rapidly-absorbed polyglactin suture (Vicryl rapide) showed that 3 out of 39 required re-suture of the wound in theatre (two following trauma from falls). There was one infection in each group. Neither of these patients required formal debridement of the wound in theatre. Rapidly-absorbed polyglactin is a safe alternative to clips for wound closure after craniofacial surgery in children and the morbidity is less because fewer patients have to return to theatre than closure with surgical clips.

Absorbable Implants↗

Effect of urate on nitric oxide microcirculatory response in the rat tail to body heating.

OBJECTIVE: The objective of this study was to determine if nitric oxide (NO)-mediated cutaneous vasodilation depends on urate concentrations. METHODS: Capillary blood cell velocities (BCV) in the tail capillary vessels of anesthetized, heat-stressed Sprague-Dawley rats were measured by the videomicroscopy method, and the femoral mean arterial pressure (MAP) was recorded on a Grass polygraph. The effects of urate or urate and NO production on the above parameters were determined by using specific inhibitors of these compounds, for example, allopurinol (All) or All or N-nitro-L-arginine (NNA), respectively. Urate concentrations were determined by an enzymatic, colorimetric method, and total nitrite levels were measured fluorometrically. RESULTS: During heat stress, All or All and NNA significantly decreased plasma urate or urate and total nitrite concentrations, respectively, and the response of vascular conductance (estimated as a ratio of BCV to MAP). Urate administration, after All and NNA pretreatment, restored plasma urate and total nitrite concentrations and increased BCV/MAP. CONCLUSIONS: Urate at physiological concentration helps to maintain vascular conductance of cutaneous capillaries in the rat tail during body heating. The effect of urate on vascular conductance may be mediated by NO.

Allopurinol↗

Physical therapy in spasticity.

Physiotherapists are part of the rehabilitation team involved in the management of adult spasticity. Physical therapy is one part of the armoury in the fight against this disabling symptom of the upper motor neurone syndrome. Identifying the physiological changes brought about by physical therapy or physiotherapy, is difficult. As with many interventions in rehabilitation, this area is poorly studied and, until recently, there was little or no evidence for its effectiveness. The aim of this presentation is to identify key components of a physiotherapy approach and outline specific techniques. The key components considered are: education of the patient and their carers; the 'intervention cycle' - involving accurate assessment, careful measurement, intervention and evaluation; accurate goal setting and a staged stepwise approach over prolonged periods. The specific techniques used include treatments targeted at: muscle length changes, muscle strengthening and functional performance. Broadly these techniques can be divided into biomechanical, cognitive and neurophysiological, each being interdependent on the others. Physiotherapy combined with the other available treatments should meet the challenge arising from adult spasticity.

Humans↗

Selective renal embolisation for renovascular hypertension?

An 11 year old girl developed hypertensive encephalopathy and renal failure from reflux nephropathy. Resection of her shrunken left kidney did not control her hypertension. Two selective arterial embolisations of the scarred right lower pole produced only transient benefit, but a heminephrectomy gave good control. Embolisation may delay definitive treatment.

Child↗

Safety evaluation of a glutaraldehyde modified tyrosine adsorbed housedust mite extract containing monophosphoryl lipid A (MPL) adjuvant: a new allergy vaccine for dust mite allergy.

A new allergy vaccine is currently under clinical evaluation for the prevention or relief of symptoms caused by specific housedust mites. It consists of a 50:50 mixture of the mite Dermatophagoides pteronyssinus and D. farinae protein derived from aqueous extracts of the mites which is chemically modified by glutaraldehyde and adsorbed onto L-tyrosine with addition of the immunostimulatory adjuvant, monophosphoryl lipid A (MPL) "Polymite". A specific preclinical safety testing strategy was developed to support clinical use and comprised single and repeat dose toxicity, reproduction toxicity and local tolerance studies. Dose levels of up to 0.5ml for the mouse and up to 1ml for both the rat and the rabbit were used. Overall, the product was shown to produce no toxicological findings of significance at levels greatly in excess to those proposed for clinical use. A not unexpected, but relatively minor, immunostimulatory effect was seen following repeated dosing (once weekly for 13 weeks) at 1ml per rat; the Polymite formulation also resulted in injection site reaction which can largely be attributed to the presence of tyrosine. No reproduction toxicity was found.

Adjuvants, Immunologic↗