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Biomedical subjects

W A Chambers

Publications and source records attributed to W A Chambers.

At least 37 records · Page 2Linked to original sources
PubMed1999

A retrospective cohort study of post mastectomy pain syndrome.

Post mastectomy pain syndrome is a condition which can occur following breast surgery and has until recently been regarded as uncommon. Recent reports have suggested that it may affect 20% or more of women following mastectomy. The symptoms are distressing and may be difficult to treat however treatment for neuropathic pain can be successful. This paper reports a retrospective cohort of consecutive mastectomy cases over a six year period in one region of whom 511 survivors were traced and eligible for survey. A total of 408 completed a questionnaire survey which revealed that 175 (43%) had ever suffered from postmastectomy pain syndrome and 119 (29%) reported current symptoms although the majority were decreasing in intensity. A striking finding was the very high cumulative prevalence in younger women (65%) decreasing to 26% in the over 70 year group. The details of the onset, frequency and intensity of symptoms are described along with their natural history. The age effect on the frequency of the syndrome influences the marital status, employment status, housing, and educational status of those who report typical symptoms. Body weight and height are also associated with the frequency of post mastectomy pain syndrome. Relationship between the frequency of post mastectomy pain syndrome and radiotherapy, chemotherapy and the use of tamoxifen are difficult to unravel because of the combinations of pre and post operative treatments received confounded by age. The implications of a much higher frequency of post mastectomy pain are discussed with regard to management and counselling. The high frequency of the syndrome in the younger women is important and possible explanations are explored.

Adult↗
PubMed1999

Chronic pain in primary care.

Chronic pain is a very common cause of suffering, disability and economic adversity in the community. It is a complex problem that needs to be understood in a multi-dimensional way for effective management. Most research to date has been based in specialist clinics rather than in primary care, with consequently limited findings. Chronic pain differs from acute pain in that management follows a rehabilitative rather than a treatment model, though these are not mutually exclusive. Full assessment of the patient, preferably multi-disciplinary, will improve his or her outlook. Management should be holistic, rigorous in the application of conventional therapies (including analgesics and physical therapy) and ready to admit an improved understanding of psychological and social techniques. There may be a role for complementary therapies. As a large proportion of chronic pain presents only in the community, there may be a role for greater primary care input to management.

Chronic Disease↗
PubMed1998

Epidural anaesthesia as a method of pre-emptive analgesia for abdominal hysterectomy.

The effect of pre- versus postincisional epidural blockade without the use of systemic opioids was investigated in a randomised, double-blind study of two groups of 25 patients undergoing abdominal hysterectomy performed under general anaesthesia. The first group received, via a lumbar epidural catheter, 0.9% saline (16 ml) 15 min prior to surgical incision and 0.5% bupivacaine (15 ml) and fentanyl 50 micrograms (1 ml) 15 min prior to skin closure. The second group of 25 patients received the same amount of bupivacaine and fentanyl 15 min pre-incision and saline prior to skin closure. Visual analogue pain scores and patient-controlled morphine consumption were measured at specified times for 48 h. We were unable to detect any significant difference in either of the outcome measures of the two groups and thus were unable to demonstrate that epidural blockade using local anaesthetic and opioid has a pre-emptive effect.

Adult↗
PubMed1998

Minor morbidity after day-case surgery.

The number of patients and procedures considered suitable for day-case anaesthesia and surgery continues to grow and it is hoped that 50-60% of all operations in the UK will eventually be performed on a day-patient basis. However, minor but troublesome post-operative side effects remain common. We have examined the incidence of the most common causes of minor morbidity, namely headache, nausea/vomiting and pain occurring after a wide variety of day-case surgical and diagnostic procedures. Patient satisfaction with treatment and the impact of day case surgery on the workload of the general practitioner was also assessed. The anaesthetic records of the patients involved were reviewed in an attempt to determine if there was any association between the anaesthetic technique and an adverse outcome. A simple postal questionnaire completed on the morning after surgery was returned by 553 patients (response rate over 87%). More than 50% of respondents complained of some morbidity, with 40% complaining of pain, 19% of headache and 9% of nausea and vomiting. One third self-medicated to modify their symptoms, and in most cases (81%) this was effective. However, 6% of patients called their GP for advice and 2% received a home visit. No patient required readmission. A total of 92 patients (17%) would have preferred treatment as an in-patient. Analysis of the anaesthetic drugs and techniques suggested that the commonly used anti-emetics droperidol and metoclopramide had little effect on the incidence of postoperative nausea and vomiting. Intubation was associated with a significantly higher incidence of minor morbidity although this may be related to surgical factors.

Adolescent↗
PubMed1997

The Chronic Pain Grade questionnaire: validation and reliability in postal research.

The Chronic Pain Grade questionnaire has been proposed as an interview-administered, multi-dimensional measure of chronic pain severity in selected populations with chronic pain in the United States of America. It has not previously been tested in the United Kingdom, in self-completion form or in an unselected general population. We undertook a postal survey to assess its reliability, validity and acceptability in these circumstances, using a general practice population in Scotland, with a practice population of 11202 patients. A random sample of 400 patients aged over 18 was drawn, stratified for age, gender and receipt or non-receipt of regular prescriptions for pain-relieving medication. The dimensions and sub-scales of the Chronic Pain Grade were compared with the SF-36 general health questionnaire and questions relating to duration of any pain and attempts to seek treatment for this. The methodological approach proposed by Streiner and Norman (1989) was used to assess validity and reliability. A response rate of 76% was achieved. Cronbach's alpha was > 0.9 and item-total correlations were all high, indicating good internal consistency and reliability. Validity was confirmed by psychometric testing, including confirmatory factor analysis. Good correlations with comparable dimensions of the SF-36 general health questionnaire confirmed convergent validity. Construct validity was confirmed by testing scores against duration of pain and treatment sought for pain. We concluded that the Chronic Pain Grade questionnaire is a useful, reliable and valid measure of severity of chronic pain. It translates well into UK English and is acceptable in general population postal research.

Chronic Disease↗
PubMed1994

Regulatory concerns in the development of topical recombinant ophthalmic and cutaneous wound healing biologics.

The use of recombinant DNA technology has enabled the development of an increasing number of endogenous growth regulatory peptides for potential use as therapeutic biologics. Numerous such recombinant peptides are now licensed, and many are in various stages of pharmaceutical development. Although currently there are a number of "Points to Consider" and related guidance documents available concerning various issues of biotechnology-derived products, the purpose of this article is to focus on the use of these biologics in topical ophthalmic and chronic cutaneous wound healing. Regulatory expectations with respect to product quality, safety, and efficacy that may be particularly germane to these products will be discussed. Providing regulatory guidance on these issues may not only facilitate the introduction of safe and effective new biologic therapies into clinical trials at the investigational level but also provide appropriate information to aid in their eventual approval for licensure and widespread clinical use.

Journal Article↗
PubMed1994

Ketorolac as a component of balanced analgesia after thoracotomy.

Ketorolac 10 mg or 30 mg i.m., 6 hourly or placebo was given to 75 patients who had undergone thoracotomy, in a randomized double-blind study. All subjects were given intercostal nerve blocks with bupivacaine and had access to i.v. patient-controlled morphine. I.m. ketorolac improved the success rate of the analgesic regimen, with fewer patients withdrawing from the study because of inadequate pain relief.

Adult↗
PubMed1994

Teaching airway management on anaesthetised patients.

In order to assess the availability of appropriate resources for a programme of in-theatre teaching of airway skills using anaesthetised patients, two surveys of airway management on anaesthetised patients with identification of those suitable for teaching airway care; and a questionnaire to senior anaesthetists assessing attitudes to such teaching were performed. The results demonstrated that, of all patients undergoing general anaesthesia 45% were intubated and of these 29% were regarded as suitable for teaching intubation. The introduction of the Laryngeal Mask Airway (LMA) into clinical practice has reduced the number of patients having their airways maintained by either bag and mask or tracheal intubation, with implications for learning those skills. In our survey 16% had a Laryngeal Mask Airway (LMA) placed for airway securement and of these 29% would have been intubated had the LMA not been available. Finally, amongst anaesthetists in our survey there is a wide variety of attitudes to teaching airway skills using anaesthetised patients.

Allied Health Personnel↗
PubMed1993

Criteria for in vitro alternatives for the eye irritation test.

A proposal encompassing considerations and criteria for the development of in vitro alternatives to the eye irritation test has been developed and is presented here. Two factors need to be considered initially in developing an alternative test. The first is to determine whether the alternative assay is to be used as a screen or as a replacement for the eye irritation test. Less stringent acceptance criteria are required for an assay used as a screen than for that used as a replacement test. A screen is a preliminary test for the assessment of eye irritation. It is used for making preliminary decisions or establishing the direction for further testing. Screens answer fewer and less complex questions than a replacement test would, since the results from screens are usually confirmed by more definitive testing. A replacement test, however, must provide the same answers as in vivo methods for the assessment of eye irritation and must provide data for making a definitive toxicological assessment of eye irritation. The second factor to be considered is knowledge of the in vivo assay intended to be replaced. This knowledge should include the procedural aspects of the test and the regulatory information it provides. The following may be considered as criteria for in vitro tests used as screens or as replacements for the eye irritation test in rabbits: rationale (there should be a clear statement regarding the rationale for the use of a particular test in relation to the availability of other tests); relevance (the in vitro endpoint should have biological or physiological relevance to the effect to be detected in vivo); and validational (intralaboratory as well as interlaboratory validation must be conducted).

Animal Testing Alternatives↗
PubMed1993

Screening procedures for eye irritation.

Screens aid in identifying some severe irritants or corrosives and eliminating them from consideration for in vivo eye irritation testing. Products may be evaluated for ocular irritation potential in a stepwise progression as follows: (1) products at pH extremes of 2 or below or of 11.5 or above may be considered to be ocular irritants; (2) based on chemical structure-activity considerations, some products may be judged to have ocular irritation potential; (3) validated and accepted in vitro systems may possibly be used as a screen in the future; (4) when a test material demonstrates severe acute dermal toxicity (lethality at < or = 200 mg/kg body weight), further testing for either dermal or ocular irritation may not need to be undertaken; (5) if a substance shows a primary dermal irritation index of 5 or above, it may be considered to be an ocular irritant; (6) materials that are not removed from consideration based on these proposed screens may then be considered for testing for ocular irritation in rabbits under accepted procedures. In a survey given to participants in the workshop, a high percentage believed that screens should be used. However, opinions on the use of the individual screens varied between the different interested groups attending, with the possible future use of in vitro screens for specific product lines having the highest percentage of agreement (57-100%).

Animal Testing Alternatives↗
PubMed1993

Use of ophthalmic topical anaesthetics.

Pretreatment of the eyes of rabbits with a topical anaesthetic can be viewed as a refinement of the test for eye irritation. It reduces pain at the time of test-material administration, decreases animal distress and permits easier application of the test agent to the eye. In some cases, however, use of an anaesthetic either alone or in combination with the test substance may alter ocular responses or provide little benefit. Although anaesthetic pretreatment may result in decreased pain at the time of test-compound administration, it does not affect possible pain after the effects of the anaesthetic have dissipated. Some anaesthetics are themselves irritating to eyes. In addition, anaesthetics reduce blinking and tearing, thereby maintaining the test-material concentration at the surface of the eye longer. Corneal permeability may also be increased with pretreatment use of an anaesthetic, and may bring the test agent into contact with more structures of the eye. Some anaesthetics delay healing after ocular injury. All of these varied effects may result in increased irritation to the eye. Overall, pretreatment with anaesthetics has usually resulted in a tendency for slightly higher irritation scores; eye irritancy classification is usually unaffected.

Anesthetics, Local↗
PubMed1993

The use of low-volume dosing in the eye irritation test.

The Draize rabbit eye test was developed to provide a method for assessing the irritation potential of materials that might come in contact with human eyes. The method involves the instillation of 0.1 ml of a test liquid (100 mg solid) into the conjunctival sac of an animal's eye. A refinement of the Draize test is the low-volume eye test in which 0.01 ml of a substance is placed directly on the cornea of the eye. Studies indicate that the low-volume method provides a better correlation to human eye irritation experience for some substances. The Interagency Regulatory Alternatives Group (IRAG) proposes that the low-volume eye test can be used to substantiate the irritancy of suspect severe ocular irritants that have not been eliminated by various pre-eye test 'screens'. A substance testing positive by the low-volume method can be classified as an irritant; one that tests negative will require further testing by the use of the 0.1-ml volume procedure. For all other definitive testing, the Draize test (0.1 ml) should be used. Results from a questionnaire distributed at the IRAG workshop showed that many workshop participants thought that the low-volume test should be used as an eye irritation screening procedure.

Animal Testing Alternatives↗
PubMed1993

Number of animals for sequential testing.

US regulatory agencies have used six animals in eye irritation tests. Analyses of eye irritation tests on pesticides (n = 48), consumer products and cosmetics (n = 53), Marzulli and Ruggles database (n = 139), and cleaning products and ingredients (n = 30) have greatly extended previous investigations of the merit of reducing animal sample size in the eye test. Given the existing scoring system for positive animal responses (corneal opacity > or = 1, iritis > or = 1, conjunctival redness > or = 2 and conjunctival chemosis > or = 2), the accuracy of the classification systems currently used by these agencies was determined. The US Consumer Product Safety Commission, US Food and Drug Administration, and US Occupational Safety and Health Administration use a classification system by which a substance is designated as an irritant when at least four of six animals give a positive response. This decision rule leads to a very high accuracy of at least 99% with essentially no false positive and false negative judgments. In contrast, the system used by the US Environmental Protection Agency pesticide program, in which only one or more of six treated animals result in an irritant decision, has an accuracy of only 50-80% with very high false positive rates. Analyses indicated that test sample size could be reduced to three and still preserve very good accuracy, whereas two-animal and one-animal tests did not give satisfactory responses. A two-stage test, in which two animals are tested and evaluated in the first stage before the need for testing one more animal in the second stage is determined, also demonstrated good operating characteristics. Both the one-stage/three-animal test and the two-stage test deserve consideration.

Animals↗
PubMed1993

Scoring for eye irritation tests.

Scoring of the rabbit eye test and the resulting evaluation and classification should provide useful information about the likelihood that a test material may cause injury on contact with the human eye. When an animal test is necessary, a rabbit eye test based on the following characteristics is proposed for deriving the maximum information from the fewest animals. The ocular effects of interest should include corneal opacity, iritis and conjunctival redness. Animals should be scored for each ocular effect at 24, 48 and 72 hr after the test substance is administered. If an animal is negative at all three scoring times, it can be removed from the test at 72 hr. If it shows a positive effect at a scoring time but the lesion clears at 72 hr, it can be removed at 72 hr. If it shows a positive effect that does not clear at 72 hr, it should be scored again on day 7 when the test ends. However, if an animal shows severe effects at one or more scoring times, it can be removed from the test at 72 hr. An animal is positive if any one of the following criteria is observed at 24, 48 or 72 hr: corneal opacity of 1 or above, iritis of 1 or above, or conjunctival redness of 2 or above. Severe ocular effects (noted at 24, 48 or 72 hr) that may endanger sight deserve special recognition for the classification of chemicals and include corneal opacity of 3 or above, or iritis of 2. This proposal is consistent with the opinions of the majority of respondents who attended the Workshop on Updating Eye Irritation Test Methods, Proposals for Regulatory Consensus. The most notable exception was the suggestion by respondents to add conjunctival chemosis as one of the scoring parameters.

Animals↗
PubMed1993

An eye irritation test protocol and an evaluation and classification system.

An in vivo test protocol and an evaluation and classification system for the determination of eye irritation potential of chemicals and mixtures (substances) is proposed. The protocol uses two or three rabbits and reduces distress in test animals. The test substances are classified as non-irritant, irritant or severe irritant to meet regulatory needs. They may be classified on the basis of past experience with similar compounds or mixtures. Screens such as structure-activity relationships, pH extremes, validated and accepted in vitro tests, severe dermal irritation (primary dermal irritation index > or = 5) or severe dermal toxicity (lethality at < 200 mg/kg body weight) should be used to classify irritant or severe irritant materials when one or more of the screens can provide convincing evidence. For suspected severe irritant materials, the proposed in vivo test permits the use of one rabbit and instillation of 0.01 ml (0.01 g) of the test material into the cornea. Materials that are not classified irritant or severe irritant by screens or severe irritant by one rabbit test are tested in two or three rabbits; 0.1 ml (0.1 g) is instilled into the conjunctival sac. The responses (corneal opacity, iritis and conjunctival redness) are scored according to the modified Draize scoring system at 24, 48 and 72 hr and 7 days post-instillation. A rabbit is considered positive when corneal opacity of 1 or above, iritis of 1 or above or conjunctival redness of 2 or above is present at 24, 48 or 72 hr post-instillation. The material is classified as a severe irritant when the rabbit in the one-animal test or two or more rabbits in the standard test have responses of corneal opacity of 3 or above and iritis of 2 at 24, 48 or 72 hr, or positive responses on day 7 after instillation. The material is classified as an eye irritant when two or more rabbits are positive but the responses are not severe and they clear 7 days after instillation. The material is classified as a non-irritant when no more than one rabbit is positive. The opinions expressed in this article are those of the authors and do not necessarily reflect the views of US Federal agencies.

Animals↗