The Current Application of Maximal Treadmill Stress Testing

Treadmill stress testing has many applications in the overall evaluation of ischemic heart disease, both as a diagnostic aid and as an aid in serially following patients under study. Its use in the evaluation of procedures designed to improve myocardial function and coronary perfusion is of great value, for it can supply objective evidence without recourse to more difficult procedures such as determination of blood lactate levels. Ancillary procedures which may complement treadmill stress testing may prove to be valuable additions to the study of ischemic heart disease.The reported high rate of false-positive Master two-step tests would tend to make the treadmill exercise test more attractive.     

A method for bulbospinal trigeminal nucleotomy in the treatment of facial deafferentation pain

Many types of facial pain are difficult to treat, such as postherpetic, posttraumatic, or pain following denervation procedures used in the treatment of trigeminal neuralgia (anesthesia dolorosa), all of which involve deafferentation of the spinal trigeminal nucleus.     

Chemoprevention of coronary atherosclerosis: the role of lipid interventions. A position paper of the American Council on Science and Health

Atherosclerosis is not an inexorable part of aging. Addressing unhealthy lifestyle behaviors will go a long way toward reducing the current burden of atherosclerosis without widespread drug therapy. The question is whether this is possible, given the demand of our modern culture. It is not yet clearly established precisely where pharmaceutical lipid lowering or chemoprevention fits in the broader spectrum of prevention and treatment of atherosclerosis and its complications. Anatomic interventions, such as angioplasty or bypass surgery, targeted to obstructing but stable lesions, are likely to be only of limited effectiveness. On the other hand, cholesterol interventions, not only as a long-term means of dealing with atherosclerotic sequelae but as a short-term means of reducing plaque activity and events, are demonstrably effective. Aggressive cholesterol lowering will, moreover, substantially reduce the requirement for angioplasty and bypass procedures. Although more difficult to prove, earlier intervention can almost surely lower the risk of later, potentially lethal, coronary events.     

Advanced techniques in abdominal surgery.

Almost every abdominal organ is now amenable to laparoscopic surgery. Laparoscopic appendicectomy is a routine procedure which also permits identification of other conditions initially confused with an inflamed appendix. However, assessment of appendiceal inflammation is more difficult. Almost all colonic procedures can be performed laparoscopically, at least partly, though resection for colonic cancer is still controversial. For simple patch repair of perforated duodenal ulcers laparoscopy is ideal, and inguinal groin hernia can be repaired satisfactorily with a patch of synthetic mesh. Many upper abdominal procedures, however, still take more time than the open operations. These techniques reduce postoperative pain and the incidence of wound infections and allow a much earlier return to normal activity compared with open surgery. They have also brought new disciplines: surgeons must learn different hand-eye coordination, meticulous haemostasis is needed to maintain picture quality, and delivery of specimens may be problematic. The widespread introduction of laparoscopic techniques has emphasised the need for adequate training (operations that were straight-forward open procedures may require considerable laparoscopic expertise) and has raised questions about trainee surgeons acquiring adequate experience of open procedures.     

Congenital toxoplasmosis: epidemiologic features and control.

Toxoplasmosis is caused by the parasite Toxoplasma gondii. It is acquired from undercooked meat or from food or fomites contaminated by cat feces. The disease can be transmitted to the fetus only during maternal parasitemia, which is associated with primary infection. Extrapolation from current data suggests that there are 140 to 1400 cases of congenital toxoplasmosis per year in Canada and that 70 to 280 of the infants are severely affected at birth; many of the others suffer sequelae later in life. Serologic diagnosis of primary infection in the mother is quite sensitive and specific. Diagnosis in the infant is more difficult and may take several months. Prenatal treatment of the woman and postnatal treatment of the infant are hampered by the lack of proven efficacy as well as ethical and compliance problems. Preventive serologic screening and prophylaxis have the same drawbacks. Educating young women to avoid infection is an inexpensive, low-risk intervention that would be the preferred preventive strategy if it could be shown to be effective. Immunization may prove to be the most cost-effective method of preventing congenital toxoplasmosis if a safe and effective vaccine is developed.     

Opioids and treatment of chronic pain: understanding pain patterns and the role for rapid-onset opioids

Chronic pain is a frequent medical condition that has a significant impact on patients, including their ability to function and enjoy life. In addition, chronic pain has a substantial economic impact on the workplace and costs of healthcare. Although not without controversy, opioids are effective in the treatment of noncancer chronic pain. Understanding the pattern of temporal variations in a patient's pain is important in developing an opioid-based treatment plan. By understanding those times of day and activities that may precipitate severe episodes of pain, tailored opioid treatment plans can be developed that manage pain, improve patient functionality, and minimize side effects. Recently developed rapid-onset opioid formulations should be considered as part of the chronic pain management strategy in addition to more traditional long-acting, sustained-release formulations and short-acting, normal-release formulations.     

A New Tool for Real-Time Pain Assessment in Experimental and Clinical Environments

Pain measurement largely depends on the ability to rate personal subjective pain. Nevertheless, pain scales can be difficult to use during medical procedures. We hypothesized that pain can be expressed intuitively and in real-time by squeezing a pressure sensitive device. We developed such a device called “Painmouse®” and tested it on healthy volunteers and patients in two separate studies: Sixteen male participants rated different painful heat stimuli via Painmouse® and a Visual Analog Scale (VAS). Retest was done one week later. Participants clearly distinguished four distinct pain levels using both methods. Values from the first and second sessions were comparable. Thereafter, we tested the Painmouse® by asking twelve female and male leg- ulcer patients to continuously squeeze it during the whole length of their wound-dressing change. Patients rated each step of dressing change on an 11-point numeric rating scale. Painmouse® ratings were highest for the wound cleaning and debridement step. Application of the new dressing was not evaluated as very painful. On the other hand, numeric scale ratings did not differentiate between dressing change steps. We conclude that the Painmouse® enables pain assessment even under difficult clinical circumstances, such as during a medical treatment in elderly patients.     

Identification of 2,3-diaryl-pyrazolo[1,5-b]pyridazines as potent and selective cyclooxygenase-2 inhibitors

GW406381 (8), currently undergoing clinical evaluation for the treatment of inflammatory pain is a member of a novel series of 2,3-diaryl-pyrazolo[1,5-b]pyridazine based cyclooxygenase-2 (COX-2) inhibitors, which have been shown to be highly potent and selective. Several examples of the series, in addition to possessing favourable pharmacokinetic profiles and analgesic activity in vivo, have also demonstrated relatively high brain penetration in the rat compared with the clinically available compounds, which may ultimately prove beneficial in the treatment of pain.     

Operant control of EEG and event-related and slow brain potentials

Research on operant control of brain potentials is reviewed. From single-unit firing and spontaneous EEG activity to event-related potentials such as sensory and pain evoked potentials, and slow potential shifts, most of the aspects of electrical brain activity have been investigated. Results produced by conditioning of spontaneous EEG oscillations (alpha and theta) dampened the early enthusiasm: e.g., no increase above baseline levels could be achieved and no reliable behavioral effects became manifest. Evidence accumulates, however, that operant conditioning of the sensorimotor rhythm (12–15 Hz) may lead to successful self-regulation and that epileptic patients may profit from the training. First steps in the conditioning of brainstem, as well as pain evoked potentials suggest that self-regulation of EPs can be achieved by adequate biofeedback procedures. If some of the observed behavioral effects prove to be stable, the therapeutic usefulness seems to be within reach. A comparable progress has been achieved for the operant control of slow potentials (DC-shifts across seconds). Biofeedback procedures have been used successfully as a scientific tool to achieve systematic variations on a psychological level and to record psychological covariations. This method may provide insights into the behavioral meaning of electrical brain activity.     

A Bayesian Perspective on Sensory and Cognitive Integration in Pain Perception and Placebo Analgesia

The placebo effect is a component of any response to a treatment (effective or inert), but we still ignore why it exists. We propose that placebo analgesia is a facet of pain perception, others being the modulating effects of emotions, cognition and past experience, and we suggest that a computational understanding of pain may provide a unifying explanation of these phenomena. Here we show how Bayesian decision theory can account for such features and we describe a model of pain that we tested against experimental data. Our model not only agrees with placebo analgesia, but also predicts that learning can affect pain perception in other unexpected ways, which experimental evidence supports. Finally, the model can also reflect the strategies used by pain perception, showing that modulation by disparate factors is intrinsic to the pain process.     

Disinfection procedures for controlling microorganisms in the semen and embryos of humans and farm animals

Semen and embryos generated by assisted reproductive techniques (ARTs) may be contaminated with numerous microorganisms. Contamination may arise from systemic or local reproductive tract infections in donors or the inadvertent introduction of microorganisms during ARTs, and may lead to disease transmission. This review describes sanitary procedures which have been investigated to ascertain whether they are effective in rendering semen and embryos free of pathogenic microorganisms, including internationally adopted washing procedures, which can be supplemented by antibiotics and enzymatic treatments. Other methods include treatment with antibodies or ozone, photoinactivation, acidification, and the use of novel antiviral compounds. In conclusion, despite the wide range of antimicrobial procedures available, none can be recommended as a universal disinfection method for rendering semen and embryos free from all potentially pathogenic microorganisms. However, some procedures are unsuitable, as they can compromise the viability of semen or embryos. In humans, washing by the gradient centrifugation method appears to be effective for reducing the microbial population in semen and is harmless to the spermatozoa. A useful procedure for embryos involving multiple washes in sterile medium has much to commend it for the prevention of disease transmission; furthermore, it is recommended by the International Embryo Transfer Society (IETS).     

Treatment of Kienbock's disease with capitohamate arthrodesis: pain relief with minimal morbidity

Despite the large number of procedures available for treatment of Kienbock's disease, no single method has emerged as being clearly superior. Ultimately, the goal of treatment must be the relief of pain and maintaining wrist range of motion. The authors' experience with 45 consecutive wrists that had undergone capitohamate fusion for treatment of Lichtman's stage 1, 2, or 3 Kienbock's disease is presented. Average follow-up was 32 months (range, 4 to 107 months). All arthrodeses healed with an average time to fusion of 1.9 months. Postoperatively, 93 percent of patients had either no pain or less pain than they had preoperatively, with preservation of wrist range of motion and improved grip strength (52 percent of normal preoperatively to 72 percent of normal postoperatively). The authors conclude that capitohamate arthrodesis relieves pain in 93 percent of patients with stage 1, 2, or 3 Kienbock's disease and is an effective treatment for this disease.     

Use of local anaesthesia for pain management during husbandry procedures in Australian sheep flocks

Mulesing (removal of breech skin for blowfly strike control), castration, tail-docking and ear-knotching are routine husbandry procedures conducted on many millions of lambs annually in Australia, causing considerable pain and suffering. However, establishing an effective alternative to mulesing is proving to be a difficult and prolonged process. This is particularly so for producers of high-quality fine wool from Merino sheep that have been selected over many generations for skin wrinkle to increase yields, increasing their susceptibility to flystrike by Lucilia cuprina. In late 2005, a spray-on product formulation containing two topical analgesia agents (lignocaine and bupivacaine) for pain relief at mulesing has become commercially available. Increasingly, fine-wool growers have been choosing to continue surgical mulesing, but adopting pain alleviation at surgical mulesing to reduce suffering. This product has led to the development of the “Better Choices” program, in an effort to meet international concerns that mulesing without pain relief was cruel. Studies have been conducted on the use of these products for decrease of pain induced by surgical mulesing, castration and tail-docking. A technique has been developed to measure pain through assessment of wound sensitivity using Von-Frey Hair stimulation, measuring local involuntary reflexes and central cognition. These responses were graded using a numerical rating scale. Behavioural responses to pain were analysed by video. A novel technique was developed to assess the rate of wound healing by digital photography and computerized surface area measurement. Also, a method of application was developed at castration, which enabled analgesia of the remaining scrotal contents, with impressive results compared to other methods of castration such as the use of rubber rings. Findings from a series of field and pen trials indicate that the immediate application of spray-on topical anaesthesia to mulesing, castration and tail-docking wounds, significantly reduced the pain experienced post-procedure and improved the rate of wound healing. Increasing adoption by producers of pain relief for lambs during surgical routine husbandry procedures offers a new welfare-conscious paradigm for the Australian wool industry. This development has potential application to several species undergoing many livestock procedures throughout the world and offers a simple part solution to address the increasingly important and emerging global issue of welfare conscious agriculture.     

Treatment of hepatic hydatid cysts by percutaneous aspiration and hypertonic saline injection: results of a cooperative work

Percutaneous puncture-aspiration-injection-reaspiration (PAIR) of hydatid liver cysts, was performed in 38 patients 14-80 years old, with a total of 60 liver hydatid cysts. After aspiration under computed tomography guidance, hypertonic saline was injected into the cystic cavities of patients as a scolecidal agent. No major complications were associated with the procedures. In the follow-up period of 18 months, control CT scans of 35 cysts revealed a gradual decrease in cyst size with a mean volume reduction of 66%. Complications included two cases of urticaria, one case of anaphylaxis and one subcapsular hematoma. No mortality occurred. It is concluded that percutaneous aspiration and hypertonic saline injection for liver hydatid cysts appears to be an effective form of treatment and may eventually prove to be an alternative to surgical intervention.     

Comparison of cimetidine 800 mg once daily and 400 mg twice daily in acute duodenal ulceration.

A double blind trial was conducted in seven centres to evaluate the safety and efficacy of cimetidine 800 mg given at night compared with 400 mg given at breakfast and at bedtime. Altogether 197 patients with active duodenal ulcer confirmed by endoscopy entered the study, of whom 187 were eligible for analysis. After four weeks'' treatment the ulcer was healed in 76 of 91 patients (84%) receiving the once daily regimen and in 65 of the 96 patients (68%) receiving the twice daily regimen (p less than 0.05). Both dosage regimens were equally effective in reducing ulcer pain and consumption of antacids. Pain relief was considerable within the first two weeks, and most of the patients were free of symptoms by the end of treatment. No patients were withdrawn because of adverse events as these were few and mild, consistent with the proved safety profile of cimetidine. Cimetidine 800 mg given at night is as effective as 400 mg twice daily; the single dose regimen may improve patient compliance, thus facilitating treatment.     

Lessons learnt from the painful shoulder; a case series of malignant shoulder girdle tumours misdiagnosed as frozen shoulder

Adhesive capsulitis or frozen shoulder is a common condition characterized by shoulder pain and stiffness. In patients in whom conservative measures have failed, more invasive interventions such as arthrographic or arthroscopic distension can be very effective in relieving symptoms and improving range of movement. However, absolute contraindications to these procedures include the presence of neoplasia around the shoulder girdle. We present five cases referred to our institution where the diagnosis of shoulder joint malignancy was delayed, following prolonged, ineffective treatment for frozen shoulder. These cases highlight the importance of careful review of the radiology and the need for reconsideration of the diagnosis in refractory "frozen shoulder".     

Does experimental pain response vary across the menstrual cycle? A methodological review

The findings on sex differences in human experimental pain research are inconsistent. One possible factor contributing to the inconsistent findings is the female hormonal cycle, as hormone levels may affect pain sensitivity. A number of studies suggest that women's responses to experimentally evoked pain vary across the menstrual cycle. However, at least an equal number of studies suggest a lack of variability. The purpose of this article is to review the literature with emphasis on what we believe could be the reasons for the inconsistent findings, namely, differences in populations sampled, timing of experimental sessions across the menstrual cycle, and nomenclature used to identify the time (phases) in the cycle when measurements were done, nature of the pain stimuli chosen, and outcomes measured. These inconsistencies and other methodological problems associated with most experimental pain studies make it difficult to draw inferences from this literature. For the science to improve, replication of significant findings using standardized timing of sessions, pain stimulus procedures, outcomes, and hormonal assessment is necessary.     

Dietary polyphenols and mechanisms of osteoarthritis

Osteoarthritis is a condition caused in part by injury, loss of cartilage structure and function, and an imbalance in inflammatory and anti-inflammatory pathways. It primarily affects the articular cartilage and subchondral bone of synovial joints and results in joint failure, leading to pain upon weight bearing including walking and standing. There is no cure for osteoarthritis, as it is very difficult to restore the cartilage once it is destroyed. The goals of treatment are to relieve pain, maintain or improve joint mobility, increase the strength of the joints and minimize the disabling effects of the disease. Recent studies have shown an association between dietary polyphenols and the prevention of osteoarthritis-related musculoskeletal inflammation. This review discusses the effects of commonly consumed polyphenols, including curcumin, epigallocatechin gallate and green tea extract, resveratrol, nobiletin and citrus fruits, pomegranate, as well as genistein and soy protein, on osteoarthritis with an emphasis on molecular antiosteoarthritic mechanisms.     

Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord

Bone cancer pain is common among cancer patients and can have a devastating effect on their quality of life. A chief problem in designing new therapies for bone cancer pain is that it is unclear what mechanisms drive this distinct pain condition. Here we show that osteoprotegerin, a secreted 'decoy' receptor that inhibits osteoclast activity, also blocks behaviors indicative of pain in mice with bone cancer. A substantial part of the actions of osteoprotegerin seems to result from inhibition of tumor-induced bone destruction that in turn inhibits the neurochemical changes in the spinal cord that are thought to be involved in the generation and maintenance of cancer pain. These results demonstrate that excessive tumor-induced bone destruction is involved in the generation of bone cancer pain and that osteoprotegerin may provide an effective treatment for this common human condition.     

Ethical use of covert videoing techniques in detecting Munchausen syndrome by proxy.

Munchausen syndrome by proxy is an especially malignant form of child abuse in which the carer (usually the mother) fabricates or exacerbates illness in the child to obtain medical attention. It can result in serious illness and even death of the child and it is difficult to detect. Some investigators have used video to monitor the carer''s interaction with the child without obtaining consent--covert videoing. The technique presents several ethical problems, including exposure of the child to further abuse and a breach of trust between carer, child, and the professionals. Although covert videoing can be justified in restricted circumstances, new abuse procedures under the Children Act now seem to make its use unethical in most cases. Sufficient evidence should mostly be obtained from separation of the child and carer or videoing with consent to enable action to be taken to protect the child under an assessment order. If the new statutory instruments prove ineffective in Munchausen syndrome by proxy covert videoing may need to be re-evaluated.