Mark Corson

Improvement in fibro- the application of treatment to the various orifices of nectin synthesis with both local and hepatic treatment the body quality alfuzosin 10 mg. It will be seen that the majority of the appli- has shown a positive influence in postsurgical healing cations involve infectious processes and those that do times (Arghiropol et al 1992) generic 10mg alfuzosin otc. Beneficial application Chapter 12 • Electrotherapy Modalities 549 Interestingly purchase 10 mg alfuzosin free shipping, pulsed diathermy applied to metastasiz- ing melanoma cell cultures demonstrated increased cell death for a period of 4 minutes after exposure (Hakkinen et al 1975). It is one of the oldest physiotherapy devices and has been in use since the end of the 19th century. High frequency is essentially a modified Tesla coil that produces a high frequency, high voltage current at low amperage. The rapidly oscillating currents are applied to the body through vacuum glass electrodes. As the current for non-union fracture healing is substantiated by the moves through the electrode, the partially vacuumed observed positive influence on osteoblast differentia- atmosphere inside the glass ionizes and assumes color tion (Lohmann et al 2000) and a positive influence on dependent upon the degree of vacuum. This result is substantiated common color is violet and the units are commonly by research on liver enzymes that shows a beneficial referred to as ‘violet ray’ devices. Mechanism of action and physiological effects Naturopathic indications and When the electrode is applied to the body it induces applications: validation of efficacy = 2 a local current in tissues and creates a local heating The late naturopathic physician Dr Poesnecker effect as the tissues resist the current flow. The described clinical application of pulsed short wave increased resistance promotes increased tissue per- therapy using an indirect approach to enhance organ fusion locally. His treatment was body by thin gauze, electrical sparks will shower directed to hepatic, splenic, renal and adrenal tissue, the skin with a resulting counterirritation effect. If with the goal of enhancing organ metabolism and the electrode current is concentrated into a point it detoxification. He applied this indirect approach in can be used for fulguration and is the current used chronic disorders such as chronic fatigue syndrome in hyfrecation. The effects on tissue have been the higher pulse rates, which have less thermal dis- described as a ‘cellular massage’ (Hewlett-Parsons persion due to the increased frequency, for acute 1968). It: et al 2005 Trock et al 1994) and chronic tinnitus, and inconsistent results are found with ankle sprains. Ben- • increases oxidation and local nutrition eficial observation in neural tissue repair has been (Matijaca 1919b) reported consistently in animal models (Raji 1984, Raji • produces hyperemia and stimulates circulation et al 1983, Sisken et al 1989). A study on Guillain–Barré in areas to which it is applied (this hyperemia syndrome demonstrated enhanced neurological tissue is believed to last from 10 to 24 hours) healing with pulsed short wave (Gorbunov et al 1995). Subsequently we will not rely on his- • increases the temperature where applied torical manufacturers’ recommendations and restrict • is topically germicidal, encourages leukocytosis ourselves to independent sources. The effect of the current is considered lubricants as the sparks may potentially cause igni- soothing and able to reduce inflammation (Boyle 1988, tion. Naturotherapy 1937c, Scott 1990), trachoma (Post- Graduate Study of Naturotherapy 1939b), arthritis Indications: validation of efficacy = 2 (Post-Graduate Study of Naturotherapy 1939c), mus- cular spasm, torticollis, low back pain, rheumatoid Contemporary conventional application of high- arthritis (Post-Graduate Study of Naturotherapy frequency current is primarily limited to dermatalogi- 1939b), peritonitis, pelvic adhesions, ovarian neural- cal diseases such as acne and atopic dermatitis, for gia, tic douloureux, neuritis, neuralgia, migraine, which it is considered safe and effective. Extensive therapeutic applica- apy 1938d), menstrual cramping, muscle tears, local- tions were recommended historically by manufactur- ized pain, fibroids, ovarian cysts (Blake 2006), ers of the units until prosecution in the 1950s in the bronchitis and nephritis (Scott 1990). The current is delivered using adhesive electrode pads or graphite- conducting fabric. An ampere is the rate of movement of electrons past a point in space and one millionth of an ampere is a microamp (μA). The body itself gener- ates microamperage current in every cell and mem- brane as part of its normal physiological activity. This current flow creates the polarity observed by Becker in the human system in which the body is polarized Figure 12. Photograph courtesy of more positively at the head, negatively at the feet, Silhouet-Tone more positive centrally and more negative distally Chapter 12 • Electrotherapy Modalities 551 of unmodulated direct current or non-specific fre- quency choices. The frequencies were resurrected from lists of frequencies used with wall current elec- trotherapy modalities used from 1914 to 1937. While published clinical outcomes and some preliminary animal research have been performed in order to sep- arate the effects of the microcurrent alone from any additional frequency-specific effect, further research is necessary. The research needed to separate the effects of the current alone from the additional effects of the frequency response is an area of interest but published clinical outcomes and some preliminary animal research are promising. Validation of efficacy = 4 Microcurrent has documented effects in increasing wound, tissue and fracture healing, decreasing pain Figure 12. Photograph courtesy of International and edema and treating myofascial trigger points and Medical Electronics neuropathic pain. Most microcurrent devices • Thirty hospital patients with non-healing ulcers are battery operated but some are plugged into a wall were divided into two groups, one treated with current source and current levels are stepped down to conventional wound dressings and one with microamperage. The Microcurrent creates its effects by delivering current latter group was given two 2-hour stimulation within a normal physiological range, making it par- periods per day. After 6 weeks of such ticularly consistent with naturopathic principles and treatments, the group treated with appropriate to a naturopathic practice. Most electrotherapy of wounds, using negative polarity over the devices deliver current in the milliamp range, or thou- lesions in the initial phase, and then alternating sandths of amps, to create their therapeutic effect. Both • cannot run current through a pregnant uterus microcurrent and laser were found to be significantly more effective than placebo, with • cannot run current through the brain laser slightly more effective than microcurrent. Microamperage current has been used clinically in • Frequency-specific microcurrent has been ‘off label’ uses in all of these situations except during shown to be effective in the treatment of pregnancy. In clinical usage, microcurrent is safe to myofascial trigger points and pain in the head, use with plates, pins, artificial joints and implants, neck and face, and low back (McMakin 1998, and in new injuries, chronic pain and swelling.

Requisition of study medication/device (includ- ing placebo and comparator products buy alfuzosin 10mg free shipping, if relevant) must be initiated at an early stage to allow suffi- Control of Study Medications/Devices at cient time to procure the study medications/devices Study Sites and to prepare the final labeling and packaging purchase 10mg alfuzosin otc, taking into account any special circumstances for Evidence of careful control at the study site is blind studies and for import requirements cheap alfuzosin 10mg on line. Systems to ensure and assess compliance to also allow assessment of possible detrimental with the required use of the product being studied environmental impact. The main concern for ap- place until the final report has been prepared and propriate environmental conditions is usually tem- until there is no further reason to question the perature requirements, but other factors (e. At each study visit, the that study subjects entered into a comparative study subjects should be asked to return all unused study are treated in an unbiased way. A reconciliation of the initial inventory to ensure subject safety and arose because of biases and the final returns must be undertaken and all inherent in clinical research (e. Code of Ethical Conduct for Research Involving Humans, Research Involving Patients, Royal College of Physicians of Medical Research Council of Canada, Natural Sciences and London, 1990. Engineering Research Council of Canada, Social Sciences Research on Healthy Volunteers, Royal College of Physicians of and Humanities Research Council of Canada, 1998. Pharmaceutical Products, Division of Drug Management & Bohaychuk W, Ball G, Lawrence G, SotirovK (1998) A Quan- Policies, World Health Organization, 1994. International Similarities and Differ- Assembly, Hong Kong, September 1989, the 48th General ences, In The Clinical Audit in Pharmaceutical Development, Assembly, Somerset West, Republic of South Africa, October edited by M Hamrell. As recently as 1997, a assurance, from those who seek to market drugs, physician investigator in California pled guilty to biologics, medical diagnostics or medical devices in fraud after substituting his own blood for some their countries, that these products are safe and clinical study tests. Companies gia was convicted of fraudulently diverting ap- engaged in the research, development, licensing, proximately $10 million in grants for clinical and marketing of pharmaceuticals must comply studies, and was cited for failing to participate in with regulations governing the manufacturing and the care of study subjects enrolled at his location testing of their products. It regulation of biological products (serum, vaccines also required research to be supervised by compe- and blood products) began in 1944 with the Public tent medical persons. The Fair time, protected them from remote possibilities of Packaging and Labeling Act was passed in the injury, disability, or death, and stipulated that the same year and required true and informative label- results of research studies must be intended for the ing for all consumer products involved in interstate good of society. Group Consideration of Clinical Research Proced- In 1971, in a move to affirm the Declaration of ures Deviating from Accepted Medical Practice or Helsinki, and further guarantee the protection of Involving Unusual Hazard. Congress passed the National Research Act in Following reports of birth defects associated with 1974 and created the National Commission for the the use of thalidomide in Australia and Western Protection of Human Subjects of Biomedical and Europe, public support for tougher drug regulation Behavioral Research. This legislation required drug Congress the enactment of federal regulations manufacturers, for the first time, to prove that governing ethical review of all human research by their products were effective prior to marketing, institutional review boards, including accreditation and required the affirmative act of approval by and education. Established in a way that will permit the inspection and procedures include staffing and training, quality reporting of processes and procedures without the control, facilities and maintenance, selection, possibility of coercion or pressure from the person- calibration and maintenance of equipment, pro- nel and departments that it monitors. The basic elements required to accomplish this needed to support the testing and inspection of include written quality standards, systems to in- raw materials, components and final product, as spect, control, validate, and maintain quality, well as systems to identify each of these during the systems to manage changes in quality, and records production process. Compliance to regulations throughout documentation or personnel) require investigation each phase of the research and development and appropriate corrective action, and must be process can only be assessed by routine monitoring carefully documented. This information must ation are the first steps in a quality program, and be gathered and reported to regulatory agencies quality control (testing and inspection) is the con- before the first dose of the product can be adminis- tinuing verification that validated systems remain tered for research in human subjects. Planned change and revalidation assure imperative that quality control procedures are continuing quality improvement within the regu- functioning at the beginning of the development lated environment. Animals must be adequately fed and housed vide and evaluate continuous training, and assess to ensure that they are free of diseases that might and document job performance. The number of variables increases at a time Orientation of the investigator and clinical staff when the responsibility for the quality of the to the study design and test procedures and the operation must be shared with others at remote investigational product characteristics is impera- locations. Clinical investigators must be carefully tive, to ensure that everyone has a thorough under- selected after an indication for a product has been standing of the research goals. In advance of the meeting the investigator qualified by training and experience to undertake should be provided an opportunity to review a the research. The meeting agenda should include administer treatments, conduct study-related tests, a thorough review of the protocol, case report dispense the investigational product, and record forms for data collection, investigational product the data. There should be secure, locked storage packaging and dispensing, the timing of clinical space available, away from patient traffic areas, for laboratory tests and other tests required by the the investigational product. These subjects receive documents have been filed and the study materials little in the way of benefit, except monetary com- have been delivered to the site. When a reasonably safe and reasonably it possible to verify their receipt and perform a effective dose or dose range has been identified, the complete inventory. Monitors Regulations currently stipulate that an active should be appropriately trained, and should have clinical study should be monitored at a minimum the scientific and clinical knowledge needed to of once each year, but in practical terms the rate of monitor a study adequately. It is author- consent for subjects enrolled since the previous ized to conduct the initial review of research studies monitoring visit, and an inventory of the investiga- and approve, require modification of, or disap- tional product. Adequate source documentation is informed consent, and any advertising or other in- imperative, so that clinical data can be independ- formation that will be used to direct subjects to the ently verified, and should include evidence that a clinical study. These individuals and records kept at the pharmacy, at the laborator- should be sufficiently qualified through training ies and at medico-technical departments involved and experience to consider the research in light of in the clinical study). After reviewing all of these the community and institution that they represent, items, the monitor should be able to confirm that and be knowledgeable of applicable laws, regula- the protocol is being followed, that the data are tions and standards for professional conduct and true and accurate, that there is adequate supervi- practice. Deficiencies should be addressed at the time and none of the exclusion criteria, and that they of the visit and the findings must be documented in are treated according to the study plan. The monitor must ensure that the after all subjects have completed the trial, all data study plan is followed, that all data are true and have been verified on site, and all investigational accurate, and that all regulatory requirements are products have been inventoried and reconciled. These changes must ment and regulatory agencies throughout the also be reported to their respective institutional world must perform official inspections of clinical review boards. Failure to how the monitor communicated with the investi- voluntarily correct a problem can lead to legal gator and evaluated the progress of the study. The manufacturing, control, and labeling of the complete description of available alternative pro- investigational product are substandard with cedures. A satisfactory alternative therapy becomes the documents related to a particular clinical study, available or evidence strongly suggests that including electronic databases. Complete compli- An audit of manufacturing and control processes ance was observed for only about 13% of these will include a thorough review of all of the docu- inspections and 1% uncovered violations that mentation required to demonstrate that a product were serious enough to warrant regulatory or ad- meets the requirements for its intended use, includ- ministrative sanctions, which included suspension ing requirements for marketing and consumer use, of clinical studies. The most frequently encoun- technical design and performance, regulatory and tered deficiencies have been inadequate meeting quality assurance, and product safety.

It was during his postgraduate training at Manchester University that Dr Freed first met Dr Pearson cheap 10 mg alfuzosin. In the mid-eighties purchase 10mg alfuzosin with mastercard, Dr Freed was working with an allergy therapist and dietician purchase alfuzosin 10mg line, Anna Foster. From the early eighties onwards, these northern practitioners were to become the subjects of a propaganda assault organised by Caroline Richmond and her two close friends. While at Manchester University, Pearson carried out an investigation into people who said 2 they suffered from food allergy; he later published the study. Pearson and his psychiatrically trained colleagues took a small group of individuals who either maintained that they suffered from allergy, or had been diagnosed as so suffering. Only 5 out of the 35 patients produced reproducible symptoms in a double blind test. The researchers concluded that the remaining 30 patients were suffering from psychiatric complaints. This single piece of research by Pearson was to form the basis for the next decade of campaigning against doctors working in the field of allergy. Even in those early days of the campaign against clinical ecology, the vested interests supporting orthodox allergy work were beginning to show. In November 1986, a large two-day conference of classical allergists and immunologists 4 was held in London. The conference was sponsored by a leading nutrition company, Wyeth Nutrition, and held at Regents College. About twelve doctors attended a critical seminar prior to the conference at the Royal College of Physicians, at which each paper and potential chapter was discussed. In the mid-eighties, Richmond was already developing the tactics and gathering the intelligence, which were to form the basis of her work for the Campaign Against Health Fraud. A year after the Swiss Cottage conference, in Autumn 1987, while working at the North West Allergy Clinic, David Freed received a phone call from Caroline Richmond. She introduced herself as a journalist and asked for his comments on an article which she had written about the clinic. Although there was nothing factually wrong with the article, the slant of it was antagonistic to environmental 5 medicine. In the article, Richmond accused Anna Foster of making a false diagnosis of the patient. Dr Freed, who had been present during the consultation, knew that no mistake had been made. Freed was so concerned about the style and the content of the article that he immediately rang the Medical Protection Society, who in turn put pressure on Richmond to withdraw her story. At the time, Freed recalls, there were a number of heated exchanges between himself, Foster and Richmond over the phone. By the end of 1987, Dr Freed had a very clear idea that he was considered by Caroline Richmond and her small group of campaigners to be in the enemy camp. When it became apparent that Anna Foster was not going to take part in an interview, Richmond used tactics which were to become common in later campaigns. The continual calls, as late as midnight, became so annoying that Foster was forced to refer the matter to the Press Council. The Beginning of the Campaign Against Health Fraud The major players in the British health-fraud movement, Caroline Richmond, Dr David Pearson, Dr Vincent Marks, Professor Michael Baum and Dr Nick Beard, had been coming together since 1985. They were all heavily involved in the defence of scientific medicine and most of them had a connection, however tenuous, with the Wellcome Foundation!. Each founder member also had contacts who would be drawn into the campaign and help in reporting information and publicising cases. Campbell was later to claim on a number of occasions that he had never been a member. There are, however, a number of references from the early days of the organisation which show clearly that he was involved, f f t As well as working in the Wellcome Institute, and receiving a Wellcome bursary, Richmond acquired 250 Wellcome shares in December 1986. Around the time that the Campaign was launched, Campbell had meetings with Caroline Richmond and Nick Beard. At around the same time that it became public that the Campaign was funded by the Wellcome Foundation, Campbell began to distance himself from the organising core of the Campaign, and later claimed that he had never been a member. For the purposes of this book, Duncan Campbell has been considered as an associate member of the Campaign Against Health Fraud. He used information supplied to the Campaign and was happy to use its founder members as a rich source of quotes for his articles, without questioning their vested interests. This is a clear indication that the British Campaign had links with the American Council. Following the meeting, Caroline Richmond sent round a circular to the press and interested parties. She told a number of people that she had almost lost her job as a consequence of using the Wellcome address at the bottom of the leaflet. In an attempt to correct the blunder she later replaced the Wellcome address with a box number and her home telephone number. Between the first meeting and the official launch of the Campaign in May 1989, the steering 11 committee met at the Ciba Foundation, the academic front for the drug company Ciba Geigy. Professor Sir Hermann Bondi was influential within the British Humanist Association, and Sir Alastair Pilkington was at that time one of the principal directors of the Wellcome Foundation.

Among the commonly used single photon emitting 201 99m perfusion tracers are Tl and the various Tc labelled perfusion tracers (e order 10 mg alfuzosin. While having different physical and pharmaco- kinetic properties buy cheap alfuzosin 10mg, these tracers have considerably overlapping clinical uses and will therefore be considered in parallel in this section purchase alfuzosin 10mg visa. Clinical indications The clinical indications for myocardial perfusion tomography are summarized in Table 5. The presence of extensive ischaemia or myocardium at risk indicates the need for more invasive work-up, such as coronary angiography. Conversely, the absence of significant ischaemia or myocardium at risk generally rules out the need for intervention. Myocardial perfusion imaging can be performed in various settings: in patients with suspected coronary artery disease, after myocardial infarction or for the assessment of therapy. Myocardial perfusion imaging can also be used to evaluate the patho- logical significance of coronary lesions already detected by angiography. Angiographic coronary artery disease with a normal stress myocardial perfusion scan has little prognostic significance according to accumulated data. This helps clinicians to determine which patients to manage aggressively with invasive procedures and which ones to manage conservatively. As with detecting myocardium at risk, stratification using mycardial perfusion imaging can be done in various settings: in patients with suspected coronary artery disease, after myocardial infarction as well as before non- cardiac surgery (to determine the risk of perioperative cardiac events). The term ‘viable myocardium’, in its broadest sense, denotes any myocardium that is not infarcted. For the cardiologist, however, the search for myocardial viability is primarily a quest for myocardial hibernation. Myocardial hibernation is classically defined as chronic hypoperfusion and dysfunction that reverses after revascularization. It can be distinguished from myocardial stunning, which denotes acute but transient hypoperfusion and dysfunction, typically after a myocardial infarction in adjacent tissue that does not require intervention because it recovers spontaneously. It is now accepted, however, that the line separating hibernation from stunning is not as clear as was once thought. Various modifications to basic myocardial perfusion imaging protocols have been devised in order to distinguish hibernating, viable myocardium from non-viable, infarcted myocardium. These include late redistribution, re- injection imaging (both protocols using 201Tl) and nitrate augmented rest 201 99m imaging (using either Tl or Tc labelled agents). This may then be evaluated qualitatively by viewing the images in an endless loop cine-display, or quantitatively using commercially available software. The presence of global dilatation, thinned out walls, ventricular aneurysms and increased lung uptake are all suggestive of left ventricular failure. Radiopharmaceuticals A number of single photon emitting radiopharmaceuticals may be used for imaging myocardial perfusion. The three most commonly used at present are 201Tl and the 99mTc labelled tracers sestamibi and tetrofosmin. Thallium-201 also has gamma rays of 135 and 167 keV, which contribute little to the total image counts. The extraction fraction is linearly proportional to blood flow over a wide range of physiological flow levels, plateauing only at very high flow rates and logarithmically decreasing towards the very low flow range. Relative accumulation in the myocardium thus reflects relative regional perfusion. This radiotracer is characterized by redistribution in the myocardium, settling in equilibrium between the myocardial and blood pool concentrations. This makes 201Tl a marker of myocardial viability, which is perhaps its greatest advantage. Disadvantages Relatively long High hepatobiliary — half-life limits activity needs delay allowable dose. Protocols employing 99mTc-sestamibi involve post-injection waiting times of 45–90 min, to allow for adequate clearance of subdiaphragmatic activity. Technetium-99m-sestamibi is characterized by a minimal yet discernible amount of redistribution, which may sometimes be used as a marker of recoverable myocardium. Its main advantages are ease of preparation and faster hepatic clearance, allowing shorter post-injection waiting times of 20–30 min. Equipment (a) Cameras A single-crystal gamma camera is the basic piece of equipment required for myocardial perfusion imaging using both 201Tl and 99mTc agents. Planar imaging is not considered optimal for myocardial perfusion due to its lower sensitivity. Acquiring images in a single, symmetric energy window is adequate, although an asymmetric window as well as multiple window capability allow minimization and correction of scattered radiation. Many current gamma cameras provide an option for non-uniform attenuation correction using an attenuation map acquired with a transmission source. It is probable that transmission attenuation correction will become the standard technique in the future. With caution and experience, however, most attenuation artefacts can be identified even without special techniques or manoeuvres. For accuracy, there is still no substitute for a trained and experienced human operator. Nonetheless, automated drawings always require human verification, especially in cases of ventricles with extensive and severe perfusion defects. An effective quality control program should be strictly observed for myocardial perfusion imaging.