bluuebunny/crossref_metadata_2025 huggingface dataset:
The Investigation Of Soft Tissue Disorders: Nuclear Medicine
Authors: Dutton Jane , Fogelman Ignac
Published: November 2023

The use of nuclear medicine in the investigation of soft tissue rheumatological disorders embraces a wide variety of nuclear medicine methods including specialized techniques such as labelling white cells for imaging, single photon emission computerized tomography (SPECT), and, most recently, positron emission tomography (PET) with 18F-fluorodeoxyglucose. By far the most common scan, however, is the standard planar bone scan with 99mTc-methylene diphosphonate. This chapter attempts to give an overview of the principles of the methods employed, their indications, and examples of the abnormalities demonstrated or diagnosed by these techniques.
Soft Tissue Disorders in Chronic Disability
Authors: Kirker Stephen
Published: November 2023

Following the success of disease-modifying drugs and joint replacement surgery for rheumatic diseases, most severe chronic disability is now due to neurological disorders, in particular, stroke and multiple sclerosis. Spinal cord and traumatic brain injuries, cerebral palsy, muscular dystrophies, motor neuron disease, poliomyelitis, and chronic peripheral neuropathies are less common causes. Soft tissue pain in these conditions is associated with muscle weakness, poor support of joints, altered muscle tone, and abnormal posture.
The Management Of Pain in Soft Tissue Disorders: Pharmacological Agents
Authors: Abrahams Mark , Munglani Rajesh
Published: November 2023

The perception of pain is a physiological protective mechanism designed to act as a warning that tissue damage, has occurred, to encourage prevention of further damage and to allow the healing process to be completed. The persistent pain associated with soft tissue disorders, however, may serve no useful biological purpose. Frequently, the patient will experience pain when there is no evidence of injured tissue. Alternatively, significant irreversible tissue damage may be present but unresponsive to normal tissue healing processes. Pain sensation in these situations is, therefore, redundant. Unlike acute pain, which can serve as an indicator of disease severity or progression, the intensity of persistent pain often bears no relationship to the underlying disease process.
Acupuncture and Trigger Point Needling
Authors: Cummings Mike
Published: November 2023

Fossil evidence of trepanning indicates that man has used physical therapies in the treatment of disease since Neolithic times (circa 10,000 to 3500 BC). Whilst the Chinese are reputed to have evidence of the use of acupuncture from bone etchings dating back to 1600 BC, the recent discovery of Ötzi, the Tyrolean iceman, dates the use of a therapeutic needling technique in Europe to 3200 BC.(1) It is clear that acupuncturelike therapies have developed independently in different civilizations around the world, and this is probably due to late evolutionary features in the mammalian nervous system, combined with intelligence, and the consequent use of tools, in humans.
The Role of The Occupational Therapist And Ergonomy
Authors: Hammond Alison , Batteson Rachel
Published: November 2023

Of all soft tissue complaints, occupational therapists treat soft tissue disorders of the upper limb most frequently, and in particular those considered to be work-related upper limb disorders (WRULDS). This is therefore the main focus of this chapter. There is considerable debate about the aetiology of upper limb pain and whether this is related to frequent repetitive movements of the upper limb (which can occur occupationally as well as in other daily activities) or, at the other extreme, is a localized form of a fibromyalgia-type syndrome of multiple aetiology. A recent population-based study of working individuals with forearm pain identified a multifactorial aetiology for forearm pain (Table 1).(1)
The Management of Soft Tissue Disorders: The Role Of The Podiatrist
Authors: Prior Trevor
Published: November 2023

Whilst the role of the podiatrist in the management of skin lesions has been established for many years, this role in the management of soft tissue and skeletal abnormalities has only recently been appreciated. This chapter attempts to outline the role of the podiatrist and the treatment methods/modalities available. It is not intended to describe the conditions that are covered elsewhere in this book but the management of these conditions will be outlined.
The Lower Leg
Authors: Speed Cathy , Holloway Graham
Published: November 2023

The bones of the leg, the tibia and fibula, articulate proximally at the proximal tibiofibular joint, which communicates with the knee joint. The joint is stabilized by surrounding ligaments, capsule, and the popliteal tendon and glides when the ankle comes into dorsiflexion. It dissipates tibial bending moments and torsional loads applied to the ankle and allows distal motion of the fibula with weight-bearing. The tibia and fibula are united in the midleg by the interosseous membrane and distally by the tibiofibular syndesmosis, a continuation of the interosseous membrane in combination with four ligaments at the distal aspect of the leg. The tibial tuberosity receives the patellar tendon.
Personality and cognitive abilities
Authors: Plomin Robert , Happé Francesca , Caspi Avshalom
Published: November 2023

This chapter reviews genetic research on personality and cognitive abilities, the two major domains of behavioural genetic research on normal variation in human behaviour. Rather than considering the two domains separately, they are reviewed together because the contrasts between them are interesting in relation to quantitative and molecular genetic research. Why include a chapter on normal personality and cognitive abilities in a book on psychiatric genetics? One reason is that it seems likely that some psychopathology such as personality disorders or depression might represent the quantitative extreme of the normal range of genetic and environmental variation in personality (Cloninger 2002; Nigg and Goldsmith 1998).
Reading and language disorders
Authors: Williams Julie
Published: November 2023

A variety of disorders reflect abnormalities in the processing of language. Genetic research has concentrated predominantly on specific language impairment (SLI) and specific reading disability (SRD). Current quantitative and molecular research in these areas is producing many interesting findings that show strong evidence for the presence of a number of genes contributing to these disorders. Identifying genes will help us understand how the disorders develop and may also provide a novel insight into the biology of language processing, a crucial component of human cognition.
Molecular mechanisms of subcortical versus cortical infarction
Authors: Waxman S G
Published: November 2023

Based on differences in their cellular organization, it might be expected that different molecular mechanisms would trigger secondary cell death in white matter of the central nervous system (CNS) as opposed to grey matter. Axons and associated myelin sheaths, oligodendrocytes, and astrocytes constitute the major cellular constituents of white matter tracts. Synaptic transmission does not occur in white matter, and pre- and postsynaptic specializations are not present. Grey matter, on the other hand, is where synaptic transmission occurs; neuronal cell bodies and dendrites are present in the grey matter, and are impinged upon by synaptic terminals so that there is a high density of pre- and postsynaptic specializations. These synaptic specializations provide a substrate for excitotoxic cell injury within grey matter.
Hyperacute diagnosis of subcortical infarction
Authors: Toni D
Published: November 2023

The differential diagnosis between stroke subtypes has many implications in terms of prognostic estimates, therapeutic approaches aimed at preventing stroke recurrence (Toni and Falcou 1999), and emergent treatment aimed at saving brain tissue. This last point, in particular, becomes of utmost importance following the demonstration of the efficacy of thrombolytic revascularization (Hacke et al.1995, 1998, NlNDS 1995) and its introduction into clinical practice (Grond et al.1998, Trouillas et al.1998, Hamilton et al.1999).
Internal watershed infarction
Authors: Chambers B R , Bladin C F
Published: November 2023

Watershed infarction occurs in the borderzone between adjacent arterial perfusion beds and generally results from a critical reduction in perfusion pressure (Zuülch 1961a, Romanul and Abramowicz 1964, Adams et al. 1966, Torvik and Jørgensen 1966, Torvik 1984). Other terms include ‘borderzone’, ‘borderline’, ‘subcortical junctional’, ‘extraterritorial’, ‘distal field’, ‘terminal zone’, and ‘low-flow’ infarction. Bilateral watershed infarction may occur following prolonged severe hypotension after cardiac arrest, but more commonly one sees unilateral infarction in association with carotid occlusive disease. In such patients, regional perfusion failure may result from myocardial infarction, cardiac arrhythmia, cardiac failure, orthostatic hypotension, blood loss, or other disorders producing systemic hypotension.
Acute infarcts in the white matter medullary artery territory of the centrum ovale
Authors: Tsiskaridze A , Freitas G R de , Uldry P -A , Bogousslavsky J
Published: November 2023

Patchy or diffuse abnormalities of the white matter (the core of which is formed by the centrum ovale), seen as areas of decreased attenuation on computed tomographic (CT) scans and signal hyperintensity on magnetic resonance imaging (MRI), are common findings in the elderly. To avoid pathological and aetiological confusion, the term ‘leukoaraiosis’ has been proposed (from leuko ¼ white, and araiosis ¼ rarefied) for this radiological phenomenon (Hachinski et al. 1987), which can easily be distinguished from infarction on the basis of the CT criteria proposed by Steingart et al. (1987) (Table 22.1).
Designing a study
Authors: Armstrong David , Grace John
Published: November 2023

Chapter 1 looked at the types of research questions that can be asked, and at ways to check to what extent the answer was known. Once the research question(s) has been chosen the next step is to identify the research plan or design that will be appropriate for answering it.
Medical audit and clinical governance
Authors: Armstrong David , Grace John
Published: November 2023

One of the key characteristics of being a member of a profession was the freedom to exert control over the content of everyday work. For the medical profession this translated as clinical autonomy, as being free to act in the best interests of the patient. However, in recent years this freedom has come in for criticism, especially in the light a number of high-profile cases of clinical incompetence exhibited by individual practitioners. The conclusion is that clinical autonomy cannot always deliver good quality care and that we can no longer rely on the individual practitioners acting independently on behalf of his or her patients. The solution has been to encourage the profession to begin to take some sort of collective responsibility for the behaviour of its members. In that way, the patients who might suffer on account of clinical weaknesses of individual practitioners might gain some protection from the interest of other practitioners in the skills and abilities of each other.
The four processes of drug therapy
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

The processes of drug therapy are very complex, although not more complex than the processes that underlie the illness for which therapy is being given. Historically, modern drug therapy has developed from the herbal and folklore medicine of the past, with its mixture of magic, empirical pharmacology, and faith of the patient in the doctor. Some cynics might hold that not much has changed. However, there have been changes, even though the apparent magic of drug therapy is still a potent force in its success. The changes that have occurred are in the understanding of the mechanisms of action of the drugs we use and in the optimal use of those drugs in the treatment of disease. Underlying all this is an immense amount of research in the sciences of basic and clinical pharmacology.
The pharmaceutical process: Is the drug getting into the patient?
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

A prescription is a complicated, often rather imprecise, set of instructions. Consider the following list of drugs that a patient admitted under our care was taking. She was a 60-year-old woman admitted as an emergency with atrial fibrillation, heart failure, hypertension, diabetes mellitus, osteoarthritis, depression, insomnia, and a urinary tract infection. For the meanings of the abbreviations used here, see p. 188.) There may have been medical justification for the prescription of each of these drugs at the time they were first prescribed. However, it was a formidable task for the patient to organize herself to remember to take 18 tablets a day, three drugs to be taken three times a day, one drug twice a day, three drugs once a day in the morning, and one at bedtime. Indeed, on most days, she had probably failed to do all this correctly.
Monitoring drug therapy
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

In this Chapter, we shall examine the ways in which we can obtain information to help answer these questions in clinical practice and to help to rationalize drug therapy. Questions 1 and 2 can sometimes be answered by measuring drug and metabolite concentrations in body fluids. Question 3 can sometimes be answered by direct measurement of some pharmacological effect of the drug. Question 4 can sometimes be answered by direct measurement of the therapeutic outcome.
Drug therapy in young and old people
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

Paediatricians tell us that neonates, infants, and children are not just small adults, and that is certainly true of the ways in which they absorb, distribute, eliminate, and respond to drugs. Although some dosage schedules for children have already been determined by clinical trial or experience, many are based on some formula relating the body weight, age, or body surface area of the child to the adult dose. Probably the best way to scale down dosages from adult dosages is in proportion to the body surface area:Dose = (patient’s body surface area/adult body surface area) adult dose.
Patient compliance/ concordance
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

Patient compliance with drug therapy can be defined as the extent to which the patient follows a prescribed drug regimen. The extent of non-compliance varies widely, and in different studies has been recorded to be as low as 10 per cent and as high as 92 per cent. Some regard the term ‘non-compliance’ as being pejorative, implying as it does that the patient is behaving badly; they prefer other terms, such as ‘adherence’, ‘observance’, or ‘concordance’. Of course, patients have the right to refuse to accept any help that the doctor offers, whether outright or tacitly, and currently medicine taking is regarded as a partnership between doctor and patient; however, it helps if the doctor understands the factors that encourage concordance.
Drug discovery and development: the pharmaceutical industry and the regulatory authorities
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

Almost all the drugs mentioned in this book have been synthesized and developed by pharmaceutical companies. Doctors and patients depend on high and predictable standards of quality of formulation and proper ethical evaluation of the safety and efficacy of drugs, and the standards of the pharmaceutical industry with regard to the development of new drugs are in general high and are regulated by law.
Introduction to drug therapy
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

In Section I, we discussed the basic principles of clinical pharmacology, breaking down drug therapy into its component processes (pharmaceutical, pharmacokinetic, pharmacodynamic, and therapeutic). In Section II, we discussed some principles relating to the prescribing of drugs. Section IV (the Pharmacopoeia) contains details of the properties of individual drugs or groups of drugs. In this section, it is our aim to marry the properties of the drugs with the basic principles, and to link both with the pathology of the disease and its manifestations, in order to illustrate the ways in which drugs are used in the treatment of disease.
The drug therapy of infectious diseases
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

We shall deal with each of these classes of drug separately, and shall also cover the prevention of infections using vaccines and immunoglobulins. Many specific infections are dealt with in other Chapters (for example infective endocarditis in Chapter 23, pneumonias in Chapter 24, meningitis in Chapter 30).However, because sexually transmitted disorders are generally dealt with by specialists in the branch of infectious diseases known as genitourinary medicine, we shall deal with them in a separate section at the end of this Chapter.
The drug therapy ofcardiovascular disorders
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

Hypertension can be either of unknown cause (so-called ‘essential’) or secondary to some definite abnormality, for example renal parenchymal disease, renovascular disease, a variety of endocrine diseases, coarctation of the aorta, and drugs. In the majority of cases, there is no underlying cause, but an underlying cause should always be sought and should be particularly actively pursued in young patients with severe hypertension resistant to therapy.
The drug therapy of respiratory disorders
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

When there is hypoxia (as in the conditions listed in Table 24.1), it is therapeutically useful to increase the concentration of oxygen in the inspired air (normal oxygen concentration about 20 per cent). Oxygen can be added to the inspired air to produce concentrations ranging from 24 to 60 per cent. The dose depends not simply on the degree of hypoxia, but also on the presence or absence of hypercapnia.
The drug therapy of endocrine and metabolic disorders
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

Reduced function of the anterior pituitary gland results in underactivity of the organs that are normally stimulated by the pituitary trophic hormones, of which the most important, because deficiency is life-threatening, are ACTH (the adrenocorticotrophic hormone, corticotrophin) and TSH (thyroid-stimulating hormone). In children, growth hormone deficiency is also important, although deficiency in adults may be more important than has been previously recognized. Gonadotrophin deficiency, although not directly life-threatening, requires treatment. ACTH deﬁciency For adrenal insufficiency secondary to hypopituitarism, it is usual to use a glucocorticoid that also has some mineralocorticoid activity, such as hydrocortisone 20–30 mg orally. In order to mimic diurnal variation in the normal daily production of endogenous corticosteroids, the total dose can be divided into two doses, two-thirds to be taken in the morning and one-third in the evening; however, some divide the daily requirements into three doses, on the grounds that it produces a more desirable pattern of serum cortisol concentrations during the day (see adrenocortical insufficiency below).
The drug therapy of blood disorders
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

The aims in treating iron deficiency anaemia are to remove the cause and to increase red cell mass by giving iron. The main causes of iron deficiency anaemia are listed in Table 28.1. Iron can be given orally or parenterally, and in almost all patients the oral route is satisfactory. Iron in oral formulations is in the ferrous form, since that is the form in which iron is absorbed, mostly from the upper jejunum. Normal dietary iron absorption is 1–2 mg from a dietary intake of 10–20 mg, balancing the daily losses, which are mainly from sloughing of cells from the gastrointestinal tract and skin, and from urinary losses.
The drug therapy of disorders of bones and joints
Authors: Grahame-Smith D G , Aronson J K
Published: November 2023

The drug therapy of the most common types of arthritis, osteoarthritis and rheumatoid arthritis, was not one of the great successes of 20th century therapeutics. Simple non-opioid analgesia has not progressed beyond aspirin and paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs), although partly effective as both analgesics and anti-inflammatory drugs, cause many serious adverse reactions, particularly in elderly people, in whom they are used very commonly. In rheumatoid and other inflammatory types of arthritis (in contrast to osteoarthritis), there are several so-called ‘disease-modifying drugs’ (DMARDs), now often called ‘slow-acting anti-rheumatic drugs’ (SAARDs), each of which is only partly effective and has its own range of serious adverse reactions.
Immunosuppression and the drug therapy of allergies, connective tissue disorders, and primary immunodeﬁciencies
Authors: Grahame-Smith D G
Published: November 2023

Although the precise details of the mechanisms of action of the drugs that are used in the treatment of allergic and immune diseases have not been fully worked out, sufficient is known to fit them into a scheme that depends on an understanding of the four different types of immune reaction. The drugs used are listed in Table 37.1.Type I allergic reactions are those in which exposure to an antigen in a predisposed individual leads to the production of IgE antibodies, which bind to the cell surfaces of mast cells and basophil polymorphonuclear leukocytes. A subsequent exposure of the individual to the antigen leads to an antigen–antibody reaction at the cell surface and the activation of a system that leads to the release of inflammatory mediators from the cell.
Pretransplant medical evaluation for pancreas transplant candidates
Authors: McCauley Jerry , Corry Robert J
Published: November 2023

Pancreas transplantation has rapidly moved from an experimental procedure associated with high rates of morbidity and mortality to a mainstream technique with excellent patient and graft survival. The rate of pancreas transplantation increased from less than 200 per year in 1987 to approximately 1000 per year in 1998. [1,2] Recent Medicare funding for simultaneous kidney and pancreas transplantation (SPK) and pancreas after kidney (PAK) transplantation in the United States will likely fuel more rapid growth. The recent proliferation of new immunosuppressant agents will also likely contribute further to improve graft survival in patients with PAK and pancreas transplantation alone (PTA) and increase the rate of transplantation in these patients as well. The medical evaluation prior to transplantation is crucial since many arrive with pre-existing cardiac disease and other complications of diabetes, which may substantially increase the risk of graft loss and death. The indications for pancreas transplantation is in evolution and may be highly affected by the preferences of the transplant centre, improvements in allograft survival related to improved immunosuppression, and surgical technique. The indications for pancreas transplantation are also evolving and are not uniformly accepted by the rapidly growing number of pancreas transplant centres.
Donor management and selection for pancreas transplantation
Authors: Frezza Eldo Ermenegildo , Corry Robert J
Published: November 2023

Pancreas transplantation is a well-established treatment for patients with insulin-dependent diabetes. Over the last decade, the procedure has been refined, and immunosuppressive regimens have improved such that, at major centres, 1-year graft survival routinely exceeds 80 per cent [1]. Recent evidence supports the beneficial effect of pancreas transplantation on the maintenance of normoglycaemia, and the arrest and possible reversal of diabetic complications such as vasculopathy, neuropathy, and nephropathy [2–4].
Procurement and benchwork preparation of the pancreatic graft
Authors: Hakim Nadey S , Papalois Vassilios E
Published: November 2023

The selection criteria for pancreas donors are similar to those for other solid organs [1,2]. Ideally, donor age ranges between 18 and 45 years and donor weight between 40 to 100 kg. A history of diabetes mellitus, acute necrotizing pancreatitis, and chronic pancreatitis are obvious contraindications. Despite a reported history of pancreatitis, it is always worthwhile examining the pancreas at the time of procurement to assess the suitability of the organ. It should be remembered that after brain death the serum amylase levels are often high in the absence of pancreatitis, and hyperglycaemia may occur in the absence of diabetes. The direct inspection of the pancreas is therefore justified before deciding whether or not to procure.
Pancreas preservation
Authors: Spiegel H U , Palmes D
Published: November 2023

The evolution of organ transplantation into a clinical reality is due mainly to the development of surgical technique, the introduction of immunosuppressant drugs with better selectivity and fewer side effects, and the devising of more effective means of organ preservation and protection. The immense success of organ transplantation has broadened its indications to include conditions which do not threaten life, but where the gain in quality of life out weights the risks of lifelong immunosuppression, for example, pancreas transplants in patients with insulin-dependent type I diabetes mellitus (IDDM) who are not adequately controlled even by carefully adjusted insulin therapy [1–5]. The steadily rising demand for donor organs can no longer be met by the numbers of potential organ donors. New strategies will therefore have to be devised for procuring better supplies of donor organs, for example, enlargement of the donor pool by recruitment of living donors and of ‘marginal’ donors with minor impairment of organ function; adequate utilization of available donor organs must be also ensured.
Surgical techniques of pancreas transplantation
Authors: Krishnamurthi Venkatesh , Stephen T Bartlett
Published: November 2023

Insulin-dependent diabetes mellitus (IDDM) affects 1 million people in the United States and 30 000 new patients annually [1]. In addition to being the leading cause of endstage renal disease (ESRD), IDDM is also the leading cause of blindness, amputations, and impotence in adults. Data from the Diabetes Control and Complication Trial (DCCT) conclusively demonstrate that tight glucose control reduces the incidence of secondary complications [2]. The benefits of intensive control were not without risk however, as severe hypoglycaemia episodes and weight gain occurred more frequently in patients treated with intensive control. Moreover, as was concluded by the DCCT Research Group, there was no minimal glycaemic threshold below which complications would not occur [3]. These findings reinforce the belief that exogenous insulin administration is, at best, an imperfect solution for IDDM.
Surgical complications of pancreas transplantation
Authors: Benedetti Enrico , Sileri Pierpaolo , Gruessner Angelika C , Cicalese Luca
Published: November 2023

Pancreas transplantation is currently considered an extremely effective therapeutic option for selected patients affected by type I diabetes. According to the International Pancreas Transplantation Registry 2000 Midyear Update [1], over 1400 pancreas transplants have been performed annually worldwide since 1995. In 1999, the majority of cases were simultaneous kidney and pancreas transplants (SPK, 86 per cent), followed by pancreas after kidney (PAK, 10 per cent), and pancreas transplant alone (PTA, 4 per cent). Current 1-year and 5-year patient survival rates exceed 90 and 80 per cent, respectively, without significant differences between the different procedures for cases performed between 1996 and July 2000. Pancreatic graft survival rates at 1 year were 84 per cent for SKP, 73 per cent for sequential PAK, and 70 percent for PTA. These excellent outcomes, much improved in comparison to older data, have been achieved due to a marked decrease in immunological graft loss and technical failures over the last 10 years. This chapter will focus on surgical complications after pancreas transplantation.
Medical and urological complications of pancreas and kidney/pancreas transplantation
Authors: Pham Phuong-Thu T , Pham Phuong-Chi T , Wilkinson Alan H
Published: November 2023

Simultaneous pancreas and kidney transplantation (SPKTx) is a well-established therapeutic option for selected patients with endstage renal disease (ESRD) secondary to type I diabetes mellitus. Refinements in surgical techniques and important advances in immunosuppressive therapy have allowed patient and graft survival to reach levels comparable to those seen in kidney alone (KA) transplantation. Nevertheless, morbidity in pancreas transplants remains high, in part due to special problems that are inherent to pancreas transplantation. Variations in surgical techniques may result in different types and incidence of both surgical and medical complications. Urinary diversion of exocrine secretions of pancreas allografts may result in unique acid–base and electrolyte disorders, whereas systemic venous drainage of the endocrine system may lead to peripheral hyperinsulinaemia and peripheral insulin resistance.
Histology of the pancreas transplant
Authors: Klassen David K
Published: November 2023

The early detection and effective treatment of acute rejection has been a major challenge in pancreas transplantation. Numerous non-invasive markers of pancreas rejection and function have been studied such as serum or urine levels of amylase, lipase, or anodal trypsinogen or functional measures such as glucose disappearance rates. [1–3]. Although widely used, none of these biochemical markers or functional measures have proven to be specific for acute rejection. Similarly imaging studies such as magnetic resonance imaging (MRI) scanning or ultrasound have not shown adequate sensitivity or specificity on which to base treatment of rejection [4–6]. The diagnosis of acute pancreas rejection has until recently relied on evidence of renal allograft rejection in patients receiving simultaneous kidney and pancreas transplantation. In these patients, renal allograft dysfunction is used as a surrogate marker for pancreas rejection as most rejection episodes occur simultaneously in both the kidney and pancreas, and the renal allograft is easily biopsied.
Fetal and neonatal pancreatic tissue transplantation
Authors: Tuch Bernard E
Published: November 2023

The first record of transplanting fetal pancreatic tissue into humans was by Fischera in 1928. He allografted the tissue in three sites, beneath the tunica vaginalis, into muscle, and preperitoneally (reported in [1]). More systematic transplants of fetal pancreas did not occur until six decades later [2–4].

The systematic desire to examine the use of immature pancreatic tissue occurred in the 1970s at a time when all types of pancreatic tissue were being examined as possible sources for replacing the -cells destroyed in type 1 diabetes. Whole pancreas, islets, and fetal tissue were identified as possible sources of viable -cells.

At the dawn of the new millennium, the role of the whole pancreas as a therapy for type 1 diabetes is known [5]. Problems that had to be overcome to achieve this goal have included optimizing methods to retrieve the pancreas from brain-dead donors, which immunosuppressive drugs are needed to prevent rejection, and the best site to transplant the pancreas. These issues are discussed elsewhere in this book. Whole pancreas transplants are reserved for those people with advanced complications, especially those with renal failure requiring a kidney transplant. Success rates are on a par with other whole organ transplants. The percentage of grafts still functioning 1 year after being transplanted is 83 per cent [5].
Experimental approaches to the prevention of islet rejection
Authors: Kenyon Norma Sue
Published: November 2023

Various animal models of pancreatic islet cell transplantation have been utilized to test novel approaches for the prevention of graft rejection. In the setting of type 1 diabetes, prevention of recurrent autoimmunity has also been a critical focus. Production of proinflammatory mediators by macrophages and endothelial cells that are activated subsequent to intrahepatic islet infusion can be detrimental to islet survival and function, thus leading to early islet loss or primary non-function (PNF), and can also serve to augment specific immune responses to the graft. Experimental approaches to the prevention of rejection must, therefore, target rejection, recurrent autoimmunity, and events associated with PNF. Furthermore, agents must be identified that do not have adverse effects on islet cell function.
Normal Tendon
Authors: Stanish William D , Curwin Sandra , Mandel Scott
Published: November 2023

Muscles vary greatly in size, shape, and complexity (Fig. 1.1). Some are broad and flat, with wide, short tendons such as the gluteus maximus or rectus abdominis. Others, such as the fusiform biceps, have smaller, rounded, cord-like tendons. In general, the shorter and broader tendons are associated with muscles that create high levels of force, while longer and narrower ten¬ dons are associated with muscles that make precision movements, such as those seen in the hand (Jozsa and Kannus 1997). it is unrealistic to consider and discuss tendon in isolation from its accompanying muscle, and we encourage the reader to bear this in mind throughout the following pages.
Etiology of tendinitis
Authors: Stanish William D , Curwin Sandra , Mandel Scott
Published: November 2023

with one oriented in the tendon’s long axis. The size of each vector is determined by the angle of orientation of the muscle fibres. The lateral components largely cancel each other out, if both parts of pennate muscle are equally active, leaving a tensile force to be applied to the tendon in series with the muscle. Pennate muscles, therefore, exert less ten¬ sile force on the tendon because of the greater angle between the longitudinal axis of the muscle and the tendon. This is true even though muscle fibres of fusiform and pennate muscles are capable of producing equal amounts of force (Alexander and Vernon 1975).
Humeral epicondylitis
Authors: Stanish William D , Curwin Sandra , Mandel Scott
Published: November 2023

We concur with this opinion, but narrow our definition of tennis elbow to elbow pain that can be related to the extensor movements of the wrist joint. These extensors commonly attach to the lateral epicondyle, so the term lateral epicondylitis is preferable to tennis elbow, especially since the syndrome com monly occurs in non-athletes whose occupations involved repeated gripping activities, such as carpenters, The lateral epicondyle of the humerus is a point of origin for the wrist extensors, including extensor carpi radialis longus, extensor carpi radialis brevis, extensor digitorum, and extensor digitiminimi. These muscles attach jointly to the lateral epicondyle via a tendinous expansion known as the common extensor tendon, or extensor aponeurosis (Fig. 6.1). In addition, the supinator muscle partially attaches to the lateral epicondyle and lies underneath the wrist extensor muscles mentioned above
Othertendinitides
Authors: Stanish William D , Curwin Sandra , Mandel Scott
Published: November 2023

There are numerous other tendinitides that can be equally difficult to treat. The purpose of this chapter is to review some of these disorders, their etiologies, and possible avenues of treatment. We do not advocate the use of eccentric exercises in treating all types of tendinitis and not all the clinical entities mentioned in this chapter are necessarily amenable to treatment with eccentric exercise. We present what we feel is the best method of treatment or the most widely used.
Clinical results
Authors: Stanish William D , Curwin Sandra , Mandel Scott
Published: November 2023

The development of the eccentric exercise program was prompted by our disappointment with traditional treatment methods and the growing realization that we were not employing our knowledge of the behavior of soft tissue under different physical conditions. Dr Howard Lamb, research fellow at the Nova Scotia Sport Medicine Clinic in 1978, questioned our ‘standard’ treatment of tendinitis, which at that time consisted of physical modalities, oral anti-inflammatories, flexibility exercises, ice application, transcutaneous neurologic stimulation (TNS), and so forth. Dr Lamb reasoned that the tensile strength of the tendon was being exceeded during activity and that this action was causing the micro ruptures that led to injury. Moreover, he felt that only by addressing the problem of tensile strength instability directly would it be solved. That is, the tendon must be gradually and progressively overloaded, thereby increasing its tensile strength. Immobility or disuse of the tendon (and, in fact, all soft tissues) simply weakened it. Thus, we encouraged our patients to remain active, and we avoided the use of rest as a treatment modality except where absolutely necessary.
Franklin ‘s Experiment: The Observation
Authors: Tanford Charles
Published: November 2023

It is appropriate to divide the published account of Franklin ‘s experiment into two parts: the observation and the interpretation. This chapter describes the observation and includes the experiment itself and the circumstances that led to it. Chapter 13 will give Franklin ‘s attempt to interpret his observations in molecular terms. Most of the present chapter consists of a verbatim copy of Franklin ‘s own words, with a minimum of annotation.
How Small Is a Molecule? The Calculation Franklin Did Not Make
Authors: Tanford Charles
Published: November 2023

Here’s puzzle, posed before but never answered. Ben Franklin knew that a drop of oil, when spread out over an area of half an acre, becomes astonishingly thin, thin enough to exhibit the prismatic colors, and even thinner than that, so that the presence of the oil would have been undetectable but for the smoothing of the waves.

waves.
Ernest Overton—Gentle Genius
Authors: Tanford Charles
Published: November 2023

We go backward in time here, but forward in understanding. The preceding chapter has given mixed reviews to bio-logical science around the turn of the century. There was brilliant progress in some areas, but neglect and confusion in relation to cell membranes. Charles Ernest Overton was an exception, someone whose comprehension of cell membrane composition and function was never confused. On the contrary, “prescient ” would in retrospect be a good description. Overton ’s work is outside the main theme of this book, in the sense that he himself never experimented with films of oil on water surfaces, but it establishes a physiological context and shows that some areas of physiology were crying out for just the kind of insight that surface film measurements could provide.
Gorter and Grendel: A Factor of Two
Authors: Tanford Charles
Published: November 2023

After Langmuir, was there more to be learned from spreading oil on water and measuring surface areas, using the same simple rectangular trough that Pockels and Langmuir had used? As it turned out, there was indeed new and important information to be gained for biology by applying Langmuir ’s method to molecules taken directly from living cells. This chapter deals with a single experiment in this category, a beautiful and simple experiment, exactly right for clearing the air of foggy conceptions about cell membranes. The experiment was conceived by a great Dutch pediatrician, Evert Gorter, and was carried out in his laboratory at the University of Leiden.
Introduction
Authors: Gill Stephen
Published: November 2023

Anyone trying to construct a biography of Wordsworth faces a problem: the poet spent a lifetime sifting, selecting, and ordering much of the material for it himself. Officiaily he was opposed to biography. It was clear, of course, to both admirers and detractors that autobiography was the well-spring of his creative powers. His, as Keats said, was the poetry of the ‘egotistical sublime’. Wordsworth wrote about real places and events, about the River Wye, Grasmere, London, Bruges, the Yarrow, about tours of Scotland and Italy. He memorialized his own experiences and recollections, his family, people met with in chance encounters, and old friends. The Preface to The Excursion (1814), the notes appended to particular lyrics, and the tantalizingly brief but revealing personal words in the 1842 volume Poems, Chiefly of Early and Late Years even encouraged interest in the poet by sketching in a biographical context for the work. But further biographical probing was always thwarted. ‘In truth my life has been unusually barren of events’, he told Anne Taylor in 1801, formulating a useful untruth which he repeated thirty-six years later when parrying another probe with the remark that his life was ‘bare of entertainment and interest’.2 He forbade Barron Field, an intelligent disciple, to publish his Memoirs of Wordsworth and was so appalled by the unauthorized use made of letters and recollections after Coleridge’s death that he declared he hoped not a scrap of his own correspondence would survive.
1787–1792
Authors: Gill Stephen
Published: November 2023

In his very popular poem The Minstrel James Beattie upbraids those spirits vouchsafed ‘a portion of celestial fire’: and in the story of Edwin, the minstrel, he illustrates the sentiment. To the indulgent eye of Dorothy the fact that ‘the whole character of Edwin resembles much what William was when first I knew him after my leaving Halifax’ just gave her brother added charm. To his guardians, however, the identification, had they recognized it, could only have given cause for further anxiety. This was not the time for high-souled rejection of the world of men, but for diligent attention in Cambridge to whatever was necessary to secure a career and independence. Happily there was no real reason to doubt that Wordsworth would be successful in worldly terms. Hawkshead was a good school which had prepared him as well as any of its numerous pupils already welcomed in the University. He had, in addition, connections who could ease the way to academic and Church preferment. But within five years it was clear that Wordsworth had thrown away every advantage. After an excellent start he had abandoned serious academic competition, taking only a pass degree. He had alienated relatives and seemed determined not to accept the proffered opening of a career in the Church. He had marked his coming of age by fathering a child on a Frenchwoman without the means to support the child or marry the mother. Just as important for his future prospects, he had been infected by the virulent contagion of radicalism, becoming one of’that odious class of men called democrats’3 just at the time when authority was not discriminating too subtly between shades of political principle but dividing up citizens into simple categories, the ‘loyal’ and the ‘seditious’.
1795–1797
Authors: Gill Stephen
Published: November 2023

Place-Names are used in an interesting way in most accounts of Wordsworth’s poetic development. Writers on, say, Dickens or Yeats, when identifying moments of artistic growth, refer to books—to the transitional form, for example, of Martin Chuzzlewit, or to the self-conscious maturity of Responsibilities. Lovers of Wordsworth might do likewise, pointing to An Evening Walk, or Lyrical Ballads, or The Prelude, as key writings, but they are at least as likely to mark out the poet’s spiritual odyssey by referring to ‘Windy Brow’, ‘Racedown’, ‘Alfoxden’, ‘Dove Cottage’, ‘Rydal Mount’. These were places, it is understood, in which self-discovery or achievement or consolidation occurred, whose particular nature, which may or may not be in evidence in specific poems, can be evoked by naming that one special place.
1798–1799
Authors: Gill Stephen
Published: November 2023

At II a.m. on 16 September 1798 the German packet slipped out of Yarmouth to the open sea. At once the passengers began to turn frog-coloured—’Wordsworth shockingly ill’, Coleridge reported, ‘his Sister worst of all—vomiting, & groaning, unspeakably!’ They were delayed by fog at the mouth of the Elbe and when they reached Hamburg on the nineteenth had difficulty in finding accommodation in a dirty, stinking city, where children defecated in the streets and shopkeepers (they were convinced) gloated over their skill at cheating foreigners.* It was not an auspicious start to a tour which, as a tour, turned out for the Wordsworths a complete failure.
1800-1802
Authors: Gill Stephen
Published: November 2023

Grasmere, William Wilberforce remarked, ‘gives one the idea of Rasselas’s happy Valley’. He was not thinking hard about the implications of Johnson’s fable, just echoing Gray’s earlier comment that this was a ‘little unsuspected paradise’. It is easy to see why. Grasmere is surrounded in three quarters by hills—Dunmail Raise, Stone Arthur, and the Fairfield mass to the north and east, Helm Crag and Silver How to the west, and from any one of them, but especially from Silver How and Red Bank at the southerly end of the lake, the water and the village marked out by the church tower seem grouped expressly for picturesque composition. Even on the more open south approach, the road leads over the little hill of White Moss Common and seems to harmonize the scene by leading the eye from the grandeur of the views to the north and west down to the little group of houses at Town End. From their cottage the Wordsworths looked over a meadow to the lake and all that is needed is De Quincey’s account of their main room ‘very prettily wainscotted from the floor to the ceiling with dark polished oak’, dimly lit by ‘a perfect and unpretending cottage window, with little diamond panes, embowered at almost every season of the year, with roses’, for one to imagine that the Wordsworths moved into a ready-made rural idyll.3 But it was not so. They arrived in a period of severe frost—∼ Wordsworth was soon skating on nearby Rydal—at a six-roomed cottage which would have fitted into any one floor at Racedown and Alfoxden. It was damp, gloomy, and almost unfurnished. Their first task was to make it a home.
Cloning and Individuality
Authors: Gardner R L
Published: November 2023

Organisms that are genetically identical constitute a clone. The essence of cloning is to produce new individuals without the intervention of sexual reproduction, which generates diversity. Cloning is accomplished naturally by the repeated production of new individuals directly from parts of existing ones by such processes as cell division and budding. Particularly in microbes, plants, and lower animals, clones can be very large indeed. Cloning also occurs naturally in man as a result of the unexplained development of more than one fetus from a single fertilized egg. Whilst two genetically identical fetuses are the most common outcome, triplets, quads, and even quins can originate in this way. With increasing use of ultrasound imaging it is now clear that such monozygotic twins are more common during pregnancy than at birth. Thus, competition between intimately associated fetuses must sometimes lead to the demise of one, not infrequently at so early a stage that no trace of it remains when the survivor is born.
Who Should have Access to Genetic Information?
Authors: Knoppers Bartha Maria
Published: November 2023

No discussion of a ‘should we’ question can ignore an even more preliminary one, a question that sets the stage for any present and future resolution of an issue, that is, ‘where are we?’ Obviously, this series, The Genetic Revolution and Human Rights, is meant to do just that. Nevertheless, permit me a few introductory remarks on the relationship between that fundamental exercise and the issue of access to genetic information.