Structural progression rate decreases over time on serial radiography and magnetic resonance imaging of sacroiliac joints and spine in a five-year follow-up study of patients with ankylosing spondylitis treated with tumour necrosis factor inhibitor.

OBJECTIVE: To investigate temporal changes in structural progression assessed by serial conventional radiography and magnetic resonance imaging (MRI) of the sacroiliac joints (SIJs) and spine in patients with ankylosing spondylitis (AS) treated with tumour necrosis factor (TNF) inhibitor for 5 years. METHOD: Forty-two patients were included and 33 patients were followed for 5 years in a prospective investigator-initiated study. Conventional radiographs were required four times and MRI seven times. The modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS); Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ and Spine Inflammation, and SPARCC MRI SIJ Structural Score (SSS) for Fat, Erosion, Backfill, and Ankylosis; and the Canada-Denmark MRI scores for Spine Inflammation, Fat, Erosion, and New Bone Formation (NBF) were applied. RESULTS: Compared with baseline, MRI Inflammation had decreased significantly at week 22 (spine)/week 46 (SIJ) and thereafter. MRI SIJ Fat (from week 22), SIJ Ankylosis, Spine NBF, and mSASSS had increased significantly at week 46 and thereafter. SIJ Erosion had decreased from year 2. The annual progression rate in mSASSS was significantly higher during weeks 0-46 compared to week 46 to year 3. In multivariate regression analyses, baseline SIJ Inflammation and Backfill were independent predictors of 5 year progression in SIJ Ankylosis. Spine Erosion predicted progression in Spine NBF. Longitudinally, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, MRI Spine Inflammation, Fat, and Erosion scores were significantly associated with mSASSS. SIJ Inflammation, Fat, Erosion, and Backfill scores were longitudinally associated with SIJ Ankylosis. Structural progression was not associated with body mass index, smoking, or Assessment of SpondyloArthritis international Society Non-Steroidal Anti-Inflammatory Drug Index. CONCLUSION: In a 5 year follow-up study of patients with AS treated with TNF inhibitor, structural progression decreased over time.

Monitoring total-body inflammation and damage in joints and entheses: the first follow-up study of whole-body magnetic resonance imaging in rheumatoid arthritis.

OBJECTIVE: To investigate changes in whole-body magnetic resonance imaging (WBMRI) inflammatory and structural lesions in most joints and entheses in patients with rheumatoid arthritis (RA) treated with adalimumab. METHODS: WBMRI was obtained at weeks 0, 6, 16, and 52 in a 52 week follow-up study of 37 RA patients starting treatment with adalimumab. Readability and reliability of WBMRI were investigated for 76 peripheral joints, 23 discovertebral units, the sacroiliac joints, and 33 entheses. Changes in WBMRI joint and entheses counts were investigated. RESULTS: The readability of peripheral and axial joints was 82-100%, being less for elbows and small joints of the feet. For entheses, 72-100% were readable, except for entheses at the anterior chest wall, elbow, knee, and plantar fascia. The intrareader agreement was high for bone marrow oedema (BMO), bone erosion (80-100%), and enthesitis (77-100%), and slightly lower for synovitis and soft tissue inflammation (50-100%). All synovitis, BMO, and soft tissue inflammation counts decreased numerically during treatment. The 26-joint synovitis WBMRI count decreased significantly during the first 16 weeks for patients with a good European League Against Rheumatism (EULAR) response (from median 6 to 4, p < 0.05), but not for patients with a moderate or no EULAR response. There were no overall changes in structural lesions. CONCLUSIONS: WBMRI allows simultaneous monitoring of most axial and peripheral joints and entheses in RA patients and can visualize a decrease in inflammatory counts during treatment. This first WBMRI follow-up study of patients with RA encourages further investigation of the usefulness of WBMRI in RA.

The World Health Organisation analgesic ladder: its place in modern Irish medical practice.

Pain is the single most common reason why patients seek medical care. Worldwide, there are 10 million new cases of cancer each year, with 6 million deaths annually. The World Health Organisation (WHO) first published Cancer Pain Relief in 1986, designed to be a simple, intuitive and accessible guide to the management of cancer pain that would be applicable and useful whatever the language, culture, economy, country and clinical setting. In Ireland today, we have ready access to many different opioids, and the WHO guidelines may seem inadequate and outdated. This article describes the evolution and use of the WHO guidelines, as viewed from the global perspective of its 193 member nations. The WHO ladder still remains valid today in Ireland, even as we await the imminent publication of new evidence-based national cancer pain guidelines this year.

Evidence for cardioprotective, renoprotective, and vasculoprotective effects of vasopeptidase inhibitors in disease.

In both the natriuretic peptide and renin-angiotensin systems, peptidases play an important role in the inactivation or activation of the system. Angiotensin-converting enzyme is responsible for the conversion of angiotensin I to angiotensin II, while neutral endopeptidase is one of the pathways involved in the degradation of the natriuretic peptides. The vasopeptidase inhibitors, which simultaneously inhibit neutral endopeptidase and angiotensin-converting enzyme, appear to offer distinct therapeutic advantages in treating hypertension, heart failure, and endothelial dysfunction.

Vasopressin receptor antagonism--a therapeutic option in heart failure and hypertension.

The precise role of vasopressin in the pathophysiology of cardiovascular disease is controversial, but this peptide hormone is important for several reasons. Firstly, circulating concentrations of vasopressin are elevated in heart failure and some forms of hypertension. Secondly, there is evidence that vasopressin is synthesized not only in the hypophysial-pituitary axis but also in peripheral tissues including the heart where it acts as a paracrine hormone. Thirdly, vasopressin has vasoconstrictor, mitogenic, hyperplastic and renal fluid retaining properties which, by analogy with angiotensin II, may have deleterious effects when present in chronic excess. Finally, the availability of orally active non-peptide vasopressin receptor antagonists allows vasopressin receptor antagonism to be considered as a therapeutic option in cardiovascular disease.

Beneficial renal and cardiac effects of vasopeptidase inhibition with S21402 in heart failure.

S21402 is a vasopeptidase inhibitor that simultaneously inhibits neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE). This study determined whether chronic treatment with S21402 produced different effects on sodium and water excretion, hormonal parameters, and cardiovascular structure compared with selective inhibition of ACE and NEP in a rat model of myocardial infarction-induced congestive heart failure (CHF). CHF rats received the vasopeptidase inhibitor (S21402, 100 mg. kg(-1). d(-1)), an ACE inhibitor (captopril, 50 mg. kg(-1). d(-1)), a NEP inhibitor (SCH42495, 60 mg. kg(-1). d(-1)), or vehicle for 4 weeks. S21402 alone caused a diuresis and natriuresis (P<0.01) in CHF. After 4 weeks, blood pressure was lowered by captopril but not other treatments (P<0.01). Both S21402 and captopril increased plasma renin activity (P<0.01), all treatment lowered plasma aldosterone (P<0.05) and plasma natriuretic peptide levels were unchanged. In the kidney, S21402 inhibited NEP and ACE (P<0.01), SCH42495 inhibited NEP (P<0.01), and captopril inhibited ACE (P<0.01). Heart mass was reduced by all active treatments; captopril reduced left ventricular mass (P<0.01), SCH42495 reduced right ventricular mass (P<0.01), and S21402 decreased left (P<0.05) and right ventricular mass (P<0.01), atrial mass (P<0.05), and lung mass (P<0.01). In CHF, vasopeptidase inhibition with S21402 produces effects that differ from those of selective NEP or ACE inhibition. S21402 improved sodium and water excretion, reduced pulmonary congestion, and attenuated both right and left ventricular remodeling. These effects, which occurred in the absence of any hypotensive action, suggest that S21402 may offer several advantages over ACE inhibition alone in the treatment of heart failure.

Airbag mediated death of a two-year-old child wearing a shoulder/lap belt.

Airbag injuries have resulted in the deaths of several infants and small children, and such deaths are generally associated with rearward-facing infant seats or unrestrained children in front passenger seats of cars equipped with airbags. An airbag can also cause death in a small child wearing a shoulder/lap belt, however, as this case report illustrates. A two-year-old female was involved in a low-speed collision while riding in the front passenger seat of a dual-airbag-equipped automobile. Secondary impact with the airbag caused catastrophic occipitoatlantoaxial disarticulation with traumatic spinal cord separation, thermal injury and abrasions of the right forearm and distinctive patterned abrasions of the face. The possibility of airbag injury should be considered in all low-speed traffic fatalities, and the confirmatory injuries sought at postmortem examination.

Gas flames, closed spaces, and hypoxia.

The investigation of the deaths of an elderly couple found in a small hotel room that was tightly sealed and heated by an open flame gas heater is presented. Autopsy and toxicologic studies did not reveal a definitive cause of death. Subsequent research and an experiment to duplicate the conditions support the contention that the cause of death was hypoxia due to oxygen depletion by the gas flame.

The missing link. An unusual case of embolization.

Embolization is a well-recognized phenomenon in medicine and forensic pathology and generally involves formed blood elements, bone, air, amniotic fluid, or more exotic items such as bullets. We report the embolization of a chain-saw link. The case demonstrates how, without complete autopsy and investigation, a penetrating sharp-force injury could be misdiagnosed and a false conclusion as to the commission of a crime could occur. Although the forensic literature is replete with examples of bizarre emboli, from bullets to suspected crystals of methylmethacrylate, a literature review failed to find a single case of penetrating chain-saw-link injury as a cause of traumatic death. Most reports of chain-saw incidents cite accidental injuries to hands and arms or dramatic facial injuries due to entrapment and recoil (1,2). One fatality occurred from a skull fracture and cerebral injury when a 19-year-old man fell onto a saw.

Diagnosis of electrical skin injuries. A review and a description of a case.

This paper presents a brief review of the results of research in the area of electrical skin injuries. It also includes a case report of a 5-year-old girl noted on her admission to the hospital to have injuries to the skin of her chest and left arm. Histological examinations demonstrated that the skin lesions were segmental and showed necrosis and inflammation. Deposits of calcium salts distinctly located to collagen fibers were observed below the regenerated epidermis at the periphery of two skin lesions of the chest wall, in the lower part of dermis at the periphery of a skin lesion of the left arm, and within connective tissue adjacent to elastic arteries and peripheral nerves from the thoracic cavity. The pattern of calcification localized to collagen fibers and situated both superficially and deeply in the skin in a zone of viable tissue close to necrotic tissue is characteristic of electrically induced lesions. Although there have been reports of deposition of calcium salts on collagen fibers after application of calcium salts in high concentration at the skin surface, the collagen calcification in the pattern observed in this patient is probably diagnostic of electrical injury.