Showing papers by "St Thomas' Hospital published in 1999"

Acute inflammatory responses in the airways and peripheral blood after short-term exposure to diesel exhaust in healthy human volunteers.

Abstract: Several epidemiologic studies have demonstrated a consistent association between levels of particulate matter (PM) in the ambient air with increases in cardiovascular and respiratory mortality and morbidity. Diesel exhaust (DE), in addition to generating other pollutants, is a major contributor to PM pollution in most places in the world. Although the epidemiologic evidence is strong, there are as yet no established biological mechanisms to explain the toxicity of PM in humans. To determine the impact of DE on human airways, we exposed 15 healthy human volunteers to air and diluted DE under controlled conditions for 1 h with intermittent exercise. Lung functions were measured before and after each exposure. Blood sampling and bronchoscopy were performed 6 h after each exposure to obtain airway lavages and endobronchial biopsies. While standard lung function measures did not change following DE exposure, there was a significant increase in neutrophils and B lymphocytes in airway lavage, along with increases in histamine and fibronectin. The bronchial biopsies obtained 6 h after DE exposure showed a significant increase in neutrophils, mast cells, CD4+ and CD8+ T lymphocytes along with upregulation of the endothelial adhesion molecules ICAM-1 and VCAM-1, with increases in the numbers of LFA-1+ cells in the bronchial tissue. Significant increases in neutrophils and platelets were observed in peripheral blood following DE exposure. This study demonstrates that at high ambient concentrations, acute short-term DE exposure produces a well-defined and marked systemic and pulmonary inflammatory response in healthy human volunteers, which is underestimated by standard lung function measurements.

The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways

Abstract: Many damage-sensing neurons express tetrodotoxin (TTX)-resistant voltage-gated sodium channels. Here we examined the role of the sensory-neuron-specific (SNS) TTX-resistant sodium channel a subunit in nociception and pain by constructing sns-null mutant mice. These mice expressed only TTX-sensitive sodium currents on step depolarizations from normal resting potentials, showing that all slow TTX-resistant currents are encoded by the sns gene. Null mutants were viable, fertile and apparently normal, although lowered thresholds of electrical activation of C-fibers and increased current densities of TTX-sensitive channels demonstrated compensatory upregulation of TTX-sensitive currents in sensory neurons. Behavioral studies demonstrated a pronounced analgesia to noxious mechanical stimuli, small deficits in noxious thermoreception and delayed development of inflammatory hyperalgesia. These data show that SNS is involved in pain pathways and suggest that blockade of SNS expression or function may produce analgesia without side effects.

Genetic Control of the Circulating Concentration of Transforming Growth Factor Type β1

Abstract: The concentration of transforming growth factor beta (TGF-beta) in plasma has been correlated with the development of several diseases, including atherosclerosis and certain forms of cancer. However, the mechanisms that control the concentration of TGF-beta in plasma are poorly understood. In a study of 170 pairs of female twins (average age 57.7 years) we show that the concentration of active plus acid-activatable latent TGF-beta1 [(a+l) TGF-beta therefore is predominantly under genetic control (heritability estimate 0.54). Single strand conformation polymorphism (SSCP) mapping of the TGF-beta1 gene promoter has identified two single base substitution polymorphisms. The two polymorphisms (G-->A at position -800 bp and C-->T at position -509 bp) are in linkage disequilibrium (correlation coefficient Delta = 0.215, P < 0.01). The C-509T polymorphism is significantly associated with the plasma concentration of (a+l) TGF-beta1, explaining 8.2% of the additive genetic variance of (a+l) TGF-beta1 concentration. It is therefore possible that predisposition to atherosclerosis, bone diseases or various forms of cancer may be correlated with the presence of particular alleles at the TGFB1 locus.

Measurement of Delusional Ideation in the Normal Population: Introducing the PDI (Peters et al. Delusions Inventory)

Abstract: The Peters et al. Delusions Inventory (PDI) was designed to measure delusional ideation in the normal population, using the Present State Examination as a template. The multidimensionality of delusions was incorporated by assessing measures of distress, preoccupation, and conviction. Individual items were endorsed by one in four adults on average. No sex differences were found, and an inverse relationship with age was obtained. Good internal consistency was found, and its concurrent validity was confirmed by the percentages of common variance with three scales measuring schizotypy, magical ideation, and delusions. PDI scores up to 1 year later remained consistent, establishing its test-retest reliability. Psychotic inpatients had significantly higher scores, establishing its criterion validity. The ranges of scores between the normal and deluded groups overlapped considerably, consistent with the continuity view of psychosis. The two samples were differentiated by their ratings on the distress, preoccupation, and conviction scales, confirming the necessity for a multidimensional analysis of delusional thinking. Possible avenues of research using this scale and its clinical utility are highlighted.

Retroversion of the acetabulum: A CAUSE OF HIP PAIN

Abstract: We describe a little-known variety of hip dysplasia, termed 'acetabular retroversion', in which the alignment of the mouth of the acetabulum does not face the normal anterolateral direction, but inclines more posterolaterally. The condition may be part of a complex dysplasia or a single entity. Other than its retroversion, the acetabulum is sited normally on the side wall of the pelvis, and its articular surface is of normal extent and configuration. The retroverted orientation may give rise to problems of impingement between the femoral neck and anterior acetabular edge. We define the clinical and radiological parameters and discuss pathological changes which may occur in the untreated condition. A technique of management is proposed.

Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit.

Abstract: Dexmedetomidine, a highly selective and potent alpha2-adrenergic agonist, has a potentially useful role as a sedative agent in patients requiring intensive care. As part of a larger European multicentre trial, a total of 119 postoperative cardiac and general surgical patients requiring ventilation and sedation in an intensive care unit were enrolled in four centres in the United Kingdom. One hundred and five patients were randomly allocated to receive either dexmedetomidine or placebo with rescue sedation and analgesia provided by midazolam and morphine, respectively. Compared with the control group, intubated patients receiving dexmedetomidine required 80% less midazolam [mean 4.9 (5.8) microg.kg-1.h-1 vs. 23.7 (27.5) microg.kg-1.h-1, p < 0.0001], and 50% less morphine [11.2 (13.4) microg.kg-1.h-1 vs. 21.5 (19.4) microg.kg-1.h-1,p = 0.0006]. Cardiovascular effects and adverse events could be predicted from the known properties of alpha-2 agonists. In conclusion, dexmedetomidine is a useful agent for the provision of postoperative analgesia and sedation.

Genetic influences on cervical and lumbar disc degeneration: A magnetic resonance imaging study in twins

Abstract: Objective Degenerative intervertebral disc disease is common; however, the importance of genetic factors is unknown. This study sought to determine the extent of genetic influences on disc degeneration by classic twin study methods using magnetic resonance imaging (MRI). Methods We compared MRI features of degenerative disc disease in the cervical and lumbar spine of 172 monozygotic and 154 dizygotic twins (mean age 51.7 and 54.4, respectively) who were unselected for back pain or disc disease. An overall score for disc degeneration was calculated as the sum of the grades for disc height, bulge, osteophytosis, and signal intensity at each level. A “severe disease” score (excluding minor grades) and an “extent of disease” score (number of levels affected) were also calculated. Results For the overall score, heritability was 74% (95% confidence interval [95% CI] 64–81%) at the lumbar spine and 73% (95% CI 64–80%) at the cervical spine. For “severe disease,” heritability was 64% and 79% at the lumbar and cervical spine, respectively, and for “extent of disease,” heritability was 63% and 63%, respectively. These results were adjusted for age, weight, height, smoking, occupational manual work, and exercise. Examination of individual features revealed that disc height and bulge were highly heritable at both sites, and osteophytes were heritable in the lumbar spine. Conclusion These results suggest an important genetic influence on variation in intervertebral disc degeneration. However, variation in disc signal is largely influenced by environmental factors shared by twins. The use of MRI scans to determine the phenotype in family and population studies should allow a better understanding of disease mechanisms and the identification of the genes involved.

Immunonutrition in the critically ill: A systematic review of clinical outcome

Abstract: Objective:To perform a meta-analysis addressing whether enteral nutrition with immune-enhancing feeds benefits critically ill patients after trauma, sepsis, or major surgeryData Sources:Studies were identified by MEDLINE search (1967 to January 1998) for original articles in English using the searc

The autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria.

Abstract: One-third of patients with chronic idiopathic urticaria (CIU) have circulating functional autoantibodies against the high affinity IgE receptor FceRI, or IgE. The intradermal injection of autologous serum causes a weal and flare reaction in many patients with CIU, and this reaction forms the basis of the autologous serum skin test (ASST). We have determined the parameters of the ASST which define the optimal sensitivity and specificity for the identification of patients with autoantibodies. Two physicians (R.A.S. and C.E.H.G.) performed ASSTs in a total of 155 patients with CIU, 40 healthy control subjects, 15 patients with dermographism, nine with cholinergic urticaria and 10 with atopic eczema. Patients were classified as having functional autoantibodies by demonstrating in vitro serum-evoked histamine release from the basophils of two healthy donors. There were significant differences (P < 0.001) in the mean weal diameter, weal volume, weal redness and flare area of the intradermal serum-induced cutaneous responses at 30 min between patients with CIU with autoantibodies and either those without autoantibodies or control subjects. The optimum combined sensitivity and specificity of the ASST was obtained if a positive test was defined as a red serum-induced weal with a diameter of ≥ 1.5 mm than the saline-induced response at 30 min. For R.A.S. and C.E.H.G., the ASST sensitivity was 65% and 71% and specificity was 81% and 78%, respectively. Using these criteria, the following subjects had positive ASSTs: none of 15 dermographics, none of 10 atopics, one of nine cholinergics and one of 40 controls.

Incidence and risk factors for radiographic knee osteoarthritis in middle‐aged women: The Chingford Study

Abstract: Objective To examine the natural history, role of risk factors, and incidence of knee osteoarthritis (OA) in a prospective study of women from a population cohort. Methods Women from the Chingford Study who had been recruited in 1989 were followed up with knee radiographs 4 years later. A total of 715 paired radiographs (71% of the original sample) were graded for osteophytes and 644 for joint space narrowing (JSN). Women whose radiographs had been graded as 0 in 1989 and as ≥14 years later were classified as having incident disease. Incident cases were compared with controls for associations with a number of risk factors. Results Eighty-one women (12.6%) developed JSN of the knee, equating to an incidence of 3.1% per year. No clear risk factors for JSN were identified. Reproducibility of measures of joint space is poor, however, leading to inaccuracy of definition. Incident knee osteophytes developed in 95 women (13.3%), equating to an incidence of 3.3% per year. Compared with controls, women with incident knee osteophytes were older, heavier, and had more hand OA and knee symptoms. Women in the top tertile of obesity (body mass index >26.4) had a significantly increased risk of incident knee osteophytes (odds ratio [OR] 2.38, 95% confidence interval [95% CI] 1.29–4.39). Incident knee osteophytes increased by 20% per 5-year age increase. A nonsignificant protective effect for incident knee osteophytes was seen with current estrogen replacement therapy (ERT) (OR 0.41, 95% CI 0.12–1.42). No effect was associated with smoking, physical activity, hysterectomy, or previous knee injury. Conclusion Obesity and aging are associated with a high risk of new knee OA developing in women. Evidence of a protective effect of ERT was seen. No clear association was found for incident JSN, suggesting that different etiologic mechanisms are operating or that standard radiographs are an inaccurate measure of incident narrowing.

Behçet's disease, the Silk Road and HLA-B51: historical and geographical perspectives.

Abstract: Behcet’s disease (BD), also known as the Silk Road disease, is a blinding inflammatory disorder of young adults found predominantly between the Mediterranean basin and the Orient, and is strongly associated with the major histocompatibility complex (MHC) antigen HLA-B51. In this article we review the history of Behcet’s disease since its first description by Hippocrates, the development of the trading routes collectively known as the Silk Road and the effect of population movement on the distribution of HLA-B51. The global distribution of this antigen among healthy control populations bears a striking similarity both to the ancient trading routes and the distribution of Behcet’s disease, suggesting a genetic risk that migrated in parallel with population movement between the Mediterranean and Asia. However, certain indigenous Amerindian peoples have a high prevalence of HLA-B51 but no reported cases of BD. Furthermore, a clear genealogical relationship exists between eastern, but not central, Siberian populations with the Amerindians. Since a high level of recombination within the MHC is known to have occurred in these eastern populations before their migration into Beringia, we suggest that disruption of genetic loci in linkage disequilibria with HLA-B51 may be one reason for the absence of disease in these high HLA-B51-bearing populations. However, a contributory influence of environmental factors is not excluded by this data, and the wide variation that exists in relative risk of HLA-B51 even within Europe would support other non-genetic risk factors on the Silk Road which may be absent, or non-contributory to disease, in the Americas.

Effects of sildenafil citrate on human hemodynamics.

Abstract: Nitric oxide (NO) induces the formation of intracellular cyclic guanosine monophosphate (cGMP) by guanylate cyclase. Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in men with erectile dysfunction. The NO–cGMP pathway also plays an important role in mediating blood pressure. It is, therefore, possible that the therapeutic doses of sildenafil used to treat erectile dysfunction may have clinically significant effects on human hemodynamics. Three studies were undertaken to assess the effects of intravenously, intra-arterially, and orally administered doses of sildenafil on blood pressure, heart rate, cardiac output, and forearm blood flow and venous compliance in healthy men. A fourth study evaluated the hemodynamic effects of intravenous sildenafil in men with stable ischemic heart disease. In healthy men, significant (p

The Pathogenesis of Edema in Diabetic Maculopathy

Abstract: Diabetic maculopathy is characterized by the accumulation of extracellular fluid in Henle's layer and the inner nuclear layer of the retina. The localization of the edema is likely to be due, in part, to the relative barrier properties of the inner and outer plexiform layers. The origin of the extracellular fluid is from the intravascular compartment. Although changes to retinal blood flow may partly explain the extravasation of fluid, the most important mechanism is breakdown of the blood retinal barriers. Both the inner blood retinal barrier formed by the retinal capillary endothelial cell tight junctions and the outer barrier formed by the retinal pigment epithelial cell tight junctions can be affected. The mechanism of breakdown of the blood retinal barriers is likely to be changes to the tight junction proteins including occludin and ZO-1. The biochemical messenger inducing these changes may be vascular endothelial growth factor. The origin of this or other cofactors may be the retinal glial cells. The underlying biochemical stimulus to the production of vascular endothelial growth factor is chronic hyperglycaemia, but it is uncertain by what pathway this is effected.

Detailed chromosomal and molecular genetic analysis of single cells by whole genome amplification and comparative genomic hybridisation

Abstract: Molecular genetic analysis of isolated single cells and other minute DNA samples is limited because there is insufficient DNA to perform more than one independent PCR amplification. One solution to this problem is to first amplify the entire genome, thus providing enough DNA for numerous subsequent PCRs. In this study we have investigated four different methods of whole genome amplification performed on single cells, and have identified a protocol that generates sufficient quantities of DNA for comparative genomic hybridisation (CGH) as well as more than 90 independent amplification reactions. Thus, numerous specific loci and the copy number of every chromosome can be assessed in a single cell. We report here the first reliable application of CGH to single cells from human preimplantation embryos (blastomeres) and to single fibroblasts, buccal cells and amniocytes.

Brain-derived neurotrophic factor is an endogenous modulator of nociceptive responses in the spinal cord

Abstract: The primary sensory neurons that respond to noxious stimulation and project to the spinal cord are known to fall into two distinct groups: one sensitive to nerve growth factor and the other sensitive to glial cell-line-derived neurotrophic factor. There is currently considerable interest in the ways in which these factors may regulate nociceptor properties. Recently, however, it has emerged that another trophic factor—brain-derived neurotrophic factor (BDNF)—may play an important neuromodulatory role in the dorsal horn of the spinal cord. BDNF meets many of the criteria necessary to establish it as a neurotransmitter/neuromodulator in small-diameter nociceptive neurons. It is synthesized by these neurons and packaged in dense core vesicles in nociceptor terminals in the superficial dorsal horn. It is markedly up-regulated in inflammatory conditions in a nerve growth factor-dependent fashion. Postsynaptic cells in this region express receptors for BDNF. Spinal neurons show increased excitability to nociceptive inputs after treatment with exogenous BDNF. There are both electrophysiological and behavioral data showing that antagonism of BDNF at least partially prevents some aspects of central sensitization. Together, these findings suggest that BDNF may be released from primary sensory nociceptors with activity, particularly in some persistent pain states, and may then increase the excitability of rostrally projecting second-order systems. BDNF released from nociceptive terminals may thus contribute to the sensory abnormalities associated with some pathophysiological states, notably inflammatory conditions.

The effects of 10 years of recombinant human growth hormone (GH) in adult GH-deficient patients.

Abstract: The long term effects of GH replacement in adult GH-deficient (GHD) patients have not yet been clarified. We studied 21 GHD adults who originally took part in a randomized, double blind, placebo-controlled trial of GH treatment in 1987. After completion of that trial, 10 patients received continuous GH replacement for the subsequent 10 yr, whereas 11 did not. A group of 11 age- and sex-matched normal controls were also studied in 1987 and 1997. Lean body mass, as assessed by total body potassium measurement and computed tomography scanning of the dominant thigh, increased in the GH-treated group (P < 0.01 for both) only (P < 0.05 between groups for total body potassium). Low density lipoprotein cholesterol decreased in the GH-treated group (P < 0.05) only. Carotid intima media thickness was significantly greater (P < 0.05) in the untreated group than in the GH-treated group. Assessment of psychological well-being using the Nottingham Health Profile revealed improvement in overall score, energy levels, and emotional reaction in the GH-treated group compared with those in the untreated group (P < 0.02). In conclusion, GH treatment for 10 yr in GHD adults resulted in increased lean body and muscle mass, a less atherogenic lipid profile, reduced carotid intima media thickness, and improved psychological well-being.

Why patients do not attend cardiac rehabilitation: role of intentions and illness beliefs

Abstract: Objective—Many patients fail to attend cardiac rehabilitation. Attempts to identify sociodemographic or clinical predictors of non-attendance have not been very successful; therfore, this study aimed to determine whether the illness beliefs held during hospitalisation by patients who had suVered acute myocardial infarction or who had undergone coronary artery bypass graft surgery could predict cardiac rehabilitation attendance. Subjects and methods—152 patients were prospectively studied of whom 41% had attended cardiac rehabilitation at six months. Results—In addition to being older, less aware of their cholesterol values, and less likely to be employed, non-attenders were less likely to believe their condition was controllable and that their lifestyle may have contributed to their illness. Conclusion—It should now be determined whether interventions aimed at optimising certain perceptions could promote cardiac rehabilitation uptake among those patients who could benefit the most. (Heart 1999;82:234‐236)

Retroversion of the acetabulum

Abstract: We describe a little-known variety of hip dysplasia, termed ‘acetabular retroversion’, in which the alignment of the mouth of the acetabulum does not face the normal anterolateral direction, but inclines more posterolaterally.The condition may be part of a complex dysplasia or a single entity. Other than its retroversion, the acetabulum is sited normally on the side wall of the pelvis, and its articular surface is of normal extent and configuration. The retroverted orientation may give rise to problems of impingement between the femoral neck and anterior acetabular edge.We define the clinical and radiological parameters and discuss pathological changes which may occur in the untreated condition. A technique of management is proposed.

The influence on survival of delay in the presentation and treatment of symptomatic breast cancer.

Abstract: The aim of this study was to examine the possible influence on survival of delays prior to presentation and/or treatment among women with breast cancer. Duration of symptoms prior to hospital referral was recorded for 2964 women who presented with any stage of breast cancer to Guy’s Hospital between 1975 and 1990. Median follow-up is 12.5 years. The impact of delay (defined as having symptoms for 12 or more weeks) on survival was measured from the date of diagnosis and from the date when the patient first noticed symptoms to control for lead-time bias. Thirty-two per cent (942/2964) of patients had symptoms for 12 or more weeks before their first hospital visit and 32% (302/942) of patients with delays of 12 or more weeks had locally advanced or metastatic disease, compared with only 10% (210/2022) of those with delays of less than 12 weeks (P< 0.0001). Survival measured both from the date of diagnosis (P< 0.001) and from the onset of the patient’s symptoms (P= 0.003) was worse among women with longer delays. Ten years after the onset of symptoms, survival was 52% for women with delays less than 12 weeks and 47% for those with longer delays. At 20 years the survival rates were 34% and 24% respectively. Furthermore, patients with delays of 12–26 weeks had significantly worse survival rates than those with delays of less than 12 weeks. Multivariate analyses indicated that the adverse impact of delay in presentation on survival was attributable to an association between longer delays and more advanced stage. However, within individual stages, longer delay had no adverse impact on survival. Analyses based on ‘total delay’ (i.e. the interval between a patient first noticing symptoms and starting treatment) yielded very similar results in terms of survival to those based on delay to first hospital visit (delay in presentation).

A high incidence of vertebral fracture in women with breast cancer.

Abstract: Because treatment for breast cancer may adversely affect skeletal metabolism, we investigated vertebral fracture risk in women with non-metastatic breast cancer. The prevalence of vertebral fracture was similar in women at the time of first diagnosis to that in an age-matched sample of the general population. The incidence of vertebral fracture, however, was nearly five times greater than normal in women from the time of first diagnosis [odds ratio (OR), 4.7; 95% confidence interval (95% CI), 2.3-9.9], and 20-fold higher in women with soft-tissue metastases without evidence of skeletal metastases (OR, 22.7; 95% CI, 9.1-57.1). We conclude that vertebral fracture risk is markedly increased in women with breast cancer.

Haploinsufficiency of desmoplakin causes a striate subtype of palmoplantar keratoderma.

Abstract: Desmosomes are highly organized intercellular adhesive junctions that are particularly prominent in epidermis and other tissues experiencing mechanical stress. Desmoplakin, a constitutive component of the desmosomal plaque, is the most abundant protein present in such junctions and plays a critical role in linking the intermediate filament network to the plasma membrane in these tissues. Here we report the first mutation in the gene encoding desmoplakin. The identified mutation, resulting in a null allele and haploinsufficiency, was observed in genomic DNA from a kindred with the dominantly inherited skin disorder, striate palmoplantar keratoderma. Affected individuals had a linear pattern of skin thickening on the fingers and palms and circumscribed areas of skin thickening on the soles. Affected skin demonstrated loosening of intercellular connections, disruption of desmosome‐keratin intermediate filament interactions and a proportion of rudimentary desmosomal structures. The disorder mapped to chromosome 6p21 with a maximum lod score of 10.67. The mutation was a heterozygous C∀ T transition in exon 4 of the desmoplakin gene and predicted a premature termination codon in the N-terminal region of the peptide. This is the first reported mutation of desmoplakin and also the first inherited skin disorder in which haploinsufficiency of a structural component has been implicated. It identifies dosage of desmoplakin as critical in maintaining epidermal integrity.

Substantial superiority of semiflexed (MTP) views in knee osteoarthritis: a comparative radiographic study, without fluoroscopy, of standing extended, semiflexed (MTP), and schuss views.

Abstract: Objective. To improve the radiographic assessment of cartilage loss, as measured by joint space width (JSW) in patients with osteoarthritis (OA) of the knees required to detect the effect of structure modifying drugs in OA trials. This was achieved by determining which of 3 nonfluoroscopic radiographic views - standing extended, semiflexed, and schuss - produced the most accurate radioanatomic positioning of the joint and greater reproducibility in joint repositioning and JSW measurement. Methods. Knees from 74 patients with OA of the knees who had medial tibiofemoral compartment JSW ≥2 mm in all views were studied. For all 3 radiographic views, accuracy in the radioanatomic positioning of the knee was determined for both joint rotation and flexion. Reproducibility in joint repositioning and JSW measurement were determined from the difference between repeat examinations taken within 2 h. Results. About 86% of knees in the 3 views had accurate rotational position of the joint at each visit. Radioanatomically, knees in the semiflexed view were significantly more accurately positioned in regard to knee flexion (p < 0.0005) than in the schuss view, which in turn was better (p < 0.014) than in the extended knee view. Joint repositioning was significantly more reproducible in the semiflexed (p <0.0001) than in the extended knee, which was better (p <0.013) than in the schuss position. JSW measurement was significantly more reproducible in the semiflexed (p < 0.014) than both schuss and extended knee positions, which were not significantly different from each other. Conclusion. Protocols defining the nonfluoroscopic radiographic procedures for the semiflexed view provide the most accurate radioanatomic joint positioning, and the most reproducible joint repositioning and JSW measurement. Using this method significantly fewer knees would be required to detect significant JSW changes in a structure modifying drug trial compared to the schuss and the extended knee positions.

Thoughts on sensitizers in a standard patch test series. The European Society of Contact Dermatitis.

Abstract: Patch testing is the predominant method of establishing contact allergy. The present patch test technique is the result of a continuous process of development and improvement since its first application in the late 19th century. The perfect patch test should give no false-positive and no false-negative reactions. The ideal patch test should also cause as few adverse reactions as possible, particularly no patch test sensitization. Even though the history and examination of a patient with suspected allergic contact dermatitis will give clues to possible sensitizers, it is not sufficient to patch test only with initially suspected sensitizers; unsuspected sensitizers used for patch testing frequently turn out to be the real cause of the dermatitis. Fortunately, a small number of substances are considered to account for the majority of delayed hypersensitivity reactions. Therefore, generally 20-25 test preparations consisting of chemically defined compounds, mixes of allergens, and natural and synthetic compounds, are grouped into a standard test series. The requirements to be fulfilled by a sensitizer in a standard patch test series are discussed in this article. A procedure of investigations is proposed before a sensitizer is included in a standard series.