Recent record of the U.K. to publication in top dermatology journals.
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Bibliometrics↗
Biomedical subjects
J L Rees
Publications and source records attributed to J L Rees.
A 2005 survey of clinical academic staff in U.K. dermatology.
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Career Choice↗
Pathology of the torn rotator cuff tendon. Reduction in potential for repair as tear size increases.
We have studied cellular and vascular changes in different stages of full thickness tears of the rotator cuff. We examined biopsies from the supraspinatus tendon in 40 patients with chronic rotator cuff tears who were undergoing surgery and compared them with biopsies from four uninjured subscapularis tendons. Morphological and immunocytochemical methods using monoclonal antibodies directed against leucocytes, macrophages, mast cells, proliferative and vascular markers were used. Histological changes indicative of repair and inflammation were most evident in small sized rotator cuff tears with increased fibroblast cellularity and intimal hyperplasia, together with increased expression of leucocyte and vascular markers. These reparative and inflammatory changes diminished as the size of the rotator cuff tear increased. Marked oedema and degeneration was seen in large and massive tears, which more often showed chondroid metaplasia and amyloid deposition. There was no association between the age of the patient and the duration of symptoms. In contrast, large and massive tears showed no increase in the number of inflammatory cells and blood vessels. Small sized rotator cuff tears retained the greatest potential to heal, showing increased fibroblast cellularity, blood vessel proliferation and the presence of a significant inflammatory component. Tissue from large and massive tears is of such a degenerative nature that it may be a significant cause of re-rupture after surgical repair and could make healing improbable in this group.
Adult↗
A repetitive movement detector used for automatic monitoring and quantification of scratching in mice.
We have designed an economical non-invasive movement detector for small animal studies and used it for monitoring and quantifying itch in mice. The system is based on a sensitive force transducer positioned below a recording platform holding a lightweight polystyrene recording box in which an animal is placed. A programmed micro-controller is used to discriminate between non-specific movement, grooming behaviour, and scratching movements made by the animal's hind limb. Following sub-dermal injection of histamine receptor agonists into the neck of a mouse, dose-related scratching occurred which was detected and quantified. There was 91% correlation between bouts of scratching as counted manually from playback of the video recording and recorded by the detector. The detector was also able rapidly to count the individual scratch movements of the hind limb that comprise a bout, with 95% accuracy in comparison with manual counting during slow motion playback of video tape, something that is impossible for an unaided observer to achieve because individual scratch movements are too fast to discriminate by eye. Separate detectors were used for the efficient non-invasive study of four animals simultaneously, and this number could easily be increased by adding more platforms. The system could also be modified to record the animal's position within the box, which would be of value in studies involving exploratory behaviour. In summary, the non-invasive multichannel repetitive movement detector will be very useful for accurate measurement of scratching during pruritus studies in small animals, with considerable savings in staff time and effort. It should therefore be a valuable tool for helping to investigate pruritus and in the evaluation of anti-pruritic drugs.
Animals↗
Real in vivo kinematic differences between mobile-bearing and fixed-bearing total knee arthroplasties.
We did an in vivo fluoroscopic study comparing the sagittal plane kinematics of mobile-bearing and fixed-bearing total knee arthroplasties in a unique group of patients. These patients were part of a larger bilateral randomized controlled outcome trial with each patient having received both types of total knee arthroplasties. Invited patients did three exercises with each of their different knee replacements; extension against gravity, flexion against gravity, and a step-up. These exercises were recorded using video fluoroscopy, and a series of still digital images over the flexion range were retrieved. The relationship of patella tendon angle to knee flexion angle for each patient was derived. The patella tendon angle to knee flexion angle of the mobile-bearing knee behaved in a linear manner more closely replicating the normal knee, whereas the fixed-bearing knee behaved in a nonlinear, more variable manner. This pattern of results was similar for all three exercises with each patient having one knee replacement that behaved differently in the sagittal plane when compared with their other knee replacement. These kinematic differences may explain the clinical differences observed in the randomized controlled trials that compared these two total knee arthroplasties.
Adult↗
Involvement of histamine H4 and H1 receptors in scratching induced by histamine receptor agonists in Balb C mice.
The role of histamine H(1), H(2), H(3) and H(4) receptors in acute itch induced by histamine was investigated in female BalbC mice. Scratching was induced by intradermal injections of pruritogen into the back of the neck and "itch" assessed by quantifying the scratching evoked. Histamine (0.03-80 micromol), histamine-trifluoromethyl-toluidine (HTMT, H(1) agonist, 0.002-2 micromol), clobenpropit (H(4) agonist, H(3) antagonist, 0.002-0.6 micromol) and to a lesser extent imetit (H(3)/H(4) agonist, 0.03-3 micromol) all induced dose-dependent scratching. Dimaprit (H(2) agonist, 0.04-40 micromol) did not cause scratching. Mepyramine (H(1) antagonist, 20 mg kg(-1), i.p.) reduced scratching evoked by histamine and HTMT, but not that caused by H(3) or H(4) agonists. Thioperamide (H(3)/H(4) antagonist, 20 mg kg(-1), i.p.) reduced scratching induced by histamine, H(3) and H(4) agonists, but not that caused by HTMT. The non-sedating H(1) antagonist, terfenadine, also significantly reduced the scratching induced by the H(1) agonist, HTMT. Cimetidine (H(2) antagonist, 20 mg kg(-1), i.p.) did not affect histamine-induced scratching. These results indicate that activation of histamine H(4) receptors causes itch in mice, in addition to the previously recognised role for H(1) receptors in evoking itch. Histamine H(4) receptor antagonists therefore merit investigation as antipruritic agents.
Animals↗
Minimally invasive Oxford unicompartmental knee arthroplasty: functional results at 1 year and the effect of surgical inexperience.
Oxford medial unicompartmental arthroplasty (UCA) is now routinely performed through a short incision without dislocation of the patella. We present the 1 year results of the first 104 knees operated in Oxford using this technique and the learning curve associated with it. The patient's average age at surgery was 68 years. The average American Knee Society 'knee score' improved from 37 to 94 points and the average 'functional score' from 50 to 92 points. Average maximum flexion improved from 117 to 131 degrees. The average knee score during a surgeon's first 10 cases was 88 points, which was significantly less (P<0.03) than the score achieved for subsequent cases after the first 10 (95 points). These data suggest for the first time that a learning curve exists with worse results being achieved during a surgeon's first 10 cases. However, the results during the learning curve are still similar to that achieved after total knee arthroplasty.
Aged↗
Defining the quantitative contribution of the melanocortin 1 receptor (MC1R) to variation in pigmentary phenotype.
The melanocortin 1 receptor (MC1R) is a key determinant of pigmentary phenotype. Several sequence variants of the MC1R have been described, many of which are associated with red hair and cutaneous sensitivity to ultraviolet radiation even in the absence of red hair. Red hair approximates to an autosomal recessive trait, and most people with red hair are compound heterozygote or homozygous for limited numbers of mutations that show impaired function in in vitro assays. There is a clear heterozygote effect on sun sensitivity (even in those without red hair) and with susceptibility to the most common forms of skin cancer.
Animals↗
A mobile-bearing total knee prosthesis compared with a fixed-bearing prosthesis. A multicentre single-blind randomised controlled trial.
Before proceeding to longer-term studies, we have studied the early clinical results of a new mobile-bearing total knee prosthesis in comparison with an established fixed-bearing device. Patients requiring bilateral knee replacement consented to have their operations under one anaesthetic using one of each prosthesis. They also agreed to accept the random choice of knee (right or left) and to remain ignorant as to which side had which implant. Outcomes were measured using the American Knee Society Score (AKSS), the Oxford Knee Score (OKS), and determination of the range of movement and pain scores before and at one year after operation. Preoperatively, there was no systematic difference between the right and left knees. One patient died in the perioperative period and one mobile-bearing prosthesis required early revision for dislocation of the meniscal component. At one year the mean AKSS, OKS and pain scores for the new device were slightly better (p < 0.025) than those for the fixed-bearing device. There was no difference in the range of movement. We believe that this is the first controlled, blinded trial to compare early function of a new knee prosthesis with that of a standard implant. It demonstrates a small but significant clinical advantage for the mobile-bearing design.
Aged↗
Safety to drive after common limb fractures.
One hundred Orthopaedic Consultants in the UK were randomly selected and asked to complete a postal questionnaire indicating when they felt patients with treated, pain free, common limb fractures could return to driving. Seventy-two questionnaires were returned. Six were not completed leaving 66 completed questionnaires. Analysis revealed a clear mandate to allow or prevent driving in patients with certain treatment modalities and stages of union. In the lower limb there was majority agreement of suitability to drive in 61% of the 28 presented scenarios. Opinion was more divided for the upper limb, with only 43% of the scenarios having majority agreement. Our results show that while for some common limb fractures there is a clear body of opinion supporting safety to drive, for other common fractures opinion is less clear cut. This has important financial, medico-legal and legal implications that could be resolved by formal testing.
Arm Injuries↗
Defining the femoral axis on lateral knee fluoroscopy.
The methodological detail about determining the femoral axis on lateral fluoroscopic images of the knee is lacking. This paper reports on the use of the posterior border of the lower femoral diaphysis to represent the axis. This method is accurate, simple, reliable and can be used by researchers studying knee joint kinematics using dynamic video fluoroscopy. It is also useful in the outpatient clinic to assess the flexion/extension position of femoral components after knee arthroplasty.
Arthroplasty, Replacement, Knee↗
Accelerated recovery for unicompartmental knee replacement--a feasibility study.
A pilot study assessed the feasibility of discharging NHS patients undergoing knee replacement within a day of surgery. Seven patients with medial compartment osteoarthritis were recruited after fulfilling strict exclusion criteria. Pre-operative assessment revealed that all patients had significant dysfunction and pain before operation. They had medial unicompartmental replacement through a short incision without dislocation of the patella. Each patient underwent an accelerated recovery program that included pain control, physiotherapy and self-assessment. Patients were mobilised immediately after operation. Follow-up assessment was performed at 1, 2 and 6 weeks after surgery. All patients, except one (who failed to go home because of an administrative error), returned home the day after surgery. The average pain score for the first 2 weeks after surgery was 2/10. At 6 weeks, knee flexion averaged 125 degrees and all patients were walking independently and painfree. The new protocol allows for early, safe discharge of patients undergoing unicompartmental knee replacement.
Aged↗
A kinematic study of lateral unicompartmental arthroplasty.
When the Oxford unicompartmental meniscal bearing arthroplasty (UCA) is used in the lateral compartment 10% of the bearings dislocate. A fluoroscopic study was performed to investigate if abnormal mid-sagittal plane kinematics was related to bearing dislocation. Video fluoroscopy is an accepted means of determining in-vivo knee kinematics in the sagittal plane. Video fluoroscopy was obtained of 5 Oxford lateral UCAs 10 years post-operatively and of five normal knees. Patellar tendon angle (PTA), derived from dynamic fluoroscopic images, was used to describe the joint kinematics. This in-vivo experiment demonstrated that the PTA/knee relationship for the Oxford lateral UCA is similar to the normal knee. Both the normal knee (r(2)=0.99) and the Oxford lateral UCA (r(2)=0.98) demonstrated a linear relationship between flexion angle and PTA. No significant difference in PTA was found between the normal knee and the Oxford lateral UCA. This study demonstrated normal kinematics, as indicated by PTA, ten years after implantation of the Oxford lateral UCA. It is therefore reasonable to suggest that abnormal kinematics is not a significant factor relating to meniscal bearing dislocation in the lateral compartment.
Adult↗
What is the 'true' function of skin?
Conventional textbook wisdom portrays the skin as an organ that literally enwraps whatever each of us stands for as a more or less functional, individual member of the mammalian species, and has it that the skin primarily establishes, controls and transmits contacts with the external world. In addition, the skin has long been recognized to protect the organism from deleterious environmental impacts (physical, chemical,microbiological), and is well-known as crucial for the maintenance of temperature, electrolyte and fluid balance. Now, ever more studies are being published that show the skin to also operate as a huge and highly active biofactory for the synthesis,processing and/or metabolism of an astounding range of e.g. structural proteins, glycans, lipids and signaling molecules. Increasingly, it becomes appreciated that the skin, furthermore, is an integral component of the immune, nervous and endocrine systems, with numerous lines of cross-talk between these systems established intracutaneously (e.g. Ann NY Acad Sci Vol 885, 1999; Endocrine Rev 21:457-487, 2000; Physiol Rev 80:980-1020, 2001; Exp Dermatol 10: 349-367, 2001). All these emerging cutaneous functions beyond the classical image of the skin as a barrier and sensory organ are immediately relevant for many of the quandaries that clinical dermatology, dermatopathology, and dermatopharmacology are still struggling with to-date, and offer the practising dermatologist attractive new targets for therapeutic intervention. Yet, many of these skin functions are not even mentioned in dermatology textbooks and await systematic therapeutic targeting. Following a suggestion by Enno Christophers, the current 'Controversies' feature brings together an unusually diverse council of biologists and clinicians, who share their thought-provoking views with the readers and allow us to peek into the future of research in cutaneous biology, not the least by reminding us of the -- often ignored -- evolutionary and embryonal origins of our favorite organ. Hopefully, this unique discussion feature will foster an understanding of the 'true' skin functions that is both more comprehensive and more profound than conventional teaching on this topic, and will stimulate more than 'skin-deep' reflections on the full range of skin functions.
Aging↗
Dislocation of the bearing of the Oxford lateral unicompartmental arthroplasty. A radiological assessment.
When the Oxford unicompartmental meniscal bearing arthroplasty is used in the lateral compartment of the knee, 10% of the bearings dislocate. A radiological review was carried out to establish if dislocation was related to surgical technique. The postoperative radiographs of 46 lateral unicompartmental arthroplasties were analysed. Five variables which related to the position and alignment of the components were measured. Dislocations occurred in six knees. Only one of the five variables, the proximal tibial varus angle, had a statistically significant relationship to dislocation. This variable quantifies the height of the lateral joint line. The mean proximal tibial varus angle for knees the bearings of which had dislocated was 9 degrees and for those which had not it was 5 degrees. In both groups it was greater than would be expected in the normal knee (3 degrees). Our study suggests that a high proximal tibial varus angle is associated with dislocation. The surgical technique should be modified to account for this, with care being taken to avoid damage to or overdistraction of the lateral soft tissues.
Aged↗
Functional variation of MC1R alleles from red-haired individuals.
Red hair in humans is associated with variant alleles of the alphaMSH receptor gene, MC1R. Loss of MC1R function in other mammals results in red or yellow hair pigmentation. We show that a mouse bacterial artificial chromosome (BAC) which contains Mc1r will efficiently rescue loss of Mc1r in transgenic mice, and that overexpression of the receptor suppresses the effect of the endogenous antagonist, agouti protein. We engineered the BAC to replace the mouse coding region with the human MC1R sequence and used this in the transgenic assay. The human receptor also efficiently rescued Mc1r deficiency, and in addition, appeared to be completely resistant to the effects of agouti, suggesting agouti protein may not play a role in human pigmentary variation. Three human variant alleles account for 60% of all cases of red hair. We engineered each of these in turn into the BAC and find that they have reduced, but not completely absent, function in transgenic mice. Comparison of the phenotypes of alphaMSH-deficient mice and humans in conjunction with this data suggests that red hair may not be the null phenotype of MC1R.
Alleles↗
Expression, candidate gene, and population studies of the melanocortin 5 receptor.
In mouse the melanocortin 5 receptor is known to regulate sebaceous gland function. To clarify its role in man, we have studied melanocortin 5 receptor expression in skin, and allelic variation at the melanocortin 5 receptor locus in diverse human populations and candidate disease groups. Melanocortin 5 receptor protein and mRNA expression were studied by immunohistochemistry and reverse transcriptase polymerase chain reaction. Melanocortin 5 receptor mRNA was detected in normal skin and cultured keratinocytes but not in cultured fibroblasts or melanocytes. Immunohistochemistry revealed melanocortin 5 receptor immunoreactivity in the epithelium and appendages, including the sebaceous gland, eccrine glands, and apocrine glands, as well as low level expression in the interfollciular epidermis. In order to screen for genetic diversity in the melanocortin 5 receptor that might be useful for allelic association studies we sequenced the entire melanocortin 5 receptor coding region in a range of human populations. One nonsynonymous change (Phe209Leu) and four synonymous changes (Ala81Ala, Asp108Asp, Ser125Ser, and Thr248Thr) were identified. Similar results were found in each of the populations except for the Inuit in which only the Asp108Asp variant was seen. The apparent "global distribution" of melanocortin 5 receptor variants may indicate that they are old in evolutionary terms. Variation of melanocortin 5 receptor was examined in patients with acne (n = 21), hidradenitis supprativa (n = 4), and sebaceous gland lesions comprising sebaceous nevi, adenomas, and hyperplasia (n = 13). No additional mutations were found. In order to determine the functional status of the Phe209Leu change, increase in cAMP in response to stimulation with alpha-melanocyte-stimulating hormone was measured in HEK-293 cells transfected with either wild-type or the Phe209Leu variant. The variant melanocortin 5 receptor was shown to act in a concentration-dependent manner, which did not differ from that of wild type. We have therefore found no evidence of a causative role for melanocortin 5 receptor in sebaceous gland dysfunction, and in the absence of any association between variation at the locus and disease group, the pathophysiologic role of the melanocortin 5 receptor in man requires further study.
Acne Vulgaris↗
The relation between melanocortin 1 receptor genotype and experimentally assessed ultraviolet radiation sensitivity.
Pigmentary phenotype is a key determinant of an individual's response to ultraviolet radiation with the presence of phaeomelanin thought to be of particular importance. Reports of minimal erythema testing, however, have failed to show a consistent difference between skin type I and other skin types. The melanocortin 1 receptor is a key genetic determinant of the cutaneous response to ultraviolet radiation. In this study we investigate the relation between experimentally induced erythemal response to ultraviolet radiation and the melanocortin 1 receptor genotype. Phototesting was performed in 20 redheads and 20 nonredheaded subjects, the majority of whom were also screened for the presence of melanocortin 1 receptor variants. The majority of redheads sequenced (89%) had two melanocortin 1 receptor variants previously found to be associated with red hair compared to none of the controls. There was no significant difference between the groups in minimal erythema dose: the median minimal erythema dose in redheads was 44 mJ per cm2 (interquartile range 34-56) and in the nonredheaded group was 40 mJ per cm2 (interquartile range 40-56). Objective measurements of ultraviolet-B-induced erythema were performed using reflectance instrument measurements of erythema intensity and dose-response curves constructed for each subject. The slope of the dose-response curve in the redheaded group was statistically greater than in the nonredheaded group (median in redheads 4.08 vs 3.56 for controls, 95% confidence interval for the difference between the medians being 0.01-1.23, p = 0.043). In addition the ratio D0.05:D0.025 was significantly lower for the redheaded group (median in redheads 1.22, interquartile range 1.18-1.26; median in nonreds 1.28, interquartile range 1.23-1.32; p < 0.05). Thus, although the minimal erythema dose values were not different, subjects with red hair develop greater intensity of erythema than nonredheaded individuals when doses greater than the minimal erythema dose are given. Importantly, when analyzed by genotype alone rather than phenotype, the slope of the erythema dose-response differed between those persons who were homozygous or heterozygous mutants and wildtype/pseudo-wildtype (p = 0.026).
Adult↗