Norbert Kang

Hypoxia upregulates angiogenesis and synovial cell migration in rheumatoid arthritis

IntroductionRheumatoid arthritis (RA) is characterised by invasion of cartilage, bone and tendon by inflamed synovium. Previous studies in our laboratory have shown that hypoxia is a feature of RA synovitis. In the present study, we investigated the consequences of hypoxia on angiogenesis and synovial fibroblast migration in RA.MethodsSynovial tissue was harvested from RA patients, and synovial membrane cells were cultured under conditions either of hypoxia (1% oxygen) or normoxia (21% oxygen). Protein levels of matrix metalloproteinases (MMPs) and angiogenic factors were measured, while RNA was extracted for PCR quantification of MMPs/tissue inhibitors of MMP (TIMPs) and angiogenic factors. Migration of RA synovial fibroblasts through collagen, and the effect of RA synovial cell supernatants in an in vitro angiogenesis assay, were utilised to determine the functional relevance of changes in mRNA/protein.ResultsWe observed upregulation under hypoxic conditions of MMPs responsible for collagen breakdown, specifically collagenase MMP-8, and the gelatinases MMP-2 and MMP-9, at both mRNA and protein levels. Increased MT1-MMP mRNA was also observed, but no effect on TIMP-1 or TIMP-2 was detected. RA fibroblast migration across collagen was significantly increased under hypoxic conditions, and was dependent on MMP activity. Furthermore, expression of angiogenic stimuli, such as vascular endothelial growth factor (VEGF), and VEGF/placental growth factor heterodimer, was also increased. Crucially, we show for the first time that hypoxia increased the angiogenic drive of RA cells, as demonstrated by enhanced blood vessel formation in an in vitro angiogenesis assay.ConclusionsHypoxia may be responsible for rendering RA synovial lining proangiogenic and proinvasive, thus leading to the debilitating features characteristic of RA.

A morphometric study of the human ear

AIMS We examined variations in the shape of the human ear according to age, sex and ethnic group with particular attention to ear prominence. METHODS 420 volunteers were recruited. Measurements included; head height and length, ear height and axis, antihelix taken off angle, earlobe length and width, ear width at the helical root and tragus. Prominence was measured at the helical root and tragus (conchomastoid angle, conchal bowl depth and helical-mastoid distance). RESULTS Good symmetry was shown for all measurements. Ethnically Indian volunteers had the largest ears (both length and width), followed by Caucasians, and Afro-Caribbeans. This trend was significant in males (p<0.001), but not significant in females (p=0.087). Ears increased in size throughout life. Subjectively, only 2% of volunteers felt their ears were prominent compared to 10% in the opinion of the principal investigator. No objective measurements were identified that accurately predicted subjective perceptions of prominence. CONCLUSIONS We found consistent trends in ear morphology depending on ethnic group, age and sex. Our study was unable to define an objective method for assessing ear prominence. Decisions about what constitutes a prominent ear should be left to personal and aesthetic choice.

Patient satisfaction and aesthetic outcomes after ear reconstruction with a Branemark-type, bone-anchored, ear prosthesis: A 16 year review

INTRODUCTION Reconstruction of the human ear with a bone-anchored prosthesis is a widely accepted alternative when autologous reconstruction is technically impossible or declined by the individual. However, there are relatively few data in the literature documenting patient satisfaction with this form of reconstruction. METHODS This study examines different aspects of patient satisfaction using an eighteen-point postal questionnaire to measure patient outcomes against a Likert rating scale. The questionnaire was sent to 33 patients who completed prosthetic ear reconstruction over a 16 year period at a specialist plastic surgery unit in the United Kingdom. Medical case notes for these cases were also reviewed. Twenty completed questionnaires were returned. RESULTS The response rate was 61%. The majority of patients were satisfied with the aesthetics, ease of handling and comfort of the bone-anchored implant and prosthesis. However, the majority of patients was only moderately satisfied or was dissatisfied with this method of reconstruction. Specifically, 15 of the respondents reported skin problems around the abutments of the bone-anchored implant with 10 patients reporting ongoing skin complications. Granulation tissue was the most common skin problem (12 cases) followed by local infection (10 cases). Interestingly, despite the chronic skin problems, most patients indicated that they would undergo the same procedure again or would recommend it to others. DISCUSSION Our survey shows that patients fitted with a Branemark-type bone-anchored implant for ear reconstruction are pleased with the aesthetic appearance but experience multiple, chronic, skin complications and other implant related problems. These affect their satisfaction with this method of reconstruction. Our findings may have significant implications for patients and surgeons considering this form of reconstruction and for the institutions making decisions about funding this treatment.

Use of ITAP implants for prosthetic reconstruction of extra-oral craniofacial defects

We report the outcomes of a single-stage, surface-mounted implant used as a bone-anchor for prosthetic reconstruction of complex facial defects. The implant used differs from other designs of osseointegrated bone-anchor because it was designed to be implanted in one-stage with the added intention of integrating with the adjacent soft-tissue. Our aim was to extend the principles underlying the intraosseous transcutaneous amputation prosthesis (ITAP) into the design of infection-free implants suitable for direct skeletal attachment of a prosthesis to the craniofacial skeleton. The implants were manufactured incorporating a porous flange structure coated with hydroxyapatite to encourage soft-tissue integration. These were inserted into the cranial facial skeleton at a number of different sites in 6 adult patients. A total of 16 implants were inserted using a one-stage procedure and implants were followed up for periods of 18 months - 7 years. One implant loosened at 3 months. This implant experienced multiple episodes of infection and was replaced with another ITAP implant 4 years later. The replacement is now stable and has never been infected at 18 months after insertion. One other patient experienced a few minor episodes of superficial infection (not requiring antibiotics) in the first year but no episodes thereafter. One patient died during follow-up (death unrelated to implant surgery). Patients were asked for their personal opinions using a structured questionnaire. All the patients were either very satisfied, or satisfied with their ITAP implants. Two patients reported problems with skin irritation under their prosthesis. All would be happy to undergo this type of surgery again. We conclude that a single-stage, surface-mounted implant designed to incorporate the principles of ITAP can be used to produce an effective bone-anchor for an external prosthesis in the reconstruction of complex craniofacial defects.

Epithelioid hemangioendothelioma: Occasionally encountered and potentially harmful

Epithelioid hemangioendothelioma (EH) is a rare neoplasm which can arise from any vascularised tissue and has the potential to metastasise. Correct diagnosis can be challenging as it has a variety of presentations and can mimic other pathology. We present a case arising from the brachial artery at the level of the antecubital fossa. Incision biopsies showed benign fatty tissue only; leading to delayed diagnosis, delayed excision and prolonged patient discomfort. This case shows the importance of exercising clinical judgement as negative incision biopsies were, with hindsight, not representative of the lesion.

Reconstruction in the axilla with a pedicled pectoralis minor muscle flap.

Covering large defects in the axillary fossa can be challenging because of its complex shape. A variety of local skin, fasciocutaneous and musculocutaneous flaps have been described, with a number of inherent advantages and disadvantages. The use of the pectoralis minor muscle as a pedicled transposition flap has been described for immediate reconstruction of the breast, anterior shoulder reconstruction and the treatment of bronchopleural fistula. We now describe the use of a pedicled pectoralis minor muscle flap for soft tissue coverage of the axillary contents after wide excision of the axilla. This has not been previously described.

Correction of the hypertrophic conchal bowl without cartilage excision

We present our technique for conchal bowl reduction. The procedure is fast, easy to learn and reproducible. The technique has now been used in a consecutive series of 208 ears. We describe the steps taken and the outcomes. The main aims of this procedure were; the preservation of conchal bowl width and avoidance of cartilage excision. This cartilage can then be used for grafting if a rhinoplasty is considered in the future.

Defining Normal Parameters for the Male Nipple-Areola Complex: A Prospective Observational Study and Recommendations for Placement on the Chest Wall

Background The nipple-areola complex (NAC) is important aesthetically and functionally for both sexes. Methods for positioning the NAC in males are less well established in the literature compared to females but are just as important. Objectives This study aims to determine the normal parameters for the male NAC, to review literature, and to present a reliable method for preoperative placement. Methods Normal male patients, with no prior chest wall conditions, were prospectively recruited to participate. General demographics and chest wall dimensions were recorded-sternal notch to nipple (SNND), internipple (IND), anterior axillary folds distances (AFD), NAC, and chest circumference were measured. Comparisons were made using t test and ANOVA. Results One hundred and fifty-eight patients were recruited (age range, 18-90 years); mostly (86.7%) with normal or overweight BMI. The IND averaged 249.4 mm, the SNND averaged 204.2 mm, and the AFD averaged 383.8 mm. Areola diameter averaged 26.6 mm and for the nipple, 6.9 mm. The IND:AFD ratio was 0.65. There was no statistical difference in the IND:AFD ratio, SNND, or NAC parameters comparing different ethnic groups. The SNND increased with greater BMI (P ≤ 0.001). Using these data, we suggest ideal NAC dimensions and devised a simple method for positioning of the NAC on the male chest wall. Conclusions This is the largest study, with the widest range in age and BMI, to date on this topic. Although fewer men than women undergo surgery to the breast, there is a growing awareness for enhancing the appearance of the male chest wall. Level of Evidence 4

Earfold: A New Technique for Correction of the Shape of the Antihelix: Earfold for Correction of Prominent Ears

An absent or poorly defined antihelix often plays a central role in the perception of the prominent ear. A wide variety of otoplasty techniques have been described over the last 50 years that aim to reshape, create, or enhance the definition of the antihelix, which can, in turn, help to reduce the prominence of an ear. In addition to conventional suture and cartilage‐scoring techniques, a permanent implantable clip system (Earfold®) has recently become available that is placed using a minimally invasive approach performed under local anesthesia. In this review, we summarize conventional otoplasty techniques to correct the antihelix and compare these with the Earfold implantable clip system. Laryngoscope, 128:2282–2290, 2018

Ectopic Dupuytren's disease in the wrist compressing the palmar cutaneous branch of the median nerve

A case report to describe the occurrence of Dupuytrens disease in the wrist leading to compression of the palmar cutaneous branch of the median nerve. A 60-year-old male presented with a lump on the volar aspect of the left wrist with reduced sensation in the thenar eminence. Intra-operatively this was found to be a nodule integrated within the palmaris longus tendon and positioned superficially to the palmar cutaneous branch of the median nerve. Histological findings were consistent with Dupuytrens disease and the patients symptoms improved post excision of the nodule. Although Dupuytrens nodules occur rarely in the wrist, they should be considered as part of the differential diagnosis of wrist lumps and they have the potential to impact on nearby neural structures.