First report of an imported case of haemorrhagic fever with renal syndrome in South Africa.

Haemorrhagic fever with renal syndrome (HFRS) is caused by hantavirus infection. Hantaviruses are not endemic to South Africa, and we report the first detection of an imported case of HFRS in the country. The case involved a traveller from Croatia who presented to a Johannesburg hospital with an acute febrile illness with renal dysfunction. The patient reported visiting rurally located horse stables in Croatia before falling ill, and that a worker in the stables with similar illness was diagnosed with HFRS. Given the exposure history and clinical findings of the case, a clinical diagnosis of HFRS was made and confirmed by laboratory testing.

A rare complication of radiofrequency treatment for cellulite of the lower leg.

Radiofrequency (RF) is increasingly used as an aesthetic treatment for a variety of purposes ranging from the treatment of acne scarring, cellulite correction and skin and soft tissue rejuvenation. The majority of patients experience no complications, and the treatment is therefore also frequently administered by non-medically trained staff. We present a patient, who developed severe 3rd degree burn after RF treatment requiring reconstructive surgery with a split thickness skin graft.

Necrotizing fasciitis caused by mono-bacterial gram-negative infection with E. coli - the deadliest of them all: A case series and review of the literature.

INTRODUCTION: Unlike other skin and soft tissue infections, necrotizing fasciitis (NF) is a very rare but potentially fatal condition. Common organisms causing NF are poly-microbial (type I) infection with mixed organisms and mono-bacterial gram-positive infection with mainly streptococci (type II). Mono-bacterial gram-negative NF is a rare form of NF that is not included in the current classification. CASE SERIES: We report four cases of mono-bacterial gram-negative NF caused by E. coli. All patients presented in septic shock and showed landscape-like skin necrosis and pain out of proportion. Radical debridement and escalation of antibiotic treatment was performed in all patients. Short-term survival was 50%. Two patients died of multiorgan failure. Two patients survived short term: One patient was amputated through the knee but died six months later of metastatic prostate cancer. One patient was covered with split thickness skin grafts and died three months later of catheter-associated sepsis with endocarditis. DISCUSSION: Recent findings suggest adding a type III fasciitis, which is caused by mono-bacterial gram-negative organisms. As patients are getting older with even more comorbidities, mono-bacterial gram-negative NF will be an increasing problem for physicians treating soft tissue and skin infections.In oncologic diseases, liver cirrhosis, renal diseases or otherwise immunocompromised patients, mono-bacterial gram-negative NF with E. coli is underestimated. Therefore, in these patients, antibiotic treatment should cover Gram-negative organisms including E. coli. However even with adjusted antibiotic treatment and radical debridement, the short-term survival and long-term outcome are poor.

Neuromuscular reinnervation efficacy using a YFP model.

INTRODUCTION: The gold standard reconstruction for facial reanimation is the functional muscle transfer. The reinnervation of a muscle is never complete, and clinical results are variable with 20% not achieving a satisfactory outcome. We hypothesise that this may be due to a mismatch between the characteristics of the donor nerve and transferred muscle. METHOD: 81 YFP-16 and 14 YFP-H mice were studied in three intervention groups over three time periods. Two parameters were investigated: the number and surface area of reinnervated neuromuscular junctions and regenerating axons. An assessment was made of motor unit proportions. RESULTS: All cases of nerve repair and nerve graft, the neuromuscular junctions (NMJ) were completely reinnervated by regenerating axons. The number and calibre of the regenerating axons were significantly different from controls for both intervention groups. The motor units were smaller in both intervention groups. DISCUSSION: Reinnervation occurs after nerve repair or graft; however, the arbour was reinnervated by large numbers of much smaller axons. These axons showed some evidence of remodelling in the repair group, but not in the graft group. Neither group achieved the parameters of the control group. There were persistent qualitative changes to the morphology of both axons and junctions. Imaging documented both synkinesis and alterations that resemble those seen in ageing. CONCLUSION: Overall, the efficacy of reinnervation is very high with all NMJ reoccupied by regenerating axons. The way small axons are remodelled is different in the nerve repairs compared with the nerve grafts.

Epidemiology of human rabies in South Africa, 2008 - 2018.

BACKGROUND: Human rabies cases continue to be reported annually in South Africa (SA). Previous investigations have shown the association between the occurrence of human rabies cases and dog rabies cases in the country. OBJECTIVES: To describe the epidemiology of laboratory-confirmed human rabies cases in SA for the period 2008 - 2018. METHODS: A retrospective document review of laboratory-confirmed human rabies cases for the period 2008 - 2018 was performed using a case register and related documentation available from the National Institute for Communicable Diseases. RESULTS: A total of 105 human rabies cases were laboratory confirmed from 2008 to 2018, with cases reported from all the provinces of SA except the Western Cape. Children and adolescents were most affected by the disease during the study period. In almost half of the cases, medical intervention was not sought after exposure. When victims did seek healthcare, deviations from post-exposure prophylaxis protocols were reported in some cases. CONCLUSIONS: The epidemiological trends of human rabies cases reported in SA for the period 2008 - 2018 remained largely the same as in previous reports. Dog-mediated rabies remains the main source of human rabies in SA.

Reanimation surgery in patients with acquired bilateral facial palsy.

Acquired bilateral facial palsy is rare and causes difficulty with speech and eating, but dynamic reanimation of the face can reduce the effect of these problems. Of 712 patients who had these procedures during our study period, two had an acquired bilateral facial paralysis. In both, reanimation was completed in a single operation using a free-functional transfer of the latissimus dorsi muscle that was coapted to the masseteric branch of the trigeminal nerve. Both patients achieved excellent non-spontaneous excursion and an improvement in function. Careful evaluation of the available donor nerves including thorough examination and electromyographic testing should always be completed before operation.

Reanimation of the brow and eye in facial paralysis: Review of the literature and personal algorithmic approach.

Facial palsy patients suffer an array of problems ranging from functional to psychological issues. With regard to the eye, lacrimation, lagophthalmos and the inability to spontaneously blink are the main symptoms and if left untreated can compromise the cornea and vision. There are a multitude of treatment modalities available and the surgeon has the challenging prospect of choosing the correct intervention to yield the best outcome for a patient. The accurate assessment of the eye in facial paralysis is described and by approaching the brow and the eye separately the treatment options and indications are discussed having been broken down into static and dynamic modalities. Based on our unit's experience of more than 35 years and 1000 cases of facial palsy, we have developed a detailed approach to help manage these patients optimally. The aim of this article is to provide the reader with a systematic algorithm that can be used when consulting a patient with eye problems associated with facial palsy.

The growth factors involved in flexor tendon repair and adhesion formation.

Flexor tendon injuries remain a significant clinical problem, owing to the formation of adhesions or tendon rupture. A number of strategies have been tried to improve outcomes, but as yet none are routinely used in clinical practice. Understanding the role that growth factors play in tendon repair should enable a more targeted approach to be developed to improve the results of flexor tendon repair. This review describes the main growth factors in tendon wound healing, and the role they play in both repair and adhesion formation.

The use of a free vascularised fibula to reconstruct the radius following the resection of an osteosarcoma in a paediatric patient.

Osteosarcoma is the most common high grade bone malignancy in children and the surgical treatment traditionally involves amputation. In our case, a 6-year-old girl was diagnosed with an osteosarcoma of the left distal radius after presenting with forearm pain. After initially being offered an amputation, a second opinion was sought and a limb salvage procedure was offered using a free vascularised fibula bone flap. This resulted in limb preserving surgery which allowed the potential for growth with the maximal preservation of function.

A review of fetal scarless healing.

Wound healing is a complex process involving a number of processes. Fetal regeneration has been shown to have a number of differences compared to scar-forming healing. This review discusses the number of differences identified in fetal regeneration. Understanding these differences may result in new therapeutic targets which may reduce or even prevent scarring in adult healing.

The mechanics of flexor tendon adhesions.

The mechanics of adhesions at a local tissue level have not been extensively studied. This study compared microstrains and macrostrains in adhesions of immobilized and mobilized partially lacerated flexor digitorum profundus tendons in a New Zealand White rabbit model. At 2 weeks, 50 digits were randomized to either gross tensile testing or micromechanical assessment, in which the movement of fluorescently labelled cell nuclei, acting as dynamic markers, was visualized using real-time confocal microscopy. The structural stiffness and load at failure of immobilized adhesions were 140% and 160% of that of mobilized adhesions, respectively, and both differences were statistically significant. Micromechanically, different patterns of loading and failure were observed. Mobilized adhesions exhibited over a three-fold higher local strain, which was less uniformly distributed. Confocal microscopy provided an accurate measure of local strain. For the first time, it has been possible to visualize, define, and quantify local adhesion tissue mechanics. Mobilization appears to favour the formation of sites expressing increased local strain responses or those predisposed to heterogeneity and localized failure.

The attachment of intrinsic and extrinsic, mobilized and immobilized adhesion cells to collagen and fibronectin.

This study investigated the attachment of intrinsic and extrinsic, mobilized and immobilized adhesion cells to the extracellular matrix. Five New Zealand White rabbit forepaws were dissected to isolate the flexor tendon core, tendon surface and synovial sheath, which were explanted separately. A further 10 animals were subjected to flexor tendon injuries, randomized to either mobilization or immobilization, and adhesions were explanted at 2 weeks. Cell groups were tested for attachment to collagen type-I or fibronectin and morphometric analysis was made. The attachment of intrinsic tendon cells and adhesion cells from mobilized tendons to both matrix proteins was statistically significantly greater than that of extrinsic tendon cells and adhesion cells from immobilized tendons. Adhesion cells from mobilized tendons were statistically significantly more elongated, which may correlate with the deposition of a more organized matrix. Because the synovial sheath cells were least attached to matrix proteins, selective treatments that reduce cell attachment may be used to exclude them, without inhibiting intrinsic tendon healing.

Shear-aggregated fibronectin with anti-adhesive properties.

Biomaterials based on proteins, such as fibronectin, have the potential to guide cell and tissue behaviour during healing as a function of their unique mechanical and bioactive properties. Fibronectin has been reported as a scaffold for attachment of fibroblasts and subsequent deposition of collagen. We have recently developed a derivative process of shear-aggregated fibronectin that prevents cell attachment without causing cell death. This has potential applications in clinical situations where adhesions form across gliding surfaces and cause loss of function, e.g. peritoneal or flexor tendon adhesions. This in vitro study tested this derivative fibronectin biomaterial and its effects on aggressive adhesion-forming cells, using rabbit flexor tendon synovial fibroblasts. We investigated degradation of the novel biomaterial, and attachment of fibroblasts to glass coated with the biomaterial, relative to fibroblast attachment to uncoated and fibronectin-coated glass. We assessed infiltration of the derivative fibronectin biomaterial by fibroblasts and cytotoxicity of the biomaterial to fibroblasts. The interaction between fibroblasts and the derivative fibronectin biomaterial was visualized using time-lapse photography. The derivative fibronectin biomaterial dissolved by 88% of its mass by 3 weeks. Fibroblast attachment to the novel biomaterial was significantly reduced at 6 h. After 24 h of exposure to the novel biomaterial, fibroblasts did not migrate into it, there was no cell death and no attachment was seen using time-lapse. This novel derivative fibronectin biomaterial combines inhibition of fibroblast attachment with barrier effects and has suitable mechanical properties for surgical use in preventing adhesions in vivo.

The role of an MMP inhibitor in the regulation of mechanical tension by Dupuytren's disease fibroblasts.

Mechanical tension and contracture are two related facets of tissue biology. This study assessed the effect of ilomastat, a broad-spectrum matrix metalloprotease (MMP) inhibitor, on generation of tension by Dupuytren's disease fibroblasts. Nodule and cord-derived fibroblasts were isolated from five patients with Dupuytren's disease; flexor retinaculum acted as the control. A culture force monitor (CFM) provided an in vitro model of tissue organization to assess development of mechanical tension, lattice contraction and spatial remodelling by fibroblasts. Responses to ilomastat were compared to treatment with a control peptide. Nodule and cord-derived fibroblasts exhibited a two-fold increase in tension compared with flexor retinaculum. Ilomastat significantly inhibited development of tension by nodule and cord but not flexor retinaculum derived fibroblasts at 100 microM. These results imply that MMP activity mediates regulation of tensile strength by Dupuytren's disease fibroblasts and may be an important therapeutic target in patients with Dupuytren's disease.

Diagnosis of skin lesions by trainee surgeons: experience improves accuracy.

INTRODUCTION: Accurate clinical diagnosis depends on the reliable recognition of signs and symptoms. This expertise comes from experience in seeing patients which has been traditionally gained over a long training period. Shortened specialist training (Modernising Medical Careers) has led to a greater reliance on structured teaching and skills transfer programmes. The accuracy of clinical diagnosis and the rate at which diagnostic skills improve during training is important for the assessment of trainees, and the delivery of care. PATIENTS AND METHODS: This study assessed the accuracy of clinical diagnosis of skin lesions by two junior plastic surgery trainees. They were asked to diagnose 120 consecutive skin lesions seen in a pigmented skin lesion clinic in 2005, with the histological diagnosis being confirmed following subsequent excision. The process was repeated a year later in 2006 to enable the rate of correct diagnosis to be compared. RESULTS: Initially, 53.3% of diagnoses were correct. A year later, this had risen to 65.0%. Twenty-two different skin pathologies were present in excised specimens, and skin cancers comprised 30%. The trainees demonstrated 93.8% sensitivity in their initial diagnosis of malignancy (95% CI, 79.2-99.2) and 97.4% a year later (95% CI, 86.5-99.9). However, specificity was 69.3% (95% CI, 58.6-78.7) in 2005 and 71.6% (95% CI, 60.5-71.4) in 2006. CONCLUSIONS: Accuracy in the diagnosis of the wide range of skin conditions presenting to an out-patient clinic was shown to increase over a 1-year period. We feel that this improvement resulted from regular clinical exposure supported by a structured learning programme. The shortening of the specialist training period may affect the acquisition of diagnostic skills by trainees and impact on the confidence with which they commence consultant practice.

In vitro flexor tendon cell response to TGF-beta1: a gene expression study.

PURPOSE: Adhesion formation around zone II flexor tendon repairs remains an important clinical challenge. Tendon healing is complex, and when uncontrolled it may lead to adhesion formation. Transforming growth factor-beta1 (TGF-beta1) is a multipotent growth factor known to be involved in wound healing and scar formation. It has also been shown to have a role in both tendon healing and adhesion formation. METHODS: Uninjured rabbit flexor tendons were divided into endotenon, epitenon, and sheath cells and cultured separately. The in vitro effect of TGF-beta1 gene expression was determined on quiescent tendon cells using real-time polymerase chain reaction for collagen type 1, collagen type 3, fibronectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA). RESULTS: Endotenon-derived cells showed a statistically significant down-regulation of collagen type I gene expression in response to TGF-beta1 compared with untreated endotenon cells and with both epitenon and sheath cells at a number of time points. However, endotenon cells showed an increase in collagen type 3 gene expression compared with untreated cells and epitenon cells. All cells showed a statistically significant increase in fibronectin in the later time points compared with the untreated cells. Endotenon-derived cells showed an early increase in PAI-1, whereas sheath cells showed a later increase. CONCLUSIONS: We have shown that cells cultured from 3 separate parts of the flexor tendon-sheath complex respond in different ways when stimulated with TGF-beta1. The down-regulation of collagen types 1 and 3 in endotenon cells may give further insight into the effects of TGF-beta1 in tendon healing. Also, the upregulation of fibronectin and PAI-1, combined with a down-regulation of tissue plasminogen activator, could explain the association of TGF-beta1 with tendon adhesion formation. Treatments aimed at improving tendon healing and the prevention of adhesions may arise from modification of the effects of TGF-beta1.

Transforming growth factor beta1 signalling, wound healing and repair: a multifunctional cytokine with clinical implications for wound repair, a delicate balance.

Transforming growth factor beta1 (TGFbeta1) is a multifunctional cytokine known to be involved in a number of human diseases. It is believed to play an important role in wound healing and repair, as it is a key regulator of the production and remodelling of the extracellular matrix through its effect on mesenchymal cells. Over the last few years, it has become evident that the signalling pathway of TGFbeta is complex with numerous receptor-ligand interactions, intracellular pathways and a number of mechanisms, which not only control the signalling but may also decide the response to the TGFbeta signal. This review focuses on TGFbeta1 signalling and the role that TGFbeta1 plays in wound healing, repair and scarring.

An alphavirus replicon-derived candidate vaccine against Rift Valley fever virus.

Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus (genus Phlebovirus) associated with severe disease in livestock and fatal encephalitis or haemorrhagic fever in a proportion of infected humans. Although live attenuated and inactivated vaccines have been used in livestock, and on a limited scale in humans, there is a need for improved anti-RVFV vaccines. Towards this goal, Sindbis virus replicon vectors expressing the RVFV Gn and Gc glycoproteins, as well as the non-structural nsM protein, were constructed and evaluated for their ability to induce protective immune responses against RVFV. These replicon vectors were shown to produce the RVFV glycoproteins to high levels in vitro and to induce systemic anti-RVFV antibody responses in immunized mice, as determined by RVFV-specific ELISA, fluorescent antibody tests, and demonstration of a neutralizing antibody response. Replicon vaccination also provided 100% protection against lethal RVFV challenge by either the intraperitoneal or intranasal route. Furthermore, preliminary results indicate that the replicon vectors elicit RVFV-specific neutralizing antibody responses in vaccinated sheep. These results suggest that alphavirus-based replicon vectors can induce protective immunity against RVFV, and that this approach merits further investigation into its potential utility as a RVFV vaccine.

Development and evaluation of a real-time reverse transcription-loop-mediated isothermal amplification assay for rapid detection of Rift Valley fever virus in clinical specimens.

This paper reports on the development and validation of a real-time reverse transcription-loop-mediated isothermal amplification assay (RT-LAMP) targeting the genomic large RNA segment of Rift Valley fever virus (RVFV). The set of six designed RT-LAMP primers identified strains of RVFV isolated in geographically distinct areas over a period of 50 years; there was no cross-reactivity with other genetically related and unrelated arboviruses. When testing serial sera and plasma from sheep experimentally infected with wild-type RVFV, there was 100% agreement between results of the RT-LAMP, a TaqMan-based real-time PCR, and virus isolation. Similarly, the assay had very high levels of diagnostic sensitivity and specificity when testing various clinical specimens from humans and animals naturally infected with the virus during recent outbreaks of the disease in Africa. The detection of specific viral genome targets in positive clinical specimens was achieved in less than 30 min. As a highly accurate, rapid, and very simple nucleic acid detection format, the RT-LAMP has the potential to be used in less-well-equipped laboratories in Africa and as a portable device during RVF outbreaks in remote areas, and it can be a valuable tool for the differential diagnosis of viral hemorrhagic fevers.