Effects of human rhinovirus on epithelial barrier integrity and function in children with asthma.

BACKGROUND: Bronchial epithelial tight junctions (TJ) have been extensively assessed in healthy airway epithelium. However, no studies have yet assessed the effect of human rhinovirus (HRV) infection on the expression and resultant barrier function in epithelial tight junctions (TJ) in childhood asthma. OBJECTIVES: To investigate the impact of HRV infection on airway epithelial TJ expression and barrier function in airway epithelial cells (AECs) of children with and without asthma. Furthermore, to test the hypothesis that barrier integrity and function is compromised to a greater extent by HRV in AECs from asthmatic children. METHODS: Primary AECs were obtained from children with and without asthma, differentiated into air-liquid interface (ALI) cultures and infected with rhinovirus. Expression of claudin-1, occludin and zonula occluden-1 (ZO-1) was assessed via qPCR, immunocytochemistry (ICC), in-cell western (ICW) and confocal microscopy. Barrier function was assessed by transepithelial electrical resistance (TER; RT ) and permeability to fluorescent dextran. RESULTS: Basal TJ gene expression of claudin-1 and occludin was significantly upregulated in asthmatic children compared to non-asthmatics; however, no difference was seen with ZO-1. Interestingly, claudin-1, occludin and ZO-1 protein expression was significantly reduced in AEC of asthmatic children compared to non-asthmatic controls suggesting possible post-transcriptional inherent differences. HRV infection resulted in a transient dissociation of TJ and airway barrier integrity in non-asthmatic children. Although similar dissociation of TJ was observed in asthmatic children, a significant and sustained reduction in TJ expression concurrent with both a significant decrease in TER and an increase in permeability in asthmatic children was observed. CONCLUSION: This study demonstrates novel intrinsic differences in TJ gene and protein expression between AEC of children with and without asthma. Furthermore, it correlates directly the relationship between HRV infection and the resultant dissociation of epithelial TJ that causes a continued altered barrier function in children with asthma.

Impaired airway epithelial cell responses from children with asthma to rhinoviral infection.

BACKGROUND: The airway epithelium forms an effective immune and physical barrier that is essential for protecting the lung from potentially harmful inhaled stimuli including viruses. Human rhinovirus (HRV) infection is a known trigger of asthma exacerbations, although the mechanism by which this occurs is not fully understood. OBJECTIVE: To explore the relationship between apoptotic, innate immune and inflammatory responses to HRV infection in airway epithelial cells (AECs) obtained from children with asthma and non-asthmatic controls. In addition, to test the hypothesis that aberrant repair of epithelium from asthmatics is further dysregulated by HRV infection. METHODS: Airway epithelial brushings were obtained from 39 asthmatic and 36 non-asthmatic children. Primary cultures were established and exposed to HRV1b and HRV14. Virus receptor number, virus replication and progeny release were determined. Epithelial cell apoptosis, IFN-ß production, inflammatory cytokine release and epithelial wound repair and proliferation were also measured. RESULTS: Virus proliferation and release was greater in airway epithelial cells from asthmatics but this was not related to the number of virus receptors. In epithelial cells from asthmatic children, virus infection dampened apoptosis, reduced IFN-ß production and increased inflammatory cytokine production. HRV1b infection also inhibited wound repair capacity of epithelial cells isolated from non-asthmatic children and exaggerated the defective repair response seen in epithelial cells from asthmatics. Addition of IFN-ß restored apoptosis, suppressed virus replication and improved repair of airway epithelial cells from asthmatics but did not reduce inflammatory cytokine production. CONCLUSIONS: Collectively, HRV infection delays repair and inhibits apoptotic processes in epithelial cells from non-asthmatic and asthmatic children. The delayed repair is further exaggerated in cells from asthmatic children and is only partially reversed by exogenous IFN-ß.

Common bacterial infections of the hand.

Infections of the hand are commonly encountered in general practice. Delay in diagnosis increases the risk of tissue loss and functional impairment. Staphyloccocal infections are most common, but polymicrobial infections are often seen in immunocompromised patients. In this pictorial essay, important and common conditions are illustrated to demonstrate key points and pitfalls in diagnosis and management.

A case report of mycobacterium marinum infection of the hand.

We report a case of Mycobacterium marinum infection of the hand presenting initially as triggering of the digits. We like to highlight the unusual source of the infection and difficulty of diagnosis in this case as well as the various treatment modalities.

Extraarticular villonodular synovitis of the tendoachilles: a case report.

Extraarticular form of pigmented villonodular synovitis is rare and usually presents as an extension of a primary intraarticular process. Purely extraarticular lesions are even less common. Pigmented villonodular synovitis involving the synovium around the tendoachilles has not been reported. We report a unique case in a healthy 22-year-old male who presented with a swelling around the tendoachilles for a year. It became painful following a traumatic event 4 weeks prior to consultation. Magnetic resonance imaging (MRI) revealed an extraarticular soft tissue mass moulded to the posterior surface of the calcaneum. It was excised and histology revealed pigmented villonodular synovitis.

Comparison of first carpometacarpal joint arthrodesis with contralateral excision arthroplasty in a patient with bilateral saddle joint arthritis: a case report.

A post-menopausal patient with bilateral primary osteoarthritis of the first carpometacarpal joint (CMCJ) was treated by 2 different surgical techniques. The non-dominant left CMCJ was arthrodesed in 1992 while excision of trapezium and tendon suspensionplasty was done for the dominant right side in 1997. She reported good pain relief with both procedures and she was able to fully oppose both thumbs at 6 years after arthrodesis and 1 year after arthroplasty. The grip and pinch strength was stronger on the arthrodesed side while hand function tests revealed the arthroplasty side to be more dexterous. Subjectively, she preferred the right thumb. Radiographs showed no peritrapezial arthritis in the arthrodesed CMCJ and no proximal migration of the metacarpal on the reconstructed side. Both procedures offered excellent relief of symptoms and she was able to return to work as a machine operator.

Ilizarov's technique used to expand skin from a groin flap.

We report a case in which a groin flap was used to cover the degloved fingers. Subsequently, Ilizarov's technique was used to expand the groin flap before the syndactylized digits were separated.

An unusual case of multiple recurrence of a glomangioma.

Glomus tumour is a benign lesion arising from the glomus apparatus of the skin and subcutaneous tissue. Glomangioma is the angiomatous variant, which is uncommon. We report a very rare presentation of a glomangioma with multiple recurrences. We advocate preoperative angiography to delineate the extent of the lesion to facilitate complete excision.

Clinical experience with management of "near-miss" cases in obstetrics.

Near-miss cases in life-threatening obstetric patients occurring over a one year period are analysed retrospectively with regards to morbidity measured in terms of hospital stay, utilisation of high dependency ward and intensive care beds and adequacy of clinical management. One-hundred and twenty two cases occurred among 9932 deliveries. Massive obstetric haemorrhage (54.2%) and hypertensive disorders of pregnancy (36.9%) were the two main diagnostic groups. Seventy one (58.2%) cases were referred from peripheral centres for obstetric management and 77 (63.1%) were not booked at this hospital for antenatal care. A majority were not ill-looking (92 cases) at the time of admission but turned for the worse in the course of labour. Interventional measures taken in clinical management were considered appropriate in all cases. Delay in instituting treatment was present in 6 cases. Remediable measures were recognised in 15 (12.3%). This study, apart from supplementing mortality audits, demonstrates that high risk obstetric patients can be triaged at the time of admission to labour wards by trained midwives and junior doctors in busy obstetric units without compromising standards of care.

Customized staple fixation in hand and wrist surgery.

Fixation of small bones in the adult and the child's hands remains a challenge. The authors present a technique of bone fixation using customized staples made intraoperatively from K-wires (0.9-1.6 mm in diameter). Their specific purpose was to provide axial alignment and rotational stability for carpal bone fixation and for epiphysiodesis in phalanges. This technique was used in 14 cases (11 adult and three paediatric). No bone shattering, implant breakage, implant loosening or infection occurred. As K-wires are quite malleable, custom sized and shaped staples which follow the bone contours could be made to give a more exact fixation. All cases had satisfactory outcomes, achieving the preoperative objectives of bony fixation. This method is safe, precise and technically easy. It is also relatively cheap and only requires simple, standard instruments.

Hand infections in patients with diabetes.

Twenty-five hand infections in adult patients with diabetes were reviewed. Eighty percent of the patients were younger than 60 years of age and had diabetes mellitus for less than 5 years' duration. Secondary neurologic, vascular, or cutaneous changes in the hands were present in 5 (20%) patients. A documented instance of trauma was present in 16% of patients. None of the patients had nosocomial infections. Of the 24 (96%) patients who required surgery, 21 had debridement alone and 3 needed amputation of the digit or digits or hand, either as a primary procedure or after initial debridement. Multiple organisms were found in 55% of the positive cultures. Gram negative organisms were documented in 73% of the positive cultures. An antibiotic combination of gentamicin, penicillin G, and cloxacillin covered the entire spectrum of the causative organisms. An aggressive treatment protocol comprising hospital admission, intravenous combination antibiotics, surgical debridement, appropriate diabetic control, and strict elevation of the hand was important in the management of the sepsis, reduction of morbidity, and salvage of the hand. With a followup at 2 years, there was no instance of any repeat episode of the hand infection.

Gastric stump carcinoma: a surgical challenge.

Gastric stump carcinoma is a carcinoma arising in the stomach remnant following previous gastric resection. It is a distinct disease entity with its unique aetiology and pathogenesis. We report 3 cases of gastric stump carcinoma encountered in the department over the past 5 years and review current literature pertaining to its clinical presentation, aetiology, pathogenesis, treatment strategy and the role of screening endoscopy. The disease is characterised by its late presentation and dismal prognosis and will continue to pose a surgical challenge in the years to come.