Mary Leader

Diphenylhydantoin sodium promotes early and marked angiogenes is and results in increased collagen deposition and tensile strength in healing wounds

BACKGROUND Sodium diphenylhydantoin (DpH) (phenytoin) was first introduced as an antiepileptic in 1938. One of its side effects, gingival hyperplasia, prompted investigation into the possible application of this drug as a promoter of wound healing. Since the late 1950s phenytoin has been used in a variety of clinical situations. However, its exact mechanism of action is still debated. The aim of this study was to determine the effect of DpH on wound healing in an incisional rat model. METHODS A four dorsal wound model was used, and each cephalad wound had a polyvinyl alcohol sponge placed in a subcutaneous pocket just above its cephalad end. Caudal and cephalad wounds were treated with 10 mg DpH in 200 microliters carrier, and the other two wounds received an equal volume of the saline vehicle as controls on the day of wounding and on the third and sixth postoperative days. The animals were killed on the tenth postwounding day. Tensile strength of fresh and fixed scars was determined using constant speed tensiometry, and wound hydroxyproline was determined spectophotometrically. RESULTS There was a highly significant increase in both fresh and fixed wound tensile strength of all DpH-treated wounds compared with controls (p < 0.001). This was reflected by a significant increase in polyvinyl alcohol sponge hydroxyproline in DpH-treated wounds compared with saline-treated wounds (p = 0.002). Histologic examination of these wounds was performed at 3 and 6 days after wounding. There was moderate fibroblast infiltration with a marked inflammatory infiltrate and neovascularization in the DpH-treated wounds compared with controls at 3 days. By day 6, the inflammatory infiltrate had almost totally receded in the treated wounds, but fibroblast infiltration and angiogenesis were still persistently marked. In comparison, the saline-treated wounds still had moderate inflammatory and fibroblast infiltrate and mild angiogenesis. CONCLUSIONS DpH alters the natural course of wound healing and may be of benefit in clinical situations where defective wound collagen deposition may lead to poor wound healing and consequent morbidity and mortality.

Langerhans cells in benign, premalignant and malignant skin lesions of renal transplant recipients and the effect of retinoid therapy

Langerhans cells (LC) are a unique population of antigen‐presenting cells in the epidermis which may play a role in the defense mechanisms against skin tumors. Renal transplant recipients (RTRs) have a significantly increased incidence of premalignant and malignant skin lesions. Langerhans cells, which are important for local immune surveillance, may be depleted or downregulated in skin neoplasms of RTRs, facilitating their growth. We investigated the Langerhans cell densities in 29 squamous cell carcinomas (SCCs), five basal cell carcinomas (BCCs), four Bowens disease, eight dysplastic lesions (actinic keratoses), and three viral warts from 15 RTRs and compared these to the Langerhans cell densities in normal control skin. Eleven RTRs were receiving low‐dose etretinate as chemoprophylaxis for recurrent skin cancer and the effect of low‐dose retinoid therapy on Langerhans cell densities in SCCs from these patients was also assessed. Langerhans cells in frozen tissue sections were stained with the anti‐human Leu‐6 monoclonal antibody.

Altered expression of the p53-regulated proteins, p21Waf1/Cip1, MDM2, and Bax in ultraviolet-irradiated human skin

The distribution of p21WAf1/CiP1, MDM2, and Bax/Bcl-2 proteins in ultraviolet (UV)-irradiated and nonirradiated human skin was examined immunohistochemically and compared with p53 protein levels. Sun-protected buttock skin from three volunteers was exposed to solar simulated irradiation, and biopsies were performed 0.5, 1, 2, 4, and 24 hours after irradiation as well as control unirradiated skin from the opposite buttock. A similar staining pattern was observed in each of the three volunteers. P53 protein was detectable in all skin samples examined. P21Waf1/CiP1 protein was visible in the nuclei of cells at 4 hours, and staining intensity increased at 24 hours. MDM2 protein expression was noted in isolated nuclei in the epidermis at 24 hours. Bax cytoplasmic staining was evident in the basal layer of the epidermis of all samples, and this staining appeared to increase in intensity in the 4- and 24-hour specimens. There was no Bcl-2 immunohistochemical staining in any sample. These results suggest that p53 and genes/proteins under the control of p53 are altered/ activated in normal human skin in response to UV exposure.

p53 tumor suppressor gene protein expression in premalignant and malignant skin lesions of kidney transplant recipients

BACKGROUND Kidney transplant recipients have an increased incidence of skin cancer, the cause of which is likely multifactorial. Inactivation of the tumor suppressor gene p53 protein may be important. Chemoprophylaxis of skin cancer with retinoids is beneficial in these patients. OBJECTIVE Our purpose was to investigate the immunohistochemical expression of p53 protein in premalignant and malignant cutaneous lesions in kidney transplant recipients and the effect of low-dose etretinate on p53 expression. METHODS Paraffin sections were stained with the monoclonal antibody DO-7. RESULTS Immunoreactivity of p53 was observed in 59% of basal cell carcinomas and more than 60% of squamous cell carcinomas, Bowens disease, dysplastic lesions, and viral warts. No demonstrable effect of etretinate on p53 expression could be determined. CONCLUSION The high prevalence of p53 immunoreactivity in premalignant and malignant skin lesions of kidney transplant recipients supports a role for p53 protein in skin cancer. This could be caused by mutation of the p53 gene, inactivation, or failure of degradation of p53 protein.

Primary middle-ear lymphoma in a child

The case of a five year old boy who presented with a lower motor neurone facial nerve palsy secondary to primary non-Hodgkins lymphoma (NHL) of the middle ear is discussed. Any child who presents with a facial nerve palsy and conductive hearing loss requires thorough evaluation to exclude the possibility of temporal bone malignancy.

Granulomatous gastritis: Part of a vasculitic syndrome

The previously unreported association of granulomatous gastritis and mononeuritis multiplex occurring in the setting of a vasculitic syndrome is described. The two conditions are considered to be associated and to be immune mediated. The previously accepted concept of isolated granulomatous gastritis is disputed.

Loss of p16INK4A expression is associated with allelic imbalance/loss of heterozygosity of chromosome 9p21 in microdissected synovial sarcomas

Deletions of the short arm of chromosome 9 have been observed in many tumours and cell lines. This chromosomal region is frequently targeted during malignant transformation because it contains at least two known tumour suppressor genes: p16INK4 and p15INK4B. p16INK4A acts as a negative cell cycle regulator by inhibiting G1 cyclin-dependent kinases that phosphorylate the retinoblastoma protein and therefore block the progression of the cell cycle from G1 to S phase. The role of p16INK4A in the development of synovial sarcoma has not been comprehensively investigated. Ten samples of synovial sarcomas were examined for allelic imbalance/loss of heterozygosity (AI/LOH) of the 9p region and p16 protein expression. DNA was isolated from microdissected sections of normal and tumour cells, amplified by polymerase chain reaction and analysed for AI/LOH by using six microsatellite markers that map to the 9p region. Immunohistochemistry for p16 expression was done. AI/LOH with at least one microsatellite marker on 9p21 was detected in six of ten samples. The most frequent allelic deletions were observed within the coding sequence of p16INK4A. Loss of p16 immunoreactivity was detected in eight samples, six of which showed evidence of alterations at 9p21 region. These findings suggest a possible role of loss of p16INK4A in the development of synovial sarcoma.

Case report 759

Fig. 1. Radiograph of lcft tibia and fibula demonstrating multiple, small, well-defined, lytic lesions involving the tibia, fibula, and talus Fig. 2. Radiograph of the left tibia and fibula obtained 8 weeks later demonstrated an increase in size and number of lytic lesions affecting the tibia, fibula, and talus Fig. 3. Radiograph of left femur demonstrates multiple, well-defined lytic lesions involving the neck and shaft of the femur

Primary malignant melanoma of the oesophagus: a case report.

Primary malignant melanoma of the oesophagus is a rare neoplasm comprising less than 0.2% of all primary oesophageal neoplasms. There are fewer than 250 reported cases in worldwide literature. Several reports suggest that it has a mean survival rate of 2.2% at 5 years and a median survival rate of 10 months. A 48 year old male presented to our surgical service complaining of a three month history of progressively worsening dysphagia with associated regurgitation and unintentional weight loss of 14 kg. There was no prior history of cutaneous or ocular melanoma. He was treated with a combination of subtotal oesophageal resection and immunomodulatory therapy. We present herein a case of primary malignant melanoma of the oesophagus including the associated clinical, pathological and radiological findings.

In-situ neoplasia in squamous cell carcinoma of the parotid. A case report.

This case report demonstrates the origin of a primary squamous cell carcinoma of the parotid gland in squamous metaplasia of the parotid ducts. Comparison is made between parotid ductal intraepithelial neoplasia and cervical intraepithelial neoplasia. The clinical importance of establishing the primary origin of these tumours and the need for extensive tissue sampling is emphasized.