Head and Neck Merkel Cell Carcinoma: A 12-Year Single Institutional Experience.

Background: Merkel cell carcinoma (MCC) is an aggressive malignancy of presumed neuroendocrine origin. Most case series of MCC are limited by low case numbers and are not specific to head and neck tumours. The purpose of this study was to provide a focused review of head and neck MCC diagnosis and management in a single Irish institution. Methods: Patient's demographics, tumour characteristics, pathological diagnosis, surgical treatment, adjuvant treatment, subsequent management and clinical course were collected. Estimates of progression-free MCC survival rates were calculated by the Kaplan-Meier statistical model. A Pearson product-moment correlation coefficient examined the association between surgical margins and disease-free follow-up. Results: In total, 11 patients were treated for head and neck MCC with a mean age of 79.6 years (range = 69-91 years). The mean average follow-up duration of patients was 18.3 months. Of the cohort, 18% (n=2) had a sentinel node biopsy (SLNB). A selective neck dissection was subsequently performed in 18% (n=2). In total, 72% (n=8) of patients received adjuvant radiotherapy. Median disease-specific survival was 15 months for the SLNB group and 17 months for the non-SLNB group, not statistically significant (p=0.23). There was no significant association between surgical margins and disease-free follow (p=0.65). Conclusions: Our case series adds to a limited body of evidence of head and neck MCC. Surgery remains the treatment priority in localized disease, with an increasing role of SLNB for accurate prognostication and staging. Early management of stage I disease results in moderate long-term disease-free survivability.

Pancreatic islet transplantation using vascularised chambers containing nerve growth factor ameliorates hyperglycaemia in diabetic mice.

Intraportal islet transplantation has shown initial promise for the treatment of type 1 diabetes. However, the portal vein site is associated with complications such as thrombosis and hepatic steatosis, leading to transplant failure. The aims of this study were to (1) test the feasibility of an alternative islet transplantation method that utilises a FDA-approved gelatin sponge as a novel islet carrier and (2) assess if exogenous addition of nerve growth factor (NGF) has any additional beneficial effects on graft performance in diabetic mice. Mice were rendered diabetic by a single intraperitoneal injection of streptozotocin. Five hundred syngeneic islets were seeded onto a Gelitaspon((R)) disc in the presence or absence of NGF, and placed into a silicone chamber surrounding the femoral neurovascular pedicle. Islet function was assessed by weekly monitoring of blood glucose levels and an intraperitoneal glucose tolerance test performed at the end of the study. Chambers were harvested for further histological analysis. Four of five mice transplanted with islets seeded onto Gelitaspon with NGF showed a significant reduction in blood glucose levels by 4 weeks after transplantation, and demonstrated a response similar to non-diabetic mice when tested with an intraperitoneal glucose tolerance test. Chamber tissue from this group contained islets with insulin-producing beta cells adjacent to the vascular pedicle. Islets seeded onto Gelitaspon with NGF and sited on femoral vessels using a tissue-engineering chamber offer an alternative method for islet transplantation in diabetic mice. This may have potential as a method for clinical islet transplantation.

Referral of patients to plastic surgeons following self-harm: Opportunities for suicide prevention.

Self-harm is a common source of referral to plastic and hand surgery services. Appropriate management of these patients is complex and includes the need for close liaison with mental health services. Self-harm is the single biggest risk factor for completed suicide, thereby increasing the risk by a factor of 66.1 This study aimed to analyse the clinical pathway and demographics of patients referred to plastic surgeons following self-harm. This 6-year retrospective series included patients referred to plastic surgeons following self-harm within the Galway University Hospital group. Patients were identified through the Hospital inpatient enquiry system, cross-referenced with data from the National Suicide Research Foundation. Data collected included demographics, psychiatric history, details of self-harm injury, admission pathway and operative intervention. Forty-nine patients were referred to plastic surgery services during the study period, accounting for 61 individual presentations. The male-to-female ratio was 26 (53%) to 23 (47%). Mean age was 40 years (range 21-95 years). Alcohol or illicit substance use was recorded in 17 of 61 (28%) presentations. Mortality from suicide occurred in 4 patients (8%). Mental health assessment was not carried out in 9 presentations (15%). Documentation of need for close or one-to-one observation was made in 11 cases (20%) and was not referred to in 43 cases (83%) following mental health assessment. This study demonstrates significant diversity in the management of this vulnerable patient group and may inform development of referral pathways to improve the safety of transfer, surgical admission and discharge of patients following self-harm, in consultation with mental health services.

Analysis of sentinel node positivity in primary cutaneous melanoma: an 8-year single institution experience.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a standard method for determining the pathologic status of the regional lymph nodes. AIMS: The aim of our study was to determine the incidence and clinicopathologic factors predictive of SLN positivity, and to evaluate the prognostic importance of SLNB in patients with cutaneous melanoma. METHODS: We performed a retrospective analysis of a prospectively maintained database of all patients who underwent SLNB for primary melanoma at our institution from 2005 to 2012. Statistical analysis was performed using χ 2 and Fischer exact test. RESULTS: In total, 318 patients underwent SLNB, of which 65 were for thin melanoma (≤1 mm). There were 36 positive SLNB, 278 negative SLNB and in four cases the SLN was not located. The incidence rate for SLNB was 11.3% overall and 1.5% in thin melanomas alone. Statistical analysis identified Breslow thickness >1 mm (P = 0.006), Clark level ≥ IV (P = 0.004) and age <75 years (P = 0.035) as the strongest predictors of SLN positivity. Our overall false negativity rate was 20% (9/45) with one case of false-negative SLNB in thin melanomas. CONCLUSION: Breslow thickness of the primary tumour remains the strongest predictor of SLN positivity. Our findings point to a possible limited role for SLNB in thin melanoma due to its low positivity rate, associated false-negative rate and related morbidity.

Human Mu-class glutathione S-transferases present in liver, skeletal muscle and testicular tissue.

The major human Mu-class glutathione S-transferases (GST) have been purified to allow comparisons of their catalytic, physicochemical and immunochemical properties. GST isoenzymes, purified from hepatic, testicular and skeletal muscle tissue were found to comprise three distinct subunits (M1, M2 and M3) which may combine to form both homodimeric and heterodimeric proteins. Two distinct subunits, M1a and M1b, which represent allelic charge variants have been isolated but no polymorphic forms encoded at the GST M2 and M3 loci have been observed. Three GST isoenzymes (M1a-1a, M1a-1b and M1b-1b) have been purified from a single liver specimen. In addition, GST M1a-2, M1b-2, M2-2 and M2-3 have been isolated from muscle, whilst the M3-3 homodimer has been purified from human testis. The homodimeric enzymes GST M1a-1a, M1b-1b, M2-2 and M3-3 have pI values of 6.1, 5.5, 5.3 and 5.0, whilst SDS-PAGE indicated that M1a, M1b, M2 and M3 have molecular masses of 26.7, 26.6, 26.0 and 26.3 kDa, respectively. The M1, M2 and M3 subunits isolated from either liver, skeletal muscle or testis, are catalytically distinct. Both M1-type subunits (M1a and M1b) possess a high activity for trans-4-phenyl-3-buten-2-one, whereas, the skeletal muscle subunit M2 has a high activity towards 1,2-dichloro-4-nitrobenzene. By contrast, the testicular GST subunit M3 has no detectable activity towards either of these substrates. However, all three Mu-class subunits are active towards the compounds 4-hydroxynonenal and 4-hydroxydecinal, possible endogenous substrates which are produced by lipid peroxidation. The human Mu-class subunits can be distinguished immunochemically; antisera raised against the testicular GST M3-3 showed no reactivity towards either the M1 or M2 subunits. The M3 subunit has a blocked N-terminus but automated amino-acid sequencing of a CNBr-derived peptide allowed 14 residues of the M3 subunit to be identified. These data indicated that testicular GST M3-3 is likely to correspond to the brain/testis Mu-class GST cDNA described by Campbell et al. (Campbell E., Takahashi Y., Abramovitz M., Peretz M., & Listowsky I. (1990) J. Biol. Chem. 265, 9188-9193).

Variations in the glutathione S-transferase subunits expressed in human livers.

Human livers express a variety of cytosolic glutathione S-transferase isoenzymes. The enzymes are subject to a marked polymorphism and the polypeptide basis of the differences in glutathione S-transferase content of individual livers has been investigated by Western blotting, hydroxyapatite HPLC and isoelectric focusing. Collectively, the livers examined contained three distinct groups of cytosolic glutathione S-transferase. The three classes of enzyme contain subunits of different molecular mass; subunits of 24.8 kDa (Yf), 26.0 kDa (Ya) and 26.7 kDa (Yb) were found to belong to the 'acidic-type', 'basic-type' and 'neutral-type' glutathione S-transferase, respectively. All livers studied contained 26.0 kDa subunits (Ya or 'basic') but significant differences in the isoelectric points of this group of proteins were demonstrated. Five of the eight livers examined expressed 26.7 kDa subunits (Yb or 'neutral'); the native enzymes had pI values of either 6.1 or 5.5, and were isolated by hydroxyapatite HPLC. Two of the livers possessed 24.8 kDa subunits (Yf or 'acidic'), and the native enzyme, which had a pI of 4.8, was also purified by hydroxyapatite HPLC. Before undertaking a glutathione S-transferase purification it is advisable to determine the GST isoenzyme content of a number of livers. The suitability of the methods described in the present study for use as screening procedures is discussed.

The Irish contribution to the plastic surgery literature: 21 years of publications.

INTRODUCTION: The Republic of Ireland has always had an influence on medicine and has produced many renowned doctors who have helped shape its history. Furthermore, many clinical articles that have originated from Ireland have changed clinical practice throughout the world. The Irish have also had an impact on the plastic surgery literature yet it has never specifically been analyzed before. The purpose of this study was to identify and analyze all papers that have originated from the plastic surgery units in the Republic of Ireland in the medical literature over the past 21 years. METHODOLOGY: Twenty-four well-known plastic surgery, hand surgery and burns journals were selected for this study. By utilizing Scopus, the largest abstract and citation database of peer-reviewed literature, we analyzed each of our chosen 24 journals looking for Irish publications. Each paper was examined for article type, authorship, year of publication, institution of origin and level of evidence. RESULTS: Papers from the Republic of Ireland were published in 20 of the 24 journals over the past 21 years. A total of 245 articles from Ireland were published in the plastic surgery, hand surgery and burns literature over the 21-year period. Of these, 111 were original articles and 73 were case reports. The institution that published the most papers over the past 21 years was University Hospital Galway (66 publications) followed by Cork University Hospital with 54 papers. The journal with the most Irish articles was the Journal of Plastic, Reconstructive and Aesthetic Surgery with 56 papers. 2014 was the year with the most publications (28 papers). Authorship numbers also increased over time as the average number of authors in 1994 was 3.5, whereas it was 5.54 in 2014. DISCUSSION: The number of publications per year continues to increase along with authorship numbers. This mirrors the trend in other specialties. Publications are now no longer required for selection on to a higher surgical training scheme. There is now a fear that the academic output of trainees will decrease as a consequence. To prevent this, each unit must actively support and encourage research activity with their trainees.

A review of sentinel lymph node biopsy for thin melanoma.

INTRODUCTION: Although there is a lack of established survival benefit of sentinel lymph node biopsy (SLNB), this technique has been increasingly applied in the staging of patients with thin (≤1.00 mm) melanoma (T1Nx), without clear supportive evidence. METHODS: We review the guidelines and available literature on the indications and rationale for performing SLNB in thin melanoma. RESULTS: As a consequence of the paucity of evidence of SLNB in thin melanoma, there is considerable variability in the guidelines. It is difficult to define clinicopathologic factors that reliably predict the presence of nodal metastasis. SLNB does not yet inform management in thin melanoma to improve survival outcome. CONCLUSION: Based on available evidence, high risk patients with melanomas between 0.75 and 1.00 mm may be appropriate candidates to be considered for SLN biopsy after discussing the likelihood of finding evidence of nodal progression, the risks of sentinel node biopsy, and the lack of proven survival benefit from any form of surgical nodal staging.

Relationship between pituitary and other target organ responsiveness in hypothyroid patients receiving thyroxine replacement.

This study was undertaken to compare the sensitivity of the thyrotrophs to that of other tissues to T4 treatment in hypothyroid patients. To do so, we measured serum total and free thyroid hormones and TSH, in addition to several serum markers of peripheral tissue response to thyroid status, in 21 hypothyroid patients treated with 50-micrograms increments of T4 to a maximum of 200 micrograms daily (group I) and in 104 clinically euthyroid patients receiving a long term constant replacement dose (group II). In group I patients, dose-dependent increases (P less than 0.05) in serum glutathione S-transferase, sex hormone-binding globulin, and angiotensin-converting enzyme occurred, whereas serum T4-binding globulin, creatine kinase, and creatinine levels decreased (P less than 0.05). In both patient groups, abnormally high levels of glutathione S-transferase, sex hormone-binding globulin, angiotensin-converting enzyme, alanine aminotransferase, and gamma-glutamyl transferase were found in some patients during treatment. One or more of these biochemical abnormalities suggestive of hyperthyroidism occurred in 15 (71%) group I patients and 27 (26%) group II patients. These were associated with an undetectable serum TSH (less than 0.1 microU/ml) and raised free T4 concentrations in 13, and raised free T3, T4, and T3 concentrations in only 8, 6, and 1 group I patients, respectively. In group II patients, they were more closely associated with an undetectable TSH (67%) or raised free T4 (85%) level than with raised concentrations of free T3 (33%), T4 (26%), or T3 (0%). The use of high sensitivity TSH assays will permit more accurate adjustment of T4 replacement and minimize abnormalities in peripheral tissue biochemistry indicative of overtreatment.

Inhibition of platelet thrombosis using an activated protein C-loaded stent: in vitro and in vivo results.

In high-risk and complicated coronary intervention, the risk of acute closure is unpredictable. Thrombus and platelet deposition at the intervention site may also have further effects on subsequent restenosis. In vivo infusion of activated protein C has previously been shown to achieve potent anticoagulation without any haemostatic side effects. We now evaluated the in vitro and in vivo efficacy of polymer-coated coronary stents loaded with purified rabbit Activated Protein C (APC). By measuring 125I-fibrinogen/fibrin deposition APC-loaded stent-wires were antithrombotic compared to albumin-loaded, inhibited-APC-loaded, plain polymer-coated and stainless steel stent-wires. In a balloon injury rabbit iliac artery model, APC-loaded stents did not occlude (0/14) compared to plain stents (9/15) and BSA-loaded stents (2/4). Relative 111In-labelled platelet deposition showed a similarly significant degree of inhibition. In conclusion, APC-loading could render stents significantly less thrombotic. Whether an effective antithrombogenic stent like this effectively reduces restenosis rates warrants further evaluation.

Plasma glutathione S-transferase measurements in patients with alcoholic cirrhosis.

Hepatocellular damage has been assessed in 54 patients with biopsy proven alcoholic cirrhosis by measuring the activity of aspartate aminotransferase (AST) and the concentrations of glutathione S-transferase B1B1 (GST B1B1) and B2B2 (GST B2B2) in serum. The levels of AST, GST B1B1, or GST B2B2 were abnormal in 28, 28 and 17 patients respectively but abnormalities in AST and GST measurements appeared to identify different populations of patients.

Impaired hepatocellular integrity during general anaesthesia, as assessed by measurement of plasma glutathione S-transferase.

The measurement of plasma glutathione S-transferase (GST) concentrations have been used to assess the changes in hepatocellular integrity which occur following general anaesthesia. Of 20 selected patients, who received halothane for minor urological procedures, 16 showed a small transient rise in GST between 1 h and 3 h after anaesthesia. Similar changes were also observed in 8 consecutive patients who received halothane for various operative procedures. In 3 of these 28 patients a marked secondary rise in plasma GST was observed 24 h after anaesthesia. No significant changes in ALT were observed in either of the groups of patients. These data indicate two possible phases of hepatotoxicity following halothane administration which results in a transient impairment in hepatocellular integrity in the majority of patients who undergo anaesthesia with this agent.

Glutathione S-transferase levels in autoimmune chronic active hepatitis: a more sensitive index of hepatocellular damage than aspartate transaminase.

Glutathione S-transferase (GST; EC 2.5.1.18), a sensitive marker of hepatocellular damage, was measured in patients on therapy for histologically proven, autoimmune chronic active hepatitis at various stages of the disease. GST levels were elevated in 65% of serum samples despite immuno-suppressive treatment compared with aspartate transaminase (AST) which was increased in only 23% of samples. In 55% of samples with normal AST concentrations, GST was elevated. No samples demonstrated abnormal transaminase with normal GST levels. It is concluded that continuing hepatocellular damage occurs in patients with autoimmune chronic active hepatitis on immuno-suppressive treatment.

Comparison of radioimmunoassay and immunoradiometric assay for serum prostatic acid phosphatase.

We have compared the laboratory performance of immunoradiometric (IRMA) and radioimmunoassay (RIA) methods developed in this laboratory for measurement of serum prostatic acid phosphatase (PAP). The IRMA utilizes a radiolabelled mouse monoclonal anti-PAP and a solid phased rabbit polyclonal anti-PAP. The same rabbit antibody is used in the RIA. The IRMA shows excellent precision over a much wider working range (0.25-1000 micrograms/l) than the RIA (0.73-14.0 micrograms/l), and can be completed in 5 h, while the RIA requires 3 days. Levels in healthy males and in patients with benign prostatic hypertrophy are similar in both assays, upper limits of normal being 1.8 micrograms/l (IRMA) and 4.7 micrograms/l (RIA). The two assay methods correlate very well (r = 0.97) when PAP is measured in serum from prostatic cancer patients, although IRMA results are generally lower than those obtained by RIA. About 20% of patients with non-metastatic prostatic carcinoma had elevated serum PAP, whereas about 80% of those with metastatic disease had raised levels. The diagnostic efficiencies of the RIA and IRMA appeared similar. The value of the IRMA in follow-up and staging remains to be determined.

Intravenous N-acetylcysteine, hepatotoxicity and plasma glutathione S-transferase in patients with paracetamol overdosage.

The concentration of glutathione S-transferase B1 (GST B1) subunits was measured in sequential plasma samples taken at frequent intervals for 48 h from ten patients with severe paracetamol poisoning who were treated with intravenous N-acetylcysteine. No significant increase in plasma GST B1 concentration was observed over the study period and with 4 h of starting treatment with N-acetylcysteine there were significant decreases in plasma GST B1 concentrations. None of the patients subsequently developed significant liver damage. At the dose used for the treatment of paracetamol poisoning, N-acetylcysteine has no hepatotoxic effects.

Microsurgical replantation of an ear with no venous repair.

Replantation of an avulsed ear was completely successful with only arterial repair (to the superficial temporal artery) and the use of medicinal leeches.