Digital papillary adenocarcinoma: An important differential diagnosis for digital soft tissue masses.

Digital papillary adenocarcinoma (DPAC) is a rare, aggressive cancer with significant metastatic potential which arises from digital sweat glands. We present a case of a DPAC managed with surgical excision and reconstruction with a reversed homodigital island flap. Level of evidence: V.

Outcomes of skin cancer excision in frail patients: A retrospective cohort study.

BACKGROUND: Non-melanoma skin cancer (NMSC) is the most common cancer type and incidence increases with age. As a consequence, an increasing number of frail patients are being referred for consideration of skin cancer surgery. However, some of these patients may not live long enough to experience benefit from surgery, while being at risk of postoperative complications. OBJECTIVES: To investigate the treatment burden of surgical excision of skin cancers in frail individuals. METHODS: We conducted a single-center retrospective cohort study analyzing outcomes of skin cancer excision in frail versus non-frail patients. RESULTS: Eighty-eight patients were included. The complication rate was higher in frail versus non-frail patients: 12 (27.9%) versus 9 (18.8%), with 5 unplanned postoperative hospital attendances leading to 3 hospital admissions in the frail cohort. Nine patients in the frail group (21%) died within 6 months of their procedure versus no deaths in the non-frail group (p < 0.001 Fisher's Exact test), with no deaths attributed to skin cancer. CONCLUSION: Treatment-related complications and mortality are common in frail patients after surgical excision of skin lesions clinically suspicious for skin cancer. Careful consideration should be given, and patients should be adequately counseled about treatment risks and alternative management options, including active surveillance, in particular, if the lesions are expected to remain asymptomatic.

Management of purpura fulminans skin loss at a regional burns centre: Sixteen-year experience.

INTRODUCTION: Purpura fulminans (PF) is a rare syndrome of cutaneous purpura which is the consequence of severe circulatory shock causing intravascular thrombosis, haemorrhagic necrosis, and consequent tissue loss. The aim of this study was to present our 16-year experience of managing PF in a regional burns centre. METHODS: We performed a single-centre retrospective case series of all patients admitted to the St Andrews Burns Centre at Broomfield Hospital, Chelmsford, Essex, UK, between June 2006 and July 2022 with a diagnosis of PF. Data were extracted by retrospectively searching hospital case notes. RESULTS: Thirteen individuals were identified [five children (mean age 5, range 1-14) and eight adults (mean age 39, range 24-54)]. The total body surface area of cutaneous necrosis ranged from 5% to 80%, with a mean of 27.2%. Patients were treated with an established surgical sequence of total wound debridement and immediate coverage with a cadaveric allograft, followed by staged wound autografting. The mean time from disease onset to wound autografting was 37.3 days (range 20-64 days). Eight individuals (61.6%) required major amputation of at least one limb (proximal to the ankle or wrist joint). Only one mortality (of 80% total body surface area skin loss) was observed in the identified cohort. CONCLUSIONS: The large body surface areas often involved in PF cases make management of these wounds well suited for burns centres, wherein established facilities and multidisciplinary teams exist that are familiar with managing large cutaneous burns. We provide a suggested algorithm to aid the management of PF.

Failure or relapse predictors for the STREAM Stage 1 short regimen for RR-TB.

BACKGROUND: STREAM (Standardised Treatment Regimens of Anti-tuberculosis drugs for Multidrug-Resistant Tuberculosis) Stage 1 demonstrated non-inferior efficacy of a short regimen for rifampicin-resistant TB (RR-TB) compared to a long regimen as recommended by the WHO. The present paper analyses factors associated with a definite or probable failure or relapse (FoR) event in participants receiving the Short regimen.METHODS: This analysis is restricted to 253 participants allocated to the Short regimen and is based on the protocol-defined modified intention to treat (mITT) population. Multivariable Cox regression models were built using backwards elimination with an exit probability of P = 0.157, equivalent to the Akaike Information Criterion, to identify factors independently associated with a definite or probable FoR event.RESULTS: Four baseline factors were identified as being significantly associated with the risk of definite or probable FoR (male sex, a heavily positive baseline smear grade, HIV co-infection and the presence of costophrenic obliteration). There was evidence of association of culture positivity at Week 8 and FoR in a second model and Week 16 smear positivity, presence of diabetes and of smoking in a third model.CONCLUSION: The factors associated with FoR outcomes identified in this analysis should be considered when determining the optimal shortened treatment regimen.

A systematic review of observational management of cutaneous basal cell carcinoma.

BACKGROUND: Cutaneous basal cell carcinoma (BCC) is the commonest cancer in the United Kingdom and United States. Surgical excision is the most common treatment. This review summarises all published outcomes of observational/non-interventional management of cutaneous BCC. METHODS: This PRISMA-compliant systematic review searched MEDLINE, EMBASE and CENTRAL databases from inception-June 2021. All studies reporting outcomes of observational management for BCC were included. RESULTS: We identified 2529 titles, from which 4 full-text articles were eligible, reporting on 2298 individuals. Two studies were randomised controlled trials (RCTs) comparing histological clearance rates and adverse events following treatment with an inactive strategy (placebo cream) versus topical 5%-imiquimod (at different frequencies) for 6-12 weeks. Clearance rates ranged from 52-100% for imiquimod and 2-19% for placebo, with more adverse events associated with imiquimod. The other two studies used prospective cohort designs. One study assessed the natural history of BCCs managed expectantly in 39 individuals aged ≥80years. During the 15.8-month follow-up, 46.2% of lesions did not increase in size and 10.3% resolved. The remaining study compared treatment patterns of 1360 patients with non-melanoma skin cancer (NMSC) in individuals with or without limited life-expectancy (LLE). The LLE subgroup had a 5-year mortality rate of 43.3%, with no deaths attributed to NMSC. Only 3.3% of individuals with LLE underwent observational treatment. No study examined quality-of-life or cost-effectiveness. CONCLUSION: There has been limited investigation of observational management of BCC, despite possible advantages of this strategy. Future RCTs should compare quality-of-life outcomes and utility-adjusted survival following interventional or observational management of BCC.

Mortality from abdominal aortic aneurysm: trends in European Union 15+ countries from 1990 to 2017.

BACKGROUND: This observational study assessed trends in abdominal aortic aneurysm (AAA) death rates in European Union (EU) 15+ countries for the years 1990 to 2017. METHODS: Age-standardized death rates (ASDRs) were extracted from the Global Burden of Disease Study Global Health Data Exchange. Trends were analysed using joinpoint regression analysis. RESULTS: Between 1990 and 2017, ASDRs from AAA decreased in all 19 EU15+ countries for women, and in 18 of 19 countries for men. Increasing AAA mortality was observed only for men in Greece (+5·3 per cent). The largest relative decreases in ASDR between 1990 and 2017 were observed in Australia (men -65·6 per cent, women -50·4 per cent) and Canada (men -60·8 per cent, women -48·6 per cent). Over the 28-year interval, the smallest decreases in ASDR for women were noted in Greece (-2·3 per cent) and in Italy (-2·5 per cent). In 2017, the highest mortality rates were observed in the UK for both men and women (7·5 per 100 000 and 3·7 per 100 000 respectively). The lowest ASDR was observed in Portugal for men (2·8 per 100 000) and in Spain for women (1·0 per 100 000). ASDRs for AAA in 2017 were higher for men than women in all 19 EU15+ countries. The most recent trends demonstrated increasing AAA ASDRs in 14 of 19 countries for both sexes; the increases were relatively small compared with the improvements in the preceding years. CONCLUSION: This observational study identified decreasing mortality from AAA across EU15+ countries since 1990. The most recent trends demonstrated relatively small increases in AAA mortality across the majority of EU15+ countries since 2012.

ANTECEDENTES: Este estudio observacional evalúa las tendencias en las tasas de mortalidad del aneurisma de aorta abdominal (abdominal aortic aneurysm, AAA) en los 19 países integrantes del acrónimo conocido como EU15+ en los aóos 1990-2017. MÉTODOS: Se obtuvieron las tasas de mortalidad estandarizadas por la edad del Global Burden of Disease Study Global Health Data Exchange. Las tendencias se analizaron utilizando el análisis de regresión por puntos de inflexión (joinpoint). RESULTADOS: Entre 1990 y 2017, las tasas de muerte estandarizadas por edad (age-standardized death rates, ASDR) del AAA disminuyeron en todos los 19 EU15+ países para las mujeres, y en 18 de los 19 países para los varones. Solamente se observó un incremento de la mortalidad del AAA para los varones en Grecia (+5,3%). El mayor descenso relativo de ASDR entre 1990-2017 se observó en Australia (varones -65,6%, mujeres -50,4%) y Canadá (varones -60,8%, mujeres -48,6%). A lo largo del periodo de 28 aóos, en el caso de las mujeres, los menores descensos en ASDR se observaron en Grecia (-2,3%) y en Italia (-2,5%). En 2017, las tasas de mortalidad más elevadas se observaron en el Reino Unido tanto para varones como para mujeres (7,5/100.000 y 3,7/100.000 para varones y mujeres, respectivamente). La ASDR más baja se observó en Portugal para varones (2,8/100.000) y Espaóa para mujeres (1,0/100.000). Las ASDRs para AAA en 2017 fueron más altas para varones que para mujeres en todos los 19 países EU15+. Las tendencias más recientes demostraron aumentos de las ASDRs por AAA en 14 de 19 países para varones y mujeres; los aumentos fueron relativamente pequeóos cuando se compararon con las mejorías observadas dentro de los aóos precedentes. CONCLUSIÓN: En este estudio observacional de los países EU15+, se ha identificado una disminución en la mortalidad de los AAA entre los países integrantes de EU15+ desde 1990. Las tendencias más recientes demuestran aumentos relativamente pequeóos de la mortalidad del AAA en la mayoría de los países EU15+ desde 2012.

Comparison between a multicentre, collaborative, closed-loop audit assessing management of supracondylar fractures and the British Orthopaedic Association Standard for Trauma 11 (BOAST 11) guidelines.

Aims: Supracondylar fractures are the most frequently occurring paediatric fractures about the elbow and may be associated with a neurovascular injury. The British Orthopaedic Association Standards for Trauma 11 (BOAST 11) guidelines describe best practice for supracondylar fracture management. This study aimed to assess whether emergency departments in the United Kingdom adhere to BOAST 11 standard 1: a documented assessment, performed on presentation, must include the status of the radial pulse, digital capillary refill time, and the individual function of the radial, median (including the anterior interosseous), and ulnar nerves. Materials and Methods: Stage 1: We conducted a multicentre, retrospective audit of adherence to BOAST 11 standard 1. Data were collected from eight hospitals in the United Kingdom. A total of 433 children with Gartland type 2 or 3 supracondylar fractures were eligible for inclusion. A centrally created data collection sheet was used to guide objective analysis of whether BOAST 11 standard 1 was adhered to. Stage 2: We created a quality improvement proforma for use in emergency departments. This was piloted in one of the hospitals used in the primary audit and was re-audited using equivalent methodology. In all, 102 patients presenting between January 2016 and July 2017 were eligible for inclusion in the re-audit. Results: Stage 1: Of 433 patient notes audited, adherence to BOAST 11 standard 1 was between 201 (46%) and 232 (54%) for the motor and sensory function of the individual nerves specified, 318 (73%) for radial pulse, and 247 (57%) for digital capillary refill time. Stage 2: Of 102 patient notes audited, adherence to BOAST 11 standard 1 improved to between 72 (71%) and 80 (78%) for motor and sensory function of the nerves, to 84 (82%) for radial pulse, and to 82 (80%) for digital capillary refill time. Of the 102 case notes reviewed in stage 2, only 44 (43%) used the quality improvement proforma; when the proforma was used, adherence improved to between 40 (91%) and 43 (98%) throughout. Conclusion: Adherence to BOAST 11 standard 1 is poor in hospitals across the country. This is concerning as neurovascular deficit may be an indication for emergent surgery, and missed neurovascular injury can cause long-term, or even permanent, functional impairment. We present a simple proforma that improves adherence to this standard, can easily be implemented into emergency departments, and may improve patient safety. Cite this article: Bone Joint J 2018;100-B:346-51.

Pathology in skeletons of Peale's dolphin Lagenorhynchus australis from southern South America.

Peale's dolphin Lagenorhynchus australis is frequently seen off the coast of southern South America, where it feeds among coastal kelp beds and occasionally strands. We searched for macroscopic evidence of skeletal lesions in 78 specimens of Peale's dolphin from 2 museum collections, which contain almost all of the species' skeletons known in collections worldwide. Thirty-two specimens (41%) had some type of osteological abnormalities. In 21 cases (66%), congenital deformations were the most predominant abnormality found. Acquired lesions included (1) induced trauma: abnormal curvature (n=5 specimens) and fractures (n=2); (2) infectious diseases: spondylo-osteomyelitis (n=3); and (3) degenerative diseases: exostoses (n=8) and spondylosis deformans (n=4). It is noteworthy that all of these animals died incidentally in gillnet entanglement and were presumably healthy at the time of death. The effect that different osseous lesions may have on an animal's quality of life may depend on the area of the spine affected and the number of vertebrae involved.

Skull shapes of the Lissodelphininae: radiation, adaptation and asymmetry.

Within Delphinidae, the sub-family Lissodelphininae consists of 8 Southern Ocean species and 2 North Pacific species. Lissodelphininae is a result of recent phylogenetic revisions based on molecular methods. Thus, morphological radiation within the taxon has not been investigated previously. The sub-family consists of ecologically diverse groups such as (1) the Cephalorhynchus genus of 4 small species inhabiting coastal and shelf waters, (2) the robust species in the Lagenorhynchus genus with the coastal La. australis, the offshore La. cruciger, the pelagic species La. obscurus and La. obliquidens, and (3) the morphologically aberrant genus Lissodelphis. Here, the shapes of 164 skulls from adults of all 10 species were compared using 3-dimensional geometric morphometrics. The Lissodelphininae skulls were supplemented by samples of Lagenorhynchus albirostris and Delphinus delphis to obtain a context for the variation found within the subfamily. Principal components analysis was used to map the most important components of shape variation on phylogeny. The first component of shape variation described an elongation of the rostrum, lateral and dorsoventral compression of the neurocranium and smaller temporal fossa. The two Lissodelphis species were on the high extreme of this spectrum, while Lagenorhynchus australis, La. cruciger and Cephalorhynchus heavisidii were at the low extreme. Along the second component, La. cruciger was isolated from the other species by its expanded neurocranium and concave facial profile. Shape variation supports the gross phylogenetic relationships proposed by recent molecular studies. However, despite the great diversity of ecology and external morphology within the subfamily, shape variation of the feeding apparatus was modest, indicating a similar mode of feeding across the subfamily. All 10 species were similar in their pattern of skull asymmetry, but interestingly, two species using narrowband high frequency clicks (La. cruciger and C. hectori) were among the most asymmetric species, contradicting previous interpretations of odontocete skull asymmetry. J. Morphol. 277:776-785, 2016. © 2016 Wiley Periodicals, Inc.

The skin of Commerson's dolphins (Cephalorhynchus commersonii) as a biomonitor of mercury and selenium in Subantarctic waters.

The skin of bycaught Commerson's dolphins was tested for mercury (Hg) and selenium (Se) biomonitoring in Subantarctic environments. The correlation of levels detected in the skin with those found in internal tissues - lung, liver, kidney and muscle - was assessed to evaluate how skin represents internal Hg and Se distribution for monitoring purposes. Mercury in skin had a concentration range of 0.68-3.11 µg g(-1) dry weight (DW), while Se had a higher concentration range of 74.3-124.5 µg g(-1) DW. There was no significant correlation between selenium levels in any of the analyzed tissues. Thus, the skin selenium concentration did not reflect the tissular Se levels and did not provide information for biomonitoring. The lack of correlation is explained by the biological role of Se, provided that each tissue regulates Se levels according to physiological needs. However, the skin Hg level had significant positive correlation with the levels in internal tissues (ANOVA p<0.05), particularly with that of muscle (R(2)=0.79; ANOVA p=0.0008). Thus, this correlation permits the estimation of Hg content in muscle based on the multiplication of skin biopsy levels by a factor of 1.85. Mercury bioindication using skin biopsies is a non-lethal approach that allows screening of a large number of specimens with little disturbance and makes possible an adequate sampling strategy that produces statistically valid results in populations and study areas. The correlation between Hg levels in the skin and internal tissues supports the use of the epidermis of Commerson's dolphins for Hg biomonitoring in the waters of the Subantarctic, which is a poorly studied region regarding Hg levels, sources and processes.

Restoration of anti-tetanus toxoid responses in patients initiating highly active antiretroviral therapy with or without a boost immunization: an INITIO substudy.

INITIO is an open-labelled randomized trial evaluating first-line therapeutic strategies for human immunodeficiency virus-1 (HIV-1) infection. In an immunology substudy a tetanus toxoid booster (TTB) immunization was planned for 24 weeks after initiation of highly active antiretroviral therapy (HAART). All patients had received tetanus toxoid immunization in childhood. Generation of proliferative responses to tetanus toxoid was compared in two groups of patients, those receiving a protease inhibitor (PI)-sparing regimen (n = 21) and those receiving a PI-containing (n = 54) regimen. Fifty-two participants received a TTB immunization [PI-sparing (n = 15), PI-containing (n = 37)] and 23 participants did not [PI-sparing (n = 6) or PI-containing (n = 17)]. Cellular responses to tetanus antigen were monitored by lymphoproliferation at time of immunization and every 24 weeks to week 156. Proportions with a positive response (defined as stimulation index > or = 3 and Delta counts per minute > or = 3000) were compared at weeks 96 and 156. All analyses were intent-to-treat. Fifty-two participants had a TTB immunization at median 25 weeks; 23 patients did not. At weeks 96 and 156 there was no evidence of a difference in tetanus-specific responses, between those with or without TTB immunization (P = 0.2, P = 0.4). There was no difference in the proportion with response between those with PI-sparing or PI-containing regimens at both time-points (P = 0.8, P = 0.7). The proliferative response to tetanus toxoid was unaffected by initial HAART regimen. Anti-tetanus responses appear to reconstitute eventually in most patients over 156 weeks when treated successfully with HAART, irrespective of whether or not a TTB immunization has been administered.

Randomised controlled trial and economic evaluation of podophyllotoxin solution, podophyllotoxin cream, and podophyllin in the treatment of genital warts.

OBJECTIVES: To evaluate the efficacy and cost effectiveness of self applied podophyllotoxin 0.5% solution and podophyllotoxin 0.15% cream, compared to clinic applied 25% podophyllin in the treatment of genital warts over 4 weeks. METHODS: We conducted a randomised controlled trial in 358 immunocompetent men and women with genital warts of 3 months' duration or less. RESULTS: In the principal analysis both podophyllotoxin solution (OR 2.93, 95% CI 1.56 to 5.50) and podophyllotoxin cream (OR 1.97, 95% CI 1.04 to 3.70) were associated with significantly increased odds of remission of all warts compared to podophyllin. We performed two further analyses. When subjects defaulting from follow up were assumed to have been cured odds of remission of all warts were also significantly increased both for podophyllotoxin solution (OR 3.04, 95% CI 1.68 to 5.49) and for podophyllotoxin cream (OR 2.46, 95% CI 1.38 to 4.40). When subjects defaulting from follow up were assumed not to have been cured odds of remission of all warts were significantly increased for podophyllotoxin solution (OR 1.92, 95% CI 1.13 to 3.27), but not for podophyllotoxin cream (OR 1.17, 95% CI 0.69 to 2.00). Local side effects were seen in 24% of subjects, and recurrence of warts within 12 weeks of study entry in 43% of all initially cleared subjects, without statistically significant differences between the treatment groups. Direct, indirect, and total costs were similar across the three treatment groups. Podophyllotoxin solution was the most cost effective treatment, followed by podophyllotoxin cream, with podophyllin treatment being the least cost effective. CONCLUSIONS: Self treatment of anogenital warts with podophyllotoxin showed greater efficacy and cost effectiveness than clinic based treatment with podophyllin.

Origin and radiation of Southern Hemisphere coastal dolphins (genus Cephalorhynchus).

The genus Cephalorhynchus (Gray 1846) consists of four species of small coastal dolphins distributed in cool temperate waters around the Southern Hemisphere. Each species is sympatric with other members of the subfamily Lissodelphininae but widely separated from other congeners. To describe the origin and radiation of these species, we examined 442 bp of mitochondrial DNA control region sequences of 307 individuals from the genus Cephalorhynchus and compared these to sequences from other members of the subfamily Lissodelphininae. We investigate the hypotheses that Cephalorhynchus is a monophyletic genus or, alternatively, that the four species have arisen separately from pelagic Lissodelphine species and have converged morphologically. Our results support the monophyly of Cephalorhynchus within the Lissodelphininae and a pattern of radiation by colonization. We confirm a pattern of shallow but diagnosable species clades with Heaviside's dolphin as the basal branch. We further examine the monophyly of maternal haplotypes represented by our large population sample for each species. Based on this phylogeographic pattern, we propose that Cephalorhynchus originated in the waters of South Africa and, following the West Wind Drift, colonized New Zealand and then South America. The Chilean and Commerson's dolphins then speciated along the two coasts of South America, during the glaciation of Tierra del Fuego. Secondary radiations resulted in genetically isolated populations for both the Kerguelen Island Commerson's dolphin and the North Island Hector's dolphin. Our results suggest that coastal, depth-limited odontocetes are prone to population fragmentation, isolation and occasionally long-distance movements, perhaps following periods of climatic change.

Bronchopulmonary Kaposi's sarcoma in 106 HIV-1 infected patients.

The objectives of this study were to describe the clinical and radiological features at presentation, and the natural history of HIV-related bronchopulmonary Kaposi's sarcoma. A retrospective review of medical records and chest radiographs was performed in 106 HIV-infected homosexual men with bronchopulmonary Kaposi's sarcoma diagnosed at bronchoscopy between September 1988 and November 1994. The majority of patients had evidence of advanced HIV disease at diagnosis (median CD4 cell count was 15 x 10(6)/l, range 0-288), and 93% had had a diagnosis of cutaneous Kaposi's sarcoma for a median duration of 11 months prior to diagnosis of their bronchopulmonary disease. The most frequent symptoms at presentation were cough (92%), dyspnoea (69%), pleuritic pain (20%), haemoptysis (13%) and wheezing (10%). The most common radiological finding in 73% of our series was of poorly defined and confluent opacities, with predominant middle and lower zone involvement. Median survival was 4 months (range 0-37 months) from diagnosis and 9 months (range 1-25) from the onset of symptoms. Treatment with either chemotherapy or radiotherapy was associated with a significantly reduced risk of death (hazards ratio (HR)=0.48, 95% CI=0.26-0.87). Factors associated with a poor survival, after adjustment for treatment effect were older age (HR=1.79, 95% CI=1.22-2.84) for each 10-year increase in age; a history of pleuritic pain (HR=2.97, 95% CI=1.39-6.32); presence of pleural effusion on X-ray (HR=2.01, 95% CI=1.13-3.59) and a prior diagnosis of cutaneous Kaposi's sarcoma (HR=1.8, 95% CI=1.00, 3.24). Bronchopulmonary Kaposi's sarcoma occurs mainly in patients with advanced HIV disease and a prior history of cutaneous disease. Survival is poor, and adverse prognostic factors include older age at diagnosis and the presence of pleural disease.

Nickel-57-doxorubicin, a potential radiotracer for pharmacokinetic studies using PET: production and radiolabelling.

The clinical use of anthracyclines, such as doxorubicin (DXR), is hampered by tumour development of multidrug resistance (MDR). The drug efflux associated with MDR could be characterised in vivo using Positron Emission Tomography (PET) in conjunction with a suitable radiolabelled drug. We are investigating DXR labelled with the positron emitter 57Ni as a potential analogue of the parent drug. Essential to this work is the production of a high purity radionuclide in a suitable chemical form for the preparation of radiolabelled DXR. To optimise production parameters, excitation functions (reaction cross section as a function of beam energy) for proton induced reactions in cobalt were measured up to 60 MeV. The excitation function for the 59Co(p,3n)57Ni reaction shows a maximum cross section of 13.8 +/- 1.5 mb at 38 MeV. The optimum energy range for production of 57Ni was found to be 41-->26 MeV resulting in an experimental thick target yield of 17.8 MBq/muAh. The level of the 56Ni impurity is only 0.21% at the end of bombardment. A radiochemical procedure, based on cation-exchange chromatography, has been developed for the separation of radionickel from the cobalt target and other radiochemical and chemical impurities. The 57Ni activity was eluted, using 2M HCl, from a Dowex-50Wx8(H+) column, in a 95% radiochemical yield. Optimum labelling of DXR has been investigated in terms of pH, reaction time and temperature, achieving radiochemical yields > 94%. DXR labelled with 57Ni therefore shows promise as a radiotracer for pharmacokinetic studies using PET.

Evaluation of the expression levels of nm23-H1 mRNA in primary breast cancer, benign breast disease, axillary lymph nodes and normal breast tissue.

Expression levels of nm23-H1 were evaluated in a variety of normal benign and malignant breast tissues by Northern and slot blot. Tissues from 153 patients presenting with palpable breast lesions were studied: 132 primary infiltrating breast cancers, 9 pure duct carcinoma in situ lesions, a phyllodes tumor, 9 benign lesions and 2 local recurrences of carcinoma. In addition to lesional tissue, 49 samples of macroscopically normal breast tissue, 37 axillary lymph nodes and 9 samples from patients undergoing cosmetic reduction mammoplasty were studied. Sets of normal breast tissue, primary tumor and lymph node tissue from individual patients were available for comparison in 37 cases. A wide range of gene expression was detected in the various tissue types. The highest levels of expression were detected in malignant samples with in situ carcinomas being associated with the highest levels of gene expression. The expression levels of nm23-H1 in normal breast tissue were lower than the corresponding tumors from the same patients (p < 0.0005). Benign breast lesions (including 6 fibroadenomas) had levels of gene expression approximating those of the normal tissue samples. Normal axillary lymph nodes had significantly lower levels of nm23-H1 expression than nodes with metastatic deposits (p < 0.03). No significant association was observed between nm23-H1 expression levels and axillary node status in patients with infiltrating carcinoma, although there was a slight trend toward lower nm23-H1 mRNA levels in the node negative group.(ABSTRACT TRUNCATED AT 250 WORDS)

Early experience with laparoscopic herniorrhaphy: results after the first 60 procedures.

The results of the first 60 consecutive laparoscopic hernia repairs performed in Calderdale are presented. These results are encouraging as recovery from surgery is much quicker and allows a shorter hospital stay and a speedier return to work than conventional operations. The laparoscopic procedure takes longer to perform, although this does not seem unacceptable once experience is gained. At present it remains quite expensive and further reductions in hospital stay will need to be achieved to ensure that there is no overall increase in the financial resources required.

The 62 MeV proton beam for the treatment of ocular melanoma at Clatterbridge.

A second treatment room and beam line has been constructed at the Cyclotron Unit at Clatterbridge for the purpose of using 62 MeV protons for the treatment of ocular melanoma. A uniform beam is produced by a double foil scattering system. The initial Bragg peak is spread across the target volume by the use of beam modulators. These are rotating four-vaned stepped absorbers made from Perspex. Two beam lines can be configured with different positions of modulators and range limiters. The first has a maximum penetration of 31.9 +/- 0.2 mm in water and the second a penetration of 31.2 +/- 0.2 mm. The second configuration has the advantage of less variation in beam penumbra, with a typical value of 1.7 +/- 0.1 mm for the 90% to 10% decrement lines. The patients are treated with individually shaped collimators. Beam output varies by less than 2% over the range of collimator areas used. The resulting whole-body dose equivalent to patient has also been assessed. In the first three years of operation over 250 patients have been treated.

Efficacy and distribution of single-dose preoperative antibiotic prophylaxis in high-risk gastroduodenal surgery.

Although a single preoperative dose of antibiotic is now the accepted means of preventing postoperative surgical infection, the method has not been investigated adequately. In patients at high risk of infection who underwent gastroduodenal operations, the authors compared single-dose prophylaxis by intravenous cefotaxime (26 patients) with short-course perioperative prophylaxis (27 patients). No wound infection occurred, but in one patient in each group a subphrenic abscess developed after leakage at the anastomosis. The half-life of cefotaxime (1.23 +/- 0.12 hours) and its apparent volume of distribution (16.7 +/- 2.6 L/1.73 m2 resulted in perioperative levels of the antibiotic in blood (34.76 +/- 4.21 micrograms/mL), gastric mucosa (32.04 +/- 5.22 micrograms/mL) and subcutaneous fat (24.98 +/- 5.89 micrograms/mL) more than twice the usual minimal inhibitory concentration of the drug for organisms grown from the stomach contents and wound fat. These clinical and pharmacologic findings validate the efficacy of a single preoperative intravenous dose of the antibiotic in preventing postoperative infection in high-risk patients who undergo gastroduodenal surgery.