Centralisation of rectal cancer care has improved patient survival in the republic of Ireland.

BACKGROUND: Centralisation of rectal cancer surgery to designated centres was a key objective of the Irish national cancer control program. A national audit of rectal cancer surgery indicated centralisation was associated with improved early surgical outcomes. This study aimed to determine the impact of implementation of the national cancer strategy on survival from rectal cancer. MATERIALS AND METHODS: Data were collected from the National Cancer Registry of Ireland to include all patients with Stage I-III rectal cancer undergoing rectal cancer surgery with curative intent between 2003 and 2012. Five-year overall survival and cancer-specific survival was compared between patients in the pre-centralisation (2003-2007) and post-centralisation period (2008-2012) and between patients receiving surgery in designated cancer centres and non-cancer centres. RESULTS: The proportion of rectal cancer surgery performed in a designated cancer centre increased from 42% during 2003-2007 to 58% during 2008-2012. Five-year overall survival increased from 66.1% in 2003-2007 to 73.5% in 2008-2012 (p < 0.001). Five-year cancer-specific survival increased from 75.3% in 2003-2007 to 81.9% in 2008-2012 (p < 0.001). Surgery in a cancer centre and surgery post-centralisation were significantly associated with overall and cancer specific survival using Cox proportional hazards regression. CONCLUSION: Survival following resection of rectal cancer was significantly improved following implementation of a national cancer strategy incorporating centralisation of rectal cancer surgery.

Mucinous and non-mucinous colorectal cancers show differential expression of chemotherapy metabolism and resistance genes.

Previous research has identified differences in mutation frequency in genes implicated in chemotherapy resistance between mucinous and non-mucinous colorectal cancers (CRC). We hypothesized that outcomes in mucinous and non-mucinous CRC may be influenced by expression of genes responsible for chemotherapy resistance. Gene expression data from primary tumor samples were extracted from The Cancer Genome Atlas PanCancer Atlas. The distribution of clinical, pathological, and gene expression variables was compared between 74 mucinous and 521 non-mucinous CRCs. Predictors of overall survival (OS) were assessed in a multivariate analysis. Kaplan-Meier curves were constructed to compare survival according to gene expression using the log rank test. The median expression of 5-FU-related genes TYMS, TYMP, and DYPD was significantly higher in mucinous CRC compared to non-mucinous CRC (p < 0.001, p = 0.003, p < 0.001, respectively). The median expression of oxaliplatin-related genes ATP7B and SRPK1 was significantly reduced in mucinous versus non-mucinous CRC (p = 0.004, p = 0.007, respectively). At multivariate analysis, age (odds ratio (OR) = 0.96, p < 0.001), node positive disease (OR = 0.49, p = 0.005), and metastatic disease (OR = 0.32, p < 0.001) remained significant negative predictors of OS, while high SRPK1 remained a significant positive predictor of OS (OR = 1.59, p = 0.037). Subgroup analysis of rectal cancers demonstrated high SRPK1 expression was associated with significantly longer OS compared to low SRPK1 expression (p = 0.011). This study highlights that the molecular differences in mucinous CRC and non-mucinous CRC extend to chemotherapy resistance gene expression. SRPK1 gene expression was associated with OS, with a prognostic role identified in rectal cancers.

Microsatellite instability and response to neoadjuvant chemoradiotherapy in rectal cancer: A systematic review and meta-analysis.

BACKGROUND: Response to neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer is variable. Identification of biomarkers to predict response is desirable in order to provide prognostic information and targeted therapy. Several studies have investigated microsatellite instability (MSI) as a predictor of response to CRT with contradictory results. This study aims to clarify the effect of MSI status on response to CRT in locally advanced rectal cancer through systematic review and meta-analysis. METHODS: A systematic search of PubMed, Embase and Cochrane databases was performed for all studies relating to MSI and response to CRT in rectal cancer using the search algorithm (Microsatellite Instability) AND (Chemoradiotherapy) AND (Rectal Cancer). From each included study the number of patients with MSI tumors and Microsatellite Stable (MSS) tumors and the numbers achieving pathological complete response (pCR) were recorded. Pooled outcome measures were determined using a random effects model and the odds ratio estimated with variance and 95% confidence interval. RESULTS: Nine published studies were identified reporting data on MSI and its effect on outcome after CRT for locally advanced rectal cancer. Five studies describing 5,877 patients included data on MSI and the number of patients achieving pCR. There was no significant association between MSI and pCR (MSI Vs MSS: 10.1% Vs 6.6%, OR 1.38, 95% CI: 0.7-2.72, p = 0.35). CONCLUSION: This meta-analysis concludes that there appears to be no significant difference in pCR rate following CRT in patients with MSI versus MSS rectal tumors.

Risk of colorectal cancer associated with BRCA1 and/or BRCA2 mutation carriers: systematic review and meta-analysis.

BACKGROUND: Carriers of the BRCA1 and/or BRCA2 mutation incur a lifetime risk of up to 85 per cent for breast cancer, and between 20 and 40 per cent for ovarian cancer. Efforts to estimate the lifetime risk of developing colorectal cancer for BRCA mutation carriers have produced conflicting results. Consequently, there are no formal guidelines regarding the need for bowel screening for individuals with BRCA1 and/or BRCA2 mutations. This systematic review and meta-analysis determined the risk of colorectal cancer associated with BRCA carrier mutations. METHODS: The primary outcome was incidence of colorectal cancer in BRCA mutation carriers. Secondary outcomes were the incidence in BRCA1 and BRCA2 carriers, Ashkenazi Jews, and age- and sex-matched cohorts. RESULTS: Eleven studies were included in the review, with an overall population of 14 252 and 4831 colorectal cancers identified. Nine studies were included in the meta-analysis. There was no increase in colorectal cancer among patients carrying a BRCA mutation (odds ratio 1·03, 95 per cent c.i. 0·80 to 1·32; P = 0·82). After adjustment for Ashkenazi heritage, and age and sex estimates, there was no increased odds of developing colorectal cancer (with no heterogeneity, I2  = 0 per cent). CONCLUSION: BRCA1 and/or BRCA2 mutation carriers are not at a higher risk of colorectal cancer.

ANTECEDENTES: Las portadoras de la mutación BRCA1 y/o BRCA2 presentan un riesgo a lo largo de la vida de hasta un 85% para presentar un cáncer de mama y entre 20-40% para el cáncer de ovario. Los esfuerzos para estimar el riesgo de desarrollar cáncer colorrectal (colorectal cancer, CCR) a lo largo de la vida en portadoras de mutaciones BRCA han dado resultados contradictorios. En consecuencia, no existen pautas formales con respecto a la necesidad de realizar el cribado de CRC en personas portadoras de mutaciones BRCA1 y/o BRCA2. Esta revisión sistemática y metaanálisis analiza el riesgo de CRC asociado en pacientes portadoras de mutaciones BRCA. MÉTODOS: Se incluyeron nueve estudios en el metaanálisis. La población general del estudio fue de 18.839 pacientes, con 4.978 con CRC identificado. La variable principal fue la incidencia de cáncer colorrectal en portadoras de mutaciones BRCA. Las variables secundarias incluyeron el análisis de la incidencia de subgrupos en BRCA 1, BRCA 2, etnia judía Ashkenazi y cohortes emparejadas por edad y sexo. RESULTADOS: No hubo un aumento de CRC en pacientes con una mutación BRCA (razón de oportunidades, odds ratio, OR 1,03; i.c. del 95% 0,80-1,32; P = 0,82). Cuando se ajustó de acuerdo con la ascendencia Ashkenazi y las estimaciones de edad y sexo, no hubo mayores probabilidades de desarrollar cáncer colorrectal (sin heterogeneidad en los estudios (I2 = 0)). CONCLUSIÓN: Este metaanálisis concluye que el riesgo de cáncer colorrectal no fue significativamente mayor en las portadoras de mutaciones BRCA1 y/o BRCA2. Sin embargo, se requiere más evidencia antes de no recomendar la colonoscopia de cribado a las portadoras de la mutación BRCA1/2. Las pruebas de inmunoquímica fecal pueden ser una alternativa apropiada en esta población.

Diversity and bioactivity of fungi associated with the marine sea cucumber Holothuria poli: disclosing the strains potential for biomedical applications.

AIMS: Identification of the mycobiota associated to the marine echinoderm Holothuria poli and investigation of cytotoxic and pro-osteogenic potential of isolated strains. METHODS AND RESULTS: Fungal strains were isolated from the animal's body-wall, intestine and faeces. The species identification was based on DNA barcoding and morphophysiological observations. Forty-seven species were identified, all are Ascomycota and mainly belonging to Aspergillus and Penicillium genera. Sixteen strains were grown on three media for chemical extraction. Cytotoxic activity was tested on a hepatic cancer cell line (HepG2), the cells viability was evaluated after treatment using a resazurin based assay (AlamarBlue). Pro-osteogenic activity was tested on human Mesenchymal stem cell, differentiation was measured as the alkaline phosphatase production through reaction with p-nitrophenylphosphate or as the cells ability to mineralize calcium using a colorimetric kit (StanBio). Cytotoxic activity was recorded for four fungal species while five of 48 extracts highlighted bioactivity towards human mesenchymal stem cells. CONCLUSIONS: The presence of relevant animal-associated mycobiota was observed in H. poli and selected strains showed cytotoxic potential and pro-osteogenic activity. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work represents the first report of a Mediterranean Sea cucumber mycobiota and highlights the isolates potential to synthetize compounds of pharmaceutical interest for regenerative medicine.

The utility of preoperative radiological evaluation of early rectal neoplasia: a systematic review and meta-analysis.

AIM: The diagnostic role for preoperative imaging of clinically benign rectal adenomas is unclear. The objective of this systematic review and meta-analysis was to examine the diagnostic accuracy of preoperative imaging in distinguishing benign adenomas from rectal cancer. METHOD: A systematic search was performed for all studies published that correlated staging of clinically benign rectal adenomas with endorectal ultrasound (ERUS) or MRI and histology. Imaging was compared with postoperative histology and data on the numbers of true positives, false positives, true negatives and false negatives were extracted. Summary estimates of sensitivity and specificity with 95% CIs were calculated using a bivariate random effects model. The QUADAS2 tool was used to determine the methodological quality of included studies. RESULTS: Eleven studies describing 1511 patients were retrieved. A total of 1134 patients underwent local excision and 377 had a formal proctectomy. A benign rectal adenoma was diagnosed in 840 and 214 had a T1 rectal cancer. For confirming benign adenomas, the pooled sensitivity of ERUS was 0.81 (95% CI 0.69-0.89) and specificity was 0.85 (95% CI 0.68-0.93). For detecting occult T1 tumours, the pooled sensitivity of ERUS was 0.50 (95% CI 0.33-0.66) and specificity was 0.89 (95% CI 0.82-0.94). Quantitative analysis of MRI could not be performed due to insufficient studies. CONCLUSION: This study demonstrates the limited accuracy of preoperative ERUS in distinguishing benign adenomas from T1 rectal cancer. Preoperative imaging must be interpreted with caution to prevent over-staging and unnecessary proctectomy. We propose that clinically benign lesions may undergo local excision, with subsequent management based on final histology.

PATI: Patient accessed tailored information: A pilot study to evaluate the effect on preoperative breast cancer patients of information delivered via a mobile application.

OBJECTIVES: The information needs of cancer patients are highly variable. Literature suggests an improved ability to modulate personalised stress, increased patient involvement with decision making, greater satisfaction with treatment choices and reduced anxiety levels in cancer patients who have access to information. The aim of this project was to evaluate the effects of a mobile information application on anxiety levels of patients undergoing surgery for breast cancer. MATERIALS AND METHODS: An application was developed for use with Apple iPad containing information on basic breast cancer biology, different treatments used and surgical techniques. Content and face validity studies were performed. A randomized control trial was designed, with a 1:2 allocation. Data collected include basic demographics and type of surgery. Questionnaires used included: the HADS, Mini-MAC, information technology familiarity and information satisfaction. RESULTS: A total of 39 women participated. 13 women had access to an iPad containing additional information and 26 women acted as controls. The mean age was 54 and technology familiarity was similar among both groups. Anxiety and depression scores at seven days were significantly lower in control patients without access to the additional information provided by the mobile application (p = 0.022 and 0.029 respectively). CONCLUSION: Anxiety and depression in breast cancer patients is both multifactorial and significant, with anxiety levels directly correlating with reduced quality of life. Intuitively, information should improve anxiety levels, however, we have demonstrated that surgical patients with less information reported significantly lower anxiety. We advise the thorough testing and auditing of information initiatives before deployment.

Late cardiac effects of chemotherapy in breast cancer survivors treated with adjuvant doxorubicin: 10-year follow-up.

Doxorubicin (Dox), a mainstay of adjuvant breast cancer treatment, is associated with cardiac toxicity in the form of left ventricular dysfunction (LVD), LV diastolic dysfunction, or LV systolic dysfunction. Study objectives were to evaluate the prevalence of LVD in long-term breast cancer survivors treated with Dox and determine if brain-type natriuretic peptide (BNP) may help identify patients at risk for LVD. Patients who participated in prospective clinical trials of adjuvant Dox-based chemotherapy for breast cancer with a baseline left ventricular (LV) ejection fraction evaluation from 1999 to 2006 were retrospectively identified from the St Vincent's University Hospital database. Patients were invited to undergo transthoracic echocardiography, BNP analysis, and cardiovascular (CV) risk factor assessment. LVDD was defined as left atrial volume index >34 mL/m(2) and/or lateral wall E prime <10 m/s, and LVSD as LVEF <50 %. Of 212 patients identified, 154 participated, 19 patients had died (no cardiac deaths), and 39 declined. Mean age was 60.7 [55:67] years. A majority of the patients (128, 83 %) had low CV risk (0/1 risk factors), 21 (13.6 %) had 2 RFs, and 5 (3.2 %) ≥3 RFs. BMI was 27.2 ± 4.9 kg/m(2). Median Dox dose was 240 mg/m(2) [225-298]; 92 patients (59.7 %) received ≤240 mg/m(2) and 62 (40.3 %) > 240 mg/m(2). Baseline LVEF was 68.2 ± 8 %. At follow-up of 10.8 ± 2.2 years, LVEF was 64.4 ± 6 %. Three (1.9 %) subjects had LVEF <50 % and one (0.7 %) had LVDD. Dox >240 mg/m2 was associated with any LVEF drop. BNP levels at follow-up were 20.3 pg/ml [9.9-36.5] and 21.1 pg/ml [9.8-37.7] in those without LVD and 61.5 pg/ml [50-68.4] in those with LVD (p = 0.04). Long-term prospective data describing the impact of Dox on cardiotoxicity are sparse. At over 10 years of follow-up, decreases in LVEF are common, and dose related, but LVD as defined is infrequent (2.6 %). Monitoring with BNP for subclinical LVD needs further evaluation.

Conservative management of neurocysticercosis in a patient with hematopoietic stem cell transplantation: a case report and review.

Neurocysticercosis, an infection of the central nervous system with the larval stage of the cestode Taenia solium, is common in developing countries but its occurrence and management in allogeneic hematopoietic stem cell transplantation (HSCT) has not been reported previously, to our knowledge. We report the case of an immigrant female patient who underwent a matched-related allogeneic HSCT for acute lymphoblastic leukemia and was incidentally found to have a solitary viable neurocysticercosis lesion. However, despite severe immunosuppression, the size of the cyst did not increase. More importantly, restoration of the immune system did not induce significant inflammation or seizures. Subsequent follow-up demonstrated complete resolution of the neurocysticercosis lesion. Thus, in the setting of HSCT, an asymptomatic patient with a single neurocysticercosis lesion was successfully managed without the use of anthelmintics, steroids, or anti-epileptics.

Post-traumatic immunosuppression is reversed by anti-coagulated salvaged blood transfusion: deductions from studying immune status after knee arthroplasty.

Major trauma increases vulnerability to systemic infections due to poorly defined immunosuppressive mechanisms. It confers no evolutionary advantage. Our objective was to develop better biomarkers of post-traumatic immunosuppression (PTI) and to extend our observation that PTI was reversed by anti-coagulated salvaged blood transfusion, in the knowledge that others have shown that non-anti-coagulated (fibrinolysed) salvaged blood was immunosuppressive. A prospective non-randomized cohort study of patients undergoing primary total knee arthroplasty included 25 who received salvaged blood transfusions collected post-operatively into acid-citrate-dextrose anti-coagulant (ASBT cohort), and 18 non-transfused patients (NSBT cohort). Biomarkers of sterile trauma included haematological values, damage-associated molecular patterns (DAMPs), cytokines and chemokines. Salvaged blood was analysed within 1 and 6 h after commencing collection. Biomarkers were expressed as fold-changes over preoperative values. Certain biomarkers of sterile trauma were common to all 43 patients, including supranormal levels of: interleukin (IL)-6, IL-1-receptor-antagonist, IL-8, heat shock protein-70 and calgranulin-S100-A8/9. Other proinflammatory biomarkers which were subnormal in NSBT became supranormal in ASBT patients, including IL-1ß, IL-2, IL-17A, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and annexin-A2. Furthermore, ASBT exhibited subnormal levels of anti-inflammatory biomarkers: IL-4, IL-5, IL-10 and IL-13. Salvaged blood analyses revealed sustained high levels of IL-9, IL-10 and certain DAMPs, including calgranulin-S100-A8/9, alpha-defensin and heat shock proteins 27, 60 and 70. Active synthesis during salvaged blood collection yielded increasingly elevated levels of annexin-A2, IL-1ß, Il-1-receptor-antagonist, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IFN-γ, TNF-α, transforming growth factor (TGF)-ß1, monocyte chemotactic protein-1 and macrophage inflammatory protein-1α. Elevated levels of high-mobility group-box protein-1 decreased. In conclusion, we demonstrated that anti-coagulated salvaged blood reversed PTI, and was attributed to immune stimulants generated during salvaged blood collection.

The novel toluidine sulphonamide EL102 shows pre-clinical in vitro and in vivo activity against prostate cancer and circumvents MDR1 resistance.

BACKGROUND: Taxanes are routinely used for the treatment of prostate cancer, however the majority of patients eventually develop resistance. We investigated the potential efficacy of EL102, a novel toluidine sulphonamide, in pre-clinical models of prostate cancer. METHODS: The effect of EL102 and/or docetaxel on PC-3, DU145, 22Rv1 and CWR22 prostate cancer cells was assessed using cell viability, cell cycle analysis and PARP cleavage assays. Tubulin polymerisation and immunofluorescence assays were used to assess tubulin dynamics. CWR22 xenograft murine model was used to assess effects on tumour proliferation. Multidrug-resistant lung cancer DLKPA was used to assess EL102 in a MDR1-mediated drug resistance background. RESULTS: EL102 has in vitro activity against prostate cancer, characterised by accumulation in G2/M, induction of apoptosis, inhibition of Hif1α, and inhibition of tubulin polymerisation and decreased microtubule stability. In vivo, a combination of EL102 and docetaxel exhibits superior tumour inhibition. The DLKP cell line and multidrug-resistant DLKPA variant (which exhibits 205 to 691-fold greater resistance to docetaxel, paclitaxel, vincristine and doxorubicin) are equally sensitive to EL102. CONCLUSION: EL102 shows potential as both a single agent and within combination regimens for the treatment of prostate cancer, particularly in the chemoresistance setting.

A role for MRP8 in in stent restenosis in diabetes.

OBJECTIVE: The most common cause of death in diabetes mellitus is cardiovascular disease. Patients frequently undergo vascular intervention such as stenting. The occurrence of in stent restenosis (ISR) has been reduced by the use of drug eluting stents in non-diabetic patients but the incidence of restenosis and stent thrombosis remains higher in diabetic patients. We investigated the pathogenesis of in stent restenosis in an animal model of type 2 diabetes mellitus. METHODS AND RESULTS: Stents were placed in Zucker Fatty rat (ZFR) and wild type rat carotid arteries, and tissues were harvested 14 days post surgery for morphometric analysis. Unstented carotid arteries from both groups were harvested for microarray analysis. In vitro apoptosis, proliferation and migration assays were performed on rat and human aortic endothelial cells (EC). ZFRs developed an exaggerated intimal response to stent placement compared to wild type controls 14 days post stent placement. MRP8 and MRP14 were up-regulated in unstented ZFR carotid arteries in comparison to controls. Expression of MRP8/14 was also elevated in EC exposed to high glucose conditions. EC function was impaired by high glucose concentrations, and this effect could be mimicked by MRP8 over-expression. MRP8 knockdown by shRNA significantly restored EC function after exposure to high glucose concentrations. MRP8 expression in glucose exposed cells was also inhibited using pharmacological blockade of glucose-induced pathways. CONCLUSIONS: EC dysfunction caused by elevated glucose levels could be mimicked by MRP8/14 over-expression and reversed/prevented by MRP8 knockdown. Thus, MRP8/14 likely plays a role in exaggerated ISR in diabetes mellitus, and MRP8 inhibition may be useful in improving outcome after stent placement in diabetes mellitus.

Young adults' preferred options for receiving chlamydia screening test results: a cross-sectional survey of 6085 young adults.

We investigated how young adults aged 18-29 years would like to be notified of chlamydia screening test results, and, when they test positive, their willingness and preferred mechanism for informing their partners. We conducted a cross-sectional survey of 6085 young adults and found that a call to their mobile phone was their preferred way of receiving positive test results (selected by 50%), followed by email. Text messages (short message service [SMS]) and calls to landline phones were unpopular options, selected by between 5 and 10%. Over 75% of respondents stated they would inform their current partner of a positive chlamydia diagnosis, and 50% would inform their previous partners. Most were willing to receive yearly reminders to go for a chlamydia test. Young adults preference for being informed of chlamydia test results by mobile phone call, rather than by email or SMS text, especially if they test positive, suggests they place high value on the security of the communication mechanism. Offering a range of mechanisms for receipt of test results may increase the acceptability and coverage of sexually transmitted infection (STI) control strategies.

Visual outcomes and graft survival following corneal transplants: the need for an Irish National Corneal Transplant Registry.

PURPOSE: To evaluate visual outcomes and corneal graft survival at 12 months postoperatively, and to demonstrate the need for an Irish National Corneal Transplant Registry. METHODS: Retrospective, single surgeon, single center, analysis of 44 consecutive corneal transplants was performed between 2001 and 2005. RESULTS: Forty-four eyes of 41 patients underwent penetrating keratoplasty (n = 37), lamellar keratoplasty (n = 6) or limbal graft (n = 1). Indications for surgery (%) were keratoconus 45.45%; bullous keratopathy 2.7%; graft failure 9%; Fuchs endothelial dystrophy 2 4.5%; Irido corneal endothelial syndrome 2.27% and tectonic 15.9%. Visual outcome at 1 year (%) were as follows: improved by one or more Snellen lines (79.5%); disimproved by one or more Snellen lines (9%); unchanged (11.5%). Graft survival at 1 year was 93%. DISCUSSION: Although our findings compare favourably with those of the Australian Corneal Graft Registry, there is no Irish Corneal Transplant Registry with which to compare our results.

Ocular injury in hurling.

OBJECTIVES: To describe the clinical characteristics of ocular injuries sustained in hurling in the south of Ireland and to investigate reasons for non-use of protective headgear and eye wear. METHODS: Retrospective review of the case notes of 310 patients who attended Cork University Hospital or Waterford Regional Hospital between 1 January 1994 and 31 December 2002 with ocular injuries sustained during a hurling match. A confidential questionnaire on reasons for non-use of protective headgear and eye wear was completed by 130 players. RESULTS: Hurling related eye injuries occurred most commonly in young men. Fifty two patients (17%) required hospital admission, with hyphaema accounting for 71% of admissions. Ten injuries required intraocular surgical INTERVENTION: retinal detachment repair (5); macular hole surgery (1); repair of partial thickness corneal laceration (1); repair of globe perforation (1); enucleation (1); trabeculectomy for post-traumatic glaucoma (1). Fourteen eyes (4.5%) had a final best corrected visual acuity (BCVA) of <6/12 and six (2%) had BCVA <3/60. In the survey, 63 players (48.5%) reported wearing no protective facemask while playing hurling. Impairment of vision was the most common reason cited for non-use. CONCLUSIONS: Hurling related injury is a significant, and preventable, cause of ocular morbidity in young men in Ireland. The routine use of appropriate protective headgear and faceguards would result in a dramatic reduction in the incidence and severity of these injuries, and should be mandatory.

Familial interstitial lung disease in children: response to chloroquine treatment in one sibling with desquamative interstitial pneumonitis.

We describe a male infant with biopsy-confirmed interstitial lung disease (ILD) who responded to chloroquine, after he failed to improve on oral corticosteroids or cyclophosphamide. The infant presented at 8 days of age with respiratory distress and cyanosis. Lung biopsy at 8 weeks of age was consistent with desquamative interstitial pneumonitis (DIP). He was treated with corticosteroids at 2 weeks of age because of a family history of two siblings who died during infancy and who had DIP on postmortem examination. At 8.5 months, our patient was treated with cyclophosphamide because of lack of response to corticosteroids therapy. At 14 months of age, he began treatment with chloroquine in addition to corticosteroids and had a dramatic response within 3 weeks. The patient has been maintained successfully on continuous treatment with chloroquine alone for more than 9 years since this treatment was started.

An information system to improve the safety and efficiency of chemotherapy ordering.

We developed a computer application to support the ordering of chemotherapy. Key goals were to guard against errors in chemotherapy ordering and dosing, to, coordinate the outpatient and inpatient chemotherapy services, and to support the overall process flow of a chemotherapy cycle. In a six-month period, 512 daily-dose and 386 weekly-dose warnings were generated; 167 (19%) resulted in a cancellation or re-evaluation of the dose. The system has been well accepted, and has helped to coordinate the efforts of the many members of the oncology care team.

Characterization of cDNAs encoding the murine interleukin 2 receptor (IL-2R) gamma chain: chromosomal mapping and tissue specificity of IL-2R gamma chain expression.

The IL-2R gamma chain (IL-2R gamma) is an essential component of high- and intermediate-affinity IL-2Rs, playing critical roles for ligand binding and internalization. Recently, our laboratory has demonstrated that IL-2R gamma mutation results in X chromosome-linked severe combined immunodeficiency in humans, suggesting that IL-2R gamma plays a vital role in thymic maturation of human T cells. We now report the isolation and characterization of cDNAs encoding murine IL-2R gamma. The open reading frame encodes 369 aa, identical in length to that encoded by the human IL-2R gamma cDNA. Murine IL-2R gamma and human IL-2R gamma have 69% and 70% identity at the nucleotide and amino acid levels, respectively. As expected, the murine IL-2R gamma retains the WSXWS motif and four cysteine residues characteristic of cytokine receptor superfamily members. IL-2R gamma mRNA distribution shows significant tissue specificity, with particularly high-level expression in spleen and thymus, and higher expression in single-positive (CD4+8- or CD4-8+)-enriched thymocytes than in double-negative (CD4-8-) thymocytes. Finally, we have localized the murine IL-2R gamma gene, Il2rg, to the X chromosome between Rsvp and Plp and demonstrated that a defect in IL-2R gamma is not responsible for the X chromosome-linked xid mutation, which maps to this same region. The cloning of the murine IL-2R gamma cDNA will facilitate the investigation of the role of this protein in lymphocyte function and thymic development.

Unusual diffuse pulmonary lymphatic proliferation in a young boy.

We describe a 4-year-old boy who died of an unusual generalized pulmonary lymphatic proliferation. His condition cannot clearly be categorized with any of the previously described pulmonary lymphatic disorders.

Exercise cardiorespiratory function in adolescents with pectus excavatum. Observations before and after operation.

We studied 12 children with pectus excavatum (mean age, 13.8 years) using pulmonary function and exercise testing. Eight patients had surgical repair and were studied before and after repair. Four patients did not have repair and were tested twice. The degree of chest wall deformity in the two groups was similar. All patients reached 86% or more of their maximal predicted heart rate with exercise. Total lung capacity decreased 8% (p less than 0.01) after operation. In the nonoperated control group, total lung capacity was similar during both studies. The ratio of ventilation at maximal exercise to maximal voluntary ventilation was 68% +/- 12% before and 66% +/- 9% after operation in the operated group and 69% +/- 18% and 79% +/- 30% at two studies in the nonoperated group (nonsignificant changes). Maximal oxygen uptake was 36.1 +/- 4.4 ml/kg/min preoperatively and 38.1 +/- 8.1 postoperatively and 41.2 +/- 7.3 ml/kg/min and 43.0 +/- 6.9 on two studies in the nonoperated group (nonsignificant changes). Cardiac output and stroke volume increased appropriately with exercise both before and after operation. Operation had no physiologically significant effect on the cardiorespiratory response to exercise. Slight changes in cardiorespiratory function occurred in both operated and nonoperated subjects. These results emphasize the importance of studying patients before and after operation and of using a control group.