Tuberculosis incidence in the Irish Traveller population in Ireland from 2002 to 2013.

The health status of the Irish Traveller ethnic minority is low compared to the general population in Ireland in terms of infant mortality rates and life expectancies. Respiratory disease is an area of health disparity manifested as excess mortalities in Traveller males and females. In this study, we examined the available data with regard to tuberculosis (TB) notifications in Ireland from 2002 to 2013. We found an increase in TB notifications in Irish Travellers from 2010 onwards. This resulted in a crude incidence rate for TB in Irish Travellers that was approximately threefold higher than that of the white Irish-born population in 2011 and 2012. An outbreak of TB in Irish Travellers in 2013 increased this differential further, but when outbreak-linked cases were excluded, a higher incidence rate was still observed in Irish Travellers relative to the general population and to white Irish-born. The mean age of a TB patient was 26 years in Irish Travellers compared to 43 years in the general population, and 49 years in white Irish-born. Based on available data, Irish Travellers exhibit a higher incidence rate and younger age distribution of TB compared to white Irish-born and the general population. These observations emphasize the importance of routine use of ethnicity identifiers in the management of TB and other notifiable communicable illnesses in Ireland. They also have implications for the orientation of preventive services to address health disparities in Irish Travellers and other ethnic minority groups.

Clinical pregnancy from a vitrified/warmed human blastocyst.

The first pregnancy after vitrification of a human blastocyst (day 5 of embryo culture) was reported by Yokota et al. in 2000. Since then more attention has been given to the technique of vitrification and its safe application in ART. To the best of our knowledge, this is the first report of a clinical pregnancy resulting in a live birth from the transfer of a vitrified/ warmed human blastocyst in the Republic of Ireland.

Molecular epidemiology of multi- and extensively-drug-resistant Mycobacterium tuberculosis in Ireland, 2001-2014.

OBJECTIVES: The primary objective of this work was to examine the acquisition and spread of multi-drug resistant (MDR) tuberculosis (TB) in Ireland. METHODS: All available Mycobacterium tuberculosis complex (MTBC) isolates (n = 42), from MDR-TB cases diagnosed in Ireland between 2001 and 2014, were analysed using phenotypic drug-susceptibility testing, Mycobacterial-Interspersed-Repetitive-Units Variable-Number Tandem-Repeat (MIRU-VNTR) genotyping, and whole-genome sequencing (WGS). RESULTS: The lineage distribution of the MDR-TB isolates comprised 54.7% Euro-American, 33.3% East Asian, 7.2% East African Indian, and 4.8% Indo-Oceanic. A significant association was identified between the East Asian Beijing sub-lineage and the relative risk of an isolate being MDR. Over 75% of MDR-TB cases were confirmed in non-Irish born individuals and 7 MIRU-VNTR genotypes were identical to clusters in other European countries indicating cross-border spread of MDR-TB to Ireland. WGS data provided the first evidence in Ireland of in vivo microevolution of MTBC isolates from drug-susceptible to MDR, and from MDR to extensively-drug resistant (XDR). In addition, they found that the katG S315T isoniazid and rpoB S450L rifampicin resistance mutations were dominant across the different MTBC lineages. CONCLUSIONS: Our molecular epidemiological analyses identified the spread of MDR-TB to Ireland from other jurisdictions and its potential to evolve to XDR-TB.

Neuraminidase activity in bacterial meningitis.

The relation of neuraminidase to morbidity and mortality was examined in patients with Haemophilus influenzae, meningococcal, and pneumococcal meningitis. Ten strains of H. influenzae and eight strains of meningococci from infected cerebrospinal fluid (CSF) did not elaborate neuraminidase. Each of 27 strains of pneumococci from infected CSF elaborated both neuraminidase and N-acetylneuraminic acid (NANA) aldolase. There was no correlation between amount of neuraminidase secreted in vitro and survival of patients. Values for free and total NANA concentrations were derived from admission CSF samples of 63 patients with meningitis; 18 patients infected with Neisseria meningitidis, 10 with H. influenzae and 35 with Diplococcus pneumoniae. Mean values for total NANA were elevated in each type of bacterial meningitis; however, abnormal concentrations of free CSF NANA were detected only in 17 patients with pneumococcal meningitis. 11 of 18 patients with pneumococcal meningitis showing normal free CSF NANA concentrations were cured, whereas only 4 patients with abnormal free NANA levels survived without residua. Both coma and bacteremia occurred significantly more often among patients with elevated concentrations of free CSF NANA. The association of elevated concentrations of free CSF NANA with coma and with an adverse prognosis suggested that neuraminidase may be a factor in the pathogenesis of penumococcal meningitis.

Multidisciplinary approach for patients with pelvic fractures and hemodynamic instability.

The hemodynamically unstable patient with a pelvic fracture presents a diagnostic and therapeutic challenge. The care of these patients requires a unique multidisciplinary approach with input and expertise from many different specialists. An understanding of pelvic anatomy and fracture patterns can help guide the diagnostic evaluation and treatment plan. The initial management of these patients must focus on rapid airway and hemorrhage control while preparing for ongoing blood loss. Rapid temporary fracture stabilization with simple bedside modalities is crucial in limiting additional blood loss. An exhaustive search must also be performed to evaluate for concomitant injuries that commonly accompany major pelvic fractures and the treatment of these other injuries must be appropriately prioritized. For patients who are unresponsive to standard resuscitation and bedside attempts at limiting hemorrhage, angiographic embolization is often utilized as the next step to attain hemodynamic stability. The key to successful management of these patients lies in the careful coordination of different specialists and the expertise that each brings to the clinical care of the patient.

Fixation of displaced femoral neck fractures in young adults: Fixed-angle devices or Pauwel screws?

BACKGROUND: We sought to compare the incidence of complications after fixation of displaced femoral neck fractures in young adults treated with fixed-angle devices versus multiple cancellous screws and a trochanteric lag screw (Pauwel screw). METHODS: We conducted a retrospective cohort study at a level I trauma centre. Sixty-two skeletally mature patients (age range, 16-60 years) with displaced femoral neck fractures were included in the study. Forty-seven were treated with a fixed-angle device (sliding hip plate with screw or helical blade) and 15 with multiple cancellous screws placed in a Pauwel configuration. The main outcome measure was postoperative complication of osteonecrosis or nonunion treated with a surgical procedure. RESULTS: Significantly fewer failures occurred in the fixed-angle group (21%) than in the screws group (60%) (p=0.008). Osteonecrosis was rare in the fixed-angle group, occurring in 2% of cases versus 33% of cases in the screws group (p=0.002). Consistent with previous studies, good to excellent reductions were associated with a failure rate of 25% and fair to poor reductions were associated with a failure rate of 55% (p=0.07). The best-case scenario of a good to excellent reduction stabilised with a fixed-angle device yielded a success rate of 85%. CONCLUSION: In young patients with displaced high-energy femoral neck fractures, fixed-angle devices resulted in fewer treatment failures than did Pauwel screws.

Chemotherapy of drug-resistant ovarian cancer: a Southwest Oncology Group Study.

We present a final analysis, including pathology review, of a cooperative group study of drug-resistant ovarian cancer. Of 200 patients registered, 112 were eligible and evaluable, with a response rate of 26% and median survival of 7 months. Because these results are poorer than those reported in the preliminary and interim analyses of this study, we scrutinized the 88 excluded patients, most of whom failed to meet our strict pathologic criteria for a diagnosis of ovarian cancer of epithelial type, and who, as a heterogeneous group, fared better than patients who did meet the eligibility criteria. We believe this analysis provides insight into the spectrum of diseases that are frequently called ovarian cancer, but might be more properly labeled abdominal carcinomatosis.

Improved therapeutic index of carboplatin plus cyclophosphamide versus cisplatin plus cyclophosphamide: final report by the Southwest Oncology Group of a phase III randomized trial in stages III and IV ovarian cancer.

PURPOSE: To compare cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide as primary chemotherapy for stage III (suboptimal) and stage IV ovarian cancer. PATIENTS AND METHODS: Three hundred forty-two patients were randomly assigned to treatment with six courses of intravenous (i.v.) cisplatin 100 mg/m2 plus i.v. cyclophosphamide 600 mg/m2, or i.v. carboplatin 300 mg/m2 plus i.v. cyclophosphamide 600 mg/m2. RESULTS: The estimated median survivals were 17.4 and 20.0 months for the cisplatin and carboplatin study arms, respectively. The null hypothesis of a 30% survival superiority with the cisplatin arm was rejected at the P = .02 level. Clinical response rates were 52% for the cisplatin arm and 61% for the carboplatin arm. Pathologic complete response rates were similar for both study arms. There was less thrombocytopenia on the cisplatin arm (P less than .001); however, there was less nausea and emesis (P less than or equal to .001 for courses 1 to 5), renal toxicity (P less than .001), anemia (P = .01), hearing loss (P less than .001), tinnitus (P = .01), neuromuscular toxicities (P = .001), and alopecia (P less than .001) on the carboplatin arm. CONCLUSION: Carboplatin-cyclophosphamide proved to have a significantly better therapeutic index than cisplatin-cyclophosphamide in patients with stage III (suboptimal) and stage IV ovarian cancer.

Unusual giant cell tumor arising in a male breast.

An unusual giant cell tumor of the breast of a 72 year old man is reported. The microscopic and ultrastructural features of the tumor are presented in detail. Unusual and previously unreported myofibroblastic an myoepithelial differentiation of the spindle cell component is described. The possible histogenesis of the tumor is discussed.

Pure cutaneous histiocytosis X of the vulva.

Histiocytosis X of the vulva is extremely rare. In most reported cases, vulvar disease is associated with multiple organ involvement and systemic disease manifestations aiding in the diagnosis. Reported is a case of histiocytosis X presenting solely with vulvar lesions for eight years' duration. The diagnosis, pathology, and subsequent management are discussed. The literature of histiocytosis X of the vulva is reviewed, and its presentations and treatments summarized. Vulvar lesions unresponsive to therapy warrant biopsy and other causes of histiocytic reactions must be excluded to establish the diagnosis.

Carboplatin therapy in advanced endometrial cancer.

A phase II study of the effectiveness and toxicity of carboplatin in the treatment of metastatic or locally advanced endometrial cancer was carried out by the Southwest Oncology Group. Thirty-two patients were registered in the study and 23 were fully evaluable for response and toxicity. Carboplatin was administered in a dose of 400 mg/m2 at 28-day intervals without concomitant hydration if blood counts had recovered sufficiently. There were seven responses (two complete and five partial responses) among the 23 evaluable patients, for an overall response rate of 30%. Four (two of two complete responders and two of five partial responders) of the seven responding patients remain alive at 839+ to 987+ days from the start of therapy. The two complete responders and one of the partial responders had small-volume disease, which may have contributed to their prolonged survival. Myelosuppression was the most prominent toxicity encountered. Seventeen of 27 patients evaluable for toxicity developed platelet counts of less than 75 X 10(3)/muL during therapy, but no hemorrhagic complications were encountered. Leukopenia was less prominent, with only nine of 27 patients developing white blood cell counts of less than 3.0 X 10(3)/microL. No important nephrotoxicity or neurotoxicity was observed. Emesis occurred in ten of 27 patients but was not dose-limiting. No unexpected toxicities were encountered. Carboplatin appears to be an active agent in the treatment of endometrial carcinoma.

Measuring and developing suturing technique with a virtual reality surgical simulator.

BACKGROUND: We have developed an interactive virtual reality (VR) surgical simulator for the training and assessment of suturing technique. The surgical simulator is comprised of surgical tools with force feedback, a 3-dimensional graphics visual display of the simulated surgical field, physics-based computer simulations of the tissues and tools, and software to measure and evaluate the trainee's performance. STUDY DESIGN: This study uses the simulator to measure and compare the skills of 8 experienced vascular surgeons versus 12 medical students when performing a virtual reality suturing task. Eight parameters of the suturing task were measured: total tissue damage, accuracy of needle puncture, peak tissue tearing force, time to complete the task, damage to the surface of the tissue, angular error in needle technique, total distance traveled by the tool tip, and a measure of overall error. Three test conditions (dominant hand, nondominant hand, and 3-dimensional needle guide) were tested. Statistical significance was defined as a univariate two-sided p value < or = 0.05. RESULTS: The surgeons' average performance was significantly better than the students' average performance for three of the measured parameters (total tissue damage, time to complete the task, and total distance traveled by the tool tip) for each of the test conditions. For the test condition most similar to surgery (using the dominant hand to suture) one additional parameter was also significantly different (the measure of overall error). The medical students showed improvements for 6 of the 7 parameters for which the users received feedback during the training process. The surgeons also had significant improvement for 4 of the 7 parameters. The students had a larger improvement than the surgeons for 6 of the parameters, but these differences were not statistically significant. CONCLUSIONS: Data indicate differences between surgeon and nonsurgeon performance and in improvement in performance with training. One possible explanation for the superior performance of the surgeons is that their suturing skills applied well to the simulated suturing task. Additional research is required to confirm or deny the similarity between actual and simulated surgical tasks and the relevance of virtual reality surgical simulation to surgical skill assessment and training.

Experimental pneumococcal meningitis. Effects of neuraminidase and other pneumococcal constituents on cerebrospinal fluid in the intact dog.

The intracisternal administration of a Type I pneumococcus to mongrel dogs resulted in spinal fluid abnormalities and clinical course and outcome similar to those of meningitis in humans. In order to define the pathogenic role of pneumococcal neuraminidase and other pneumococcal extracts in experimental meningitis, the following preparations were derived from the same Type I pneumococcus: crude neuraminidase, partially purified neuraminidase, heat-inactivated crude neuraminidase, and heat-killed pneumococci. These preparations were administered intracisternally daily for 5 days to a series of mongrel dogs. These substances did not produce clinical morbity similar to that observed in infected animals, even though there was significant decrease in the NANA content of cortical brain subcellular structures in the neuraminidase-treated dogs. It was concluded that the substances investigated were not responsible for morbidity and mortality in experimental pneumococcal meningitis. Both heat-killed pneumococci and the crude neuraminidase preparation elicited significant alterations in spinal fluid glucose and protein concentrations which were similar to those recorded in infected animals; however these abnormalities were not associated with significant morbidity. It is proposed that spinal fluid glucose and protein abnormalities may not be directly linked to brain damage or dysfunction in this experimental model, or in man.

Flow cytometric analysis of DNA content as a prognostic indicator in squamous cell carcinoma of the tongue.

The mortality of squamous cell carcinoma of the tongue has not significantly improved in decades. Much of the information that has been gathered to date has been based on retrospective analyses. There is little consensus on treatment of the disease. In an attempt to define an objective prognostic indicator of aggressiveness of these tumors, a retrospective analysis of 15 paraffin-embedded specimens using flow cytometry was performed. Ten patients (67 percent) had aneuploid tumors and had a 5 year disease-free survival rate of 33 percent, whereas patients with diploid tumors (33 percent) had a 5 year disease-free survival rate of 80 percent. Although the number of patients was small, it appears that flow cytometry may be an objective prognostic indicator in patients with squamous cell carcinoma of the tongue. Larger series of archival paraffin-embedded flow cytometry analyses are recommended, as well as examination of variables other than the disease-free survival rate.

Follow-up on flow cytometric DNA analysis of squamous cell carcinoma of the tongue.

Preliminary data from this institution suggested that flow cytometric DNA analysis was an objective prognostic indicator in archival localized squamous cell carcinoma of the tongue. Technical improvements were made, including analysis of tumor, normal tissue, and a combination of the two; standardized cursor placement; mathematic determination of tetraploid populations; and development of a statistical analysis. A larger number of patients (60) with this disease were reviewed. DNA content was related to disease-free survival, local recurrence, regional metastasis, and incidence of second primary tumors. There was no significant difference between aneuploid and diploid tumors with respect to the variables analyzed. We believe these technical improvements will enhance flow cytometric DNA analysis of paraffin-embedded tissues. However, in this retrospective review of localized squamous cell carcinoma of the tongue, DNA analysis was not a valuable prognostic indicator. Only prospective studies will address this issue.

A phase II evaluation of esorubicin in ovarian cancer. A Southwest Oncology Group study.

Patients with a pathologically confirmed diagnosis of metastatic or advanced epithelial-type ovarian carcinoma were entered into a Phase II trial of esorubicin. Eligibility criteria included measurable disease; performance status (SWOG) 0-2; no more than one prior chemotherapeutic regimen; and no prior doxorubicin therapy. The starting esorubicin dosing schedule was 30 mg/m2 every 3 weeks for good risk patients and 25 mg/m2 every 3 weeks for poor risk patients. Twenty-one patients were eligible for evaluation of response and toxicity to treatment. These patients received a median of 3 courses of esorubicin (range 1-13 courses). None of the 21 patients experienced a response to esorubicin. Median survival was 5.5 months. Leukopenia was the major toxicity. Eleven (79%) of the good risk patients and 2 (29%) of the poor risk patients experienced severe to life-threatening leukopenia. Mild to severe anemia was seen in 10 (71%) of the good risk patients and 7 (100%) of the poor risk patients. We conclude that esorubicin is ineffective in the treatment of ovarian cancer patients who have received primary chemotherapy.

Phase II study of fludarabine phosphate (NSC-312887) in patients with advanced ovarian cancer. A Southwest Oncology Group Study.

Fourteen evaluable patients with advanced ovarian cancer refractory to one prior chemotherapy regimen were treated with a 5-day schedule of fludarabine phosphate. No responses were noted. The major toxicity was granulocytopenia with 50% of patients having granulocyte counts of less than 1,000/microliter. Based on this study and one other previously published trial, fludarabine phosphate does not appear to be an active agent for patients with refractory ovarian cancer.

Randomized comparison of cisplatin plus epirubicin or doxorubicin for advanced epithelial ovarian carcinoma. A multicenter trial.

Stage III and IV epithelial ovarian cancer patients were prospectively randomized to receive eight courses of 60 mg/m2 of cisplatin plus either 75 mg/m2 of epirubicin (62 patients) or 60 mg/m2 of doxorubicin (54 patients). Clinical response rates for cisplatin/epirubicin of 42% [15% complete response (CR) and 27% partial response (PR)] and for cisplatin/doxorubicin of 55% (24% CR and 31% PR) were not statistically different (p = 0.14). The negative second look rate was 35% (10/29) for cisplatin/doxorubicin and 17% (5/30) for cisplatin/epirubicin (p = 0.12). The progression-free interval for cisplatin/epirubicin (13 months) was not statistically different (p = 0.09) from that for cisplatin/doxorubicin (19 months). The median survivals for cisplatin/epirubicin (756 days) and cisplatin/doxorubicin (739 days) were similar (p = 0.70). Cardiotoxicity was greater for the cisplatin/doxorubicin group (p = 0.0003). With similar survival and less cardiotoxicity, the cisplatin/epirubicin regimen had the more favorable therapeutic index.

Antiestrogenic potency of toremifene and tamoxifen in postmenopausal women.

In this nonblinded, controlled multicenter trial, postmenopausal women were randomly assigned to receive graded doses of toremifene and tamoxifen or no antiestrogen to assess dose-response levels and evaluation methodology. For standardization, transdermal estradiol (Estraderm-Ciba Geigy) was applied to all women for 38 days. The antiestrogens were added on days 29-38. For control and all treatment groups, there were no significant changes in serum chemistries or serum hormone levels, nor were there differences in adverse effects. The use of continuous estradiol precluded any meaningful assessment of the estrogenicity of tamoxifen or toremifene. As measured by vaginal superficial cytologic cell count changes, the antiestrogenic activity of toremifene doses ranging from 20 to 200 mg/day could not be distinguished from that of 20 mg/day of tamoxifen, the clinically recommended dose in North America.