Management and outcome of severe Guillain-Barre syndrome

Seventy-nine patients with Guillain-Barré syndrome admittedto a neurological intensive therapy unit (ITU) between 1985and 1992 were studied retrospectively. The mean age was 49.8years (range 16–86) and the time between the first neurologicalsymptom and admission to ITU was 10.2 days (0–62). Admissionwas precipitated by a combination of respiratory failure requiringventilatory support (73.4%), bulbar weakness (57.0%), autonomicfeatures (11.4) and general medical factors (10.1%). Specifictreatments included plasma exchange (65.8%), intravenous immunoglobulin(13.9%) and methylprednisolone/placebo (12.7%). Significantcomplications included lower respiratory tract infections (45.6%),hyponatraemia (25.3%), dysautonomia (19.0%), urinary tract infection(12.7%) and cognitive disturbances (8.9%). Four patients (5.1%) died during the acute illness. Duration of nadir correlatedwith duration of ventilation, duration of ITU stay and outcomesat 3 months, 6 months and 1 year. However, time to nadir, anindicator of rapidity of deterioration, did not correlate withany outcome. The low mortality in this series of acutely illand severely disabled patients suggests that specialized intensivetherapy units continue to have an important role in the managementof acutely ill patients with Guillain-Barre syndrome.     

Ex vivo effect of JAK inhibition on JAK-STAT1 pathway hyperactivation in patients with dominant-negative STAT3 mutations

Journal of Clinical Immunology - STAT1 gain-of-function (GOF) and dominant-negative (DN) STAT3 syndromes share clinical manifestations including infectious and inflammatory manifestations. Targeted...     

Examining Nurse Consultant connectivity: An Australian mixed method study

The nurse consultant (NC) role in Australia is a senior classification of advanced practice nurse has been described as enhancing health care outcomes largely through extensive collaboration with consumers, nurses, and other health professionals. However, little is known about the actual nature, amount, and quality of NC interactions. This study examines the connectivity of the NC role across metropolitan and rural contexts, using a mixed method sequential design with an online survey and focus groups with NCs and other stakeholders. Results demonstrated that NCs most commonly have high density connectivity patterns with other nursing colleagues, medical staff, patients/clients, and administrative staff. Position grade (1, 2 or 3) influences density of connectivity, as does location, with those based in metropolitan roles engaging significantly less with other clinicians. Findings demonstrate that many NCs are highly collaborative and predominantly embedded into interprofessional practice models. This study provides valuable insight into the diverse and often complex NC role and the way in which NC expertise and influence is deployed and integrated across a large local health district.     

The immune response of allophenic mice to 2,4-dinitrophenyl (DNP)-bovine gamma globulin. I. Allotype analysis of anti-DNP antibody

The question of whether or not lymphoid cells can cooperate across a histocompatibility difference barrier has been studied in several laboratories. Using an adoptive transfer system, Katz et al. (1) first showed that T cells from (low responder × high responder) F(1) mice, primed to the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT), could collaborate with 2,4-dinitrophenyl (DNP)-primed B cells from a high responder, but not a low responder strain, in response to DNP-GLT. The response to GLT is under H- 2-1inked Ir gene control. In contrast, studies with mouse bone marrow chimeras have shown that T cells can interact with H-2-histoincompatible B cells in response to antigens not under Ir gene control (2-4). Another type of chimera, the allophenic mouse, has been used to study possible histoincompatible cell interactions to a number of antigens, including DNP-L- glutamic acid, L-lysine, L-alanine; L-glutamic acid, L-alanine, L-tyrosine; L-glutamic acid, L-lysine, L-phenylalanine; and poly-L (Tyr, Glu)-poly D,L- Ala-poly-L-Lys[T,G)-A-L] (5-9). The response to each of these antigens is under H-2-1inked Ir gene control. It was initially reported (8, 9) that in allophenic mice containing both high and low responder cells, the antibody to (T,G)-A-L was of both the high and low responder allotype. This was interpreted to mean that high responder T cells had cooperated with low responder B cells across a histocompatibility difference barrier in the environment of the allophenic mice. However, Press and McDevitt (10) have recently reported that additional and more accurate analyses of these allophenic mouse sera failed to detect any anti-(T,G)-A-L antibody of the low responder allotype. Moreover, in an experiment using bone marrow chimeras, there was no low responder allotype antibody produced in response to (T,G)-A- L(10). The present study was undertaken to test the immune response of allophonic mice to an antigen, DNP-bovine gamma globulin (DNP(56)BGG), known to be controlled by genes both inside and outside the H-2 complex (11, 12).(1) When high and low responder cells to DNP(56)BGG are present in allophenic mice, only antibody of the high responder allotype is produced. The results suggest that cell cooperation in allophenic mice cannot occur across a histocompatibility difference barrier in response to an antigen whose genetic control is at least partially within the H-2 complex.     

Bridging the Gap between Clinical Research and Knowledge Translation in Pediatric Emergency Medicine

In 2006, a multidisciplinary group of researchers from across Canada submitted a successful application to the Canadian Institutes for Health Research for a Canadian Institutes for Health Research Team in Pediatric Emergency Medicine. The conceptual foundation for the proposal was to bring together two areas deemed critical for optimizing health outcomes: clinical research and knowledge translation (KT). The framework for the proposed work is an iterative figure-eight model that provides logical steps for research and a seamless flow between the development and evaluation of therapeutic interventions (clinical research) and the implementation and uptake of those interventions that prove to be effective (KT). Under the team grant, we will conduct seven distinct projects relating to the two most common medical problems affecting children in the emergency department: respiratory illness and injury. The projects span the research continuum, with some projects targeting problems for which there is little evidence, while other projects involve problems with a strong evidence base but require further work in the KT realm. In this article, we describe the history of the research team, the research framework, the individual research projects, and the structure of the team, including coordination and administration. We also highlight some of the many advantages of bringing this research program together under the umbrella of a team grant, including opportunities for cross-fertilization of ideas, collaboration among multiple disciplines and centers, training of students and junior researchers, and advancing a methodological research agenda.     

Parotid gland sparing IMRT for head and neck cancer improves xerostomia related quality of life

Background

To compare two strategies of dynamic intensity modulated radiation therapy (dIMRT) with 3-dimensional conformal radiation therapy (3DCRT) in the setting of hypofractionated high-risk prostate cancer treatment.

Methods

3DCRT and dIMRT/Helical Tomotherapy(HT) planning with 10 CT datasets was undertaken to deliver 68 Gy in 25 fractions (prostate) and simultaneously delivering 45 Gy in 25 fractions (pelvic lymph node targets) in a single phase. The paradigms of pelvic vessel targeting (iliac vessels with margin are used to target pelvic nodes) and conformal normal tissue avoidance (treated soft tissues of the pelvis while limiting dose to identified pelvic critical structures) were assessed compared to 3DCRT controls. Both dIMRT/HT and 3DCRT solutions were compared to each other using repeated measures ANOVA and post-hoc paired t-tests.

Results

When compared to conformal pelvic vessel targeting, conformal normal tissue avoidance delivered more homogenous PTV delivery (2/2 t-test comparisons; p < 0.001), similar nodal coverage (8/8 t-test comparisons; p = ns), higher and more homogenous pelvic tissue dose (6/6 t-test comparisons; p < 0.03), at the cost of slightly higher critical structure dose (D_dose, 1–3 Gy over 5/10 dose points; p < 0.03). The dIMRT/HT approaches were superior to 3DCRT in sparing organs at risk (22/24 t-test comparisons; p < 0.05).

Conclusion

dIMRT/HT nodal and pelvic targeting is superior to 3DCRT in dose delivery and critical structure sparing in the setting of hypofractionation for high-risk prostate cancer. The pelvic targeting paradigm is a potential solution to deliver highly conformal pelvic radiation treatment in the setting of nodal location uncertainty in prostate cancer and other pelvic malignancies.     

Breast implant–associated anaplastic large cell lymphoma and effusions: A review with emphasis on the role of cytopathology

Breast implants are surgically implanted by the hundreds of thousands every year worldwide for reconstructive or aesthetic purposes. Complications related to breast implants include early and late effusions that are often submitted for cytopathological analysis, particularly to exclude the possibility of breast implant–associated anaplastic large cell lymphoma (BIA-ALCL), a rare disease that generally follows an indolent clinical course, although it is becoming clearer that a subset of patients with adverse features have a poorer prognosis. Since a late-onset breast implant–associated effusion is the most common initial presentation of BIA-ALCL, cytopathological analysis of these effusions is considered the cornerstone and gold standard for rapid, efficient, reliable diagnosis and is critical for appropriate management and treatment. The National Comprehensive Cancer Network recently published clinical guidelines for the diagnosis and management of BIA-ALCL and stresses the essential role of cytopathological analysis, although it remains a matter of debate if all seromas should undergo immunocytochemistry or flow cytometry, particularly for assessment of expression of CD30 irrespective of morphological appearance on cytology. Herein, we review the current knowledge on BIA-ALCL, review the key cytological findings of reactive and malignant effusions related to breast implants, and present a comprehensive cytopathological workup with the presence of atypical cells as the key and pivotal element triggering further ancillary studies. We believe this approach will ensure appropriate and cost-effective management of effusion specimens from breast implants.