Prioritise safety, optimise success! Return to rugby postpartum.

Pregnancy and childbirth involve substantial physical, physiological and psychological changes. As such, postpartum rugby players should be supported and appropriately prepared to return to the demands of rugby alongside the additional demands of motherhood. This review aims to discuss specific perinatal considerations that inform a rugby player's readiness to return-to-sport postpartum and present an approach to rehabilitation. Before engaging in full rugby training and matchplay, postpartum players should have progressed through the initial phases of rehabilitation and graded sports-specific training to prepare them for the loads they will be exposed to. Additional rehabilitation considerations include minimising deconditioning during pregnancy; medical concerns; the abdominal wall; the pelvic floor; perinatal breast changes, breastfeeding and risk of contact breast injury; body mass; nutritional requirements; hormonal considerations; athlete identity and psychological considerations; joining team training; return to contact and tackle training; evaluating player load tolerance and future research, policy and surveillance needs. A whole-systems, biopsychosocial approach following an evidence informed return-to-sport framework is recommended when rehabilitating postpartum rugby players. Health and exercise professionals are encouraged to use the perinatal-specific recommendations in this review to guide the development of postpartum rehabilitation protocols and resources.

Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus.

Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing by day 7 to 8 PE. Complete blood counts revealed lymphopenia and thrombocytopenia. Gross pathologic findings included skin lesions and congested lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7 PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered hepatocellular degeneration and cell death were also noted in the liver and, to a lesser extent, in other tissues including the haired skin, lung, heart, adrenal gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate staining for viral antigen were fibroblastic reticular cells and macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study demonstrates similarities between Lassa viral disease in human infections and experimental guinea pig infection. These shared pathologic characteristics support the utility of guinea pigs as an additional animal model for vaccine and therapeutic development under the Food and Drug Administration's Animal Rule.

Preferences of Jehovah's Witnesses regarding haematological supports in an obstetric setting: experience of a single university teaching hospital.

BACKGROUND: Jehovah's Witnesses have been shown to be at increased risk of mortality and morbidity as a consequence of obstetric haemorrhage and refusal of blood products. Since 2004, however, Jehovah's Witnesses have been allowed to accept minor fractions of blood at their own discretion. We sought to determine the preferences of pregnant Jehovah's Witnesses regarding haematological supports since this policy change. METHODS: This is a retrospective observational study of consecutive Jehovah's Witnesses attending a university-affiliated tertiary referral centre between 1 January 2007 and 31 December 2013. The main outcome measure was the proportion of women who would be willing to accept blood products and other haematological supports in the event of life-threatening bleeding, should it occur. RESULTS: Seventy-six Jehovah's Witnesses attended for obstetric care during the study period. Major fractions of blood (red cells, plasma or platelets) were acceptable to 7.9% and 50% would accept some minor fractions. Some blood components were acceptable to 70.3% of nulliparous women compared to 48.9% of multiparous women. In women with advance directives some blood components were acceptable to 70.5% compared with 37.5% of those without. Recombinant factor VIIa was acceptable to 53.9%. Black African women had the lowest acceptance of any ethnic group of any blood products. CONCLUSION: The spectrum of acceptance of blood products is wide ranging within our obstetric Jehovah's Witnesses population. Recombinant factors are not universally acceptable despite their identification as non-blood products. A multidisciplinary approach with individualized consent is recommended.

Pathogenesis of Bolivian Hemorrhagic Fever in Guinea Pigs.

Machupo virus, the cause of Bolivian hemorrhagic fever, is a highly lethal viral hemorrhagic fever with no Food and Drug Administration-approved vaccines or therapeutics. This study evaluated the guinea pig as a model using the Machupo virus-Chicava strain administered via aerosol challenge. Guinea pigs (Cavia porcellus) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and sequential changes in serum chemistry and hematology. The incubation period was 5 to 12 days, and complete blood counts revealed leukopenia with lymphopenia and thrombocytopenia. Gross pathologic findings included congestion and hemorrhage of the gastrointestinal mucosa and serosa, noncollapsing lungs with fluid exudation, enlarged lymph nodes, and progressive pallor and friability of the liver. Histologic lesions consisted of foci of degeneration and cell death in the haired skin, liver, pancreas, adrenal glands, lymph nodes, tongue, esophagus, salivary glands, renal pelvis, small intestine, and large intestine. Lymphohistiocytic interstitial pneumonia was also present. Inflammation within the central nervous system, interpreted as nonsuppurative encephalitis, was histologically apparent approximately 16 days postexposure and was generally progressive. Macrophages in the tracheobronchial lymph node, on day 5 postexposure, were the first cells to demonstrate visible viral antigen. Viral antigen was detected throughout the lymphoid system by day 9 postexposure, followed by prominent spread within epithelial tissues and then brain. This study provides insight into the course of Machupo virus infection and supports the utility of guinea pigs as an additional animal model for vaccine and therapeutic development.

Anatomical characterisation of the cricothyroid membrane in females of childbearing age using computed tomography.

BACKGROUND: In the event of failure to secure the airway by conventional means, it may be necessary to perform invasive airway access via the cricothyroid membrane. No studies have addressed anatomy of this structure in the obstetric population. We aimed to review the anatomical variation of this structure in a population of childbearing age. METHODS: We searched the radiology database for computed tomography studies of the neck performed in a 13-month period in consecutive patients aged 15-55 years. Studies on 18 females and 22 males were reviewed. Male patients were included for comparison. Data were reconstructed using a high spatial frequency algorithm to optimise spatial resolution. Five parameters were measured: distance from the skin to the membrane, maximum midline height of the membrane in the vertical plane, maximum transverse diameter of the membrane, neck diameter and cartilaginous calcification. RESULTS: The distance (mean range) from skin to the membrane was similar in females and males (16.2 [3-33] vs. 13.9 [3-37] mm, P = 0.42). The vertical height (9.9 [7-17] vs. 11.4 [8-15] mm, P = 0.04) and maximum width of the membrane (14.5 [10-17] mm vs. 12.5 [10-15] mm, P < 0.01) were greater in males. Cartilaginous calcification was low and did not differ between genders. CONCLUSIONS: The cricothyroid membrane is not necessarily a superficial structure and consequently may be difficult to palpate. The smallest dimensions of the membrane indicate that smaller than recommended cricothyroidotomy devices may be required in some patients as the external diameter of commercial trocar devices and tracheal tubes may exceed 7 mm.

Molecular cytogenetic analysis of follicular lymphoma (FL) provides detailed characterization of chromosomal instability associated with the t(14;18)(q32;q21) positive and negative subsets and histologic progression.

We analyzed a cohort of 61 follicular lymphomas (FL) with an abnormal G-banded karyotype by spectral karyotyping (SKY) to better define the chromosome instability associated with the t(14;18)(q32;q21) positive and negative subsets of FL and histologic grade. In more than 70% of the patients, SKY provided additional cytogenetic information and up to 40% of the structural abnormalities were revised. The six most frequent breakpoints in both SKY and G-banding analyses were 14q32, 18q21, 3q27, 1q11-q21, 6q11-q15 and 1p36 (15-77%). SKY detected nine additional sites (1p11-p13, 2p11-p13, 6q21, 8q24, 6q21, 9p13, 10q22-q24, 12q11-q13 and 17q11-q21) at an incidence of >10%. In addition to the known recurring translocations, t(14;18)(q32;q21) [70%], t(3;14)(q27;q32) [10%], t(1;14)(q21;q32) [5%] and t(8;14)(q24;q32) [2%] and their variants, 125 non-IG gene translocations were identified of which four were recurrent within this series. In contrast to G-banding analysis, SKY revealed a greater degree of karyotypic instability in the t(14;18) (q32;q21) negative subset compared to the t(14;18)(q32;q21) positive subset. Translocations of 3q27 and gains of chromosome 1 were significantly more frequent in the former subset. SKY also allowed a better definition of chromosomal imbalances, thus 37% of the deletions detected by G-banding were shown to be unbalanced translocations leading to gain of genetic material. The majority of recurring (>10%) imbalances were detected at a greater (2-3 fold) incidence by SKY and several regions were narrowed down, notably at gain 2p13-p21, 2q11-q21, 2q31-q37, 12q12-q15, 17q21-q25 and 18q21. Chromosomal abnormalities among the different histologic grades were consistent with an evolution from low to high grade disease and breaks at 6q11-q15 and 8q24 and gain of 7/7q and 8/8q associated significantly with histologic progression. This study also indicates that in addition to gains and losses, non-IG gene translocations involving 1p11-p13, 1p36, 1q11-q21, 8q24, 9p13, and 17q11-q21 play an important role in the histologic progression of FL with t(14;18)(q32;q21) and t(3q27).

Gas-phase detection of trinitrotoluene utilizing a solid-phase antibody immobilized on a gold film by means of surface plasmon resonance spectroscopy.

A multilayered biosensor was constructed and found to detect trinitrotoluene (TNT) in ppb concentrations in air both prior to and after detonation of TNT without use of a liquid phosphate buffered saline (PBS) superstrate. The biosensor surface was fabricated from a monoclonal antibody for TNT covalently bound to an 11,11'-dithio-bis(succinimidoylundecanoate) (DSU) self-assembled monolayer immobilized on a thin gold film bonded to a BK7 glass slide. The binding between the immobilized antibody and TNT antigen was detected using surface plasmon resonance spectroscopy (SPRS). Biosensor specificity for TNT was demonstrated with chemical homologues as well as against an unrelated explosive, RDX.

Development of interstitial cells of Cajal in a full-term infant without an enteric nervous system.

The relationship between the development of the enteric nervous system and interstitial cells of Cajal (ICC) in the human small intestine was investigated in a full-term infant who presented with intestinal pseudo-obstruction. Immunohistochemistry revealed absence of enteric nerves and ganglia but abundant c-Kit immunoreactivity associated with Auerbach's plexus (ICC-AP). However, c-Kit immunoreactivity associated with the deep muscular plexus (ICC-DMP) and intermuscular ICC was absent. Electron microscopy showed ICC-AP with a normal ultrastructure; ICC-DMP were seen but were severely injured, suggesting degeneration. In vitro recording of intestinal muscle showed slow wave activity as well as response to cholinergic stimulation. Fluoroscopic examination of the small bowel showed a variety of motor patterns, including rhythmic, propagating contractions. In conclusion, total absence of enteric nerves was associated with absence of normal ICC-DMP. However, a normal musculature, including a network of ICC-AP, allowed for generation of rhythmic, propagating contractile activity, suggesting the presence of functional motor activity.

Regulation of slow wave frequency by IP(3)-sensitive calcium release in the murine small intestine.

Slow waves determine frequency and propagation characteristics of contractions in the small intestine, yet little is known about mechanisms of slow wave regulation. We propose a role for intracellular Ca(2+), inositol 1,4,5,-trisphosphate (IP(3))-sensitive Ca(2+) release, and sarcoplasmic reticulum (SR) Ca(2+) content in the regulation of slow wave frequency because 1) 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a cytosolic Ca(2+) chelator, reduced the frequency or abolished the slow waves; 2) thapsigargin and cyclopiazonic acid (CPA), inhibitors of SR Ca(2+)-ATPase, decreased slow wave frequency; 3) xestospongin C, a reversible, membrane-permeable blocker of IP(3)-induced Ca(2+) release, abolished slow wave activity; 4) caffeine and phospholipase C inhibitors (U-73122, neomycin, and 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate) inhibited slow wave frequency; 5) in the presence of CPA or thapsigargin, stimulation of IP(3) synthesis with carbachol, norepinephrine, or phenylephrine acting on alpha(1)-adrenoceptors initially increased slow wave frequency but thereafter increased the rate of frequency decline, 6) thimerosal, a sensitizing agent of IP(3) receptors increased slow wave frequency, and 7) ryanodine, a selective modulator of Ca(2+)-induced Ca(2+) release, had no effect on slow wave frequency. In summary, these data are consistent with a role of IP(3)-sensitive Ca(2+) release and the rate of SR Ca(2+) refilling in regulation of intestinal slow wave frequency.

The myogenic component in distention-induced peristalsis in the guinea pig small intestine.

In an in vitro model for distention-induced peristalsis in the guinea pig small intestine, the electrical activity, intraluminal pressure, and outflow of contents were studied simultaneously to search for evidence of myogenic control activity. Intraluminal distention induced periods of nifedipine-sensitive slow wave activity with superimposed action potentials, alternating with periods of quiescence. Slow waves and associated high intraluminal pressure transients propagated aborally, causing outflow of content. In the proximal small intestine, a frequency gradient of distention-induced slow waves was observed, with a frequency of 19 cycles/min in the first 1 cm and 11 cycles/min 10 cm distally. Intracellular recording revealed that the guinea pig small intestinal musculature, in response to carbachol, generated slow waves with superimposed action potentials, both sensitive to nifedipine. These slow waves also exhibited a frequency gradient. In addition, distention and cholinergic stimulation induced high-frequency membrane potential oscillations (~55 cycles/min) that were not associated with distention-induced peristalsis. Continuous distention produced excitation of the musculature, in part neurally mediated, that resulted in periodic occurrence of bursts of distally propagating nifedipine-sensitive slow waves with superimposed action potentials associated with propagating intraluminal pressure waves that caused pulsatile outflow of content at the slow wave frequency.

Developmental supervision for nurses.

Developmental supervision is gaining increasing recognition in nursing as a form of clinical supervision that will promote professional growth and ultimately lead to improved patient care. Benner's (1984) model of career development is used as a framework in which to examine appropriate forms of supervision for each developmental stage. Directive, collaborative and non-directive supervision are applied to each of these developmental levels.

Interstitial cells of cajal and inflammation-induced motor dysfunction in the mouse small intestine.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) play an important role in the control of gastrointestinal motility. We aimed to determine a potential role for ICC in the pathophysiology of inflammation-induced motor disorders. METHODS: Effects of Trichinella spiralis infection on electrical pacemaker activity, the structure of ICC associated with Auerbach's plexus, and in vivo motor patterns were studied in the mouse small intestine. RESULTS: Between days 1 and 15 after infection, structural damage occurred in the network of ICC, particularly in the processes connecting ICC to each other and to smooth muscle cells. This was associated with desynchronization of electrical pacemaker activity. Abnormal slow wave activity occurred, including doubling of frequency and electrical quiescence, leading to the development of ectopic pacemaker activity in vivo. In vivo motor patterns in the small intestine changed from consistent peristaltic contractile activity in control animals to periods of quiescence alternating with both orally and aborally propagating contractile activity in the presence of inflammation. Sixty days after infection, all parameters studied had returned to normal values. CONCLUSIONS: Inflammation-induced alterations in the network of ICC of the small intestine associated with Auerbach's plexus lead to disorganization of motor patterns. Because of the strong temporal correlation between damage to the ICC network, electrical uncoupling, the appearance of ectopic pacemaker activity, and the occurrence of retrograde peristalsis, it is concluded that ICC can play a major role in inflammation-induced motor disturbances.

High-dose chemoradiotherapy and autologous stem cell transplantation for patients with primary refractory aggressive non-Hodgkin lymphoma: an intention-to-treat analysis.

High-dose chemoradiotherapy (HDT) with autologous stem cell transplantation (ASCT) is the treatment of choice for patients with relapsed aggressive non-Hodgkin lymphoma (NHL). However, its role in the treatment of patients with primary refractory disease is not well defined. The outcomes of 85 patients with primary refractory aggressive NHL who underwent second-line chemotherapy with ICE with the intent of administering HDT/ASCT to those patients with chemosensitive disease were reviewed. Patients were retrospectively classified as induction partial responders (IPR) if they attained a partial response to doxorubicin-based front-line therapy or as induction failures (IF) if they had less than partial response. Forty-three patients (50.6%) had ICE-chemosensitive disease; there was no difference in the response rate between the IPR and the IF groups. Intention-to-treat analysis revealed that 25% of the patients were alive and 21.9% were event-free at a median follow-up of 35 months. Among 42 patients who underwent transplantation, the 3-year overall and event-free survival rates were 52.5% and 44.2%, respectively, similar to the outcomes for patients with chemosensitive relapsed disease. No differences were observed between the IPR and IF groups, and there were no transplantation-related deaths. More than one extranodal site of disease and a second-line age-adjusted International Prognostic Index of 3 or 4 before ICE chemotherapy were predictive of poor survival. These results suggest that patients with primary refractory aggressive NHL should receive second-line chemotherapy, with the intent of administering HDT/ASCT to those with chemosensitive disease. Newer therapies are needed to improve the outcomes of patients with poor-risk primary refractory disease.

Granulocyte-colony stimulating factor (G-CSF) may improve disease outcome in elderly patients with diffuse large cell lymphoma (DLCL) treated with CHOP chemotherapy.

Advanced age is an adverse prognostic factor in patients with DLCL. CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has frequent dose-limiting toxicities, including myelosuppression. We retrospectively reviewed 50 consecutive patients > 60 years of age (median age 72) with B-cell DLCL who received CHOP with G-CSF. Patients received CHOP (median 6 cycles) at three-week intervals. G-CSF was given following all cycles of chemotherapy ("prophylactic G-CSF") in 28 of 50 patients, and following an episode of febrile neutropenia and thereafter in 19 patients, according to ASCO guidelines. Dose intensity, treatment delays, episodes of febrile neutropenia, complete response (CR) rate, disease-free survival, time-to-treatment failure, and overall survival were all analyzed according to the age-adjusted International Prognostic Index (aaIPI). The actual dose intensity for cyclophosphamide was 225.9 mg/m2/week and 0.90, respectively and for doxorubicin was 14.9 mg/m2/week (90% of ideal CHOP dosing for both drugs). Median followup was 4 years for the patients still living. Treatment delays and episodes of febrile neutropenia were less frequent among patients receiving G-CSF with all cycles of CHOP. The CR rates were 100%, 81%, 85%, and 36% for the low, low-intermediate, high-intermediate, and high aalPI risk groups, respectively. The 5-year actuarial relapse-free and overall survival for our patients were comparable to that of the cohort < or = 60 years of age and superior to the > 60 years of age cohort used to establish the aaIPI. With optimization of CHOP dosing, advanced age may not be an adverse prognostic factor for patients with DLCL. The routine use of G-CSF in elderly patients with DLCL should be further investigated.

Colonic epithelial physiology is altered in response to the bacterial superantigen Yersinia pseudotuberculosis mitogen.

Because bacteria are implicated in the pathophysiology of gut inflammation, the ability of the superantigen Yersinia pseudotuberculosis mitogen (YPM) to alter epithelial ion transport and permeability was examined by two model systems: epithelial (T84) monolayers cocultured with peripheral blood mononuclear cells (PBMC) with or without YPM and colonic segments from YPM-treated mice. YPM immune activation in vitro caused reduced active ion transport responses to the prosecretory agent forskolin (increases cAMP) and increased permeability. Similar changes in T84 function were evoked by conditioned medium (CM) from YPM-activated PBMC, and tumor necrosis factor-alpha and interferon-gamma were mediators of these events. Inclusion of piroxicam in the CM prevented increases in epithelial permeability but did not ameliorate the perturbed ion transport. Colonic tissue from YPM-treated mice displayed diminished responsiveness to cAMP-mediated secretagogues and nerve stimulation. Thus, Y. pseudotuberculosis enteric symptomatology may be at least partially due to YPM, and superantigens have the potential to initiate or exacerbate gut dysfunction.

Resident expectations of morning report: a multi-institutional study.

BACKGROUND: Morning report, a cornerstone of inter nal medicine residency programs for many years, involves a diverse group of teachers and learners with heterogeneous learning goals. METHODS: We distributed a self-administered, cross sectional survey to internal medicine residents to clarify the objectives of the learners at morning report. We selected a convenience sample of internal medicine residents at community- and university-based programs Questions were answered in a Likert scale or multiple-choice format. RESULTS: Residents from 13 residency programs in 7 states participated. We received 356 completed surveys, which represented a 63% response rate. The house staff in our sample preferred that half of the guest attending physicians be generalists. They indicated that the primary function of morning report should be educational, and preferred to discuss the management of a few interesting cases rather than review all patients admitted the previous day. The majority of respondents (60.8%) favored a stepwise presentation of cases to simulate the chronology of receiving information. Disease process, diagnostic workup, and evaluation of tests and procedures were all considered important topics for discussion, while medical ethics and research methods were viewed as less important. Responses varied little when stratified by sex, postgraduate year, type of residency program, subspecialty fellowship plans, or location of medical school. CONCLUSIONS: Residents from a diverse group of programs expressed remarkably similar opinions about morning report. Consistent with the recently increased emphasis on ambulatory care and general internal medicine in residency training, they expressed a desire for about 50% of the guest attending physicians to be generalists. In addition, they preferred a style in which challenging cases were presented in a stepwise manner.