The potential roles of strigolactones and brassinosteroids in the autoregulation of nodulation pathway.

BACKGROUND AND AIMS: The number of nodules formed on a legume root system is under the strict genetic control of the autoregulation of nodulation (AON) pathway. Plant hormones are thought to play a role in AON; however, the involvement of two hormones recently described as having a largely positive role in nodulation, strigolactones and brassinosteroids, has not been examined in the AON process. METHODS: A genetic approach was used to examine if strigolactones or brassinosteroids interact with the AON system in pea (Pisum sativum). Double mutants between shoot-acting (Psclv2, Psnark) and root-acting (Psrdn1) mutants of the AON pathway and strigolactone-deficient (Psccd8) or brassinosteroid-deficient (lk) mutants were generated and assessed for various aspects of nodulation. Strigolactone production by AON mutant roots was also investigated. KEY RESULTS: Supernodulation of the roots was observed in both brassinosteroid- and strigolactone-deficient AON double-mutant plants. This is despite the fact that the shoots of these plants displayed classic strigolactone-deficient (increased shoot branching) or brassinosteroid-deficient (extreme dwarf) phenotypes. No consistent effect of disruption of the AON pathway on strigolactone production was found, but root-acting Psrdn1 mutants did produce significantly more strigolactones. CONCLUSIONS: No evidence was found that strigolactones or brassinosteroids act downstream of the AON genes examined. While in pea the AON mutants are epistatic to brassinosteroid and strigolactone synthesis genes, we argue that these hormones are likely to act independently of the AON system, having a role in the promotion of nodule formation.

SCUAD and chronic rhinosinusitis. Reinforcing hypothesis driven research in difficult cases.

BACKGROUND: Our objective is to present recent research findings on recalcitrant chronic rhinosinusitis (CRS) in relation to "Severe Chronic Upper Airway Disease" (SCUAD). METHODOLOGY: Literature review using Medline and Em base databases (search terms 'chronic rhinosinusitis'; "chronic sinusitis" or"Severe Chronic Upper Airway Disease") limited to articles published in the English language. RESULTS: Complex pathophysiological mechanisms characterize various forms of chronic rhinitis and rhinosinusitis (CRS), where inflammation persists in spite of adequate medical treatment. In these cases, a multifactorial etiology often underlies the development of sino-nasal inflammation. The interaction between chronic upper and lower airway inflammation via neurogenic and systemic pathways may complicate the therapy of these patients, and lead to insufficient symptom control. CONCLUSION: The recently introduced definition of"Severe Chronic Upper Airway Disease" (SCUAD) increases awareness of those patients with persistent inflammation and symptoms despite guideline-driven pharmacologic treatment. The concept of SCUAD may prove helpful in directing research towards clarifying the definition, diagnosis and pathophysiology of rhinitis and rhinosinusitis,their limits and overlap. In this review, a hypothesis on SCUAD immunopathology is also presented.

New insights into the role of PML in tumour suppression.

The PML gene is involved in the t(15;17) translocation of acute promyelocytic leukaemia (APL), which generates the oncogenic fusion protein PML (promyelocytic leukaemia protein)-retinoic acid receptor alpha. The PML protein localises to a subnuclear structure called the PML nuclear domain (PML-ND), of which PML is the essential structural component. In APL, PML-NDs are disrupted, thus implicating these structures in the pathogenesis of this leukaemia. Unexpectedly, recent studies indicate that PML and the PML-ND play a tumour suppressive role in several different types of human neoplasms in addition to APL. Because of PML's extreme versatility and involvement in multiple cellular pathways, understanding the mechanisms underlying its function, and therefore role in tumour suppression, has been a challenging task. In this review, we attempt to critically appraise the more recent advances in this field and propose new avenues of investigation.

Microbial and acute phase stimuli disrupt promyelocytic leukemia tumor suppressive nodes.

The promyelocytic leukaemia (PML) nuclear domain (PML-ND) is a nuclear sentinel for stress. Each PML-ND cradles a delicate scaffold of nucleoproteins, many of which can trigger the apoptotic death cascade if disrupted. Given their place in integrating stress and death, PML-NDs are obvious targets for excision from injury pathways by viruses and cancers. Viruses express proteins dedicated to silencing the PML-ND network and their failure can presage the suppression of viral replication. To understand how PML-NDs protect the cell from stress we must discover those damage pathways with which they connect. Such data will reveal the panoply of signal pathways lost in PML null cells and the extent to which infection and cancer can desensitise the cell to therapeutic intervention. A convenient and sensitive method with which to detect PML-ND stress induction is its biophysical reorganisation, as well defined dose responsive modifications of PML protein accompany damage recognition. The experiments that we present in this manuscript arose from an observation that lipid mediated transfection of plasmid DNA triggered a dramatic modification of PML-NDs that was identical to that seen following their recognition of DNA damage. In later experiments, we identified lipoprotein and IL-6 as potential mediators of this response. Collectively these data are the first to link an endotoxin component and IL-6 to the PML-ND compartment and, given the role of PML in cell fate, suggest increasing complexity at the interface of immunity and carcinogenesis.

Severe panniculitis caused by homozygous ZZ alpha1-antitrypsin deficiency treated successfully with human purified enzyme (Prolastin).

Severe panniculitis caused by alpha1-antitrypsin deficiency is very rare even though the ZZ phenotype occurs in 1 : 3500 of the population of northern Europe. We describe a 33-year-old woman with rapidly progressing panniculitis and extensive skin necrosis with multiple life-threatening complications. Initial treatment followed by maintenance therapy with human purified enzyme (Prolastin, Bayer, Bridgend, U.K.) has been life-saving.

Care for adolescent pregnancy and childbirth.

The rise in adolescent pregnancy in the 20th century has been influenced by declining age at menarche, increased schooling, delay of marriage, inadequate contraception and poverty. The main problems are preterm labor, hypertensive disease, anemia, more severe forms of malaria, obstructed labor in very young girls in some regions, poor maternal nutrition and poor breastfeeding. In many regions HIV infection is an important problem. The infants of adolescent mothers are more prone to low birth weight and increased neonatal mortality and morbidity. Antenatal care is often inadequate. The most important problem is the increased incidence of preterm labor and delivery, the youngest age groups running the highest risk. Technically, care of adolescents during labor need not differ from care of older women; most adolescents are not at increased risk during labor, although, they are more in need of empathic support. Generally, care of pregnant adolescents should be adjusted to their specific needs.

Unsafe abortion in adolescents.

Every year, an estimated 2.0-4.4 million adolescents resort to abortion. In comparison with adults, adolescents are more likely to delay the abortion, resort to unskilled persons to perform it, use dangerous methods and present late when complications arise. Adolescents are also more likely to experience complications. Consequently, adolescents seeking abortion or presenting with complications of abortion should be considered as a medical emergency. Issues requiring special attention in the management of abortion complications in adolescents are identified. Approaches to adolescent abortion should involve all levels of the health care system, as well as the community, and should include not only management of the consequences of unsafe abortion, but also post-abortion contraception and counseling. Prevention of unwanted pregnancy by providing information on sexuality, ensuring that reproductive health services are adolescent-friendly, creating a supportive environment, building young people's social and decision-making skills, and offering counseling in times of crisis are highlighted.

A study of the effect of nasal steroid sprays in perennial allergic rhinitis patients with rhinitis medicamentosa.

OBJECTIVE: To determine if rebound congestion can be reduced with concomitant nasal steroid spray usage. STUDY DESIGN AND SETTING: Randomized, double blind, controlled single center study. PARTICIPANTS: Twenty subjects with perennial allergic rhinitis with nasal congestion. INTERVENTION: All subjects received 3 weeks of twice-daily oxymetazoline. After 2 weeks, subjects were randomized to 2 additional weeks of concomitant budesonide aqueous nasal spray (n = 9) or placebo (n = 10). In the sixth week, all sprays were stopped. RESULTS: Both groups showed subjective and objective evidence of rebound congestion 24 hours after cessation of oxymetazoline (P < 0.05). Subjective rebound congestion resolved in 48 hours in the budesonide aqueous nasal spray group but persisted for over 1 week in the placebo group. CONCLUSION: Rebound congestion is objectively present in patients with perennial allergic rhinitis after 3 weeks of oxymetazoline spray. Rebound congestion is reduced by concomitant budesonide aqueous nasal spray use. SIGNIFICANCE: This study supports the common clinical practice of nasal steroid sprays to ameliorate rebound congestion concomitant with and after cessation of topical decongestant sprays.

Eosinophilic mucin rhinosinusitis: a distinct clinicopathological entity.

BACKGROUND: Allergic fungal sinusitis (AFS) was recognized in 1981. Since 1983, a form of sinusitis histologically similar to AFS except for the absence of fungal hyphae has also been noted. The designation "eosinophilic mucin rhinosinusitis (EMRS)" is proposed. Its relationship to AFS is controversial and problematic. OBJECTIVE: To determine whether distinctive clinical and immunological differences exist to differentiate the histological entity of EMRS from AFS. STUDY DESIGN: Literature review and comparison of cases of AFS (n = 418) to EMRS (n = 40) from the literature, as well as cases of AFS (n = 13) and EMRS (n = 29) accrued in the present study. RESULTS: A total of 431 AFS patients were compared with 69 EMRS patients. The mean age of patients with AFS was significantly younger than patients with EMRS (30.7 y compared with 48.0 y, respectively; P < .001). Male-to-female ratios were 1.03:1 and 1.26:1 for AFS and EMRS, respectively, and were not significantly different. Forty-one percent of patients with AFS were asthmatic compared with 93% of patients with EMRS (P < .0001). Thirteen percent of patients with AFS were aspirin sensitive compared with 54% of patients with EMRS (P < .0001). Polyp occurrence was almost 100% in both groups. Eighty-four percent of patients with AFS had allergic rhinitis (AR), while only 63% of patients with EMRS had AR (P = .004). Fifty-five percent of AFS patients had bilateral disease, in contrast to the 100% of EMRS patients with bilateral disease (P < .0001). Although average total immunoglobulin E (IgE) was elevated in both groups, it was significantly more elevated in AFS patients (range, 12-13,084 mg/ dL; mean, 1,941 mg/dL) compared with EMRS patients (range, 14-1,162 mg/dL; mean, 267 mg/dL; P < .001). Total immunoglobulin G (IgG) and IgG subclasses were seldom reported in the cases available from the literature of either AFS or EMRS. However, in the present series of EMRS, IgG1 deficiency occurred in 50% of evaluated patients (mean, 475 +/- 175 mg/dL; range, 250-869 mg/dL; normal, 422 to 1,200 mg/dL) but in no cases of AFS reported in the literature. CONCLUSIONS: Significant clinical and immunological differences exist to distinguish AFS from EMRS. It is postulated that AFS is an allergic response to fungi in predisposed individuals, while EMRS occurs because of a systemic dysregulation of immunological controls. Because EMRS is a systemic disease, unilateral disease is not seen. In contrast, AFS, an allergic response to fungi, may occur unilaterally or bilaterally depending on the antigenic stimulation. EMRS also has a significantly higher association with asthma, an increased incidence of aspirin sensitivity, and an increased incidence of IgG1 deficiency. Therapy with a systemic steroid, a potent and indiscriminant anti-inflammatory agent, is a useful adjunct in both disorders. Fungal immunotherapy following surgical extirpation of AFS is useful in preventing AFS recurrence. It is predicted that fungal immunotherapy and antifungal agents will be ineffective in patients with EMRS. It is important to differentiate these two similar histopathological entities in future trials assessing therapeutic efficacy. Inclusion of both entities in a study could obscure recognition of the true effectiveness of intervention, because of the possible variable response differences between the two entities. This study shows that significant clinical and immunological differences exist between EMRS and AFS. The future awaits an exploration of the pathophysiological basis of these differences.

Definitions of fungal rhinosinusitis.

Classification of fungal rhinosinusitis is important for the accurate prediction of prognosis and direct therapy. The most important distinction is between invasive and noninvasive fungal rhinosinusitis. Within the invasive division are acute invasive and chronic invasive (granulomatous and nongranulomatous forms) rhinosinusitis. Within the noninvasive division are saprophytic colonization, fungus balls, and allergic fungal rhinosinusitis. This article briefly outlines the definition and management of each of these manifestations.

Mucormycosis of the nose and paranasal sinuses.

Rhinocerebral mucormycosis is an invasive fungal infection initiated in the paranasal sinuses that frequently progresses to orbital and brain involvement. If recognized early, involvement is limited to the nasal cavity and paranasal sinuses. Diabetics in poor control are at greatest risk, however, any immunocompromised individual may be infected. The mainstays of therapy are reversal of immunosuppression, systemic amphortericin B, and surgical débridement. Survival has improved dramatically, yet deaths still occur if the infection is not recognized and not treated early in its course or if the source of immunocompromise is not reversible. Several case examples illustrate the clinical course of this unusual, but potentially fatal, fungal infection. Taxonomy, clinical presentation, diagnosis, and management of mucormycosis of the paranasal sinuses are reviewed in detail.

Fungus balls of the paranasal sinuses.

Fungus balls of the paranasal sinuses represent a noninvasive manifestation of fungal sinusitis. Patients are immunocompetent but no more allergic than the general population. There is little tissue reaction to the tangled mat of hyphae. If the patient becomes immunocompromised, then the fungus ball may become invasive, as illustrated by an included case report. One hundred sixty-three additional cases of patients with paranasal sinus fungus balls are reviewed from the literature.

Geographic variation in allergic fungal rhinosinusitis.

Allergic fungal rhinosinusitis (AFRS) has a worldwide distribution. This survey of 20 otolaryngologic practices throughout the United States confirmed a variation in the frequency of AFRS relative to endoscopic sinus procedures performed for all other diagnoses. The highest incidence occurred in Memphis, Tennessee at 23%, with three other southern practices reporting a frequency of at least 10%. In the northern locations the frequency ranged from 0 to 4%. No correlation with mould counts was demonstrated, possibly because of incomplete mould data relative to most of the surgical locations.

Quantitative analysis of microdebriders used in endoscopic sinus surgery.

PURPOSE: To develop a standardized in vitro model for evaluating efficacy of the microdebriders and to assess whether differences in efficacy exist among available microdebriders. Microdebriders combine suction of tissue with amputation by a hollow rotating cutter. Several models are available, and they are increasingly popular in endoscopic sinus surgery. MATERIALS AND METHODS: Seven microdebriders were tested by using a standardized soft tissue model (standard fresh raw oysters excluding muscle) and a firm tissue model (standard fresh raw oyster muscle). Efficacy was measured in grams of tissue aspirated per minute. Models to simulate lamina papyracea (eggshell) and dura (egg sac) were also tested with each microdebrider. RESULTS: Statistically significant differences in soft tissue aspiration were found between most microdebriders ranging from the Xomed (Jacksonville, FL) Straight Shot/4.0-mm blade (147 g/min); the ESSential Shaver (Smith & Nephew, Memphis, TN)/4.0-mm blade (99 g/min), the Linvatec (Largo, FL)/4.2-mm blade and Dyonics (Burscheid, Germany)/3.5-mm blade and Wizard Plus/4.0-mm blade (range 43 to 46 g/min), followed by the Hummer II (Stryker, Santa Clara, CA) 4.0-mm blade (22.5 g/min), and finally the Xomed Wizard Plus/3.5-mm blade at 16 g/min. The Xomed Straight Shot/4.0 blade was statistically superior to all other microdebriders in efficiency of aspiration in the firm tissue model. All microdebriders were able to abrade a "bony" spicule and intact "dura," whereas none could abrade intact "bone." CONCLUSIONS: Significant differences exist among the various microdebriders in this standardized model of efficiency of aspiration. Additional clinical factors including cost, safety, ease of use, and adaptability should also be considered in the choice of a microdebrider.