Saving the Savings Clause in Federal Habeas Jurisprudence

The Great Writ of habeas corpus, safeguarded by our Constitution as an essential guarantor of liberty, took its current shape over the course of American history as Congress established, expanded, and eventually limited the power of federal courts to issue the writ. Although the Antiterrorism and Effective Death Penalty Act of 1996 imposed harsh new limitations for federal prisoners seeking habeas relief more than once in the same case, Congress’s amendment of the relevant procedural statutes left intact the “savings clause,” allowing such prisoners to file additional requests for relief where the prisoners’ prior requests were “inadequate or ineffective to test the legality” of their imprisonment. Recent splits in circuit court authority have threatened to write the savings clause out of the federal habeas statutes. Although the Fourth Circuit in United States v. Wheeler has recognized the continuing applicability of the savings clause in appropriate cases, the Sixth Circuit in Hueso v. Barnhart announced sharply more limited reasoning, holding the savings clause to be restricted by narrow procedural requirements established elsewhere in the 1996 habeas amendments. Similarly, the Eleventh Circuit in In re Baptiste has held that federal prisoners may never file additional requests for relief on the same underlying claim, regardless of circumstances or the savings clause, while the Ninth Circuit in Jones v. United States has rejected this position and allowed for continuing operation of the savings clause in circumstances where justice so requires. Courts should interpret the savings clause to allow federal prisoners the broadest access to the writ. Such an interpretation is true to the text of the federal habeas statutes, accords with canons of statutory construction, is in line with the legislative history of the 1996 amendments, and respects the constitutional requirement that access to the writ must not be suspended absent extraordinary circumstances. Applying the savings clause in this manner will best honor the letter and spirit of the great writ of liberty

Allergic rhinitis is a local disease: the role of local IgE production, basophils and mast cells

The introduction to this thesis summarizes the literature which indicates that there is a discrepancy between sensitisation and allergic disease. Two aspects which might play a role in this discrepancy are the differences between production and funtion of local versus systemic lgE and the differences in mast cell and basophil function in the blood compared to in the tissues. Mast cells, basophils and IgE are key players in the allergic inflammation. The aim of the studies described in this thesis was to focus on these differences between local and systemic function of these key factors. The research questions addressed in this thesis are: Mast cells and basophils seem to play an important role in the pathogenesis of allergic rhinitis. Do the phenotypes of mast cells and basophilic cells changed by allergen provocation in the nasal mucosa of allergic rhinitis patients (Chapter 3)? The developmental relationship bet\veen mast cells and basophils has not yet been totally resolved. What is the relation bet\veen basophil progenitors, mast cell progenitors, basophils and mast cells in the circulation and in the nasal mucosa (Chapter 3)? Allergic mucosa inflammation is regulated by the local production and release of several Th2 cytokines. Which increase in cytokines and chemokines is correlated to inflammatory cells and symptomatology of the patient? What is the time line of the various cytokines and chemokines after allergen provocation (Chapter 4)? Is it possible to develop a method to detect specific lgE in tissues. Does production of specific IgE take place locally in the nasal mucosa (Chapter 5)? Where do basophils and mast-cell of allergi

Evaluation of Real-Life Investigational Use of Enoximone in Asthma, the Third Step in Drug Repurposing:A Preliminary Report

BACKGROUND: The population of uncontrolled asthma patients represents a large therapeutic burden. The PDE3-inhibitor enoximone is a strong and quick bronchodilator and is known to successfully treat life-threatening bronchial asthma (status asthmaticus). Translational mice models showed anti-inflammatory effects when PDE3 was targeted. METHODS: Here, we investigated the effectiveness of PDE3-inhibitor enoximone as oral treatment for chronic asthma in a real-life off-label setting. Investigational use of PDE3-inhibitor enoximone: 51 outpatients (age 18–77) with chronic asthma were followed using off-label personalized low doses of the PDE3-inhibitor enoximone. Duration of treatment was 2–8 years. RESULTS: Four groups could be distinguished as follows: The first group includes patients who use enoximone as an add-on, because it helps them in maintaining a better general wellbeing; they still use their traditional medication (n = 5). The second group consists of patients who use enoximone and were able to phase down their traditional medication without deterioration of their asthma symptoms (n = 11). The third group comprises patients who were able to discontinue their traditional medication and use only enoximone without deterioration of their asthma symptoms (n = 24). The last one has patients who, after having used enoximone for some time, saw their symptoms disappear and now use no medication at all, not even enoximone (n = 11). All patients reported improvement or at least alleviation of their asthma symptoms. All patients reported a better quality of life and greater drug compliance. CONCLUSION: The evaluation shows that PDE3-inhibitor enoximone is a viable alternative for or addition to current asthma therapeutics, as both add-on and stand-alone, considerably reducing the use of LABAs/SABAs/ICS, with no or negligible side effects. Additional studies are advisable

Phosphodiesterase 3 and 4 Inhibition: Facing a Bright Future in Asthma Control

A recent status on asthmaticus multiple case report by Beute demonstrated the beneficial effects of phosphodiesterase III (PDE3) and phosphodiesterase IV (PDE4) inhibition. This chapter reviews the possible underlying mechanisms, beside the known effect, for the beneficial effects of a mixed PDE3/4 inhibitor in allergic airway inflammation. Structural cells of the lung and immune system express PDE3 and 4. PDE3 and 4 inhibition have a number of consequences related to physical function and cytokine production. The most direct effect of PDE3 inhibition being relaxation of smooth muscle cells results in bronchodilation. However, PDE3 inhibition appears to go further than a mere inhibitory activity in bronchial smooth muscle. It also affects structural cells, and more importantly, it creates an improved barrier function in endothelial cells. PDE3 and 4 inhibition therefore strengthens the immune barrier; but in addition, it modifies the cells of the immune system itself, as these also express PDE3 and 4 activity, thus changing their function. All aspects of asthma-related pathophysiology seem to be affected by PDE3 and 4 inhibition. Clinical use of a mixed PDE3/4 inhibitor in respiratory diseases is currently limited to a few studies, including life-threatening asthma in which mixed PDE3/4 inhibition has a beneficial effect

Differences in nasal cellular infiltrates between allergic children and age-matched controls

Little is known about the cellular infiltrates in the nasal mucosa of children. This study was set up to compare the nasal cellular infiltrates in biopsy specimens from allergic children and controls. Atopic children were distinguished from controls on the basis of symptoms of allergic rhinitis and/or asthma, total serum immunoglobulin (Ig)E, family history and specific serum IgE to food and aeroallergens. Fifteen allergic patients (median age 4.3 yrs) and 15 age-matched nonallergic control subjects were evaluated. The number of cells positive for CD1a, CD4, CD8, CD19, CD68, chymase, tryptase, IgE and major basic protein was determined in the mucosa of the inferior turbinate. A significantly higher number of IgE-positive cells and mast cells was found in the epithelia of the allergic group. In the lamina propria, higher numbers of IgE-positive cells and eosinophils were found. Langerhans' cells positive for IgE were only seen in allergic children with specific serum IgE against aeroallergens. These children also had a higher number of IgE-positive mast cells compared to controls and atopic children without specific serum IgE. These results show that the nasal cellular infiltrates of allergic children differ from nonallergic control subjects. Prior to the detection of specific serum immunoglobulin E, cellular changes can be found in the nasal mucosa of atopic children

Allogeneic chondrogenically differentiated human bone marrow stromal cells do not induce dendritic cell maturation

Bone marrow stromal cell (BMSC)-mediated endochondral bone formation may be a promising alternative to the current gold standards of autologous bone transplantation, in the development of novel methods for bone repair. Implantation of chondrogenically differentiated BMSCs leads to bone formation in vivo via endochondral ossification. The success of this bone formation in an allogeneic system depends upon the interaction between the implanted constructs and the host immune system. The current study investigated the effect of chondrogenically differentiated human bone marrow stromal cell (hBMSC) pellets on the maturation and function of dendritic cells (DCs) by directly coculturing bone forming chondrogenic hBMSC pellets and immature or lipopolysaccharide (LPS)-matured DCs in vitro. Allogeneic chondrogenic hBMSC pellets did not affect the expression of CD80, CD86, or HLADR on immature or LPS-matured DCs following 24, 48, or 72 hr of coculture. Furthermore, they did not induce or inhibit antigen uptake or migration of the DCs over time. IL-6 was secreted by allogeneic chondrogenic hBMSC pellets in response to LPS-matured DCs. Overall, this study has demonstrated that maturation of immature DCs was not influenced by allogeneic chondrogenic hBMSC pellets. This suggests that allogeneic chondrogenic hBMSC pellets do not stimulate immunogenic responses from DCs in vitro and are not expected to indirectly activate T cells via DCs. For this reason, allogeneic chondrogenic bone marrow stromal cell pellets are promising candidates for future tissue engineering strategies utilising allogeneic cells for bone repair