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2.
Hum Vaccin Immunother ; 11(8): 1910-6, 2015.
Article in English | MEDLINE | ID: mdl-26125249

ABSTRACT

A new tuberculosis vaccine is needed to replace or enhance BCG, which induces variable protection against Mycobacterium tuberculosis pulmonary infections in adults. Development of new TB vaccine candidates is severely hampered by the lack of a correlate of immunity, unproven animal models, and limited funding opportunities. One candidate, MVA85A, recently failed to meet its efficacy endpoint goals despite promising early-phase trial data. As a result, some in the field believe we should now shift our focus away from product development and toward a research-oriented approach. Here, we outline our suggestions for this research-oriented strategy including diversification of the candidate pipeline, expanding measurements of immunity, improving pre-clinical animal models, and investing in combination pre-clinical/experimental medicine studies. As with any evolution, this change in strategy comes at a cost but may also represent an opportunity for advancing the field.


Subject(s)
Mycobacterium tuberculosis/immunology , Tuberculosis Vaccines/immunology , Tuberculosis Vaccines/isolation & purification , Tuberculosis/prevention & control , Animals , Biomarkers/analysis , Biomedical Research/trends , Disease Models, Animal , Drug Discovery/trends , Humans , Tuberculosis/immunology
3.
Intensive Care Med ; 40(3): 370-9, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24257969

ABSTRACT

PURPOSE: Cognitive impairment after critical illness is common and debilitating. We developed a cognitive therapy program for critically ill patients and assessed the feasibility and safety of administering combined cognitive and physical therapy early during a critical illness. METHODS: We randomized 87 medical and surgical ICU patients with respiratory failure and/or shock in a 1:1:2 manner to three groups: usual care, early once-daily physical therapy, or early once-daily physical therapy plus a novel, progressive, twice-daily cognitive therapy protocol. Cognitive therapy included orientation, memory, attention, and problem-solving exercises, and other activities. We assessed feasibility outcomes of the early cognitive plus physical therapy intervention. At 3 months, we also assessed cognitive, functional, and health-related quality of life outcomes. Data are presented as median (interquartile range) or frequency (%). RESULTS: Early cognitive therapy was a delivered to 41/43 (95%) of cognitive plus physical therapy patients on 100% (92-100%) of study days beginning 1.0 (1.0-1.0) day following enrollment. Physical therapy was received by 17/22 (77%) of usual care patients, by 21/22 (95%) of physical therapy only patients, and 42/43 (98%) of cognitive plus physical therapy patients on 17% (10-26%), 67% (46-87%), and 75% (59-88%) of study days, respectively. Cognitive, functional, and health-related quality of life outcomes did not differ between groups at 3-month follow-up. CONCLUSIONS: This pilot study demonstrates that early rehabilitation can be extended beyond physical therapy to include cognitive therapy. Future work to determine optimal patient selection, intensity of treatment, and benefits of cognitive therapy in the critically ill is needed.


Subject(s)
Cognitive Behavioral Therapy/methods , Cognitive Dysfunction/therapy , Critical Illness/rehabilitation , Exercise Therapy/methods , Intensive Care Units/statistics & numerical data , Adult , Aged , Feasibility Studies , Female , Humans , Male , Middle Aged , Occupational Therapy/methods , Pilot Projects , Quality of Life , Surveys and Questionnaires , Treatment Outcome
4.
Dig Dis Sci ; 31(11): 1254-64, 1986 Nov.
Article in English | MEDLINE | ID: mdl-2429807

ABSTRACT

The effect of pancreatic duct obstruction on the activities of amylase and three nonexocrine pancreatic enzymes was studied in the rat. gamma-Glutamyl transferase (GGTase) activity, which is localized primarily in the plasma membrane of acinar cells, disappeared from the acinar basolateral plasma membrane and declined in specific activity by 80% over a seven-day experimental period. Mg-ATPase, localized primarily in the apical plasma membrane of acinar cells, simultaneously declined in activity in acinar cells but increased in activity in connective tissue. Mg-ATPase specific activity rose 3.5-fold. The histochemical results showed that the ductlike cells resulting from obstruction were derived primarily from acinar cells. Alkaline phosphatase (APase) activity, which is localized in vascular endothelium and the stroma of interlobular ducts, exhibited a dramatic increase in the periacinar, periductal, and interlobular stroma, and specific activity rose 11-fold. Amylase-specific activity declined as did the protein to DNA ratio. Gel electrophoresis showed that the amount of zymogen granule polypeptides declined after duct obstruction, whereas a few other polypeptides increased in amount.


Subject(s)
Alkaline Phosphatase/metabolism , Amylases/metabolism , Ca(2+) Mg(2+)-ATPase/metabolism , Pancreas/enzymology , Pancreatic Ducts/physiology , Pancreatitis/etiology , gamma-Glutamyltransferase/metabolism , Animals , Ligation , Male , Pancreatitis/enzymology , Rats , Rats, Inbred Strains
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