Whidden Memorial Hospital

PURPOSE: Adoptive cellular immunotherapy is a promising approach to eradicate established tumors. However, a significant hurdle in the success of cellular immunotherapy involves recently identified mechanisms of immune suppression on cytotoxic T cells at the effector phase. Transforming growth factor-beta (TGF-beta) is one of the most important of these immunosuppressive factors because it affects both T-cell and macrophage functions. We thus hypothesized that systemic blockade of TGF-beta signaling combined with adoptive T-cell transfer would enhance the effectiveness of the therapy. EXPERIMENTAL DESIGN: Flank tumors were generated in mice using the chicken ovalbumin-expressing thymoma cell line, EG7. Splenocytes from transgenic OT-1 mice (whose CD8 T cells recognize an immunodominant peptide in chicken ovalbumin) were activated in vitro and adoptively transferred into mice bearing large tumors in the presence or absence of an orally available TGF-beta receptor-I kinase blocker (SM16). RESULTS: We observed markedly smaller tumors in the group receiving the combination of SM16 chow and adoptive transfer. Additional investigation revealed that TGF-beta receptor blockade increased the persistence of adoptively transferred T cells in the spleen and lymph nodes, increased numbers of adoptively transferred T cells within tumors, increased activation of these infiltrating T cells, and altered the tumor microenvironment with a significant increase in tumor necrosis factor-alpha and decrease in arginase mRNA expression. CONCLUSIONS: We found that systemic blockade of TGF-beta receptor activity augmented the antitumor activity of adoptively transferred T cells and may thus be a useful adjunct in future clinical trials.

Many narrow QRS complex tachycardias are benign, but some require rapid intervention. The review, EKG strips, and algorithm you'll find here will help you get to the source of the problem without delay.

Ischemic cardiomyopathy is one of the most common causes of congestive heart failure. Despite multiple therapeutic options, morbidity and mortality remain high. Revascularization is one of the best options to improve ejection fraction and survival in patients with hibernating myocardium. This article discusses the role of positron emission tomography (PET), single-photon emission computed tomography (SPECT), dobutamine stress echocardiography (DSE), and magnetic resonance imaging (MRI)-based viability studies and their comparative evaluation.

Isolated left ventricular non-compaction is a rare congenital cardiomyopathy. Patients frequently present with signs of heart failure and dyspnea on exertion. Myocardial perfusion tests using single photon emission computed tomography are frequently used for evaluation of ischemia. In this case report we present myocardial perfusion images of isolated left ventricular non-compaction from a patient who was referred to our center for evaluation of dyspnea on exertion.

Atrial fibrillation is the most common sustained cardiac arrhythmia. The rhythm in atrial fibrillation is irregular. Correct interpretation of the electrocardiogram (ECG) is essential. Atrial flutter can present as regular or irregular narrow QRS complex tachycardia. Knowledge of the ECG features of atrial flutter will help to differentiate it from paroxysmal supraventricular tachycardia. The treatment strategy in atrial fibrillation should focus on rhythm control vs. rate control, and anticoagulation should be started based on the calculated risk of systemic embolisation. Atrial flutter is a unique arrhythmia that has similar management strategies to those of atrial fibrillation; however, radiofrequency ablation is increasingly preferred due to its higher rate of efficacy and safety compared to pharmacological therapy.

This issue of Work highlights Swedish models of health care, particularly in the area of rehabilitation. It is natural, for one whose cultural and clinical experience has been concentrated in the United States, to compare and contrast the underlying assumptions of the approaches taken in the two countries.

Diagnosis: Kaposi's varicelliform eruption (eczema herpeticum). Vesicular lesions on the patient's face (figures 1 and 2) were unroofed. Direct fluorescent antibody staining was positive for herpes simplex virus type 1 (HSV-1) (figure 3) and negative for HSV-2 and varicella zoster virus. Culture of the overlying purulence grew methcillin-sensitive Staphylococcus aureus and group B β-hemolytic streptococcus at <24 h. A diagnosis of Kaposi's varicelliform eruption (KVE; eczema herpeticum) with staphylococcal superinfection was made. The patient had no previous history of symptomatic HSV infection. The patient was treated with intravenous acyclovir and nafcillin. His fever, headache, and malaise resolved over the next 24 h, his vesicular lesions became scabbed and dry, and the purulent exudate resolved. An ophthalmologic examination also revealed HSV keratitis, which was treated with topical trifluridine solution. On hospital day 5, the patient was discharged with a regimen of oral famciclovir and dicloxacillin. Vesiculopapular lesions on the patient's face, characteristic of those seen on much of his body. Vesiculopapular lesions on the patient's face, characteristic of those seen on much of his body. Purulent exudate covering posterior auricular skin folds Purulent exudate covering posterior auricular skin folds Direct fluorescent antibody stain for herpes simplex virus type 1 of a fluid sample obtained from a facial vesicle. Direct fluorescent antibody stain for herpes simplex virus type 1 of a fluid sample obtained from a facial vesicle. KVE is a generalized vesiculobullous eruption caused by widespread cutaneous viral infection in a patient with an underlying skin disorder. As in this case, the differential diagnosis may include, but is not limited to, disseminated HSV or varicella zoster virus infection, acute HIV infection, smallpox, disseminated Neisseria gonorrhoeae infection, and drug eruption. KVE has been associated with primary or reactivated HSV-1 and HSV-2 infection; in these cases, the term “eczema herpeticum,” rather than KVE, may be used to refer to the condition. Other associated viral infections include vaccinia virus infection (i.e., eczema vaccinatum) and coxsackie virus infection. Although eczema is the most common predisposing condition, KVE has also been reported in patients with systemic lupus erythematosis, psoriasis, pemphigus vulgaris, bullous pemphigoid, multiple myeloma, and cutaneous T cell lymphoma, among other conditions [1–4]. Infectious skin conditions (e.g., scabies, dermatophyte infection, and impetigo) and mechanical skin damage (e.g., burns and dermabrasion) have also been implicated as predisposing factors [5, 6]. Impaired barrier function of the inflamed epidermis and concomitant immunosuppressive therapies are risk factors for viral superinfection in these syndromes. KVE may represent true disseminated infection (with keratitis, meningitis and/or encephalitis, or hepatitis), but it more commonly remains a cutaneous infection [2, 5]. Classically presented here, the diagnosis of KVE is often suspected when fever accompanies what is initially thought to be a “flare” of the patient's underlying skin disease. Samples of vesicle contents can confirm the diagnosis when evidence of viral infection is noted, including positive Tzanck smears, multinucleated giant cells or herpes cytopathic effect seen on hematoxylin and eosin stain, direct fluorescent antibody testing for HSV, viral culture, or viral PCR. If HSV is suspected or confirmed, intravenous or oral acyclovir is the recommended therapy, with additional antimicrobial therapy, if needed, for staphylococcal superinfection. The prognosis is usually excellent; when recurrent episodes occur, they are generally milder than initial presentations. Potential conflicts of interest. All authors: no conflicts.