Imaging surveillance of the breast in a patient diagnosed with scleroderma after breast-conserving surgery and radiotherapy

Abstract:  Collagen vascular disease (CVD), particularly scleroderma, is a contraindication to radiation therapy because of increased risk of fibrosis. We report a patient with early stage breast cancer diagnosed with scleroderma after breast-conserving surgery and radiation. She developed marked breast fibrosis, rendering mammographic, sonographic, and clinical surveillance ineffective. She has subsequently been followed with magnetic resonance imaging (MRI) of the breast. We illustrate this case and review the literature relating to CVD and radiation therapy. MRI may be a suitable surveillance method in this situation.     

Time of day is associated with postoperative morbidity: an analysis of the national surgical quality improvement program data

OBJECTIVE: To examine the association between surgical start time and morbidity and mortality for nonemergent procedures. SUMMARY BACKGROUND DATA: Patients require medical services 24 hours a day. Several studies have demonstrated a difference in outcomes over the course of the day for anesthetic adverse events, death in the ICU, and dialysis care. The relationship between operation start time and patient outcomes is yet undefined. METHODS: We performed a retrospective cohort study of 144,740 nonemergent general and vascular surgical procedures performed within the VA Medical System 2000-2004 and entered into the National Surgical Quality Improvement Program Database. Operation start time was the independent variable of interest. Logistic regression was used to adjust for patient and procedural characteristics and to determine the association between start time and, in 2 independent models, mortality and morbidity. RESULTS: Unadjusted later start time was significantly associated with higher surgical morbidity and mortality. After adjustment for patient and procedure characteristics, mortality was not significantly associated with start time. However, after appropriate adjustment, operations starting between 4 pm and 6 pm were associated with an elevated risk of morbidity (OR = 1.25, P < or = 0.005) over those starting between 7 am and 4 pm as were operations starting between 6 pm and 11 pm (OR = 1.60, P < or = 0.005). CONCLUSIONS: When considering a nonemergent procedure, surgeons must bear in mind that cases that start after routine "business" hours within the VA System may face an elevated risk of complications that warrants further evaluation.     

Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study

BACKGROUND: Optimal use of disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis is vital if progression of disease is to be reduced. Methotrexate (MTX) and sulfasalazine (SASP) are widely used inexpensive DMARDs, recently often combined despite no firm evidence of benefit from previous studies. Aim: To establish whether a combination of SASP and MTX is superior to either drug alone in patients with rheumatoid arthritis with a suboptimal response to 6 months of SASP. METHODS: A randomised controlled study of step-up DMARD treatment in early rheumatoid arthritis. In phase I, 687 patients received SASP for 6 months. Those with a disease activity score (DAS) > or =2.4 were offered additional treatment in phase II (SASP alone, MTX alone or a combination of the two). The primary outcome measure was change in DAS. RESULTS: At 6 months, 191 (28%) patients had a DAS <2.4, 123 (18%) were eligible but did not wish to enter phase II, 130 (19%) stopped SASP because of reversible adverse events and 165 (24%) entered phase II. DAS at 18 months was significantly lower in those who received combination treatment compared with those who received either SASP or MTX: monotherapy arms did not differ. Improvement in European League Against Rheumatism and American College of Rheumatology 20, 50 and 70 scores favoured combination therapy. CONCLUSIONS: In this "true-to-life" study, an inexpensive combination of DMARDs proved more effective than monotherapy in patients with rheumatoid arthritis with a suboptimal response to SASP. There was no increase in toxicity. These results provide an evidence base for the use of this combination as a component of tight control strategies.     

Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells

Dendritic cells (DCs) play a key role in immune homeostasis and maintenance of self-tolerance. Tolerogenic DCs can be established by an encounter with apoptotic cells (ACs) and subsequent inhibition of maturation and effector functions. The receptor(s) and signaling pathway(s) involved in AC-induced inhibition of DCs have yet to be defined. We demonstrate that pretreatment with apoptotic but not necrotic cells inhibits activation of IkappaB kinase (IKK) and downstream NF-kappaB. Notably, receptor tyrosine kinase Mer (MerTK) binding of ACs is required for mediating this effect. Monocyte-derived DCs lacking MerTK expression (MerTKKD) or treated with blocking MerTK-specific antibodies (Abs) are resistant to AC-induced inhibition and continue to activate NF-kappaB and secrete proinflammatory cytokines. Blocking MerTK activation of the phosphatidylinositol 3-kinase (PI3K)/AKT pathway prevents AC-induced inhibition. These results demonstrate an essential role for MerTK-mediated regulation of the PI3K/AKT and NF-kappaB pathways in AC-induced inhibition of monocyte-derived DCs.     

Brain metastasis from non-seminomatous germ cell tumor of the testis

Brain metastasis occurs rarely in patients with testicular cancer in the modern era where cisplatin-based chemotherapy regimens are used. The occurrence of brain metastasis can be synchronous or metachronous (with or without concurrent systemic disease). Long-term survival can be achieved in some patients. The vast majority of testicular cancer cases with brain metastasis reported in the literature involve nonseminomatous germ cell tumor and this subtype will be the focus of this review. This article reviews the literature of the diagnosis and management of brain metastasis from nonseminomatous germ cell tumor of the testis.     

Regional radiotherapy versus an axillary lymph node dissection after lumpectomy: a safe alternative for an axillary lymph node dissection in a clinically uninvolved axilla in breast cancer. A case control study with 10 years follow up

Background

To correlate the metabolic changes with size changes for tumor response by concomitant PET-CT evaluation of lung cancers after radiotherapy.

Methods

36 patients were studied pre- and post-radiotherapy with¹⁸FDG PET-CT scans at a median interval of 71 days. All of the patients were followed clinically and radiographically after a mean period of 342 days for assessment of local control or failure rates. Change in size (sum of maximum orthogonal diameters) was correlated with that of maximum standard uptake value (SUV) of the primary lung cancer before and after conventional radiotherapy.

Results

There was a significant reduction in both SUV and size of the primary cancer after radiotherapy (p < 0.00005). Among the 20 surviving patients, the sensitivity, specificity, and accuracy using PET (SUV) were 94%, 50%, 90% respectively and the corresponding values using and CT (size criteria) were 67%, 50%, and 65% respectively. The metabolic change (SUV) was highly correlated with the change in size by a quadratic function. In addition, the mean percentage metabolic change was significantly larger than that of size change (62.3 ± 32.7% vs 47.1 ± 26.1% respectively, p = 0.03)

Conclusion

Correlating and incorporating metabolic change by PET into size change by concomitant CT is more sensitive in assessing therapeutic response than CT alone.     

Tonically active GABAA receptors in hippocampal pyramidal neurons exhibit constitutive GABA-independent gating

Phasic and tonic inhibitory currents of hippocampal pyramidal neurons exhibit distinct pharmacological properties. Picrotoxin and bicuculline methiodide inhibited both components, consistent with a role for GABAA receptors; however, gabazine, at a concentration that abolished miniature GABAergic inhibitory postsynaptic currents and responses to exogenous GABA, had no effect on tonic currents. Because all GABA-activated GABAA receptors in pyramidal neurons are gabazine-sensitive, it follows that tonic currents are not GABA-activated. Furthermore, picrotoxin-sensitive spontaneous single-channel events recorded from outside-out patches had the same chord conductance as GABA-activated channels and were gabazine-resistant. Therefore, we hypothesize that GABAA receptors, constitutively active in the absence of GABA, mediate tonic current; the failure of gabazine to block tonic current reflects a lack of negative intrinsic efficacy of the antagonist. We compared the negative efficacies of bicuculline and gabazine using the general anesthetic propofol to directly activate GABAA receptors native to pyramidal neurons or alpha1beta3gamma2 receptors recombinantly expressed in human embryonic kidney 293 cells. Propofol activated gabazine-resistant, bicuculline-sensitive currents when applied to either preparation. Although gabazine had negligible efficacy as an inhibitor of propofol-activated currents, it prevented inhibition by bicuculline, which acts as an inverse agonist inhibiting GABA-independent gating. Recombinant alpha1beta1/3gamma2 receptors also mediated agonist-independent tonic currents that were resistant to gabazine and inhibited by bicuculline. Thus, gabazine is a competitive antagonist with negligible negative efficacy and is therefore unable to inhibit GABAA receptors that are active in the absence of GABA because of either anesthetic or spontaneous gating. Moreover, spontaneously active GABAA receptors mediate gabazine-resistant tonic currents in pyramidal neurons.     

Immunity in syphilis. Studies in active immunity.

Support for the concept of the development of immunity during the course of syphilis is avaiable in the literature. In experimental syphilis in rabbits, some immunity is present approximately 3 weeks after infection with Treponema pallidum. Resistance to re-infection increases to a maximum at approximately 3 months after infection. Termination of this state by penicillin treatment within this 3-month period may enable re-infection to be accomplished. Attempts to reproduce this state of immunity experimentally by injection of T. pallidum itself, or protein derivatives, or ultrasonic disintegrates obtained from T. pallidum or non-pathogenic treponemes, have been unsuccessful. However, promising results in rabbits have resulted from injecting T. pallidum suspensions attenuated by storage at 4 degrees C, penicillin, or gamma irradiation, and also by suspensions preserved by glutaraldehyde. In the present study, partial resistance to intratesticular challenge in rabbits with T. pallidum has been obtained by immunization with a variety of non-pathogenic treponemes, as exemplified by the strains Nichols, Kazan 2, 4, 5, and 8, Treponema minutum, Treponema ambigua, Treponema refringens and Treponema microdentium. Success is attributed to the processing of immunizing antigens at 4 degrees C and storage until use at -20 degrees C. Attempts to attenuate T. pallidum by immunological means, namely, passage through a limited number of immunized rabbits, were unsuccessful.