Influence of built environment on quality of life changes in African-American patients with non-metastatic breast cancer.

Research links the built environment to health outcomes, but little is known about how this affects quality of life (QOL) of African American breast cancer patients, especially those residing in disadvantaged neighborhoods. Using latent trajectory models, we examined whether the built environment using Google Street View was associated with changes in QOL over a 2-year follow-up in 228 newly diagnosed African American breast cancer patients. We measured QOL using the RAND 36-Item Health Survey subscales. After adjusting for covariates, improvement in emotional well-being and pain over time was greater for women living on streets with low-quality (vs. high-quality) sidewalks.

Metastatic breast cancer in patients with schizophrenia.

Breast cancer is a major health problem worldwide. The median survival duration for patients with metastatic breast cancer is two to three years. Approximately 1% of populations worldwide have schizophrenia. The manner in which schizophrenic patients fare when diagnosed with metastatic breast carcinoma (MBC) was evaluated. We queried the National Department of Veterans Affairs (DVA) datasets using computer codes for a pre-existing diagnosis of schizophrenia and a later diagnosis of breast carcinoma. Chart-based data concerning the identified subjects were then requested. Previously determined inclusion and exclusion criteria were applied to select evaluable patients from the medical records, prior to extracting demographic details and data concerning the treatment course in each subject. Ten patients had distant metastases at initial diagnosis, while seven developed MBC following prior curative-intent treatment. Two patients refused therapy. Ten did not comply with recommended management. Five harmed or threatened physicians, other caregivers or themselves. Schizophrenic patients with MBC often fail to understand the nature of their illnesses. Often they do not accept palliative treatment, while a number of them do not comply with therapy, once initiated. They often exhibit behaviors that are detrimental to themselves or others. Formal psychiatric consultation is therefore necessary in patients. Several detrimental behaviors may be predicted reliably by history alone.

A look into the ductoscope: its role in pathologic nipple discharge.

OBJECTIVE: Mammary ductoscopy allows direct visualization of the ductal system and a method for directed excision and pathologic diagnosis. We reviewed our experience with mammary ductoscopy in the evaluation of pathologic nipple discharge. METHODS: We reviewed all patients who underwent ductoscopy for pathologic nipple discharge at our institution from 2006-2010. All procedures were performed by a single surgeon. Data included patient and imaging characteristics, indications, operative findings, and pathologic outcomes. Descriptive statistics were used for data summary. RESULTS: During the study period, 121 patients underwent ductoscopy and directed duct excision for pathologic nipple discharge, including 66 (55%) with bloody discharge. Breast imaging [mammography, ultrasound, and/or magnetic resonance imaging (MRI)] revealed BIRADS category I/II/III findings in 112 (93%), BIRADS category IV findings in 6 (5%), and was unknown in 3 (2%) patients. Final pathology revealed papillomas in 64 (53%) patients, duct ectasia and associated benign findings in 48 (40%) patients, ductal carcinoma in situ (DCIS) in 7 (6%) patients, and atypical ductal hyperplasia in 2 (1%) patients. None of the patients with DCIS underwent preductoscopy MRI, but all had BIRADS category I/II/III breast imaging. The extent of DCIS identified by ductoscopy and subsequent surgical excision ranged from <1 cm to 10 cm (median 3 cm). CONCLUSIONS: The majority of patients with pathologic nipple discharge have benign nonproliferative findings or benign papillomas. Although atypia and malignancy were diagnosed in only 7% of patients who underwent ductoscopy for pathologic nipple discharge, there were no routine imaging findings indicative of these diagnoses preoperatively.

Immunogenicity of L(d+) transgenic mouse hearts.

BACKGROUND: C57BL/6 mice transfected with the L(d) gene coupled to the alpha-myosin heavy chain promoter result in transgenic mice with L(d) antigen expressed only on cardiac tissue. These transgenic animals allow the examination of immune reactivity against cardiac L(d) by "self" or by adoptively transferred L(d) specific 2C cells, and the response of nontransgenic C57BL/6 mice to the transplanted L(d+) heart. METHODS: Naïve cardiac L(d+) transgenic mice were examined for evidence of L(d) "autoimmunity." Forty million fresh 2C cells or 2C cells sensitized in vitro for 7 days against Balb/c (L(d+)) + interleukin-2 were also given intravenously to L(d+) transgenic mice. At 5 and 12 days after injection, heart-infiltrating lymphocytes were analyzed by fluorescence-activated cell sorter. The L(d+) transgenic hearts were also transplanted to syngeneic L(d-) nontransgenic C57BL/6 to evaluate the heart's immunogenicity. RESULTS: Naïve L(d+) transgenic mice did not exhibit any evidence of lymphocytic infiltration on histologic examination. Adoptive transfer of either fresh or in vitro sensitized 2C cells was also unable to reject the native L(d+) heart in transgenic mice (100% of the mice survived long term [more than 60 days]). Sensitization of the L(d+) transgenic mice with a Balb/c skin graft and interleukin-2 pump infusion (7 days) beginning 1 day before 2C cell injection also did not promote rejection of the native L(d+) heart. However, fluorescence-activated cell sorter analysis did reveal that a significantly greater number of in vitro sensitized 2C cells homed to the L(d+), but not L(d-), heart after both 5 and 12 days (P <.01, P <.001). In contrast, C57BL/6 mice rejected the L(d+) (C57BL/6 background) transgenic heart in a mean survival time of 17 +/- 9.7 days (P <.01), whereas a syngeneic C57BL/6 heart transplant was accepted indefinitely. Lymphocytic infiltration consistent with rejection was present in all animals receiving an Ld+ transgenic heart transplant, whereas no infiltrate was present in those receiving a syngeneic C57BL/6 heart transplant. CONCLUSIONS: Although the class I L(d) transgene is not recognized in its native host, its immunogenicity is shown by the homing of anti-L(d) 2C cells to the heart in situ and rejection of L(d+) heart grafts when transplanted into syngeneic C57BL/6 mice.

How surgeon age affects post-treatment surveillance strategies for melanoma patients.

The intensity of post-treatment melanoma patient follow-up varies widely among physicians. We investigated whether physician age accounts for the observed variation in surveillance intensity among plastic surgeons. A custom-designed questionnaire was mailed to USA and non-USA surgeons, all of whom were members of the American Society of Plastic and Reconstructive Surgeons. Subjects were asked how they use 14 specific follow-up modalities during years 1-5 and 10 following primary treatment for patients with cutaneous melanoma. Repeated-measures analysis of variance was used to compare practice patterns by TNM stage, year post-surgery, and age. Of the 3,032 questionnaires mailed, 1,142 (38%) were returned. Of those returned, 395 (35%) were evaluable. Non-evaluability was usually due to lack of melanoma patient follow-up in surgeons' practices. Follow-up strategies for most of the 14 modalities were highly correlated across TNM stages and years post-surgery, as expected. The pattern of testing varied significantly by surgeon age for 3 modalities (complete blood count, liver function tests, and chest X-ray), but the variation was quite small. We concluded that the post-treatment surveillance practice patterns of ASPRS members caring for patients with cutaneous melanoma vary only marginally with physician age. Continuing medical education could account for this observation.

Organ transplant specificity of tolerance to skin grafts with heart or kidney grafts plus nondepleting anti-CD4 monoclonal antibody (RIB 5/2) and intravenous donor alloantigen administration.

BACKGROUND: CD4+ T cells play an essential role in allograft rejection. Monoclonal anti-rat CD4 antibody, RIB 5/2, has been shown to modulate the CD4 glycoprotein without eliminating recipient T cells. A single dose of monoclonal anti-rat CD4 antibody RIB 5/2 plus donor splenocytes results in donor-specific unresponsiveness to heart and kidney allografts, but not skin allografts. This study examined whether tolerance to the more resistant skin graft could also be achieved with RIB 5/2. METHODS: Buffalo (RT1(b)) recipients were given a single dose (20 mg/kg) of monoclonal antibody RIB 5/2 IP plus IV Lewis (RT1(l)) splenocytes (25 x 10(6)) 21 days before Lewis heart, kidney, or skin grafts. In addition, Lewis skin was grafted either simultaneously with or after long- term Lewis heart or kidney allograft acceptance (>50 days). RESULTS: While IV alloantigen plus RIB 5/2 results in long-term acceptance of both heart and kidney, skin allografts are rejected when transplanted alone. Simultaneous transplantation with a Lewis kidney, but not with a Lewis heart, resulted in long-term Lewis skin graft acceptance. However, recipients tolerant to Lewis kidney or heart alone will not accept subsequent Lewis skin grafts, while recipients of simultaneous Lewis skin and kidney grafts subsequently accept a second Lewis, but not third-party Brown Norway (RT1(n)), skin graft. CONCLUSION: RIB 5/2 plus Lewis donor splenocytes tolerize for donor-specific heart and kidney but not skin grafts. However, Lewis skin grafted simultaneously with a Lewis kidney, but not Lewis heart, is accepted and protects a subsequent donor-specific Lewis skin graft.

Intrathymic alloantigen-mediated, tolerant, completely major histocompatibility complex-mismatched mouse hearts are specifically rejected by adoptively transferred anti-class I L(d+)-specific 2C cells.

BACKGROUND: Tolerance to cardiac allografts can be induced in mice and rats by the injection of donor alloantigen into the thymus in combination with a CD4 T-cell-depleting antibody. CD8(+) cells in these animals are hyporesponsive to graft-specific alloantigens. Most of the CD8(+) T cells in the transgenic 2C mouse express a T-cell receptor specific for the class I major histocompatibility complex L(d+) locus. This study was designed to determine whether the adoptive transfer of these 2C T cells could precipitate rejection of a tolerant, completely major histocompatibility complex-mismatched L(d+) or L(d-) heart. METHODS: C57BL/6 mice (L(d-)) were given 10 x 10(6) cells of BALB/c (L(d+)) or dm2 (BALB/c background lacking L(d) [L(d-)]) splenocytes intrathymically and GK1. 5 (10 mg/kg) intraperitoneally. Twenty-one days later, BALB/c or dm2 hearts were transplanted. On the day of transplantation or after long-term allograft acceptance, recipients received naive 2C cells or 2C cells sensitized by in vitro mixed lymphocyte culture with BALB/c (L(d+)). RESULTS: Mean survival time of BALB/c cardiac allografts in untreated C57BL/6 mice was 7.3 days, although 73% of the mice that were pretreated with BALB/c splenocytes IT plus GK1.5 accepted the donor antigen-specific heart allografts indefinitely. All recipients that were pretreated with the intrathymic plus GK1.5 and that were injected with naive 2C cells at the time of heart transplantation experienced rejection of the BALB/c (L(d+)), but not the dm2 (L(d-)) hearts. In contrast, naive 2C cells could not reject tolerant (>30 days acceptance) BALB/c (L(d+)) hearts. 2C cells sensitized in vitro against L(d) were able to reject established BALB/c hearts but could not reject the L(d-) dm2 hearts. CONCLUSIONS: L(d)-specific 2C T-cell receptor transgenic T cells that are adoptively transferred to recipients will precipitate the rejection of accepted hearts that express class I L(d+) in mice rendered tolerant by an intrathymic injection of alloantigen plus anti-CD4 monoclonal antibodies.

MnSOD expression is increased in metastatic gastric cancer.

BACKGROUND: Manganese superoxide dismutase (MnSOD) catalyzes the scavenging of superoxide radicals in order to protect cells from the damage caused by reactive oxygen species. Previous studies implicate MnSOD in cancer progression, but its role in gastric cancer metastasis is poorly understood. MATERIALS AND METHODS: To determine whether MnSOD expression correlates with gastric cancer metastasis, we compared immunostaining for MnSOD in the primary tumors of gastric cancer patients with (n = 15) and without (n = 9) nodal metastases. These patients were matched for risk factors associated with gastric cancer metastasis, such as tumor site, depth, and grade. MnSOD expression was scored positive (increased) if MnSOD staining of tumor cells was more intense than MnSOD staining in corresponding normal gastric epithelial cells. Statistical analyses were via chi(2) test and Fisher's exact test. RESULTS: MnSOD expression was increased in 14 of the 15 (93%) metastatic tumors, compared to only 4 of the 9 (44%) nonmetastatic tumors (P = 0.015). There was no significant difference in staining when the two groups were compared based on tumor grade (P = 0.70) or depth of tumor cell invasion (T stage) (P = 0.22). CONCLUSIONS: MnSOD expression is upregulated in the primary tumors of gastric cancer patients with lymph node metastases. This finding supports an involvement of MnSOD and possibly the reactive oxygen status of the gastric tumor microenvironment in gastric cancer metastasis.

Cholecystectomy is an effective treatment for biliary dyskinesia.

BACKGROUND: An increasing number of reports indicate symptomatic relief of biliary colic symptoms after cholecystectomy for biliary dyskinesia. Despite this, cholecystectomy as a treatment for biliary dyskinesia remains controversial. Our aim was to determine efficacy of cholecystectomy in alleviating biliary dyskinesia symptoms and the correlation with histologic findings. METHODS: Records of patients with gallbladder ejection fraction <35% between January 1994 and February 1999 were reviewed. Gallbladder pathology and degree of symptomatic improvement were determined on follow-up. RESULTS: Of the 27 cholecystectomy patients, 24 (89%) had significant improvement, 2 (7%) had partial improvement, and 1 (4%) had minimal improvement. Ten patients (43%) had normal gall-bladder, and 9 (90%) of them had significant improvement after cholecystectomy. Of the 6 nonsurgical patients, none had significant improvement, 4 (67%) had partial improvement, and 2 (33%) had minimal improvement. CONCLUSIONS: Biliary dyskinesia patients who underwent cholecystectomy had significantly greater symptom improvement compared with nonsurgical patients. Pathologic correlation suggests chronic inflammation may not be the only cause of gallbladder dysfunction. Cholecystectomy should be a first-line therapy for biliary dyskinesia patients.

Regulation of pituitary-adrenocortical activity by free fatty acids in vivo and in vitro.

Virtually every metabolic disorder characterized by elevated plasma free fatty acid (FFA) levels is also associated with hypercorticoidism. For example, the glucocorticoid response to insulin-hypoglycemia is shown in this report to be greatly potentiated in Type I diabetic rats. Since glucocorticoids (corticosterone, in rats) potentiate lipolysis and promote gluconeogenesis, they exacerbate diabetes. We found that elevation of circulating FFA levels in normal rats (via Intralipid/heparin infusion) increased plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, and resulted in hyperglycemia. In vitro, however, cultured pituitary cells were relatively unaffected by FFA except at very high concentrations. Neither basal ACTH secretion nor the ACTH response to corticotropin-releasing hormone (CRH) was affected by pathophysiological molar ratios of FFA:BSA. Thus, the ACTH secretory response to FFA in vivo likely is mediated via neuroendocrine activation. Cultured adrenocortical cells, however, were stimulated by oleic acid and, to a lesser extent, by linoleic acid; saturated fatty acids were without effect. The latencies of oleic acid-induced steroidogenesis in vitro and Intralipid-induced corticosterone secretion in vivo were both about 60 min. We conclude that pathophysiological levels of circulating FFA (typical of diabetes, obesity, starvation, and consumption of high-fat diets) initiate a positive feedback loop between the adipocyte and the HPA axis, which ultimately exacerbates the symptoms of these disorders.