Leptomeningeal Carcinomatosis: A Rare Complication of Metastatic Gastric Cancer.

Leptomeningeal disease, also known as leptomeningeal carcinomatosis, occurs when cancer metastasizes to the meninges. This rare complication is associated with a poor prognosis. It is most commonly seen in patients with metastatic breast cancer, lung cancer, and melanoma. However, it is extremely rare in patients with metastatic gastric cancer. A 64-year-old female with poorly differentiated gastric adenocarcinoma metastatic to the peritoneum developed new neurological symptoms twelve months after initiating palliative chemotherapy. Her uptrending tumor markers, brain magnetic resonance imaging (MRI) findings, and lumbar puncture results were consistent with leptomeningeal disease. The patient was started on treatment with intrathecal methotrexate (IT MTX), which resulted in significant improvement in her neurological symptoms. Leptomeningeal disease in gastric cancer has limited treatment options due to poor blood-brain barrier penetration. IT MTX is a potentially effective treatment for patients with leptomeningeal disease from gastric cancer.

A cluster randomized controlled trial to increase breast cancer screening among African American women: the black cosmetologists promoting health program.

BACKGROUND: African American women have disproportionately higher rates of breast cancer mortality than all other ethnic groups, thus highlighting the importance of promoting early detection. METHODS: African American women (N = 984) from San Diego, California, participated in a randomized controlled trial testing the efficacy of breast cancer education sessions offered in beauty salons. Cosmetologists received ongoing support, training, and additional culturally aligned educational materials to help them engage their clients in dialogues about the importance of breast cancer early detection. Posters and literature about breast cancer early detection were displayed throughout the salons and cosmetologists used synthetic breast models to show their clients how breast cancer lumps might feel. Participants in the control group received a comparable diabetes education program. Baseline and 6-month follow-up surveys were administered to evaluate changes in women's breast cancer knowledge, attitudes, and screening behaviors. RESULTS: This intervention was well received by the participants and their cosmetologists and did not interfere with or prolong the client's salon visit. Women in the intervention group reported significantly higher rates of mammography compared to women in the control group. Training a single educator proved sufficient to permeate the entire salon with the health message, and salon clients agreed that cosmetologists could become effective health educators. CONCLUSIONS: Cosmetologists are in an ideal position to increase African American women's breast cancer knowledge and adherence to breast cancer screening guidelines.

Prostate Cancer Metastatic to the Peritoneum: A Road Less Traveled by a Common Malignancy.

A 70-year-old Indian male with a history of a Gleason 7 (3+4) prostate cancer presented with abdominal ascites. Imaging was remarkable for peritoneal carcinomatosis as well as possible metastases to the bladder and seminal vesicle. Given the atypical pattern of presentation, further investigation was performed with studies of the ascites fluid. Cytology from the ascites fluid returned consistent with malignant cells of prostatic origin. His treatment course included androgen deprivation therapy (ADT), docetaxel, abiraterone, and cabazitaxel. He had eventual progression and worsening of his disease and performance status and was transitioned to hospice. This case demonstrated the importance of pursuing a thorough diagnostic evaluation, when faced with a rare presentation of a common malignancy. Furthermore, it illustrated the challenges incurred when tailoring standard regimens to best address the needs of the whole patient and not simply their disease.

Human-Centered Design of a Low Molecular Weight Heparin Order Set to Reduce Medication Errors.

Inpatient anticoagulation medication errors for venous thromboembolism (VTE) therapy are common. Our VTE Team identified frequent dosing and duplicate order errors for therapeutic-dose low molecular weight heparin, which (lacking computerized physician order entry) was ordered using blank forms. To decrease such errors, a nonmandatory order form with weight-based dosing and prechecked orders discontinuing existing injectable anticoagulation was developed using human-centered design innovation principles/processes emphasizing end-user engagement in all phases: observation, exploring solutions, and rapid prototyping/feedback. Three physicians independently reviewed ordering errors the year before versus after implementation. Before implementation, 11% of orders contained any error versus 10.5% after implementation (p = .82); 6.2% had a dosing or duplicate therapy error versus 4.2% after implementation (all made when the form was not used; p = .19). No dosing or duplicate therapy errors were made when the form was used. Were the form mandatory, all such ordering errors would likely have been eliminated, leaving 11% before versus 6.3% after implementation orders with any error (p = .015), and 6.2% before versus 0% after implementation orders with duplicate or dosing therapy errors (p < .001). Human-centered design of an anticoagulation order form can reduce anticoagulation order errors; such principles can be applied to other health care innovations, including electronic order sets.

Breast cancer knowledge, attitudes, and screening behaviors among African American women: the Black cosmetologists promoting health program.

BACKGROUND: African American women have higher rates of breast cancer mortality than their white counterparts. Studies have suggested that this is partly caused by discovery of cancer at a later stage, highlighting the importance of encouraging early detection of breast cancer in this population. To guide the creation of a breast cancer education intervention and help focus other health educators' and clinicians' health promotion efforts, this study explored whether a cohort of African American women living in San Diego would demonstrate the possession of adequate baseline knowledge about breast cancer screening and adherence to widely recommended screening guidelines. METHODS: African American women (N = 1,055) from San Diego, California participated in a beauty salon-based survey about breast cancer knowledge, attitudes, and screening practices. Women's ages ranged from 20 to 94 years, with average age of 42.20 (SD = 13.53) years. Thirty-four percent reported completing college and/or some graduate school training, and 52% reported having some college or post high school formal training. Seventy-five percent of the sample reported working outside their home. Participating cosmetologists and their salons were recruited to the study through word-of-mouth referral by highly respected African American community leaders. RESULTS: Salon clients reported low rates of adherence to recommended breast cancer screening guidelines. Of the 1,055 participants, 31% reporting performing breast self-exam every month. Of those participants 40 and older, 57% reported having had a clinical breast exam and 43% reported having had a mammogram in the past year. Knowledge of breast cancer was associated with adherence to screening guidelines. While women recognized the serious health threat that breast cancer poses and that early detection of breast cancer is important, only 30% of women reported feeling well informed about the disease. Many participants demonstrated a lack of basic knowledge about breast cancer. The Health Belief Model postulates that access to such information is an essential element in the progression toward engaging in screening behaviors. CONCLUSION: Data from this study reflect a continuing need for increased breast cancer education for African American women. In light of the considerable mainstream information available related to breast cancer, these data reinforce the need for more breast cancer education programs that are clearly intended to attract the attention of African American women.

Hemophagocytic lymphohistiocytosis associated with Epstein-Barr virus in the central nervous system.

Hemophagocytic lymphohistiocytosis (HLH) is a rare immune hyperactivation syndrome which may be primary (genetic) or secondary to various immune-related conditions including infection, immunodeficiency, and malignancies. Rapid diagnosis and treatment are essential because it can be associated with significant morbidity and mortality. Epstein-Barr virus (EBV) is a known infectious cause of acquired HLH, but EBV-associated HLH involving the central nervous system is rare and not well characterized neuropathologically. We report a case of fatal EBV-associated HLH with severe involvement of the central nervous system showing florid hemophagocytosis in the choroid plexus, with extensive neuron loss and gliosis in the cerebrum, cerebellum, and brainstem.

Cardiovascular risk factors among Chamorros.

BACKGROUND: Little is known regarding the cardiovascular disease risk factors among Chamorros residing in the United States. METHODS: The Chamorro Directory International and the CDC's Behavioral Risk Factor Surveillance System Questionnaire (BRFSS) were used to assess the health related practices and needs of a random sample of 228 Chamorros. RESULTS: Inactivity, hypertension, elevated cholesterol and diabetes mellitus were more prevalent in this Chamorro sample compared to the US average. Participants who were 50-and-older or unemployed were more likely to report hypertension, diabetes and inactivity, but they were also more likely to consume more fruits and vegetables than their younger and employed counterparts. Women were more likely to report hypertension and diabetes, whereas men were more likely to have elevated BMI and to have never had their blood cholesterol checked. CONCLUSION: The study provides data that will help healthcare providers, public health workers and community leaders identify where to focus their health improvement efforts for Chamorros and create culturally competent programs to promote health in this community.

Complementary functions of the Saccharomyces cerevisiae Rad2 family nucleases in Okazaki fragment maturation, mutation avoidance, and chromosome stability.

Rad2 family nucleases, identified by sequence similarity within their catalytic domains, function in multiple pathways of DNA metabolism. Three members of the Saccharomyces cerevisiae Rad2 family, Rad2, Rad27, and exonuclease 1 (Exo1), exhibit both 5' exonuclease and flap endonuclease activities. Deletion of RAD27 results in defective Okazaki fragment maturation, DNA repair, and subsequent defects in mutation avoidance and chromosomal stability. However, strains lacking Rad27 are viable. The expression profile of EXO1 during the cell cycle is similar to that of RAD27 and other genes encoding proteins that function in DNA replication and repair, suggesting Exo1 may function as a back up nuclease for Rad27 in DNA replication. We show that overexpression of EXO1 suppresses multiple rad27 null mutation-associated phenotypes derived from DNA replication defects, including temperature sensitivity, Okazaki fragment accumulation, the rate of minichromosome loss, and an elevated mutation frequency. While generally similar findings were observed with RAD2, overexpression of RAD2, but not EXO1, suppressed the MMS sensitivity of the rad27 null mutant cells. This suggests that Rad2 can uniquely complement Rad27 in base excision repair (BER). Furthermore, Rad2 and Exo1 complemented the mutator phenotypes and cell cycle defects of rad27 mutant strains to differing extents, suggesting distinct in vivo nucleic acid substrates.

Diabetes management in San Diego's Chamorro community.

PURPOSE: The purpose of this study was to assess the diabetes risk status, incidence, and morbidity within San Diego's Chamorro community as a foundation to help community leaders and health care providers create culturally customized health promotion interventions. METHODS: The Behavioral Risk Factor Surveillance Survey was used to query a randomly selected, convenience sample of San Diego Chamorros (N = 228) drawn from the Chamorro Directory International. Based on individual survey responses, participants were mailed personalized health-promoting information. Subsequently, they received information that addressed the most commonly observed overall threats to the Chamorro community's health. RESULTS: A higher than average prevalence of diabetes and gestational diabetes was reported by study participants along with a high prevalence of the risk factors associated with the premature onset of diabetes and its consequences. CONCLUSION: Collaborative partnerships between health professionals and community leaders can help identify opportunities and strategies for improving the health of the nation's population subgroups. San Diego's Chamorro community leaders now have a clearer understanding of the prevalence of diabetes risk factors within their community and can begin working with public health educators to create culturally aligned diabetes prevention and management programs. Given the willingness of Chamorro leaders to get involved in the development of a diabetes awareness campaign and the community's closely knit social network, it should be possible to promote (1) community participation in the intervention program, (2) an increase in the community's adherence to recommended behavioral changes, and (3) identification of additional program modifications that will further enhance the program's cultural relevance.

Suppression of Saccharomyces cerevisiae rad27 null mutant phenotypes by the 5' nuclease domain of Escherichia coli DNA polymerase I.

RNA primer removal from Okazaki fragments during lagging-strand replication and the excision of damaged DNA bases requires the action of structure-specific nucleases, such as the mammalian flap endonuclease 1 (FEN-1). This nuclease contains two conserved motifs enriched with acidic amino acid residues that are important for catalytic function. Similar motifs have been identified in nucleases found in viruses, archebacteria, eubacteria, and in eukaryotes ranging from yeast to humans. Unique among these proteins, the putative FEN-1 homologue in Escherichia coli is contained within the N-terminal region of the DNA polymerase I (PolN). To demonstrate that the cellular functions of FEN-1 reside in PolN, we cloned and expressed the amino terminal domain (323 amino acid residues) of PolI in a Saccharomyces cerevisiae strain lacking the FEN-1 homologue RAD27. Overexpression of PolN suppressed, to varying degrees, phenotypes associated with a rad27 null strain. These include temperature sensitivity, Okazaki fragment processing, a mutator phenotype, a G2/M cell cycle arrest, minichromosome loss, and methyl methane sulfonate sensitivity. We purified Rad27 and PolN proteins in order to determine whether differences in their intrinsic nuclease activities or interaction with proliferating cell nuclear antigen (PCNA) could explain the partial suppression of some phenotypes. We found that the in vitro nuclease activities of Rad27 were more potent than those of PolN and the activity of Rad27, but not PolN, was stimulated by PCNA. We conclude that the N-terminal nuclease domain of E. coli polymerase I encodes a functional homologue of FEN-1.

Cancer risk factor assessment among Chamorro men in San Diego.

BACKGROUND: Little is known about the health of Chamorros residing in the United States. METHOD: The CDC's Behavioral Risk Factor Surveillance System was used to assess cancer-related behavioral risk factors in San Diego's Chamorro men, and the Chamorro Directory International was used to recruit them. RESULTS: Of the 100 Chamorro men, 19% smoked, 38.4% reported eating 5 or more fruits and vegetables daily, 48.8% reported being current on their prostate cancer screening, and 74.4% reported being current on their colorectal cancer screening. CONCLUSIONS: This sample of Chamorro men reported higher rates of health-promoting practices than nationwide averages.