Natural product-drug conjugates for modulation of TRPV1-expressing tumors.

We report the design, synthesis and biological evaluation of natural product-drug conjugates for treatment of prostate cancers over-expressing the transient receptor potential vanilloid 1 (TRPV1) channel. We validate the relevance of TRPV1 as a target in prostate cancer patients by using a bioinformatics approach and provide proof-of-concept for the drug delivery strategy through bioorthogonal chemistry and stability assays under simulated physiological conditions. In cell-based assays, the constructs displayed modest activity. Moreover, we serendipitously discover that a stoichiometric combination of a TRPV1 agonist with a small, positively charged cytotoxic may provide new research avenues in personalized medicines for prostate cancer.

Sitagliptin and Roux-en-Y gastric bypass modulate insulin secretion via regulation of intra-islet PYY.

AIMS: The gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux-en-Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by the proteolytic enzyme dipeptidyl peptidase IV (DPP-IV) has not been investigated and the impact of DPP-IV inhibition on islet PYY function remains unexplored. Here we have addressed these gaps and their effects on glucose-stimulated insulin secretion (GSIS). We have also investigated changes in pancreatic PYY in diabetes and following RYGB. METHODS: Immunohistochemistry and gene expression analysis were used to assess PYY, NPYRs and DPP-IV expression in rodent and human islets. DPP-IV activity inhibition was achieved by sitagliptin. Secretion studies were used to test PYY and the effects of sitagliptin on insulin release, and the involvement of GLP-1. Radioimmunoassays were used to measure hormone content in islets. RESULTS: PYY and DPP-IV localized in different cell types in islets while NPYR expression was confined to the beta-cells. Chronic PYY application enhanced GSIS in rodent and diabetic human islets. DPP-IV inhibition by sitagliptin potentiated GSIS; this was mediated by locally-produced PYY, and not GLP-1. Pancreatic PYY was markedly reduced in diabetes. RYGB strongly increased islet PYY content, but did not lead to full restoration of pancreatic GLP-1 levels. CONCLUSION: Local regulation of pancreatic PYY, rather than GLP-1, by DPP-IV inhibition or RYGB can directly modulate the insulin secretory response to glucose, indicating a novel role of pancreatic PYY in diabetes and weight-loss surgery.

Implementation of the NCAA Sickle Cell Trait Screening Policy: A Survey of Athletic Staff and Student-athletes.

OBJECTIVE: To describe the perspectives and experiences of athletic trainers, coaches, and student-athletes approximately three years post-implementation of the NCAA sickle cell trait (SCT) screening policy. PARTICIPANTS: Two-hundred and eight student-athletes, 32 athletic trainers, and 43 coaches from 10 NCAA Division I (DI) institutions in North Carolina from January to June 2014. METHODS: Two online surveys were used to assess knowledge, perspectives, and experiences. RESULTS: Athletic staff were more supportive than student-athletes of the need for the policy. Noted challenges included variation in implementation and follow-up for SCT-positive athletes, financial costs to institutions and athletes, and timing of the screening. CONCLUSIONS: More education about SCT is needed for student-athletes and athletic staff in order to help make the implementation more successful. All parties need to be in agreement regarding the importance of knowing which student-athletes have SCT and how that information will be utilized.

Perspectives and Practices of Athletic Trainers and Team Physicians Implementing the 2010 NCAA Sickle Cell Trait Screening Policy.

Sickle cell trait (SCT) is usually benign. However, there are some conditions that may lead to SCT-related problems and put athletes with the trait at particular risk. In 2010 the National Collegiate Athletic Association (NCAA) issued a policy that required all Division I (DI) student-athletes to confirm their SCT status or sign a liability waiver to opt out of testing. Athletic trainers and team physicians play key roles in the policy implementation and we examined their perceptions and practices. Between December 2013 and March 2014 we interviewed 13 head athletic trainers and team physicians at NCAA Division I colleges and universities in North Carolina. We used an interview guide with open-ended questions covering knowledge of SCT, historical screening and education practices, current implementation, and policy benefits and challenges. Participants were knowledgeable about SCT and thought the policy was beneficial in providing SCT health information to and for student-athletes. Schools varied in provision of genetic counseling, offering the waiver, SCT tests administered, and other aspects. Challenges included: insufficient guidance from the NCAA; financial considerations; and misunderstanding of the relationships of race and ancestry to SCT risk. Athletic staff found the policy valuable, but felt it needs clarity and standardization.

Contribution of Sickle Cell Disease to the Pediatric Stroke Burden Among Hospital Discharges of African-Americans-United States, 1997-2012.

BACKGROUND: Approximately 10-20% of children with sickle cell disease (SCD) develop stroke, but few consistent national estimates of the stroke burden for children with SCD exist. The purpose of this study is to determine the proportion of diagnosed stroke among African-American pediatric discharges with and without SCD. PROCEDURE: Records for African-Americans aged 1-18 years in the Kids' Inpatient Database (KID) 1997-2012 with ≥1 ICD-9-CM diagnosis code for stroke were included. Data were weighted to provide national estimates. A total of 2,994 stroke cases among African-American children were identified. Diagnoses co-existing with ischemic or hemorrhagic stroke were frequency ranked separately. RESULTS: From 1997 through 2012, SCD was present in 24% of stroke discharges, with 89% being ischemic stroke. For hospital discharges of African-American children, SCD is the highest co-existing risk factor for ischemic stroke (29%). Stroke in children with SCD occurred predominantly in children aged 5-9 years, older than previously reported. The trend of stroke discharges significantly decreased for children with SCD from 1997 to 2012 for children aged 10-14 years. CONCLUSIONS: SCD is a leading risk factor to pediatric stroke in African-American children. Reducing the number of strokes among children with SCD would have a significant impact on the rate of strokes among African-American children. Preventative intervention may be modifying initial age of presentation of stroke in children with SCD.

Social vulnerability and traumatic brain injury hospitalizations from sports and recreation among pediatric patients in the United States.

PURPOSE: This study examined the associations between individual as well as neighborhood social vulnerability and sports and recreation-related traumatic brain injury (SR-TBI) hospitalizations among pediatric patients in the U.S. METHODS: We obtained 2009, 2010 and 2011 hospitalization data in the U.S. from the National Inpatient Sample (NIS) database, linked it to 2010 neighborhood social vulnerability index (SVI) data from the Centers for Disease Prevention and Control (CDC), and assigned U.S. hospitals to one of four SVI quartiles. SR-TBI outcomes studied include: odds of hospitalization, length of stay (LOS), and discharge to post-acute care (DTPAC). RESULTS: We found associations between race/ethnicity and all SR-TBI outcomes; however, sex, primary payer, and neighborhood overall SVI were only associated with LOS. Compared to White children, Native American children had almost three times higher odds of hospitalization for SR-TBI (OR: 2.82, 95% CI: 1.30, 6.14), 27% longer LOS (ß: 27.06, 95% CI: 16.56, 38.51), but 99.9% lower odds of DTPAC (OR: 0.001, 95% CI: 0.00, 0.01). Compared to children with private insurance, children with public insurance had 11% longer LOS (ß: 10.83, 95% CI: 8.65, 13.05). Hospitalization in neighborhood with higher overall SVI was associated with longer LOS (p < 0.0001). CONCLUSIONS: These findings suggest that individual and neighborhood social vulnerability can have a significant impact on the health outcomes of children, especially in the context of SR-TBI.

[A case for the inclusion of oculocutaneous albinism as a skin-related Neglected Tropical Disease]. / Plaidoyer pour une intégration de l'albinisme oculocutané au sein des Maladies tropicales négligées dermatologiques.

Oculocutaneous albinism (OCA) is genetically transmitted. In this paper we advocate for this disease to be included in the NTD list of the WHO. OCA type 2 is the most common form of albinism in sub-Saharan Africa, with a prevalence of 1 in 7900 among the Bamileke of Cameroon, 1 in 3900 in South Africa and 1 in 1100 among the Ibos of Nigeria, as compared to a prevalence of 1 in 10,000 among African Americans and 1 in 36,000 among White Americans and Europeans. The medical problems related to ophthalmological aspects (poor visual acuity, ametropia, nystagmus, photophobia) and dermatological aspects of albinism (sensitivity to UV rays from the sun and development of skin cancers) are well known. However, their management is often challenging for persons with albinism in sub-Saharan Africa because of their financial burden and the difficulty of accessing medical specialists. In many African countries, persons with albinism are also very often the subject of social, cultural, medical, moral and economic discrimination, which can limit their access to education, employment and community life. They are considered 'white Africans', intermediary and incomplete, with innate powers for good and evil. This particularity has made persons with albinism the targets of mutilations and/or ritual attacks for the purposes of using their body parts in the preparation of charms to bring good luck, health or prosperity. On 13 June 2013, as a result of lobbying by the Canadian NGO Under the Same Sun and African albinism associations, United Nations bodies including UNESCO and the WHO (World Health Organization) responded and a Resolution addressing the discrimination and attacks was voted in. The date has since become International Albinism Awareness Day and is celebrated on a different theme each year with great energy and impact, especially by French, English and Portuguese speaking albinism associations across sub-Saharan Africa. In 2015 the Human Rights Council created the position of Independent Expert on Albinism to better collect and analyse data on the rights of persons with albinism around the world, and especially in countries where ritual attacks occur. The data collected by albinism associations and the authorities thus go directly to the UN Human Rights Directorate. Despite this international attention to the attacks on persons with albinism, one of the biggest threats is skin cancer, which very often leads to early death. In 2022, the WHO launched a strategic framework for the control and management of neglected skin-related neglected tropical diseases - an additional reason to include oculocutaneous albinism as an NTD. Although the focus is currently limited to dermatoses of an infectious nature, we argue here for the integration of oculocutaneous albinism among NTDs because the deadliness of these carcinomas in sub-Saharan Africa is well-known and has been examined in a number of medical publications. Here, we propose that oculocutaneous albinism in sub-Saharan Africa be classified as an NTD to help people with albinism have access to health, economic, social and cultural rights.

Patient-reported outcomes in vasculitis.

Systemic vasculitis encompasses a group of multisystem disorders; both the diseases and the treatment strategies can have a significant impact on a patient's health-related quality of life (HRQoL). Using patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) to evaluate the patient's view of their condition, treatments, and healthcare journey is essential to the patient-centered care approach. In this paper, we discuss the use of generic, disease-specific, and treatment-specific PROMs and PREMs in systemic vasculitis and future research goals.

Impact of Race, gait speed and arch height on plantar loading.

Diabetes is a leading cause for death in the United States, with African Americans (AA) being twice as likely to die from diabetes than White Americans (WA). AA are twice as likely to experience diabetes-related foot amputation due to foot ulcers, which are most often caused by high plantar pressure. While it is known that arch height, sex, family history of diabetes, Body Mass Index (BMI), age, and gait speed can impact plantar loading, there is a need to test the hypothesis that race in combination with the previously mentioned variables are significant predictors of plantar loading. To answer this question, plantar loading data was collected from 107 participants using an EMED pressure-measurement system (Novel Electronics, Inc, St Paul, MN, USA). Each participant walked barefoot at a self-selected walking pace ten times. Contact area, maximum force, and were force-time integral collected for each step on the pressure plate. A multiple linear regression was used to test if race, age, Arch Height Index (AHI), gait speed, sex assigned at birth, family history of diabetes, and BMI significantly predicted plantar loading. Race, age, AHI, gait speed, sex, and BMI were considered significant predictor variables for plantar loading. Most importantly, race was a significant predictor of maximum force in the hallux (ß = 6.46, p < 0.001), rearfoot (ß = -6.36, p < 0.001), and lateral midfoot (ß = -2.72, p < 0.001), and the force-time integral in the hallux (ß = 2.37, p < 0.001), rearfoot (ß = -2.14, p < 0.001), and lateral midfoot (ß = -0.65, p < 0.001). These findings could help with understanding why AA are more likely to develop diabetic foot ulcers than WA.

The Prognostic Role of Preoperative Hematological and Inflammatory Indices in Canine Appendicular Osteosarcoma.

Hematological indices play a prognostic role in human osteosarcoma (OSA), but data are limited in dogs. The aim of this retrospective multicentric cohort study was to investigate the prognostic significance of pre-operative hematological/inflammatory indices in a cohort of client-owned dogs with appendicular OSA receiving standardized treatment. Cut-offs associated with progression-free survival (PFS) for pre-operative hematological values/ratios were established using the minimal p-value approach. Historical prognostic factors were also assessed. Statistical analyses were performed for the whole population and after the exclusion of sighthounds. Fifty-nine dogs were included (13 were sighthounds). Multivariable analysis revealed that a low neutrophil count (<4.37 × 109/L, HR0.28, CI 95% 0.13-0.61, p = 0.001), a high red blood cell count (≥7.91, HR3.5, CI 95% 1.56-7.9, p = 0.002), and a proximal humerus location (HR3.0, CI 95% 1.48-6.1, p = 0.002) were associated with shorter PFS. In the sighthound-only population, only OSA location was significantly associated with PFS in univariable analysis. When sighthounds were excluded, a low neutrophil count, a low monocyte count, and a proximal humerus location were associated with shorter PFS, in multivariable analysis. Neutrophil count and possibly monocyte and red blood cell counts can be useful prognostic markers in canine OSA treated with amputation and adjuvant carboplatin. However, not all indices are appropriate in sighthounds.

Risk of COVID-19 breakthrough infection and hospitalization in individuals with comorbidities.

BACKGROUND: The successful development of multiple COVID-19 vaccines has led to a global vaccination effort to reduce severe COVID-19 infection and mortality. However, the effectiveness of the COVID-19 vaccines wane over time leading to breakthrough infections where vaccinated individuals experience a COVID-19 infection. Here we estimate the risks of breakthrough infection and subsequent hospitalization in individuals with common comorbidities who had completed an initial vaccination series. METHODS: Our study population included vaccinated patients between January 1, 2021 to March 31, 2022 who are present in the Truveta patient population. Models were developed to describe 1) time from completing primary vaccination series till breakthrough infection; and 2) if a patient was hospitalized within 14 days of breakthrough infection. We adjusted for age, race, ethnicity, sex, and year-month of vaccination. RESULTS: Of 1,218,630 patients in the Truveta Platform who had completed an initial vaccination sequence between January 1, 2021 and March 31, 2022, 2.85, 3.42, 2.75, and 2.88 percent of patients with CKD, chronic lung disease, diabetes, or are in an immunocompromised state experienced breakthrough infection, respectively, compared to 1.46 percent of the population without any of these four comorbidities. We found an increased risk of breakthrough infection and subsequent hospitalization in individuals with any of the four comorbidities when compared to individuals without these four comorbidities. CONCLUSIONS: Vaccinated individuals with any of the studied comorbidities experienced an increased risk of breakthrough COVID-19 infection and subsequent hospitalizations compared to the people without any of the studied comorbidities. Individuals with immunocompromising conditions and chronic lung disease were most at risk of breakthrough infection, while people with CKD were most at risk of hospitalization following breakthrough infection. Patients with multiple comorbidities have an even greater risk of breakthrough infection or hospitalization compared to patients with none of the studied comorbidities. Individuals with common comorbidities should remain vigilant against infection even if vaccinated.

Neighborhood risk factors for sports and recreational injuries: a systematic review of studies applying multilevel modeling techniques.

BACKGROUND: Sports and recreational activities are the most commonly reported cause of injury-related emergency department (ED) visits among children and young adults in developed countries, yet studies about the effect of neighborhood environment on sports and recreational injuries (SRI) are very limited. The aim of this study was to systematically review studies that apply multilevel modeling approach in examining the relationships between SRI and neighborhood-level risk factors. DATA SOURCES: A systematic search of peer reviewed English language articles was conducted in four electronic databases including PubMed (1992-2020), CINAHL (2000-2020), Sports Medicine and Education Index (1996-2020), and Web of Science (1991-2020). STUDY SELECTION: Selected studies were observational or experimental studies of people of all ages across the world that assessed neighborhood risk factors for SRI (or all injuries including SRI) using multilevel regression analysis. DATA SYNTHESIS: Nine studies-five cross-sectional, two prospective cohort, and two incidence studies-were selected out of a potential 1510. Six studies used secondary data and three used primary data. Only three studies examined SRI as the main or one of the main outcomes. These studies showed that neighborhood-level factors, such as higher socioeconomic context, lower street connectivity, and living or attending schools in urban communities, were associated with increased risk of SRI. Most studies did not provide a justification for the use of multilevel regression and the multilevel analytical procedure employed and quantities reported varied. The Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies (National Institutes of Health) was used to assess the quality or risk of bias of each study. Four quality assessment criteria out of 15 were met by all nine studies. The quality assessment ratings of the reviewed studies were not correlated with the quality of information reported for the multilevel models. CONCLUSION: Findings from this review provide evidence that neighborhood-level factors, in addition to individual-level factors, should be taken into consideration when developing public health policies for injury prevention. Considering the limited numbers of studies that were identified by this systematic review, more multilevel studies are needed to strengthen this evidence in order to better inform SRI prevention policy decisions.

Lessons in Linkage: combining administrative data using deterministic linkage for surveillance of sports and recreation injuries in Florida, United States.

Objectives: Previous and ongoing epidemiological surveillance of sports and recreation injuries (SRI) has been cross-sectional in nature, utilised a subset of injuries based on athletic trainer availability, or focused on elite and professional athletes. In the United States, surveillance is often prohibitively expensive and not well funded by national organisations or agencies, except for the case of some professional and elite sports. This paper details the methodology, barriers, and successes of using deterministic linkage to combine emergency department and hospitalisation data with a single identifier for use in surveilling sports injuries for persons aged 5 to 18 years. Design: Data linkage of a population cohort. Methods: We performed deterministic linkage of administrative emergency department and hospitalisation data from the state of Florida in the US. Data was acquired from the Florida Agency for Health Care Administration. With limited identifiers available due to privacy, we combined data across multiple years using a near universal identifier. We identified sport and recreation injuries using a modified External Cause of Injury Morbidity Matrix and ICD codes across all possible diagnoses. Finally, we obtained descriptive statistics of records that were successfully linked and those that were not to assess similarities between the groups. Results: We found 384,731 visits for SRI over a seven-year period. We were able to link approximately 70% of the records using a single identifier. There were statistically significant differences by age, sex, payer, and race/ethnicity for the records that were linked compared to the records that were not linked. Conclusions: This study is significant because while similar methods have been used to examine other conditions (e.g. asthma), few have linked multiple types of administrative data especially with nearly no identifiers to examine sports and recreation injuries. This method was found useful to identify injuries over time for the same individuals seeking care in emergency departments, or in hospital inpatient settings, though future work will need to address the limitations of this method. If we expect to move health surveillance forward as budgets for it become even more limited, we must develop and improve methods to do it with fewer resources, including using data that has great limitations.

Racial inequality in COVID-treatment and in-hospital length of stay in the US over time.

Introduction: Demonstrated health inequalities persist in the United States. SARS-CoV-2 (COVID) has been no exception, with access to treatment and hospitalization differing across race or ethnic groups. Here, we aim to assess differences in treatment with remdesivir and hospital length of stay across the four waves of the pandemic. Materials and methods: Using a subset of the Truveta data, we examine the odds ratio (OR) of in-hospital remdesivir treatment and risk ratio (RR) of in-hospital length of stay between Black or African American (Black) to White patients. We adjusted for confounding factors, such as age, sex, and comorbidity status. Results: There were statistically significant lower rates of remdesivir treatment and longer in-hospital length of stay comparing Black patients to White patients early in the pandemic (OR for treatment: 0.88, 95% confidence interval [CI]: 0.80, 0.96; RR for length of stay: 1.17, CI: 1.06, 1.21). Rates became close to parity between groups as the pandemic progressed. Conclusion: While inpatient remdesivir treatment rates increased and length of stay decreased over the beginning course of the pandemic, there are still inequalities in patient care.

Hair as a marker for pesticides exposure.

Rats were orally treated with mixtures of chlorinated pesticides. Hair was collected and analyzed for pesticide residues over a period of up to four weeks. Quantitative and qualitative analysis of the recovered pesticides in hair were determined using gas chromatography with electron capture detector. Results suggest that hair can be used as a biomarker for the monitoring of organochlorinated pesticide residues at low parts per billion levels. Chlorinated pesticides were also detected in human hair of environmentally exposed and occupationally exposed individuals, which indicates that hair can be used for monitoring pesticides exposure.

The time is now: why we must identify and address health disparities in sport and recreation injury.

BACKGROUND: Social and structural determinants of health (SDOH) are the conditions in which individuals are born, live, learn, work, play, worship, and age. These drivers of health are integral in contextualizing the understanding and prevention of sport and recreation injury (SRI), and recognizing their impact is necessary to provide a complete and accurate picture of health and health outcomes related to injury. MAIN: Reducing disparities and achieving equity in sports and recreation is possible in part by improving data collection methodologies and utilization. Often, many SDOH have considerable effect on SRI. Although SRI epidemiology frequently examines differences by sex, there is limited inclusion of factors such as socioeconomic status, housing, gender, and food security, in sport specific data sources or in analysis of sport recreation and injury using other sources (e.g. administrative data). The ongoing dual epidemics in the United States - racism and COVID-19 - have emphasized the importance of having and utilizing SDOH data to reduce the burden of injury and disproportionate effects on our diverse population. CONCLUSION: Moving forward, to address disparities in SRI, SDOH must be included as a part of research priorities, health related goals, and policies. This difference can be made in developing consistency in data collection and utilization. This will provide an accurate picture of the intersections and interdisciplinary changes required to design the best approach to problems to develop solutions. Future data collection and utilization should prioritize SDOH.

Allosteric Antagonist Modulation of TRPV2 by Piperlongumine Impairs Glioblastoma Progression.

The use of computational tools to identify biological targets of natural products with anticancer properties and unknown modes of action is gaining momentum. We employed self-organizing maps to deconvolute the phenotypic effects of piperlongumine (PL) and establish a link to modulation of the human transient receptor potential vanilloid 2 (hTRPV2) channel. The structure of the PL-bound full-length rat TRPV2 channel was determined by cryo-EM. PL binds to a transient allosteric pocket responsible for a new mode of anticancer activity against glioblastoma (GBM) in which hTRPV2 is overexpressed. Calcium imaging experiments revealed the importance of Arg539 and Thr522 residues on the antagonistic effect of PL and calcium influx modulation of the TRPV2 channel. Downregulation of hTRPV2 reduces sensitivity to PL and decreases ROS production. Analysis of GBM patient samples associates hTRPV2 overexpression with tumor grade, disease progression, and poor prognosis. Extensive tumor abrogation and long term survival was achieved in two murine models of orthotopic GBM by formulating PL in an implantable scaffold/hydrogel for sustained local therapy. Furthermore, in primary tumor samples derived from GBM patients, we observed a selective reduction of malignant cells in response to PL ex vivo. Our results establish a broadly applicable strategy, leveraging data-motivated research hypotheses for the discovery of novel means tackling cancer.

Phase I, pharmacokinetic and biological correlative study of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, and cisplatin in patients with solid tumors.

PURPOSE: To evaluate the safety and describe the pharmacokinetic profile of OSI-7904L, a novel liposomal thymidylate synthase inhibitor, in combination with cisplatin (CDDP) in adults with advanced solid tumors. EXPERIMENTAL DESIGN: CDDP was administered as a 2-h intravenous infusion followed by OSI-7904L intravenously over 30 min, both given every 3 weeks. Doses of each drug were escalated in separate cohorts of patients. Five dose levels of CDDP/OSI-7904L were explored: 60/6, 60/9, 60/12, 60/7.5, and 75/7.5 mg/m2. Pharmacokinetic samples, baseline plasma homocysteine, and genotype polymorphisms were evaluated. RESULTS: Twenty-seven patients were treated with 101 total courses of CDDP/OSI-7904L. Dose-limiting toxicity was observed in 2 patients in the CDDP/OSI-7904L 60/12 mg/m2 cohort. One patient experienced rash, stomatitis, dehydration, renal failure, hyperbilirubinemia, and fatal neutropenic sepsis, whereas the other patient experienced grade 3 nausea, vomiting, and ileus. Therefore, the CDDP/OSI-7904L 60/9 mg/m2 cohort was expanded, with 2 of 6 patients reporting significant fatigue. Other toxicities were mild or moderate. Intermediate dose levels of 60/7.5 and 75/7.5 mg/m2 were evaluated, and the latter was identified as the recommended dose for phase II studies. No major pharmacokinetic interactions between CDDP and OSI-7904L were observed. Three patients had partial responses (gastric adenocarcinoma and heavily pretreated breast cancer). There was no significant relationship between baseline homocysteine and toxicity. CONCLUSIONS: The recommended doses for CDDP and OSI-7904L administered once every 3 weeks are 75 and 7.5 mg/m2, respectively. Pharmacokinetic interaction between the agents was not apparent. Preliminary clinical activity was observed in breast and gastric cancer.

Spontaneous splenic rupture in a patient with infectious mononucleosis.

We present a case of spontaneous, atraumatic splenic rupture secondary to Epstein-Barr virus (EBV) infection, in a young, female patient. Splenic rupture is a rare complication of EBV infection, but is associated with the highest mortality. Additionally, this case illustrates the diagnostic challenge in a patient presenting in atypical manner, with only left-sided pleuritic chest pain, and lacking any of the classical tonsillitis symptoms associated with EBV infection.