Showing papers by "Renee A. Desmond published in 2003"

Autosomal recessive polycystic kidney disease: the clinical experience in North America.

Abstract: Objective.We designed a longitudinal clinical database for autosomal recessive polycystic kidney disease (ARPKD), recruited patients from pediatric nephrology centers in the United States and Canada, and examined their clinical morbidities and survival characteristics. We initially targeted enrollment to children who were born and diagnosed after January 1, 1990, so as to capture a cohort that is representative of ARPKD patients born in the last decade. When a significant number of older ARPKD patients were also referred, we extended our database to include all patients who met our inclusion criteria, thereby allowing direct comparisons between a long-term survivor subset and a cohort that included both neonatal survivors and nonsurvivors. Design.Patient entry into our database required either compatible histopathology or ultrasonographic evidence of enlarged, echogenic kidneys and the presence of at least 1 of the following additional criteria: a) biopsy-proven ARPKD in a sibling; b) biliary fibrosis based on either clinical or histopathologic evidence; c) no sonographic evidence of renal cysts in the parents (parents must be >30 years of age); or d) parental consanguinity, eg, first-cousin marriage. Clinical questionnaires (primary data form and follow-up data form) were developed to collect initial patient data and follow-up data at yearly intervals. Results.Thirty-four centers provided clinical information for 254 patients and of these, 209 had sufficient data for analyses. When stratified by date of birth, 166 (79.4%) were born on or after January 1, 1990 (younger cohort) and 43 children (20.6%) were born before 1990 (older cohort). The gender distribution was equal in both cohorts. The median age at diagnosis was significantly later in the older cohort and no deaths were reported among these patients, suggesting that this group is biased toward long-term survivors. In the younger cohort, 74.7% of the patients are alive, with a median age of 5.4 years. In this group, 40.5% of patients required ventilation and 11.6% developed chronic lung disease. Hypertension was a common, but not universal finding in both cohorts. The relative risk for developing hypertension was higher in the older cohort, but the median age at diagnosis was significantly earlier in the younger cohort. Chronic renal insufficiency (CRI) was reported in ∼40% of patients with no significant difference in the relative risk between age groups. However, in the younger cohort, the median age at diagnosis was significantly earlier and the age of diagnosis of CRI and hypertension were significantly correlated. Clinically significant morbidities related to periportal fibrosis were more common in the older cohort. There was a trend toward increasing frequency of portal hypertension with age in both cohorts. Portal hypertension was not significantly correlated with either systemic hypertension or CRI. Conclusions.The ARPKD Clinical Database represents the largest single cohort of ARPKD patients collected to date. Our initial data analysis provides several new clinical insights. First, in our subset of long-term survivors, ARPKD has a slower rate of disease progression, as assessed by age of ARPKD diagnosis, as well as age of diagnosis of clinical morbidities. Second, neonatal ventilation was strongly predictive of mortality as well as an earlier age of diagnosis in those who developed hypertension or chronic renal insufficiency. However, for infants who survive the perinatal period, the long-term prognosis for patient survival is much better than generally perceived. Third, although systemic hypertension and CRI were significantly correlated with respect to age of diagnosis, similar relationships with portal hypertension were not evident, suggesting that disease progression may have organ-specific patterns. Fourth, only a subset of patients may be at risk for developing clinically significant manifestations of periportal fibrosis. Based on these observations, the next challenges will be to determine how various factors, such as specific mutations in the ARPKD gene, PKHD1(polycystic kidney and hepatic disease 1), variations in modifying gene loci, modulation by as yet unspecified environmental factors, and/or gene-environment interactions contribute to the marked variability in survival and disease expression observed among ARPKD patients.

Axillary lymph node status, but not tumor size, predicts locoregional recurrence and overall survival after mastectomy for breast cancer.

Abstract: Five percent to 10% of breast cancers are locally advanced (Table 1) at the time of diagnosis. 1 In the past, treatment of locally advanced breast cancer with mastectomy alone resulted in high rates of locoregional and distant failure. 2,3 Today, it is generally accepted that patients with locally advanced breast cancer require a multimodality approach combining chemotherapy (and/or hormonal therapy), surgery, and radiation. Randomized trials have demonstrated that postmastectomy radiation (PMR) reduces locoregional recurrence (LRR) after both radical and modified radical mastectomies. However, no consistent overall survival benefit has been established. 4–6 Table 1. LOCALLY ADVANCED BREAST CANCER Controversy regarding PMR increased when an overview of eight postmastectomy trials (1949–1976) demonstrated that patients surviving 10 years or longer had significantly poorer survival thereafter if they had received PMR. 7 In 1994, a second overview of the same trials was presented, which detailed longer patient follow-up and cause-specific mortality data. 8 This overview did not demonstrate reduced survival after 10 years in the PMR patients but did show that cardiac-related mortality rates were significantly worse. Recently, two studies have shown improved survival for breast cancer patients after PMR. In both the Danish Breast Cancer Group 82B (DBCG 82B) trial 9 and the British Columbia trial, 10 premenopausal node-positive patients received cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy after mastectomy and were randomized to either observation or PMR. In both trials, patients with one to three and four or more positive axillary lymph nodes benefited from PMR (Table 2). No excess deaths from radiation toxicity were reported. Table 2. SURVIVAL IN PREMENOPAUSAL WOMEN WITH BREAST CANCER WITH OR WITHOUT POST-MASTECTOMY RADIATION We have studied prospective clinical data for patients accrued to the Alabama Breast Cancer Project between 1975 and 1978. 11 This report examines the importance of axillary lymph node status and tumor size for predicting LRR and overall survival after standardized surgery for breast cancer. The utility of PMR is discussed in the context of our findings.

Expression of Extracellular Matrix Metalloprotease Inducer in Laryngeal Squamous Cell Carcinoma

Abstract: Objectives/Hypothesis Head and neck cancer tumor cell invasion is responsible for both local destruction and distant metastasis. Invasion is largely mediated by matrix metalloproteases that are thought to be induced by tumor cell derived extracellular matrix metalloprotease inducer (EMMPRIN) in surrounding fibroblasts. We hypothesize that EMMPRIN is overexpressed in laryngeal cancer. Study Design Retrospective analysis of patients with supraglottic laryngeal cancer. Methods Total protein immunoblotting and immunohistochemical analysis of normal and malignant tissue were performed to determine EMMPRIN expression. EMMPRIN immunoreactivity in 33 patients was correlated with clinicopathological features and survival. Results Whole-tissue lysates of tumors (n = 8) and metastatic lymph nodes (n = 2), but not normal skin (n = 8) or mucosa (n = 6), expressed significant amounts of EMMPRIN by immunoblotting. EMMPRIN membrane immunoreactivity (transmembrane EMMPRIN score) was associated with nodal positivity (P = .07), and it was a borderline significant predictor of survival (Hazards Ratio = 2.4; 95% CI, 0.88–6.55). As a categorical variable, higher transmembrane EMMPRIN score was associated with higher mortality. Conclusions The present study helps to establish EMMPRIN as a widely expressed protein in dysplastic mucosa and supraglottic laryngeal cancer, but not in normal epithelial counterparts.

Prevalence and factors associated with gonorrhea and chlamydial infection in at-risk females presenting to an urban emergency department.

Abstract: Background: Patients without a regular healthcare source are less likely to be tested, diagnosed, and treated effectively for sexually transmitted diseases (STDs). Emergency departments (EDs) are a major healthcare source for patients without health insurance or primary care providers. Goal: This study evaluated the prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae in women aged 15 to 35 years presenting to a metropolitan ED with genitourinary or pregnancy-related complaints and the frequency with which patients were effectively treated for these infections during routine ED care. Study Design: Women completed an interviewer-administered questionnaire and submitted urine for ligase chain reaction (LCR) testing for C trachomatis and N gonorrhoeae. Results: The combined prevalence of gonorrhea and chlamydia was 16.4 % (n = 62), and factors associated with infection included younger age and greater numbers of sex partners over 30 days. Problem-oriented care failed to detect infection in most cases, and 58% of infected women left the ED without effective therapy. Through a close working relationship with the local health department, we documented that 92% had received effective follow-up therapy. Conclusion: Continued efforts to refine and develop tools for the diagnosis and management of cervical infections for at-risk women seen in EDs are warranted.

Production of an EGFR targeting molecule from a conditionally replicating adenovirus impairs its oncolytic potential.

Abstract: Oncolytic virotherapy with conditionally replicating viruses is a promising approach for treating advanced cancers. Promiscuous tropism and low tumor transduction have represented limiting issues, which targeting approaches seek to overcome. An approach utilizing a secretory targeting molecule for the epidermal growth factor pathway (sCAR-EGF) has previously been shown to be compatible with replicating adenoviruses, when an E1-deleted vector was used in a dual-virus system in conjunction with a replication-competent agent. Here, we constructed a virus that replicates in cancer cells and codes for sCAR-EGF. Interestingly, the oncolytic potency of the novel agent was not improved over nontargeted controls in vitro or in vivo. These results suggest that the expression of biologically active proteins can be counterproductive to virus replication.