N-cadherin haploinsufficiency increases survival in a mouse model of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is often detected at a late stage, hence the identification of new therapies that have potential to block tumor progression is critical for this lethal disease. N-cadherin upregulation has been observed in many cancers including PDA, however, a causal role for this cell adhesion receptor in disease progression has yet to be defined. The concomitant expression of oncogenic Kras(G12D) and mutant p53 (Trp53(R172H)) in the murine pancreas results in metastatic PDA that recapitulates the cognate features of human pancreatic cancer providing an excellent animal model to identify genes required for tumor progression. Here we determine the consequences of genetically manipulating N-cadherin expression in a mouse model of PDA. Remarkably, mice with reduced N-cadherin expression (that is, Ncad(-/+)) survived 25% longer (177 vs 142 days, P<0.05) than animals expressing two wild-type N-cadherin (Cdh2) alleles. The survival benefit is likely due to a cumulative effect of N-cadherin's role in different aspects of tumorigenesis including tumor-cell survival, growth, migration and invasion. Interestingly, reduced hedgehog signaling may contribute to the better prognosis for the Ncad(-/+) mice. Moreover, the matrix metalloproteinase MMP-7, associated with poor prognosis in PDA, was reduced in Ncad(-/+) tumors. Finally, Ncad(-/+) tumor cells exhibited decreased FGF-stimulated ERK1/2 activation consistent with N-cadherin's ability to promote FGFR signaling. These data support a critical role for N-cadherin in PDA and its potential prognostic value. Additionally, this study provides in vivo genetic evidence that the cell-surface protein N-cadherin represents a promising therapeutic target for the treatment of pancreatic cancer.

Chronic stress is associated with high cortisol levels and emotional coping mechanisms in amnestic mild cognitive impairment.

BACKGROUND/AIMS: To investigate the association between cortisol levels, chronic stress and coping in subjects with amnestic-type mild cognitive impairment (aMCI). METHODS: Cortisol levels were measured using morning saliva samples from 33 individuals with aMCI and from 41 healthy elderly. Chronic stress was evaluated with the Stress Symptoms List (SSL), whereas coping strategies were assessed using the Jalowiec Coping Scale. RESULTS: aMCI subjects with high SSL scores presented higher cortisol levels (p = 0.045). Furthermore, aMCI subjects who employed emotion-focused coping had higher SSL scores (p = 0.023). CONCLUSION: The association between increased cortisol secretion, chronic stress and coping strategies may be modulated by the presence or absence of cognitive impairment, where memory defi- cit awareness constitutes an additional potential factor involved in high stress severity.

The perioperative process: a system of providing quality, convenient, cost-effective surgical services.

In the current health care environment, many customary procedures, developed in an era when cost containment and market competition were not major concerns are no longer compatible with the operation of a successful surgery service. This article outlines a perioperative system that accomplishes the goals of cost containment and patient and surgeon satisfaction without sacrificing quality of care. This system entails streamlining the entire perioperative process, from the initial interface with the surgeon's office to discharge from the facility. In addition, the system eliminates unnecessary waste that remains rampant in most surgery departments, and addresses scheduling problems that limit efficiency.

Human babesiosis in New York State: Review of 139 hospitalized cases and analysis of prognostic factors.

BACKGROUND: Babesiosis infections are infrequent, occur in limited geographic locations, and range from asymptomatic infection to severe illness and death. METHODS: Descriptive clinical and epidemiological information on human babesiosis cases was collated from state communicable disease reports and medical records of patients hospitalized from 1982 to 1993. Univariate and multivariate analyses were performed to determine prognostic factors associated with severe disease outcome (hospitalization ending in death, duration of hospitalization > 14 days, or intensive care unit stay > 2 days). RESULTS: Between 1982 and 1993, 139 patients were hospitalized with babesiosis in New York State. Nine patients (6.5%) died, 35 (25.2%) were admitted to the intensive care unit, and 35 (25.2%) required hospitalization for more than 14 days. Mean age at first hospitalization was 62.5 years. Sixty-two percent were male, and 91% resided in Suffolk County, Long Island. The most common symptoms were fatigue/malaise/weakness (91%), fever (91%), shaking chills (77%), and diaphoresis (69%). Past medical records showed that 52% of patients had a history of chronic disease; 12% had a history of Lyme disease; 12% had undergone a splenectomy; and 2% had undergone a blood transfusion. There was a 12- to 14-day delay between onset of symptoms and initiation of appropriate antibiotic treatment. Univariate analyses showed alkaline phosphatase levels greater than 125 U/L, white blood cell counts greater than 5 x 10(9)/L, history of cardiac abnormality, history of splenectomy, presence of heart murmur, and parasitemia values of 0.04 or higher to be significantly associated with disease severity. Multiple logistic regression analyses indicated that male sex, alkaline phosphatase values greater than 125 U/L, and white blood cell counts greater than 5 x 10(9)/L remained strong predictors of severe outcome. CONCLUSIONS: Human babesiosis is a rare but debilitating and potentially fatal illness, especially in the elderly. Prompt disease diagnosis and treatment are essential but are often delayed, as seen in our series. This delay reinforces the need for enhanced public and physician education targeted toward residents and visitors to the few high-risk geographic areas where disease and Ixodes scapularis ticks are endemic. Patients presenting with certain prognostic indicators (male sex, alkaline phosphatase values > 125 U/L, and white blood cell counts >5 x 10(9)/L) require comprehensive and aggressive medical care to prevent further deterioration. Since babesiosis is only 1 of 3 currently recognized diseases transmitted by I scapularis ticks, primary prevention recommendations will also reduce human exposure to Lyme disease and human granulocytic ehrlichiosis.

Population-based study of the adequacy of well-child care services: a rural county's report card.

OBJECTIVE: To determine the adequacy of well-child care services using a population-based study. DESIGN: The medical records of all county providers and the immunization records at the local health department were reviewed. A county birth cohort, identified using electronic birth certificates, was compared with those who migrated into the area (hereafter, in-migrants). SETTING: All primary care sites (private, network, etc) in a rural county. PATIENTS: Two-year-old children born between May 31, 1993, and May 30, 1994. MAIN OUTCOME MEASURES: Immunization rates and preventive screenings. RESULTS: A total of 674 medical records were reviewed. Of these, 377 (56%) belonged to a county birth cohort and 297 (44%) were in-migrants. Medical records of 64% of the birth cohort were reviewed. Among all 2-year-olds, 80% received 4 doses of diphtheria and tetanus toxoids and pertussis vaccine; 89%, 3 doses of Haemophilus influenzae type b (Hib); 75%, 4 doses of Hib; 77%, 3 doses of hepatitis B vaccine; 85%, measles-mumps-rubella vaccine; 85%, 3 doses of oral poliovirus vaccine; 17%, varicella live virus vaccine (Varivax). The 4:3:1 rate was 75% at age 2 years. Sixty-eight percent had had 1 hematocrit, 74% had 1 lead screening test, and 43% had 2 lead screening tests. A total of 64% had had 6 well-child visits and 30% had had 9. The mean number of weights and heights measured was 4.8 and 4.5, respectively, at age 1 year and 7.3 and 6.8, respectively, at age 2 years. The birth cohort had notably higher rates of documented immunization and preventive screening than in-migrants. CONCLUSIONS: This study demonstrated immunization coverage at or below the national average, and well-child care service provisions below American Academy of Pediatrics standards at a county level. This study enabled individual primary care sites to assess their well-child care provision and provided a useful baseline for targeting the improvement of well-child care services in the county.

The impact of WIC and AFDC in screening and delivering childhood immunizations.

Two publicly funded programs, the Special Supplemental Food Program for Women, Infants and Children (WIC) and Aid to Families with Dependent Children (AFDC), serve large numbers of children who may be at risk for poor immunization status. A review of the literature as well as conference abstracts and program reports for studies of immunization initiatives carried out in these settings was conducted. Although the available literature is limited, it does indicate that children in these programs have low immunization levels and that interventions to improve their immunization status can be successful. Measures to improve immunization status should be implemented through WIC and AFDC.