The Circadian Variations in Systemic Blood Pressure, Ocular Perfusion Pressure, and Ocular Blood Flow: Risk Factors for Glaucoma?

Intraocular pressure, a major risk factor for glaucoma, is known to vary throughout the day, yet glaucoma continues to progress in some patients despite it being well controlled. It is important to understand how other glaucomatous risk factors are affected by circadian variations. The purpose of this review is to analyze the literature concerning circadian variations in systemic blood pressure, ocular perfusion pressure, and ocular blood flow and to identify consensus findings regarding their impact on glaucoma. This review suggests that nonphysiologic nocturnal blood pressure dipping and wider circadian fluctuations in ocular perfusion pressure are linked with the development and progression of glaucoma. No consensus concerning circadian variations in ocular blood flow exists in the current literature, and future investigations of nocturnal changes in blood flow and glaucoma progression are required.     

High imaging technology and health care expenditures

Health care expenditures constitute a large part of the gross domestic product of the industrialized world and are growing at an alarming rate in some countries, particularly in the United States. Although the expenditures of radiology represented only 3.5% of the total health-care bill in the United States in 1990, the high price of certain high-technology instruments, such as magnetic resonance imagers, attracts attention. Yet, high imaging technology properly used reduces the cost of health care as can be seen from many examples. High imaging technology is non-invasive and often replaces procedures that would require hospitalization. Ethical considerations, such as large expenditures during the last year of life and some inappropriate uses, presently counterbalance the savings that the use of high technology could otherwise offer. By controlling its proper uses, high imaging technology can be a very useful tool. Correspondence to: A. Margulis     

Probability of appendicitis before and after observation

STUDY OBJECTIVE: To examine patients with abdominal pain for changes in probability of appendicitis during observation. STUDY DESIGN: Retrospective cohort study. SETTING: University-affiliated community hospital. METHODS: 252 patients with abdominal pain who were examined underwent short-term (10.4 hours) observation (95% confidence interval [CI], 8.7, 12.1) before the decision to operate during a one-year period. Alvarado's scoring system and a probability-of-diagnosis nomogram were used to assign scores and estimate probability of appendicitis. MEASUREMENTS AND RESULTS: In the study group, mean score of patients with appendicitis increased after observation from 6.8 (95% CI, 6.2, 7.4) to 7.8 (95% CI, 7.3, 8.3), corresponding to a change in probability of appendicitis from 50% to 65%. Mean score of patients without appendicitis decreased from 3.8 (95% CI, 3.5, 4.1) to 1.6 (95% CI, 1.58, 1.62), corresponding to a change in probability from 35% to 22%. The difference between mean scores for patients with and without appendicitis increased from 2.6 (95% CI, 2.0, 3.2) to 6.2 (95% CI, 6.15, 6.25) during observation. The study group initially had intermediate probability of appendicitis (score, 4.35; 95% CI, 4.04, 4.66) compared with high probability for patients who went directly to surgery after their initial evaluation (63 patients; score, 7.59; 95% CI, 7.05, 8.73) and low probability for patients with abdominal pain who were sent home after their initial evaluation without observation or surgery (2,097 patients; score, 1.87; 95% CI, 1.48, 2.26). CONCLUSION: In this group of patients with intermediate initial probability of appendicitis, observation improved the ability to distinguish patients with from those without appendicitis.     

Enhanced TNF-alpha-induced apoptosis in Fanconi anemia type C-deficient cells is dependent on apoptosis signal-regulating kinase 1

Fanconi anemia (FA) is a chromosomal instability disorder characterized by progressive bone marrow failure. Experimental evidence suggests that enhanced oxidant and myelosuppressive cytokine-mediated apoptosis of hematopoietic stem and progenitor cells contributes to the pathogenesis of marrow failure in FA. However, the molecular mechanisms responsible for the apoptotic phenotype in hematopoietic cells are incompletely understood. Recent data in Fancc-/- murine embryonic fibroblasts (MEFs) implicate increased oxidant-induced apoptotic signaling through the redox-dependent protein, apoptosis signal-regulating kinase 1 (Ask1). Here, we examined whether altered Ask1 signaling participated in the proapoptotic phenotype of primary Fancc-/- MEFs and hematopoietic progenitors treated with the myelosuppressive cytokine tumor necrosis factor-alpha (TNF-alpha). Our data indicate that TNF-alpha induces hyperactivation of Ask1 and the downstream effector p38 in Fancc-/- MEFs. In addition,Ask1 inactivation in Fancc-/- MEFs and hematopoietic progenitors restored survival to wild-type (WT) levels in the presence of TNF-alpha. Furthermore, targeting the Ask1 pathway by using either antioxidants or a p38 inhibitor protected Fancc-/- MEFs and c-kit+ cells from TNF-alpha-induced apoptosis. Collectively, these data argue that the predisposition of Fancc-/- hematopoietic progenitors to apoptosis is mediated in part through altered redox regulation and Ask1 hyperactivation.     

Gastrointestinal disease associated with meningococcemia

Despite the multiple organ involvement seen in meningococcal disease, there is little in the literature to support gastrointestinal symptoms as the predominant finding. In the past year four patients with meningococcemia and meningitis presented with gastrointestinal symptoms. In three cases the gastrointestinal findings were of such severity that the diagnosis of meningococcemia was obscured.