Life cycles of traumatized teeth: long‐term observations from a cohort of dental trauma victims – series 2

In this the second of a series of life cycles of dental trauma victims, the short and particularly long‐term responses of four survivors of either multiple luxation injuries or avulsions have been documented over periods varying up to 41 years. The development of ankylosis, either in the short or longer term post trauma, proved a common feature in the series and management strategies have been outlined. External invasive resorption was also identified as a complicating response for which the topical application of trichloracetic acid, intracanal dressing and root canal obturation proved effective in resorption management. Long‐term observations indicate that some compromised teeth can be functionally and aesthetically retained for extended periods, but follow‐up examinations are important so that treatment interventions can be implemented if adverse responses are diagnosed.     

Patent foramen ovale, systemic embolization and closure

The recognition, evaluation and treatment of patent foramen ovale has attracted increasing interest as the importance and frequency of paradoxical embolism has become better understood. The interest in this field has been driven largely by the widespread application of echocardiography with identification of a patent foramen ovale and/or an atrial septal aneurysm. The evaluation of the role of a patent foramen ovale in patients with a neurologic event is complex because the patent foramen ovale or atrial septal aneurysm may either be an innocent bystander or could be the etiologic mechanisms involved in the paradoxical embolus. In patients younger than 55 years, a causal relationship between a patent foramen ovale/atrial septal aneurysm and a neurologic ischemic event is considerably stronger than in those patients older than 55 years. In patients with a presumed diagnosis of paradoxical embolus in the setting of a patent foramen ovale, percutaneous closure is now possible and 2 devices are relatively widely used. Both of these devices reliably close the defect with a very acceptable risk profile and have been found in the longer term to be associated with excellent outcome. The exact role, however, that these devices play vis a vis continued medical therapy for prevention of recurrent events is being tested in 2 randomized clinical trials. The field continues to change with new technology being developed and with new applications. A recently exciting finding has been the identification that closure of a patent foramen ovale may be associated with dramatic improvement in symptoms of patients with disabling migraine headaches. Other potential applications of these devices include those patients who are deep-sea divers, in whom the potential for "bends" exists, or high altitude airplane pilots.     

The effect of prostaglandins E1 and E2 on macrophage progenitor cells with high proliferative potential in mouse bone marrow in vitro

High proliferative potential macrophage progenitor cells (HPP-CFC) in 5- fluorouracil (FU) treated and normal mouse bone marrow (BM) have been shown to be less sensitive to inhibition of proliferation by prostaglandins of the E series (PGE) than low proliferative potential macrophage progenitor cells (LPP-CFC) in normal BM in agar cultures. The growth of large colonies (diameter greater than 0.5 mm) derived from HPP-CFC in FU BM, which require a combination of macrophage colony- stimulating factor (CSF-1) plus a new growth factor called synergistic activity (SA), are inhibited by 50% in the presence of 5.5 X 10(-6) M PGE1. On the other hand, LPP-CFC in normal BM, which form smaller colonies (diameter less than or equal to 0.5 mm) in the presence of CSF- 1 alone, require only 5 X 10(-8) M PGE1 for the same level of inhibition. Addition of appropriate concentrations of PGE1 to the agar culture assay should improve detection of HPP-CFC by inhibiting the proliferation of LPP-CFC. These observations suggest that the apparent negative feedback control of macrophage production by PGE operates largely on the LPP-CFC, which respond to CSF-1 alone, and is probably not involved in the regulation of the more primitive HPP-CFC.     

Sialylated O-glycans and L-selectin sequentially mediate myeloid cell rolling in vivo

Leukocyte rolling precedes firm adhesion and emigration in inflammatory cell recruitment. Both P-selectin, an endothelial lectin that binds to sialylated O-glycans containing sialyl-Lewisx (sLex) on the granulocyte surface, and leukocyte L-selectin have been shown to mediate leukocyte rolling in vivo. Here, we investigate rolling of isolated human neutrophils (PMN), HL-60 promyelocytes, and an L-selectin-transfected cell line (300.19-L) during trauma-induced inflammation in rat mesenteric venules. HL-60 cells, which express no L-selectin but abundant sLex, rolled effectively immediately after abdominal surgery. HL-60 cell rolling was almost completely abolished by pretreatment with sialidase or monoclonal antibody (MoAb) AM-3 recognizing sLex, and was reduced by about 80% by O-sialoglycoprotein-endopeptidase (OSGP). By contrast, 300.19-L cells rolled poorly immediately after surgery but rolled well between 40 and 120 minutes after surgery. Their rolling was completely inhibited by the blocking L-selectin MoAb LAM1-3, but not by a binding control MoAb. PMN express both L-selectin and clustered, sialylated glycoproteins including P-selectin glycoprotein ligand-1 (PSGL-1). PMN showed effective rolling at all times, which was abolished by sialidase or MoAb AM-3 pretreatment during the first 30 minutes after surgery, but not later, when PMN rolling was largely L- selectin-dependent. We conclude that in trauma-induced inflammation, a two-step mechanism accounts for most of myeloid cell rolling, which initially requires O-glycans and subsequently depends on L-selectin function.     

Subtypes of cutaneous T-cell lymphoma defined by expression of leu-1 and Ia

Monoclonal antibodies were used to characterize immunohistologically the expression of cellular antigens in 25 patients with cutaneous T- cell lymphoma (CTCL). Although all cases expressed the Leu-2a-/Leu-3a+ immunophenotype characteristic of helper T cells, four subtypes were defined based on variable expression of Leu-1 and Ia. In individual patients, the immunophenotype was constant irrespective of body compartment sampled or interim therapy. Ia+ non T-cells typically constituted one-third of the cellular infiltrate. Along with neoplastic cells, Ia+/T6+ dendritic cells were observed within Pautrier microabscesses, dermis, and individually throughout the epidermis. It will be important to determine if different CTCL immunophenotypes represent different biologic subsets of disease or have prognostic relevance. Prospective studies will be facilitated by single- and double-label immunohistologic techniques that allow the simultaneous evaluation of cellular antigen expression and architectural detail.     

Measurement of ejection fraction after myocardial infarction in the population

OBJECTIVES: To assess the secular trends in left ventricular ejection fraction (LVEF) assessment after myocardial infarction (MI) and to identify the determinants of testing. DESIGN: A population-based MI incidence cohort. METHODS: The use of tests measuring LVEF (echocardiography, radionuclide, and left ventricular [LV] angiography) was examined among all consecutive residents of Olmsted County, MN, hospitalized for a validated incident MI between 1979 and 1998. Baseline characteristics and outcome were ascertained from community medical records. RESULTS: Among 2,317 patients with incident MI, LVEF assessment increased from 1979 to 1986 (22 to 85%; p value for trend = 0.0001) to stabilize thereafter until 1998. During the most recent decade, LVEF was measured during the hospital stay in 81% of the patients. Characteristics associated with lesser use of tests included older age and measurement of ejection fraction within 1 year prior to the index MI. Larger MI size, prolonged hospital stay, and involvement of a cardiologist as a care provider were positively associated with determination of LVEF. CONCLUSIONS: Measurement of LVEF after MI increased in the last 2 decades, but there continues to be a group of patients in whom it is not done. Given the potential benefits of LVEF measurement, including knowledge for risk stratification and therapeutic choices as underscored in recent practice guidelines, there may be additional opportunities for improving outcomes by ensuring its more consistent use. However, as testing for LVEF differs according to patient characteristics, reliance on selected clinically performed LVEF measurements will result in biased estimates of the prevalence of LV dysfunction after MI.     

Comparative Effectiveness of Mitoxantrone Plus Prednisone Versus Prednisone Alone in Metastatic Castrate‐Resistant Prostate Cancer After Docetaxel Failure

Background.

Mitoxantrone was approved for use in metastatic castrate-resistant prostate cancer (mCRPC) based on pain palliation without observed survival benefit in a small phase III trial in 1996. To re-evaluate for possible survival benefits in a larger contemporary sample and to demonstrate analytic uses of the newly available Project Data Sphere online resource, we used data from control arms of completed clinical trials to compare survival and toxicity among patients with postdocetaxel mCRPC treated with mitoxantrone and prednisone.

Patients and Methods.

Control arm data from two phase III randomized control trials, SUN 1120 and TROPIC, were used to examine the efficacy of mitoxantrone plus prednisone (n = 305) versus prednisone alone (n = 257) among patients with postdocetaxel mCRPC. Propensity score matching was used to balance patient characteristics between the separate trials, conditioned on age and key prognostic variables of survival. The primary outcome was overall survival. Secondary endpoints evaluated safety.

Results.

Median survival was similar among patients receiving mitoxantrone plus prednisone versus prednisone alone (385 days vs. 336 days; deceleration factor = 0.04; 95% confidence interval: −0.12 to 0.22). Prevalence of several any-grade toxicity, including fatigue, back pain, and peripheral neuropathy, was increased among patients who received mitoxantrone.

Conclusion.

There was no significant survival benefit for mitoxantrone plus prednisone over prednisone alone among men with mCRPC after docetaxel therapy. This finding is consistent with prior studies showing no survival advantage with mitoxantrone in the predocetaxel setting. Furthermore, our data suggest that mitoxantrone may be associated with increased toxicity compared with prednisone alone.