Citations

Coronary artery disease (CAD) accounts for a large fraction of the morbidity, mortality, and cost of diabetes. Recognizing this, nearly 10 years ago the American Diabetes Association published a consensus recommendation that clinicians consider a risk factor–guided screening approach to early diagnosis of CAD in both symptomatic and asymptomatic patients. Subsequent clinical trial results have not supported those recommendations. Since the prior consensus statement, newer imaging methods, such as coronary artery calcium scoring and noninvasive angiography with computed tomography (CT) techniques, have come into use. These technologies, which allow quantitation of atherosclerotic burden and can predict risk of cardiac events, might provide an approach to more widespread coronary atherosclerosis screening. However, over this same time interval, there has been recognition of diabetes as a cardiovascular disease (CVD) equivalent, clear demonstration that medical interventions should provide primary and secondary CVD risk reduction in diabetic populations, and suggestive evidence that percutaneous coronary revascularization may not provide additive survival benefit to intensive medical management in patients with stable CAD. This additional evidence raises the question of whether documenting asymptomatic atherosclerosis or ischemia in people with diabetes is warranted. More data addressing this issue will be forthcoming from the BARI 2-D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Until then, for patients with type 2 diabetes who are asymptomatic for CAD, we recommend that testing for atherosclerosis or ischemia, perhaps with cardiac CT as the initial test, be reserved for those in whom medical treatment goals cannot be met and for selected individuals in whom there is strong clinical suspicion of very-high-risk CAD. Better approaches to identify such individuals based on readily obtained clinical variables are sorely needed.

Nasal obstruction and recurrent sinusitis are among the most common problems encountered by rhinologists in daily practice. Unfortunately, the occurrence of primary ciliary dyskinesia and the symptoms common to this entity often lead to months or years of delayed diagnosis. Many testing methods have been used including phase contrast and electron microscopy although consensus on diagnosis and treatment has not been established. Described in this report is a male adolescent with this disorder and a new method of ciliary testing we have developed to aid in diagnosis.

Background— Ranolazine, a piperazine derivative, reduces ischemia via inhibition of the late phase of the inward sodium current (late I Na ) during cardiac repolarization, with a consequent reduction in intracellular sodium and calcium overload. Increased intracellular calcium leads to both mechanical dysfunction and electric instability. Ranolazine reduces proarrhythmic substrate and triggers such as early afterdepolarization in experimental models. However, the potential antiarrhythmic actions of ranolazine have yet to be demonstrated in humans. Methods and Results— The Metabolic Efficiency With Ranolazine for Less Ischemia in Non–ST-Elevation Acute Coronary Syndrome (MERLIN)–Thrombolysis in Myocardial Infarction (TIMI) 36 (MERLIN-TIMI 36) trial randomized 6560 patients hospitalized with a non–ST-elevation acute coronary syndrome to ranolazine or placebo in addition to standard therapy. Continuous ECG (Holter) recording was performed for the first 7 days after randomization. A prespecified set of arrhythmias were evaluated by a core laboratory blinded to treatment and outcomes. Of the 6560 patients in MERLIN-TIMI 36, 6351 (97%) had continuous ECG recordings that could be evaluated for arrhythmia analysis. Treatment with ranolazine resulted in significantly lower incidences of arrhythmias. Specifically, fewer patients had an episode of ventricular tachycardia lasting ≥8 beats (166 [5.3%] versus 265 [8.3%]; P <0.001), supraventricular tachycardia (1413 [44.7%] versus 1752 [55.0%]; P <0.001), or new-onset atrial fibrillation (55 [1.7%] versus 75 [2.4%]; P =0.08). In addition, pauses ≥3 seconds were less frequent with ranolazine (97 [3.1%] versus 136 [4.3%]; P =0.01). Conclusions— Ranolazine, an inhibitor of late I Na , appears to have antiarrhythmic effects as assessed by continuous ECG monitoring of patients in the first week after admission for acute coronary syndrome. Studies specifically designed to evaluate the potential role of ranolazine as an antiarrhythmic agent are warranted.

Pathologic conditions involving the sphenoid sinus alone are rare. A retrospective chart review was performed of 182 cases of isolated sphenoid sinus lesions seen at the Mayo Clinic between 1935 and 1998. There were 53 cases of sinusitis, 44 mucoceles, and 15 fungus-related cases (61.5%), and the rest of the cases were divided among numerous other pathologic entities. Symptoms, differential diagnosis, and various therapeutic modalities are discussed. We believe that these data will be useful to clinicians considering multiple pathologic possibilities when faced with a lesion involving the sphenoid sinus alone.

Abstract B7 coregulatory ligands can be aberrantly expressed in human disease. In the context of cancer, these ligands may act as antigen-specific inhibitors of T-cell–mediated antitumoral immunity. We recently reported that B7-H1 expression by carcinomas of the kidney and bladder portends aggressive disease and diminished survival. The expression of these proteins in prostate cancer, however, has not been investigated. We evaluated B7-H3 and B7-H1 protein expression in the pathologic specimens of 338 men treated for clinically localized prostate cancer between 1995 and 1998 with radical retropubic prostatectomy. Expression levels of B7-H3 in prostate cancer were correlated with pathologic indicators of aggressive cancer as well as clinical outcome. We report that B7-H3 is uniformly and aberrantly expressed by adenocarcinomas of the prostate, high-grade prostatic intraepithelial neoplasia, and four prostate cancer cell lines, whereas B7-H1 is rarely expressed. B7-H3 is expressed by benign prostatic epithelia, although at a more reduced level relative to neoplastic tissue. Increasing levels of B7-H3 intensity correlate with worsening clinicopathologic features of prostate cancer. Marked B7-H3 intensity, present in 67 (19.8%) specimens, confers a &gt;4-fold increased risk of cancer progression after surgery (risk ratio, 4.42; P &lt; 0.001). A survey of normal tissues revealed that B7-H3 is expressed within the liver, urothelium, and fetal kidney. In summary, B7-H3 is aberrantly expressed in all prostate cancers and represents an independent predictor of cancer progression following surgery. Moreover, B7-H3 encompasses a novel diagnostic and potential therapeutic target for the clinical management of prostate cancer and, perhaps, other malignancies as well. [Cancer Res 2007;67(16):7893–900]

Patients who experience chronic recurring head and face pain present a diagnostic and therapeutic challenge. Treatment options for Sluder's neuralgia, an uncommon cause for recurring head and face pain, are controversial. We reviewed the outcomes of patients who underwent intranasal phenolization of the sphenopalatine ganglion for the treatment of Sluder's neuralgia. Eight patients were treated with intranasal cauterization of the sphenopalatine ganglion between 1990 and 1995. Patients were treated an average of 13 times. Overall, patients experienced a 90% decrease in head and face pain for an average of 9.5 months duration. Interestingly, the patients described recurrent pain as less severe, less frequent, and of shorter duration. Intranasal phenolization of the sphenopalatine ganglion appears to be a safe and effective, although temporary, treatment for patients with Sluder's neuralgia. This article will review the symptomatology, differential diagnosis, and phenolization technique for treatment of Sluder's neuralgia.

In the graft depleted revision rhinoplasty patient and the patient with major tissue needs, alternatives to septal and conchal cartilage grafts are needed. The costal cartilage graft and rib bone/costal cartilage combination graft are excellent alternatives. In this study 14 patients received 40 grafts from 20 autogenous ribs harvested during septorhinoplasty. Materials were harvested for use as septal replacement grafts, cantilevered grafts, dorsal onlay grafts, columellar struts, and tip grafts. Patient followup was 6 to 31 months, and no evidence of graft resorption or warpage was evident during that period. Complications of harvest were minimal, and harvest techniques are detailed.

A persistent cerebrospinal fluid (CSF) leak is potentially lethal, and surgical treatment is often required. CSF leak repair is an infrequently performed procedure, and only limited information is available on the long term success of the surgical techniques that are used. This retrospective chart review includes 95 patients who underwent various types of repair surgery for CSF rhinorrhea at the Mayo Clinic. The purpose of this study was to extract factors such as the choice of sealing material, etiology, location of defect(s), surgical approach, and previous procedures, and to analyze their association with the long term success and failure of surgical repair. The mean time interval in this study between unsuccessful surgery and recurrence was 50.8 months, and the mean follow-up 109 months. Among the various approaches, defects repaired endonasally had the lowest recurrence rate. Local nasal mucosa advancement flaps failed more frequently (83.3% failure) than other types of graft material (p = 0.023). These failures took place in a delayed fashion (mean interval until failure: 80 months). Local osteo-mucoperiosteal or chondro-mucoperichondrial flaps (22.2% recurrence rate) and free graft material (15.6% recurrence rate) had the best outcome. The use of fibrin glue to fixate free grafts did not improve the result in this series. Transcranial procedures were associated with a higher complication rate than extracranial procedures (12.9% versus 3.2%). Overall, successful repair was achieved in 91.6% of the patients. We discourage the use of mucosa advancement flaps and advocate free grafts or pedicled osteomucoperiosteal or chondro-mucoperichondrial flaps as sealing material of choice in the majority of cases. The occurrence of delayed failure has to be considered when evaluating reports of CSF rhinorrhea after surgical repair.

Although asthmatic children spend a significant amount of time in child care programs, little is known about child care program directors' knowledge about asthma and what factors influence directors' level of knowledge about asthma. A telephone interview was conducted with directors of a randomly selected sample of all licensed child care centers and group day care homes in Connecticut. Directors of most child care programs were willing to admit asthmatic children to their programs, but their knowledge about asthma needs to be improved. Directors who have served for long periods of time may be a target group for additional education about asthma.