Citations

Background— The prevalence and characteristics of sleep-disordered breathing in patients with asymptomatic left ventricular (LV) dysfunction are unknown. Therefore, we evaluated the prevalence of sleep-disordered breathing in patients with LV dysfunction without overt heart failure and tested the hypothesis that sleep-disordered breathing is linked to greater hemodynamic and autonomic impairment. Methods and Results— We studied 47 patients with LV ejection fractions ≤40% without any history of heart failure. Central sleep apnea (CSA), as defined by an apnea-hypopnea index ≥15/h, was present in 26 patients (55%), 17 (36%) of whom had severe CSA (apnea-hypopnea index ≥30/h). Obstructive sleep apnea was evident in 5 patients (11%). The prevalence and severity of CSA were higher in patients with ischemic cardiomyopathy than in patients with nonischemic cardiomyopathy ( P <0.05). Exercise tolerance and echocardiographic indices of systolic and diastolic function were similar in patients without CSA, with mild CSA, and with severe CSA. Heart rate variability was markedly depressed in patients with CSA ( P <0.05). Patients with severe CSA also had a higher incidence of nonsustained ventricular tachycardia ( P =0.05). Conclusions— CSA is highly prevalent in patients with asymptomatic LV dysfunction. The severity of CSA may not be related to the severity of hemodynamic impairment. Severe CSA is associated with impaired cardiac autonomic control and with increased cardiac arrhythmias.

A combination of magnetic cell sorting (MACS) and fluorescent in situ hybridization (FISH) techniques was used to detect clonal cytogenetic markers in different myeloid and lymphoid cell types of the peripheral blood from 4 patients with myelofibrosis with myeloid metaplasia (MMM) that was associated with either a 13q− or a 20q− karyotypic abnormality. Interphase cytogenetics studies demonstrated abnormal clonal FISH signal patterns in neutrophil, myeloid, erythroid, megakaryocyte, and B- and T-cell preparations in 3 of the 4 patients. In one patient, FISH results were within normal limits in T cells and slightly abnormal in B cells. In general, the percentage of abnormal nuclei was variable in both lymphocyte populations but always higher in B lymphocytes compared with T lymphocytes. The current study provides direct evidence for the clonal involvement of both B and T lymphocytes in MMM. A larger study is needed to clarify the relevance of the observed interpatient heterogeneity in clonal constitution.

The allergic reaction begins with the antigen-induced aggregation of occupied high-affinity IgE receptors expressed on mast cell surface, their activation, and the release of proinflammatory mediators that cause the “early phase” of this process. In addition, mast cell activation induces the onset of a “late phase” reaction characterized by the tissue infiltration of inflammatory cells, mainly eosinophils. We have hypothesized that during the late phase mast cells interact with and are activated by eosinophils. Here we report that highly purified human lung mast cells became responsive to eosinophil major basic protein (MBP) when in coculture with human lung fibroblasts. In addition, cord blood–derived mast cells maintained in coculture with 3T3 fibroblasts released more histamine and prostaglandin D2 (PGD2) compared with cells maintained in suspension. The fibroblast-derived membrane form of stem cell factor (SCF) was found to be involved in the mast cell increased responsiveness to MBP. In fact, cord blood–derived mast cells cocultured with 3T3 in the presence of antisense for SCF or cocultured with fibroblasts that do not express the membrane form of SCF were inhibited in their histamine-releasing activity toward MBP. In addition, this form of SCF induced the expression of a pertussis toxin–sensitive Gi protein, Gi3 that interacts with MBP to trigger mast cell non-IgE–dependent activation in a manner similar to other cationic compounds such as compound 48/80. Mast cell responsiveness to eosinophil mediators is a potentially novel evidence for an alternative pathway of allergen-independent activation able to contribute to the perpetuation of allergy.

Angiogenesis plays an important role in the biology of multiple myeloma (MM) and has prognostic importance in this disease. Solitary plasmacytoma is a localized plasma cell malignancy that progresses to MM in a significant number of patients. We examined if angiogenesis is increased in solitary plasmacytoma and if it can help identify patients likely to progress to myeloma. We studied angiogenesis in plasmacytoma biopsy samples and bone marrow biopsies from 25 patients. High-grade angiogenesis was present in 64% of plasmacytomas. In contrast, bone marrow angiogenesis was low in all patients. Patients with high-grade angiogenesis in the plasmacytoma sample were more likely to progress to myeloma and had a shorter progression-free survival compared with patients with low-grade angiogenesis (P = .02). Angiogenesis is increased in solitary plasmacytoma and is a significant predictor of progression to myeloma and provides further evidence of its importance in the pathogenesis of myeloma.

OBJECTIVEWe sought to compare methods for determining intrabolus cricopharyngeal pressure as a possible indicator for cricopharyngeal myotomy.STUDY DESIGNWe determined multiple intrabolus pressures in the cricopharyngeal region of 20 normal volunteers, of whom 12 were 20 to 35 years old and 8 were older than 75 years. Data were collected using a commercially available manofluorography system and a 6‐sensor unidirectional solid‐state 2‐ x 4‐mm catheter. Each subject underwent 5 5‐mL and 5 10‐mL liquid barium swallows. Data were analyzed, and young subjects were compared with old subjects.RESULTSThe mean mid‐bolus pressures in young subjects were 5.2 ± 4.9 mm Hg and 7.2 ± 6.5 mm Hg for the 5‐mL and 10‐mL swallows, respectively, and in older subjects, 10.8 ± 8.8 mm Hg and 12.3 ± 7.4 mm Hg. The mean gradient pressures across the 3‐cm cricopharyngeal region in young subjects were 2.02 ± 5.0 mm Hg, and −0.91 ± 4.8 mm Hg for the 5‐mL and 10‐mL swallows, respectively, and for older subjects, 4.38 ± 3.1 mm Hg and 2.82 ± 3.4 mm Hg.CONCLUSIONSCricopharyngeal intrabolus pressures were lower in young than in older subjects. The mid‐bolus pressure and the gradient pressure across the cricopharyngeal region appeared to be the most consistent methods for evaluating intrabolus pressures.SIGNIFICANCEIntrabolus pressure anomalies in the cricopharyngeal region have been proposed as an indicator for selecting patients who would benefit from cricopharyngeal myotomy. The methods of determining intrabolus pressures vary, with resulting variations in recommendations.

OBJECTIVEThe study goal was to determine whether treatment of the tympanic membrane at the time of ventilation tube (VT) removal affects closure of the perforation.STUDY DESIGNWe conducted a retrospective chart review and telephone follow‐up of children who underwent VT removal from 1995 through 1998.RESULTSAmong 109 patients (162 ears; 58% male), the mean age at VT removal was 6.7 years. Most VTs (59%) were T‐tubes, and most (91%) were removed because of prolonged retention (mean 2.3 years). After VT removal, 111 ears (69%) received treatment, most commonly (44%) with 25% trichloroacetic acid (TCA). At the latest follow‐up, 151 of the ears (93%) had healed without additional treatment. Treatment failure occurred more frequently in ears not initially treated with TCA (TCA 3% failure, other treatment 13%, no treatment 8%) and in ears with VTs removed because of otorrhea.CONCLUSIONSMost perforations healed. TCA may promote closure, but a large randomized clinical trial is needed to eliminate physician bias.

OBJECTIVESCD62L was evaluated as a determinant of human pre‐effector T cells.STUDY DESIGN AND SETTINGPhenotype and cytokine secretion profiles of CD62L cells were determined based on activation status.RESULTSCD62LLow T cells demonstrated significantly higher secretion of interleukin (IL)‐10 and interferon (IFN)‐Γ than did CD62LHigh T cells. After activation, the majority of cells expressed high levels of the CD62L surface marker. Postactivation levels of IL‐10 production remained elevated or unchanged. In a murine B16 melanoma model, freshly isolated CD62LLow tumor draining lymph nodes (TDLN) T cells showed increased secretion of IL‐2 and IL‐4 but not of IL‐10 or IFN‐γ. The surface expression of CD62L and cytokine secretion patterns were maintained after activation with concomitant increases in IL‐10.CONCLUSIONOur results provide evidence that CD62LLow T cells in TDLNs of progressively growing squamous cell carcinoma of the head and neck differ phenotypically and functionally from those of mouse origin.SIGNIFICANCECharacterization of this human CD62LLow T cell population provides initial insight regarding novel surface markers in TDLN T cells that might correlate with antitumor reactivity.

OBJECTIVESLymphoscintigraphy with sentinel node dissection and 18 fluoro‐2‐deoxyglucose positron emission tomography (PET) are being used independently in the management of many intermediate and thick melanomas of the head and neck. We report a series of patients with melanoma of the head and neck with Breslow depths greater than 1.0 mm and clinically negative regional nodes that were evaluated prospectively with PET and lymphoscintigraphy.STUDY DESIGN AND SETTINGBetween July 1, 1998 and December 30, 2000 PET scans were obtained preoperatively on 18 patients undergoing resection of head and neck melanoma. Lymphoscintigraphy and sentinel node dissection was performed. Resection of the primary lesion was then carried out with adequate margins and the defects were reconstructed.RESULTSSentinel node(s) were found in 17/18 patients (94.4%); 5/18 (27.8%) of cases had metastases. PET detected nodal metastasis preoperatively in 3 patients (16.7%), one of which had a positive sentinel node dissection.CONCLUSIONPET and lymphoscintigraphy offer complimentary ways of evaluation for metastatic melanoma.