Faculty Bibliography

Introduction: Airway dysfunction has been detected by oscillometry in obese subjects despite normal large airway function as assessed by spirometry. This has been attributed to lung/airway compression as reflected by reduced FRC; we previously demonstrated improvement of abnormalities towards normal upon voluntary inflation to predicted FRC (AJRCCM 2010; 181:A2532). However, other causes of airway dysfunction such as inflammation or concomitant intrinsic airway disease may coexist and could not be excluded. The present study re-evaluated these subjects following bariatric surgery induced weight loss to evaluate for residual abnormality. Methods: 22 morbidly obese subjects without history of smoking and/or cardiopulmonary disease, underwent evaluation pre/post bariatric surgery (20% reduction in weight). Spirometry, plethysmography and impulse oscillometry (IOS) were performed. IOS parameters included resistance at 5Hz (R5), resistance at 20Hz (R20) frequency dependence of resistance (R5-20) and reactance at 5Hz (X5).IOS was also performed at an elevated lung volume (~1 liter) targeted to restore FRC to predicted values. All IOS measurements were repeated post bronchodilator. Results: Baseline weight and BMI were 256+/-43 kg and 46+/-7 kg/m², respectively. All subjects lost >20% of body weight, but obesity persisted in all subjects (weight 182 kg, BMI 33 kg/ m2). FEV /FVC was normal at baseline and remained unchanged post weight loss 1 (81+/-3% vs 83+/-4%) indicating normal large airway function. FRC and ERV improved post weight loss but values remained abnormal (FRC from 60+/-12 to 77+/-21% predicted, ERV from 46+/-16 to 75+/-38% predicted, p<0.05). Although IOS parameters improved following weight loss, data remained above the upper limit of normal (R5 from 6.8+/-1.8 to 5.1+/-1.4 cmH₂O/l/s, R₂₀ from 4.7+/-1.1 to 3.9+/-0.9 cmH₂O/l/s, R_5-20 from 2.1+/-1.1 to 1.2+/-0.9 cmH_2O /l/s, X₅ from -3.2+/-1.7 to -1.8+/-0.9 cmH₂O /l/s, p<0.05). Since FRC remained abnormal following weight loss, IOS was repeated following voluntary lung inflation (FRC 142+/-30%). While R20 corrected to normal at the elevated FRC (R₂₀ 3.1+/-1.0 cmH₂ O/l/s), R5, R5-20 and X5 remained abnormal indicating residual distal airway dysfunction (R₅ 4.2+/-1.4 cmH₂O/l/s, , R_5-20 1.1+/-0.7 cmH₂O /l/s, X₅ -2.0+/-0.8 cmH₂O /l/s); these residual oscillometric abnormalities were present in 11/22 subjects. Residual airway dysfunction was demonstrated by low specific conductance (assessed at 5HZ) despite restoration of FRC to supranormal values. Conclusions: Distal airway dysfunction persisted following weight loss and was not attributable to persistent mass loading in a subgroup of patients without clinical evidence of airway disease. These abnormalities may represent either functional abnormalities due to persistent obesity and/or intrinsic airway disease

Introduction: Pulmonary function evaluation in patients with cystic fibrosis (CF) has demonstrated disparity between spirometric and oscillometric assessments. Most studies have indicated that oscillometry may appear normal despite significant abnormalities on spirometry. However, normal values for impulse oscillometry (IOS) in pediatric populations are limited and vary by study. The present study assessed the role for IOS by assessment of both the acute response to bronchodilator and the chronic response to treatment. Methods: Patients hospitalized with exacerbations of CF were evaluated with both spirometry and oscillometry. Data were obtained pre and post bronchodilator administration and related to published normative data. When feasible, lung volumes were assessed by plethysmography. Serial testing was performed during and following standard therapy which included vigorous chest physical therapy and intravenous antibiotics targeted to the predominate organism isolated from sputum or bronchoscopy specimens. Results: Data were available in 5 patients with CF with age ranging from 5 to 44 years. Abnormal spirometry was evident in 4 subjects. Although FEV₁/FVC was mildly reduced in these subjects (68+5%), the predominant abnormality was reduction in vital capacity (50+12%). HRCT demonstrated severe mucous plugging in multiple airways and bronchoscopy in one patient confirmed total occlusion of the bronchial lumen form respiratory secretions. Despite these spirometric and radiographic abnormalities, oscillometric assessment of resistance assessed was within published normal limits in these subjects. However, a positive response to bronchodilator was observed in 3 patients and serial testing in one subject demonstrated further improvement in airway resistance by IOS. These changes in oscillometric data occurred with minimal change in FVC and FEV₁. Conclusions: Although IOS parameters in an individual patient may be within published normal limits, reduction in resistance may be apparent either acutely post bronchodilator or chronically following treatment. These improvements in IOS parameters may not be apparent on spirometry, providing a potential role for IOS in the evaluation of patients with CF. These data suggest that improvement in post bronchodilator measurements of airway resistance may be a useful adjunct to guide the appropriate length of treatment for CF exacerbations

BACKGROUND: Models of autism spectrum disorders (ASD) as neural disconnection syndromes have been predominantly supported by examinations of abnormalities in corticocortical networks in adults with autism. A broader body of research implicates subcortical structures, particularly the striatum, in the physiopathology of autism. Resting state functional magnetic resonance imaging has revealed detailed maps of striatal circuitry in healthy and psychiatric populations and vividly captured maturational changes in striatal circuitry during typical development. METHODS: Using resting state functional magnetic resonance imaging, we examined striatal functional connectivity (FC) in 20 children with ASD and 20 typically developing children between the ages of 7.6 and 13.5 years. Whole-brain voxelwise statistical maps quantified within-group striatal FC and between-group differences for three caudate and three putamen seeds for each hemisphere. RESULTS: Children with ASD mostly exhibited prominent patterns of ectopic striatal FC (i.e., functional connectivity present in ASD but not in typically developing children), with increased functional connectivity between nearly all striatal subregions and heteromodal associative and limbic cortex previously implicated in the physiopathology of ASD (e.g., insular and right superior temporal gyrus). Additionally, we found striatal functional hyperconnectivity with the pons, thus expanding the scope of functional alterations implicated in ASD. Secondary analyses revealed ASD-related hyperconnectivity between the pons and insula cortex. CONCLUSIONS: Examination of FC of striatal networks in children with ASD revealed abnormalities in circuits involving early developing areas, such as the brainstem and insula, with a pattern of increased FC in ectopic circuits that likely reflects developmental derangement rather than immaturity of functional circuits

Nasal positive expiratory pressure (nEPAP) delivered with an expiratory valve (ProventVentus Medical) has recently been shown to have a beneficial effect on sleep disordered breathing (Rosenthal, JCSM 2009; 5:532). The mechanism of action is not fully understood but effects on lung volume have been invoked (Patel, JCSM in press). In the present study we evaluate the effect of nEPAP on functional residual capacity (FRC) and upper airway (UA) dimensions. Methods: Fast MRI was used to acquire 4-5 images/sec in the awake state during multiple cycles of nose breathing with and without nEPAP in 6 patients with S

Contrary to a clinical aphorism that early head and neck cancer is painless, we show that patients who develop head and neck cancer experience significant pain at the time of initial diagnosis. We compared orofacial pain sensitivity in groups of patients with normal oral mucosa, oral precancer, and newly diagnosed oral cancer. The University of California San Francisco Oral Cancer Pain Questionnaire was administered to these patients at their initial visit, before being prescribed analgesics for pain and before any treatment. In contrast to those with biopsy-proven normal oral mucosa and oral precancer, only oral cancer patients reported significant levels of spontaneous pain and functional restriction from pain. Moreover, oral cancer patients experienced significantly higher function-related, rather than spontaneous, pain qualities. These findings suggest an important predictor for the transition from oral precancer to cancer may be the onset of orofacial pain that is exacerbated during function. Screening patients who have new-onset orofacial pain may lead to a diagnosis of early resectable head and neck cancer and may improve quality of life and survival for head and neck cancer patients. An important predictor for the transition from oral precancer to oral cancer may be the onset of orofacial pain that is exacerbated during function

BACKGROUND AND PURPOSE: Small oral cavity tumors are an imaging challenge. Intimate apposition of vestibular oral mucosa to the alveolar mucosa makes tumor assessment difficult. In CT imaging, the 'puffed cheek' method has been used to separate surfaces, though this is not feasible with long MR imaging sequences. We implemented placement of 2 x 2 inch (6.45 cm) gauze into the oral vestibule before the MR imaging examination, to determine whether this might improve tumor visualization. MATERIALS AND METHODS: MR imaging examinations of all T1 oral malignant tumors treated at University of California, San Francisco, by the Oral and Maxillofacial Department were reviewed by 2 neuroradiologists. Nine patients were included in the final analysis. Six patients were imaged by using a standard protocol. Three patients were imaged with gauze placement. The radiologists evaluated the MR images, assessing whether they could see the tumor and then fully delineate it and its thickness. RESULTS: Fisher exact analysis was performed on questions 1, 2, and 4 with the following results: P value = .048, Can you see the tumor? P value = .012, Can you fully delineate? P value of .012, How confident are you? MR imaging examinations with gauze clearly delineated the tumor with the tumor thickness measurable. MR imaging examinations without gauze did not clearly show the tumor or its thickness. Confidence of interpretation of the findings was also increased when gauze was used. CONCLUSIONS: A 2 x 2 inch (6.45 cm) rolled gauze in the oral vestibule significantly improved tumor localization and delineation at MR imaging. This technique is simple and provides superior preoperative imaging evaluation and treatment planning of small oral cavity tumors

Vascular endothelial growth factor (VEGF) is critical to angiogenesis and vascular permeability. It is also important in the endocrine system, in which VEGF mediates the vascular effects of estrogens in target tissues such as the uterus, a response attributed to an estrogen response element on the VEGF gene. Here we asked whether 17beta-estradiol increases VEGF levels in the brain. We focused on the hippocampus, in which 17beta-estradiol and VEGF both have important actions, and used immunocytochemistry to evaluate VEGF protein. VEGF immunoreactivity was compared in adult female rats sampled during the estrous cycle when serum levels of 17beta-estradiol peak (proestrous morning) as well as when they are low (metestrous morning). In addition, adult rats were ovariectomized and compared after treatment with 17beta-estradiol or vehicle. The results demonstrated that VEGF immunoreactivity was increased when serum levels of 17beta-estradiol were elevated. Confocal microscopy showed that VEGF immunofluorescence was predominantly nonneuronal, often associated with astrocytes. Glial VEGF labeling was primarily punctate rather than diffuse and labile because glial VEGF immunoreactivity was greatly reduced if tissue sections were left in an aqueous medium overnight. We conclude that VEGF protein in normal female hippocampus is primarily nonneuronal rather than neuronal and suggest that glial VEGF immunoreactivity has been underestimated by past studies with other methods because there is a labile extracellular pool. We suggest that estrogens may exert actions on female hippocampal structure and function by increasing hippocampal VEGF