Tube feeding increases the gastric-emptying rate determined by gastroesophageal scintigraphy.

OBJECTIVE: The aim of this study was to determine whether tube feeding affects the rate of gastric emptying determined by gastroesophageal reflux scintigraphy in pediatric patients. METHODS: Gastroesophageal reflux scintigraphy studies of 700 pediatric patients aged 1 week to 16 years were retrospectively analyzed. From these, 350 subjects received their study meal via a feeding tube, and 350 subjects received their meal as oral feeding. Gastric-emptying rate at 60 minutes was calculated, and the results compared. Stratification analysis for age, sex, and type and volume of administered meal was also performed. RESULTS: The average rate of the gastric emptying was higher in the tube feeding compared with oral feeding group (52.9% ± 17.9% vs 44.2% ± 15.1% gastric emptying at 1 hour, P < 0.01). The prevalence of fast gastric emptying, defined as greater than 50% emptying at 60 minutes, was also higher in the tube feeding group, being registered in 59.7% (209/350 cases) versus only 31.4% (110/350 cases) in the oral feeding group, P < 0.01. The difference persisted following stratification analysis for sex, age, and type and volume of ingested meal. CONCLUSIONS: Our findings show that tube feeding increases the rate of gastric emptying determined by gastroesophageal reflux scintigraphy in pediatric patients. The effect proved independent on such factors as sex, age, and type or volume of ingested meal.

Incidental detection of unsuspected pulmonary embolism on oncologic FDG PET/CT imaging.

Incidental findings are not infrequent on integrated FDG PET/CT scans by the virtue of obtaining images from skull base to mid thigh. These can be on the FDG PET portion or the CT portion of the study and can be clinically significant. We report a case of FDG PET/CT imaging performed for staging of head and neck cancer that led to the detection of unsuspected pulmonary embolism. Our case reinforces the importance of careful interpretation of incidental findings on FDG PET/CT imaging as they can have a significant effect on patient management.

FDG PET/CT imaging suggests lymphoma involving prostate may be more resistant to treatment.

FDG PET imaging is generally not useful for prostate cancer. Nevertheless, incidental intense FDG uptake in the prostate warrants further evaluation to assess for prostatic malignancy. We report a case where intense FDG uptake was incidentally noted in an enlarged prostate on FDG PET/CT scan performed for a large left hilar/mediastinal mass (that was also intensely FDG avid along with several additional FDG-avid lesions elsewhere). Biopsy of the prostate and mediastinal lesions revealed large B-cell non-Hodgkin lymphoma at both sites. Serial FDG PET/CT imaging in this patient revealed that the prostatic lymphomatous lesions showed a slower and incomplete response to chemotherapy compared with other sites of lymphomatous involvement (that showed a rapid and complete response to chemotherapy) in the same patient.

PET and PET-CT imaging of gynecological malignancies: present role and future promise.

In this article, we have reviewed the current role of PET/PET-computed tomography (CT) in the management of gynecological malignancies. The promise of this technique is becoming increasingly evident, based upon several studies conducted in these malignancies. 2-fluoro-2-deoxy-D-glucose-PET appears to have a potential role in assessing response to treatment and forecasting prognosis. For cervical carcinoma, the modality has proven useful in both the staging of untreated advanced cervical cancer and restaging of the disease. Its role in prognostication of the disease and in detecting lesions in the setting of post-treatment unexplained tumor-marker elevation appears promising. PET is of great benefit as a diagnostic tool in ovarian carcinoma when there is an increase in serum CA-125 and CT/MRI or conventional imaging are inconclusive or negative. With regard to its role in endometrial carcinoma, its benefit is particularly emphasized in the setting of post-therapy surveillance of the disease, although, in a limited series, it also appears to give additional information in the pretreatment states. PET may be of value in detecting the extra-uterine lesions that are not visualized with CT/MRI. Data on the role of 2-fluoro-2-deoxy-D-glucose-PET imaging in the management of vulvar and vaginal cancer are relatively sparse at this time but the modality appears to be of value in staging disease and is more effective than conventional diagnostic modalities with respect to detecting nodal metastasis in both malignancies.

Coordinated molecular control of otic capsule differentiation: functional role of Wnt5a signaling and opposition by sfrp3 activity.

Wnt proteins constitute one of the major families of secreted ligands that function in developmental signaling, however, little is known of the role of Wnt5a during inner ear development. It is hypothesized that Wnt5a acts as a mediator of chondrogenesis in the developing otic capsule, a cartilaginous structure that surrounds the developing inner ear and presages the formation of the endochondral bony labyrinth. We report the pattern of expression of Wnt5a protein and mRNA in the developing mouse inner ear using immunohistochemistry, whole-mount in situ hybridization and RT-PCR, and the ability of exogenous Wnt5a to stimulate otic capsule chondrogenesis when added to high-density cultures of periotic mesenchyme containing otic epithelium (periotic mesenchyme + otic epithelium), a well-established model of otic capsule formation. We show that in the presence of secreted frizzled related protein 3 (sfrp3), a Wnt antagonist expressed in the developing inner ear, or Wnt5a-specific antisense oligonucleotide, which diminishes endogenous Wnt5a, otic capsule chondrogenesis is suppressed in culture. We determined by histological analysis and aggrecan immunoreactivity that chondrogenic differentiation is disturbed in Wnt5a null embryos, and provide evidence that the periotic mesenchyme + otic epithelium harvested from Wnt5a null mice is compromised in its ability to differentiate into cartilage when interacted in culture. We propose a model whereby sfrp3 and Wnt5a act antagonistically to ensure appropriate patterns of chondrogenesis and provide coordinated control of otic capsule formation. Our findings support Wnt5a and sfrp3 as regulators of otic capsule formation in the developing mouse inner ear.

PET and PET/CT in Pediatric Gastrointestinal Tract Oncology.

PET and PET/CT imaging are increasingly used in pediatric oncology; however, their role is still evolving. Studies have shown an incremental impact of PET imaging on the management of childhood malignancies. Gastrointestinal tumors have low incidence in children and PET has proved useful in many of them. Overall, the published data support the exceptional diagnostic capability of PET and PET-CT imaging. This article presents insight through the available literature on pediatric gastrointestinal oncology.

Oral ethanol potentiates the loss of outer hair cells in cisplatin-exposed rats.

OBJECTIVE: The aim of this study was to examine the effect of oral ethanol on cisplatin ototoxicity. STUDY DESIGN AND SETTING: Twenty-seven-week-old, female Fisher 344 rats were divided into 4 experimental groups. The animals were administered per os (PO) saline (group 1), PO ethanol (group 2), PO saline with intraperitoneal (IP) cisplatin (group 3), or PO ethanol with IP cisplatin (group 4). After 3 days, scanning electron microscopy and counts of outer auditory hair cells were performed. RESULTS: A 2-fold increase in outer hair cell loss was obtained in the basal cochlear turn of rats receiving concomitant cisplatin and ethanol compared with animals receiving cisplatin and saline. No hair cell loss was observed in the middle cochlear turn of any experimental group. CONCLUSION: Our findings support potentiation of ototoxicity when cisplatin is combined with oral ethanol. SIGNIFICANCE: Contraindications for alcohol use in cancer patients receiving cisplatin are implicated.

Intercostal muscle contraction or rib bone marrow activity?: Look for ancillary clues.

Diffuse and uniform FDG uptake in the ribs and the intercostal muscles might appear similar on FDG-PET images and a reliable differentiation between the two is important for accurately identifying the underlying process. The former usually suggests excessive contraction of intercostal muscles mostly due to chronic obstructive pulmonary disease, whereas the latter signifies either bone marrow stimulation or involvement by a pathologic process. At times, images may appear confusing and may be misinterpreted. However, in both clinical settings, there are additional ancillary signs, which are helpful in making a correct diagnosis. We herein present 2 case vignettes from each category in which other ancillary signs helped to distinguish FDG rib uptake from intercostal muscle uptake.

Etiopathologies associated with intercostal muscle hypermetabolism and prominent right ventricle visualization on 2-deoxy-2[F-18]fluoro-D-glucose-positron emission tomography: significance of an incidental finding and in the setting of a known pulmonary disease.

OBJECTIVES: The present study was undertaken to investigate the significance of 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) uptake in the intercostal muscles (ICM) and prominent visualization of right ventricle (RV) in FDG-positron emission tomography (PET) scans and its implications. METHODS: Patients identified to have FDG uptake in the ICM with or without prominent visualization of the RV either incidentally or in the background of an existing explanatory cause at the time of FDG-PET studies were included in this retrospective study. These patients had undergone FDG-PET either for ruling out malignancy or for disease monitoring purposes in setting a proven malignancy. We reviewed the clinical and investigational records (including computed tomography [CT] thorax, chest X-ray, 2-D echo and pulmonary function tests, and arterial blood gas analysis) of the group with incidental FDG uptake for revelation of a pathology explaining such uptake. RESULTS: A total of 14 cases with 16 FDG-PET studies were identified from the retrospective examination of case records. One patient had three FDG-PET at different time points of his disease course. The patient population included 13 males and one female with age range 46-88 years. The patients were classified into two groups: (1) cases with isolated ICM uptake (n=10); (2) cases with both ICM and RV uptake (n=4). Among 10 patients with isolated ICM uptake, in six patients it was a serendipitous observation, whereas four patients had existing explanatory cause at the time of FDG-PET. The causes found to be associated included COPD, asthma, recent heart failure, interstitial lung disease (post external radiotherapy) and pulmonary embolism, atelectasis with pleural effusion. In all four cases with associated RV uptake, there was evidence of pulmonary hypertension (PH). Among these, in one patient this was a serendipitous observation. He had evidence of interstitial lung disease (ILD) in CT thorax, and 2-D echo showed moderate PH. The remaining three patients had cor pulmonale secondary to COPD, pneumoconiosis, and Swyer James Syndrome with associated severe PH. The SUVmax ratio of the RV-to-LV free wall ranged from 0.53 to 1.04 in the cases with prominent RV uptake. One patient had multiple FDG-PET studies and have shown reduction of RV uptake in the last scan consistent with the clinical impression of improvement of cor pulmonale. CONCLUSION: Both intercostal muscle and prominent RV uptake in FDG-PET can be associated with a spectrum of causes (including both obstructive and restrictive airway diseases) that lead to breathing exertion. These are important markers, which could signify underlying pulmonary disease and pulmonary hypertension, respectively. Associated prominent RV uptake strongly indicates presence of pulmonary hypertension and the uptake in the right heart can subserve a valuable surrogate marker in the treatment-monitoring scenario of a known PH.

Clinical Significance of Incidental Focal Versus Diffuse Thyroid Uptake on FDG-PET Imaging.

The number of incidentally detected thyroid lesions found with (18)F-fluorodeoxyglucose positron emission tomography is increasing. Malignant cases incidentally found with this technique are mainly primary thyroid cancers, particularly papillary thyroid carcinoma, which tend to harbor a higher rate of unfavorable prognostic features than routinely diagnosed primary thyroid cancers. The significance of standardized uptake values in predicting malignancy of incidental thyroid fluorodeoxyglucose uptake is controversial, and more studies are needed to establish its role in differentiating benign and malignant incidental thyroid fluorodeoxyglucose uptake. In this article, we review recent publications regarding incidental thyroid lesions found on fluorodeoxyglucose positron emission tomography and their differential diagnosis, including the risk for malignancy.

The Role of CT, MR Imaging, and Ultrasonography in Endocrinology.

Many disorders commonly affect various organs of the endocrine system. The nuclear medicine physician and radiologist must be aware of the manifestations of these disorders that may be detected on structural imaging modalities. In this article, we provide a brief review of the advantages and disadvantages of CT, MR imaging, and ultrasonography. We then discuss the role of these structural imaging modalities in the evaluation of disorders affecting the endocrine organs. In particular, we focus our review on imaging evaluation of the pituitary gland, the thyroid gland, the parathyroid glands, and the adrenal gland. Specific examples of some of the disease entities affecting these organs are also reviewed.

Cisplatin ototoxicity to the rat inner ear: a role for HMG1 and iNOS.

Cisplatin is a chemotherapeutic agent that causes toxic damage to the inner ear (ototoxicity). Although much attention has been directed at identifying ways to protect the inner ear against cisplatin ototoxicity, little is known about the mechanisms by which cisplatin causes damage to the inner ear. Binding of high-mobility group (HMG1) protein to cisplatin-modified DNA participates in mediating the antitumor effects of cisplatin. This study seeks to determine if HMG1 may also participate in the ototoxicity of cisplatin. To address this, patterns and levels of expression of HMG1 have been evaluated in the rat cochlea in response to cisplatin chemotherapy. Our findings demonstrate a marked upregulation of HMG1 protein in the spiral (auditory) ganglion cells of cisplatin-treated rats in comparison to levels of expression of HMG1 in the spiral ganglion cells of untreated control animals. Increased levels of HMG1 were observed in the cisplatin-treated kidney, a peripheral target tissue of cisplatin, but not in the heart, a tissue not typically affected by cisplatin chemotherapy, suggesting HMG1 specificity in cisplatin toxicity. Furthermore, levels of inducible nitric oxide synthase (iNOS), an HMG-regulated enzyme associated with cochlear pathology, are increased in the spiral ganglion cells of cisplatin-treated rats 1 day post the cisplatin-mediated upregulation in HMG1. This increase in HMG1 and iNOS can be prevented in the cochleae of cisplatin-treated rats by administration of l-methionine, an established method of protection against cisplatin ototoxicity. Our results support a role for HMG1 and iNOS in mechanisms of cisplatin ototoxicity in the rat inner ear.

Oxymetazoline solutions inhibit middle ear pathogens and are not ototoxic.

OBJECTIVES: This study was performed to explore the antimicrobial activity of two commercially available oxymetazoline hydrochloride preparations against the common pathogens of otitis media and to demonstrate the lack of ototoxicity of these agents and of United States Pharmacopeia (USP) oxymetazoline in a standard animal model. METHODS: Disc diffusion assays and minimum inhibitory concentration studies against American Type Culture Collection reference strains of common middle ear pathogens were used to evaluate the antimicrobial activity of oxymetazoline solutions and fluoroquinolone drops, and outer hair cell counts were performed on scanning electron micrographs of guinea pig basal cochlear segments after chronic exposure to oxymetazoline solutions and positive and negative controls. RESULTS: Oxymetazoline nasal spray and eyedrops had activity against all species tested except Haemophilus influenzae and Pseudomonas aeruginosa. The USP oxymetazoline had limited antimicrobial activity. Oxymetazoline nasal spray, oxymetazoline eyedrops, and USP oxymetazoline had ototoxicity profiles indistinguishable from that of the saline solution control. CONCLUSIONS: Commercially available oxymetazoline solutions are active against several of the common pathogens of otitis media. This antimicrobial activity is not due to oxymetazoline, and is more likely due to preservatives present in the solutions. The solutions tested are not ototoxic to guinea pig outer hair cells. Oxymetazoline solutions are potential substitutes for broad-spectrum antibiotic drops after tympanostomy tube placement.

Transforming growth factor-beta1 signaling participates in the physiological and pathological regulation of mouse inner ear development by all-trans retinoic acid.

BACKGROUND: Retinoic acid (RA) is a vitamin A derivative that participates in patterning and regulation of inner ear development. Either excess RA or RA deficiency during a critical stage of inner ear development can produce teratogenic effects. Previous studies have shown that in utero exposure of the developing mouse inner ear to a high dose of all-trans RA (atRA) results in severe malformations of the inner ear that are associated with diminished levels of endogenous transforming growth factor-beta1 (TGF-beta(1)) protein. METHODS: In this study, the effects of a teratogenic level of atRA on levels and patterns of expression of TGFbeta receptor II (TGFbetaRII) and Smad2, a downstream component of the TGFbeta signal transduction pathway, are investigated in the developing mouse inner ear. The expression pattern of endogenous RA receptor alpha (RARalpha) and the ability of an RARalpha(1)-specific antisense oligonucleotide (AS) to modulate otic capsule chondrogenesis are demonstrated in the inner ear and in culture. RESULTS: Endogenous TGFbetaRII and Smad2 are downregulated in the inner ear following in utero atRA treatment. In addition, a reduction in endogenous TGFbeta(1) and a marked suppression of chondrogenesis occur in RARalpha(1) AS-treated cultures in comparison to untreated or oligonucleotide-treated control cultures. This chondrogenic suppression can be partially overcome by supplementation of RARalpha(1) AS-treated cultures with exogenous TGFbeta(1) protein. CONCLUSIONS: Our findings support a role for TGFbeta in the physiological and pathological effects of RA on inner ear development.

Bone morphogenetic protein 4 (BMP4): a regulator of capsule chondrogenesis in the developing mouse inner ear.

Formation of the cartilaginous otic capsule is directed by otic epithelial-periotic mesenchymal interactions. In response to induction by otic epithelium, condensations of mesenchyme appear in the periotic region and form a chondrified otic capsule that serves as the template for the subsequent formation of the endochondral bony labyrinth. Previous studies indicate that members of the transforming growth factor beta superfamily, including transforming growth factor beta(1), participate in guiding these tissue interactions. In this study, we report the localization of bone morphogenetic protein 4 (BMP4) to the mesenchymal and epithelial-derived tissues of the mouse inner ear between 10.5 and 14 days of embryonic development. We demonstrate modulation of chondrogenesis in cultured mouse periotic mesenchyme by exogenous BMP4 protein and investigate the function of endogenous BMP4 in otic capsule chondrogenesis. We show that in the presence of the BMP antagonist, Noggin, otic capsule chondrogenesis is suppressed in culture in a dose-dependent manner. Consistent with this finding, addition of BMP4-specific antisense oligonucleotide to cultures of mouse periotic mesenchyme containing otic epithelium decreases levels of endogenous BMP4 protein and suppresses the chondrogenic response of the cultured periotic mesenchyme, providing evidence of the necessity for BMP4 in mediating otic capsule chondrogenesis. Supplementation of either Noggin- or BMP4 antisense oligonucleotide-treated cultures with BMP4 protein can restore the extent of chondrogenesis to normal levels. Our findings support BMP4 as an essential mediator of chondrogenesis in the developing otic capsule in situ.

Salicylate protects hearing and kidney function from cisplatin toxicity without compromising its oncolytic action.

Salicylate has recently been demonstrated to protect against the auditory and vestibular side effects of aminoglycoside antibiotics. Similarities in the toxic mechanisms suggest salicylate as a treatment strategy to prevent the ototoxic side effects of cisplatin (CDDP). We first tested protection of the inner ear in Wistar rats receiving a single infusion of 16 mg CDDP/kg body weight with or without treatment with 100 mg/kg salicylate (bid) for 5 days beginning one day before the CDDP infusion. Cisplatin induced a threshold shift of more than 30 dB (at 14 kHz; measured by auditory evoked brain stem response) that was significantly reduced by salicylate. We then examined the protective potential of salicylate on the cochlea, peripheral nerves, and kidney in a rat model of breast cancer--Fisher344 rats implanted with highly metastatic MTLn3 breast cancer cells. Animals received 3 x 5 mg CDDP/kg (given every third day), and salicylate was administered at 100 mg/kg (bid) from 2 days before to 3 days after CDDP treatment. Salicylate significantly attenuated the CDDP-induced threshold shift from approximately 20 dB (at 16 and 24 kHz) to approximately 5 dB, and drastically reduced the loss of cochlear outer hair cells. Likewise, salicylate protected kidney function (measured as plasma blood urea nitrogen and creatinine levels) from CDDP toxicity. Protection of nerve conduction velocities of both sensory and motor nerves was minimal. The chemotherapeutic efficacy of CDDP on suppression of tumor mass and cancer cell metastasis remained unaffected by salicylate. The results suggest that administration of salicylate may become the basis of an effective therapeutic intervention against the ototoxic and nephrotoxic side effects associated with CDDP chemotherapy.