Fibroblast Growth Factor-23 Concentration in Dogs with Chronic Kidney Disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with hyperphosphatemia, decreased vitamin D metabolite concentrations, and hyperparathyroidism. This syndrome is known as CKD-mineral bone disorder (CKD-MBD). Recently, it has been shown that an increase in fibroblast growth factor-23 (FGF-23) concentration is an early biomarker of CKD in people. It is an independent risk factor for both progression of renal disease and survival time in humans and cats with CKD. Information about FGF-23 in healthy dogs and those with CKD is lacking. OBJECTIVES: To measure FGF-23 concentration in dogs with different stages of CKD and determine its association with factors involved in CKD-MBD, including serum phosphorus and parathyroid hormone (PTH) concentrations. A secondary aim was to validate an ELISA for measurement of plasma FGF-23 concentration in dogs. ANIMALS: Thirty-two client-owned dogs with naturally occurring CKD and 10 healthy control dogs. METHODS: Prospective cross-sectional study. An FGF-23 ELISA was used to measure plasma FGF-23 concentration in dogs and their association with serum creatinine, phosphorus, calcium, and PTH concentrations. RESULTS: Plasma FGF-23 concentrations increased with severity of CKD and were significantly different between IRIS stages 1 and 2 versus stages 3 and 4 (P < .0001). Increases in FGF-23 concentrations were more frequent than hyperparathyroidism or hyperphosphatemia in this cohort. Serum creatinine and phosphorus concentrations were the strongest independent predictors of FGF-23 concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma FGF-23 concentrations increase in dogs with CKD as disease progresses. Plasma FGF-23 concentrations appear to be useful for further study of the pathophysiology of CKD-MBD in dogs.

Association of Vitamin D Metabolites with Parathyroid Hormone, Fibroblast Growth Factor-23, Calcium, and Phosphorus in Dogs with Various Stages of Chronic Kidney Disease.

BACKGROUND: Hypovitaminosis D is associated with progression of renal disease, development of renal secondary hyperparathyroidism (RHPT), chronic kidney disease-mineral bone disorder (CKD-MBD), and increased mortality in people with CKD. Despite what is known regarding vitamin D dysregulation in humans with CKD, little is known about vitamin D metabolism in dogs with CKD. OBJECTIVES: The purpose of our study was to further elucidate vitamin D status in dogs with different stages of CKD and to relate it to factors that affect the development of CKD-MBD, including parathyroid hormone (PTH), fibroblast growth factor-23 (FGF-23), calcium, and phosphorus concentrations. METHODS: Thirty-seven dogs with naturally occurring CKD were compared to 10 healthy dogs. Serum 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)2 D], and 24,25-dihydroxyvitamin D [24,25(OH)2 D], and PTH and FGF-23 concentrations were measured. Their association with serum calcium and phosphorus concentrations and IRIS stage was determined. RESULTS: Compared to healthy dogs, all vitamin D metabolite concentrations were significantly lower in dogs with International Renal Interest Society (IRIS) stages 3 and 4 CKD (r [creatinine]: -0.49 to -0.60; P < .05) but not different in dogs with stages 1 and 2 CKD. All vitamin D metabolites were negatively correlated with PTH, FGF-23, and phosphorus concentrations (r: -0.39 to -0.64; P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: CKD in dogs is associated with decreases in all vitamin D metabolites evaluated suggesting that multiple mechanisms, in addition to decreased renal mass, affect their metabolism. This information could have prognostic and therapeutic implications.

Measured Head CT/CTA Skin Dose and Intensive Care Unit Patient Cumulative Exposure.

BACKGROUND AND PURPOSE: Estimates of cumulative CT/CTA radiation dose based on volumetric CT dose index have raised concern that neurological intensive care unit patient exposures may reach thresholds for deterministic skin injury. Because the accuracy of volumetric CT dose index for this purpose in unknown, we set out to directly measure head CT and CTA peak skin dose, assess the relationship of volumetric CT dose index to measured peak skin dose, and determine whether multiple CT/CTA exposures in typical patients in the neurological intensive care unit produce cumulative doses approaching or exceeding single-dose deterministic thresholds for skin injury. MATERIALS AND METHODS: In a prospective study from 2011-2013, nanoDot optical stimulated luminescence dosimeters were used to measure head CT/CTA peak skin dose in 52 patients (28 female, 24 male; mean age, 63 years) divided equally between 2 CT scanners. Volumetric CT dose index and dose-length product were recorded for each examination. Peak skin dose was also measured on an acrylic skull phantom in each scanner. A 2-tailed, unpaired t test was used to compare mean patient skin doses between the 2 scanners. The measured peak skin doses were then used to calculate cumulative peak skin dose in 4 typical patients in intensive care units who received multiple CT/CTA scans. RESULTS: Head CT/CTA peak skin dose agreed between scanners in patients and phantoms: (scanner 1 CT/CTA: patients, 39.2 ± 3.7 mGy and 98.9 ± 5.3 mGy, respectively, versus phantom, 40.0 mGy and 105.4 mGy, respectively; scanner 2 CT/CTA: patients, 42.9 ± 9.4 mGy and 98.8 ± 7.4 mGy, respectively, versus phantom, 37.6 mGy and 95.2 mGy, respectively). Volumetric CT dose index overestimated peak skin dose by a factor of 1.4-1.9 depending on examination and CT scanner. Cumulative doses in 4 patients in the intensive care unit estimated from measured CT/CTA peak skin dose ranged from 1.9-4.5 Gy. CONCLUSIONS: Directly measured radiation skin doses from head CT/CTA patient examinations are substantially lower than volumetric CT dose index. Measured peak skin dose confirms that multiple head CT/CTA examinations in representative patients in the neurological intensive care unit may produce cumulative doses exceeding the single-dose deterministic threshold for skin injury.

Clival invasion on multi-detector CT in 390 pituitary macroadenomas: correlation with sex, subtype and rates of operative complication and recurrence.

BACKGROUND AND PURPOSE: Clival invasion, a rare but potentially significant complication of pituitary adenoma, is difficult to detect on MR imaging. Because CT is widely used in adjunct guidance of pituitary surgery and it has recently been suggested that preoperative CT may add useful diagnostic information in addition to pituitary MR imaging, we performed the first large cross-sectional imaging study to define the image attributes, clinical correlates, and prognostic implications of clival invasion on CT for pituitary adenoma surgical guidance. MATERIALS AND METHODS: Preoperative CT images from 390 patients with histopathologically diagnosed pituitary macroadenoma were reviewed retrospectively and classified by the presence and degree of clival invasion. Tumor volume, tumor subtype, patient sex, operative complication, and recurrence rates were compared between groups. RESULTS: After we corrected for multiple correlations, the most significant independent risk factor for clival invasion was female sex (OR=3.62, P=.014, multinomial logistic regression), followed by large tumor volume (OR=1.08, P<.001), and null-cell subtype (OR=5.47, P<.001). Larger tumor volume correlated with null-cell subtype (Mann-Whitney U test, P=.006), incidence of clival invasion (P<.001), and extent of clival invasion (P=.038). Clival invasion was associated with a significantly higher ratio of operative complications (15.63%, χ(2)=7.067, P=.008) and recurrence (57.14%, χ(2)=10.739, P=.001). CONCLUSIONS: CT detection of clival invasion by pituitary macroadenoma is significantly more common in women, in patients with large tumors, and in patients with null-cell tumors, and it is associated with a higher rate of operative complications and recurrences. Attention to the presence of clival invasion on preoperative CT and prospective investigation of its prognostic significance are indicated. Attention to this finding on pituitary guidance CT is warranted.

Can family affectedness inform infant sibling outcomes of autism spectrum disorders?

BACKGROUND: Difficulties in communication and reciprocal social behavior are core features of autism spectrum disorders (ASD) and are often present, to varying degrees, in other family members. This prospective longitudinal infant sibling study examines whether social-communicative features of family members may inform which infants are at increased risk for ASD and other developmental concerns. METHOD: Two hundred and seventeen families participated in this study. Infant siblings were recruited from families with at least one older child diagnosed with an ASD (n = 135) or at least one typically developing older child (n = 82). Families completed the Social Responsiveness Scale to assess social and communication features of the broader autism phenotype (BAP), sometimes called quantitative autistic traits (QAT). Family affectedness was assessed in two ways: categorically, based on number of affected older siblings (i.e., typical, simplex, multiplex risk groups) and dimensionally, by assessing varying degrees of QAT in all family members. Infant siblings were assessed at 36 months of age and completed the Autism Diagnostic Observation Schedule and the Mullen Scales of Early Learning. RESULTS: In structural equation models, comparisons between multiplex, simplex and typical groups revealed the highest rates of QAT in the multiplex group followed by the simplex and typical groups. Infant sibling outcomes were predicted by gender, family risk group, proband QAT, and additional sibling QAT. CONCLUSIONS: Replicating previous cross-sectional and family history findings, the present study found elevated social and communication features of the BAP in siblings and fathers of ASD families, but not in mothers. While social and communication features of the BAP in mothers, fathers, and undiagnosed siblings did not predict infant sibling outcomes, having more than one affected older sibling did. Infant siblings from multiplex families were at significantly higher risk for ASD than infant siblings from simplex families in this sample.

MR imaging of adenomas of the nonpigmented ciliary epithelium of the eye.

BACKGROUND AND PURPOSE: ANPCEs are rare benign tumors of the eye arising from the NPCE in adults, which may be clinically mistaken for melanoma. This study was undertaken to delineate clinical and MR imaging features of these tumors. MATERIALS AND METHODS: Clinical presentation and MR imaging findings of 8 patients (6 women and 2 men; median age, 51 years) with pathologically confirmed ANPCEs were retrospectively reviewed. Location, size, shape, margin, signal intensity, and gadolinium-enhancement characteristics of all tumors were evaluated. Signal intensity and degree of enhancement were graded in comparison with the ipsilateral lacrimal gland. RESULTS: MR imaging revealed a circumscribed enhancing mass within the ciliary body of the eye in all 8 patients. The mass was ovoid in 6 patients and spheric in 2. Gadolinium enhancement was marked in 4 lesions and moderate in the other 4. Both T1 and T2 relaxation times were qualitatively identical to those in the lacrimal gland in 2 tumors. In the remaining 6 tumors, the T1 was identical to and the T2 longer than that in the lacrimal gland. CONCLUSIONS: ANPCE should be included in the differential diagnosis of a spheric or ovoid enhancing ciliary body mass with T1 similar to that in the lacrimal gland and T2 equal to or longer than that in the lacrimal gland.

Spin-echo echo-planar perfusion MR imaging in the differential diagnosis of solitary enhancing brain lesions: distinguishing solitary metastases from primary glioma.

Unlike the more widely reported gradient-echo echo-planar perfusion-weighted imaging (EPI-PWI) technique, spin-echo (SE) EPI relative cerebral blood volume maps select for blood volume in microvessels <8 microm in diameter. This first report of SE-EPI PWI for distinguishing brain metastasis from high-grade glioma demonstrated 88% sensitivity and 72% specificity in 83 patients. We discuss differences in microvessel architecture between high-grade glioma and brain metastasis that may explain the surprising success of SE-EPI in this application and may deserve further investigation.

Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence.

BACKGROUND: Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, may have activity in recurrent malignant gliomas. At recurrence some patients appear to develop nonenhancing infiltrating disease rather than enhancing tumor. METHODS: We retrospectively reviewed 55 consecutive patients with recurrent malignant gliomas who received bevacizumab and chemotherapy to determine efficacy, toxicity, and patterns of recurrence. Using a blinded, standardized imaging review and quantitative volumetric analysis, the recurrence patterns of patients treated with bevacizumab were compared to recurrence patterns of 19 patients treated with chemotherapy alone. RESULTS: A total of 2.3% of patients had a complete response, 31.8% partial response, 29.5% minimal response, and 29.5% had stable disease. Median time to radiographic progression was 19.3 weeks. Six-month progression-free survival (PFS) was 42% for patients with glioblastoma and 32% for patients with anaplastic glioma. In 23 patients who progressed on their initial therapy, bevacizumab was continued and the concurrent chemotherapy agent changed. In no case did the change produce a radiographic response, but two patients had prolonged PFS of 20 and 31 weeks. Recurrence pattern analysis identified a significant increase in the volume of infiltrative tumor relative to enhancing tumor in bevacizumab responders. CONCLUSIONS: Combination therapy with bevacizumab and chemotherapy is well-tolerated and active against recurrent malignant gliomas. At recurrence, continuing bevacizumab and changing the chemotherapy agent provided long-term disease control only in a small subset of patients. Bevacizumab may alter the recurrence pattern of malignant gliomas by suppressing enhancing tumor recurrence more effectively than it suppresses nonenhancing, infiltrative tumor growth.

Creutzfeldt-jakob disease involvement of rolandic cortex: a quantitative apparent diffusion coefficient evaluation.

BACKGROUND: Previous reports have suggested that abnormally reduced water diffusivity and T2 prolongation involving cerebral gray matter in patients with early sporadic Creutzfeldt-Jakob disease (sCJD) involves all areas of neocortex with similar frequency, except for primary sensorimotor cortex (Rolandic cortex) and visual cortex. Rolandic cortex often appears to be spared even in the presence of extensive surrounding neocortical signal intensity abnormality in adjacent frontal and parietal gray matter. A quantitative apparent diffusion coefficient (ADC) analysis was designed to investigate whether this unusual pattern results from pathophysiologic sparing of Rolandic cortex or from reduced conspicuity of signal intensity abnormality on MR imaging echo-planar diffusion-weighted images (epiDWI) related to unknown underlying features of Rolandic cortex. METHODS: ADC maps were derived from epiDWI of 6 patients with sCJD and 8 control patients. Bilateral regions of interest were manually selected in precentral gyri, superior frontal gyri, postcentral gyri, supramarginal gyri, thalamus, putamen, and caudate nuclei. ADC and relative ADC (rADC) values were calculated for each region of interest. RESULTS: Patients with CJD had significantly lower ADC values than control patients in all areas (P < or = 0.05). The trend toward decreased ADC values in the deep nuclei correlates well with previously published reports. rADC were not significantly different between CJD and control groups in any area (P > 0.25 in all cases). CONCLUSION: Quantitative ADC measurements in patients with early sCJD demonstrate a similar degree of reduced water diffusivity in the primary somatosensory cortex as in other neocortical areas, despite the normal appearance of these areas on visual inspection of epiDWI.

MR imaging of human herpesvirus-6-associated encephalitis in 4 patients with anterograde amnesia after allogeneic hematopoietic stem-cell transplantation.

MR imaging is typically obtained during the work-up of patients who have undergone allogeneic hematopoietic stem-cell transplant who present with unexplained change in mental status, amnesia, or seizures. Although the differential diagnosis is broad in this setting, the presence of T2 prolongation limited to the medial aspect of one or both temporal lobes with or without associated reduced water diffusion may help limit the possible diagnoses. A frequent etiology seen in this context is human herpesvirus-6 (HHV6) infection. We report the evolution of MR imaging findings and clinical course in 4 patients with limbic encephalitis probably related to HHV6.

Utility of esophageal biopsy in the diagnosis of nonerosive reflux disease.

This study evaluated the accuracy of esophageal biopsy for the diagnosis of nonerosive reflux disease (NERD) in adults. Thirty-five patients with reflux symptoms and a normal endoscopy were prospectively evaluated using esophageal biopsies, 24-h ambulatory pH monitoring and symptomatic response 4 weeks after an increase in antireflux therapy. Biopsies were scored for the total number of typical histologic reflux features seen. Patients were considered to have NERD if both pH-metry was positive and step-up therapy was successful. Biopsies were then compared to this predefined gold standard. Biopsy was most sensitive (62%) but poorly specific (27%) when one or more histologic reflux features were seen. A threshold of three or more histologic features improved the specificity (91%) but reduced sensitivity (31%). Response to step-up therapy was associated with 100% sensitivity and 100% negative predictive value when compared to biopsy and pH-metry as an alternate combined gold standard. In conclusion, biopsy is insensitive in diagnosing NERD but reasonably specific if three or more typical histologic reflux features are present.

Urologic applications of the holmium laser.

The holmium laser has various urologic applications. It is important for urologic nurses and associates to be familiar with the laser physics and safety recommendations of the holmium laser, as well as to understand the applications and surgical techniques associated with this therapy.

Felinization of the esophagus.

Transient transverse folds of the esophageal mucosa as seen by barium esophagography and on endoscopic examination have been termed "felinization." This finding has been considered a normal variant or has been associated with reflux esophagitis. No symptoms have been associated with its presence. In 280 unselected patients undergoing upper gastrointestinal endoscopy in our clinic, felinization was identified in 24% by prospective visual examination. It was not correlated with sex, age, symptom complex, or common coexistent endoscopic findings. These transverse esophageal folds, although visually interesting, appear to have no clinical significance. The endoscopist should recognize and differentiate them from fixed or persistent folds that can be associated with mucosal disease.

Lung transplantation in Louisiana: report of the first twenty lung transplants performed in the state.

Lung transplantation is a successful alternative treatment for a variety of end-stage lung diseases. The first 20 lung transplants performed in Louisiana between November 1990 and July 1994 are reported from Ochsner Foundation Hospital. Transplant procedures included 1 heart-lung, 11 bilateral sequential lung, and 8 single-lung transplants in 8 males and 11 females (1 retransplantation). The average age was 38 years (range 7-60), and the median waiting time was 34.5 days (range 1-329). Indications for transplant included emphysema, pulmonary fibrosis, pulmonary hypertension, cystic fibrosis, bronchiectasis, and bronchiolitis obliterans. Overall 1-year and 3-year survival were 65.0% and 58.5%, respectively. Infection was the major cause of morbidity and mortality. Rejection episodes were observed but treated successfully in all 20 patients. Lung transplantation has proved to be a successful treatment for a variety of severely limiting and terminal pulmonary conditions for patients in our state.

Characterization of solubilized bradykinin B2 receptors from smooth muscle and mucosa of guinea pig ileum.

Bradykinin (BK) B2 receptors in guinea pig ileum were characterized in both membrane and soluble form. [3H]BK bound to a single class of sites with almost identical affinities in membranes prepared from the longitudinal muscle, circular muscle and mucosal layers of the ileum. The pharmacology of the binding in the distinct layers was indistinguishable. The detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS) maximally solubilized nearly 80% of membrane binding activity in a very stable conformation. In soluble preparations, [3H]BK labeled a single class of sites but with about 10-fold lower affinity. The affinities of BK analogs in competition studies were similarly reduced. There was no difference in the pharmacology of the binding in soluble receptors prepared from the different layers of the ileum. The results show that the ileum is a good source of solubilized B2 receptors and that the receptors in the smooth muscle and the mucosa are very similar.

Cloning and pharmacological characterization of a human bradykinin (BK-2) receptor.

A human BK-2 bradykinin receptor was cloned from the lung fibroblast cell line CCD-16Lu. The cDNA clone encodes a 364 amino acid protein that has the characteristics of a seven transmembrane domain G-protein coupled receptor. The predicted amino acid sequence of the human BK-2 receptor is 81% identical to the smooth muscle rat BK-2 receptor (1). Transfection of the human BK-2 receptor cDNA into COS-7 cells results in the expression of high levels of specific BK binding sites. Saturation binding analysis indicates that the human BK-2 receptor expressed in COS-7 cells binds BK with a KD of 0.13 nM. Pharmacological characterization of the expressed BK receptor is consistent with the cDNA encoding a receptor of the BK-2 subtype. The BK-2 receptor antagonist Hoe 140 (2), D-Arg0[Hyp3, Thi5, D-Tic7, Oic8]BK has a high affinity (IC50 = 65 pM) for the cloned human receptor. The tissue distribution of the human BK-2 receptor was analyzed by competitive PCR with human tissue cDNA and is similar to that determined for the BK-2 receptor in the rat.