Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Comparison of metaiodobenzylguanidine scintigraphy with positron emission tomography in the diagnostic work-up of pheochromocytoma and paraganglioma: a systematic review.

AIM: The aim of this paper was to systematically review published data about the comparison of radiolabelled metaiodobenzylguanidine (MIBG) scintigraphy and positron emission tomography (PET) with different radiopharmaceuticals in patients with pheochromocytoma and paraganglioma (Pheo/PGL). METHODS: A comprehensive literature search of studies published in PubMed/MEDLINE and Embase databases through September 2012 and regarding MIBG scintigraphy and PET imaging with different radiopharmaceuticals in patients with Pheo/PGL was carried out. RESULTS: Twenty-eight studies comprising 852 patients who underwent both MIBG scintigraphy and PET or PET/CT with different radiopharmaceuticals were included and discussed. Three studies evaluated carbon-11-hydroxyephedrine ([11C]HED) as PET radiopharmaceutical, nine studies fluorine-18-dopamine ([18F]DA), eight studies fluorine-18-dihydroxyphenylalanine ([18F]DOPA), twelve studies fluorine-18-fluorodeoxyglucose ([18F]FDG) and five studies gallium-68-somatostatin analogues. CONCLUSIONS: Despite the heterogeneity of the studies included in the analysis, it can be concluded that the diagnostic performance of PET with various agents is clearly superior to that of MIBG scintigraphy in patients with Pheo/PGL, mainly for familial, extra-adrenal and metastatic diseases; however, MIBG maintains a unique role in selecting patients suitable for 131I-MBG therapy. Further larger prospective studies comparing MIBG and different PET tracers in patients with Pheo/PGL as well as a cost-effectiveness analysis of the two techniques are needed.

Role of (18)F-FDG PET-CT in head and neck squamous cell carcinoma.

The role of PET-CT imaging in head and neck squamous cell carcinoma during pre-treatment staging, radiotherapy planning, treatment response assessment and post-therapy follow-up is reviewed with focus on current evidence, controversial issues and future clinical applications. In staging, the role of (18)F-FDG PET-CT is well recognized for detecting cervical nodal involvement as well as for exclusion of distant metastases and synchronous primary tumours. In the evaluation of treatment response, the high negative predictive value of (18)F-FDG PET-CT performed at least 8 weeks from the end of radio-chemotherapy allows prevention of unnecessary diagnostic invasive procedures and neck dissection in many patients, with a significant impact on clinical outcome. On the other hand, in this setting, the low positive predictive value due to possible post-radiation inflammation findings requires special care before making a clinical decision. Controversial data are currently available on the role of PET imaging during the course of radio-chemotherapy. The prognostic role of (18)F-FDG PET-CT imaging in head and neck squamous cell carcinoma is recently emerging, in addition to the utility of this technique in evaluation of the tumour volume for planning radiation therapy. Additionally, new PET radiopharmaceuticals could provide considerable information on specific tumour characteristics, thus overcoming the limitations of (18)F-FDG.

Impact of non-linear smoking effects on the identification of gene-by-smoking interactions in COPD genetics studies.

BACKGROUND: The identification of gene-by-environment interactions is important for understanding the genetic basis of chronic obstructive pulmonary disease (COPD). Many COPD genetic association analyses assume a linear relationship between pack-years of smoking exposure and forced expiratory volume in 1 s (FEV(1)); however, this assumption has not been evaluated empirically in cohorts with a wide spectrum of COPD severity. METHODS: The relationship between FEV(1) and pack-years of smoking exposure was examined in four large cohorts assembled for the purpose of identifying genetic associations with COPD. Using data from the Alpha-1 Antitrypsin Genetic Modifiers Study, the accuracy and power of two different approaches to model smoking were compared by performing a simulation study of a genetic variant with a range of gene-by-smoking interaction effects. RESULTS: Non-linear relationships between smoking and FEV(1) were identified in the four cohorts. It was found that, in most situations where the relationship between pack-years and FEV(1) is non-linear, a piecewise linear approach to model smoking and gene-by-smoking interactions is preferable to the commonly used total pack-years approach. The piecewise linear approach was applied to a genetic association analysis of the PI*Z allele in the Norway Case-Control cohort and a potential PI*Z-by-smoking interaction was identified (p=0.03 for FEV(1) analysis, p=0.01 for COPD susceptibility analysis). CONCLUSION: In study samples of subjects with a wide range of COPD severity, a non-linear relationship between pack-years of smoking and FEV(1) is likely. In this setting, approaches that account for this non-linearity can be more powerful and less biased than the more common approach of using total pack-years to model the smoking effect.

An unusual case of adrenal metastasis from colorectal cancer: computed tomography and fluorine 18-fluoro-deoxy-glucose positron emission tomography-computed tomography features and literature review.

Incidentally discovered adrenal masses are a common diagnostic problem. While computed tomography (CT) and magnetic resonance (MR) imaging can adequately characterize most benign or malignant adrenal masses, in some cases the results are indeterminate. We report and discuss a case of an adrenal metastasis with misleading clinical and CT features, in which an abnormal metabolic uptake detected through fluorine 18-fluoro-deoxy-glucose positron emission tomography ((18)F-FDG PET)-CT raised the suspicion of adrenal metastasis relatively early compared with apparently normal results on repeated follow-up CT examinations.

Development of predictive models for airflow obstruction in alpha-1-antitrypsin deficiency.

Alpha-1-antitrypsin deficiency is a genetic condition associated with severe, early-onset chronic obstructive pulmonary disease (COPD). However, there is significant variability in lung function impairment among persons with the protease inhibitor ZZ genotype. Early identification of persons at highest risk of developing lung disease could be beneficial in guiding monitoring and treatment decisions. Using a multicenter, family-based study sample (2002-2005) of 372 persons with the protease inhibitor ZZ genotype, the authors developed prediction models for forced expiratory volume in 1 second (FEV(1)) and the presence of severe COPD using demographic, clinical, and genetic variables. Half of the data sample was used for model development, and the other half was used for model validation. In the training sample, variables found to be predictive of both FEV(1) and severe COPD were age, sex, pack-years of smoking, bronchodilator responsiveness, chronic bronchitis symptoms, and index case status. In the validation sample, the predictive model for FEV(1) explained 50% of the variance in FEV(1), and the model for severe COPD exhibited excellent discrimination (c statistic = 0.88).

Pharyngocutaneous fistula onset after total laryngectomy: scintigraphic analysis.

Pharyngocutaneous fistula is the most common non-fatal complication following total laryngectomy. To start oral feeding and exclude the presence of a pharyngocutaneous fistula, a subjective test and instrumental assessments using videofluoroscopy, have been described. The aim of this study was to evaluate the effectiveness of oral-pharyngo-oesophageal scintigraphy as an objective and non-invasive tool to establish presence, site and dimensions of the fistula. Observations were performed on 3 male patients, mean age 65 years, who underwent total laryngectomy and mono or bilateral neck dissection after failure of radiotherapy in 2 cases and of conservative laryngeal surgery in the third case, complicated by post-operative pharyngocutaneous fistula. Oral-pharyngo-oesophageal scintigraphy dynamic study with sequential images were obtained during the swallowing phases. In case 1, the test showed a wide pharyngocutaneous fistula the internal orifice of which was at the level of the base of the tongue: on the scintigraphic images, the radiomarked water bolus, from the fistulous orifice, descended along the stoma walls and only a small part reached the oesophagus. In the other two patients, the pharyngocutaneous fistula was small and the internal fistulous orifice was detected in the lower part of T-suture line. In conclusion, scintigraphy offered the possibility to precisely identify presence of pharyngocutaneous fistula and location of its internal orifice and to monitor its spontaneous closure. Therefore, important information could be obtained regarding the suture line status and the possibility of deciding whether to remove the nasogastric tube or to leave it in place. Finally, these data showed that oral-pharyngo-oesophageal scintigraphy could be performed in the early post-operative period to optimize starting safe oral feeding.

Impact of 111In-DTPA-octreotide SPECT/CT fusion images in the management of neuroendocrine tumours.

PURPOSE: Somatostatin receptor scintigraphy with [(111)In]-diethylene triamine pentaacetate acid (DTPA)-octreotide is an accurate method for detecting neuroendocrine tumours (NETs) but often does not provide clear anatomical localisation of lesions. The aim of this study was to assess the clinical usefulness of anatomical-functional image fusion. MATERIALS AND METHODS: Fifty-four patients with known or suspected NET were included in the study. Planar and single-photon-emission computed tomography (SPECT) imaging was performed using a dual-head gamma camera equipped with an integrated X-ray transmission system, and the images were first interpreted alone by two nuclear medicine physicians and then compared with SPECT/CT fusion images together with a radiologist. The improvement provided by SPECT/CT in the interpretation of SPECT data alone and any modification in patient management were recorded. RESULTS: Fusion images improved SPECT interpretation in 23 cases, providing precise anatomical localisation of increased tracer uptake in 20 cases and disease exclusion in sites of physiological uptake in 5. In 10 patients, SPECT/CT allowed definition of the functional significance of lesions detected by diagnostic CT. SPECT/CT data modified clinical management in 14 cases by changing the diagnostic approach in 8 and the therapeutic modality in 6. CONCLUSIONS: Our study demonstrates that image fusion is clearly superior to SPECT alone, allowing precise localisation of lesions and reducing false-positive results.

Clinical significance of focal and diffuse thyroid diseases identified by (18)F-fluorodeoxyglucose positron emission tomography.

(18)F-Fluorodeoxyglucose positron emission tomography (FDG-PET) thyroid incidentalomas are defined abnormal FDG uptake in the thyroid gland found at PET scan performed as part of a staging protocol and follow-up of patients with various kinds of malignancies. In the present study we report two cases of FDG PET thyroid incidentalomas, and review the literature with regard to the meaning of this new category of thyroid "disease". Since the advent of whole body FDG PET scan, a relatively high incidence of cases of thyroid FDG uptake has been reported as an incidental finding as in one of our patient. Focal uptake was found to be more likely associated to a malignant lesion, while a diffuse thyroid uptake to a benign thyroid disease. However, differential diagnosis is difficult, and reported data in literature are somewhat discordant. A focal thyroid uptake of FDG incidentally discovered at PET scan cannot be invariably considered a malignant thyroid nodule, however a prompt and complete work-up including laboratory examinations, ultrasonography and fine needle aspiration cytology, should be obtained to exclude a thyroid carcinoma. On the other hand, patients with a PET finding of diffuse FDG uptake can be considered at low risk of malignancy, being more likely associated to chronic thyroiditis or diffuse thyroid autonomy.

Evaluation of the surgical completeness after total thyroidectomy for differentiated thyroid carcinoma.

BACKGROUND: To quantify the rate of patients without thyroid remnants, to identify predictive factors for the absence of residual thyroid tissue and to evaluate number, site, size and function of thyroid remnants after total thyroidectomy for differentiated thyroid carcinoma (DTC). METHODS: Thousand one hundred and seventy-eight patients who underwent total thyroidectomy for DTC were evaluated; 343 patients with lymph node or distant metastases and 115 patients with detectable thyroglobulin autoantibodies (TgAb) were excluded. (131)I ablative treatment (RAI) without preliminary diagnostic (131)I whole body scans (DxWBS), and 24-h (131)I quantitative neck uptake (RAIU test) and thyroglobulin (Tg) off L-T4 evaluation were performed in the remaining 720 pts. In 252 patients a 99mTc-pertechnetate pre-operative thyroid scan (99mTc-scan) was used for comparison with (131)I neck scans after RAI to evaluate site of thyroid remnants. Only patients with thyroid remnants were evaluated for successful ablation 6-10 months after RAI. RESULTS: Post-treatment whole body scan (TxWBS) demonstrated lack of thyroid remnants in 50/720 patients and the best predictive factors for the absence of residual thyroid tissue were RAIU <1% and undetectable Tg off L-T4. Thyroid remnants were present in 670/720 patients. In 252 patients with (99m)Tc-scan, 617 sites of functioning thyroid tissue were found: 381 within and 236 outside the thyroid bed. Complete successful ablation was achieved in 610/670 patients with thyroid remnants. CONCLUSIONS: This study confirms that most patients (93.1%) have thyroid remnant after total thyroidectomy for DTC. Most thyroid remnants were contralateral to tumour site and were even observed outside thyroid bed. However, a real total thyroidectomy, demonstrated by negative TxWBS, RAIU <1% and undetectable Tg off L-T4, was achieved in 6.9% of patients.

Prevalence of home artificial nutrition in Italy in 2005: a survey by the Italian Society for Parenteral and Enteral Nutrition (SINPE).

AIM: To determine the prevalence (cases per million inhabitants) of home artificial nutrition (HAN), enteral (HEN) and parenteral (HPN), in Italy, grouped according to administrative regions, patient age and primary disease, and to analyze the impact both of the presence of an HAN regional regulation and of demographic characteristics. METHODS: In April 2005, the Regional Coordinators of the Italian Society for Parenteral and Enteral Nutrition (SINPE) recorded all the ongoing cases of HAN using a structured questionnaire and were asked to estimate the representativeness of the collected sample with respect to the total expected HAN. RESULTS: A total of 6955 cases of HAN (93.5% adults, 6.5% pediatric patients < or = 18 years) were recorded in 16 of the 20 Italian regions (80% of the Italian population; sample representativeness 78%). HAN prevalence 152.6 (83.9% HEN, 16.1% HPN); the HAN range among the regions was: prevalence 28.1-519.8; oncological disease 13.8-75.7%, neurological disease 15.5-79.9%, intestinal failure 1.3-14.0%. An HAN regulation was present in 11 regions. A positive association (P=0.012) was found between the number of years since the regulation was issued and the HAN prevalence, and also between the % neurological patients and the population density (P=0.130) and the % inhabitants > or = 75 years (P=0.040). CONCLUSIONS: The need for HAN regards a great number of patients throughout the country; there are substantial differences between the regions with respect to both the prevalence and the use of HAN in various disease categories. A specific regulation may favor the development of HAN.

Calcitriol plus hydrochlorothiazide prevents transient post-thyroidectomy hypocalcemia.

BACKGROUND: The aim of our double-blinded randomized prospective placebo-controlled study was to test if a week long pre-treatment with hypercalcemic drugs may prevent transient post-thyroidectomy hypocalcemia and reduce hospital stay. METHODS: Forty-two patients undergoing total thyroidectomy were randomized into two groups. Group 1: 22 patients treated with calcitriol 1.5 mcg/die plus hydrochlorothiazide; Group 2: 20 patients only treated with placebo (mineral integrates) as control group. Calcium and PTHi serum levels were assayed baseline and the days before and after thyroidectomy. RESULTS: Baseline calcium and PTHi did not differ between the two groups. Pre-surgery calcemia significantly increased in group 1 (p<0.05) while PTHi significantly decreased (p<0.05). Post-surgery calcemia and PTHi further significantly decreased in both groups, hypocalcemia (<2.10 mmol/l) occurring in 1 out of 22 patients in group 1 without symptoms and in 10 out of 20 in controls (20% developing symptoms) (p<0.01). The hospital stay resulted significantly shorter in group 1 (2.4+/-0.6 days) in respect to the control group (3.6+/-1.4 days, p<0.05). CONCLUSION: The administration of calcitriol plus hydrochlorothiazide is able to prevent transient post-thyroidectomy hypocalcemia and to reduce hospital stay.

Prevalence of HCV antibodies in autoimmune thyroid disease.

BACKGROUND AND OBJECTIVES: Auto-immune thyroid disease (AITD) has often been reported during interferon-alpha therapy for chronic viral C hepatitis (HCV) or other diseases. Recently, a high AITD prevalence has been reported in HCV independently on alpha-interferon therapy. The aim of our study is to investigate the possible relationship between AITD and HCV and HBV virus infections, and their influence on the thyroid function. MATERIAL AND METHODS: We prospectively studied 112 patients with AITD (94 women and 18 men; mean age: 49.8 +/- 14.9 yrs) and 88 patients with non-toxic goitre (NTG) (73 women and 15 men; mean age: 50.2 +/- 13.5 yrs) as controls. In all patients HCV antibodies, HBsAg and anti-HBs antibodies, TSH, FT3 and FT4 serum levels, circulating anti-thyroid-peroxidase antibodies (TPO-Ab) and anti-thyroglobulin antibodies (TG-Ab) were measured. RESULTS: HCV antibodies were positive in 11.6% of AITD patients (13/112) and in 2.3% of controls (2/88) (P < 0.05), the prevalence of HCV in the controls being similar to the expected value in the general population (about 2%). HBsAg and anti-HBs were found only in 2.6% of AITD patients (3/112) and 1.1% of controls (1/88) (P = NS), according to the expected value in the general population (about 2.5%). No difference in thyroid function was observed between positive and negative HCV subgroups. CONCLUSION: A significant association between HCV infection and AITD was found. This finding confirms that HCV, but not HBV, could be one of the environmental factors responsible for the breakdown of immunological tolerance. Therefore detection of TPO-Ab and TG-Ab in all HCV patients, independently of IFN therapy, is suggested and the utility of a screening for HCV in all AITD patients is stressed.

Cognitive dysfunction in patients with obstructive sleep apnea (OSA): partial reversibility after continuous positive airway pressure (CPAP).

The aims of this study were to assess cognitive function in obstructive sleep apnea (OSA) patients and to evaluate the effect of short- and long-term treatment with continuous positive airway pressure treatment (CPAP). A battery of neuropsychological tests, the Epworth Sleepiness Scale (ESS), and the Beck Inventory Scale were administered to 23 patients with severe OSA (age: 56.5+/-6.13; AHI: 54.9+/-13.37) and to 23 age- and education-matched controls. The OSA patients were evaluated in a baseline condition and in two follow-up treatment sessions (after 15 days and 4 months of CPAP, respectively). At baseline, OSA patients had a significant impairment, compared to controls, in tests of sustained attention, visuospatial learning, executive function, motor performance, and constructional abilities. The longitudinal evaluation showed that after a 15-days CPAP treatment attentive, visuospatial learning, and motor performances returned to normal levels. A 4-months CPAP treatment did not result in any further improvement in cognitive tests. Performance on tests evaluating executive functions and constructional abilities was not affected by short- and long-term treatment with CPAP. The findings of this study confirm the hypothesis of partial reversibility of cognitive dysfunction in OSA patients after CPAP.

Prospective evaluation of the clinical usefulness of an antigen-specific assay (MAIPA) in idiopathic thrombocytopenic purpura and other immune thrombocytopenias.

The diagnosis of idiopathic immune thrombocytopenia remains a clinical diagnosis based on the exclusion of other causes of immune and nonimmune thrombocytopenia. Measurement of platelet-associated Ig (PAIg), while sensitive, is nonspecific for the diagnosis of immune thrombocytopenia. Published experience of antigen capture assays (including monoclonal antibody immobilization of platelet antigens or MAIPA) suggest a high sensitivity and specificity (70% to 80%) in selected groups of patients. In a prospective evaluation of 158 patients with thrombocytopenia from all causes, we report a sensitivity of 51% and specificity of 80% for direct MAIPA assays. MAIPA was considerably better in discriminating immune from nonimmune thrombocytopenia than two assays of PAIgG. Antiplatelet antibodies detected by MAIPA were more frequently directed against the glycoprotein (GP) IIb/IIIa than the GP Ib/IX complex. Our experience suggests that MAIPA assays are useful in the laboratory assessment of thrombocytopenia, should be performed before therapy, and that some patients with 'nonimmune' thrombocytopenia may have genuine antiplatelet antibodies.

The molecular mechanism of platelet adhesion.

One of the most primitive of host-defence mechanisms is haemostasis, the ability to control blood loss. In response to vascular trauma, platelets rapidly adhere to the exposed subendothelial matrix, a process that ultimately results in the sealing of the vessel by a plug of platelets stabilised by fibrin. Paradoxically, it is the same cascade of events that leads to thrombosis and vessel occlusion, resulting in heart attack and stroke. The molecular events involved in platelet adhesion have therefore been the subject of intense investigation. In all but the largest blood vessels, the initial contact adhesion of platelets is mediated by subendothelial matrix bound von Willebrand Factor (vWF) and a specific vWF receptor on platelets, the glycoprotein (GP) Ib-V-IX complex. Our understanding of this process arose from analysis of two congenital bleeding disorders, von Willebrand's disease and the Bernard-Soulier syndrome, in which vWF or the GP Ib-V-IX, respectively, are either absent or dysfunctional. This overview discusses our current molecular understanding of platelet adhesion and how engagement of vWF by the GP Ib-V-IX complex on platelets initiates the subsequent events in platelet activation leading to either haemostasis or thrombosis.

A comparison among different inversion methods for multi-exponential NMR relaxation data.

The inversion of data to be represented by sums or continuous distributions of exponentials is done by different algorithms and compared. The published CONTIN program presents a chosen solution with an appropriate amount of detail. An in-house program EXDISTR allows operative choice of various constraints in order to show the consequences in quality of fit of allowing various features such as extra maxima or minima. Another in-house program based on the system theory approach, IDENT, treats the data as the output samples of a linear, time-invariant, autonomous dynamic system.