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1.
Bone Rep ; 15: 101151, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34926730

ABSTRACT

Two cases of advanced alkaptonuria (AKU) with co-existing osteoporosis are described. Case 1 developed multiple non-vertebral fragility fractures, while Case 2 developed vertebral fragility fractures, both refractory to bisphosphonates. Difficulties in diagnosing osteoporosis in AKU complicated by extensive calcifying and ossifying spondylosis are discussed. Both patients continued to fracture despite nitisinone therapy for metabolic control of AKU, as well as bisphosphonate antiresorptive therapy for osteoporosis. Subsequently the patients were treated with teriparatide 20 µg subcutaneous injections daily for two years, leading to reduction in fractures soon after commencing therapy in both cases. Markers of bone remodelling P1NP and CTX were stimulated. No complications due hypercalcaemia or calcification were encountered in either case. We conclude that teriparatide is an effective adjunct in the treatment of AKU when bisphosphonates prove ineffective.

2.
Osteoporos Int ; 32(5): 927-938, 2021 May.
Article in English | MEDLINE | ID: mdl-33118050

ABSTRACT

Osteoporosis and fractures are common features of alkaptonuria. INTRODUCTION: A large cohort of alkaptonuria (AKU) patients was studied to better recognise and characterise osteoporosis and fractures in AKU. METHODS: Assessments including questionnaire analysis, DEXA and CT densitometry at the neck of femur (FN), total hip (TH) and lumbar spine (LS) were performed on patients at baseline when 2 mg nitisinone was commenced, and yearly thereafter. Blood and urine samples were collected for chemical measurement. CT BMD Z-scores were generated. RESULTS: Between June 2007 and March 2020, 87 AKU patients attended the NAC. At baseline, there were 48 fractures in 39 patients. Prevalence of osteoporosis was 3.1 at FN, 10.8 at TH and 24.7% at LS respectively. Prevalence of fragility fractures was greatly increased at 44.8%. The group with fractures showed increased ochronosis scores (p < 0.05). CT LS showed an inverse relationship with fractures (R = - 0.28; p < 0.05). CT LS was significantly lower in the fracture group (p < 0.002). Following nitisinone only, CT FN and CT TH decreased significantly (p < 0.05 and 0.01 respectively). Following nitisinone plus antiresorptive therapy, CT FN, CT TH and CT LS all increased significantly (p < 0.05, 0.05 and 0.001 respectively). However, patients on nitisinone plus antiresorptive had more fractures than nitisinone and no-treatment groups (p < 0.05). CONCLUSIONS: Osteopenia and fragility fractures are common in AKU.. Anti-resorptive therapy increased BMD in AKU without decreasing fragility fractures. Bone densitometry measurements by DXA are less reliable than quantitative CT at the LS in AKU.


Subject(s)
Alkaptonuria , Fractures, Bone , Osteoporosis , Alkaptonuria/complications , Alkaptonuria/diagnosis , Alkaptonuria/drug therapy , Bone Density , Data Analysis , Humans , Osteoporosis/diagnosis , Osteoporosis/drug therapy , Osteoporosis/epidemiology , United Kingdom
6.
J Oncol Pharm Pract ; 25(8): 1897-1906, 2019 Dec.
Article in English | MEDLINE | ID: mdl-30823852

ABSTRACT

PURPOSE: Existing studies evaluating patient adherence to oral targeted therapies such as tyrosine kinase inhibitors focus on small populations with single malignancies. This study evaluated patterns of use of oral agents in a larger population across multiple hematologic malignancies. METHODS: Adult patients diagnosed with a hematologic malignancy and prescribed oral targeted therapy between 2011 and 2016 (N = 18,976) were identified from the MarketScan Commercial Claims and Encounters, and Medicare Supplemental databases. Eligible patients were enrolled in monthly prescription plans 6 months before and 12 months after the index date (date of first prescription claim; n = 2442). Multivariable logistic regressions were used to determine predictors of adherence using the medication possession ratio (MPR) and persistence through prescription refill gaps. RESULTS: The overall median adherence was 0.9 (MPR ≥ 80%) and was comparable between once-daily (QD) and twice-daily (BID) groups. Overall, 59% of patients were persistent at 12 months. Patients on QD and BID products did not have any significant differences in adherence (fixed-interval MPR, odds ratio 0.94; 95% confidence interval (CI), 0.75-1.18) or persistence (odds ratio 0.93; 95% CI, 0.75-1.17) 12 months from index. Significant predictors of adherence and persistence included patient age, total inpatient admissions, number of adverse events, and total hospital visits. CONCLUSION: Patient-specific clinical factors, rather than regimen-specific factors, were the main predictors of oral targeted therapy adherence and persistence. Adherence to oral targeted therapies appears to be similar for patients on QD and BID regimens in the real-world setting.


Subject(s)
Antineoplastic Agents/administration & dosage , Hematologic Neoplasms/drug therapy , Medication Adherence , Molecular Targeted Therapy , Administration, Oral , Adolescent , Adult , Aged , Cohort Studies , Databases, Factual , Drug Administration Schedule , Female , Humans , Male , Managed Care Programs , Middle Aged , Retrospective Studies , Young Adult
7.
Data Brief ; 20: 1620-1628, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30263914

ABSTRACT

Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots.

8.
Med J Malaysia ; 73(3): 141-146, 2018 06.
Article in English | MEDLINE | ID: mdl-29962497

ABSTRACT

BACKGROUND: Imaging such as Tc99m-HMPAO single photon emission computed tomography (SPECT), and positron emission tomography/ computed tomography (PET/CT) amyloid scans are used to aid the diagnosis of Alzheimer's disease (AD). OBJECTIVE: We aimed to correlate the ability of these modalities to differentiate Probable AD and Possible AD using the clinical diagnosis as a gold standard. We also investigated the correlation of severity of amyloid deposit in the brain with the diagnosis of AD. METHODS: A retrospective study of 47 subjects (17 Probable AD and 30 Possible AD) who were referred for PET/CT amyloid scans to our centre was conducted. Hypoperfusion in the temporo-parietal lobes on Tc99m-HMPAO SPECT and loss of grey-white matter contrast in cortical regions on PET/CT Amyloid scans indicating the presence of amyloid ß deposit were qualitatively interpreted as positive for AD. SPECT and PET/CT were also read in combination (Combo reading). The severity of amyloid ß deposit was semiquantitatively assessed in a visual binary method using a scale of Grade 0-4. The severity of amyloid ß deposit was assessed in a visual binary method and a semi-quantitative method using a scale of Grade 0-4. RESULTS: There was significant correlation of Tc99m-HMPAO SPECT, PET/CT amyloid findings and Combo reading with AD. The sensitivity, specificity, PPV and NPV were 87.5%, 73.7%, 58.3% and 93.3% (SPECT); 62.5%, 77.4%, 58.8% and 80.0% (PET/CT) and 87.5%, 84.2%, 70.0% and 30.0% (Combo reading) respectively. The grade of amyloid deposition was not significantly correlated with AD (Spearman's correlation, p=0.687). CONCLUSION: There is an incremental benefit in utilizing PET/CT amyloid imaging in cases with atypical presentation and indeterminate findings on conventional imaging of Alzheimer's disease.


Subject(s)
Alzheimer Disease/diagnostic imaging , Brain/diagnostic imaging , Adult , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Amyloid beta-Peptides/metabolism , Female , Humans , Male , Middle Aged , Neuroimaging , Positron-Emission Tomography , Retrospective Studies , Technetium Tc 99m Exametazime , Tomography, Emission-Computed, Single-Photon
9.
Mol Genet Metab ; 125(1-2): 127-134, 2018 09.
Article in English | MEDLINE | ID: mdl-30055994

ABSTRACT

QUESTION: Does Nitisinone prevent the clinical progression of the Alkaptonuria? FINDINGS: In this observational study on 39 patients, 2 mg of daily nitisinone inhibited ochronosis and significantly slowed the progression of AKU over a three-year period. MEANING: Nitisinone is a beneficial therapy in Alkaptonuria. BACKGROUND: Nitisinone decreases homogentisic acid (HGA), but has not been shown to modify progression of Alkaptonuria (AKU). METHODS: Thirty-nine AKU patients attended the National AKU Centre (NAC) in Liverpool for assessments and treatment. Nitisinone was commenced at V1 or baseline. Thirty nine, 34 and 22 AKU patients completed 1, 2 and 3 years of monitoring respectively (V2, V3 and V4) in the VAR group. Seventeen patients also attended a pre-baseline visit (V0) in the VAR group. Within the 39 patients, a subgroup of the same ten patients attended V0, V1, V2, V3 and V4 visits constituting the SAME Group. Severity of AKU was assessed by calculation of the AKU Severity Score Index (AKUSSI) allowing comparison between the pre-nitisinone and the nitisinone treatment phases. RESULTS: The ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, in the SAME group, was significantly lower at two (0.32 ±â€¯0.19) and three (0.15 ±â€¯0.13) years post-nitisinone when compared to pre-nitisinone (0.65 ±â€¯0.15) (p < .01 for both comparisons). Similarly, the ALL AKUSSI rate of change of scores/patient/month, in the VAR group, was significantly lower at one (0.16 ±â€¯0.08) and three (0.19 ±â€¯0.06) years post-nitisinone when compared to pre-nitisinone (0.59 ±â€¯0.13) (p < .01 for both comparisons). Combined ear and ocular ochronosis rate of change of scores/patient/month was significantly lower at one, two and three year's post-nitisinone in both VAR and SAME groups compared with pre-nitisinone (p < .05). CONCLUSION: This is the first indication that a 2 mg dose of nitisinone slows down the clinical progression of AKU. Combined ocular and ear ochronosis progression was arrested by nitisinone.


Subject(s)
Alkaptonuria/drug therapy , Cyclohexanones/administration & dosage , Nitrobenzoates/administration & dosage , Ochronosis/drug therapy , 4-Hydroxyphenylpyruvate Dioxygenase/metabolism , Alkaptonuria/epidemiology , Alkaptonuria/metabolism , Alkaptonuria/pathology , Disease Progression , Female , Homogentisic Acid/metabolism , Humans , Male , Middle Aged , Ochronosis/epidemiology , Ochronosis/metabolism , Ochronosis/pathology , United Kingdom
10.
Radiography (Lond) ; 23(3): 191-196, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28687285

ABSTRACT

PURPOSE: Two types of CT images (modalities) are acquired in PET/CT: for attenuation correction (AC) and diagnosis. The purpose of the study was to compare nodule detection and localization performance between these two modalities. METHODS: CT images, using both modalities, of an anthropomorphic chest phantom containing zero or more simulated spherical nodules of 5, 8, 10 and 12 mm diameters and contrasts -800, -630 and 100 HU were acquired. An observer performance study using nine observers interpreting 45 normal (zero nodules) images and 47 abnormal images (1-3 nodules; average 1.26) was conducted using the free-response receiver operating characteristic (FROC) paradigm. Data were analysed using an R software package implemented jackknife alternative FROC (JAFROC) analysis. Both empirical areas under the equally weighted AFROC curve (wAFROC) and under the highest rating inferred ROC (HR-ROC) curve were used as figures of merit (FOM). To control the probability of Type I error test alpha was set at 0.05. RESULTS: Nodule detection as measured by either FOM was significantly better on the diagnostic quality images (2nd modality), irrespective of the method of analysis, [reader averaged inter-modality wAFROC FOM difference = -0.07 (-0.11,-0.04); reader averaged inter-modality HR-ROC FOM difference = -0.05 (-0.09, -0.01)]. CONCLUSION: Nodule detection was statistically worse on images acquired for AC; suggesting that images acquired for AC should not be used to evaluate pulmonary pathology.


Subject(s)
Positron Emission Tomography Computed Tomography/methods , Radiography, Thoracic/methods , Solitary Pulmonary Nodule/diagnostic imaging , Humans , Phantoms, Imaging
11.
Br J Cancer ; 108(7): 1440-8, 2013 Apr 16.
Article in English | MEDLINE | ID: mdl-23492685

ABSTRACT

BACKGROUND: Peptide receptor radionuclide therapy (PRRT) is an established treatment for patients with metastatic neuroendocrine tumours (NETs), although which factors are associated with an improved overall survival (OS) remains unclear. The primary aim of this study is to determine to what extent a radiological response to (90)Y-DOTATOC/(90)Y-DOTATATE PRRT is associated with an improved OS. The association of biochemical and clinical response to OS were assessed as secondary outcome measures. METHODS: A retrospective analysis was conducted on 57 patients: radiological response was classified using RECIST criteria, biochemical response was classified using WHO criteria and clinical response was assessed subjectively. Responses were recorded as positive response (PR), stable disease (SD) or progressive disease (PD), and survival analysed. RESULTS: Radiological response was achieved in 71.5% (24.5% PR, 47% SD) and was associated with a greater OS (51 and 56 months, respectively), compared with PD (18 months). A biochemical or clinical response post PRRT were not associated with a statistically significant improvement in OS. However, when combined with radiological response a survival benefit was observed according to the number of outcomes (radiological, biochemical, clinical), in which a response was observed. Mild haematological toxicity was common, renal toxicity was rare. CONCLUSION: In patients with progressive metastatic NETs receiving (90)Y-DOTATOC/(90)Y-DOTATATE PRRT, a radiological response with either a PR or a SD post therapy confers a significant OS benefit.


Subject(s)
Neuroendocrine Tumors/radiotherapy , Octreotide/analogs & derivatives , Organometallic Compounds/therapeutic use , Radiopharmaceuticals/therapeutic use , Yttrium Radioisotopes/therapeutic use , Female , Humans , Intestinal Neoplasms/metabolism , Intestinal Neoplasms/pathology , Intestinal Neoplasms/radiotherapy , Intestine, Small/pathology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/radiotherapy , Male , Middle Aged , Neuroendocrine Tumors/metabolism , Neuroendocrine Tumors/pathology , Octreotide/therapeutic use , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/radiotherapy , Receptors, Peptide/metabolism , Retrospective Studies , Survival Analysis , Treatment Outcome
12.
Diabetologia ; 54(6): 1304-7, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21359581

ABSTRACT

AIMS/HYPOTHESIS: GFR is commonly estimated using the four-variable Modification of Diet in Renal Disease (MDRD) formula and this forms the basis for classification of chronic kidney disease (CKD). We investigated the effect of obesity on the estimation of glomerular filtration rate in type 2 diabetic participants with CKD. METHODS: We enrolled 111 patients with type 2 diabetes mellitus in different stages of CKD. GFR was measured using (51)Cr-labelled EDTA plasma clearance and was estimated using the four-variable MDRD formula. RESULTS: The bias between estimated and measured GFR was -22.4 (-33.8 to -11.0) p < 0.001 in the obese group compared with -6.04 (-17.6 to -5.5) p = 0.299 in the non-obese group. When GFR was indexed to body surface area of 1.73 m(2), the bias remained significant at -9.4 (-13.4 to -5.4) p < 0.001 in the obese participants. CONCLUSIONS/INTERPRETATION: This study suggests that the four-variable MDRD formula significantly underestimates GFR in obese type 2 diabetic participants with CKD.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Feeding Behavior , Food, Formulated , Glomerular Filtration Rate/physiology , Kidney Diseases/physiopathology , Obesity/physiopathology , Aged , Body Mass Index , Body Surface Area , Chronic Disease , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Kidney Diseases/epidemiology , Male , Middle Aged , Obesity/epidemiology
13.
Transplant Proc ; 40(5): 1324-8, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18589097

ABSTRACT

Because death with a functioning graft remains one of the most important causes of long-term renal transplant failure, cardiac risk stratification and screening for coronary artery disease are essential components of pretransplant assessment. Pretransplant screening for occult coronary artery disease in a subset of these patients may improve outcome. The UK follows the European Best practice guideline 1.5.5 E. Although echocardiography, thallium myocardial perfusion scanning (MPS), dobutamine stress echocardiography, and coronary angiography have been suggested as means of cardiovascular assessment, the best means of assessment remains undetermined. Therefore, we investigated the role of 99m technetium sestamibi myocardial perfusion scanning as an assessment tool for identifying those patients with end-stage renal failure at high risk of cardiovascular death after renal transplantation. Retrospectively, we studied 126 patients that had a MPS as part of their pretransplant assessment. Overall unadjusted survival was 65% at 3 years. Twelve deaths resulted from cardiovascular causes. A reversible defect on MPS was associated with a fatal cardiac event and all-cause mortality. The unadjusted hazard ratio of cardiac event with reversible defect on MPS was 3.1 (95% confidence interval, 1.1 to 18.2) and hazard ratio of death with reversible defect on MPS was 1.92 (95% confidence interval, 1.1 to 4.4). Thus, MPS may be a useful tool in cardiac risk stratification and in selecting patients with a favorable outcome after renal transplantation. Our patients with a reversible defect in particular have increased cardiac mortality. This group may benefit from coronary angiography.


Subject(s)
Coronary Angiography , Heart/diagnostic imaging , Kidney Transplantation , Preoperative Care , Technetium Tc 99m Sestamibi , Coronary Disease/diagnostic imaging , Coronary Disease/epidemiology , Dobutamine , Exercise Test , Female , Heart Diseases/diagnostic imaging , Heart Diseases/therapy , Humans , Male , Middle Aged , Risk Assessment , Tomography, Emission-Computed, Single-Photon , United Kingdom
14.
Br J Cancer ; 98(6): 1053-8, 2008 Mar 25.
Article in English | MEDLINE | ID: mdl-18283308

ABSTRACT

(131)I-metaiodobenzylguanidine ((131)I-MIBG) is a licensed palliative treatment for patients with metastatic neuroendocrine tumours. We have retrospectively assessed the consequences of (131)I-MIBG therapy in 48 patients (30 gastroenteropancreatic, 6 pulmonary, 12 unknown primary site) with metastatic neuroendocrine tumours attending Royal Liverpool University Hospital between 1996 and 2006. Mean age at diagnosis was 57.6 years (range 34-81). (131)I-MIBG was administered on 88 occasions (mean 1.8 treatments, range 1-4). Twenty-nine patients had biochemical markers measured before and after (131)I-MIBG, of whom 11 (36.7%) showed >50% reduction in levels post-therapy. Forty patients had radiological investigations performed after (131)I-MIBG, of whom 11(27.5%) showed reduction in tumour size post-therapy. Twenty-seven (56.3%) patients reported improved symptoms after (131)I-MIBG therapy. Kaplan-Meier analysis showed significantly increased survival (P=0.01) from the date of first (131)I-MIBG in patients who reported symptomatic benefit from therapy. Patients with biochemical and radiological responses did not show any statistically significant alteration in survival compared to non-responders. Eleven (22.9%) patients required hospitalisation as a consequence of complications, mostly due to mild bone marrow suppression. (131)I-MIBG therefore improved symptoms in more than half of the patients with metastatic neuroendocrine tumours and survival was increased in those patients who reported a symptomatic response to therapy.


Subject(s)
3-Iodobenzylguanidine/adverse effects , 3-Iodobenzylguanidine/therapeutic use , Iodine Radioisotopes/therapeutic use , Neuroendocrine Tumors/therapy , Radiopharmaceuticals/therapeutic use , Adult , Aged , Aged, 80 and over , Female , Hematologic Diseases/etiology , Humans , Liver Neoplasms/secondary , Male , Middle Aged , Neoplasm Metastasis , Neuroendocrine Tumors/mortality , Neuroendocrine Tumors/pathology , Radiopharmaceuticals/adverse effects , Survival Analysis
15.
J Clin Endocrinol Metab ; 92(8): 3230-8, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17550963

ABSTRACT

BACKGROUND: Osteoclast resorptive activity, which is known to demonstrate circadian rhythmicity, is regulated by various endocrine hormones and cytokines. PTH suppresses osteoprotegerin (OPG), a regulator of osteoclast activity that has recently been shown to have a circadian rhythm in healthy controls. We studied the differences in the relationship between PTH, OPG, and type I collagen C-telopeptide (betaCTX) over a 24-h period in premenopausal women, elderly postmenopausal women, and elderly men. METHODS: Hourly peripheral venous blood samples were obtained from 18 healthy non-osteoporotic volunteers: premenopausal women (n = 6; mean age, 30.2 +/- 2.2 yr), postmenopausal women (n = 6; mean age, 68.2 +/- 2.6 yr), and elderly men (n = 6; mean age, 68.2 +/- 2.3 yr). Plasma PTH (1-84), OPG, betaCTX, and calcium were measured on all samples. Cosinor analysis was performed to analyze the circadian rhythm parameters. Cross-correlation analysis was used to determine the relationship between the time series of the variables. RESULTS: The 24-h mean PTH, OPG, and betaCTX concentrations were significantly higher in postmenopausal women as compared with premenopausal women and elderly men (P < 0.001). Significant circadian rhythms were observed for PTH (P < 0.05), OPG (P < 0.05), and betaCTX (P < 0.001) in all subjects. PTH secretion was characterized by two peaks in premenopausal women and elderly men and by a sustained increase in PTH concentration in postmenopausal women. OPG secretion was circadian with a daytime increase and nocturnal decrease, and a greater percent decrease in OPG secretion was observed in the postmenopausal women between 1600 and 2400 h. OPG secretion was inversely related to PTH (r = -0.4) and betaCTX (r = -0.6) secretion over a 24-h period. CONCLUSION: This report confirms a circadian rhythm for circulating OPG. The nocturnal decline in circulating OPG is greater in postmenopausal women as compared with premenopausal women and elderly men. Altered PTH secretion may contribute to the OPG secretory pattern in postmenopausal women resulting in increased nocturnal bone resorption.


Subject(s)
Circadian Rhythm/physiology , Osteoprotegerin/blood , Parathyroid Hormone/metabolism , Adult , Aged , Bone Density/physiology , Calcium/blood , Collagen Type I/blood , Densitometry , Female , Humans , Male , Middle Aged , Peptides/blood
16.
Br J Cancer ; 95(10): 1424-31, 2006 Nov 20.
Article in English | MEDLINE | ID: mdl-17031404

ABSTRACT

The -1p/-19q genotype predicts chemosensitivity in oligodendroglial neoplasms, but some with intact 1p/19q also respond and not all with 1p/19q loss derive durable benefit from chemotherapy. We have evaluated the predictive and prognostic significance of pretherapy (201)Tl and (18)F-FDG SPECT and genotype in 38 primary and 10 recurrent oligodendroglial neoplasms following PCV chemotherapy. 1p/19q loss was seen in 8/15 OII, 6/15 OAII, 7/7 OIII, 3/11 OAIII and was associated with response (Fisher-Exact: P=0.000) and prolonged progression-free (log-rank: P=0.002) and overall survival (OS) (log-rank: P=0.0048). Response was unrelated to metabolism, with tumours with high or low metabolism showing response. Increased (18)F-FDG or (201)Tl uptake predicted shorter progression-free survival (PFS) in the series (log-rank: (201)Tl P=0.0097, (18)F-FDG P=0.0170) and in cases with or without the -1p/-19q genotype. Elevated metabolism was associated with shorter OS in cases with intact 1p/19q (log-rank: (18)F-FDG P=0.0077; (201)Tl P=0.0004) and shorter PFS in responders (log-rank: (18)F-FDG P=0.005; (201)Tl P=0.0132). (201)Tl uptake and 1p/19q loss were independent predictors of survival in multivariate analysis. In this initial study, (201)Tl and (18)F-FDG uptake did not predict response to PCV, but may be associated with poor survival following therapy irrespective of genotype. This may be clinically useful warranting further study.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/genetics , Fluorodeoxyglucose F18/metabolism , Neoplasm Recurrence, Local/genetics , Oligodendroglioma/genetics , Adult , Aged , Alleles , Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Chromosomes, Human, Pair 1/genetics , Chromosomes, Human, Pair 19/genetics , Disease Progression , Female , Genetic Predisposition to Disease , Genotype , Humans , Lomustine/therapeutic use , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/pathology , Oligodendroglioma/drug therapy , Oligodendroglioma/pathology , Procarbazine/therapeutic use , Prospective Studies , Survival Rate , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed , Treatment Outcome , Vincristine/therapeutic use
17.
Int J Clin Pract ; 59(4): 496-500, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15853870

ABSTRACT

A retrospective audit of (99m)Tc-HMPAO SPECT scans was undertaken to assess the utility of brain perfusion imaging in a cohort of young cognitively impaired patients in whom diagnostic uncertainty remained after standard clinical and neuropsychological assessment and structural brain imaging. SPECT scans were assessed by five raters (two neurologists and three nuclear medicine specialists) on two occasions 6 months apart, first without any clinical data and second with brief pertinent clinical information. SPECT diagnoses were compared with criterion diagnoses subsequently established by the two neurologists with access to all clinical, neuropsychological and neuroimaging data. Despite reasonable intra- and interrater reliability, diagnostic accuracy ranged from 32 to 58%. SPECT scan normality or abnormality in blind and informed viewings gave respective sensitivities of 77 and 71%, specificities of 44 and 38%, positive predictive values of 88 and 87% and negative predictive values of 27 and 18%. Calculating pairwise disease group comparisons, likelihood ratios suggested some diagnostic gain in differentiating AD from 'not AD' and from FTD/focal syndromes. SPECT scanning was of little help in establishing diagnoses in this cohort of patients, a finding which supports the conclusion of the American Academy of Neurology evidence-based review that SPECT imaging cannot be recommended for either the initial or the differential diagnosis of suspected dementia because it has not demonstrated superiority to clinical criteria.


Subject(s)
Dementia/diagnostic imaging , Radiopharmaceuticals , Technetium Tc 99m Exametazime , Tomography, Emission-Computed, Single-Photon/methods , Adult , Aged , Diagnosis, Differential , Female , Humans , Likelihood Functions , Male , Medical Audit , Middle Aged , Observer Variation , Retrospective Studies , Sensitivity and Specificity , Tomography, Emission-Computed, Single-Photon/standards
18.
Dig Surg ; 22(1-2): 55-61; discussion 62, 2005.
Article in English | MEDLINE | ID: mdl-15838173

ABSTRACT

BACKGROUND: Positron emission tomography (PET) has been proposed for pancreatic cancer diagnosis and staging. METHODS: 112 patients with suspected pancreatic cancer underwent 18F-fluoro-2-deoxy-D-glucose gamma camera PET and computed tomography (CT), of whom 62 also had laparoscopic ultrasonography and 70 underwent abdominal exploration for potential resection. The final diagnosis was malignancy in 78 and benign disease in 34 patients (25 with chronic pancreatitis). RESULTS: The diagnostic sensitivity and specificity for PET were 73 and 60% compared to 89 and 65% for CT respectively (Cohen's kappa = 0.59). In 30 patients CT was equivocal with cancer in 14 and benign disease in 16. PET correctly diagnosed 13 of these patients (cancer in 6 and benign disease in 7), interpreted 4 as equivocal (cancer in 3 and benign disease in 1) but was incorrect in the remaining 13 patients (cancer in 5 and benign disease in 8). The sensitivity and specificity for detecting small volume metastatic disease were 20 and 94% for CT and 22 and 91% for PET, respectively. CONCLUSION: PET had a similar accuracy to that of CT for imaging pancreatic cancer but it did not provide any additional information in patients with equivocal CT findings and currently would seem of little benefit for the staging of pancreatic cancer.


Subject(s)
Carcinoma, Pancreatic Ductal/diagnostic imaging , Pancreatic Neoplasms/diagnostic imaging , Positron-Emission Tomography , Adult , Aged , Aged, 80 and over , Chronic Disease , Diagnosis, Differential , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Pancreatitis/diagnosis , Radiopharmaceuticals , Sensitivity and Specificity , Tomography, X-Ray Computed
19.
Pancreatology ; 4(5): 417-33; discussion 434-5, 2004.
Article in English | MEDLINE | ID: mdl-15249710

ABSTRACT

The two main types of hereditary pancreatic neuroendocrine tumours are found in multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL), but also in the rarer disorders of neurofibromatosis type 1 and tuberous sclerosis. This review considers the major advances that have been made in genetic diagnosis, tumour localization, medical and surgical treatment and palliation with systemic chemotherapy and radionuclides. With the exception of the insulinoma syndrome, all of the various hormone excess syndromes of MEN-1 can be treated medically. The role of surgery however remains controversial ranging from no intervention (except enucleation for insulinoma), intervening for tumours diagnosed only by biochemical criteria, intervening in those tumours only detected radiologically (1-2 cm in diameter) or intervening only if the tumour diameter is > 3 cm in diameter. The extent of surgery is also controversial, although radical lymphadenectomy is generally recommended. Pancreatic tumours associated with VHL are usually non-functioning and tumours of at least 2 cm in diameter should be resected. Practice guidelines recommend that screening in patients with MEN-1 should commence at the age of 5 years for insulinoma and at the age of 20 years for other pancreatic neuroendocrine tumours and variously at 10-20 years of age for pancreatic tumours in patients with VHL. The evidence is increasing that the life span of patients may be significantly improved with surgical intervention, mandating the widespread use of tumour surveillance and multidisciplinary team management.


Subject(s)
Endocrine Gland Neoplasms/genetics , Pancreatic Neoplasms/genetics , Endocrine Gland Neoplasms/diagnosis , Endocrine Gland Neoplasms/therapy , Humans , Multiple Endocrine Neoplasia Type 1/diagnosis , Multiple Endocrine Neoplasia Type 1/therapy , Neurofibromatosis 1/diagnosis , Neurofibromatosis 1/therapy , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/therapy , Tuberous Sclerosis/diagnosis , Tuberous Sclerosis/therapy , von Hippel-Lindau Disease/diagnosis , von Hippel-Lindau Disease/therapy
20.
Nucl Med Commun ; 24(6): 707-13, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12766608

ABSTRACT

Left ventricular systolic dysfunction (LVSD) in asymptomatic patients is associated with the development of heart failure (HF) and the degree of LVSD predicts prognosis. Whether left ventricular diastolic dysfunction (LVDD) predicts the development of HF or mortality is not known. Our objective was to investigate the predictive value of LVDD evaluated by radionuclide ventriculography (RN). All patients referred for RN during a 12 month period were included. Medical records were reviewed to determine characteristics of the patients at the time of RN and events occurring during a 5 year follow-up. Data from 195 patients were analysed. During the follow-up period 49 patients (25.1%) died, 41 (21.0%) were admitted to hospital and 25 (12.3%) developed HF. An ejection fraction (EF) <40% was associated with mortality (relative risk (RR), 2.04; P=0.001) and hospital admissions (RR, 1.33; P=0.002). Patients who developed subsequent HF had, on average, lower EF at baseline. In a multivariate analysis the lower the EF the more likely patients were to develop new onset HF (odds ratio, 0.92; 95% CI 0.88-0.97; P=0.003). LVDD evaluated with peak filling rate and time to peak filling rate was not associated with any of the outcomes. However, a higher proportion of patients with pre-existing HF at the time of the RN had abnormal LVDD than patients with no HF. LVDD evaluated by RN is associated with symptoms of HF at the time of assessment but is not a good predictor of mortality, hospitalization or new onset HF. EF remains a better predictor of outcomes.


Subject(s)
Heart Failure/diagnostic imaging , Heart Failure/mortality , Hospitalization/statistics & numerical data , Radionuclide Ventriculography/methods , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Comorbidity , Diastole , Disease-Free Survival , Female , Humans , Male , Middle Aged , Risk Assessment/methods , Risk Factors , Sensitivity and Specificity , Survival Analysis , United Kingdom/epidemiology
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