Myocardial scintigraphy with 99mTc MIBI. The use of a single-day protocol in a multiregional center: a comparison between planar and tomographic imaging]

The use of a single-day protocol for 99mTc MIBI myocardial scintigraphy is particularly well-suited for the nuclear medicine departments that are the referral centres for the cardiology departments of several community hospitals. The aim of the study was to compare, in the same patient population, the diagnostic accuracy of planar and SPECT imaging with 99mTc MIBI using a single-day protocol. Thirty-nine patients (31 males and 8 females, age range 32-69 years) were studied because of effort chest pain. Of them, 7 had a pre-test probability of coronary artery disease less than 2.5%; coronary angiography demonstrated significant coronary obstructions in the remaining 32 subjects and 21 of them also had a history of previous myocardial infarction. All patients underwent 99mTc MIBI myocardial scintigraphy with acquisition of planar and SPECT images after injection of a low dose (370 MBq) at rest and after a second higher dose (1110 MBq), injected approximately four hours later during exercise stress testing. The normalcy rate in the 7 patients with low pre-test probability was 100% using both imaging techniques. For the diagnosis of previous infarction, the sensitivities of planar and SPECT images were 71% and 96% respectively. For the diagnosis of effort ischemia the sensitivity values were 34% and 88%, respectively, using planar and SPECT imaging. With regard to the classification of the diseased coronary arteries, the sensitivities of planar and SPECT studies were 42% and 79% respectively, and the related specificities were 91% and 77%. We may conclude that using a single-day protocol planar imaging seems to allow lower levels of diagnostic accuracy both for the diagnosis of effort ischemia and the classification of the diseased vessels as compared to SPECT, which appears therefore in a similar setting the imaging technique of choice.     

GSTMI and NAT2 genotypes and urinary mutagens in coke oven workers

The influence of the metabolic genotypes GSTMI and NAT2 on theurinary excretion of mutagens in 46 coke oven workers (27 ofthem smokers) was studied. Exposure to polycyclic aromatic hydrocarbons(PAH) was estimated from urinary 1-pyrenol levels, which variedfrom 0.23 to 5.59 µmol/mol creatinine. Fourteen urinesamples (30.4%), all but one belonging to smokers, were positivefor mutagenic activity (i.e. at least one of the assayed doseswas able to double the number of spontaneous revertants). Nineof the urine-positive subjects were both GSTMI-null and NAT2-ss(64.3%), while the same combination of genotypes was found innine out of 31 urine-negative subjects (29.0%) (P < 0.05).Significantly more smoking workers with the genotype combinationGSTM1-null/NAT2-ss showed positive urine mutagenicity than theother subjects (75.0 versus 28.6%, P< 0.05). Smokers withthe slow acetylator genotype showed a significantly higher frequencyof positive urine samples than smoking fast acetylators (64.7versus 22.2%, P < 0.05). Our results suggest that smokingcoke oven workers with genotypes unfavourable for detoxificationof aromatic amines (NAT2-ss) and PAH (GSTM1-null) may have anincreased risk of developing bladder cancer.     

Low Diastolic Ambulatory Blood Pressure Is Associated with Greater All-Cause Mortality in Older Patients with Hypertension

OBJECTIVES: To assess the relationship between office and ambulatory systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) and total mortality in elderly patients with hypertension.
DESIGN: Observational prospective cohort study.
SETTING: Hypertension outpatient clinic in a geriatric academic hospital.
PATIENTS AND METHODS: Eight hundred five older (≥60) subjects with hypertension underwent office and ambulatory BP measurement. Mortality was assessed after a mean follow-up of 3.8 years.
RESULTS: In a total of 3,090 person-years of follow-up, 107 participants died (average mortality rate 3.5% per year). With bivariate analysis, participants who died had higher SBP and PP and lower DBP, with office and ambulatory measurements. Mortality rates were greater with higher SBP and lower with higher DBP. As a combined effect of these trends, PP was associated with the widest death rate gradients, from 12 to 66, 13 to 63, and 9 to 70 per 1,000 person-years across office, 24-hour, daytime, and nighttime PP quartiles, respectively. Multivariate Cox analysis confirmed these trends; the adjusted hazard of death increased linearly with increasing ambulatory SBP and PP, whereas it decreased significantly with increasing ambulatory DBP. A five times greater risk of death was detected when comparing night-time PP quartile 4 (median PP value 78 mmHg) with quartile 1 (median PP value 46 mmHg).
CONCLUSION: In older patients with hypertension, low DBP and high PP, particularly when measured using ambulatory BP monitoring, are associated with greater risk of death. The achievement of an SBP treatment goal should not be obtained at the expense of an excessive DBP reduction.     

Urinary mutagenicity on TA98 and YG1024 Salmonella typhimurium strains after a hamburger meal: influence of GSTM1 and NAT2 genotypes

Mutagenicity on TA98 and YG1024 Salmonella typhimurium strainsof pan–fried hamburger extracts and of 24 h post–mealurine from 32 non–smoking volunteers was evaluated. Eachparticipant in the study was GSTM1 and NAT2 genotyped. Aftercooking the meat showed mutagenic activity (mean ± SD)on strains TA98 and YG1024 of 114 ± 129 and 1437 ±1536 net revertants/g respectively. Twenty three of 32 urinesamples showed clear mutagenic activity (i.e. caused at leasta doubling of the number of spontaneous revertants) on the 0-acetyltransferaseoverproducing strain YG1024, while none of the post-meal 24h urine samples was clearly mutagenic on strain TA98. Total24 h post–meal YG1024–active urinary mutagens werewell correlated with the levels of mutagen intake with the meal(r² = 0.5977, F = 44.58, P < 0.01). In the group under studyGSTM1 genotypes did not influence urinary mutagenicity. Highlyexposed subjects (n = 15) with the NAT2–ss genotype showedsignificantly increased levels of urinary mutagenicity on strainYG1024 in comparison with NAT2-R subjects (mutagen intake-adjustedtotal 24 h mutagen excretion = 1.00 ± 0.29 versus 0.66± 0.32, Mann-Whitney U test, U = 12.5, P < 0.05).Our results suggest that the levels of urinary mutagens derivedfrom diets rich in heterocyclic aromatic amines, which are specificallydetected by the YG1024 Salmonella strain, are modulated by NAT2-dependentenzyme activity, slow acetylators having higher levels of mutagensin their urine. Subjects with the rapid acetylator genotype,who are known to be at risk for colon cancer, seem to be partiallyprotected with respect to the risk of bladder cancer. ⁴To whom correspondence should be addressed. Tel: 498216637; Fax: 498216621; Email: clonfero{at}uxl.unipd.it     

Preliminary results of neoadjuvant treatment of adenocarcinoma of the gastro-esophageal junction

The prognosis of adenocarcinoma of the gastro-oesophageal junction is poor and only surgery yields long-term survival in no more than 30% of patients. We tested a new neoadjuvant chemo-radiotherapy regimen based on the administration of weekly docetaxel and cisplatin and continuous infusion of 5-FU with concurrent radiotherapy in order to evaluate its feasibility and efficacy. Thirty-three patients enrolled in a dose-finding study and observed at the 1st Division of General Surgery of the University of Verona between January 2000 and October 2003 underwent neoadjuvant chemo-radiotherapy for gastro-oesophageal junction adenocarcinoma (Siewert type I and II). The induction treatment was completed in 97.0% of cases with no treatment-related mortality. After completion of chemo-radiation 30 patients underwent surgery (90.9%) while three patients did not (progression in 2 cases and chemotherapy toxicity in one). Two operated patients did not undergo resection because of liver metastasis at laparotomy (respectability: 84.8%) and 3 more cases had incomplete tumour resection (R0-resectability: 75.8%). No postoperative in-hospital mortality was observed. A complete response (pT0N0) was achieved in 7 cases (23.3%) while minimal residual disease without evidence of lymph node involvement was found in a further 5 cases (16.7%). Worthy of note is the high rate of positive histopathological responses in the later period (6 out of 8) with 4 cases presenting complete responses. This protocol regimen proved to be feasible and well tolerated. Surgery-related deaths and morbidity were not increased. A high rate of positive pathological responses was obtained particularly in the later period of the study with the increased dosage of the protocol regimen.     

Therapeutic usability of two different fiducial gold markers for robotic stereotactic radiosurgery of liver malignancies:A pilot study

AIM: To assess how the application of different types of markers affects the tracking accuracy of Cyber Knife's.METHODS: Fifteen patients were recruited and subjected to the ultrasound-guided placement of markers. Two different type of needles 25 gauge(G) and 17 G containing two different fiducial marker, gold notched flexible anchor wire 0.28 mm × 10 mm(25 G needle) and gold cylindrical grain 1 mm × 4 mm(17 G), were used. Seven days after the procedure, a Cyber Knife planning computed tomography(CT) for the simulation of radiation treatment was performed on all patients.A binary CT score was assigned to the fiducial markers visualization. Also, the CT number was calculated for each fiducial and the values compared with a specific threshold.RESULTS: For each patient from 1 to 5, intra-hepatic markers were placed(one in 2 patients, three in 8 patients, four in 3 patients, and five in 2 patients). A total of 48 needles were used(thirty-two 17 G and sixteen 25 G) and 48 gold markers were placed(32 Grain shaped markers and 16 Gold Anchor). The result showed that the CT visualization of the grain markers was better than the anchor markers(P = 5 × 10~(-9)). Furthermore, the grain markers were shown to present minor late complications(P = 3 × 10~(-6)), and the best CT threshold number(P = 0.0005). CONCLUSION: The study revealed that the Gold Anchor fiducial marker is correlated with a greater number of late minor complications and low visualization by the CT.     

The genetic burden of inflammatory bowel diseases: implications for the clinic?

Introduction: Inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are characterized by chronic intestinal inflammation. Their etiology is multifactorial, with complex interactions between genetic and environmental factors, which are still largely unclear.

Areas covered: The influence of genetics is clearly demonstrated by important epidemiological data, including familial aggregation and concordance in twins. In 2001, the first genetic susceptibility gene for IBD, the NOD2 gene, was identified. Currently, thanks to genetic wide association studies, over 200 susceptibility genetic markers are know.

Expert commentary: However, clinically highly relevant gene associations are still very limited and the usefulness of these information in the current clinical strategies for treatment and surveillance of IBD is weak. Nevertheless, the recent identification of some genetic risk variants has clarified some newbiological pathways of these diseases thus paving the way for the discoveries in the near future of new targeted therapies.