Use of somatostatin analogue scintigraphy in the localization of recurrent medullary thyroid carcinoma

Detection of recurrence of medullary thyroid carcinoma (MTC) remains a diagnostic problem. Increased serum tumour marker levels frequently indicate recurrence while conventional imaging techniques (CIT) are non-diagnostic. In this study, we performed indium-111 octreotide scintigraphy and CIT in a series of 20 patients with MTC presenting with elevated serum tumour markers after surgery. ¹¹¹In-octreotide whole-body studies detected 15 pathological uptake foci in 11 of the 20 patients studied and CIT detected 17 lesions in 11 of the 20 patients. Ten patients underwent reoperation, five of them with positive ¹¹¹In-octreotide scintigraphy and CIT and two with positive isotopic exploration and negative CIT. Surgical findings demonstrated that the results of isotopic study and CIT had been false-positive for MTC in one case (sarcoidosis). The six patients with true-positive ¹¹¹In-octreotide studies had significantly higher basal calcitonin (CT) and carcinoembryonic antigen (CEA) levels than the patients with negative isotopic studies. The expression of somatostatin receptor (SSTR) subtypes by PC-PCR could be investigated in four cases with a positive isotopic study. Among the three cases with a true-positive study, SSTR2, the SSTR subtype that preferentially binds to the somatostatin analogue octreotide, was detected in two, SSTR5 was demonstrated in the three, and SSTR3 was detected in one. No subtype of SSTR was detected in the case with a final diagnosis of sarcoidosis. We conclude that ¹¹¹In-octreotide has limited sensitivity in detecting recurrence in patients with MTC, although its sensitivity may improve with high serum CT levels. This radionuclide imaging technique should be employed when conventional imaging techniques are negative or inconclusive or when the presence of somatostatin receptors may provide the basis for treatment with somatostatin analogues. Received 5 April and in revised form 27 July 1998     

Comparison of the Cozart DDS 801 on-site drug test device and gas chromatography/mass spectrometry (GC/MS) confirmation results of cannabis and cocaine in oral fluid specimens

Driving under the influence of drugs (DUID) is a problem around the world. The objective of this study is to assess the reliability of the oral fluid screening device the Cozart DDS 801 by comparing the on-site results with confirmatory gas chromatography/mass spectrometry (GC/MS) oral fluid analysis. The study was carried out in Catalonia (Spain) with a sample of 2180 oral fluid specimens taken from subjects suspected of driving under the influence of drugs of abuse, and collected by police officers during 2009–2010. Statistical parameters of the tests were determined for cannabis and cocaine. The sensitivity, specificity, predictive positive value, predictive negative value, likelihood positive ratio and likelihood negative ratio for cocaine were 92%, 90%, 95%, 85%, 9.44, and 0.09 respectively. Sensitivity, specificity, predictive positive value, predictive negative value, likelihood positive ratio and likelihood negative ratio for cannabis were 87%, 86%, 94%, 73%, 6.15 and 0.6 respectively. Accuracy was 91% for cocaine and 86% for cannabis. The Cozart DDS 801 drug test system is a simple to use screening tool for cocaine and cannabis in oral fluid, at initial screening cut-off established by the manufacturer, confirmed with a GC/MS analysis. The system has demonstrated its acceptable performance.     

Is there a specific mutation of p53 gene due to radon exposure? A systematic review

Purpose: To review the existing literature analysing the influence of radon exposure on mutations in tumour protein 53 gene (TP53) in lung cancer patients.

Material and methods: Medline and EMBASE databases along with the International Agency for Research on Cancer (IARC) monographies were revised. Studies that had radon concentration as exposure variable and TP53 mutations as a result variable were included.

Results: Eight studies were obtained, with a total of 578 individuals. They had been carried out on miners and on general population. A 26% of the miners' tumours had a mutation in gene TP53, versus a 24% in the population exposed to residential radon. A predominance of the AGG^ARG→ ATG^MET (Arginine to Methionine) mutation in miners was observed.

Conclusions: The available results are not consistent in order to support the existence of a radon hotspot in TP53 gene. Future research should focus at least on exons 5 to 8, where most of the mutation clusters in lung tumours are observed.     

Unconsciousness and sedation as precipitating factors of diabetic ketoacidosis

The aim of this study was to identify medico-legal situations characterized by increased vitreous glucose concentrations, potentially lethal blood 3-hydroxybutyrate levels and conditions that could either incapacitate or lead to death on their own. The above was investigated in order to verify whether prolonged states of unconsciousness may play a role in precipitating diabetic ketoacidosis. Six groups of medico-legal situations (corresponding to 206 autopsy cases) were identified. Among these, three cases were characterized by pathologically increased vitreous glucose and blood 3-hydroxybutyrate levels. In one case diabetic ketoacidosis coexisted with underlying features that might have potentially incapacitated or lead to death on their own, whereas in two cases it corresponded with potentially lethal or lethal drug concentrations. The results of this study highlight the usefulness of systematically performing biochemistry in order to identify diabetic ketoacidosis-related deaths, even when autopsy and toxicology results provide apparently conclusive findings.     

High variation in hypoxanthine determination after analytical treatment of vitreous humor samples

In the field of legal medicine the correct determination of the time of death is of great importance because an error in calculating the post-mortem interval (PMI) could be crucial in a criminal investigation. The quantification of hypoxanthine (Hx) concentration in the vitreous humor (VH) as a means to estimate PMI is useful when dealing with a recent time interval of death and has several advantages over other biological matrices. However, due to its viscous nature, VH has to be liquefied prior to its analysis, and the different procedures to liquefy it may cause alterations in Hx concentration, and hence in estimation of PMI. The aim of this study was to determine differences in Hx concentration after applying several pre-analytical treatments to different aliquots of the same VH sample. Enzymatic digestion, sonication, centrifugation and heat were the liquefying methods applied to reduce the viscosity of 105 VH samples. Analysis was performed using solid phase extraction and liquid chromatography in tandem with mass spectrometry. Statistically significant differences in the measured Hx concentrations were found between enzymatic digestion and the other three methods analyzed (sonication, centrifugation, and heat). Additionally, high data dispersion was found under heat treatment but was not observed for centrifugation or sonication, where similar and more moderate results were found. We conclude that high variations in Hx determination are observed when enzymatic digestion or heat treatment is used and we therefore recommend sonication or centrifugation to quantify Hx concentration in the VH.     

Close-looped graft suturing improves mechanical properties of interference screw fixation in ACL reconstruction

Purpose

In anterior cruciate ligament reconstruction with looped soft-tissue grafts, an interference screw is frequently used for tibial fixation. This study compared three alternatives thought to improve the initial mechanical properties of direct bioabsorbable interference screw fixation: suturing the graft to close the loop, adding a supplementary staple, or increasing the oversize of the screw diameter relative to the bone tunnel from 1 to 2 mm.

Methods

Twenty-eight porcine tibiae and porcine flexor digitorum profundus tendons were randomized into four testing groups: a base fixation using 10-mm-diameter screw with open-looped graft, base fixation supplemented by an extracortical staple, base fixation but closing the looped graft by suturing its ends, and base fixation but using an 11-mm screw. Graft and bone tunnel diameters were 9 mm in all specimens. Constructs were subjected to cyclic tensile load and finally pulled to failure to determine their structural properties.

Results

The main mode of failure in all groups was pull-out of tendon strands after slippage past the screw. The sutured graft group displayed significantly lower residual displacement (mean value reduction: 47–67 %) and higher yield load (mean value increase: 38–54 %) than any alternative tested. No other statistical differences were found.

Conclusions

Suturing a soft-tissue graft to form a closed loop enhanced the initial mechanical properties of tibial fixation with a bioabsorbable interference screw in anterior cruciate ligament reconstructions using a porcine model, and thus, this may be an efficient means to help in reducing post-operative laxity and early clinical failure. No mechanical improvement was observed for an open-looped tendon graft by adding an extracortical staple to supplement the screw fixation or by increasing the oversize of the screw to tunnel diameter from 1 to 2 mm.     

Molecular subtypes of breast cancer: metabolic correlation with 18F-FDG PET/CT

Purpose

To determine whether the metabolic features of breast tumours differ among molecular subtypes.

Methods

This prospective study included 168 women diagnosed with locally advanced breast cancer. PET/CT was requested in the initial staging before neoadjuvant treatment (multicentre study, FISCAM grant). All patients underwent an ¹⁸F-FDG PET/CT scan with a dual time-point acquisition. Both examinations (PET-1 and PET-2) were evaluated qualitatively and semiquantitatively with calculation of SUVmax (SUV-1 and SUV-2, respectively), and the percentage variation in the SUVs and retention indexes (RI) between PET-1 and PET-2 in the breast tumour were calculated. Biological prognostic parameters, including the steroid receptor status, HER-2 expression, proliferation rate (Ki-67) and grading, were determined from primary tumour tissue. Tumour subtypes were classified following the recommendations of the 12th International Breast Conference, by immunohistochemical surrogates as luminal A, luminal B-HER2(?), luminal B-HER2(+), HER2(+) or basal. Metabolic semiquantitative parameters and molecular subtypes were correlated.

Results

Of the 168 tumours, 151 were classified: 16 were luminal A, 53 were luminal B-HER2(?), 29 were luminal B-HER2(+), 18 were HER2(+) and 35 were basal. There were significant differences between SUV-1 and SUV-2 and the different subtypes, with higher SUVs in HER2(+) and basal tumours. No significant differences were found with respect to RI.

Conclusion

Semiquantitative metabolic parameters showed statistically significant differences among the molecular subtypes of the tumours evaluated. Therefore, there seems to be a relationship between molecular and glycolytic phenotypes.     

Comparison of different methods of spatial normalization of FDG-PET brain images in the voxel-wise analysis of MCI patients and controls

Objective

One of the most interesting clinical applications of 18F-FDG PET imaging in neurodegenerative pathologies is that of establishing the prognosis of patients with mild cognitive impairment (MCI), some of whom have a high risk of progressing to Alzheimer’s disease (AD). One method of analyzing these images is to perform statistical parametric mapping (SPM) analysis. Spatial normalization is a critical step in such an analysis. The purpose of this study was to assess the effect of using different methods of spatial normalization on the results of SPM analysis of 18F-FDG PET images by comparing patients with MCI and controls.

Methods

We evaluated the results of three spatial normalization methods in an SPM analysis by comparing patients diagnosed with MCI with a group of control subjects. We tested three methods of spatial normalization: MRI-DARTEL and MRI-SPM8, which combine structural and functional images, and FDG-SPM8, which is based on the functional images only.

Results

The results obtained with the three methods were consistent in terms of the main pattern of functional alterations detected; namely, a bilateral reduction in glucose metabolism in the frontal and parietal cortices in the patient group. However, MRI-SPM8 also revealed differences in the left temporal cortex, and MRI-DARTEL revealed further differences in the left temporal cortex, precuneus, and left posterior cingulate.

Conclusions

The results obtained with MRI-DARTEL were the most consistent with the pattern of changes in AD. When we compared our observations with those of previous reports, MRI-SPM8 and FDG-SPM8 seemed to show an incomplete pattern. Our results suggest that basing the spatial normalization method on functional images only can considerably impair the results of SPM analysis of 18F-FDG PET studies.     

Myocardial sympathetic innervation in the athlete's sinus bradycardia: Is there selective inferior myocardial wall denervation?

BACKGROUND: Sinus bradycardia in trained athletes is predominantly a manifestation of increased vagal tone, but it is not known whether an alteration in the cardiac sympathetic system can contribute to blunted chronotropic response. This study assessed the integrity of the sympathetic system in trained athletes with sinus bradycardia by means of the iodine-123-metaiodobenzylguanidine (123I-MIBG) procedure. METHODS AND RESULTS: Fourteen athletes with sinus bradycardia and 8 athletes with a normal heart rate were explored by means of planar and single photon emission computed tomography MIBG studies. The heart/mediastinum ratio, regional myocardial distribution, and percent of regional myocardial MIBG uptake were evaluated. The heart/mediastinum ratio in athletes with sinus bradycardia was 1.87+/-0.10, and in athletes with a normal heart rate, the heart/mediastinum ratio was 1.86+/-0.16 (P = not significant). In athletes with sinus bradycardia, the regional distribution of MIBG showed an inferior and apical uptake defect in 8 athletes, an inferior, apical, and septal defect in 3 athletes, an inferior defect in 1 athlete, and normal distribution in 2 athletes (14%). In athletes with a normal heart rate, the regional distribution of MIBG showed an apical uptake defect in 3 athletes and normal distribution in 5 athletes (63%). The percent of regional MIBG uptake in the inferior region was significantly reduced in athletes with sinus bradycardia (44%+/-13% vs. 72%+/-11%, P<.01). CONCLUSION: These results show severely reduced myocardial MIBG distribution in the inferior region in athletes with sinus bradycardia, suggesting selective inferior myocardial wall sympathetic denervation, which may be related to increased vagal tone.     

Conjunctivitis with Regional Lymphadenopathy in a Trainee Microbiologist

We report a case of conjunctival tuberculosis in a trainee microbiologist caused by direct inoculation. The resident strain was analyzed by DNA fingerprinting, and an identical pattern was found in an isolate from sputum handled by the resident. After 6 months of treatment, the patient was cured.