Detection of local recurrence of soft-tissue sarcoma with positron emission tomography using [18F]fluorodeoxyglucose

Background: It is often difficult to detect a local recurrence of soft-tissue sarcomas due to disturbance of the normal anatomy by previous surgery and radiotherapy. The aim of this study was to assess the value of positron emission tomography (PET) with [¹⁸F]fluoro-2-deoxy-d-glucose (FDG) for detecting local recurrences. Methods: In the period 1992–1995, 17 patients with proven or suspected local recurrence of soft-tissue sarcoma were examined using FDG-PET. Fifteen of these patients were ultimately proven to have a recurrence. Results: Recurrence was visualized in 14 patients (93%). Small tumors (maximum diameter 0.5 cm) were as easily visible as large lesions (maximum diameter 20 cm). In one patient the PET scan was positive, but the recurrence could not be proven histologically. Recurrence was proven 1 year later. A recurrent low-grade liposarcoma was not visualized. The two patients with benign lesions had a negative PET scan. The mean glucose metabolic rate was calculated to be 13.2 μmol/100 g/min (range 1.9–28.4). A correlation was found between the histological malignancy grade and the metabolic rate (p<0.05; Kruskal-Wallis). Conclusion: PET with FDG is a useful addition to the diagnostic armamentarium for detecting local recurrence of soft-tissue sarcomas and provides an indication of the malignancy grade of the recurrent lesion. Presented at the 47th Annual Meeting of The Society for Surgical Oncology, Houston, Texas, March 17–20, 1994.     

Initial evaluation of123|-5-|-R91150, a selective 5-HT2A ligand for single-photon emission tomography, in healthy human subjects

The mapping of 5-HT₂ receptors in the brain using functional imaging techniques has been limited by a relative lack of selective radioligands. Iodine-123 labelled 4-amino-N-[1-[3-(4-fluorophenoxy)propyl]-4-methyl-4-piperidinyl]-5-iodo-2-methoxybenzamide (¹²³I-5-I-R91150 or¹²³I-R93274) is a new ligand for single-photon emission tomography (SPET), with high affinity and selectivity for 5-HT_2A receptors. This study reports on preliminary¹²³I-5-I-R91150 SPET, wholebody and blood distribution findings in five healthy human volunteers. Maximal brain uptake was approximately 2% of total body counts at 180 min post injection (p.i.). Dynamic SPET sequences were acquired with the brain-dedicated, single-slice multi-detector system SEM-810 over 200 min p.i. Early peak uptake (at 5 min p.i.) was seen in the cerebellum, a region free from 5HT_2A receptors. In contrast, radioligand binding in the frontal cortex increased steadily over time, up to a peak at approximately 100–120 min p.i. Frontal cortex-cerebellum activity ratios reached values of 1.4, and remained stable from approximately 100 min p.i. onwards. Multi-slice SPET sequences showed a pattern of regional variation of binding compatible with the autoradiographic data on the distribution of 5-HT_2A receptors in (cerebral cortex>striatum>cerebellum). These findings suggest that¹²³I-5-I-R91150 may be used for the imaging of 5-HT_2A receptors in the living human brain with SPET.     

The Canadian Psychiatric Association practice profile survey: I. Methods and general sample characteristics.

OBJECTIVE: To describe the rationale, methodology, and general sample characteristics of the Canadian Psychiatric Association (CPA) practice profile survey, a national survey of psychiatrists and psychiatric practice. METHOD: Mail-in interviews were sent to all Canadian psychiatrists listed in their provincial registers and to all active CPA members (total = 3628). Respondents provided general information about their professional activities for one 24-hour day and detailed information for 1 randomly selected hour. Patient information--including sociodemographics, diagnostic profiles, functioning levels, risk of harm to self or others, and disposition--was elicited for 1 patient seen during the random hour as well as for the most seriously ill patient receiving clinical services that day. RESULTS: There was a 45.5% response rate. Questionnaires completed by nonpsychiatrists or with a large percentage of missing or incorrect data were eliminated (107 surveys), resulting in a final sample size of 1570. CPA members and those from Western Canada responded at a higher rate to the survey. The results suggest some cause for concern about future manpower shortages. Most psychiatrists practise eclectically, seeing patients across the life-span, and working in both community and institutional settings. The old and the young appear to be underserviced, compared with adults. CONCLUSIONS: This study represents an important step forward in evaluating the profile and activities of the profession.     

Assessment of autonomic dysfunction in Parkinson's disease: the SCOPA-AUT.

We developed a questionnaire to assess autonomic symptoms in patients with Parkinson's disease (PD) and evaluated its reliability and validity. Based on the results of a postal survey in 46 PD patients, 21 multiple system atrophy patients, and 8 movement disorders specialists, items were included according to their frequency, burden, and clinical relevance. The questionnaire was evaluated in 140 PD patients and 100 controls, and test-retest reliability was established in a sample of 55 PD patients. The SCOPA-AUT consists of 25 items assessing the following regions: gastrointestinal (7), urinary (6), cardiovascular (3), thermoregulatory (4), pupillomotor (1), and sexual (2 items for men and 2 items for women) dysfunction. Test-retest reliability was good. Autonomic problems increased significantly with increasing disease severity for all autonomic regions, except sexual dysfunction. We conclude that SCOPA-AUT is a reliable and valid questionnaire that evaluates autonomic dysfunction in PD.     

Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study

Background  

Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking.     

Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle.

Defects in the ubiquitin-proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z-lle-Glu(OtBu)-Ala-Leu-al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 mul of 70% ethanol over a 2-week-period. We found significant decreases in nigrostriatal dopamine in PSI-treated mice compared with saline-treated mice. However, we observed similar decreases in the ethanol-treated vehicle control group. Administration of ethanol alone led to significant long-term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model.     

Optimization of localized 19F magnetic resonance spectroscopy for the detection of fluorinated drugs in the human liver.

Fluorine MR spectroscopy ((19)F MRS) is an indispensable tool for assessing the pharmacokinetics of fluorinated drugs. Since the metabolism of 5-fluorouracil (5FU), a frequently used cytotoxic drug, is expected to be different in normal liver and in tumor tissue, spatial localization is required for detection by MRS. In this study, three independent signal-to-noise ratio (SNR) optimizations were combined to enable chemical shift imaging (CSI) as a localization method in the detection of 5FU and its metabolites in tumor tissue. First, the hardware was optimized by using circularly polarized coils together with integrated preamplifiers. Second, the optimal pulse angle (Ernst angle) was determined on the basis of T(1) relaxation time measurements of 5FU. Finally, averaging of CSI phase-encoding steps was optimized by using the applied Hamming filter as a weighting function. The combination of these three methods enables the in vivo detection of 5FU and alpha-fluoro-beta-alanine (FBAL) by (19)F MRS, localized in three dimensions in tumor and liver tissue at a time resolution of 4 min at 1.5 Tesla.     

Research priorities for family assessment and intervention in pediatric oncology.

Four broad areas of research priority related to family assessment and intervention in pediatric oncology are outlined. The importance of a contextual, systemic approach is highlighted along with the value of systematic empirical assessment of psychosocial risk at diagnosis. Research to advance the development and application of standards of care during treatment is also advocated. The chapter concludes with opportunities for family-oriented research related to survivorship and end-of-life care.     

Potential problem with fluorescence polarization immunoassay cross-reactivity to vancomycin degradation product CDP-1: its detection in sera of renally impaired patients

During the development of a homogeneous immunoassay for the antibiotic vancomycin, we observed in certain patient samples a quantitation difference between the enzyme multiplied immunoassay technique (EMIT) method and the comparison method, fluorescence polarization immunoassay (FPIA). This prompted us to evaluate the integrity of vancomycin in samples from renally impaired patients. Since it has been reported in the scientific literature that vancomycin degrades into an antibiotically inactive crystalline degradation product (CDP-1) in vitro, we developed high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) methods to determine whether CDP-1 is present in patient sera. HPLC and LC/MS analysis on samples from renally impaired patients positively identified CDP-1 in fresh samples. Next, we tested the cross-reactivity of three currently available vancomycin immunoassays, radioimmunoassay (RIA) FPIA, and EMIT, to CDP-1 prepared in our laboratory. Our data suggest that CDP-1 is recognized by FPIA and RIA, both polyclonal antibody-based methods, but not by EMIT, which uses a monoclonal antibody.