Effect of chronic antipsychotic treatment on striatal phosphodiesterase 10A levels: a [¹¹C]MP-10 PET rodent imaging study with ex vivo confirmation.

A number of phosphodiesterase 10A (PDE10) inhibitors are about to undergo clinical evaluation for their efficacy in treating schizophrenia. As phosphodiesterases are in the same signalling pathway as dopamine D2 receptors, it is possible that prior antipsychotic treatment could influence these enzyme systems in patients. Chronic, in contrast to acute, antipsychotic treatment has been reported to increase brain PDE10A levels in rodents. The aim of this study was to confirm these findings in a manner that can be translated to human imaging studies to understand its consequences. Positron emission tomography (PET) scanning was used to evaluate PDE10A enzyme availability, after chronic haloperidol administration, using a specific PDE10A ligand ([(11)C]MP-10). The binding of [(11)C]MP-10 in the striatum and the cerebellum was measured in rodents and a simplified reference tissue model (SRTM) with cerebellum as the reference region was used to determine the binding potential (BPND). In rats treated chronically with haloperidol (2 mg kg(-1) per day), there was no significant difference in PDE10A levels compared with the vehicle-treated group (BPND±s.d.: 3.57 ± 0.64 versus 2.86 ± 0.71). Following PET scans, ex vivo analysis of striatal brain tissue for PDE10A mRNA (Pde10a) and PDE10A enzyme activity showed no significant difference. Similarly, the PDE10A protein content determined by western blot analysis was similar between the two groups, contrary to an earlier finding. The results of the study indicate that prior exposure to antipsychotic medication in rodents does not alter PDE10A levels.

Negishi coupling reactions as a valuable tool for [11C]methyl-arene formation; first proof of principle.

The Negishi coupling reaction between arylzinc halide reagents and (11)CH3I has been used to synthesise (11)C-methylated arene species via a palladium-mediated process. The metabotropic glutamate receptor subtype-5 radiotracer [(11)C]MPEP has been radiolabelled using this technique.

A case-based discussion on a patient with non-otogenic fungal skull base osteomyelitis: pitfalls in diagnosis.

OBJECTIVE: To discuss the diagnostic pitfalls and limitations of imaging investigations in non-otogenic skull base osteomyelitis. CASE REPORT: This paper reports a fatal case of non-otogenic fungal skull base osteomyelitis in an immunosuppressed patient. The patient initially presented with headache and later diplopia during multiple hospital admissions. A retrospective review of the initial imaging studies of his skull base revealed subtle signs of early infection at the inferior portion of the nasopharynx. Biopsies were taken from the posterior nasopharyngeal wall. Fungal cultures isolated Aspergillus fumigatus and mucor species. CONCLUSION: The insidious onset of the clinical features and the limitations of the currently available investigations make early diagnosis of skull base osteomyelitis difficult. This case highlights that skull base osteomyelitis should be suspected in immunocompromised patients with subtle radiological abnormalities on initial imaging. There is still controversy regarding the

Minimal preparation computed tomography instead of barium enema/colonoscopy for suspected colon cancer in frail elderly patients: an outcome analysis study.

AIM: To evaluate the efficacy of minimal preparation computed tomography (MPCT) in diagnosing clinically significant colonic tumours in frail, elderly patients. MATERIALS AND METHODS: A prospective study was performed in a group of consecutively referred, frail, elderly patients with symptoms or signs of anaemia, pain, rectal bleeding or weight loss. The MPCT protocol consisted of 1.5 l Gastrografin 1% diluted with sterile water administered during the 48 h before the procedure with no bowel preparation or administration of intravenous contrast medium. Eight millimetre contiguous scans through the abdomen and pelvis were performed. The scans were double-reported by two gastrointestinal radiologists as showing definite (>90% certain), probable (50-90% certain), possible (<50% certain) neoplasm or normal. Where observers disagreed the more pessimistic of the two reports was accepted. The gold standard was clinical outcome at 1 year with positive end-points defined as (1) histological confirmation of CRC, (2) clinical presentation consistent with CRC without histological confirmation if the patient was too unwell for biopsy/surgery, and (3) death directly attributable to colorectal carcinoma (CRC) with/without post-mortem confirmation. Negative end-points were defined as patients with no clinical, radiological or post-mortem findings of CRC. Patients were followed for 1 year or until one of the above end-points were met. RESULTS: Seventy-two patients were included (mean age 81; range 62-93). One-year follow-up was completed in 94.4% (n=68). Mortality from all causes was 33% (n=24). Five histologically proven tumours were diagnosed with CT and there were two probable false-negatives. Results were analysed twice: assuming all CT lesions test positive and considering "possible" lesions test negative [brackets] (95% confidence intervals): sensitivity 0.88 (0.47-1.0) [0.75 (0.35-0.97)], specificity 0.47 (0.34-0.6) [0.87 (0.75-0.94)], positive predictive value 0.18 [0.43], negative predictive value 0.97 [0.96], positive likelihood ratio result 1.6 [5.63], negative likelihood ratio result 0.27 [0.29], kappa 0.31 [0.43]. Tumour prevalence was 12%. A graph of conditional probabilities was generated and analysed. A variety of unsuspected pathology was also found in this series of patients. CONCLUSIONS: MPCT should be double-reported, at least initially. "Possible" lesions should be ignored. Analysis of the graph of conditional probability applied to a group of frail, elderly patients with a high mortality from all causes (33% in our study) suggests: (1) if MPCT suggests definite or probable carcinoma, regardless of the pre-test probability, the post-test probability is high enough to warrant further action, (2) frail, elderly patients with a low pre-test probability for CRC and a negative MPCT should not have further investigation, (3) frail, elderly patients with a higher pre-test probability of CRC (such as those presenting with rectal bleeding) and a negative MPCT should have either double contrast barium enema (DCBE) or colonoscopy as further investigations or be followed clinically for 3-6 months. MPCT was acceptable to patients and clinicians and may reveal significant extra-colonic pathology.

Autoamputation of a congenital oropharyngeal hairy polyp.

Hairy polyps or dermoids are rare, benign congenital tumours of the oronasopharynx containing elements of both ectodermal and mesodermal origin. They occur most commonly in young infants and can cause respiratory distress or failure to thrive due to feeding difficulties. Computed tomography, magnetic resonance imaging, and barium video fluoroscopy can be useful in delineating the origin and extent of these lesions. Treatment usually consists of surgical removal. We describe a case of spontaneous resolution of symptoms in an 11-week-old baby due to autoamputation of the lesion.

Responsiveness of carotenoids to a high vegetable diet intervention designed to prevent breast cancer recurrence.

Epidemiological studies suggest that a high vegetable diet may reduce risk for breast cancer and may also improve prognosis after the diagnosis of breast cancer. Circulating carotenoids may serve as a biomarker of vegetable and fruit intake, although several factors affect their bioavailability from food sources and may influence concentrations. One purpose of this study was to identify factors predictive of serum carotenoid, retinol, and alpha-tocopherol concentrations in 79 postsurgically resected breast cancer patients at enrollment and at 12 months in a feasibility study of a high vegetable, low fat diet intervention to reduce risk for cancer recurrence. Another purpose was to identify variables associated with change in these serum concentrations 12 months after randomization into control and intervention groups. The diet intervention (versus control) group had significantly greater increases in carotenoid intakes (P < 0.03) and significantly greater increases in serum concentrations of lutein, alpha- and beta-carotene, lycopene, and retinol (P < 0.04). Stepwise multiple regression revealed the level of dietary intake to be predictive of most serum carotenoid concentrations at baseline and 12 months, with additional associations between selected micronutrient concentrations and serum cholesterol, body mass index, age, percentage of energy intake from fat, and alcohol intake also observed at these time points. Intervention group change in serum carotenoid concentrations was inversely associated with baseline level, age, and change in serum cholesterol concentration and positively associated with change in carotenoid and alcohol intake. Circulating carotenoid concentrations are responsive to a high vegetable diet intervention, which also included reduced dietary fat and increased fiber intakes, to reduce risk for breast cancer recurrence.

Feasibility of a randomized trial of a high-vegetable diet to prevent breast cancer recurrence.

Epidemiologic evidence supports the concept that diet influences risk for breast cancer and suggests that prognosis after the diagnosis of breast cancer may also be related to modifiable nutritional factors. The purpose of this study was to investigate the feasibility of a randomized trial of a high-vegetable, reduced-fat, and increased-fiber diet intervention to reduce risk for recurrence among breast cancer survivors. This major change in dietary pattern was promoted through intensive telephone counseling. Participants were 93 women who had been diagnosed with breast cancer (stages I, II, and IIIA) within the previous four years and who had completed their initial treatment. We assessed adherence to the study diet using repeated 24-hour dietary recalls at 6 and 12 months and measurement of circulating carotenoid concentrations. Six months after randomization, the intervention group had significantly increased their mean intake of vegetables (+4.6 servings/day), fruit (+0.7 servings/day), and fiber (+6.4 g/1,000 kcal) and significantly reduced their intake of dietary fat (-9.9% of energy) compared with the control group. Circulating concentrations of carotenoids also increased in the intervention group. These changes persisted at the 12-month visit. Results of this study demonstrate that telephone counseling can be a useful approach in diet intervention and that breast cancer survivors can adopt and maintain a high-vegetable, reduced-fat dietary pattern.

Screening for alcoholism in general hospitals.

In a recently completed study at the North Bay Psychiatric Hospital, a tertiary resource serving a population of about 600,000 in Northern Ontario, systematic screening on admission showed a very high proportion of past or present alcoholism. Fifty-seven percent of the patients were identified as having a life prevalence of (current or past) alcohol-related problems through a combination of a questionnaire and a liver function test. This figure is much higher than what is generally observed in mental hospitals. Does it reflect a widespread prevalence of alcoholism in Northeastern Ontario or is it distorted by the pattern of referral to the North Bay Psychiatric Hospital which typically serves an under-privileged segment of the population? In an attempt to answer this question, this study was carried out in general hospitals (medical and surgical wards). It confirms a higher prevalence of alcohol-related problems (biological, psychological and/or social) in Northern Ontario general hospitals, compared with Southern Ontario general hospitals, using identical methods of screening and assessment in both populations. The regional difference (odds ratio) is more evident in higher social classes. A diagnosis of alcohol abuse or dependence (currently active or in remission) was confirmed in 83.5% of the cases with positive screening who underwent the Diagnostic Interview Schedule (revised). This is a robust confirmation of the value of screening. These findings confirm the importance of systematic screening for alcoholism in general hospitals.