Thalamic and prefrontal FDG uptake in never medicated patients with schizophrenia

OBJECTIVE: Because neuroleptic treatment may cause long-lasting changes in brain structure and function, a group of patients with schizophrenia who had never been medicated was recruited to examine regional glucose metabolic rates in the frontal-striato-thalamic circuit. METHOD: Twelve never medicated patients with schizophrenia (seven men, five women; mean age=29 years) and 13 normal volunteers (eight men and five women; mean age=28.5 years) underwent (18)F-fluorodeoxyglucose (FDG) positron emission tomography, and coregistered anatomical magnetic resonance imaging scans were also obtained. During FDG uptake, subjects performed a spatial attention task previously shown to activate the pulvinar region of the thalamus. RESULTS: Diminished regional glucose metabolism was found in the medial dorsal nucleus, posterior thalamus, and prefrontal cortex of patients with schizophrenia relative to normal volunteers, extending earlier results from studies of medicated and previously medicated patients. CONCLUSIONS: The finding of lower relative metabolic rates in the frontothalamic circuits of patients with schizophrenia is consistent with extended circuit deficits involving interactions of frontal executive areas with thalamic sensory and association processes.     

Metabolic disconnection between the mediodorsal nucleus of the thalamus and cortical Brodmann's areas of the left hemisphere in schizophrenia

OBJECTIVE: The authors' goal was to examine interregional correlations of thalamocortical metabolic activity during a verbal learning task in schizophrenia. METHOD: They used [18F]fluorodeoxyglucose positron emission tomography in 41 unmedicated patients with schizophrenia and 59 normal comparison subjects. RESULTS: A metabolic disconnection was observed in patients with schizophrenia in the left hemisphere between the mediodorsal nucleus and widespread frontotemporal cortical regions, and stronger-than-normal intercorrelations were found between the pulvinar and superior temporal, selected parietal, posterior cingulate, and occipital areas. CONCLUSIONS: Deficits in the functional interrelationships between the left frontotemporal cortices and the left mediodorsal nucleus of the thalamus complement inferences from postmortem and magnetic resonance imaging volumetric studies identifying a thalamic diathesis in schizophrenia.     

Prevalence of urinary incontinence and associated risk factors in a cohort of nuns

OBJECTIVE:To estimate the prevalence of urinary incontinence among a group of nulliparous nuns and to assess risk factors for developing incontinence.METHODS:Information on symptoms of urinary incontinence, as well as medical history and demographic data were obtained from 149 nuns. The prevalence of urinary incontinence was determined, and a logistic regression model was used to estimate the impact of demographic and medical risk factors on the likelihood of incontinence.RESULTS:The mean (+/- standard deviation) age of our sample of nuns was 68 (+/-11.7). All but one were white, 96% were postmenopausal, and 25% were taking hormone replacement therapy (HRT). Their mean body mass index (BMI) was 27.3 +/- 5.6. According to their self-reported symptoms, half the nuns had urinary incontinence. Of these, 22 nuns (30%) had stress incontinence, 18 (24%) had urge incontinence, 26 (35%) had mixed incontinence, and 8 (11%) had urine loss unrelated to stress and urge. More than half the incontinent nuns used sanitary pads for protection. From univariate analyses, statistically significant risk factors for urinary incontinence included BMI, current HRT use, multiple urinary tract infections, hypertension, arthritis, depression, hysterectomy, and previous spinal surgery. From multivariate logistic regression, only BMI, multiple urinary tract infections, and depression remained statistically significant after adjusting for the other variables.CONCLUSION:The prevalence of incontinence in nulliparous, predominantly postmenopausal nuns is similar to rates reported in parous, postmenopausal women. Even in the absence of pelvic floor trauma from childbirth, urine loss is associated with symptoms of stress incontinence more often than with symptoms of urge incontinence.     

Striatal size,glucose metabolic rate,and verbal learning in normal aging

The striatum has recently been implicated as an area that may mediate age-associated cognitive decline because of diminution of volume and functional activity. We used 18F-fluorodeoxyglucose (FDG) with positron emission tomography (PET) and high-resolution magnetic resonance imaging (MRI) to examine the effects of age on striatal glucose metabolic rate and size in 70 healthy, normal subjects. During the FDG tracer uptake period, subjects performed a serial verbal learning task, based on the California Verbal Learning Test. PET images were co-registered to the MR images. The interrelations among striatal glucose metabolic rate, size, and performance on the verbal learning task were examined with repeated-measures analysis of variance and correlational analysis. As age increased, relative glucose metabolic rate (GMR) increased in the putamen and decreased in the caudate. Female subjects had lower relative GMR than male subjects in the caudate, but equal in the putamen. Striatal size remained relatively constant across the lifespan in men but was lower in women aged 50-70 than in men. While there were significant associations between striatal activity and performance on the uptake task, these findings were mostly accounted for by age. The findings are consistent with our earlier report on the same cohort that demonstrated an age-related shift from anterior to posterior cortical metabolism, as the putamen receives primarily posterior cortical input and the caudate receives relatively more anterior cortical input. Findings of significant involvement of striatal functioning in verbal learning are most likely accounted for by age and suggest an age-related shift from anterior to posterior circuitry in the human telencephalon.     

Effect of fluoxetine on regional cerebral metabolism in autistic spectrum disorders: a pilot study

The regional metabolic effects of fluoxetine were examined in patients with autism spectrum disorders. Six adult patients with DSM-IV and Autism Diagnostic Interview (ADI) diagnoses of autism (n = 5) and Asperger's syndrome (n = 1), entered a 16-wk placebo-controlled cross-over trial of fluoxetine. The patients received (18)F-deoxyglucose positron emission tomography with co-registered magnetic resonance imaging at baseline and at the end of the period of fluoxetine administration. After treatment, the patients showed significant improvement on the scores of the Yale--Brown Obsessive--Compulsive Scale -- Obsessions subscale and the Hamilton Anxiety Scale; Clinical Global Impressions -- Autism scores showed 3 of the patients much improved and 3 unchanged. Relative metabolic rates were significantly higher in the right frontal lobe following fluoxetine, especially in the anterior cingulate gyrus and the orbitofrontal cortex. Patients with higher metabolic rates in the medial frontal region and anterior cingulate when unmedicated were more likely to respond favourably to fluoxetine. These results are consistent with those in depression indicating that higher cingulate gyrus metabolic rates at baseline predict SRI response.     

Gene therapy for the treatment of cancer

The delineation of the molecular basis of neoplasia provides the possibility of specific intervention by gene therapy through the introduction of genetic material for therapeutic purposes. In this regard, several gene therapy approaches have been developed for the treatment of cancer: mutation compensation, genetic immunopotentiation, molecular chemotherapy, inhibition of angiogenesis, replicative vector oncolysis, and chemosensitization or radiosensitization. Clinical trials have been initiated to evaluate safety, toxicity, and efficacy of each of these approaches, based on promising preclinical results. Various limitations that have been identified include lack of in vivo selective tumor delivery of vectors, minimal expression of therapeutic genes, immune response against vectors, and normal tissue toxicity. Combined modality therapy with gene therapy and chemotherapy or radiation therapy has shown promising results. It is expected that as new therapeutic targets and approaches are identified, combined with advances in vector design, that gene therapy will play an increasing role in clinical cancer treatment.