In vivo MRI of cancer cell fate at the single-cell level in a mouse model of breast cancer metastasis to the brain.

Metastasis (the spread of cancer from a primary tumor to secondary organs) is responsible for most cancer deaths. The ability to follow the fate of a population of tumor cells over time in an experimental animal would provide a powerful new way to monitor the metastatic process. Here we describe a magnetic resonance imaging (MRI) technique that permits the tracking of breast cancer cells in a mouse model of brain metastasis at the single-cell level. Cancer cells that were injected into the left ventricle of the mouse heart and then delivered to the brain were detectable on MR images. This allowed the visualization of the initial delivery and distribution of cells, as well as the growth of tumors from a subset of these cells within the whole intact brain volume. The ability to follow the metastatic process from the single-cell stage through metastatic growth, and to quantify and monitor the presence of solitary undivided cells will facilitate progress in understanding the mechanisms of brain metastasis and tumor dormancy, and the development of therapeutics to treat this disease.     

Drinking History Is Related to Persistent Blood Pressure Dysregulation in Postwithdrawal Alcoholics

We have previously demonstrated that alcoholics with transitory (< 72 hr) elevations in blood pressure (BP) during withdrawal continue to show residual cardiovascular dysregulation up to 4 weeks of abstinence. The present study replicates and extends these findings. Alcoholic inpatients were divided into three subgroups ( ns = 14) based on BP during the first 72 hr of withdrawal: transitory hypertensives (tHTs; BP > 160/95 mm Hg), transitory borderline hypertensives (tBHs; 140/90 BP < 160/95), and normotensives (NTs; all BPs < 140/90). All patients had normal resting pressures after 72 hr of withdrawal. At 3–4 weeks postadmission, the alcoholics and 14 nonalcoholic controls (CONTs) were tested at rest and during a 5-min handgrip task. The tHTs showed an exaggerated systolic and diastolic BP response to handgrip compared with NTs and CONTs, with tBHs intermediate ( ps < 0.05). Drinking history showed the tHTs had the highest reported level of alcohol consumption and severity of withdrawal symptoms ( ps < 0.05). Regression analyses indicated that consumption of hard liquor was the variable most predictive of admission BPs; further, parental history of hypertension potentiated this relationship for systolic BP. Age and consumption of nicotine and caffeine were not significant predictors of admission BP. The results suggest a persistent cardiovascular dysregulation in alcoholics showing transient hypertensive withdrawal BPs. These alcoholics may be at increased risk for future alcohol-related cardiovascular disorder.     

Initial lithium augmentation improves the antidepressant effects of standard TCA treatment in non-resistant depressed patients

The hypothesis was tested that an initial lithium-tricyclic antidepressant (TCA) combination has a better antidepressant effect than standard TCA treatment in non-refractory depression at the beginning of an episode. Twenty bipolar melancholic type depressed inpatients under lithium-TCA treatment were compared with 20 patients with the same diagnosis and TCA-placebo treatment for 5 weeks under double-blind conditions. All patients were male. Initial lithium-TCA treatment reduced depressive symptoms significantly more than antidepressant treatment with TCA and placebo after 5 weeks, but not in weeks 1 or 2. It can be concluded that lithium augmentation of TCA treatment should be started even at the beginning of antidepressant TCA treatment to provide a better treatment response in those patients who will profit from long-term lithium prophylaxis, e.g. bipolar patients with melancholic type depression.     

Dopamine transporters, D2 receptors, and glucose metabolism in corticobasal degeneration.

Alterations in presynaptic and postsynaptic dopaminergic system and cerebral glucose metabolism in corticobasal degeneration (CBD) were assessed to evaluate the potential usefulness of different imaging methods for CBD. (123)I-FP-CIT/(123)I-beta-CIT SPECT and (123)I-IBZM SPECT as well as (18)F-FDG PET were performed in eight CBD patients. Decreased presynaptic dopamine transporter binding was found in all CBD patients while D2 receptor binding was reduced in only one patient. (18)F-FDG PET displayed a contralateral hypometabolism in cortical and subcortical areas in seven out of eight patients. Our results demonstrate that glucose metabolism and DAT are reduced, while D2 receptors may be frequently preserved in CBD.     

Initial steps taken by nine primary care practices to implement alcohol screening guidelines with hypertensive patients: the AA-TRIP project.

Many medical conditions are caused or exacerbated by heavy drinking, necessitating alcohol screening and discussion in primary care practices. This is particularly true of hypertension, the most common primary diagnosis in the United States, which has been linked to the regular consumption of 3 or more standard alcoholic beverages a day. The Accelerating Alcohol Screening-Translating Research into Practice (AA-TRIP) project was designed to improve detection and management of alcohol problems in primary care patients with hypertension. Medical providers are being trained using the Practice Partner Research Network's- Translating Research into Practice (PPRNet-TRIP) quality improvement model. This includes a multi-method intervention (electronic medical records, on-site academic detailing, practice feedback reports and annual network meetings) to help practices increase adherence to clinical guidelines. Qualitative analyses of initial steps taken by nine primary care practices toward the routine implementation of alcohol screening guidelines are presented. Organizational factors and provider and patient characteristics all influenced the method and consistency of alcohol screening and intervention. Perceived time constraints, patient sensitivity to questions about alcohol, and possible stigma associated with a diagnosis of alcoholism were also relevant barriers requiring problem solving.     

Helicobacter pylori and luminal gastric pH

The relationships between gastric pH and Helicobacter pylori infection were studied in 37 consecutive subjects affected with nonulcer dyspepsia. Each underwent esophagogastroduodenoscopy with multiple gastric biopsies for both H. pylori and histologic assessment, and 24-hr antral pH monitoring. H. pylori was harbored by 59.5% of the subjects with whole gastric spread of infection in all but one patient. Histologic gastritis was shown in 70.3% of the subjects. H. pylori was strongly associated with gastritis, both antral nonatrophic and multifocal atrophic. The ranges of 24-hr pH values were 1.3-6.9 in the H. pylori-positive and 1.2-6.8 in the H. pylori-negative group. Differences in pH values between the two groups were not significant. Moreover, the mean percent time duration of pH above 2, 4, and 6 did not significantly differ between the two groups. Therefore, this study has shown that chronic H. pylori infection is not related to luminal gastric pH.     

Mediation as a new technique for resolving disputes in the mental health system

In the mental health service system, disputes take on various forms and exist in both clinical practice and management. Existing policy and administrative practice has favored a combination of medical and judicial/legal models to handle conflicts among consumers, mental health professionals, and others. The authors propose the addition of mediation as a third form of resolving issues, explicate some of the differences between mediation and current methods of resolving conflicts, and suggest benefits of using mediation.Noel Mazade is Executive Director, National Association of State Mental Health Program Directors Research Institute and a practicing mediator. Andrea Blanch is Director of Community Support Programs for the New York Office of Mental Health in Albany, NY.The views presented in this article are those of the authors only. Endorsement by the authors' organizational affiliations is not implied nor should it be inferred.     

Effect of climacteric transition and hormone replacement therapy on body weight and body fat distribution.

In the present study we evaluated the effects of climacteric modifications on body weight and fat distribution. From women attending a menopause clinic we selected 2175 untreated, normal healthy women who were divided into three groups: premenopausal (n = 540), perimenopausal (n = 750) and postmenopausal (n = 885), and compared them with 354 postmenopausal women receiving different forms of hormone replacement therapy (HRT). The total body fat tissue mass and distribution were analyzed using dual-energy X-ray absorptiometry. Body weight and body mass index (BMI) were significantly higher in perimenopausal and postmenopausal than in premenopausal women. Mean total body fat and fat as a percentage of soft tissue were significantly (p < 0.05) higher in the perimenopausal and postmenopausal groups than in the premenopausal group. Fat tissue and regional fat tissue as a percentage of total fat tissue were higher in the trunk (p < 0.0001) and arms (p < 0.0001) in perimenopausal and postmenopausal than in premenopausal women. In postmenopausal women, leg fat tissue was significantly (p < 0.05) lower than in premenopausal and perimenopausal groups. Total body and leg lean tissue were significantly lower (p < 0.05) in postmenopausal than in premenopausal and perimenopausal women. In age-matched women with similar BMI, total body fat as a percentage of soft tissue was significantly (p < 0.001) higher in the perimenopausal and postmenopausal groups than in the premenopausal group. As for body fat distribution, fat as a percentage of total fat tissue was significantly higher in the trunk (p < 0.0001) region in perimenopausal and postmenopausal women compared with the premenopausal group. In the legs, fat as a percentage of total fat tissue was significantly higher (p < 0.05) in the premenopausal than in the postmenopausal group. In the arms a slight but not significant (p < 0.18) difference was shown in fat distribution between the three untreated groups. In age-matched HRT-treated postmenopausal women, the fat tissue was similar to that in the premenopausal group. The present results confirm that endocrine changes during the menopausal transition, rather than the aging process, are related to changes in body weight and fat distribution. Perimenopausal and postmenopausal women show a shift to a central, android fat distribution that can be counteracted by HRT.