Early imaging in heart failure: Exploring novel molecular targets

Conclusions  Noninvasive imaging of neurohumoral upregulation in remodeled myocardium suggests that an imaging strategy can be developed for predicting the rate of remodeling and likelihood of HF development. This should allow a more judicious use of neurohumoral antagonists especially in subjects who do not have manifest HF.⁷⁴ In others specific targeted imaging may allow timely selection of individualized treatment strategies and ensure optimization of therapeutic intervention. Similar to ACE and AII receptors, multiple other targets in the hormonal cascades can identify the likelihood of adverse and favorable remodeling.⁷⁴     

Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study

Brain morphology was examined using magnetic resonance imaging in 30 first-episode patients with a schizophreniclike psychosis, 15 chronic schizophrenics, and 20 neurological controls. Statistical analyses of computer-generated measurements of regions of interest were controlled for gender, age, social class, and total brain volume. Lateral ventricular size was increased in both first-episode and chronic schizophrenic patients, with greater significance on the left than on the right side. Only the chronic patients, however, had reduced temporal lobe size, which also was greater on the left side. No major correlations of regional brain morphological measurements with cognitive functioning were found, although some measurements of verbal memory were correlated with parahippocampal size. This is a report of a preliminary study that suggests that some morphological brain changes may be present at the time of first treatment for a psychotic illness, whereas others may occur later in the course of illness. Future prospective studies may determine the clinical significance of these changes and whether they progress with the development of illness chronicity.     

Chemical traumatization of adult mouse olfactory epithelium in situ stimulates growth and differentiation of olfactory neurons in vitro

This study demonstrates that ZnSO₄ induced chemical trauma results in an in situ regeneration of the olfactory epithelium which, when maintained in vitro, provides an enriched population of olfactory neurons. Therefore, the ability of the olfactory epithelium to respond to chemical trauma with increased mitotic activity can be used to increase growth of neurons in culture. Tissue obtained from normal or vehicle-treated adult mice produced few olfactory neurons, when maintained in culture, compared to cultures established from tissue following an in situ ZnSO₄ trauma. Maximal neuronal yields were obtained in cultures established from tissue that was removed 4–6 days following chemical trauma. The morphological appearance and the presence of cell specific intermediate filament proteins were used to classify the cell types in these olfactory epithelial cultures. Single cells and aggregates of cells which were immunopositive for keratin, but immunonegative for neurofilament protein and GFAP, were identified as epithelioid. Flattened polygonal cells immunopositive for GFAP were identified as glia. A small population of flattened cells was immunonegative for all of the antibodies used in this study. Cells that had processes were immunonegative for GFAP and keratin. Some were immunopositive for 200 kDa and 160 kDa neurofilament proteins but immunonegative for the 68 kDa neurofilament protein. A few of these cells showed positive immunoreactivity with the olfactory marker protein (OMP) antibody and most likely represented the most mature olfactory neurons in the cultures. This trauma-induced culture model using olfactory tissue from adult mice can serve as a source of CNS neurons for comparison with cultured embryonic neurons.     

Elimination kinetics of maternally derived thyrotropin receptor-blocking antibodies in a newborn with significant thyrotropin elevation.

OBJECTIVE--To determine the course of maternally derived elevations in thyrotropin-binding inhibitory immunoglobulins in a neonate. DESIGN--Case report. SETTING--University pediatric endocrinology clinic and endocrine immunology laboratory in Ohio. PARTICIPANTS--An infant with elevated thyrotropin levels but near-normal total thyroxine levels, and her mother. INTERVENTIONS--None. MEASUREMENTS/MAIN RESULTS--Thyroid hormone, thyrotropin, and thyrotropin-blocking immunoglobulin concentrations were serially measured in a woman and her infant, who was found to have elevated thyrotropin levels (234 mU/L) and borderline low thyroxine levels (95 nmol/L). As infant thyroxine concentrations remained normal (125 to 145 nmol/L), no thyroxine supplementation was given. Thyrotropin levels decreased concomitantly with thyrotropin-blocking inhibitory immunoglobulin levels, and normalized by day 56 of life. The apparent elimination half-life of thyrotropin-blocking immunoglobulins was 7.5 days. CONCLUSIONS--The observed parallel elimination kinetics suggest that the thyrotropin receptor antibody acts as a thyrotropin antagonist, resulting in compensatory thyrotropin elevations. The duration of such elevations may be predicted on the basis of such elimination.     

Mucous cyst of the distal interphalangeal joint: treatment by simple excision or excision and rotation flap

Thirty-five patients who had thirty-seven mucous cysts excised from the distal interphalangeal joints were reviewed not less than one year later. Seven out of 25 which had been treated by simple excision recurred, whereas only one out of twelve treated by excision and skin closure with a rotation flap recurred.     

Definition of An Optimal First-line Chemotherapy in Metastatic Breast Cancer

Single-agent chemotherapy of metastatic breast cancer is the treatment of choice in patients with slow tumor progression and asymptomatic disease. In this patient group, the choice of drugs is based more on good tolerability than on efficacy. By contrast, symptomatic or rapidly progressing disease requires the use of highly active regimens where more weight is put on reliable antitumor activity. While anthraycline-based combination regimens have set the standard of effective treatment, the addition of docetaxel (and to a lesser extent paclitaxel) has improved tumor response, but failed to induce a consistent prolongation of survival. Based on retrospective analyses, it is hypothesised that the combined use of anthracyclines and taxanes in first-line therapy may be most beneficial in defined subgroups: after adjuvant chemotherapy, in patients with HER-2 gene amplification, possibly also in patients with rapidly progressing visceral disease.