Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration.

PURPOSE: To compare the impact of sustained supplementation using different macular carotenoid formulations on macular pigment (MP) and visual function in early age-related macular degeneration (AMD). PATIENTS AND METHODS: Sixty-seven subjects with early AMD were randomly assigned to: Group 1 (20 mg per day lutein (L), 0.86 mg per day zeaxanthin (Z); Ultra Lutein), Group 2 (10 mg per day meso-zeaxanthin (MZ), 10 mg per day L, 2 mg per day Z; Macushield; Macuhealth), Group 3 (17 mg per day MZ, 3 mg per day L, 2 mg per day Z). MP was measured using customised heterochromatic flicker photometry and visual function was assessed by measuring contrast sensitivity (CS) and best-corrected visual acuity (BCVA). AMD was graded using the Wisconsin Age-Related Maculopathy Grading System (AREDS 11-step severity scale). RESULTS: At 3 years, a significant increase in MP from baseline was observed in all groups at each eccentricity (P<0.05), except at 1.75° in Group 1 (P=0.160). Between 24 and 36 months, significant increases in MP at each eccentricity were seen in Group 3 (P<0.05 for all), and at 0.50° in Group 2 (P<0.05), whereas no significant increases were seen in Group 1 (P>0.05 for all). At 36 months, compared with baseline, the following significant improvements (P<0.05) in CS were observed: Group 2-1.2, 6, and 9.6 cycles per degree (c.p.d.); Group 1-15.15 c.p.d.; and Group 3-6, 9.6, and 15.15 c.p.d. No significant changes in BCVA, or progression to advanced AMD, were observed. CONCLUSION: In early AMD, MP can be augmented with a variety of supplements, although the inclusion of MZ may confer benefits in terms of panprofile augmentation and in terms of CS enhancement.

Development and application of a GFP-FRET intracellular caspase assay for drug screening.

Apoptosis is a crucial biological process, and activation of caspase endoproteases is essential for proper regulation and execution of apoptosis. Because caspases also appear to be central players in several pathological states, there is a practical need within the biopharmaceutical research community for facile, noninvasive cellular assays for the discovery of compounds that modulate caspase activity. Tandem molecules of green fluorescent protein (GFP) stably expressed within cells can serve as a genetically encoded sensor of protease activity. Using this technology, we have developed a stable cellular system for the screening of agents that modulate activation of the caspase cascade. This assay technology allows for the real-time monitoring of apoptosis in situ, using conventional fluorescent plate reader detection. By applying this assay system to an actual compound screen, small-molecule inducers of cell apoptosis were reliably identified. Follow-up pharmacology confirmed that the rank-order potency of primary hits using the intracellular GFP assay corresponded to that found using a conventional, cell lysis-based assay method.

1H-magnetic resonance spectroscopy of the left temporal and frontal lobes in schizophrenia: clinical, neurodevelopmental, and cognitive correlates.

Twenty eight schizophrenic patients and 20 normal volunteers underwent proton magnetic resonance spectroscopy (MRS) on the left temporal and frontal lobe regions. Male patients showed a significant reduction in frontal but not temporal n-acetylaspartate (an intraneuronally distributed metabolite) in comparison with either male controls or female patients; frontal choline was raised in male patients relative to these groups. Putative neurodevelopmental indices, including obstetric complications, family history of schizophrenia, and minor physical anomalies, proved unrelated to MRS resonances. However, multiple aspects of memory function in patients were related to temporal but not frontal creatine, a pattern that was not apparent among controls. These MRS findings complement some previous structural MRI studies and much clinical and epidemiological evidence of important gender differences in schizophrenia. The findings also suggest that memory dysfunction in patients with schizophrenia may be associated with a particular pattern of temporal lobe metabolism on MRS.

Tissue characterization and assessment of preoperative chemotherapeutic response in musculoskeletal tumors by in vivo 31P magnetic resonance spectroscopy.

This study investigates the potential of in vivo 31P magnetic resonance spectroscopy (MRS) to characterize musculoskeletal tumors and to determine preoperative levels of histological necrosis, which is an important clinical indicator of patient response. Pretherapy MRS was performed on 28 patients with large musculoskeletal tumors: 13 with osteosarcoma, 3 with chondrosarcoma, 5 with malignant fibrous histiocytoma, 1 with desmoid tumor, 1 with Ewing's, 2 with hemangioendothelioma, 1 with myxoid liposarcoma, 1 with synovial cell sarcoma, and 1 with rhabdomyosarcoma. Fifteen patients had follow-up MRS examinations after commencement of chemotherapy (mean of five/patient), eight of whom have now had surgery. Elevated levels of PMEs (P < 0.01), P(i) (P < 0.01), and PDEs (P < 0.02) as well as elevated tumor pH (P < 0.05) were observed in all patients. The synovial cell sarcoma was characterized by high levels of PMEs (> 20%) and low pH (pH 6.76). This contrasted with the spectra obtained from the malignant fibrous histiocytomas which had high levels of PDEs (17 +/- 5%). Reductions in PDE levels postchemotherapy were associated with a high degree of necrosis (> 90%) at surgery, while an increase in PDE levels was associated with a low level of histological necrosis. Likewise, reductions in the ratios PDE/NTP and PDE/PCr and an increase in P(i)/PDE were also associated with a high level of necrosis.

Bilateral paramedian thalamic infarction: a distinct but poorly recognized stroke syndrome.

Six patients with bilateral paramedian thalamic infarction were seen in a general hospital over a 4 year period. This distinct stroke syndrome was recognized by the features of disturbed vigilance, often episodic, with vertical gaze disorder. Other signs included an amnesic syndrome, convergence difficulty, third nerve palsies, eyelid retraction, dysarthria, ataxia and involuntary limb movements. Diagnosis was confirmed by CT brain scan or magnetic resonance imaging. A variety of risk factors for stroke were present. All patients improved but two had significant residual disabilities.

In vivo phosphorus-31 magnetic resonance spectroscopy of normal and pathological breast tissues.

In vivo phosphorus-31 magnetic resonance spectroscopy, at 1.5 T, in addition to magnetic resonance imaging and mammography, was performed on the breast tissue of 59 subjects, using a 40 mm or 80 mm surface coil for spectral localization. The patients were divided into three groups: Group 1, 46 control subjects; Group 2, nine patients with breast carcinoma; Group 3, four patients with benign breast disease. The relationship of age, menopausal status, breast size and pattern, use of contraceptive pill and history of breast disease to spectral characteristics of breast tissue was examined for the control group. In multivariate analysis, only menopausal status and age were found to be significantly related to tissue biochemistry. Pre-menopausal women had reduced phosphocreatine (PCr) (%) (p = 0.02), and increased phosphomonoesters (PMEs) and beta-nucleotide triphosphate (beta-NTP) (%) (p = 0.05), while the fat-to-water ratio was higher in older women (p = 0.02). No significant differences were identified between the control subjects and the patients with benign breast disease. When spectra from patients with breast carcinoma were compared with an age-matched volunteer group, alpha- and gamma-NTP (%) were found to be higher in the cancer tissue (p less than 0.01 and p = 0.01, respectively), while PCr (%) was reduced (p less than 0.01). The ratio beta-NTP:PCr was higher in the carcinoma group of patients (p less than 0.05). In vivo phosphorus-31 magnetic resonance spectroscopy is a non-invasive examination which may prove useful in the early differentiation of malignant breast disease from normal and benign conditions.

Paternalistic vs egalitarian physician styles: the treatment of patients in crisis.

According to previous reports, the quality of the physician-patient relationship plays an important role in medical outcome. A patient's responsiveness to suggestions, perceptions of treatment, and physical distress may be affected both by the type of interpersonal relationship and by the patient's anxiety. To test these hypotheses, 57 women who received elective abortions were treated by the physician in either a "paternalistic" or "egalitarian" interpersonal style. Each patient was tested for responsiveness to suggestions regarding changes in somatic perception such as heat or pain; a measure of psychological dependency on the physician was also obtained in addition to ratings of discomfort and signs of physiological distress during the medical procedure. Patient anxiety was not related to any of these variables, but patients treated in a paternalistic manner had higher responsiveness to suggestibility (P less than .001), felt they could depend more on the physician and perceived him as warmer and more supportive (P less than .01), had less discomfort during the procedure (P less than .05), and had a lower incidence of physiological distress compared with patients treated in an egalitarian manner. It was concluded that, for patients in crisis, paternalistic treatment by a physician may promote positive psychological and medical outcome.