Perspectives from the National Institute of Mental Health: Preventing or living with aids

This article provides a succinct overview of the history and current and future research priorities of the Office on AIDS at the National Institute of Mental Health (NIMH). Throughout its history and currently, the Office on AIDS has encouraged and supported research on primary prevention of human immunodeficiency virus (HIV) transmission, effects of HIV disease on the central nervous system, and coping with the sequelae of infection. Future directions for the NIMH include the dissemination of research fmdings to the community, investigation of mechanisms for involving and retaining participants in large-scale vaccine trials, and continued attention to the prevention of HIV transmission through behavior change.     

MR imaging of the pericardial cyst.

Findings obtained with magnetic resonance (MR) imaging in four patients with pericardial cyst are reported. MR imaging allowed not only localization and diagnosis in all four cases but characterization of cystic content. MR imaging, including RARE (rapid acquisition with relaxation enhancement) MR hydrography, which shows only liquids with T2s greater than 500 msec, proved to be useful in characterizing the fluid content of a mediastinal lesion and monitoring follow-up. In one case, MR imaging allowed differentiation of a pericardial cyst from a suspected necrotic lymph node in a patient with colic carcinoma, with subsequent correction of staging and therapy. The authors conclude that MR imaging is the method of choice for diagnosis (especially in unusual locations) and monitoring of pericardial cysts and for differential diagnosis of malignant mediastinal cystic tumors that show a solid part.     

Relation of endocrine and cardiac findings in acromegalics.

Cardiac involvement in 32 acromegalics was related to endocrine parameters, clinical score and duration of the disease as well as compared to that of 50 controls free of cardiac disease. Stress ECG, 24h Holter monitoring and echocardiography revealed that supraventricular premature complexes did not occur more often in acromegalics than in controls, both prevalence and severity of ventricular arrhythmia, however, were higher in patients compared to controls: 15/32 (48%) acromegalics had complex ventricular arrhythmia as compared with 6/50 (12%) normal subjects (p less than 0.01). Repetitive ventricular arrhythmia was manifest in 10/32 (31%) patients but only in 4/50 (8%) controls (p less than 0.01). Furthermore, frequency of ventricular premature complexes increased with duration of acromegaly (p less than 0.01), the severity of the former being correlated with left ventricular mass and with clinical activity score (p less than 0.01). No correlation, however, was found between the degree of ventricular arrhythmia and hormone levels. Left ventricular muscle mass was increased (p less than 0.02) due to concentric hypertrophy. Thus, compared to controls, acromegalics show more frequent and complex ventricular arrhythmia and left ventricular hypertrophy. Duration of the disease rather than hormone levels seems to be relevant for these pathological changes.     

Rapid screening of natural products for antimycobacterial activity by using luciferase-expressing strains of Mycobacterium bovis BCG and Mycobacterium intracellulare.

The object of this study was to investigate the ability of a rapid luciferase assay to detect antimycobacterial activity in plant extracts. Recombinant strains of Mycobacterium bovis BCG (rBCG) and Mycobacterium intracellulare expressing firefly luciferase were used as the test organisms. Assays were conducted in a 96-well minitube format under biosafety level 2 conditions. Control and test wells were sampled immediately after inoculation and after 3 (recombinant M. intracellulare) and 5 (rBCG) days of incubation to measure luminescence with a microplate luminometer, and the relative change in luminescence was calculated as a percentage of control values. As an alternative test method, Alamar blue was added after 12 days of incubation, and changes in color were read visually. A total of 480 extracts were tested. Sixteen extracts were active against rBCG, and of those, seven were also active against recombinant M. intracellulare. With activity defined as a relative change in luminescence of < or = 1% (i.e., > or = 99% inhibition) and a persistence of blue color after addition of Alamar blue, there was 99.0% agreement between the two methods. Our results suggest that the luciferase assay is rapid and accurate and has the potential to greatly accelerate the evaluation of antimycobacterial activity in plant extracts in vitro. With this method, it is possible to screen a large number of samples in a short period of time.     

Estradiol binds to a receptor-like cytosol binding protein and initiates a biological response in Paracoccidioides brasiliensis.

Paracoccidioidomycosis, a disease caused by Paracoccidioides brasiliensis, which is endemic to Latin America, is much more common in men than women, suggesting a role for hormonal factors. We recently showed that two other yeasts possess steroid binding proteins and postulated that these receptor-like molecules represented a mechanism by which the hormonal milieu of the host might influence an infecting pathogen. Therefore, we examined P. brasiliensis for a sex steroid binding protein. Because tritiated steroids rapidly dissociated from the other fungal binding proteins, we developed a fast binding method with Sephadex G-50 microcolumns speeded by centrifugation. This method detected specific binding of [3H]estradiol in P. brasiliensis cytosol. Other tritiated steroid hormones, including testosterone and corticosterone, failed to exhibit specific binding. Scatchard analysis of [3H]estradiol binding showed an apparent dissociation constant (Kd) of 1.7 X 10(-8) M and a maximal binding capacity (Nmax) of 235 fmol/mg of protein. Susceptibility to trypsin indicated the binding site was protein in nature. The protein had a Stokes radius of approximately equal to 32 A by HPLC exclusion column and a sedimentation coefficient of 4.4 S by sucrose gradient, consistent with an apparent Mr of approximately equal to 60,000. Competition experiments revealed that estrone, estriol, and progesterone had 25% of the affinity of estradiol, whereas diethylstilbestrol, androgens, and corticosteroids had low affinity. Investigation of steroid hormone actions in P. brasiliensis indicated that estradiol inhibited the fungal transformation from mycelial form to yeast form, the initial step of infection. This suppressive effect was dose-dependent and not found with testosterone. We hypothesize that endogenous estrogens in the host, acting through the cytosol binding protein in the fungus, inhibit mycelial-to-yeast transformation, thus explaining the resistance of women to paracoccidioidomycosis.     

Nonclinical outcomes of hospital-based palliative care

Evidence-based outcomes are commonly used in making decisions about clinical care. For healthcare executives, evidence-based outcomes also can be useful in making decisions about hospital services. Finkler and Ward (2003) suggest a model whereby cost measurement, cost control, and value assessment can be used as nonclinical, evidence-based outcome measures to provide decision support and to guide management decisions. The Finkler and Ward framework is used to understand the financial implications of establishing an inpatient palliative care unit (PCU). A longitudinal study was conducted to examine the nonclinical outcomes associated with opening and operating an inpatient PCU at a large academic medical center during the first four years of the unit's operation. First, the cost of providing inpatient palliative care was measured. Results indicated that the cost per day to care for patients hospitalized in the last 20 days leading up to their death was significantly less on the PCU than on intensive care units and non-PCUs. Average daily total charges exceeded reimbursement on the ICU and non-PCUs, but the cost on the PCU for the same population was equal to or below the average daily total charges. Second, ways to control costs when operating an inpatient PCU were identified and measured. Evidence from one organization suggests that costs can effectively be controlled by admitting patients directly to the PCU and by appropriate use of hospital resources, including staff, ancillary services, and pharmaceuticals. Third, the study assessed the value to the institution of operating an inpatient PCU. Results indicated that the inpatient PCU yielded a cost savings of nearly 1 million dollars by the third year of operations. This study highlights the nonclinical outcomes of one institution's inpatient PCU and provides guidelines for healthcare executives and managers to use in making decisions about adopting such programs.     

Investigation of different combinations of estrogen therapy and radiation therapy on prostatic adenocarcinoma (R-3327)

The relative effectiveness of different combinations of estrogen therapy and radiation therapy against the R-3327 prostatic adenocarcinoma of the Copenhagen rat was studied. Because of similar actions of estrogens and radiation in the cell cycle, and possibly antagonistic effects reported in the clinical literature, we looked for an antagonism between these two therapeutic modalities. Radiation therapy consistently showed a greater tumor inhibitory effect than estrogen therapy alone at the dose tested. Combinations of radiation therapy with hormonal manipulation did not appear to show a greater inhibition of tumor growth than radiation therapy alone. There also did not appear to be an antagonistic effect between these two modalities in this system.     

In vivo selection of androgen-insensitive cells in R3327-G rat prostate tumors: diethylstilbestrol diphosphate treatment versus orchiectomy

Tumors grown in diethylstilbestrol diphosphate (DES)-treated rats grew significantly more slowly than tumors grown in orchiectomized animals, and tumors grown in orchiectomized animals grew significantly more slowly than tumors grown in controls (intact male rats). When these tumors (phase I) were dispersed and reimplanted into DES-treated, orchiectomized, or control rats in all possible combinations (phase II), a partial selection of androgen-insensitive cells was observed in tumors grown in DES-treated animals. Tumors grown in DES-treated phase I animals responded significantly less to DES treatment or orchiectomy in phase II. In contrast, tumors from phase I orchiectomized animals showed the same responses to orchiectomy in phase II. Since the administration of exogenous testosterone propionate prevented the growth rate inhibitory effects of both DES treatment and orchiectomy, the added effect of DES seemed to be antiandrogenic.