Inhibition of murine hepatitis virus infections by the immunomodulator 2,3,5,6,7,8-hexahydro-2-phenyl-8,8-dimethoxy-imidazo[1,2a]pyridine (PR-879-317A).

PR-879-317A (2,3,5,6,7,8-hexahydro-2-phenyl-8,8-dimethoxy-imidazo [1,2a]pyridine) has been found to be a T-cell-selective immunomodulating agent. In the current studies, a series of experiments was designed to determine the potential antiviral activity of this compound in mice infected with murine hepatitis virus. In a comparative antiviral experiment, the activity seen was superior to that of levamisole, a known immunorestorative agent. This activity was characterized by an increase in the 21-day survival frequency, a decrease in hepatic discoloration, a decrease in the amount of infectious virus recoverable from the liver, and normalization of serum glutamic oxalacetate and pyruvate transaminase levels. A comparison of treatment routes indicated the relative efficacies as intraperitoneal greater than per os greater than intramuscular greater than or equal to subcutaneous. Alteration of the treatment schedule markedly affected the antiviral effect; prophylactic or therapeutic treatments once or twice daily for 3 days were usually effective. Single treatments begun 4 h before or 24 h after virus inoculation were highly efficacious. Three treatments administered on alternate days, beginning 48 h before virus inoculation, proved moderately effective. Thrice-daily treatments were ineffective, as were treatments with durations of greater than 3 days. The optimal dosage varied according to the treatment route and dosage schedule. When assessed for direct antiviral activity in vitro, PR-879-317A failed to demonstrate any significant activity against murine hepatitis virus. The positive in vivo activity noted might therefore be the result of immune modulation rather than a direct antiviral effect.     

Academic,community and state mental health program collaboration: The Oregon experience

The authors review the relationship that has evolved over the years between the Department of Psychiatry at Oregon Health Sciences University and Oregon's community and state mental health programs. They describe the compatibility that exists between the basic requirements of academic psychiatry departments and public mental health programs and demonstrate how these organizations have been able to fulfill one another's needs in Oregon. Specific examples of successful collaborations in the areas of education, administration, research, and service are presented to illustrate how relationships that have been designed to meet specific requirements of one organization can fulfill many requirements of both. Suggestions are provided for those organizations contemplating similar collaborative endeavors.     

Surgical treatment of spinal chordomas

The clinical features and results of 34 patients with chordomas treated over a seven-year period were analyzed. Surgical treatment consisted of wide local excision (n = 6), marginal resection (n = 5), intralesional resection (n = 20), and biopsy (n = 3). Eighteen patients received postoperative radiotherapy. The local recurrence rate was 65%, with 30% of patients developing distant metastases. With the introduction of computed tomography, smaller tumors are currently being diagnosed; as a result, 35% of the patients in this series are disease free, compared with 10% described previously.     

Evaluation and treatment of sexual dysfunction in men with diabetes mellitus.

Sexual dysfunction is common among men with Type I and Type II diabetes. Tests of nocturnal penile tumescence (NPT) combined with waking tumescence and questionnaires can more accurately differentiate between primary organic and primary psychogenic impotence. This ability to differentiate the etiology of erectile dysfunction avoids the inappropriate use of penile injections and costly surgical procedures which are unnecessary in treatment of diabetic patients with primary psychogenic impotence. In patients with primary organic impotence, several new treatments are available which result in high patient satisfaction.     

Adenosine A1 receptor activation mediates suppression of (-) bicuculline methiodide-induced seizures in rat prepiriform cortex

The protective effects of a series of stable adenosine analogs against generalized seizures initiated by focal injection of bicuculline methiodide into the rat prepiriform cortex (PPC) were studied by microinjection of these compounds into this brain area. The adenosine agonists, 5'-N-(ethyl)carboxamido-adenosine (NECA), cyclohexyladenosine, cyclopentyadenosine, 2-chloroadenosine and R- and S-phenylisopropyladenosine (R- and S-PIA), protected animals against seizures in a dose-dependent, and extremely potent manner. NECA, the most potent compound evaluated, completely prevented seizures at doses greater than or equal to 6.8 pmol. In contrast, heroic doses of the A2 selective ligand, 2-phenylaminoadenosine, afforded no protection against seizures. The rank order of potency of these compounds in suppressing seizures is as follows: NECA greater than cyclohexyladenosine greater than cyclopentyladenosine greater than or equal to R-PIA greater than 2-chloroadenosine greater than S-PIA much greater than 2-phenylaminoadenosine. These data suggest that the antiseizure activity of these compounds in the PPC results from activation of A1 adenosine receptors. Quantitative autoradiographic analysis of the distribution of tritiated adenosine agonists 30 min after microinjection in the PPC reveals that [3H]NECA diffuses to a significantly greater extent than R-[3H]PIA, which may contribute to the relatively greater potency of the former compound in suppressing bicuculline methiodide-induced seizures. These results suggest that adenosine A1 receptors may participate in the normal inhibitory regulation of the PPC, a forebrain area which may play a significant role in the pathobiology of epilepsy.     

Mortality Rates and Predictors of Mortality Among Late-Middle-Aged and Older Substance Abuse Patients

This study describes mortality rates and predictors of mortality among late-middle-aged and older (55+) substance abuse inpatients ( n = 21, 139) in Department of Veterans Affairs (VA) Medical Centers in the 4 years after an index episode of care. A total of 24% of the patients died; this mortality rate was 2.64 times higher than expected. Predictors of earlier mortality included older age and nonmarried status, alcohol psychosis and organic brain disorder diagnoses, and several medical diagnoses, including neoplasms, liver cirrhosis, respiratory, endocrine and metabolic, and blood system disorders. Three proxy indicators of illness severity also predicted mortality: more prior inpatient and outpatient medical care and an index episode in an extended care unit. In contrast, more prior outpatient mental health care and remitted status predicted lower mortality. These diagnostic and treatment indicators can be used to identify patients at heightened risk for premature mortality. Moreover, they show that intensive mental health aftercare and remission of substance abuse may delay mortality, even among older patients who have longstanding substance abuse problems.