Psychoneuroendocrinology of anxiety disorders

This article focuses on neuroendocrine measures in anxiety disorders and their relationships to neurotransmitter and neuroendocrine function. In particular, the hypothalamic-pituitary-somatotropin and the hypothalamic-pituitary-adrenal (HPA) axes are emphasized, and a role for extrahypothalamic corticotropin releasing factor is proposed. Additional neuroactive hormones are also considered. A nonhuman primate model of anxiety is discussed in terms of its neuroendocrine relevance. And, throughout, a hypothetical functional-anatomic model for anxiety and panic is proposed using the findings of cognitive neuroscience fear research. Finally, an effort is made to synthesize existing psychoneuroendocrinologic data into a current conceptualization of the pathophysiology of anxiety disorders.     

Prognostic value of prostate-specific antigen for women with breast cancer: a large United States cohort study

Prostate-specific antigen (PSA) is a valuable tumor marker used for diagnosis and management of prostate cancer. Recently, PSA has been found in various female tissues and body fluids. Female breasts, both normal and abnormal, including cancerous tissues, can produce PSA, and this production is regulated by androgens and progestins. Preliminary data suggested that patients with breast tumors positive for PSA may have better prognosis compared to those with PSA-negative breast tumors. This study examines the prognostic value of PSA in a large cohort study of United States patients. Using a PSA assay that has a lower detection limit of 0.001 ng/ml, we measured PSA in tumor cytosolic extracts of 953 women with primary breast cancer. Other information available for this study included age, follow-up time, survival outcome, tumor size, nodal status, steroid hormone receptor levels, DNA analysis by flow cytometry, and postoperative treatment. The median follow-up time was 73 months. During the follow-up, 200 patients relapsed and 188 died. PSA presence was found to be significantly associated with smaller tumors, tumors with low S-phase fraction, diploid tumors, younger patient age, and tumors with lower cellularity. Survival analysis indicated that the relative risks (RRs) for relapse and death were both significantly lower [RR = 0.67 (P = 0.01) for relapse; RR = 0.72 (P = 0.05) for death] in PSA-positive patients (levels higher than the 30th percentile of PSA values) than in PSA-negative patients. The reduced risks for relapse and death remained statistically significant after other clinical and pathological variables were adjusted in the multivariate analysis [RR = 0.68 (P = 0.02) for relapse; RR = 0.65 (P = 0.02) for death]. Our results suggest that the measurement of PSA in breast tumor extracts provides additional information on the prognosis of patients with primary breast cancer.     

High serum calcium in human brucellosis: a case-control study

In a retrospective case-control study of 58 cases of human brucellosis, adjusted mean serum calcium levels were found to be significantly higher in patients with brucellosis compared with controls: mean (95% confidence interval) = 2.39 (2.35-2.42) mmol/L versus 2.30 (2.26-2.34) mmol/L (P = 0.0012). The possible mechanisms underlying the cause of hypercalcemia in human brucellosis are discussed.     

A prototype Internet autopsy database. 1625 consecutive fetal and neonatal autopsy facesheets spanning 20 years

OBJECTIVE: To demonstrate that cause-of-death statements can be generated by a computer algorithm from an autopsy database composed of diagnostic terms. DATA SOURCES: Over 49 000 autopsy facesheets contributed by over a dozen institutions were collected from a publicly accessible Internet autopsy database. This database is available at the following web site: http:@www.med.jhu.edu/pathology/iad.html STUDY SELECTION: To test the feasibility of creating and using a publicly available autopsy database, and to identify the technical and medicolegal problems that may arise with such a novel resource, a prototype study was designed by selecting autopsy facesheets from fetal and neonatal deaths. An algorithm was developed to determine the cause of death from the listing of anatomic diagnoses. DATA EXTRACTION: One thousand six hundred twenty-five fetal and neonatal autopsy facesheets were selected encompassing fetal and neonatal deaths occurring up to 28 days after birth. DATA SYNTHESIS: The algorithm determined causes of death from autopsy facesheet data in all cases. On review by an experienced pediatric pathologist, these automatically generated cause-of-death statements required no modification or only slight modification in over 90% of cases. CONCLUSIONS: A large multi-institutional autopsy database composed of demographic and diagnostic information has been deposited on the Internet. This information can be freely downloaded and used by any researcher without violating patient confidentiality. As a demonstration of one possible application of the database, fetal and neonatal autopsies generated cause-of-death statements using a computer algorithm. One can anticipate that the wealth of information contained in autopsy facesheets can be assembled into a database that will serve the public interest.     

Socioeconomic status, neighborhood social conditions, and neural tube defects

OBJECTIVES: This study evaluated the contributions of lower socioeconomic status (SES) and neighborhood socioeconomic characteristics to neural tube defect etiology. The influence of additional factors, including periconceptional multivitamin use and race/ethnicity, was also explored. METHODS: Data derived from a case-control study of California pregnancies from 1989 to 1991. Mothers of 538 (87.8% of eligible) case infants/fetuses with neural tube defects and mothers of 539 (88.2%) nonmalformed infants were interviewed about their SES. Reported addresses were linked to 1990 US census information to characterize neighborhoods. RESULTS: Twofold elevated risks were observed for several SES indicators. Risks were somewhat confounded by vitamin use, race/ethnicity, age, body mass index, and fever but remained elevated after adjustment. A risk gradient was seen with increasing number of lower SES indicators. Women with 1 to 3 and 4 to 6 lower SES indicators had adjusted odds ratios of 1.6 (1.1-2.2) and 3.2 (1.9-5.4), respectively, compared with women with no lower SES indicators. CONCLUSIONS: Both lower SES and residence in a SES-lower neighborhood increased the risk of an neural tube defect-affected pregnancy, with risks increasing across a gradient of SES indicators.     

Influence of ACTH-(1-24) on free radical levels in the blood of haemorrhage-shocked rats: direct ex vivo detection by electron spin resonance spectrometry

The protein fusion technique was applied in the synthesis of an artificial dimer of ribonuclease H (305 residues). 1H NMR spectroscopy was used to analyze the structure of this dimer. Spectral profiles and pKa values of the histidine residues obtained using 1H NMR indicate that the dimer retains the secondary and tertiary structures of the intact monomer. Selective spin-lattice relaxation measurements suggest that the two monomeric units in the dimer are in tight contact. Furthermore, the 2D 1H NMR and paramagnetic relaxation filter results show that the two monomers bind together through interactions between the N- and C-terminal sites of the linked regions.     

Range of validity of alpha and beta for a generalized diversity index H (alpha, beta) due to Good

1. Many human fetuses have to adapt to a limited supply of nutrients. In doing so they permanently change their structure and metabolism. 2. These 'programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders stroke, diabetes and hypertension. 3. This review examines the evidence linking these diseases to fetal undernutrition and provides an overview of previous studies in this area.     

The genetics of aging

We present a case of a patient who is HIV positive and developed both thrombotic thrombocytopenia purpura and visceral Kaposi's sarcoma (KS) with hemorrhage. This case presents a difficult management problem in that the patient's bleeding originated from KS lesions and did not quickly abate with plasmapheresis therapy despite both clinical and laboratory improvement after 2-4 days. Chemotherapy was initiated on day 13 and the patient's condition improved markedly afterward. We believe the addition of chemotherapy to plasmapheresis hastened the improvement of our patient's thrombotic thrombocytopenic purpura (TTP) and KS-related bleeding. Therefore, under similar conditions, we recommend combining plasmapheresis and chemotherapy at the onset of therapy.     

Dose of hemodialysis and survival: differences by race and sex

CONTEXT: Although blacks receive lower doses of hemodialysis than whites, their survival when receiving dialysis treatment is better than that for whites. Previous studies of the relationship between the dose of dialysis and patient survival have not controlled for differences in patient characteristics. OBJECTIVE: To examine the association of mortality with the dose of hemodialysis for clusters of patients categorized by race and sex. DESIGN: Retrospective analysis of laboratory data and mortality outcomes from 1994, using a national database of hemodialysis patients. PATIENTS: A total of 18144 black and white patients receiving hemodialysis 3 times weekly who either lived the entire year receiving hemodialysis or died. MAIN OUTCOME MEASURES: The fractional reduction of urea in a single dialysis session as the measured hemodialysis dose (urea reduction ratio [URR]) after controlling for race, sex, age, and diabetes mellitus. Mortality was determined by strata of URRs and albumin and creatinine levels. RESULTS: Across all age categories, blacks had lower URRs than whites, and men had lower URRs than women. In an age-adjusted model for evaluating interactions among URRs, race, sex, and diabetes, the association of URR with mortality risk was weak among blacks, particularly black men. After adjustment for age and diabetes, death probability curves were most steep for white women with URR values less than 60%. The death probability curves were least steep for black men. There was no meaningful difference between death probability and albumin or creatinine concentration among the race by sex clusters. CONCLUSION: Using URR, the usual measure of hemodialysis dose, the assumption that the association between dialysis dose and survival is uniform across demographic groups appears incorrect. Comparisons of the quality of dialysis patient care should not rely on URR alone to predict patient survival.     

Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis

Uric acid, the naturally occurring product of purine metabolism, is a strong peroxynitrite scavenger, as demonstrated by the capacity to bind peroxynitrite but not nitric oxide (NO) produced by lipopolysaccharide-stimulated cells of a mouse monocyte line. In this study, we used uric acid to treat experimental allergic encephalomyelitis (EAE) in the PLSJL strain of mice, which develop a chronic form of the disease with remissions and exacerbations. Uric acid administration was found to have strong therapeutic effects in a dose-dependent fashion. A regimen of four daily doses of 500 mg/kg uric acid was required to promote long-term survival regardless of whether treatment was initiated before or after the clinical symptoms of EAE had appeared. The requirement for multiple doses is likely to be caused by the rapid clearance of uric acid in mice which, unlike humans, metabolize uric acid a step further to allantoin. Uric acid treatment also was found to diminish clinical signs of a disease resembling EAE in interferon-gamma receptor knockout mice. A possible association between multiple sclerosis (MS), the disease on which EAE is modeled, and uric acid is supported by the finding that patients with MS have significantly lower levels of serum uric acid than controls. In addition, statistical evaluation of more than 20 million patient records for the incidence of MS and gout (hyperuricemic) revealed that the two diseases are almost mutually exclusive, raising the possibility that hyperuricemia may protect against MS.