Baseline immune activation as a risk factor for the onset of depression during interferon-alpha treatment.

BACKGROUND: Major depression has been associated cross-sectionally with increased cell-mediated immune activation but causality has been difficult to establish. This study prospectively investigated the hypothesis that baseline level of immune activation predicts the development of depression during interferon-alpha (IFN-alpha) treatment. METHODS: Sixteen hepatitis C patients without psychiatric disorder underwent IFN-alpha treatment. Proinflammatory and anti-inflammatory cytokines were determined before starting treatment. Presence of a major depressive disorder (MDD) was assessed at baseline and several times during treatment. RESULTS: Baseline soluble interleukin-2 receptor (sIL-2r), interleukin-6 (IL-6), and interleukin-10 (IL-10) concentrations were significantly increased in the five subjects that developed MDD during treatment compared with those that did not, with standardized effect sizes of 1.08, 1.16, and 1.25, respectively, controlling for marijuana use, cigarette smoking, and baseline level of depressive symptoms. CONCLUSIONS: Results suggest that increased immune activation, rather than an epiphenomenon, is a causal risk factor for the development of MDD.     

Specific and sensitive diagnosis of syphilis using a real-time PCR for Treponema pallidum

A real-time PCR assay with a Taqman probe was developed that targeted the polA gene of Treponema pallidum. The test was validated using an analytical panel (n = 140) and a clinical panel of genital samples (n = 112) from patients attending a sexually transmitted infections clinic. High sensitivities and specificities of 94-100% were achieved using two real-time PCR platforms, the Rotor-Gene and the iCycler. The assay can be completed within 2 h, enabling reporting in <8 h. This fast and robust assay is suitable for implementation in routine laboratories for diagnosing primary syphilis.     

Uroscopy in the 21st century: high-field NMR spectroscopy

From the experiments described, it can be seen that there are different research approaches that can be taken and these are summarized in Table 1. Whereas much scientific research is principally hypothesis led, there remains, nevertheless, an important place for exploratory research. High resolution NMR can measure, directly and simultaneously, a wide range of endogenous metabolites in biological fluids and has the unique capability of providing structural information on the metabolites detected. It has proved to be a powerful research tool with which to study inherited metabolic diseases, renal disease, drug metabolism, and toxicity, and can be used to monitor the effects of drug therapy. For instance, by using a library of experimental toxins one can map the metabolic profile of site-specific nephron injury. With this approach in man one could eventually take an unknown disease such as Balkan nephropathy and predict the initial site of tubular injury, the mode of injury and therefore the kind of toxin capable of producing that injury. NMR spectroscopic techniques are still advancing rapidly, with ever increasing sensitivity and sophistication of NMR pulse sequences to enhance structural elucidation in complex mixtures. Given the advances in directly coupled HPLC-NMR and even HPLC-NMR-mass spectroscopy it is likely that these technologies in conjunction with pattern recognition will make major contribution to our understanding of renal processes and provide new diagnostic insights in the 21st century.      

Decision support in psychiatry – a comparison between the diagnostic outcomes using a computerized decision support system versus manual diagnosis

Background  

Correct diagnosis in psychiatry may be improved by novel diagnostic procedures. Computerized Decision Support Systems (CDSS) are suggested to be able to improve diagnostic procedures, but some studies indicate possible problems. Therefore, it could be important to investigate CDSS systems with regard to their feasibility to improve diagnostic procedures as well as to save time.     

Immunohistochemical and ultrastructural analysis of a mammary cystic hypersecretory carcinoma

Cystic hypersecretory carcinoma (CHC) is a rare variant of intraductal carcinoma. A CHC in a 50-year-old woman was excised and processed for light and electron microscopy and immunohistochemistry. The tumor had a marked cystic appearance. The walls of the cysts consisted of epithelial and myoepithelial cells and a well-developed basement membrane. The epithelial cells contained well-developed rough-surfaced endoplasmatic reticulum and Golgi apparatus. Secretory granules were not detected, with the exception of a few mucus-producing cells. The secretion was predominantly homogenous, reminiscent of thyroid colloid, and demonstrated distinct PAS positivity. The cells displayed a strong labeling with epithelial membrane antigen (EMA) and EMA-positive structures were observed within the intraluminal secretion, too. Some of these were stained by alcian blue. In addition, the colloid-like material was admixed with mucus showing a filamentous internal structure and lipid droplets resulting in some heterogenity of the secretion. Intraductal micropapillary proliferation in some of the cysts and adjacent nondistended ducts was a further defining feature of the tumor. Steroid hormone receptor and Ki-67 proliferation marker immuno his Tochemistry showed scattered positivity among the tumor cells. These results are in agreement with previous observations and further clarify the nature of this low-grade in situ cancer.     

Does crossing over repeated treatment with the dopamine reuptake inhibitors cocaine and BTCP modify their effects on cocaine-induced locomotion?

Because the dopamine reuptake inhibitors cocaine and BTCP produce different behavioral effects after repeated administration, we studied whether they could alter each other’s effects by examining the effects of crossing over repeated treatment with cocaine and BTCP on cocaine-induced locomotion. Male C57BL/6 mice were treated repeatedly with cocaine or BTCP during a first phase (days 1–3) and 3 days later, treated repeatedly with the same or the other compound during a second phase (days 7–9), after which they were administered one of several doses of cocaine on the next day. Locomotor activity was assessed after every daily treatment. The results show that 1) cocaine induced sensitization to its locomotor effects, 2) cocaine-induced sensitization was not altered by subsequent repeated treatment with BTCP, 3) initial repeated treatment with BTCP induced apparent cross-tolerance to cocaine, and 4) the initial effects of repeated BTCP were not markedly altered by subsequent repeated treatment with cocaine. The results indicate that the initial effects produced by repeated cocaine or BTCP are enduring and relatively difficult to alter by crossing over repeated treatment with the other compound. Thus, sensitization to the locomotor effects of cocaine in mice appeared to be attenuated by prior repeated treatment with BTCP but not reversed when followed by repeated treatment with BTCP. Received: 11 January 1998/Final version: 17 September 1998     

Behavioural specificity of chlordiazepoxide-produced StD

Low doses of benzodiazepines produce state-dependence (StD) of food-rewarded lever pressing in rats, and it has been hypothesized that the changes of memory states that can thus be studied constitute the mechanism whereby benzodiazepines cause their characteristic psychopharmacological actions such as anxiolysis, apparent memory loss and dependence. Non-benzodiazepine CNS agents such as NMDA antagonists also produce StD in this procedure, suggesting that the StD hypothesis of psychopharmacological drug action can be expanded to include agents other than benzodiazepines. For this expansion to be possible, however, it must be shown that the StD mechanism operates in a specific manner. The present experiments examined whether varying the extent of food deprivation affects any of a number of quantitative features of chlordiazepoxide (CDP)-induced StD of food-rewarded lever pressing in rats. The data indicate that the CDP doses required to generate StD in both drug-to-saline and dose-to-dose transfer tests, are considerably lower in relatively sated as opposed to more deprived animals; little or no difference was found in tests assaying saline-to-drug transfer. The data add behavioural to available pharmacological evidence supporting the hypothesis that changes of memory state constitute the mechanism whereby CNS agents such as benzodiazepines and NMDA antagonists cause their characteristic psychopharmacological actions. Some directions for future research are identified to explore further the pharmacological and behavioural specificity of drug-produced StD.     

Risk factors for calcification of the vertebrobasilar arteries in cardiovascular patients referred for a head CT,the SMART study

Background and purposeVertebrobasilar artery calcification (VBAC) has been associated with increased stroke occurrence. Little is known on VBAC risk factors, especially for patients with cardiovascular disease. We aimed to assess risk factors associated with VBAC in a cohort of cardiovascular patients referred for a head computed tomography (CT) scan.Materials and methodsAll patients who underwent a clinically indicated, unenhanced, thin slice head CT 6 months before or after inclusion in the SMART study were included. CTs were assessed for presence of VBAC (dichotomously). Relative risks of the associations of age, sex, diabetes mellitus (DM), obesity, body mass index, estimated glomerular filtration rate, hypertension, hyperlipidemia, use of lipid lowering medication, smoking status, high sensitivity C-reactive protein, ankle-brachial index (ABI; ≤ 0.90, ≥ 1.30, continuous), internal carotid artery stenosis ≥ 70%, and carotid intima-media thickness (IMT) with VBAC were estimated using Poisson regression analysis with robust standard errors, adjusted for age and sex.ResultsOf the 471 patients included (57% male, median age 58 [interquartile range 47–63]), 117 (24.8%) showed VBAC. Presence of VBAC was associated with older age (RR per 10 years = 1.70 [95%CI 1.46–1.99]), DM (RR = 1.45 [95%CI 1.03–2.06]), obesity (RR = 1.53 [95%CI 1.10–2.12]), ABI ≤ 0.90 (RR = 1.57 [95%CI 1.02–2.41]), and an increased carotid IMT (RR = 2.60 per mm [95%CI 1.20–5.62]). Other measurements were not associated with VBAC.ConclusionsWe identified several markers associated with VBAC in patients with cardiovascular disease referred for a head CT. Future investigation into the relationship between VBAC and stroke is warranted to determine the potential of VBAC in stroke prevention.