Comparison of PCR and other diagnostic techniques for detection of Helicobacter pylori infection in dyspeptic patients.

A sensitive and specific PCR-based assay to detect the Helicobacter pylori 16S rRNA gene present in formalin-fixed paraffin-embedded gastric biopsy specimens has been developed. A total of 95 patients with dyspepsia were evaluated for the presence of chronic active gastritis and an infection with H. pylori through the use of diagnostic assays based on biopsy specimens and serology. The "gold standard" for the presence of the bacteria was direct detection in histological sections of biopsy specimens by Giemsa stain. The results obtained with the PCR assay performed on the biopsy specimens (94% sensitivity and 100% specificity) were equivalent to the detection of H. pylori immunoglobulin G antibodies by the commercially available second-generation Cobas Core anti-H. pylori immunoglobulin G enzyme immunoassay (94% sensitivity and 98% specificity) for the diagnosis of H. pylori infection. Urease testing and bacterial culture of the biopsy specimens were inferior (88 and 70% sensitivity and 96% and 98% specificity, respectively). A Western blot (immunoblot) analysis had slightly greater sensitivity (96%), although specificity was reduced to 93%. This research prototype PCR assay was shown to be highly reliable for the detection of infection with H. pylori and the presence of chronic active gastritis in the population studied.     

Dynamic Change of Endocannabinoid Signaling in the Medial Prefrontal Cortex Controls the Development of Depression After Neuropathic Pain

Many patients with chronic pain conditions suffer from depression. The mechanisms underlying pain-induced depression are still unclear. There are critical links of medial prefrontal cortex (mPFC) synaptic function to depression, with signaling through the endocannabinoid (eCB) system as an important contributor. We hypothesized that afferent noxious inputs after injury compromise activity-dependent eCB signaling in the mPFC, resulting in depression. Depression-like behaviors were tested in male and female rats with traumatic neuropathy [spared nerve injury (SNI)], and neuronal activity in the mPFC was monitored using the immediate early gene c-fos and in vivo electrophysiological recordings. mPFC eCB Concentrations were determined using mass spectrometry, and behavioral and electrophysiological experiments were used to evaluate the role of alterations in eCB signaling in depression after pain. SNI-induced pain induced the development of depression phenotypes in both male and female rats. Pyramidal neurons in mPFC showed increased excitability followed by reduced excitability in the onset and prolonged phases of pain, respectively. Concentrations of the eCBs, 2-arachidonoylglycerol (2-AG) in the mPFC, were elevated initially after SNI, and our results indicate that this resulted in a loss of CB1R function on GABAergic interneurons in the mPFC. These data suggest that excessive release of 2-AG as a result of noxious stimuli triggers use-dependent loss of function of eCB signaling leading to excessive GABA release in the mPFC, with the final result being behavioral depression.SIGNIFICANCE STATEMENT Pain has both somatosensory and affective components, so the complexity of mechanisms underlying chronic pain is best represented by a biopsychosocial model that includes widespread CNS dysfunction. Many patients with chronic pain conditions develop depression. The mechanism by which pain causes depression is unclear. Although manipulation of the eCB signaling system as an avenue for providing analgesia per se has not shown much promise in previous studies. An important limitation of past research has been inadequate consideration of the dynamic nature of the connection between pain and depression as they develop. Here, we show that activity-dependent synthesis of eCBs during the initial onset of persistent pain is the critical link leading to depression when pain is persistent.     

Scrotal and penile papules and plaques as the initial manifestation of a cutaneous metastasis of adenocarcinoma of the prostate: case report and review of the literature

Cutaneous metastasis of prostatic adenocarcinoma is a rare phenomenon. We present a 56-year-old African American man with metastatic disease in the skin and subcutis of the suprapubic and scrotal area 2 years after his initial diagnosis presenting as scrotal and penile edema and plaque like scrotal rash. We also review the literature on this subject.     

Reactions of nifurtimox with critical sulfhydryl-containing biomolecules: their potential toxicological relevance

Nifurtimox (Nfx) is a drug used in the treatment of Chagas' disease, an endemic parasitic disease from Latin American countries. It produces undesirable side-effects in patients, frequently forcing the treatment to be stopped. Its toxic mechanism is not fully understood. In this work we describe purely chemical reactions of Nfx with relevant cellular sulfhydryl (SH) compounds. The compounds tested were glutathione (GSH), cysteine (RSH), lipoic acid (LA) and coenzyme A (CoA). All reacted with Nfx to give nitrite (NO(-) (2)). The relative reaction rates were CoA>LA>GSH>RSH. In studies with GSH and RSH the formation of nitrite was accompanied by decreases in Nfx concentration and increases in the formation of a reaction product revealed by HPLC. We failed to show the presence of liver cytosolic GST (GSH transferase activity)-mediated formation of NO2- from Nfx. These NO(-) (2)-releasing processes occurred under in vivo conditions in Nfx-treated Sprague-Dawley male rats (240-260 g body weight) at a dose of 100 mg Nfx kg(-1) p.o. In urine samples NO(-) (2) excretion was accompanied by unchanged drug and two unidentified more polar metabolites detectable by HPLC. The Nfx reactions with critical SH from molecules such as GSH, RSH, LA and CoA, and potentially others containing SH residues (e.g. enzymes or structural proteins), might have toxicological relevance not only for the Nfx side-effects but also for the chemotherapeutic effects on Trypanosoma cruzi. In addition, Nfx reactions with GSH might be crucial in Nfx detoxification.     

Predicting follow-up living setting in patients with stroke

OBJECTIVE: To examine living setting at 3- to 6-month follow-up for inpatients with functional impairments discharged from medical rehabilitation. DESIGN: Retrospective performed by using information from the Uniform Data System for Medical Rehabilitation (UDSMR) representing medical rehabilitation patients across the United States. SETTING: National survey data. PARTICIPANTS: Information submitted in 1997 and 1998 to the UDSMR by 167 facilities from 40 states was examined. A total of 9587 patient records were included in the final sample. The mean age +/- standard deviation was 70.2+/-12.4 years. The sample included 51.6% women and was comprised of 77.5% non-Hispanic white patients, with an average length of stay of 22.3+/-4.6 days. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Living setting (home vs not at home) at 3- to 6-month follow-up. RESULTS: A discriminant function training model including 8 statistically significant variables correctly classified 85.1% of the patients (n=8149). The total FIM instrument score, patient age, function-related group, and marital status were found to be useful classification variables. Wilks lambda for the model was.924 (chi(2)=1031.49, P<.000). The area under the receiver operating characteristics curve was.85. CONCLUSION: The association among functional abilities, demographic characteristics, and follow-up living setting in patients with stroke is complex. Functional variables can be used to help predict follow-up living setting. These variables change based on patient severity level.