Serum tumor markers and testicular germ cell tumors: a primer for radiologists

Abdominal Radiology - Serum tumor markers (STMs) play a critical role in the diagnosis, staging and follow-up of both seminomatous and nonseminomatous testicular germ cell neoplasms. Levels of...     

Elevated levels of the antimicrobial peptide LL‐37 in hidradenitis suppurativa are associated with a Th1/Th17 immune response

Hidradenitis suppurativa (HS) is an inflammatory skin disease with poorly understood immunopathogenic mechanisms. LL‐37 is an antimicrobial peptide, which is transcribed from the CAMP (cathelicidin antimicrobial peptide) gene. Previous reports showed upregulated levels of CAMP and LL‐37 in HS lesions, and therefore, the aim of this study was to compare levels of LL‐37 in HS to other inflammatory skin diseases and to establish immunomodulatory functions of LL‐37 in HS. We confirm an upregulation of the LL‐37 peptide in lesional HS skin with comparable levels as in psoriasis patients and are able to positively correlate the presence of LL‐37 in HS with the presence of T cells, macrophages, neutrophils, IFN‐γ, IL‐17, IL‐23, TNF‐α, IL‐32 and IL‐1β. Mechanistically, LL‐37 boosts the proliferation of unspecifically activated CD4⁺ T cells via an increased calcium signalling independent of antigen‐presenting cells. Targeting LL‐37 may therefore represent a new therapeutic option for the treatment of this recalcitrant disease, but it has to be kept in mind that LL‐37 also has an antimicrobial function.     

Preproenkephalin mRNA expression in rat dorsal striatum induced by selective activation of metabotropic glutamate receptor subtype-5

Group I metabotropic glutamate receptors (mGluR1 and mGluR5 subtypes) are positively coupled to phosphoinositide hydrolysis through G-proteins and are densely expressed in medium-sized projection neurons of striatum. Selective activation of Group I mGluRs upregulates preproenkephalin (PPE) mRNA expression in the rat dorsal striatum. This study investigated the role of one subtype of Group I receptors, mGluR5, in the regulation of PPE mRNA expression in the rat dorsal striatum using quantitative in situ hybridization. Unilateral injection of the mGluR5 selective agonist (RS)-2-Chloro-5-hydroxyphenylglycine (CHPG) into the dorsal striatum (caudoputamen) of chronically cannulated rats at doses of 50 and 200 nmol elevated basal levels of PPE mRNA in the injected dorsal striatum. The induction of PPE mRNA was evident at 1 h, remained at 3 h, and returned to normal level 6 h after CHPG injection. Pretreatment with an mGluR5 selective antagonist 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP) at a dose of 10 mg/kg (i.p.) blocked CHPG-stimulated PPE expression. MPEP also attenuated PPE expression induced by dopamine D(2) receptor blockade with eticlopride (0.5 mg/kg, i.p.). Administration of MPEP alone had no significant effects on basal levels of PPE mRNA in the striatum. The results from the present study demonstrate that glutamatergic tone on mGluR5 possesses the ability to positively regulate PPE gene expression in striatal neurons in vivo. Moreover, activation of mGluR5 participates in the mediation of D(2) antagonist-induced PPE expression.     

Human Immunodeficiency Virus and Leprosy Coinfection in Pune,India

We report eight cases and the incidence of leprosy in human immunodeficiency virus (HIV)-infected individuals after initiation of antiretroviral treatment (ART). The incidence of leprosy in patients on ART was 5.22 per 1,000 person-years (95% confidence interval, 2.25 to 10.28). This high incidence suggests that there should be regular examination of HIV-infected individuals for clinical signs of leprosy.Although there is a declining trend in the global burden of leprosy, there are 15 countries in Asia and Africa which account for 94% of the global total of the new-case detection rate. India is one of the countries where ≥1,000 new cases of leprosy were reported during 2006 (14). Human immunodeficiency virus (HIV) and leprosy both are feared due to the associated social stigma, and leprosy can manifest as immune reconstitution inflammatory syndrome (IRIS) in HIV-infected individuals (9). The first case of leprosy-associated immune reconstitution disease was reported in 2003 for a Ugandan living in London, United Kingdom (5). Later leprosy was described as a manifestation of IRIS in many instances (8, 10).Antiretroviral treatment (ART) for HIV infection is now available in resource-poor regions where leprosy is still endemic, such as South America, Africa, and Asia, including India. India accounts for half of the world''s leprosy cases due to its population of more than 1 billion, even though a nationwide prevalence of less than 1 case/10,000 population was reported in 2005 (4). In addition, India also has the third largest burden of HIV-infected individuals (12). In spite of having a large burden of both leprosy and HIV, there are very few published reports of HIV-leprosy coinfection from India. We report eight cases of incident leprosy in HIV-infected patients who were on ART and the incidence of leprosy in HIV-infected individuals on ART.This report is from the Amrita Clinic of PRAYAS, a nongovernmental organization working on HIV/AIDS in Pune, in the state of Maharashtra, India. We retrospectively analyzed data on HIV-infected patients who initiated ART between January 2003 and December 2006 and we studied their follow-up till December 2007 to evaluate the incident cases of leprosy. ART was provided following the national guidelines for treatment of HIV infection (7).Diagnosis of leprosy was based on the clinical signs and symptoms and demonstration of acid-fast bacilli in the slit skin smears by Ziehl-Neelsen staining. All patients with leprosy received multidrug treatment per the WHO guidelines (15).Several definitions of IRIS have been utilized, each incorporating the general concept that cases of IRIS need to have an inflammatory component occurring in the setting of immune reconstitution that cannot be explained by drug toxicity or a new opportunistic infection (1, 6). We have considered leprosy manifestation after starting ART with increase in CD4⁺ cell count, inflammatory response as seen by neuritis, type I or type II leprosy reaction, or need for the use of steroids for the control of inflammation as a criterion for defining leprosy manifestation as IRIS. Statistical analysis was done using STATA (version 8.0).Between January 2003 and December 2006, among the 1,002 HIV-infected patients who started ART for HIV infection and were followed up till December 2007, eight incident cases of leprosy were detected. None of them had clinical evidence of leprosy at the time of initiation of ART. Table ​Table11 describes the details of these eight patients. All the patients except for one were males, and the mean age of the patients with leprosy was 33.8 years (standard deviation [SD], 5.1 years; range, 27 to 42 years). Four patients had paucibacillary leprosy, and four patients had multibacillary leprosy. The mean CD4⁺ cell count of incident leprosy cases was 326 (median, 245; SD, 255.5; range, 99 to 892). Of these eight patients, three had other opportunistic infections such as pulmonary tuberculosis, abdominal tuberculosis, and herpes zoster. The mean number of months to develop leprosy after starting ART was 13.8 months (SD, 14.3 months; range, 2 to 43 months). All eight patients completed their leprosy treatment and recovered completely. Although eight patients developed incident leprosy, six of them developed leprosy within 2 years of starting ART and two patients had delayed manifestations, with one patient developing leprosy after 28 months and the other after 43 months. These 1,002 patients on ART contributed to 1,532.5 person-years, and hence, the overall incidence of leprosy after starting ART was 5.22 per 1,000 person-years (95% confidence interval, 2.25 to 10.28).

TABLE 1.

Details of HIV-infected patients on ART with incident leprosy^a

Postdural puncture headache: The role of prophylactic epidural blood patch

Prophylactic epidural blood patch may prevent postdural puncture headache that develops after intentional or inadvertent dural puncture. However, despite earlier reports that this procedure was of value, subsequent studies have failed to show it has significant advantages over delayed blood patch. Reports that were supportive of this technique were based on nonrandomized observational studies with significant selective bias. At the present time, most centers do not routinely offer prophylactic blood patches, and those that do report a variable success rate. A recent case study of permanent neurologic deficit after prophylactic epidural blood patch has also raised some concern about the safety of this prophylactic technique.     

Novel lytic bacteriophage AB7-IBB1 of Acinetobacter baumannii: isolation, characterization and its effect on biofilm

Acinetobacter baumannii infections are difficult to treat due to biofilm formation. The literature shows paucity of data on A. baumannii bacteriophages and their application in biofilm control. In this report, we have isolated a new lytic bacteriophage, AB7-IBB1, infecting A. baumannii. Transmission electron microscopy revealed its resemblance to members of the family Siphoviridae, with a tail size of 240 × 10 nm and an icosahedral head 50 nm in diameter. Plaques were 3-5 mm in diameter after 24 h, increasing to 7-9 mm in three days. The phage genome size was determined to be ~75 kb. AB7-IBB1 could lyse 23 of 39 (59 %) clinical isolates of A. baumannii. It exhibited rapid adsorption (>99 % adsorbed in 5 min), a latency period of 30 min and a burst size of 125 PFU/infected cell. The phage affected A. baumannii biofilm formation on an abiotic surface (polystyrene) and a biotic surface (human embryonic kidney 293 cell line). It also showed biofilm control ability on an abiotic surface (polystyrene). FESEM visualization studies confirmed the detrimental effect of phage AB7-IBB1 on host biofilm. In conclusion, this study reports a novel lytic bacteriophage, AB7-IBB1, belonging to family Siphoviridae, with promising anti-biofilm properties.