Cryptococcal lymphadenitis and meningitis in human immunodeficiency virus infection--a case report

Cryptococcal meningitis (CM) is the commonest life threatening opportunistic fungal disease in Human Immunodeficiency Virus (HIV) infected individuals. But there are very little reports of lymphadenopathy along with cryptococcal meningitis, although cases of pulmonary, Intestinal, Bone marrow and retinal involvement have been described earlier. Here we report a case of cryptococcal meningitis associated with generalized lymphadenopathy and hepatosplenomegaly.     

HER-2/neu and topoisomerase IIa gene amplification and protein expression in invasive breast carcinomas: chromogenic in situ hybridization and immunohistochemical analyses

We studied HER-2/neu (HER-2) and topoisomerase IIa (topo2a) amplification (using chromogenic in situ hybridization) and overexpression (immunohistochemical analysis) in 113 invasive breast carcinomas. A gene copy number/chromosome 17 copy number ratio of 2.0 or higher indicated amplification. A topo2a/chromosome 17 ratio of less than 0.8 indicated gene deletion. HER-2 overexpression was scored according to standard HercepTest guidelines (DAKO, Carpinteria, CA). Overexpression of topo2a was identified when nuclear staining was found in more than 5% of tumor cells. Of 113 tumors, 104 were analyzed successfully for HER-2 and topo2a amplification. Of the 104, 64 showed HER-2 amplification; 25 of these (39%) also showed topo2a amplification. No amplification was found in 40 tumors. Deletion of topo2a was seen in 7 (11%) of 64 HER-2-amplified tumors and 2 (5%) of 40 nonamplified tumors. Of 25 tumors with topo2a amplification, 18 (72%) overexpressed topo2a. Only 3 (4%) of 79 tumors without topo2a amplification overexpressed topo2a. Amplification of topo2a is associated with HER-2 amplification but not vice versa. Amplification of topo2a resulted in protein overexpression in 72% of tumors, but topo2a overexpression rarely occurred without gene amplification. Identification of topo2a and HER-2 status might have therapeutic and prognostic implications.     

Procaine-lnduced increases in limbic rCBF correlate positively with increases in occipital and temporal EEG fast activity

Summary Previous independent EEG and PET studies suggest that administration of intravenous procaine hydrochloride selectively activates limbic brain structures. To further elucidate procaine's effects and explore the relationship between quantitative EEG (qEEG) and regional cerebral blood flow (rCBF), we simultaneously recorded qEEG and sampled rCBF using O-15 water PET in 20 healthy volunteers during single-blind injections of saline (baseline condition) followed by intravenous procaine (1.84 mg/kg). After thorough screening of EEG records, a subgroup of 7 subjects with EEG data relatively free of both muscle and movement artifacts was selected for analysis. Quantitative spectral EEG data from right occipital and temporal leads were then correlated with each subject's PET rCBF values on a pixel by pixel basis, both at baseline and after procaine. The most striking finding was that the increases in occipital and temporal omega activity from baseline to procaine positively correlated with rCBF increases in the amygdala and its efferents (p<.05), in a pattern very similar to the rCBF increases seen after procaine administration. This suggests that omega activity may reflect activation of deeper brain limbic structures. Also, the convergence of EEG and PET data further supports procaine's selective limbic activation.     

Understanding the cholesterol metabolism-perturbing effects of docosahexaenoic acid by gas chromatography–mass spectrometry targeted metabonomic profiling

Purpose

Over the past few decades, docosahexaenoic acid (DHA) has gained special attention for management of cholesterol-associated metabolic disorders and neurodegenerative diseases such as Alzheimer’s disease (AD) owing to its neuroprotective, anti-inflammatory and hypolipidemic properties. Several epidemiological studies have reported the effect of DHA in reducing the risk of developing AD by lowering cholesterol. Hypercholesterolemia is a pro-amyloidogenic factor influencing the enzymatic processing of amyloid-β precursor protein (AβPP) to toxic β-amyloid. However, the mechanism by which DHA modulates the cholesterol pathway has not been established. Thus, the objective of this study was to investigate the mechanism of regulation of cholesterol metabolism by DHA in an AβPP₆₉₅ overexpressing AD cell model.

Methods

A gas chromatography/mass spectrometry method was developed and validated for the targeted profiling of 11 cholesterol metabolites in DHA-treated Chinese hamster ovary wild-type (CHO-wt) and AβPP₆₉₅ overexpressing (CHO-AβPP₆₉₅) cells. The differential metabolite profiles between DHA- and vehicle-treated groups were further analyzed using fold change values of the ratio of concentration of metabolites in CHO-AβPP₆₉₅ to CHO-wt cells. Effect of DHA on key rate-limiting enzymatic activities within the cholesterol pathway was established using biochemical assays.

Results

Our results showed that DHA reduced the levels of key cholesterol anabolites and catabolites in CHO-AβPP₆₉₅ cells as compared to CHO-wt cells. Further enzymatic studies revealed that the cholesterol-lowering effect of DHA was mediated by regulating HMG-CoA reductase and squalene epoxidase enzyme activities.

Conclusion

We demonstrate for the first time the dual effects of DHA in inhibiting HMG-CoA reductase and squalene epoxidase and modulating the sterol biosynthesis axis of the cholesterol pathway in AβPP₆₉₅ overexpressing AD. Our novel findings underscore the potential of DHA as a multi-target hypocholesterolemic agent for the prophylaxis of AD and other cholesterol-associated diseases.

     

A spiralling origin of the median nerve around an accessory coracobrachialis brevis muscle

During an ultrasound-guided axillary brachial plexus block, sonoanatomy demonstrated a delayed formation of the lateral root to the median nerve from the lateral cord, an accessory coracobrachialis brevis muscle, and a course of the lateral root to the median nerve ‘spiralling’ around the accessory muscle prior to locating lateral to the brachial artery. This rare variant is further discussed in the context of median, musculocutaneous and coracobrachialis variations.     

Prognostic Role of Receptor Tyrosine Kinase–Like Orphan Receptors in Intestinal-Type Gastric Cancer

Background:Gastric cancer (GC) is diagnosed at advanced stages and has high mortality rates. Surgical resection and adjuvant chemotherapy are the main therapeutic approaches for GC. Despite curative resection, recurrence and metastasis contribute to a high mortality rate in patients with GC. The receptor-tyrosine-kinase-like orphan receptors 1/2 (ROR1/2) are transmembrane proteins belonging to the receptor tyrosine kinase (RTK) family. ROR1 and ROR2 are known to overexpress in the tumor tissues from several types of cancer patients. However, the role of RORs in the prognosis has not been understood. Methods:This study aimed to determine the association of mRNA expression of ROR1, ROR2, and their signaling components WNT5A, NKX2-1, and FOXF1, with the survival outcome of GC patients. We performed Kaplan-Meir survival analysis on publicly available ‘The Cancer Genome Atlas (TCGA)’ data sets using ‘Kaplan-Meir Plotter.’ Results:High mRNA expression of ROR1, ROR2, NKX2-1, and FOXF1 was significantly correlated with worse overall survival (OS) of GC patients. Interestingly ROR1 and ROR showed a prognostic role in the intestinal subtype, but not in the diffuse subtype of GC. Furthermore, ROR1 was positively correlated with regulatory T cells and M2-type macrophages and negatively correlated with Th17 and natural killer T cells in the tumor stroma of patients with GC. Conclusion:We conclude that the expression of ROR1, ROR2, and their associated genes correlate with worst prognosis of GC patients, particularly in the intestinal type.Key Words: ROR1, ROR2, WNT5A, NKX2-1, FOXF1, prognosis, KM Plotter     

Successful colonoscopic fecal microbiota transplantation for active ulcerative colitis: First report from India

Forty-four-year-old male with ulcerative colitis (UC) for 11 years reported frequent relapse despite daily sulfasalazine 4 g, azathioprine 125 mg, and rectal 5-aminosalicylic acid. Repeated use of corticosteroids led to cataract. At enrollment, he was passing eight stools a day with blood with a Mayo score of 9 (3+1+3+2). Stool was negative for ova/cysts/acid fast bacilli and Clostridium difficile toxin assay. Rectal biopsy showed cryptitis, crypt abscess, and crypt distortion with no inclusion bodies, and cytomegalovirus DNA was negative. Following informed consent and approval from IEC, three sessions of fecal microbiota transplant (FMT) were performed at intervals of 2 weeks. The donor was a 34-year-old relative with no history of gastrointestinal illness, no use of antibiotics over 3 months, and free from transmissible disease as per standard protocol. At colonoscopy, 350 mL of blended and filtered donor stool, drawn into seven syringes of 50 cm³, was instilled from terminal ileum to sigmoid. Follow up sigmoidoscopy and rectal biopsy were done monthly for 6 months. There was symptomatic, colonoscopic, and histopathological improvement with the Mayo scores of 4.1 and 0 at 4.8 and 12 weeks post FMT. Azathioprine and sulfasalazine were tapered sequentially between months 4 and 6 of FMT. He remains in clinical and endoscopic remission 8 months after FMT and 2 months after withdrawal of all medication. Colonoscopic FMT may be effective in inducing drug-free remission in patients with active UC.     

Transmission of hepatitis C virus in the dialysis setting and strategies for its prevention

Hepatitis C virus (HCV) infection is more common among hemodialysis patients than the general population and transmission of HCV in dialysis clinics has been reported. In the context of the increased morbidity and mortality associated with HCV infection in the end stage renal disease population, it is important that dialysis clinics have processes in place for ensuring recommended infection control practices, including Standard Precautions, through regular audits and training of the staff. This review will summarize the epidemiology of HCV infection and risk factors for HCV transmission among hemodialysis patients. In addition, the proper protocols are required to investigate suspected cases of HCV transmission in dialysis facilities and recommendations for prevention of HCV transmission in will be reviewed.