Phase angle as a prognostic marker after percutaneous endoscopic gastrostomy (PEG) in a prospective cohort study

Objective: The phase angle identifies changes in tissue’s electrical properties assessed by bioelectrical impedance measurement and it can predict prognosis in some conditions. Percutaneous endoscopic gastrostomy (PEG) is commonly used in patients with severe nutritional problems, but there is a need to improve the clinical decision-making for using PEG. We examined if a decreased phase angle predicts complications, short-term mortality (within 60 days of PEG insertion), or inflammatory markers (high C-reactive protein [CRP] levels or low albumin levels) following PEG insertion.

Material and methods: The phase angle was assessed from body resistance and reactance as measured by bioelectrical impedance in 131 patients admitted for PEG. Anthropometrics and clinical biochemical measures were collected at the time of PEG insertion, while complications and mortality were assessed at clinical follow-ups. Multivariable logistic regression analysis provided odds ratios (ORs) with 95% confidence intervals (CIs) adjusted for sex, age, body mass index, and comorbidity.

Results: A decreased phase angle did not statistically significantly increase the probability of acute complications or short-term mortality, but predicted increased inflammatory markers (CRP?≥10?mg/L [OR 1.63, 95% CI 1.02–2.60], albumin?<30?g/L [OR 2.10, 95% CI 1.24–3.57] and a combination of CRP?≥10?mg/L and albumin?<30?g/L [OR 3.06, 95% CI 1.51–6.19]).

Conclusions: A decreased phase angle did not predict acute complications or short-term mortality after PEG insertion, but predicted increased levels of inflammatory markers.     

Novel homozygous, heterozygous and hemizygous FRMD7 gene mutations segregated in the same consanguineous family with congenital X-linked nystagmus

Congenital nystagmus (NYS) is characterized by bilateral, spontaneous, and involuntary movements of the eyeballs that most commonly presents between 2 and 6 months of life. To date, 44 different FRMD7 gene mutations have been found to be etiological factors for the NYS1 locus at Xq26-q27. The aim of this study was to find the FRMD7 gene mutations in a large eleven-generation Indian pedigree with 71 members who are affected by NYS. Mutation analysis of the entire coding region and splice junctions of the FRMD7 gene revealed a novel missense mutation, c.A917G, predicts a substitution of Arg for Gln at codon 305 (Q305R) within exon 10 of FRMD7. The mutation was detected in hemizygous males, and in homozygous and heterozygous states in affected female members of the family. This mutation was not detected in unaffected members of the family or in 100 unrelated control subjects. This mutation was found to be at a highly conserved residue within the FERM-adjacent domain in affected members of the family. Structure prediction and energetic analysis of wild-type FRMD7 compared with mutant (Q305R) revealed that this change in amino acid led to a change in secondary structure predicted to be an energetically unstable protein. The present study represents the first confirmation of FRMD7 gene mutations in a multigenerational Indian family and expands the mutation spectrum for this locus.     

Design and studies of novel 5-substituted alkynylpyrimidine nucleosides as potent inhibitors of mycobacteria

We herein report a new category of 5-substituted pyrimidine nucleosides as potent inhibitors of mycobacteria. A series of 5-alkynyl derivatives of 2'-deoxyuridine (1-8), 2'-deoxycytidine (9-14), uridine (15-17), and 2'-O-methyluridine (18, 19) were synthesized and evaluated for their antimycobacterial activity in vitro. 5-Decynyl, 5-dodecynyl, and 5-tetradecynyl derivatives showed the highest antimycobacterial potency against M. bovis and M. avium, with the 2'-deoxyribose derivatives being more effective than the ribose analogues. Nucleosides bearing short alkynyl side chains 5-ethynyl, 5-propynyl, 5-pentynyl, and 5-heptynyl were mostly not inhibitory. Incorporation of a phenylethynyl function at the 5-position diminished the antimicrobial effect. Furthermore, related bicyclic analogues (20-24) were devoid of antimycobacterial activity, indicating that an acyclic side chain at the C-5 position of the pyrimidine ring is essential for potent activity. Compounds 1-17 were synthesized by the Pd-catalyzed coupling reactions of respective alkynes with 5-iodo derivatives of 2'-deoxyuridine, 2'-deoxycytidine, and uridine. Intramolecular cyclization of 1 and 3-6 in the presence of Cu afforded the corresponding bicyclic compounds 20-24. The investigated nucleosides are recognized here for the first time to be potent inhibitors of mycobacteria. This class of compounds could be of interest for lead optimization as antimycobacterial agents.     

Effect of cacao liquor extract on tumor marker enzymes during chemical hepatocarcinogenesis in rats

This study investigated the effect of cacao liquor extract (CLE) on tumor marker enzymes--alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase (GST), and glutathione reductase (GR) activities--in plasma and/or liver of hepatocarcinogenic rats, which were induced with diethylnitrosamine and 2-acetylaminofluorene. Twenty-nine male Sprague-Dawley rats (weighing 150-330 g) were divided into four groups (n = 6-8): normal control group (N), normal group + CLE (NE), cancer group (C), and cancer group + CLE (CE). Analysis of variance showed significant differences (P<.05) in the specific activities of ALP, GGT, and GST between the C and N groups. However, GR activity for the C group was not significantly different compared with the N group. In the CE group, the specific activities of ALP, GGT, GST, and GR were significantly lower (P<.05) compared with the C group. The findings showed that CLE could lower the activity of tumor marker enzymes of rats during hepatocarcinogenesis. Based on the results obtained, polyphenol compounds present in the cacao liquor, extracted by using ethanol, have the potential in decreasing the severity of hepatocarcinogenesis.     

Prevalence of fragile histidine triad expression in tumors from saudi arabia: a tissue microarray analysis.

AIM: The fragile histidine triad (FHIT) gene was discovered and proposed as a tumor suppressor gene for most human cancers. It encodes the most active common human chromosomal fragile region, FRA3B. We studied the prevalence of loss of FHIT expression in various tumors and correlated its loss with various clinicopathologic features. METHODS: To determine whether the absence of FHIT expression correlates with clinical variables such as grade, stage, and survival time, we assessed FHIT expression using immunohistochemistry. More than 1,800 tumors from more than 75 tumor categories were analyzed by immunohistochemistry in a tissue microarray format. RESULTS: Loss of FHIT expression ranged from 19% in ovarian tumors to 67% in lung cancers. Clinical and pathologic features like grade, stage, tumor size, and lymph node metastasis showed correlation with loss of FHIT expression in some tumors. No difference was seen in the survival patterns and loss of FHIT expression in any of the tumor groups studied. CONCLUSIONS: Loss of FHIT expression is an ubiquitous event in the multistep, multifactorial carcinogenesis process. FHIT may be altered at different stages in different types of cancers. Most of the tumors with a wider prevalence of loss of FHIT expression as an early event show a correlation with clinicopathologic features. However, in some of the tumors, FHIT expression is lost as a late event and is only seen in a fraction of the tumors.     

IFN-induced depression: a role for NSAIDs

Interferon-alpha (IFN) is widely used for the treatment of viral illnesses and other chronic diseases, though its usefulness is hampered by a problematic side-effect profile. In particular, IFN-alpha induces neuropsychiatric and neurotoxic side effects, including depression, anxiety, insomnia, lethargy, confusion, and psychosis. Of particular interest, a number of patients develop full psychiatric syndromes, particularly depressive disorders. Recent evidence suggests that conventional antidepressants (especially selective serotonin reuptake inhibitors) are effective in preventing or reducing IFN-induced side-effects, but even these compounds are not 100% effective in preventing these symptoms. As such, alternative treatments must be considered. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to counteract a number of IFN-induced side effects, including cytokine activation, stress hormone release, and neurochemical alterations (reduced 5-HT [serotonin]). NSAIDs are widely recommended for various aspects of flu-like symptoms or sickness behaviors in humans, including those induced specifically by IFN. In addition, NSAIDs appear to be effective in treating premenstrual dysphoric disorder. These data indirectly specify a role for NSAIDs in syndromes with a prominent depression component. Drawing from an extensive pre-clinical and clinical research base, we hypothesize that pretreatment with NSAIDs will not only reduce the incidence of flu-like symptoms, but also prove effective for the prevention or reduction of IFN-induced depression.     

Effect of trypan blue staining on the density and viability of lens epithelial cells in white cataract

PURPOSE: To assess the effect of anterior capsule staining with trypan blue 0.0125% on the density and viability of the lens epithelial cells (LECs). SETTING: Iladevi Cataract and IOL Research Center, Ahmedabad, India. METHODS: This randomized prospective study comprised 40 eyes having phacoemulsification for white mature cataract. Patients were randomized to have the anterior capsule stained with 0.1 mL trypan blue 0.0125% solution before the anterior capsulorhexis (Group 1, n = 20) or to have no anterior capsule staining before the anterior capsulorhexis (Group 2, n = 20). The density and viability of LECs were analyzed. The first 20 samples (10 from Group 1, 10 from Group 2) were stained with hematoxylin-eosin for cell density analysis using image-analysis software. The remaining 20 samples (10 from each group) were stained with a solution containing 0.5 microM calcein AM and 5 microM propidium iodide for 10 minutes at 37 degrees C for viability assay. RESULTS: The mean cell density in Group 1 (with staining) was 3533.15 cells/mm(2) +/- 664.01 (SD). This was significantly lower than the mean of 4235.59 +/- 414.93 cells/mm(2) in Group 2 (no staining) (P = .01). The mean capsule area covered with LECs (80.75% +/- 8.04% versus 94.63% +/- 3.78%) and the mean live LECs in the covered area (51.69% +/- 11.54% versus 68.67% +/- 9.15%) were also significantly lower in Group 1 (P = .002). CONCLUSION: Staining the anterior capsule with trypan blue affected the density and viability of LECs.     

Characterization of maxillofacial soft tissue vascular anomalies by ultrasound and color Doppler imaging: an adjuvant to computed tomography and magnetic resonance imaging.

PURPOSE: The special imaging and physical properties of ultrasound and color Doppler offer opportunity for continued investigation in oral and maxillofacial surgery. This study prospectively investigated ultrasound and color Doppler in addition to computed tomography (CT) and magnetic resonance imaging (MRI) in the characterization of several vascular or suspected vascular anomalies and assesses the value of ultrasound and color Doppler in their diagnoses. PATIENTS AND METHODS: Six patients with vascular or suspected vascular anomalies seen between 1997 and 1999 composed the study group. All patients were clinically evaluated, imaged by CT with contrast and/or MRI with contrast, ultrasound, and Doppler (including color, spectral, and power). Ultrasound studies were performed in the presence of the referring oral and maxillofacial surgeons to provide consultation on anatomy and differential diagnosis as well as to witness the dynamic study. Three patients were further studied by angiography. The Mulliken/Glowacki classification (Plast Reconstr Surg 69:412, 1982) and designations and the Jackson et al modification (Plast Reconstr Surg 91:1216, 1993) are used in this study. RESULTS: A spectrum of lesions emerged in this small case series. Detailed clinical and imaging findings and a summary of diagnostic impressions allowed general and specific observations and permitted assessment of the value of ultrasound and color Doppler in the diagnosis of these lesions. The diagnostic accuracy of ultrasound and Doppler was equal to or better than that of CT and/or MRI in 4 of 6 cases. In the other 2 cases ultrasound did not specifically diagnose the lesions but did allow assessment of vascularity. In one of these cases the correct diagnosis was made by a combination of CT and angiography, and in the other the diagnosis was made by nonenhanced MRI. An ancillary study showed that the combination of nonenhanced MRI with ultrasound and Doppler provides more information than contrast-enhanced MRI alone and is more cost effective. CONCLUSIONS: 1) A single imaging modality is frequently unable to provide sufficient diagnostic information to allow confident clinical management of a vascular malformation. 2) A team approach and conferencing between imaging specialists and clinicians promote better diagnosis and management. 3) Nonenhanced MRI with ultrasound/color Doppler can be substituted for enhanced MRI to provide the best diagnostic information and at reduced cost. 4) Ultrasound/color Doppler is an important adjuvant to CT and MRI in the diagnosis of vascular or suspected vascular anomalies.