A Proteomic Approach for the Discovery of Early Detection Markers of Hepatocellular Carcinoma

Individuals chronically infected with hepatitis B or C virus (HBV, HCV) are at high risk for the development of hepatocellular carcinoma (HCC), with disease progression occurring relentlessly over many years. The diagnosis of HCC usually occurs at late stages in the disease when there are few effective treatment options and the prognosis for patients with HCC is very poor. The long latency period, together with clearly identified at risk populations, provide opportunities for earlier detection that will allow more timely and effective treatment of this devastating cancer. We are using a proteomic approach to test the hypothesis that changes in the amount of certain serum polypeptides, or changes in their post-translational modifications, can be used to predict the onset of HCC. Advances in the standardization of two dimensional gel electrophoresis (2DE) coupled with computerized image analysis now permit the reproducible resolution of thousands of polypeptides per run. Serum polypeptides from individuals at different stages in the disease continuum are being resolved by 2DE to identify those that change with disease progression. Polypeptides found by this method can be further characterized by mass spectrometry. In addition, the potential for changes in the glycan structure of certain polypeptides to serve as a marker for disease progression can be explored. The proteomic approach is expected to liberate us from the need to “cherry pick” or guess the best biomarkers and let the data tell us which are the best indicators of disease. Information may also be gleaned about the pathobiology of the disease process.     

Association of mitral annulus calcification, aortic valve sclerosis and aortic root calcification with abnormal myocardial perfusion single photon emission tomography in subjects age ≤65 years old

OBJECTIVES

We examined the hypothesis that mitral annulus calcification (MAC), aortic valve sclerosis (AVS) and aortic root calcification (ARC) are associated with coronary artery disease (CAD) in subjects age ≤65 years.

BACKGROUND

Mitral annulus calcification, AVS and ARC frequently coexist and are associated with coronary risk factors and CAD in the elderly.

METHODS

We studied 338 subjects age ≤65 years who underwent evaluation of chest pain with myocardial perfusion single photon emission computed tomography (SPECT) and a two-dimensional transthoracic echocardiogram for other indications. The association of MAC, AVS and ARC with abnormal SPECT was evaluated by using chi-square analyses and logistic regression analyses.

RESULTS

Compared with no or one calcium deposit and no or one coronary risk factor other than diabetes, multiple (≥2) calcium (or sclerosis) deposits with diabetes or multiple (≥2) coronary risk factors were significantly associated with abnormal SPECT in women age ≤55 years old (odds ratio [OR], 20.00), in women age >55 years old (OR, 10.00) and in men age ≤55 years old (OR, 5.55). Multivariate analyses identified multiple calcium deposits as a significant predictor for an abnormal SPECT in women (p < 0.001), younger subjects age ≤55 years (p < 0.05) and the total group of subjects (p < 0.01).

CONCLUSIONS

When coronary risk factors are also taken into consideration, the presence of multiple calcium deposits in the mitral annulus, aortic valve or aortic root appears to be a marker of CAD in men ≤55 years old and women.     

Urticaria

Urticaria is often classified as acute, chronic, or physical based on duration of symptoms and the presence or absence of inducing stimuli. Urticarial vasculitis, contact urticaria, and special syndromes are also included under the broad heading of urticaria. Recent advances in our understanding of the pathogenesis of chronic urticaria include the finding of autoantibodies to mast cell receptors in nearly half of patients with chronic idiopathic urticaria. These patients may have more severe disease and require more aggressive therapies. Extensive laboratory evaluation for patients with chronic urticaria is typically unrevealing and there are no compelling data that associate urticaria with chronic infections or malignancy. Pharmacologic therapy consists primarily of the appropriate use of first- and second-generation histamine H1 receptor antihistamines. Additional therapy may include leukotriene receptor antagonists, corticosteroids, and immunomodulatory agents for severe, unremitting disease. Despite our greater understanding of the pathogenesis of urticaria, the condition remains a frustrating entity for many patients, particularly those with chronic urticaria.     

Status of essential trace metals in biological samples of diabetic mother and their neonates

Objective  There is accumulating facts that the metabolism of essential trace elements is altered in diabetic patients. The aim of present study was to compare the status of essential trace elements, chromium (Cr), manganese (Mn), and zinc (Zn) in biological samples (whole blood, urine and scalp hair) of insulin dependent diabetic mothers (age ranged 30–40) and their newly born infants (n = 76). An age matched 68 non-diabetic mothers and their infants, residing in the same locality, were selected as referents. For a comparative study, the biological samples of non-diabetic and diabetic pregnant and non pregnant of same age group and socio-economics status were also analysed. Methodology  The biological samples (scalp hair, blood and urine) were collected from study and referent groups. The Cr, Mn and Zn concentrations in all three biological samples were determined by a flame/electrothermal atomic absorption spectrometer, prior to microwave assisted acid digestion. The validity and accuracy of the methodology was checked by certified reference materials (CRMs) and using conventional wet acid digestion method on same CRMs. Results  The mean values of Cr, Mn and Zn in scalp hair and blood samples of diabetic mothers and their infants were significantly lower as compared to the referent mothers-infants pairs (p < 0.01), while urinary excretion of all these elements were high in diabetic mother–infant pair samples. Conclusion  The deficiencies of essential trace elements, Cr, Mn and Zn in biological samples of diabetic women, may play role in the pathogenesis of diabetes mellitus and impacts on their neonates.     

Improved outcome from invasive adenovirus infection in pediatric patients after hemopoietic stem cell transplantation using intensive clinical surveillance and early intervention

Adenovirus is a common cause of morbidity and mortality after hemopoietic stem cell transplantation in children. Recently the incidence, risk factors, and outcome of such infections have been better defined using improved virologic detection methods, in particular polymerase chain reaction. We have introduced intensive virologic surveillance for adenovirus in our institution including at least weekly polymerase chain reaction testing of blood and stool samples. We report on 71 prospectively monitored transplants, including 40 from unrelated donors. In total, there were 8 cases of invasive adenovirus infection, 3 of whom died. Mortality was less than in previous studies as cases were managed with antiviral chemotherapy and reduction of immune suppression. In fatal cases, there was concurrent difficult graft versus host disease making withdrawal of immune suppression therapy impossible. We describe 2 cases of graft failure in association with adenovirus viremia and its treatment that were successfully managed with further donor cell infusion.     

Cognitive and emotional processing in narratives of women abused by intimate partners

This study examined relationships between cognitive and emotional processing with changes in pain and depression among intimate partner violence survivors. Twenty-five women who wrote about their most traumatic experiences completed measures of pain and depressive symptoms before the first writing session and again 4 months following the last writing session. Reduced pain was significantly associated with less use of positive and negative emotion words. Relationships between cognitive and emotional aspects of writing with changes in depressive symptoms fell short of statistical significance. The results suggest that emotional processing in narrative writing predicts changes in pain in intimate partner violence survivors.     

Effect of maxillary and mandibular extrusion arches on dentoskeletal changes in adults with anterior open bite: a quantitative analysis

ObjectiveTo quantify dentoskeletal changes accompanying the use of extrusion arches during the treatment of anterior open bite (AOB) in adults.Materials and MethodsA total of 23 adult patients with an AOB of −3.05 mm ± 1.27 mm were treated with upper and lower extrusion arches after the alignment phase. Lateral cephalograms were taken before placement of the extrusion arch, immediately after closure of the open bite (T2), and at the end of orthodontic treatment (T3). Data were statistically analyzed using repeated-measures analysis of variance and the Bonferroni post hoc test for pairwise comparisons (α = 0.05).ResultsSuccessful closure of AOB, with an overall change in overbite of 4.73 ± 1.93 mm, was achieved in an average of 3.8 months and remained stable at T3. Upper and lower incisors were significantly extruded by 2.05 mm ± 0.72 mm and 2.54 mm ± 1.63 mm, respectively, and significantly retroclined by 6.36° ± 1.63° and 8.45° ± 3.83°, respectively, with a resultant increase in the interincisal angle of 12.80° ± 2.09°. Statistically significant intrusion and mesial tipping (P < .001) of the maxillary and mandibular first molars were observed at T2. Dentoskeletal changes remained stable at T3, except for a significant reduction of the mesial tipping of the maxillary and mandibular first molars.ConclusionsThe combined use of maxillary and mandibular extrusion arches resulted in significant favorable dentoskeletal changes that led to the successful closure of AOB during a short duration of treatment.