Oesophageal reflux tests, manometry, endoscopy, biopsy, and radiology in healthy subjects

The aim was to study the exposure time of acid during 24 h at two different oesophageal levels in 15 healthy subjects and its relation to other kinds of oesophageal findings. Five centimetres above the lower oesophageal sphincter the total reflux time was 0.2% (0-1.3%), and at the 15-cm level it was 0.1% (0-0.7%). A standardized compression test during manometry and radiologic examination showed that no subject had reflux. Hiatus hernia was provoked at the radiologic examination in four subjects, one of whom also had a widened hiatus. At endoscopy, one subject had a hiatus hernia and slightly granulated oesophageal mucosa. Biopsy specimens showed slight basal cell hyperplasia in one case. Bleeding in the dermal papillae or a few intraepithelial leukocytes were seen in eight cases, findings that might be due to endoscopic trauma. Without any history of gastrointestinal disorders, gastrooesophageal reflux was minimal under standardized conditions, although hiatus hernia and mild changes in biopsy specimens could be seen.     

The psoas sign, hepatic angle, normal patients, and everyday practice

While extensive previous references in the literature leave little doubt that disease in the posterior pararenal space can obliterate the psoas margin either in its entirety or in part, little work has been done to evaluate the frequency of when the psoas cannot be visualized in normal individuals. The data presented here indicate that as the right psoas can be expected to be absent in normal patients from 16 to 43% of the time, therefore one cannot ;lean' heavily on it as a clinical tool.On the other hand, absence of the left psoas margin on a single film in the proper clinical setting may be sufficient to draw one's attention to the retroperitoneal space, more particularly the posterior pararenal space, as a possible site of abnormality. However, ancillary radiographic signs such as mass displacement, gas, calcium, or abnormal depositions of fat, should be carefully sought.Preservation of either or both psoas margins certainly does not exclude by any means significant extraperitoneal disease, as can be seen even in our small anecdotal series.The hepatic angle is absent with such frequency in normal patients that it too can only be of questionable value as a primary radiographic sign. In our normal group of patients the splenic angle was absent more frequently than it was present.     

Clinical trials update from the American Heart Association meeting 2010: EMPHASIS-HF, RAFT, TIM-HF, Tele-HF, ASCEND-HF, ROCKET-AF, and PROTECT

This article provides information and a commentary on key trials relevant to the pathophysiology, prevention, and treatment of heart failure presented at the annual meeting of the American Heart Association held in Chicago in 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. In patients with mild heart failure (HF), EMPHASIS-HF showed that the addition of eplerenone to standard therapy was well tolerated and reduced both the risk of death and hospitalization. The addition of cardiac resynchronization therapy to implantable cardioverter defibrillator (ICD) therapy reduced the incidence of all-cause mortality and HF hospitalizations in patients with NYHA class II-III HF compared with ICD alone in RAFT. Telemonitoring failed to improve outcome compared with a high standard of conventional care in patients with chronic HF (TIM-HF study) and a telephone-based interactive voice response system failed to improve outcome in patients recently hospitalized for HF (Tele-HF study). ASCEND-HF suggested that nesiritide was ineffective but safe in patients with acute decompensated HF. ROCKET-AF suggests that the factor-Xa inhibitor rivaroxaban may be as effective as warfarin in patients with atrial fibrillation. The PROTECT study provided more data to suggest that amino-terminal B-type natriuretic peptide guided therapy may be beneficial in patients with left ventricular systolic dysfunction.     

Heparanase, tissue factor, and cancer

Heparanase is an endo-beta- D-glucuronidase that is capable of cleaving heparan sulfate side chains of heparan sulfate proteoglycans on cell surfaces and the extracellular matrix, activity that is strongly implicated in tumor metastasis and angiogenesis. Evidence was provided that heparanase overexpression in human leukemia, glioma, and breast carcinoma cells results in a marked increase in tissue factor (TF) levels. Likewise, TF was induced by exogenous addition of recombinant heparanase to tumor cells and primary endothelial cells, induction that was mediated by p38 phosphorylation and correlated with enhanced procoagulant activity. TF induction was further confirmed in heparanase-overexpressing transgenic mice and correlated with heparanase expression levels in leukemia patients. Heparanase was also found to be involved in the regulation of tissue factor pathway inhibitor (TFPI). It was shown that heparanase overexpression or exogenous addition induces two- to threefold increase of TFPI expression. Similarly, heparanase stimulated accumulation of TFPI in the cell culture medium. Extracellular accumulation exceeded, however, the observed increase in TFPI at the protein level and appeared to be independent of heparan sulfate and heparanase enzymatic activity. Instead, a physical interaction between heparanase and TFPI was demonstrated, suggesting a mechanism by which secreted heparanase interacts with TFPI on the cell surface, leading to dissociation of TFPI from the cell membrane and increased coagulation activity, thus further supporting the local prothrombotic function of heparanase. As heparins are strong inhibitors of heparanase, in view of the effect of heparanase on TF/TFPI pathway, the role of heparins' anticoagulant activity may potentially be expanded.     

Age, anxiety, and self-reported health.

A sample of 472 normal males ranging in age from twenty-five to eighty-two was divided into anxious and adjusted groups on the basis of a cluster analysis of the Cattell 16PF test, and compared for scores on a self-report measure of health. While the anxious men reported more symptoms than the adjusted in the young and middle age groups, there was no difference in the old group. Although anxiety was found to be unrelated to health as evaluated by physicians' examinations, the anxious men indeed reported more health problems in eight major areas of health concern than was warranted by their actual physical health status. This relation also did not hold in the old group. Anxious men seemed to be more vagilant about their health in young and middle age groups, but not in the old group. This was interpreted as a defensive denial of symptoms in the old anxious group; for a person with trait anxiety, anxiety about approaching death and increasing health problems is just too much to bear, and he resorts to denying symptoms in an effort to diminish his anxiety.     

Fatigue,depression, and cognitive performance among aged persons

Abstract

Older and younger adults attended to lists of either pictures or words presented one at a time. At the end of each list, they attempted to recall the serial position of each member of the list. There was a pronounced effect of primacy. No recency was observed, however, except when the very last item was tested first. The usual pictorial superiority effect was abolished when pictures were drawn from a conceptually homogenous set. It was reinstated when pictures was conceptually distinctive. Number of errors on pictures was highly correlated with the judged similarity of the items in a list. The younger subjects' performance uniformly exceeded that of the older ones; but chronological age failed to interact with any experimental variable. The results imply that pictures need not be verbally labelled in order for their serial positions to be retained.     

Dysphagia lusoria: clinical aspects, manometric findings, diagnosis, and therapy

OBJECTIVE: The lusorian artery is a rare anomaly of the right subclavian artery. This artery arises from the aortic arch distal of the left subclavian artery, crossing the midline behind the esophagus. Normally this anomaly causes no symptoms. Sometimes dysphagia first appears above the age of 40 yr. METHODS: In the period of 1992-1997, the diagnosis of an aberrant right subclavian artery was made in five patients with dysphagia who were referred to a small community hospital. A sixth patient had a right-sided aorta with an aberrant left subclavian artery. RESULTS: Endoscopy revealed a pulsating impression in the esophagus of three patients. Four patients had coexisting esophageal abnormalities. Barium contrast examination of the esophagus showed a characteristic diagonal impression at the level of the fourth thoracic vertebra in all patients. Computed tomography and angiography confirmed the diagnosis and excluded aneurysms. Manometric investigation of the esophagus revealed nonspecific abnormalities in five patients. Drug treatment was sufficient in three patients (mean follow-up, 6.2 yr). Three patients were operated upon because of persistent dysphagia. Through a cervical approach the artery was ligated near its root and connected with the right carotid artery. Postoperatively two patients became symptom-free, the other patient still has intermittent dysphagia. CONCLUSION: Dysphagia can be caused by a rare anomaly of the subclavian artery. The diagnosis can be overlooked at endoscopy, but barium contrast study of the esophagus will reveal the abnormality. In patients with coexisting esophageal abnormalities the finding may be incidental and specific conservative treatment may be sufficient. Manometry cannot be used to diagnose this condition or to predict surgical outcome. When the symptoms are intractable, surgical correction should be considered even if coexisting esophageal abnormalities are present.     

Age identity, self-rated health, and life satisfaction among older adults in Dakar, Senegal

The objectives of this quantitative study were to (1) ascertain to what extent older adults aged 50 and above feel and desire to be younger than their age, and classify themselves as young versus old; (2) compare these patterns with those found among other cross-cultural populations; and (3) assess the extent to which self-rated health and life satisfaction predict age identities. This study was carried out on a sample of 500 dwellers of the Senegalese capital aged 50 and older. This sample was constructed using the quota method to strive for representativeness. Most of the respondents wanted to be younger than their chronological age (51.8 %), but only 27.8 % felt younger than they were. Moreover, 80 % of the sample claimed to be old. Self-rated health predicted felt age and the feeling of being old. Furthermore, the less-satisfied Dakar residents were with their life, the younger they wanted to be. We first discuss our results in a comparative perspective focused on how orientations toward individualism and collectivism could be related to age identity, and on demographic characteristics of the Senegalese population—where life expectancy is 59.3 years old. We then analyze the relevance of age identity dimensions as indicators of successful aging in Dakar.     

Novel,Inexpensive, and Scalable Amyloid Fibril Formation Method

Wheat flour was used as a source of protein for the in vitro synthesis of Amyloid fibrils to develop a novel and inexpensive fabrication method. Amyloid fibrillation was confirmed by Thioflavin T Fluorescence, using confocal microscopy. A morphological study was carried out by transmission electron microscopy (TEM), which revealed the high aspect ratio of the amyloid fibrils formed via a novel process. An application of the amyloid fibers produced by the novel method is shown to be melatonin sensing. Tests showed that the amyloid samples had a measurable color variation dependent on the melatonin concentration. This newly derived process could prove to be a cost-effective tool for future nano-biomaterial applications in commercial and research settings.     

Isolation,part characterization,immunogenicity, and specificity study of Plasmodium falciparum culture supernatant

A Plasmodium falciparum malaria blood stage antigen was isolated from in vitro parasite culture supernatant. The chemical composition of the antigen was studied by high-performance thin-layer chromatography, thin-layer chromatography, gas-liquid chromatography, and other chemical methods. Such analysis indicated it to be a glycophospholipid (GPL) and to be composed of xylose, mannose, galactose, and glucose linked to a phospholipid, but no inositol. The extracted and purified antigen's sensitivity and specificity properties were assessed by laser immuno assay and enzyme-linked immunosorbent assay. The results of the sensitivity study showed a very high malaria antibody-binding response compared to other known antigens. The specificity study of GPL antigen with different nonmalarial samples showed no positive response within the limit of significance. This isolated GPL antigen appears to be better than other antigens.     

Clinical trials update from the American College of Cardiology meeting 2010: DOSE,ASPIRE, CONNECT,STICH, STOP‐AF,CABANA, RACE II,EVEREST II,ACCORD, and NAVIGATOR

This article provides information and a commentary on trials relevant to the pathophysiology, prevention and treatment of heart failure presented at the annual meeting of the American College of Cardiology held in March 2010. Unpublished reports should be considered as preliminary, since analyses may change in the final publication. Results from DOSE suggest that giving diuretics using a high‐dose, bolus strategy may be better than using lower doses or a continuous infusion for patients with acute decompensated heart failure. In the ASPIRE study, addition of aliskiren to standard therapy failed to attenuate left ventricular remodelling in post‐MI patients and was associated with more adverse events. In CONNECT, remote monitoring reduced the time from CRT‐D‐ or ICD‐detected events to clinical decision and this was associated with fewer clinic visits and shorter hospitalizations. An analysis from STICH testing the effects of surgical ventricular reconstruction showed no benefit in the sub‐group of patients who achieved a greater reduction in LV volume. STOP‐AF and CABANA did not provide convincing evidence of the effectiveness or safety of catheter ablation for the treatment of AF. RACE II suggests that lenient heart rate control might be as effective as strict rate control in patients with permanent atrial fibrillation. In EVEREST II, a catheter‐based mitral valve repair procedure using the MitraClip® system had similar efficacy to traditional surgery but with fewer short‐term adverse effects. Valsartan reduced progression to diabetes in patients with impaired glucose tolerance but had no effect on cardiovascular events in NAVIGATOR. In ACCORD, strict blood pressure control failed to reduce the risk of overall cardiovascular events in high‐risk diabetic patients.     

Isomaltose excretion in health, severe injury, and disease

The excretion of urinary aldoses was studied in nine severely injured or ill surgical patients and seven healthy subjects. The disaccharide isomaltose, at first found in large amounts in the urine of two injured men, was found to be regularly present in the urine of healthy, fasting individuals in the range of 2.35–3.23 mg/24 hr(2.80 mg/24 hr). Its level decreased by the fourth day of complete caloric starvation (less than 1.5 mg/24 hr). In a group of five patients, isomaltose ranged from 9.26 to 102.12 mg/24 hr (46.7 mg/24 hr). The highest value was found in a comatose patient with a brain stem injury, and the lowest one was found in a patient treated for cardiopulmonary insufficiency. In addition to isomaltose and a few only partially identified other oligosaccharides, the most frequently and profoundly elevated urinary aldoses were mannose, lactose, and glucuronolactone. No interrelations could be established in the rise of isomaltose, glucose, and other elevated saccharides. It is suggested that their elevated excretion is a consequence of independent metabolic and functional processes. High isomaltose excretion appears to be part of the systemic glycogenolytic response of the human body to severe injury and disease.     

A randomized,double-blind,placebo-controlled study to evaluate sildenafil,ambrisentan combination therapy in pulmonary hypertension,particularly of Eisenmenger syndrome

Pulmonary arterial hypertension (PAH) - a complex and progressive disease that carries significant morbidity and mortality despite optimal medical treatment. Combination therapy for PAH can be more effective than monotherapy. The present randomized trial compared the safety and efficacy of sildenafil ambrisentan combination therapy with sildenafil monotherapy. Twenty-two patients of Eisenmenger syndrome and five patients of idiopathic PAH were randomized to two arms. There was a significant improvement in NYHA functional class and mean pulmonary artery pressure, while an insignificant improving trend was observed for 6-min walk distance and oxygen saturation, following the 12 weeks of combination therapy. An upfront combination therapy was found to be safe and effective in the management of PAH patients.     

Ends-out,or replacement,gene targeting in Drosophila

Ends-in and ends-out refer to the two arrangements of donor DNA that can be used for gene targeting. Both have been used for targeted mutagenesis, but require donors of differing design. Ends-out targeting is more frequently used in mice and yeast because it gives a straightforward route to replace or delete a target locus. Although ends-in targeting has been successful in Drosophila, an attempt at ends-out targeting failed. To test whether ends-out targeting could be used in Drosophila, we applied two strategies for ends-out gene replacement at the endogenous yellow (y) locus in Drosophila. First, a mutant allele was rescued by replacement with an 8-kb y(+) DNA fragment at a rate of approximately 1/800 gametes. Second, a wild-type gene was disrupted by the insertion of a marker gene in exon 1 at a rate of approximately 1/380 gametes. The I-SceI endonuclease component alone is not sufficient for targeting: the FLP recombinase is also needed to generate the extrachromosomal donor. When both components are used we find that ends-out targeting can be approximately as efficient as ends-in targeting, and is likely to be generally useful for Drosophila gene targeting.     

Function of Isolated Hearts from Septic, Saline-Infused, and Septic, Alcohol-Infused Rats

The aim of the present study was to determine whether hearts that demonstrate depressed myocardial reserves as a result of sustained hypermetabolic sepsis would show a potentiation of the dysfunction after an infusion of high doses of alcohol. We have previously shown that myocardial depression is present in hearts removed from hypermetabolic septic rats. Acute alcohol administration has also been shown to have a negative inotropic effect on the heart. In this study, myocardial function was assessed under in vitro conditions in which preload could be varied and aortic outflow resistance controlled and thus heart function could be determined under both low and high workloads. The alcohol-infused group increased cardiac performance as a function of increasing preload similarly to the controls. Heart rate, however, was significantly elevated compared with control. Isolated hearts from septic, saline-infused animals showed depressed cardiac performance both in terms of stroke volume and myocardial work over a range of preloads. The septic, alcohol-infused animals did not show this depression. Thus, a loss of myocardial reserve was demonstrable in hearts isolated from septic, saline-infused rats but not in septic, alcohol-infused rats. Alcohol, at least acutely, seemed to reverse or ameliorate the loss of myocardial reserve induced by sepsis possibly by increasing the ability of the heart to fill during diastole and thus perform volume work.     

Coupled cell-free synthesis, segregation, and core glycosylation of a secretory protein

mRNA from rat mammary glands 13-15 days post partum was translated in a wheat germ cell-free system either in the absence or in the presence of ribosome-denuded membranes prepared from isolated rough microsomes of dog pancreas. Newly synthesized alpha-lactalbumin was identified by immunoprecipitation with a monospecific rabbit antiserum against rat alpha-lactalbumin and was characterized by partial amino-terminal sequence determination and by lectin affinity chromatography. In the absence of membranes a presumably unglycosylated form of alpha-lactalbumin was synthesized that bound neither to concanavalin A-Sepharose nor to Ricinus communis lectin-agarose and that contained an amino-terminal signal peptide region comprising 19 amino acid residues. In the presence of membranes a processed form was synthesized that lacked the signal peptide portion and that had an amino-terminal sequence identical to that of mature alpha-lactalbumin. Furthermore, this processed form was found to be segregated, presumably within the microsomal vesicles, because it was resistant to post-translational proteolysis. It was also found to be glycosylated, and because it bound to concanavalin A-Sepharose, from which it could be eluted specifically by alpha-methyl mannoside, but not to R. communis lectin-agarose, it was presumably core-glycosylated. Processing, segregation, and core glycosylation were observed to proceed only when membranes were present during translation and not when they were added after translation.     

Association of hypertension,diabetes, stroke,cancer, kidney disease,and high-cholesterol with COVID-19 disease severity and fatality: A systematic review

Background and aimsTo undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity.MethodsA search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. Filtering of the articles was then undertaken using keywords and questions, e.g. “Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?“. The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed.FindingsA total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus.ConclusionReports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Further research regarding this relationship and its clinical management is warranted.     

Clinical trials update: IMPROVEMENT-HF, COPERNICUS, MUSTIC, ASPECT-II, APRICOT and HEART

Important new studies relevant to the field of heart failure reported at the annual congress of the European Society of Cardiology (ESC), held in Amsterdam in August 2000, are reviewed. The IMPROVEMENT of Heart Failure survey investigated the knowledge and perceptions of over 1300 primary care physicians from 14 ESC member nations and the actual practice in over 11000 of their patients. Guidelines and clinical practice were compared. The survey suggested, in this large sample, that the quality of care was higher than previous smaller surveys have suggested but have also identified important deficiencies in knowledge and management that should be rectified. The COPERNICUS study demonstrated that carvedilol was remarkably well tolerated even in patients with very severe heart failure and that treatment was associated with a substantial reduction in mortality even among patients that would conventionally not be considered, by many, for beta-blocker therapy. The MUSTIC trial suggested that cardiac resynchronisation using biventricular pacing improved patients symptomatically whether or not the patient was in atrial fibrillation. Morbidity and mortality studies of cardiac resynchronisation are now underway. The ASPECT-II and APRICOT-II studies investigated the role of warfarin, aspirin and their combination for the long-term management of myocardial infarction. One interpretation of the data from these studies is that the combination of aspirin and warfarin is about as effective as warfarin alone but with a much higher incidence of side effects. Warfarin alone appeared superior to aspirin alone. In summary, the annual congress of the ESC provided important new information for clinical practice and, to date, was, by far, the most important cardiology congress in the world this year.     

Leukocyte count,smoking, and lung function

The interrelation between leukocyte count, cigarette smoking, and pulmonary function results was examined in two work populations: 1,826 white male workers in a pulp and paper mill and 1,620 white male workers in an aluminum smelter in British Columbia. These workers took part in epidemiologic health studies that consisted of a medical-occupational questionnaire, spirometric measurements, and leukocyte count. Measurements of the air contaminants in the work environment were also carried out simultaneously by personal and area sampling. No significant increase in the prevalence of respiratory symptoms and lung function abnormalities was found between the exposed and nonexposed workers in each work population. Similarly, no difference in leukocyte count was found between exposed and nonexposed workers. Leukocyte count was found to be significantly higher among current smokers than nonsmokers and former smokers in each population. In both populations, there was an inverse correlation between leukocyte count and one-second forced expiratory volume and forced vital capacity of the workers irrespective of the smoking habit. This finding suggests that the leukocyte response to external stimuli may be another determinant of lung function measurements.     

Meeting report: American Aging Association 40th Annual Meeting, Raleigh, North Carolina, June 3-6, 2011

The focus of the 2011 American Aging Association meeting was emerging concepts in the mechanisms of aging. Many of the usual topics in aging were covered, such as dietary restriction (DR), inflammation, stress resistance, homeostasis and proteasome activity, sarcopenia, and neural degeneration. There was also discussion of newer methods, such as microRNAs and genome sequencing, that have been employed to investigate gene expression variance with aging and genetic signatures of longevity. Aging as a field continues to mature, including the following areas: Using a systems approach to tracing conserved pathways across organisms; sharpening definitions of sarcopenia, frailty, and health span; and distinguishing interventions by age tier (early-onset versus late-onset). A preconference session on late-onset intervention concluded that there are numerous benefits to deriving such interventions. Conference talks applied the biology of aging in a translational manner to intervention development. Using an individual's own stem cells to regenerate organs for transplantation and as a cell source for cellular therapies could be a powerful near-term solution to disease. Several proposed interventions were pharmaceutical, myostatin inhibition, losartan, Janus kinase (JAK) pathway inhibitors, and enalapril for frailty and sarcopenia, and metformin to promote the Nrf2 antiinflammation response. In DR, protein restriction was found to be better than general calorie restriction. Short-term fasting may be helpful in chemotherapy, surgery, and acute stress, simultaneously increasing the killing of cancer cells by chemotherapy, while improving the survival of normal cells. Immune system interventions remain elusive, although statins may help to improve cellular senescence promoted bacterial infection. Engineered enzymes may be useful in lysosomal catabolism. Dietary restriction mimetics, most promisingly involving target of rapamycin (TOR; TORC1 inhibition and rapamycin), may be more feasible than dietary restriction.