Lymphocyte interleukin 2 production and responsiveness are altered in patients with primary myelodysplastic syndrome

Immunoregulatory T and B cell functions in 15 patients with primary myelodysplastic syndrome (MDS) were studied by measuring the proliferative and the stimulatory capacity of T and B cells, respectively, in autologous (auto) and allogeneic (allo) mixed lymphocyte reaction (MLR). T cell proliferation in the auto MLR was 25% of the control (P less than .02), whereas proliferation in the allo MLR was normal. When control T cells were stimulated by MDS B cells, their proliferative response was only 57% of the control (P less than .01). The mechanism responsible for these abnormalities was studied by determining the capacity of MDS and normal T cells to produce interleukin 2 (IL 2) and to generate IL 2 receptors (IL 2R) following stimulation with control and MDS B cells. In the auto MLR of MDS patients, only 3% +/- 2% of T cells developed IL 2R positivity, whereas in control cultures 12% +/- 2% of T cells were positive, as determined by immunofluorescence, using a monoclonal antibody (MoAb) directed against the IL 2R, and FACS analysis. When MDS T cells were stimulated by control B cells, IL 2R generation and the production of IL 2 were within normal limits. In contrast, when control T cells were stimulated by MDS B cells or control B cells, the MDS B cells induced production of only 26% of IL 2 as compared with control B cells. In parallel experiments, IL 2R generation in control T cells stimulated by either MDS or control B cells was similar. We conclude that in the primary MDS, T and B cell interactions are impaired. Although MDS T cells develop normal quantities of IL 2R and produce normal amounts of IL 2 when stimulated by control B cells, they are markedly impaired when stimulated by self B cells. Similarly, MDS B cells can induce IL 2R generation in control T cells but not in MDS T cells. Myelodysplastic B cells are also defective in inducing IL 2 production by normal T cells in an allo MLR. These in vitro abnormalities strongly suggest that generation of lymphocytes with immunoregulatory functions is impaired in patients with MDS.     

Endothelial lipase promotes the catabolism of ApoB-containing lipoproteins

Endothelial lipase (EL) has been found to be a key enzyme in high-density lipoprotein (HDL) metabolism in mice, leading to the concept that inhibition of EL could be a novel strategy for raising HDL cholesterol levels. However, mice are "HDL animals" and the effect of EL on atherogenic apoB-containing lipoproteins has not been elucidated. We previously found that EL is capable of hydrolyzing very low-density lipoprotein (VLDL) and LDL lipids ex vivo. To investigate the role of EL in the metabolism of apoB-containing lipoproteins in vivo, we expressed human EL in three mouse models of elevated apoB-containing lipoproteins: apoE-deficient, LDL receptor-deficient, and human apoB transgenic mice. Unexpectedly, hepatic expression of EL resulted in markedly decreased levels of VLDL/LDL cholesterol, phospholipid, and apoB accompanied by significantly increased LDL apolipoprotein and phospholipid catabolism. To determine whether lipolytic activity is required for this effect, we also expressed a catalytically inactive form of human EL (ELS149A); unexpectedly, expression of ELS149A did not lower and in fact increased plasma lipids. Coexpression and coimmunoprecipitation studies suggested that catalytically inactive ELS149A inhibits endogenous mouse EL, accounting for the increased lipid levels. We conclude that (1) in addition to its known effects on HDL metabolism, EL influences the metabolism of apoB-containing particles; (2) catalytic activity of EL is required for its effects on apoB-containing lipoproteins; and (3) overexpressed catalytically inactive EL inhibits endogenous mouse EL, resulting in increased levels of plasma lipids. In light of these results, inhibition of EL has the potential to raise levels of atherogenic lipoproteins in addition to HDL-C levels.     

Analysis of fasting antroduodenal manometry in children

Antroduodenal manometry has been used to determine the pathophysiology associated with signs and symptoms of gastrointestinal motility disorders. The diagnostic value of antroduodenal manomentry has been limited by the paucity of data from normal children. In this study, we compared antroduodenal manometry findings from 95 patients with symptoms suggesting a gastrointestinal motility disorder to 20 control children. Phase III of the migrating motor complex (MMC) was less frequent in patients (P<0.05), especially in those who required total parenteral nutrition (P<0.001), than in controls. Abnormal migration of phase III and short intervals between phase IIIs were more frequent in patients than in controls (P<0.01 andP<0.05, respectively). During phase II, persistent low-amplitude contractions and sustained tonic-phasic contraction were found only in parenteral-nutrition-dependent children. Short or prolonged duration of phase III, absence of phase I following phase III, tonic contractions during phase III, low amplitude of phase III contractions in a single recording site and clusters of contractions or prolonged propagating contractions during phase II were not more frequent in patients than in controls. We conclude that there are five manometric features having a clear association with pediatric gastrointestinal motility disorders: (1) absence of phase III of the MMC, (2) abnormal migration of phase III, (3) short intervals between phase III episodes, (4) persistent low-amplitude contractions, and (5) sustained tonic-phasic contractions.     

Ophthalmic manifestations in the COVID-19 clinical spectrum

Purpose:The aim of this study was to determine the frequency and various types of ophthalmic manifestation of patients with COVID-19.Methods:This is a prospective observational study conducted on patients with SARS-Co-V-2 infection, at a dedicated tertiary COVID-19 hospital in South India from April 1 to July 31, 2020. At the time of their admission to the COVID hospital, demographic data such as name, age, sex was recorded. A thorough history regarding the onset, duration, progression, nature of symptoms and its associated factors, medication history, treatment history were elicited and documented. Ocular examination was performed under torchlight by an ophthalmologist posted for COVID duty. Further investigations including imaging were sought for, depending on clinical indications. Serial follow-up examinations of all patients were carried out every 72 hours or when patients complained of any ocular symptoms whichever earlier, until discharge. All relevant data were compiled and statistically analyzed.Results:A total of 2742 patients were examined. Of them, 1461 (53.28%) were males and 1281 (46.72%) were females. The mean age (±SD) was 39.46 ± 17.63 years. None of the patients in our study had any ocular symptoms or signs as the presenting complaint at the time of their admission. On subsequent follow-up, only 20 (0.72%) developed ocular manifestations, of which 19 (95%) had features suggestive of Bilateral viral conjunctivitis. However, 1 (5%) patient had orbital cellulitis secondary to pansinusitis.Conclusion:Ophthalmic manifestations in the clinical spectrum of COVID-19 infection are uncommon and unlikely to be the presenting clinical impression. However, it has broadened our view to a wider spectrum of COVID-19 presentations enhancing our clinical acumen for staunch detection of COVID-19 suspects in our daily practice, augmenting early diagnosis and management and also break the chain of transmission for the greater good of humanity.     

Nursing education and professional role acquisition. A longitudinal study of expectations and attitudes towards nurse role acquisition

This article deals with professional role acquisition in nurses and discusses results from three studies concerning expectations and attitudes towards this acquisition. The studies have been carried out in Sweden. The discussion comprises expressed expectations and attitudes of nurse students and registered nurses in relation to our theoretical perspectives presented in a former article. The theoretical perspectives concentrate on three aspects of social action: change-drama, interchange-ritual, and maintenance-routine. The results indicate that the professional nurse role is acquired according to a traditional pattern, in spite of changes in curriculum and goals of nursing education and health care. Changes made to develop and improve the conditions under which role acquisitions take place.     

Inhibition of endothelial lipase causes increased HDL cholesterol levels in vivo

Endothelial lipase (EL) is a recently discovered member of the lipoprotein lipase gene family that hydrolyzes HDL phospholipids ex vivo and reduces HDL cholesterol (HDL-C) levels when overexpressed in vivo in mice. To gain further insight into the physiological role of EL in the metabolism of HDL in vivo, studies were performed in which EL was inhibited in wild-type, hepatic lipase knockout (HL(-/-)), and human apoA-I transgenic mice by intravenous infusion of a polyclonal antibody inhibitory to murine EL. As compared with infusion of a control antibody, infusion of the inhibitory antibody resulted in a 25-60% increase in HDL-C levels in the three mouse models, with the peak HDL-C levels occurring at 48 hours after injection. Inhibition of EL also generated larger HDL particles in the HL(-/-) mice. The clearance of HDL phospholipid was significantly slower in human apoA-I transgenic mice injected with an antibody against murine EL (mEL) than in mice injected with a control antibody. We conclude that inhibition of EL results in increased HDL-C levels and that EL is an important enzyme in the physiological regulation of HDL metabolism.     

Perioperatives Management bei Diabetes mellitus

The prevalence of diabetes in hospitalized adults is conservatively estimated at 12–25% and rising. Poor glucose control and presence of diabetes complications (e.g. diabetic nephropathy, diabetic neuropathy, atherosclerosis) are commonly regarded as risk factors for perioperative morbidity and mortality. Thus it is crucial to determine diabetes comorbidities preoperatively in order to avoid perioperative renal and cardiovascular complications. Perioperative glycemic control is challenging due to preoperative changes in diabetes treatment and the effects of surgery-associated stress hyperglycemia. For patients in general surgical units, evidence for specific glycemic goals is based on epidemiologic and physiologic data rather than clinical trials. According to guidelines of the German Society of Nutrition, the approximation of normoglycemia is reasonable as long as hypoglycemia is avoided (suggested range for plasma glucose 80–145 mg/dL).     

Comparison of current guidelines for primary prevention of coronary heart disease

OBJECTIVE: In primary prevention of atherosclerotic disease, it is difficult to decide when medical treatment should be initiated. The main goal of the study was to compare different guidelines for coronary heart disease (CHD) risk assessment and initiation of lipid-lowering therapy. DESIGN: Cross-sectional evaluation. SETTING: An outpatient lipid and diabetes clinic in a university hospital. PARTICIPANTS/METHODS: Risk factor data obtained on 100 consecutive patients (58 men and 42 women) without clinical evidence of cardiovascular disease were used to compare the Framingham risk equation, the U.S. National Cholesterol Education Program (Adult Treatment Panel III) (NCEP ATP III) guidelines, the joint European Societies guidelines, the joint British guidelines, the revised Sheffield table, and the Munster Heart Study calculator (PROCAM) CHD risk assessment and lipid-lowering therapy. RESULTS: Guidelines could be applied to different subsets of the cohort, ranging from 22% (PROCAM) to 95% of the cohort (revised Sheffield table). All guidelines (except PROCAM) could be applied to a total of 62 patients. Guidelines predicted > or =20% risk for developing CHD over 10 years in 53% (NCEP ATP III), 26% (European) and 32% (British), while Framingham predicted this risk level in 34%. CHD risk was estimated to be > or =3%/year in 5% according to Sheffield, while Framingham predicted this risk in 13%. Lipid-lowering drug therapy is recommended in 52% by NCEP ATP III, while European, British, and Sheffield guidelines recommend this in 26%, 35%, and 5%, respectively. CONCLUSIONS: Guidelines for assessing CHD risk and lipid-lowering therapy differ greatly. Therefore, these algorithms must be used with caution.