The nature of antiidiotype molecules induced by antiallotype. Presence of both latent allotype and allotypic internal images

Previously (9), I found that immunization of rabbits with antibody directed against variable region heavy chain VH polypeptides of a1 allotype induced the production of antiidiotype (anti-Id) molecules that appeared to bear images of the original a1 allotype. I now show that these anti-Id molecules can be fractionated into two populations: one population (a2a3- anti-Id) that lacks the nominal VH a2 or a3 allotype of the rabbit from which it was derived, and another population (a2a3+ anti-Id) that expresses these allotypes. Both anti-Id populations display epitopes that resemble a1 since: (a) they were capable of inhibiting 125I-a1 Ig binding to rabbit anti-a1, goat anti-a1, and mouse anti-a1 mAb; and (b) immunization of normal a2a3 rabbits with either anti-Id fraction led to the formation of specific anti-a1 antibody. Reductive cleavage of the anti-Id molecules showed that the a1 determinants in the a2a3- population were fully displayed on isolated H chains, consistent with the presence of latent a1 Ig. On the other hand, as expected for internal images encoded by the antigen-combining site, the a2a3+ anti-Id population required intact H and L chains for maximal a1 expression. The a1-like images within the a2a3+ anti-Id population do not appear to be identical to nominal or latent a1, however, since a2a3- anti-Id was invariably a more efficient inhibitor of a 1 Ig-anti-a1 binding than a a2a3+ anti-Id. These results indicate that immunization with antiallotype can result in the simultaneous production of both latent allotypes and allotypic internal images.     

Determination of free apolipoprotein(a) in serum by immunoassay and its significance for risk assessment in patients with coronary artery disease.

This paper describes a new enzyme-linked ligand sorbent assay (ELLSA) to quantify free apolipoprotein(a) (apo(a)). The new test immobilizes free apo(a) utilizing a specific peptide that carries the amino acid sequence of a non-covalent apo(a) binding site on apoB3375-3405 (ligand-peptide). The ligand-peptide coupled to Sepharose was used in affinity chromatography to separate free apo(a) from whole serum. Isolated free apo(a) consisted of full length apo(a) and smaller apo(a). Additionally, free apo(a) levels determined by ELLSA as well as by electroimmunodiffusion correlated moderately well. Significantly increased serum concentrations of free apo(a) were found in coronary artery disease. The mean value of free apo(a) was three times higher in patients than in controls while the lipoprotein(a) (Lpla)) concentration was doubled. Utilizing receiver operating characteristic diagrams, it was shown that the free apo(a)-ELLSA had a better diagnostic test performance in atherosclerotic risk assessment than the Lp(a)-test: specificity free apo(a)-ELLSA 0.77, Lp(a)-test 0.81 [with (a:a)-enzyme immunoassay (EIA)] to 0.83 [with (a:B)-EIA]; sensitivity free apo(a)-ELLSA 0.57, Lp(a)-test 0.36 to 0.40. In conclusion, the new free apo(a)-ELLSA allows for the specific quantification of free apo(a). This provides an interesting indicator for atherosclerotic risk assessment.     

Multidisciplinary integrated headache care: a prospective 12-month follow-up observational study

This prospective study investigated the effectiveness of a three-tier modularized out- and inpatient multidisciplinary integrated headache care program. N = 204 patients with frequent headaches (63 migraine, 11 tension-type headache, 59 migraine + tension-type headache, 68 medication-overuse headache and 3 with other primary headaches) were enrolled. Outcome measures at baseline, 6- and 12-month follow-ups included headache frequency, Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), standardized headache diary and a medication survey. Mean reduction in headache frequency was 5.5 ± 8.5 days/month, p < 0.001 at 6 months’ follow-up and 6.9 ± 8.3 days/month, p < 0.001 after 1 year. MIDAS decreased from 53.0 ± 60.8 to 37.0 ± 52.4 points, p < 0.001 after 6 months and 34.4 ± 53.2 points, p < 0.001 at 1 year. 44.0 % patients demonstrated at baseline an increased HAD-score for anxiety and 16.7 % of patients revealed a HAD-score indicating a depression. At the end of treatment statistically significant changes could be observed for anxiety (p < 0.001) and depression (p < 0.006). The intake frequency of attack-aborting medication decreased from 10.3 ± 7.3 days/month at admission to 4.7 ± 4.1 days/month, p < 0.001 after 6 months and reached 3.8 ± 3.5 days/month, p < 0.001 after 1 year. At baseline 37.9 % of patients had experience with non-pharmacological treatments and 87.0 % at 12-month follow-up. In conclusion, an integrated headache care program was successfully established. Positive health-related outcomes could be obtained with a multidisciplinary out- and inpatient headache treatment program.     

Kringle-containing fragments of apolipoprotein(a) circulate in human plasma and are excreted into the urine.

Apolipoprotein(a) [apo(a)] contains multiple kringle 4 repeats and circulates as part of lipoprotein(a) [Lp(a)]. Apo(a) is synthesized by the liver but its clearance mechanism is unknown. Previously, we showed that kringle 4-containing fragments of apo(a) are present in human urine. To probe their origin, human plasma was examined and a series of apo(a) immunoreactive peptides larger in size than urinary fragments was identified. The concentration of apo(a) fragments in plasma was directly related to the plasma level of Lp(a) and the 24-h urinary excretion of apo(a). Individuals with low (< 2 mg/dl) plasma levels of Lp(a) had proportionally more apo(a) circulating as fragments in their plasma. Similar apo(a) fragments were identified in baboon plasma but not in conditioned media from primary cultures of baboon hepatocytes, suggesting that the apo(a) fragments are generated from circulating apo(a) or Lp(a). When apo(a) fragments purified from human plasma were injected intravenously into mice, a species that does not produce apo(a), apo(a) fragments similar to those found in human urine were readily detected in mouse urine. Thus, we propose that apo(a) fragments in human plasma are derived from circulating apo(a)/Lp(a) and are the source of urinary apo(a).     

Partners in caring: a partnership for healing

This article describes one organization's effort to create a family-friendly environment that supports the choice of patients for involvement of a family member or loved one in their care. Changing a culture requires a process that can emotionally drive the caregivers to agree with the need to change and sustain the efforts over a long period. This project, Partners in Caring, describes the philosophy, the journey of changing a culture, and the results achieved over a 7-year period. The Partners in Caring philosophy is "a commitment between a patient, care partner and healthcare team to a relationship of hands-on support based on compassion, communication and choice empowering people to heal in a nurturing manner." This concept laid a foundation for the development of a new model of care, which is described. The implementation has resulted in an improved patient and staff satisfaction and a decrease in patient complaints.     

Development of new enzyme-linked immunosorbent assay for oxidized lipoprotein(a) by using purified human oxidized lipoprotein(a) autoantibodies as capture antibody

BACKGROUND: Oxidized Lp(a) [ox-Lp(a)] has been reported to play more potent role than native Lp(a) in atherosclerosis. Ox-Lp(a), autoantibodies, and Lp(a) immune complexes have all been detected in vivo. Thus, the isolation of its autoantibodies and the investigation of ox-Lp(a) may provide a new means to explore the exact pathogenic role of ox-Lp(a). We isolated and identified human autoantibodies against ox-Lp(a) and developed a new ELISA for ox-Lp(a) by using autoantibodies as capture antibody. METHODS: Ox-Lp(a) autoantibodies were isolated and identified from healthy subjects by affinity chromatography. 2 "sandwich" ELISAs were developed for measuring ox-Lp(a) level, using autoantibodies against ox-Lp(a) or rabbit antiserum against ox-LDL as the capture antibody and quantitating with monoclonal anti-apo(a) enzyme conjugate, respectively. Ox-Lp(a) levels were studied by both the ELISAs in 100 patients with coronary heart disease (CHD) and 100 control subjects. RESULTS: The isolated ox-Lp(a) autoantibodies reacted with both apo(a) and apoB epitopes of Ox-Lp(a). Compared to control, plasma ox-Lp(a) levels in patients with CHD were significantly increased (ELISA using human autoantibodies: 24.3+/-33.4 vs. 8.4+/-9.3 microg/ml, P<0.0001; ELISA using antibodies against ox-LDL: 13.0+/-13.8 vs. 7.3+/-9.7 microg/ml, P<0.0001, respectively). Furthermore, a significantly positive relationship between ox-Lp(a) levels detected by 2 ELISAs was also found (R=0.78, P<0.0001). CONCLUSION: We isolated human autoantibodies against ox-Lp(a), which can recognize both apo(a) and apoB epitopes of ox-Lp(a). The developed ELISA for ox-Lp(a) by using human auoantibodies may more accurately reflect the state of Lp(a) oxidation in vivo. Ox-Lp(a) levels increase in patients with CHD.     

Association of lipoprotein(a) concentration and apo(a) isoform size with restenosis after percutaneous transluminal coronary angioplasty

Lp(a) is a unique class of lipoprotein particles that exhibits a considerable size heterogeneity resulting from the size polymorphism of apo(a), its unique protein component. An elevated level of Lp(a) in plasma has been proposed to be a risk factor for premature development of coronary artery disease. To evaluate the relationship between Lp(a) concentration and apo(a) isoform size with restenosis after percutaneous transluminal coronary angioplasty, Lp(a) levels and apo(a) phenotypes were determined in 204 patients who underwent a successful coronary angioplasty procedure and stent implantation. The patients were followed with clinical examinations and exercise tests at 1, 3, and 6 months, and a control coronary angiography was performed after 6 months to evaluate restenosis. Lp(a) levels were determined with an ELISA that is insensitive to the size heterogeneity of Lp(a), and the apo(a) isoforms were determined by a high-resolution agarose gel electrophoresis method followed by immunoblotting with a specific monoclonal antibody. Of the 146 patients who underwent angiographic evaluation, 57 (39%) had restenosis, whereas 89 (61%) did not. Lp(a) levels and the distribution of the expressed apo(a) phenotypes were compared in these two groups of patients. Although the mean and median Lp(a) levels were higher in the restenosed group, the difference was not statistically significant. However, a significant difference in Lp(a) values was found in women (P=0.043), even though, because of the small number of women in the study (n=35), no sound conclusions can be reached on the predictive role of Lp(a) in restenosis. There also was no difference in the distribution of apo(a) phenotypes between the two groups. Because of their wide distribution, Lp(a) values and apo(a) isoforms do not seem to be a useful indicator of risk of restenosis after percutaneous transluminal coronary angioplasty in our study cohort.     

Enigmatic role of lipoprotein(a) in cardiovascular disease

Lipoprotein (a), [Lp(a)] has many properties in common with low-density lipoprotein, (LDL) but contains a unique protein apolipoprotein(a), linked to apolipoprotein B-100 by a single disulfide bond. There is a substantial size heterogeneity of apo(a), and generally smaller apo(a) sizes tend to correspond to higher plasma Lp(a) levels, but this relation is far from linear, underscoring the importance to assess allele-specific apo(a) levels. The presence of apo(a), a highly charged, carbohydrate-rich, hydrophilic protein may obscure key features of the LDL moiety and offer opportunities for binding to vessel wall elements. Recently, interest in Lp(a) has increased because studies over the past decade have confirmed and more robustly demonstrated a risk factor role of Lp(a) for cardiovascular disease. In particular, levels of Lp(a) carried in particles with smaller size apo(a) isoforms are associated with coronary artery disease (CAD). Other studies suggest that proinflammatory conditions may modulate risk factor properties of Lp(a). Further, Lp(a) may act as a preferential acceptor for proinflammatory oxidized phospholipids transferred from tissues or from other lipoproteins. However, at present only a limited number of agents (e.g., nicotinic acid and estrogen) has proven efficacy in lowering Lp(a) levels. Although Lp(a) has not been definitely established as a cardiovascular risk factor and no guidelines presently recommend intervention, Lp(a)-lowering therapy might offer benefits in subgroups of patients with high Lp(a) levels.     

Further characterization of the plasma lipoprotein(a) distribution

The plasma lipoprotein(a) [Lp(a)] distribution in caucasians is heavily skewed to the right, with evidence of bimodality. As there is a well-described inverse relationship between apolipoprotein(a) [apo(a)] size and Lp(a) concentration, it is likely that the presence of multiple apo(a) isoforms of differing frequency has a significant impact on the final distribution of Lp(a) concentrations. We have previously described an immunoblot method for examining the relationship between apolipoprotein(a) [apo(a)] size and lipoprotein(a) [Lp(a)] mass among samples heterozygous for apo(a) size, thus eliminating confounding by null or undetected apo(a) isoforms. In the present study, this method has been applied to examine the plasma Lp(a) distribution, independent of the effects of apo(a) isoform size and frequency. Seventy subjects heterozygous for apo(a) size were studied. To take into account the inverse relationship (P <0.001) between apo(a) isoform size and Lp(a) concentration, Lp(a) data associated with each apo(a) isoform were normalized as multiples of the median Lp(a) concentration for that isoform. These apo(a) isoform-independent Lp(a) data demonstrated a strikingly multimodal distribution, with five major peaks. The relative frequencies of Lp(a) peaks 1–5 were 17.1%, 15.0%, 35.7%, 23.6%, and 8.6%, and associated median Lp(a) concentrations were 1.0, 6.2,15.0, 21.8, and 39.6 mg/dL, respectively. Multivariate analysis demonstrated that apo(a) isoform size accounted for 23% and isoform-independent Lp(a) peaks for 59.5% of the variation in Lp(a) concentration. Further investigation of the characteristics of the apo(a) isoform-independent Lp(a) distribution is warranted.     

Glycemia and peak incremental indices of six popular fruits in Taiwan: healthy and Type 2 diabetes subjects compared

The aim of this study was to evaluate the glycemic index and peak incremental indices of six popular fruits in Taiwan, comparing healthy subjects (n = 20) and patients with Type 2 diabetes (n = 17). The six kinds of fruits tested were grapes, Asian pears, guavas, golden kiwifruit, lychees and bananas. Glycemic index values were tested according to the standard glycemic index testing protocol. The glycemic index and peak incremental indices were calculated according to published formulas. In Type 2 diabetes subjects, the glycemic index values of grapes, Asian pears, guavas, golden kiwifruit, lychees and bananas were 49.0 ± 4.5, 25.9 ± 2.9, 32.8 ± 5.2, 47.0 ± 6.5, 60.0 ± 8.0 and 41.3 ± 3.5. In healthy subjects, the glycemic index values were 49.1 ± 7.3, 18.0 ± 5.4, 31.1 ± 5.1, 47.3 ± 12.1, 47.9 ± 6.8 and 35.1 ± 5.6. There was no significant difference in glycemic index values between healthy and Type 2 diabetes subjects. There was also no significant difference in PII when comparing healthy subjects and subjects with Type 2 diabetes. In conclusion, glycemic index and peak incremental indices in healthy subjects can be approximately the same for Type 2 diabetes.     

Apolipoprotein(a) phenotypes, Lp(a) concentration and plasma lipid levels in relation to coronary heart disease in a Chinese population: evidence for the role of the apo(a) gene in coronary heart disease.

Elevated lipoprotein(a) (Lp[a]) concentrations are associated with premature coronary heart disease (CHD). In the general population, Lp(a) levels are largely determined by alleles at the hypervariable apolipoprotein(a) (apo[a]) gene locus, but other genetic and environmental factors also affect plasma Lp(a) levels. In addition, Lp(a) has been hypothesized to be an acute phase protein. It is therefore unclear whether the association of Lp(a) concentrations with CHD is primary in nature. We have analyzed apo(a) phenotypes, Lp(a) levels, total cholesterol, and HDL-cholesterol in patients with CHD, and in controls from the general population. Both samples were Chinese individuals residing in Singapore. Lp(a) concentrations were significantly higher in the patients than in the population (mean 20.7 +/- 23.9 mg/dl vs 8.9 +/- 12.9 mg/dl). Apo(a) isoforms associated with high Lp(a) levels (B, S1, S2) were significantly more frequent in the CHD patients than in the population sample (15.9% vs 8.5%, P less than 0.01). Higher Lp(a) concentrations in the patients were in part explained by this difference in apo(a) allele frequencies. Results from stepwise logistic regression analysis indicate that apo(a) type was a significant predictor of CHD, independent of total cholesterol and HDL cholesterol, but not independent of Lp(a) levels. The data demonstrate that alleles at the apo(a) locus determine the risk for CHD through their effects on Lp(a) levels, and firmly establish the role of Lp(a) as a primary genetic risk factor for CHD.     

Comorbidity profiles of chronic migraine sufferers in a national database in Taiwan

Chronic migraine (CM; ≥15 headache days per month, ≥3 months) is associated with a higher prevalence of comorbidities than episodic migraine (<15 headache days per month). However, it is unclear whether a similar pattern exists in Asian patients. To examine this, a retrospective matched cohort study was conducted using the Taiwan National Health Insurance Research Database. CM cases were defined as patients with at least one neurological outpatient visit with a primary or secondary ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) code of 346.11, diagnosed by neurologists at medical centers during 2007–2008. The study group was compared with patients suffering from other migraine subtypes and non-migraineurs in the general population. Both comparison groups were matched with CM sufferers at a 4:1 ratio by age, gender, urbanization level of the residence, income, and hospital setting. Relative risk (RR) was calculated using conditional logistic regression. Compared with patients with other migraines (n = 2,226), CM sufferers (n = 681) had a higher risk of hyperlipidemia (RR = 1.32; P = 0.041), asthma (RR = 1.77; P = 0.007), depression (RR = 1.88; P < 0.0001), bipolar disorder (RR = 1.81; P = 0.022) and anxiety disorders (RR = 1.48; P = <0.0001). Compared with the non-migraineurs (n = 3,790), CM sufferers (n = 948) had significantly increased risks of cardiovascular disease, sinusitis, asthma, gastrointestinal ulcers, vertigo and psychiatric disorders by 1.6–3.9-fold. In conclusion, CM is associated with significant comorbidities in Asian patients. Differences in the comorbidity profiles of CM compared with other migraines have highlighted that patients with CM differ not just in terms of headache frequency but also in other important aspects.     

Relationship between plasma lipoprotein (a), apolipoprotein (a) phenotypes, and other coronary heart disease risk factors in a Melbourne South Asian population

BACKGROUND: High plasma lipoprotein(a) [Lp(a)] level is a strong and important risk factor for cardiovascular disease (CVD). Small-sized apolipoprotein(a) [apo(a)] isoforms (F, B, S1, and S2) are inversely correlated with the high levels of Lp(a) in plasma and significantly associated with CVD. Although the effects of apo(a) phenotypes and various risk factors on Lp(a) status in South Asian population may have been studied in other countries, there are no reports involving these risk factors in Australia. METHODS AND RESULTS: Factors contributing to variation in Lp(a) were surveyed in 402 (216 males and 186 females) South Asian Melburnians. There was a negative relationship between low alcohol beer per day and Lp(a) in men (P < 0.05). Approximately 21% of the variance of Lp(a) concentration in men and 6% in women were explained by age. Age was positively associated with Lp(a) concentrations in men but negatively in women. The most commonly occurring phenotype was apo(a) S3. In this phenotype, Lp(a) concentrations ranged from non-detectable to 811 mg/l. After adjusting for age, an inverse correlation was observed between Lp(a) concentration and apo(a) phenotypes (P < 0.01). CONCLUSIONS: Although Lp(a) has been reported to be genetically determined, there are clearly other factors contributing to variations in Lp(a) concentrations in a South Asian population.     

Usage of a defibrillator

Guideline 2010 for cardiopulmonary resuscitation was released the other day. There is no big change in the use of a defibrillator. Asynchronous defibrillation is used as a therapy for VF and pulseless VT. When you find a patient, start CPR immediately and prepare a defibrillator. About the value of energy, comply a recommended value of defibrillator's manufacturer with biphasic waveform, on the other hand, deliver 360J shock with monophasic waveform. Cardioversion is used as a therapy for supraventricular arrhythmia like atrial fibrillation. It is important to synchronize with QRS complex on ECG surely and deliver a shock. If it is not synchronized surely, there is a possibility to occur VF. Transcutaneous pacing is used as a therapy for bradycardia. It produces a depolarization of myocardium by giving current stimulus from a surface of a body, and force a heart to contract. It is usually carried out at demand mode, and confirmed that a heart contracts certainly. Defibrillator is an only device to terminate VF and pulseless VT and it is important to test defibrillator usually so that it can be used any time it is necessary.     

Coffee,Chaos, and Competence: A Day in the Life of a Radiology Nurse

The role of a radiology nurse is not clearly understood by patients or nursing colleagues. Following a radiology float nurse through a day in a complex radiology practice in a Magnet-designated facility illustrates how a radiology nurse must incorporate specialty education and training, clinical competence, and a professional nursing practice model to provide quality patient care.     

Identifying and combating the risk of pressure

Risk assessment tools for pressure sores are commonplace in most nursing settings. This article describes a situation where a woman in a maternity unit developed pressure-related injuries, and how a thorough assessment led to a solution to a surprising problem.     

CEUS in the study of bladder,method, administration and evaluation,a technical note

Purpose

Contrast-enhanced ultrasound (CEUS) is the application of ultrasound contrast agents (UCAs) to traditional medical sonography. The development of UCAs allowed to overcome some of the limitations of conventional B-mode and Doppler ultrasound techniques and enabled the display of the parenchymal microvasculature. Purpose of this paper is to delineate the elements of a solid and science-based technique in the execution of urinary bladder CEUS.

Methods

We describe the technical execution of urinary bladder CEUS and the use of perfusion softwares to perform contrast enhancement quantitative analysis with generation of time–intensity curves from regions of interest.

Results

During CEUS, normal bladder wall shows a wash-in time of 13 s, a time to peak (TTP) >40 s, a signal intensity (SI) <45 % and a wash-out time >80 s; Low-grade urothelial cell carcinoma (UCC) shows a wash-in time of 13 s, a time to peak TTP >28 s, a SI <45 % and a wash-out time of 40 s; High-grade UCC shows a wash-in time of 13 s, a TTP >28 s, a SI >50 % and a wash-out time of 58 s.

Conclusions

CEUS is a useful tool for an accurate characterization of bladder UCC although it has some drawbacks. To avoid misunderstandings, a widely accepted classification and a standardized terminology about the most significant parameters of this application should be adopted in the immediate future.     

Did you check your nursemaid's elbow?

Imagine a parent innocently swinging around a toddler ... a yank on an outstretched arm to keep a preschooler from falling ... a caregiver attempting to move a reluctant child by dragging the child by the hand ... a helping hand to lift a young child up over the curb or a high step. None of these activities is ever intended to hurt a child, yet the result of these specific activities send many children with anxious parents and caregivers to emergency departments and unscheduled pediatrician appointments each year. Nursemaid's elbow, also known as a pulled elbow or a subluxated radial head, may result from the specific activities described above and is the most common dislocation injury handled by pediatricians. Most commonly occurring in the 1-year to 4-year old age group, nursemaid's elbow is easily treated and generally has no long-term sequelae.     

Migraine and Platelet Aggregation in Patients Treated With Low Dose Acetylsalicylic Acid

SYNOPSIS
To discriminate between the general analgesic effect of acetylsalicylic acid (a.s.a.) and a specific effect by inhibition of platelets we treated 27 migraine patients with low doses of acetylsalicylic acid. In a double-blind randomized cross-over study a small change in number of migraine attacks was found which however must be ascribed to a period effect. Severity of attacks as judged by the patients was similar in the placebo and drug periods. The frequency of attacks and the effect of a.s.a. were not significantly different in patients with platelets relatively sensitive to ADP and those with a slow response to ADP. No correlation was found between number of attacks and inhibition of the ADP aggregation obtained by administration of a.s.a. We concluded that low doses of a.s.a. are not useful to reduce the number or the severity of migraine attacks, and that no correlation exists between migraine attacks and a.s.a. effects on ADP-induced platelet aggregation. High doses of a.s.a. appear to be beneficial in migraine only by a general analgesic effect.