SA Patients Research Articles

Pre-morbid and outcome correlates of first episode mania with psychosis: Is a distinction between schizoaffective and bipolar I disorder valid in the early phase of psychotic disorders?

Objectives The validity of schizoaffective disorder (SA) diagnosis has for long been a matter of controversy and its delineation from bipolar I disorders (BD) has often been questioned. However, most studies have been conducted in chronic samples and have therefore been biased towards patients with poorer outcome, which may have hampered the possibility to identify significant differences between both diagnoses. Methods 108 subjects presenting a first DSM-III-R manic episode with psychotic features were assessed at baseline and 12 months after stabilisation on symptoms and functional characteristics, and patients with BD ( n = 87) were compared with those with SA bipolar subtype (SAB) ( n = 21). Results SAB patients had a higher prevalence of first degree relatives with schizophrenia and a lower premorbid functional level. They had a longer prodromal phase, a longer duration of untreated psychosis and remained symptomatic for a longer period. They also had higher levels of positive symptoms in the acute manic phase; however, with two exceptions, the type of psychotic symptoms were similar in both groups. At stabilisation and 12 months after stabilisation, SA patients had higher levels of negative symptoms, with poorer functional level at 12 months. Conclusions These data suggest SA is a valid diagnosis in the early phase of psychotic disorders considering it defines a subgroup of first episode psychotic mania patients with distinct characteristics compared to BD. While a dimensional approach to diagnosis may be more adapted to this phase of illness, SA disorder offers, in the context of categorical classifications, a useful intermediate category that reflects a clinical reality.

Decreased Serum Fetuin-A Levels are Associated with Coronary Artery Diseases

To analyze Fetuin-A levels and soluble cellular adhesion molecules in patients with acute coronary syndrome. Serum Fetuin-A and intercellular adhesion molecule-1 (sICAM-1), vascular cellular adhesion molecule-1 (sVCAM-1) levels were examined in 127 patients who presented with chest pain. These patients were classified in three groups: stable angina (SA, n=51), myocardial infarction (MI, n=34) and non-cardiac group (n=42). Logarithmic transformations were made for Fetuin-A levels. Log-Fetuin-A levels were higher in non-cardiac subjects compared to MI and SA patients (p<0.05). Patients with SA showed lower levels than controls but higher levels as compared to MI patients. After controlling for age and gender, levels of sVCAM-1 and sICAM-1 in patients with coronary atherosclerosis were not different from those in non-cardiac subjects. Serum levels of soluble VCAM-1, ICAM-1 were not related to coronary artery disease (CAD), but fetuin-A levels seems to be decreased in SA and MI patients. Low fetuin-A may play a role in the pathophysiology of CAD.

Impulsivity and clinical symptoms among adolescents with non-suicidal self-injury with or without attempted suicide

This study examined clinical characteristics and laboratory-measured impulsive behavior of adolescents engaging in either non-suicidal self-injury with (NSSI + SA; n = 25) or without (NSSI-Only; n = 31) suicide attempts. We hypothesized that adolescent with NSSI + SI would exhibit more severe clinical symptoms and higher levels of behavioral impulsivity compared to adolescents with NSSI-Only. Adolescents were recruited from an inpatient psychiatric hospital unit and the two groups were compared on demographic characteristics, psychopathology, self-reported clinical ratings, methods of non-suicidal self-injury, and two laboratory impulsivity measures. Primary evaluations were conducted during psychiatric hospitalization, and a subset of those tested during hospitalization was retested 4–6 weeks after discharge. During hospitalization, NSSI + SA patients reported worse depression, hopelessness, and impulsivity on standard clinical measures, and demonstrated elevated impulsivity on a reward-directed laboratory measure compared to NSSI-Only patients. In the follow-up analyses, depression, hopelessness, suicidal ideation, and laboratory impulsivity were improved for both groups, but the NSSI + SA group still exhibited significantly more depressive symptoms, hopelessness, and impulsivity than the NSSI-Only group. Risk assessments for adolescents with NSSI + SA should include consideration not only of the severity of clinical symptoms but of the current level impulsivity as well.

Different impairments of semantic cognition in semantic dementia and semantic aphasia: evidence from the non-verbal domain.

Disorders of semantic cognition in different neuropsychological conditions result from diverse areas of brain damage and may have different underlying causes. This study used a comparative case-series design to examine the hypothesis that relatively circumscribed bilateral atrophy of the anterior temporal lobe in semantic dementia (SD) produces a gradual degradation of core semantic representations, whilst a deficit of cognitive control produces multi-modal semantic impairment in a subset of patients with stroke aphasia following damage involving the left prefrontal cortex or regions in and around the temporoparietal area; this condition, which transcends traditional aphasia classifications, is referred to as 'semantic aphasia' (SA). There have been very few direct comparisons of these patient groups to date and these previous studies have focussed on verbal comprehension. This study used a battery of object-use tasks to extend this line of enquiry into the non-verbal domain for the first time. A group of seven SA patients were identified who failed both word and picture versions of a semantic association task. These patients were compared with eight SD cases. Both groups showed significant deficits in object use but these impairments were qualitatively different. Item familiarity correlated with performance on object-use tasks for the SD group, consistent with the view that core semantic representations are degrading in this condition. In contrast, the SA participants were insensitive to the familiarity of the objects. Further, while the SD patients performed consistently across tasks that tapped different aspects of knowledge and object use for the same items, the performance of the SA participants reflected the control requirements of the tasks. Single object use was relatively preserved in SA but performance on complex mechanical puzzles was substantially impaired. Similarly, the SA patients were able to complete straightforward item matching tasks, such as word-picture matching, but performed more poorly on associative picture-matching tasks, even when the tests involved the same items. The two groups of patients also showed a different pattern of errors in object use. SA patients made substantial numbers of erroneous intrusions in their demonstrations, such as inappropriate object movements. In contrast, response omissions were more common in SD. This study provides converging evidence for qualitatively different impairments of semantic cognition in SD and SA, and uniquely demonstrates this pattern in a non-verbal expressive domain-object use.

The psychotic spectrum: a community‐based study

Over the last years, there has been an increasing awareness and knowledge about bipolar spectrum disorders. However, descriptive data on bipolar I disorder with psychotic features (BPI-p) in comparison with schizophrenia (SCH) and schizoaffective disorder (SA) in mental health community services are scanty in the literature. We conducted a study with the aim of assessing the prevalence, clinical characteristics and levels of functioning of SCH, SA and BPI-p in a random sample of patients with psychotic symptoms recruited in nine departments of mental health. Patients with a psychotic disorder according to their treating clinicians were assessed using the SCID and a series of questionnaires to evaluate their psychopathology and level of functioning. Patients who received a DSM-IV diagnosis of SA (N=55), SCH (N=82), or BPI-p (N=60) represented the final sample. The three diagnostic groups showed similar demographic characteristics. Independently from the diagnosis, all patients had a long duration of illness and a persistent course. Uni-variate group comparisons showed that, as compared to SCH patients, BPI-p and SA patients did better in several measures of functioning and differed in frequency of psychotic symptoms. However, a multinomial logistic regression model in which only significantly different variables were entered showed similar levels of functioning in the three groups of patients. The three groups' scores did not significantly differ on instruments that assessed dimensionally psychotic and affective symptoms during the previous month.

Plaque Characteristics of the Coronary Segment Proximal to the Culprit Lesion in Stable and Unstable Patients

Identifying vulnerable plaque is important for preventing an acute coronary event. The present study examined the relationship between the clinical presentation of coronary artery disease and the plaque characteristics of nonculprit segment assessed by virtual histology intravascular ultrasound (VH-IVUS). We performed VH-IVUS analysis on nonculprit segments with < 50% diameter stenosis in 91 patients (48 acute coronary syndrome [ACS] patients, 43 stable angina [SA] patients). ACS patients showed significantly higher ratio of dense calcium (7.9% +/- 1.0% versus 5.0% +/- 0.9%, p = 0.03) and necrotic core plaque (13.7% +/- 1.1% versus 8.6% +/- 1.1%, p = 0.001) compared with SA patients. VH-IVUS-derived thin-cap fibroatheroma (VH-TCFA) was more frequently observed in ACS patients compared with SA patients (64.6% versus 35.7%, p = 0.006). Among ACS patients, plasma high sensitivity C-reactive protein (hs-CRP) levels were significantly higher in patients with VH-TCFA than in patients without VH-TCFA (7.9 +/- 2.6 mg/l versus 1.6 +/- 0.3 mg/l, p = 0.004). ACS patients presented higher prevalence of VH-TCFA in nonculprit segment. Presence of VH-TCFA was associated with an increased level of plasma hs-CRP in ACS patients.

Neurophysiological Distinction between Schizophrenia and Schizoaffective Disorder.

Schizoaffective disorder (SA) is distinguished from schizophrenia (SZ) based on the presence of prominent mood symptoms over the illness course. Despite this clinical distinction, SA and SZ patients are often combined in research studies, in part because data supporting a distinct pathophysiological boundary between the disorders are lacking. Indeed, few studies have addressed whether neurobiological abnormalities associated with SZ, such as the widely replicated reduction and delay of the P300 event-related potential (ERP), are also present in SA. Scalp EEG was acquired from patients with DSM-IV SA (n = 15) or SZ (n = 22), as well as healthy controls (HC; n = 22) to assess the P300 elicited by infrequent target (15%) and task-irrelevant distractor (15%) stimuli in separate auditory and visual ”oddball” tasks. P300 amplitude was reduced and delayed in SZ, relative to HC, consistent with prior studies. These SZ abnormalities did not interact with stimulus type (target vs. task-irrelevant distractor) or modality (auditory vs. visual). Across sensory modality and stimulus type, SA patients exhibited normal P300 amplitudes (significantly larger than SZ patients and indistinguishable from HC). However, P300 latency and reaction time were both equivalently delayed in SZ and SA patients, relative to HC. P300 differences between SA and SZ patients could not be accounted for by variation in symptom severity, socio-economic status, education, or illness duration. Although both groups show similar deficits in processing speed, SA patients do not exhibit the P300 amplitude deficits evident in SZ, consistent with an underlying pathophysiological boundary between these disorders.

Haemophilia care in South Africa: 2004–2007 look back

The South African national haemophilia program (NHP) was officially recognized in 2000 and implemented by the National Department of Health (NDOH), haemophilia specialists of the Medical and Scientific Advisory Council (MASAC) and the South African Haemophilia Foundation (SAHF). This study aims to report on progress and challenges of haemophilia care in SA after implementation of the NHP. Haemophilia care data collected by MASAC from all treatment centres (HTCs) from 2004 to 2007 were reviewed and appraised. Data assessment included evaluation of the number and types of professional haemophilia expertise, diagnostic and human resources available, number and types of HTCs, number and types of haemophilia diagnoses, immunological complications of haemophilia, social, medical and surgical interventions, factor usage and reporting on haemophilia mortality. Over 2200 bleeding diathesis patients in SA were cared for by an average of 79 professionals in 17 HTCs. Fifty-nine per cent were haemophilia A, 21% von Willebrand's disease, 12% haemophilia B and the remainder had rare bleeding diathesis and thrombocytopathies. In 2004-2007, the number of haemophilia professionals stayed the same, clinic visits increased, new patients and inhibitor patients also increased. Surgical and medical interventions were unchanged and per capita factor usage increased from 0.65 to 0.95. National mortality rate remained below 10 deaths per year. Haemophilia care in SA is highly organized and effective in the delivery of haemophilia health services. All diagnosed uncomplicated haemophiliacs have access to state funded factor concentrate. Limited human and diagnostic resources remain major challenges.

Osteoprotegerin and B-type natriuretic peptide in acute coronary syndromes with preserved systolic function: Relation to coronary artery disease extension

Objectives To analyze Osteoprotegerin (OPG), and BNP plasma levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. Methods 155 CAD patients were classified in four groups: stable angina (SA n = 42), unstable angina (UA n = 35) non-ST elevation myocardial infarction (NSTEMI n = 45) and control group ( n = 33), measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-,2-,3 or more vessels disease), and to the stenoses degree by Duke Jeopardy score. Results OPG levels were higher in patients with CAD respect to controls ( p < 0.0001). Patients with SA showed more elevated levels than controls (2.6 ± 1.2 vs 7.4 ± 5.0 pmol/l p < 0.01). However patients with UA and NSTEMI had higher OPG level with respect to SA patients (12.2 ± 7.8 and 11.6 ± 6.1 respectively pmol/l p < 0.001). A positive relation was found between OPG levels and coronary plaques extension by Duke Jeopardy score ( r = 0.65). BNP levels were higher in patients with UA/NSTEMI respect to controls and SA patients ( p < 0.001). Besides, BNP was significantly higher in patients with multi-vessels vs 1-vessel disease ( p < 0.001). Conclusions Patients with UA and NSTEMI show high OPG and BNP levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the CAD progression.

Levels of Soluble CD163 and Severity of Malaria in Children in Ghana

CD163 is an acute-phase-regulated monocyte/macrophage membrane receptor expressed late in inflammation. It is involved in the haptoglobin-mediated removal of free hemoglobin from plasma, has been identified as a naturally soluble plasma glycoprotein with potential anti-inflammatory properties, and is possibly linked to an individual's haptoglobin phenotype. High levels of soluble CD163 (sCD163) in a malaria episode may therefore downregulate inflammation and curb disease severity. In order to verify this, the relationships between sCD163 levels, malaria severity, and selected inflammatory mediators (tumor necrosis factor alpha [TNF-alpha], interleukin-6 [IL-6], and IL-10) were assessed by enzyme-linked immunosorbent assay using plasma samples obtained from pediatric malaria patients with uncomplicated malaria (UM [n = 38]), cerebral malaria (CM [n = 52]), and severe malarial anemia (SA [n = 55]) during two consecutive malaria transmission seasons (2002 and 2003). Median sCD163 levels were higher in UM (11.9 microg/ml) patients than in SA (7.7 microg/ml; P = 0.010) and CM (8.0 microg/ml; P = 0.031) patients. Levels of sCD163 were also higher in all patient groups than in a group of 81 age-matched healthy controls. The higher sCD163/TNF-alpha ratio in UM patients, coupled with the fact that sCD163 levels correlated with TNF-alpha levels in UM patients but not in CM and SA patients, suggests inflammatory dysregulation in the complicated cases. The study showed that sCD163 levels are elevated during acute malaria. High sCD163 levels in UM patients may be due to the induction of higher-level anti-inflammatory responses, enabling them to avoid disease complications. It is also possible that UM patients simply lost their CD163 receptors from macrophages in inflammatory sites while complicated-malaria patients still had their receptors attached to activated macrophages, reflecting ongoing and higher-level inflammation associated with complicated malaria.

Relationship Between the Striatal and Cerebellar Glucose Metabolism and the Response to Levodopa Treatment in Patients With Multiple System Atrophy

Introduction: About two thirds of the patients w ith multiple system atrophy (MSA) do not respond to levodopa treatment. Postmortem pathological studies and one retrospective [F]-deoxyglucose positron em ission tom ography (FDG PET) study attributed such poor response to the stria ta l degeneration. W e prospective ly investigated the re lationsh ip between levodopa respons iveness and the m etabo lic activ ities o f the stria tum and cerebellum in M SA patients. M ethods: In 39 patients w ith M SA, the UPDRS m otor score was assessed and two sets of tim ed m otor tests were performed before and after the levodopa treatment. After quantitative FDG PET and baseline eva luation, treatm ent was started w ith 3 tab lets o f S inem et 25/250 m g a day. C lin ica l assessm ents were perform ed m onth ly for three m onths. M etabo lic activ ities o f the caudate, anterior putam en, posterior putam en, cerebe llar cortex and cerebe llar verm is were m easured. W e com pared the m easurem ents w ith m ean percentage changes of m otor function. A lso, us ing statistica l param etric m app ing (SPM ) ana lys is, we tried to find bra in areas in wh ich m etabo lism corre lated w ith the c lin ica l changes. Resu lts: M ean percentage im provem ents of UPDRS m otor scores were corre la ted w ith g lucose m etabo lism in the posterior putam en and cerebellar verm is. The m ean percentage im provem ents of perform ance in Purdue peg board test correlated w ith the glucose metabolism in the cerebellar cortex and verm is. In SPM analysis, cerebellar glucose metabolism correlated w ith the im provem ent of UPDRS m otor score and the perform ance o f two tim ed m otor tests . Conc lus ion: The integrity o f cerebe llum , as we ll as posterior putam en, m ay be an im portant factor for show ing the response to levodopa. Journal of Movement Disorders 1(1):26-32, 2008

The expression of TNF‐α converting enzyme at the site of ruptured plaques in patients with acute myocardial infarction

Tumour necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) plays an essential role in the TNF-alpha shedding process, which could affect the outcome of acute myocardial infarction (AMI). However, it remains unclear whether it originates from the ruptured plaque or represents a systemic process. This study analysed TACE-mediated TNF-alpha shedding at the site of ruptured plaques in AMI patients and compared them with a systemic mechanism. The study included 60 patients with AMI who underwent percutaneous coronary intervention (PCI) and 21 patients with stable angina pectoris (SA). Local samples from the site of plaque were taken from AMI using aspiration catheter treatment. Systemic samples were also taken from the aorta in all patients with AMI and SA. Systemic levels of TACE and TNF-alpha were higher in AMI patients than in SA patients. In AMI patients, these levels were higher in local samples than in systemic samples. A positive correlation was seen between local TACE and TNF-alpha levels in AMI patients. Thrombus material removed from the ruptured plaque showed immunostainings of TACE and TNF-alpha in infiltrating macrophages. By six months follow-up study, local TACE levels remained the only significant independent predictors of adverse cardiac events in AMI patients. This study demonstrates that local expression of TACE is related to TNF-alpha shedding at the site of ruptured plaques in AMI patients. In addition, local TACE expression at the site of ruptured plaques may play an important role in poor outcomes in patients with AMI.

Steroid Avoidance Regimens: A Comparison of Outcomes with Maintenance Steroids versus Continued Steroid Avoidance in Recipients Having an Acute Rejection Episode

Roughly 15% of kidney transplant recipients on a rapid discontinuation of prednisone (RDP) protocol have > or =1 episode of acute rejection (AR). One clinically important question is whether long-term maintenance steroids should be introduced in those recipients having AR. Of 842 adult kidney transplant recipients on an RDP protocol, 149 (17.7%) have had at least 1 AR episode. Of these, 51 (34%) started on maintenance prednisone (5 mg/day) after treatment of the AR, while 98 (66%) remained steroid free. Demographics for the two groups were similar. With mean follow-up of 26 months, 48 (32%) of the recipients have had a 2nd AR episode: 15 (29.4%) in those on maintenance steroids vs. 33 (33.7%) in those remaining steroid free (p = 0.12). Graft survival was not significantly different between the two groups. Multivariate analysis of risk factors for a 2nd episode found the histologic appearance of the initial AR episode to be the most significant risk factor. But, whether steroids were added to the maintenance regimen or not, also seemed to have an impact (RR = 2.1, p = 0.07). At present there is evidence to suggest that some SA patients should start on maintenance steroids after AR. However, longer follow-up with more patients is necessary.

Analysis of Occurrence of DRB and DQ Alleles in Sarcoidosis and Tuberculosis from Northern Poland

Sarcoidosis is a multisystem disorder of unknown etiolgy. Pathologic similarities between SA and tuberculosis (TB) suggest M. tuberculosis antigen(s) as causative agents. It seems likely that in the genetically different predisposed hosts, the same antigen(s) may cause the development of sarcoid or tuberculous immune response. The aim of this study was to compare the frequency of occurrence of HLA class II alleles in SA, TB and in the healthy individuals. To test a difference in haplotypes associated with both diseases, we compared the distribution of DQA1 and DQB1 alleles in 45 SA patients, 62 TB patients and in 143 healthy volunteers, using a PCR-SSP "low (DRB1, DQB1) and high (DQA1) resolution" method. Our results revealed that DRB1*03, DRB1*11, DQB1*02 i DQA1*0501 in Stage I of SA with Löfgrens syndrom (Ls) and DRB1*15, DQA1*0102, DQA1*0103 in Stage II of SA were more common, whereas DRB1*16, DRB1*04, DRB1*08, DQB1*02, DQB1*03, DQB1*05, DQA1*0102, DQA1*0301 in Ls and DQB1*02, DQB1*03, DQB1*05, DQA1*0102, DQA1*0301 in Stage II were less common than in the controls but after Bonferroni correction occurrence of DRB1*04, DQB1*02, DQB1*03, DQB1*05 and DQA1*0102, DQA1*0301, DQA1*0501 was significantly differ. In TB group, DRB1*16, DRB1*14, DQB1*05 i DQA1*0303 were more frequent and DRB1*11, DQB1*02, DQA1*0201, DQA1*0505 less frequently present as compared to the controls, but after correction DRB1*16, DQB1*02, DQB1*05, DQA1*0303, DQA1*0505 were significantly different. In SA, DRB1*11, DQB1*02 i DQA1*0201, DQA1*0501, DQA1*0505 in Ls and DRB1*15, DRB1*11, DQA1*0102 in Stage II were more common and DRB1*16, DRB1*04, DRB1*14, DQB1*03, DQB1*05, DQB1*06, DQA1*0301, DQA1*0302, DQA1*0303 in Ls and Stage II were less frequent than in the TB group. DQB1*02, DQA1*0501 (Ls) and DRB1*15 (Stage II) were more frequently present in SA than in TB, even after Bonferroni correction. In summary, we identified associations of HLA class II alleles in SA and TB with expression pattern specific and different for each group. In most cases, in SA patients frequency of HLA class II alleles occurrence is opposite to the frequency in TB patients.

Pro-inflammatory/anti-inflammatory cytokine imbalance in acute coronary syndromes

The aim of this study was to evaluate the presence of an imbalance between proinflammatory and anti-inflammatory mediators in patients affected by acute coronary syndromes (ACS). We considered two groups of 26 and 28 patients with acute myocardial infarction (AMI) and unstable angina (UA) respectively, compared with a group of 30 patients with stable angina and 30 healthy volunteers. We evaluated the production in cultured and stimulated lymphomonocytes of interferon (IFN)gamma and tumour necrosis factor (TNF)alpha, which are well known to possess proinflammatory effects, and of interleukin (IL)10, which has been shown to have a protective anti-inflammatory activity. We also assessed the clinical characteristics of groups and, particularly, we evaluated the circulating levels of C-reactive protein (hs-CRP). We found a significant increase of IFNgamma and TNFalpha production (P<0.01) and a significant decrease of IL10 production (P<0.05) in cultures of lymphomonocytes taken from patients with AMI and UA compared with SA patients and controls. No significant changes where found between AMI and UA patients and SA patients and controls. Circulating levels of hs-CRP were significantly increased (P<0.01) in patients with ACS compared with the other control groups. Our data showed an increased production of proinflammatory mediators in ACS that may be detectable both in circulating blood and in cell cultures where it is possible to evaluate in a better way the functional state of cells; this finding was associated with a reduced production of the antiinflammatory cytokine IL10. In conclusion, a relevant imbalance is present in ACS and this fact could contribute to plaque instability and clinical manifestations.

A comparison of sirolimus vs. calcineurin inhibitor‐based immunosuppressive therapies in liver transplantation

Sirolimus is a potent immunosuppressive agent whose role in liver transplantation has not been well-described. To evaluate the efficacy and side-effects of sirolimus-based immunosuppression in liver transplant patients. Retrospective analysis of 185 patients who underwent orthotopic liver transplantation. Patients were divided into three groups: group SA, sirolimus alone (n = 28); group SC, sirolimus with calcineurin inhibitors (n =56) and group CNI, calcineurin inhibitors without sirolimus (n = 101). One-year patient and graft survival rates were 86.5% and 82.1% in group SA, 94.6% and 92.9% in group SC, and 83.2% and 75.2% in group CNI (P = N.S.). The rates of acute cellular rejection at 12 months were comparable among the three groups. At the time of transplantation, serum creatinine levels were significantly higher in group SA, but mean creatinine among the three groups at 1 month was similar. More patients in group SA required dialysis before orthotopic liver transplantation (group SA, 25%; group SC, 9%; group CNI, 5%; P = 0.008), but at 1 year, post-orthotopic liver transplantation dialysis rates were similar. Sirolimus given alone or in conjunction with calcineurin inhibitors appears to be an effective primary immunosuppressant regimen for orthotopic liver transplantation patients. Further studies to evaluate the efficacy and side-effect profile of sirolimus in liver transplant patients are warranted.

Increased platelet reactivity in unstable angina patients is not related to C-reactive protein levels

Platelets are a major component of thrombi, and coronary thrombosis plays a key role in the pathogenesis of unstable angina (UA). Whether platelet aggregability is increased in UA patients however, is not known. Furthermore, no study has investigated the relationship between platelet reactivity and inflammation in UA patients In this study, venous blood samples were collected at admission in coronary care unit in 37 patients with unstable angina (Braunwald class IIIB) and in 37 sex- and age-matched patients with chronic stable angina (CSA). Patients taking thienopyridine or anticoagulant drugs were excluded from the study, as also were excluded patients with a history of acute myocardial infarction in the previous 12 months. Platelet aggregability was measured on flowing blood as time to occlude a ring coated with collagen-adenosine diphosphate (ADP), using the platelet function analyzer (PFA-100) system. By this method, the time to occlusion (closure time) is taken as a measure of platelet adhesion/aggregability, with shorter times indicating greater platelet reactivity.There were 23 men and 14 women in both groups, and age was 67.7 ± 8 and 67.5 ± 8 years in UA and SA, respectively (P = 0.93). Closure time was significantly reduced in UA patients (78.8 ± 14 s), compared to SA patients (93.3 ± 19 s, P < 0.001). Among UA patients, serum C-reactive protein (CRP) levels had a median value of 5.1 mg/l (bottom and top quartile levels, 1.50–7.95). There was no significant correlation between closure time and CRP levels (r = 0.22, P = 0.29). Our data show that, in patients with unstable angina there is an increase of platelet reactivity in response to ADP/collagen stimulation, which is not related to inflammation.

Factors Contributing to the Development of Anaemia in Plasmodium falciparum Malaria: What about Drug-Resistant Parasites?

A major manifestation of complicated malaria especially among children is severe anaemia, the pathogenesis of which is not well understood. Among other factors, suppression of the bone marrow's response to erythropoietin, which is rapidly reversed after successful treatment of the malaria, has been implicated in its pathogenesis. Since resolution of malaria restores erythropoiesis, we hypothesized that drug-resistant strains of Plasmodium falciparum would increase the risk of severe anaemia developing from initially uncomplicated malaria. Using both in vivo and in vitro drug-sensitivity tests we compared the prevalence of drug-resistant malaria between severe malarial anaemia SA and non-anaemic malaria NAM patients. Assessment of treatment outcome using the WHO in vivo criteria showed no significant difference in parasite resistance between the two groups. The mean parasite clearance time was also comparable. Treatment failures of about 14 per cent and 12 per cent were observed between SA and NAM patients respectively. The in vitro drug susceptibility test showed overall mean IC50 values of 0.41x10(-6) mol/l and 0.32x10(-6) mol/l blood for SA and NAM groups respectively. Geometric mean pre-treatment blood levels of chloroquine did not differ much between the two groups. Findings from this study could not therefore implicate drug-resistant parasites in the pathogenesis of severe malarial anaemia.

Preliminary results with early corticosteroid withdrawal in African American renal allograft recipients

There is a paucity of data regarding the use of steroid-avoidance immunosuppression (SAI) in African American (AA) renal allograft recipients, traditionally considered a high-risk subgroup of patients with higher reported rates of acute rejection and graft loss. We compared the outcomes of 27 AA renal allograft recipients receiving SAI (SA group; mean follow-up period, 12 +/- 3 mo) with those of 20 patients receiving a steroid taper (ST group; 24 +/- 11 mo). In both groups, thymoglobulin was used for induction, and mycophenolate mofetil and tacrolimus were used for maintenance. Four doses of methylprednisolone were given on days 0 to 3. In the SA group no further steroids were given, whereas in the ST group a prednisone taper was continued thereafter. ST patients were more likely to have current panel reactive antibody titers greater than 10%, undergo retransplantation, and receive more doses of thymoglobulin. There were no significant differences between the SA and ST groups with regard to patient survival (96% vs 95%), graft survival (96% vs 90%), acute rejection (11% vs 14%), cytomegalovirus infection (7% vs 10%), posttransplant diabetes mellitus (11% vs 24%), or mean serum creatinine concentration at 6 months (1.6 vs 1.5 mg/dL), respectively, with a trend toward less percent weight gain in SA patients at 6 months (5% vs 11%, P = .06). SAI can produce excellent short-term results in AA kidney transplant patients when compared with a conventional ST protocol. Our results will need to be verified in larger numbers of patients with longer follow-up evaluation.

Plasma levels of oxidized-low-density lipoproteins are higher in patients with unstable angina and correlated with angiographic coronary complex plaques

Objectives To measure circulating levels of oxidized-low-density lipoproteins (ox-LDL) in patients with stable and unstable angina and controls, and to investigate their correlation with the extent of coronary artery disease (CAD) and the presence of complex plaques at coronary angiography. Methods and results Circulating ox-LDL were assessed, using ELISA, in patients with unstable angina (UA, n = 26), stable angina (SA, n = 29) and in controls (C, n = 27). All patients underwent coronary angiography. The extent of CAD was evaluated using a quantitative score, while the presence of complex, vulnerable plaques was angiographically assessed. Ox-LDL were higher in UA patients than in SA patients and in C subjects, and in SA patients than in C subjects (C, 45.6 ± 12.8 U/L; SA, 58.8 ± 11.0 U/L; UA, 73.7 ± 13.6 U/L; p < 0.001). No correlation was found with the extent of atherosclerotic disease in the coronary tree. Patients with angiographic complex lesions showed significantly higher levels of ox-LDL (68.4 ± 13.9 U/L versus 55.2 ± 16.4 U/L, p < 0.001). Multiple regression analysis showed that ox-LDL were independent predictors of the presence of complex plaques ( p < 0.023). Conclusions Ox-LDL levels are higher in unstable patients and correlate with the presence of angiographically documented complex plaques. Ox-LDL might be markers of destabilization of CAD.