Passive reporting greatly underestimates the rate of transfusion-associated circulatory overload after platelet transfusion.

BACKGROUND: Transfusion-associated circulatory overload (TACO) is the second leading cause of reported transfusion-related fatalities in the United States. While its occurrence has been previously investigated after red cell and plasma transfusion, no data are available regarding its association with platelet transfusion. Our goal was to determine the rate of platelet-associated TACO at our university medical centre. STUDY DESIGN AND METHODS: This study had retrospective and prospective analyses. The 13-year retrospective analysis served to determine the historical rate of platelet-associated TACO by passive reporting. The 30-day prospective analysis included active surveillance of all non-emergently issued and non-operative platelet recipients ≥16 years old with no transfusions in the previous 6 h determined by analysis of blood bank product issue records. Data collected included demographics, vital signs pre- and posttransfusion, fluid balances, supplemental oxygen use, reports of dyspnoea, and infusion rates. For the prospective analysis, all variables were collected within 24 h of transfusion from the medical record and, when necessary, interviews with care providers and/or patients. RESULTS: In the retrospective analysis, 366 reactions were reported, of which 6 (1·6%) were TACO. The historical rate of TACO was 1:5997 transfused platelet units. During the prospective analysis, 225 eligible patients received a total of 334 units of platelets. The average platelet transfusion volume was 261 ± 26 ml, and the average infusion rate was 391 ± 198 ml/h. Two unreported TACO reactions were discovered and characterized by new-onset hypertension, crackles on lung auscultation, dyspnoea, hypoxia and supplemental oxygen requirements which resolved completely with diuresis. The rate of TACO during this prospective analysis was 1:167 transfused platelet units. CONCLUSION: Platelet-associated TACO is greatly underestimated by passive reporting in the adult patient population.

Silicon drift detector based X-ray spectroscopy diagnostic system for the study of non-thermal electrons at Aditya tokamak.

Silicon drift detector based X-ray spectrometer diagnostic was developed to study the non-thermal electron for Aditya tokamak plasma. The diagnostic was mounted on a radial mid plane port at the Aditya. The objective of diagnostic includes the estimation of the non-thermal electron temperature for the ohmically heated plasma. Bi-Maxwellian plasma model was adopted for the temperature estimation. Along with that the study of high Z impurity line radiation from the ECR pre-ionization experiments was also aimed. The performance and first experimental results from the new X-ray spectrometer system are presented.

State of the art: massive transfusion.

The aim of this article was to review recent developments in the resuscitation of both trauma and non-trauma patients in haemorrhagic shock. Strategies for the resuscitation of massively haemorrhaging patients and the use of massive transfusion protocols (MTPs) have been a major focus of the trauma literature over the past several years. The application of haemostatic resuscitation practices and MTPs to non-trauma populations has long been in practice, but has only recently been the subject of active research. Medline and PubMed were reviewed for 'massive transfusion' (MT) from 2012 to present. Non-English and paediatric articles were excluded. Articles were systematically reviewed for their relevance to MT. There were eight major areas of development identified. In recent MT literature, there was an increased focus on massively haemorrhaging non-trauma patients, the role of acute traumatic coagulopathy, the use of thromboelastography (TEG), and the impact of MTPs on blood product waste and efficiency of product delivery. Other developments included additional MT prediction tools and The PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. There was also interest in re-evaluating the clinical relevance of the current MT definition and identifying new foci for MT. These recent developments reflect efforts to better understand and manage non-traumatic haemorrhage and to address prior limitations in the trauma literature. Inevitably, new questions have been raised, which will likely direct ongoing and future research in MT.

Ascorbic acid improves membrane fragility and decreases haemolysis during red blood cell storage.

BACKGROUND: Changes that occur to red blood cells (RBCs) during routine blood bank storage include decreased deformability, increased haemolysis and oxidative damage. Oxidative injury to the RBC membrane and haemoglobin can affect changes in shape and deformability. Ascorbic acid (AA) is an antioxidant that maintains haemoglobin in a reduced state and minimises RBC oxidative injury. We hypothesised that AA would improve membrane fragility and decrease haemolysis during storage. METHODS: Whole blood derived, AS-5 preserved, pre-storage leucoreduced RBC units were exposed to either AA or saline control solutions. Several rheological and biochemical parameters were measured serially during storage, including RBC membrane mechanical fragility, percent haemolysis and methaemoglobin levels. RESULTS: AA exposure significantly reduced mechanical fragility and haemolysis over the entire storage period. The highest two concentrations of AA affected the greatest reductions in mechanical fragility and percent haemolysis. Addition of AA to the RBCs did not significantly alter their biochemical parameters compared to control RBCs incubated with saline. CONCLUSION: AA reduced RBC membrane fragility and decreased haemolysis during storage without adversely affecting other RBC biochemical parameters. The clinical significance of these findings needs to be determined.

ABO-mismatched transfusions are not over-represented in febrile non-haemolytic transfusion reactions to platelets.

ABO-mismatched plasma and platelet (PLT) transfusion have been associated with worse outcomes, including haemolysis and other reactions, compared to recipients of ABO-identical products. The immune complexes that form in a mismatched transfusion have been demonstrated to stimulate pyrogenic cytokine release in vitro. Comparing ABO identical vs. ABO mismatched PLT transfusions, we found no significant difference in the ABO compatibilities between the PLT doses implicated in causing febrile non-haemolytic transfusion reactions (FNHTR) in 162 recipients and both the baseline PLT donor/recipient ABO compatibility (P = 0·67) or the PLTs issued in the 30 days preceding the FNHTR (P = 0·92). ABO-mismatched PLT transfusions do not appear to be aetiological agents of FNHTR in a population routinely receiving both ABO-identical and ABO-mismatched transfusions.

Haemolysis and sublethal injury of RBCs after routine blood bank manipulations.

OBJECTIVES: To determine the extent of RBC sublethal injury in male donor units as measured by both the mechanical fragility index (MFI) and percentage haemolysis after RBCs underwent leucoreduction (LR), irradiation (IRRAD), and washing. BACKGROUND: RBCs frequently undergo post-collection processing to meet certain recipient's special needs. The extent of haemolysis and sublethal injury following these interventions has not been fully characterised. METHODS: Eight to ten day old male, AS-5 RBCs underwent either LR, IRRAD or washing. A control group of male, AS-5 RBCs were unmanipulated. The MFI, percent haemolysis, and plasma free haemoglobin (PFHb) were measured immediately after manipulation and, for a series of irradiated RBCs, 28 days after irradiation (IRRAD28). RESULTS: The MFI of the washed units was significantly higher than unmanipulated, LR, IRRAD, IRRAD28 units (P < 0·0001). The percent haemolysis was highest in the IRRAD28 units (1·4%) followed by the washed units (0·74%); the other three units demonstrated significantly less haemolysis (P < 0·0001). The largest mean total amount of PFHb per unit was found in the IRRAD28 units (500·5 mg/unit) followed by the washed units (149·8 mg/unit); the mean total amount of PFHb in the three other types of units was significantly less than that found in both the IRRAD28 and washed units (P at least < 0·001). CONCLUSION: There is a significant quantity of PFHb in IRRAD28 RBC units, and potentially in washed allogeneic RBC units. Clinical correlation is required to determine if this quantity of PFHb and the transfusion of potentially fragile RBCs causes adverse events.

Menopausal status affects the susceptibility of stored RBCs to mechanical stress.

The mechanical fragility index (MFI) is an in vitro measure of sublethal injury to RBCs. In our previous experiments, we demonstrated that an increase in sublethal injury (increasing MFI) was a component of the RBC storage lesion, and that the MFI was significantly higher amongst the RBC units from male donors compared to pre-menopausal female donors during storage. It was hypothesized that hormonal or menstrual factors contributed to this difference. In this study, we found that RBC units donated by post-menopausal women demonstrated an MFI that was significantly higher than those donated by pre-menopausal women throughout storage.

The use of the mechanical fragility test in evaluating sublethal RBC injury during storage.

BACKGROUND: The mechanical fragility index (MFI) is an in vitro measurement of the extent of RBC sublethal injury. Sublethal injury might constitute a component of the RBC storage lesion, thus the MFI was determined serially during routine RBC storage. METHODS: Leucoreduced AS-5- and SAGM-preserved RBCs were stored under routine blood bank conditions. The mechanical fragility (MF) of each unit was serially measured during storage. RESULTS: For both AS-5 and SAGM units, male and female RBCs demonstrated statistically significant increases in the MFI during storage. The MFI was significantly lower in AS-5 units compared to SAGM units throughout storage. Female RBCs had significantly lower MFI vs. male RBCs in both AS-5 and SAGM units at all times. No significant differences in MFI were observed between ABO groups for both genders for AS-5 RBCs. CONCLUSIONS: The MF of RBCs increases during storage. Both gender and preservation solution influenced the MFI; however, the male:female MFI ratios were similar at all time-points and remained stable, suggesting that gender-based biological differences exist independent of storage solution. The MF could be a useful test for evaluating the effect of novel interventions intended to mitigate the susceptibility of RBCs to sublethal injury during storage.

Frequent loss of heterozygosity on chromosome arm 18q in squamous cell carcinomas. Identification of 2 regions of loss--18q11.1-q12.3 and 18q21.1-q23.

OBJECTIVES: To determine the frequency and regions of loss on chromosome arm 18q in uncultured head and neck squamous cell carcinomas. DESIGN: Polymerase chain reaction amplification of DNA extracted from 18 tumor specimens (1 patient had 2 tumors) and blood samples from 17 patients with head and neck squamous cell carcinoma was performed using primers flanking 16 microsatellite repeat polymorphisms spanning most of chromosome 18q. DNA was extracted only from specimens with greater than 70% tumor nuclei. SETTING: Research university. PATIENTS: Seventeen individuals with newly diagnosed head and neck cancer. MAIN OUTCOME MEASURE: Loss of heterozygosity (LOH). RESULTS: There was LOH at more than 1 locus in 52% (9/ 17) of the tumors; 3 tumors had LOH at all informative markers. Four had loss at only 1 locus, raising the total with loss to 12 (75%) of 16. Loss of 18q11.1-q12.3 in 4 tumors without distal loss defines a proximal region of loss. Loss of heterozygosity affecting 18q21.1 in 1 tumor, without proximal loss and LOH for 18q21.1, 18q22, or 18q23 in 9 (52%) of 17 tumors defines a distal region of loss. CONCLUSIONS: Loss of heterozygosity on chromosome arm 18q is not an artifact of in vitro culture. The finding of 18q LOH in 50% to 70% tumors makes 18q an important region for study. Regions 18q11.1-q12.3 and 18q21.1-q23 are common regions of loss, indicating that there may be more than one 18q tumor suppressor gene involved in the genesis and progression of head and neck squamous cell carcinomas.

Identifying genetic changes associated with tumor progression in squamous cell carcinoma.

Tumor behavior is the result of specific genetic changes that alter gene expression. From our cytogenetic studies chromosome 18 loss emerged as a common genetic change in squamous carcinoma cell lines. In this report we summarize data that link loss of 18 to tumor progression and reduced survival, indicating that one or more tumor suppressor gene(s) are located on this chromosome. Tumors grown in vitro were karyotyped either as short-term or permanent cultures. Loss of chromosome 18 was measured by karyotype, decreased frequency of heterozygosity at the DCC locus, and loss of heterozygosity (LOH) for microsatellite repeat polymorphisms (MSRP). Loss of any part of chromosome 18 was observed in approximately 63% of cultured tumors. Primary and secondary tumors from the same individuals sometimes differed in loss of 18 indicating that this genetic change is associated with tumor progression. Heterozygosity for DCC was present in only 3/19 cultured SCC (16%), compared with 68% (11/16) of blood samples from unrelated donors, which is consistent with LOH in roughly one half of the cases. Of 4 informative cases with normal and tumor tissue, LOH was observed in 2. Microsatellite analysis also shows loss of 18q in 55% of fresh tumors. Analysis of tumor tissue and cell lines from the same patient gave identical results. There was an excess of deaths from cancer in the group with 18 loss (20/25) when compared with the group without (5/15). Loss of chromosome 18 appears to be a marker of tumor progression in SCC. It is likely that mutation affecting DCC or another gene on 18 affects tumor growth or spread, leading to more rapid progression and reduced survival.

MRI of the skull.

Thirty-four patients with a wide variety of benign and malignant incidental skull findings on routine magnetic resonance (MR) imaging of the brain were reviewed. In most instances detection of the lesions was not difficult. However, recognition of various patterns of skull involvement in different disease processes is important. This is particularly true in differentiating benign from malignant lesions, which may be a critical factor in patient management.

Magnetic resonance imaging features in melanoma.

T1 and T2 relaxation time shortening secondary to paramagnetic compounds has been described in melanoma. The purpose of this paper is to evaluate the signal behavior of melanoma involved in various body areas using short TR, TE and long TR, TE sequences. Twenty-seven sites of melanoma were evaluated with MR using T1 weighted and T2-weighted techniques. Using fat and muscle signal intensities as references tissues, lesions were graded into high, low or intermediate intensity categories for each of the sequences. Four signal patterns emerged. The typical pattern characterized by high signal on T1-weighted images and low signal on T2-weighted images reflected T1 and T2 shortening. The other pattern categories comprised of lesions demonstrating low signal T1-weighted images and high signal on T2-weighted images, high signal on both T1- and T2-weighted images and lesions showing intermediate signal on either T1- or T2-weighted images. We observed a tendency away from the typical signal pattern in extraocular melanoma cases with only one of 14 demonstrating this pattern. Moreover, only seven of thirteen ocular melanomas exhibited such behavior. Possible explanations for this findings as well as the existence of a variety of MR appearances to melanoma are offered. We conclude that while signal patterns showing T1 and T2 shortening are typical of melanoma, the absence of these does not exclude the diagnosis.

Magnetic resonance imaging and the severity of dementia in older adults.

Periventricular white-matter lesions were visualized in the brains of elderly patients being assessed for possible Alzheimer's disease. The magnitude of these lesions, expressed as lesion-brain ratios, correlated closely with the severity of dementia indicated by scores on the Blessed Dementia Scale and the Folstein Mini-Mental State Examination. Impairment in several domains of cognitive functioning tested by the Mini-Mental State Examination was also correlated with the relative quantity of periventricular lesions. Correlations were significant with systolic blood pressure, approached significance with age, and were not significant with duration of dementia or the magnitude of the lateral ventricles. These findings indicate the potential utility of structure-function correlations that are possible with magnetic resonance imaging in identifying mechanisms underlying dementia. They suggest that magnetic resonance imaging may be more useful than computed tomography in following the course of dementia.

Blepharospasm associated with olivopontocerebellar atrophy.

We report two cases of cranial dystonia (blepharospasm) associated with olivopontocerebellar atrophy (OPCA). The pathophysiology of blepharospasm appears to involve an increased excitability of the interneurons of the blink and corneal reflexes. It is hypothesized that blepharospasm associated with OPCA might be due to rostral brainstem lesions disrupting central dopaminergic and cholinergic pathways, resulting in disinhibition of brainstem reflexes or denervation supersensitivity of the facial nuclear complex.

Lanthanum potentiation of the vascular response to a protein kinase C activator in genetically hypertensive rats.

The effects of lanthanum on the contraction induced by the protein kinase C activator, 12-O-tetradecanoylphorbol-13-acetate (TPA) were studied in femoral artery rings from stroke-prone, spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). When exposed to a calcium-free buffer containing 1 mmol/l EGTA, the femoral artery rings from SHRSP and WKY, pre-contracted with TPA (10(-6) mol/l), relaxed by 52 and 24%, respectively. Treatment of the rings in this calcium-free buffer with 2.6 mmol/l lanthanum significantly potentiated the TPA-induced contractions in vascular rings from WKY (49%) and SHRSP (136%). Potentiation by lanthanum of the TPA-induced contraction in the absence of extracellular calcium suggests that this cation is acting intracellularly to increase protein kinase C activity. The increased vascular responsiveness of SHRSP to lanthanum may reflect an abnormality in protein kinase C activation in vascular smooth muscle of genetically hypertensive rats.

Compression of pulmonary artery by syphilitic thoracic aortic aneurysm: imaging.

A case of syphilitic aortitis with multiple thoracic aneurysms, one of which caused compression of the left pulmonary artery with hypoperfusion of the left lung as seen with perfusion scintigraphy, blood pool studies, CT, and magnetic resonance imaging is presented.

B-cell immunoblastic sarcoma as a cause of a photopenic lesion on bone scintigraphy: an initial description.

Photopenic metastatic lesions on bone scintigraphy have been previously reported. However, this finding is not emphasized for B-cell immunoblastic sarcoma. We report a case of B-cell immunoblastic sarcoma, which presented as an aggressive pancoast tumor with extensive rib destruction. Bone scintigraphy findings demonstrated a photopenic lesion with high gallium avidity. Correlative chest radiograph and CT scan are described.

Nifedipine and blood glucose in normal human volunteers.

The effect of nifedipine, a calcium antagonist on fasting blood glucose level, glucose tolerance, glucose-induced insulin and glucagon secretion was studied in healthy nondiabetic volunteers. Nifedipine 10mg twice daily for four weeks did not affect fasting blood glucose level, glucose tolerance, glucose-induced insulin and glucagon secretion.

MRI findings in pulmonary sarcoidosis.

Postero-anterior radiographs and magnetic resonance imaging (MRI) of the chest were performed in nine biopsy proven cases of sarcoidosis. MRI was more sensitive than a postero-anterior chest roentgenogram in detecting hilar and mediastinal adenopathy but less informative in detecting pleural and parenchymal disease.