Patterns of CD16 and CD56 expression in persistent expansions of CD3+NKa+ lymphocytes are predictive for clonal T-cell receptor gene rearrangements

Phenotypic characteristics, and correlations between the expression of membrane NK-associated (NKa) determinants (CD11b, CD16, CD56 and CD57) and T cell receptor (TCR) genotypic patterns, were examined in 25 patients with persistent (greater than 6 months) expansions of CD3+WT31+NKa+ (CD8+ and CD8dim+) lymphocytes. These studies showed that distinct NKa phenotypic profiles were restricted to cases with rearranged TCR configurations and that clonal CD3+NKa+ components could be predicted in most cases by assessing relationships between membrane CD16 and CD56 expression. For all normal NKa subpopulations, there was a high correlation (P less than 0.0001; n = 31) between the expression of these two membrane determinants. Markedly increased CD16 expression by CD3+NKa+ cells, in relation to CD56 (i.e. a high CD16:CD56 ratio), was found exclusively in cases with rearranged TCR (13/16 cases); 2/3 of the remaining cases showing significantly reduced CD16:CD56 ratios and high (greater than 2.0) CD3+CD56+ absolute numbers. In contrast, 7/9 of the germline TCR cases had a normal CD16:CD56 ratio and 2/9 a decreased ratio with low (less than 1.0) CD3+CD56+ absolute numbers. A high ratio of CD16:CD56 expression by CD3+NKa+ lymphocytes was therefore informative for 82% of TCR rearrangements in this series; and analysis of CD16 and CD56 expression was predictive for germline and rearranged TCR configurations in 24/25 persistent CD3+NKa+ expansions.     

MRI in greater trochanter pain syndrome

The greater trochanter pain syndrome refers to pain on the lateral aspect of the hip joint. This is frequently attributed to trochanteric bursitis and distension of the subgluteal bursae. Associated tears of the tendons of gluteus medius and minimus have been described and may result from repetitive frictional trauma to these tendons and their associated bursae secondary to impingement beneath the tensor fascia lata. Occasionally tendinous damage may result from acute local direct trauma or a hyperadductive strain injury. We describe MRI in two patients with chronic lateral hip pain.     

New approach to management of intraaortic balloon pumps in patients with peripheral vascular disease: Case reports of four patients requiring urgent IABP insertion

Four selected cases of emergent IABP insertion in PV patients are presented. After angiographic documentation of critical iliac stenosis, conservative peripheral angioplasty was performed prior to IABP insertion. No patient experienced a peripheral ischemic event associated with IABP use. © 1992 Wiley-Liss, Inc.     

Scale-up of Adhesive Transdermal Drug Delivery Systems

Pharmaceutical Research -     

Minimal volume,hypotense resuscitation

Large volume fluid resuscitation attempting to normalise physiological parameters in hypovolaemic shock has become the accepted management practice during the last 30 years. This doctrine, based on research in the 1950s, teaches that shock increases mortality, aggressive resuscitation improves outcome and normalisation of vital signs protects against multiple organ dysfunction. The wide acceptance of this doctrine is demonstrated by the central role it plays in the American College of Surgeons Advanced Trauma Life Support (ATLS) course and its Australian equivalent the Early Management of Severe Trauma (EMST) course. During the late 1980s, a number of animal research papers demonstrated severe limitations to the earlier work performed in the 1950s and proposed an alternative approach using hypotense or minimal fluid resuscitation. Controlled haemorrhagic shock is hypovolaemic shock in which the source of the bleeding is easily controlled without operation and hence aggressive fluid resuscitation can be pursued with minimum risk. Uncontrolled haemorrhagic shock is hypovolaemic shock due to bleeding which cannot be controlled without surgery. The restoration of blood pressure towards normal levels may lead to dislodgement of thrombus and loss of vascular spasm in damaged vessels, with a subsequent increase in blood loss. It is in this situation that hypotense resuscitation is thought to be of most value. Hypotense resuscitation is defined as the use of fluid resuscitation to maintain blood pressure at lower than normal levels which are sufficient to maintain life, but minimise the risk of exacerbating internal bleeding. Prompted by animal research a number of human studies have been undertaken to clarify the role of fluid resuscitation in uncontrolled haemorrhage. At present, there is wide acceptance of the use of hypotense or minimal volume resuscitation for ruptured abdominal aortic aneurysm and a recent demonstration that morbidity and mortality are decreased by the use of hypotense resuscitation in penetrating truncal trauma. There are however many other clinical situations that may produce uncontrolled haemorrhagic shock about which we have little clinical data to predict appropriate levels of fluid resuscitation. These include ectopic pregnancy, gastro-intestinal haemorrhage and blunt multi-system trauma. This paper will analyse the animal studies that demonstrate the physiological effects of the various fluid resuscitation regimes and discuss all the clinical papers on the subject of hypotense resuscitation. An attempt will then be made to integrate this data into current Australian practice and give broad guidelines on the modern management of uncontrolled haemorrhagic shock, based on minimal volume or hypotense resuscitation.     

Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain

The receptor mGluR5 is a metabotropic glutamate receptor with messenger RNA abundantly present throughout cortex, hippocampus, and caudate/putamen that is also coupled to phosphatidyl inositide hydrolysis and calcium mobilization. In this study, the distribution of mGluR5 was examined in rat brain by immunocytochemistry. The antibody utilized is highly specific and does not cross react with the most closely related other metabotropic glutamate receptor, as determined by Western blot analysis of nonneuronal cells transfected with metabotropic receptor coding sequences. The receptor mGluR5 is widely expressed with the highest density in olfactory bulb, caudate/putamen, lateral septum, cortex, and hippocampus, as confirmed with both immunocytochemistry and Western blot analysis. Electron microscopic studies in hippocampus and cortex indicate that the labeling is mostly on membranes of dendritic spines and shafts. Light and electron microscopic evidence indicates that some mGluR5 immunoreactivity is located in presynaptic axon terminals, suggesting that mGluR5 may function as a presynaptic receptor.     

Structure and Behavior in Hydrophilic Matrix Sustained Release Dosage Forms: 4. Studies of Water Mobility and Diffusion Coefficients in the Gel Layer of HPMC Tablets Using NMR Imaging

Purpose. The purpose of this study was to characterise the water mobility in the gel layer of hydrating HPMC tablets. Water mobility in the gel layer of different HPMCs was studied. Methods. NMR imaging, a non-invasive technique, has been used to measure the spatial distribution of self-diffusion coefficient (SDC) and T₂ relaxation times across the gel layer. Results. It has been shown that there is a water mobility gradient across the gel layer of HPMC tablets. Although SDC and T₂ relaxation times in the outer parts of the gel layer approached that of free water, in the inner parts they decreased progressively. Water mobility and SDC in the gel layer of different HPMCs appeared to vary with degree of substitution of the polymer and the lowest values were obtained across the gel layer of K4M tablets. Conclusions. Water mobility varies across the gel layer of hydrating HPMC tablets and it is dependent on the degree of substitution of the polymer.