Modelling dual isotope parathyroid scans: objective decision making for tumour detection.

Parathyroid subtraction imaging using the radioisotopes thallium-201 and technetium-99m was first described in 1983. Since then it has become a routine method for the pre-operative localization of parathyroid tumours. Despite its widespread use, the interpretation of the subtraction images remains very subjective. This paper describes and evaluates an automatic objective method for the analysis of parathyroid scans. The method is based on the calculation of a likelihood ratio (the probability of obtaining a count in a given pixel if a tumour is present divided by the probability of obtaining that same count if a tumour is not present). The likelihood ratio is calculated for each pixel in a subtraction image. The calculated value is compared with a threshold. Pixels with likelihood ratios greater than the threshold are classified as belonging to tumour sites. Pixels with likelihood ratios less than, or equal to, the threshold are classified as belonging to 'no tumour' sites. The probability density functions required were obtained from computer simulated images. The likelihood ratio technique has a similar sensitivity and specificity to that of experienced human observers analysing computer simulated images. Furthermore, it is a completely automatic method which can provide the basis of a decision support system.

The relationship between blood lactate and heart rate responses to swim bench exercise and women's competitive water polo.

The aim of this study was to explore the relationship between physiological responses to dry-land testing and to water polo playing. Eight female water polo players (mean+/-s: age 26.7+/-5.7 years, height 169+/-6 cm, body mass 65.3+/-7.0 kg) participated in two assessments. The first involved a discontinuous incremental arm test to exhaustion on an isokinetic swim bench. Blood lactate was determined from finger-prick blood samples and heart rate was recorded at increasing exercise intensities. The highest (peak) values for blood lactate (5.1+/-0.2 mmol l(-1)), exercise intensity (79+/-5.2 W) and heart rate (146+/-6 beats min(-1)) were recorded at exhaustion. Also, the exercise intensity and heart rate at a blood lactate concentration of 4 mmol l(-1) were established. The second assessment involved determination of blood lactate and heart rate immediately after each quarter of a different water polo game for each subject. The mean (+/-s(x)) blood lactate and heart rate for each quarter of the game were as follows: 3.5+/-0.4, 4.3+/-0.5, 4.3+/-0.7 and 4.6+/-0.5 mmol l(-1); 138+/-10, 149+/-12, 151+/-9 and 154+/-8 beats min(-1), respectively. None of the peak values on the swim bench correlated with blood lactate or heart rate responses to game-playing. However, the mean exercise intensity at 4 mmol l(-1) lactate (64+/-5 W) correlated with the fourth quarter values of both blood lactate concentration (r=-0.82, P=0.01) and heart rate (r=-0.93, P< 0.001). These results show that submaximal metabolic responses to exercise on a swim bench are closely correlated with metabolic responses to water polo game-playing.

In-situ simulation of one-piece metacarpophalangeal joint implants using finite element analysis.

Generally, reconstruction of the rheumatoid metacarpophalangeal (MCP) joint is achieved by means of implantation of a hinged silastic prosthesis. Whereas these implants restore some degree of mobility to the joint, they are prone to failure after a relatively short life-span, and little is known about their dynamical behaviour within the joint. In this study, the Swanson and Sutter designs of MCP implant were examined in an idealized joint environment by means of two-dimensional finite element analysis. The purpose was to assess how the differing geometry affected their behaviour as replacement joints, and whether they were inherently prone to abrasion and high stress concentrations during flexion. The results revealed the changing points of contact between the implant and the bone ends, and clearly showed the implant stems 'pistoning' in the intramedullary canals. This was found to be an effective way to provide preliminary information on the dynamic behaviour of an implant in a simulated joint. This would facilitate further optimization of design in advance of fabrication.

An examination of one-piece metacarpophalangeal joint implants using finite element analysis.

Reconstruction of the rheumatoid metacarpophalangeal (MCP) joint is generally achieved by means of implantation of a hinged silastic prosthesis. These implants reduce the pain in joint and restore some degree of mobility. However, they are prone to failure after a relatively short life-span. In this study, two popular designs of MCP implant, the Swanson and the Sutter, were compared by means of three-dimensional finite element analysis. The aim was to examine how the differing geometry effected their relative stiffness as replacement joints, and whether they were inherently prone to high stress concentrations during flexion. Although the Swanson design implant exhibited relatively greater resistance to flexion, both designs showed regions of high stress concentration and it was noted that neither was without its limitations. The use of the finite element technique was found to be an excellent way to provide preliminary design evaluation information, allowing further evolution before clinical trials.

The virtual gamma camera room.

The installation of a gamma camera is time-consuming and costly and, once installed, the camera position is unlikely to be altered during its working life. Poor choice of camera position therefore has long-term consequences. Additional equipment such as collimators and carts, the operator's workstation and wall-mounted display monitors must also be situated to maximize access and ease of use. The layout of a gamma camera room can be optimized prior to installation by creating a virtual environment. Super-Scape VRT software running on an upgraded 486 PC microprocessor was used to create a 'virtual camera room'. The simulation included an operator's viewpoint and a controlled tour of the room. Equipment could be repositioned as required, allowing potential problems to be identified at the design stage. Access for bed-ridden patients, operator ergonomics, operator and patient visibility were addressed. The display can also be used for patient education. Creation of a virtual environment is a valuable tool which allows different camera systems to be compared interactively in terms of dimensions, extent of movement and use of a defined space. Such a system also has applications in radiopharmacy design and simulation.

The physical demands of riding in National Hunt races.

Heart rate (fc) and post-competition blood lactate concentration ([La+]) were studied in seven male professional National Hunt jockeys over 30 races. The fc response for individual races followed a similar pattern for all subjects. The mean peak fc recorded during competition was 184 beats.min-1 (range 162-198 beats.min-1) with average fc during the races ranging from 136 to 188 beats.min-1. During consecutive races the recovery fc did not return to resting values. The mean [La+] was 7.1 mmol.l-1 (range 3.5-15.0 mmol.l-1). The conclusions of this study suggest that riding in National Hunt races is a physically demanding occupation. The muscular activity in this profession requires a high metabolic drive and produces a significant cardiorespiratory response.

Isolation of megakaryocytes from human placentae.

Shedding of cytoplasm from circulating megakaryocytes (MKs) within the pulmonary vasculature suggests the lungs are an important site for normal platelet production. Fetal lungs receive only a minor fraction of the circulating blood volume. The placenta may act as a site for intrauterine platelet formation. Isolation of MKs from fetal vessels within the placenta has not been previously reported. Immediately after delivery, 3 human placentae were subjected to forward and retrograde perfusion across the placental capillary bed on the fetal side. MKs in perfusates were harvested by 'whole blood filtration' and identified by morphological and immunochemical methods. All perfusates yielded MKs. Qualitatively MKs with copious cytoplasm were more commonly found in perfusates collected from fetal arteries compared with those from fetal veins. This is consistent with filtration of MKs and fragmentation of their cytoplasm within the placental microcirculation to produce platelets. Perfusion of human placentae followed by filtration of perfusates is a useful technique for harvesting fetal MKs and permitting further elucidation of their physiological role.

The fate of circulating megakaryocytes during cardiopulmonary bypass.

Megakaryocytes with intact cytoplasm normally leave the bone marrow, enter central venous blood, and are filtered in the lungs. During cardiopulmonary bypass, large megakaryocytes are not filtered by the lungs and may not be removed in the extracorporeal circuit by arterial line filters. In such circumstances, they could enter the systemic circulation and block smaller cerebral vessels, resulting in neurologic impairment. To investigate the fate of circulating megakaryocytes during cardiopulmonary bypass, central venous blood and oxygenated blood samples before and after arterial line filtration (40 microns polyester screen filter) were obtained from 10 patients undergoing cardiopulmonary bypass. Megakaryocytes were isolated by whole blood filtration and identified by their characteristic structure after May-Grunwald-Giemsa staining. In preliminary studies, megakaryocyte identification was verified by immunolabeling. All samples contained megakaryocytes with copious cytoplasm. Their frequencies in central venous blood and oxygenated blood before and after the arterial line filtration (corrected for hemodilution) were 23.4 +/- 9.3 per milliliter (mean +/- standard error of the mean, range 3.1 to 89.7 per milliliter), 21.0 +/- 8.2 per milliliter (2.0 to 84.2 per milliliter) and 17.1 +/- 7.4 per milliliter (3.1 to 80.4 per milliliter), respectively. Megakaryocytes with scant or no visible cytoplasm were also observed. The results confirm that circulating megakaryocytes are a normal physiologic component. During cardiopulmonary bypass, megakaryocytes with copious cytoplasm (mean diameter 42.7 microns, range 22 to 78 microns) can pass through the extracorporeal circuit. In the absence of filtration by the lungs, these large cells have access to the systemic circulation. This study supports a possible role for circulating megakaryocytes in the development of cerebral dysfunction after cardiopulmonary bypass.

Isolation of circulating megakaryocytes in man.

Recovery of the small numbers of megakaryocytes (MKs) known to be present in normal blood is difficult because of their low frequency. Isolation of circulating MKs was achieved using a modified filtration system in which untreated blood was passed through 5 microns polycarbonate membranes. MKs were retained while most other blood cells passed through the membranes. Four groups of MKs were identified in May Grünwald-Giemsa stained filters of blood from peripheral, central and umbilical veins and umbilical arteries. Type 1 MKs were nuclei with no visible cytoplasm. Types 2, 3 and 4 were nuclei with increasing amounts of cytoplasm. Type 4 MKs, possessing copious cytoplasm, were rarely isolated from peripheral venous blood but were more regularly encountered in central venous and cord blood. Filtration of whole blood through polycarbonate membranes is a useful technique for the isolation of circulating MKs, which are a normal physiological occurrence. Their presence is consistent with the production of platelets in the placenta during intra-uterine life, and subsequently in the pulmonary circulation.

The placenta: a site of platelet production?

Stripping of cytoplasm from circulating megakaryocytes (MKs) in the pulmonary capillary bed implicates the lungs as an important site for platelet production in normal physiology. The placenta has been proposed as an alternative location for intrauterine platelet production as fetal lungs are essentially non-functioning. To investigate this further, circulating MKs from an umbilical artery and umbilical vein of 10 human placentae were isolated using a modified whole blood filtration technique. Pretreatment of blood, which may be deleterious to MKs, was not required. Following May Grunwald Giemsa staining of filters, MKs were identified by their morphology and classified into 4 types based on subjective assessment of the amount of cytoplasm present. Blood from umbilical arteries and veins contained a mean of 37.2 MKs/0.5 ml (median 37.0; range 17-80) and 23.9 MKs/0.5 ml (median 18.5; range 5-67) respectively (p < 0.01). 43% of arterial MKs and 14% of venous MKs possessed copious cytoplasm (p < 0.01). These results demonstrate a significant reduction of MK numbers across the placenta. Removal of MK cytoplasm at this site is consistent with the hypothesis that the placenta functions as a platelet forming organ during intrauterine life, the lungs taking over this role after birth.

The size and number of bone marrow megakaryocytes in malignant lymphoma and their relationship to abnormalities in platelet count.

Platelet counts were measured routinely in 718 volunteer blood donors and 124 patients with malignant lymphoma. When considered by gender, the mean platelet counts of the patients with malignant lymphoma were significantly increased when compared to controls (P less than 0.01). In addition, 9% of males and 4% of females with lymphoma exhibited a thrombocytosis, in which their platelet counts exceeded the upper limit of the normal platelet count for control subjects (defined as 2 SDs in excess of the mean value). Megakaryocyte whole size, cytoplasmic and nuclear sizes, and megakaryocyte numbers were also quantified in bone marrow obtained from the iliac crest of 5 hematologically normal subjects and 26 patients with malignant lymphoma. Mean megakaryocyte sizes were significantly greater in subjects with lymphoma, when compared to control values (P less than 0.05). No significant differences in megakaryocyte numbers in bone marrow were observed between the two groups. For subjects with malignant lymphoma, platelet count was found to be significantly positively correlated with megakaryocyte size. The results of this study suggest that the elevated platelet count associated with malignant lymphoma is mediated by an increase in the size of the megakaryocytes in the bone marrow.

An introduction to the 'Mennen plate' and its use in treatment of fractures of the edentulous mandible.

A paraskeletal clamp plate (Mennen) offers a novel method of fixation for mandibular fractures. Its application is relatively atraumatic and this together with the minimal disruption to the local blood supply may make this clamp particularly suited to fixation of fractures of the atrophic edentulous jaw. Its use in six such cases is reported.

Electrical impedance assessment of muscle changes following exercise.

Electrical impedance measurements have been assessed as a method of detecting changes in striated muscle following vigorous exercise. Transverse and longitudinal resistivities of the calf and thigh have been measured before and after four subjects ran a half marathon (21 km). No changes were observed in longitudinal resistivity but transverse resistivity rose by an average of 7% following the race. These results are consistent with changes in the muscle fibre membranes or interstitial fluid content.

Megakaryocyte ploidy in thrombocytosis: improved microdensitometric measurements with a new image analysis system.

Megakaryocyte (MK) nuclear deoxyribonucleic acid (DNA) content was measured on a new image analysis system. Feulgen-stained bone marrow aspirate smears were analysed from 9 patients with thrombocytosis. Average optical density (OD) of stained nuclei was evaluated by pixel discrimination over 128 grey levels. Projected nuclear area was delineated manually. The product of these two parameters gave an index of nuclear DNA content. Neutrophils were used as 2N reference cells. Reproducibility of OD, nuclear area and their product was excellent for individual cells (CV less than 2.0% for MKs, less than 4.0% for neutrophils). The average CV for DNA content of 18 groups of 10 neutrophils was 5.5% (range 3.0-9.7%). A significant linear regression existed between MK nuclear area and DNA content (p much less than 0.001) for 627 MKs in essential thrombocythaemia (ET) and 346 MKs in reactive thrombocytosis (RT). Compared with RT, more 8N and 64N MKs were seen in ET (p less than 0.05). 128N MKs were unique to ET. Image analysis of MK ploidy may assist the clinical discrimination between primary and secondary thrombocytosis.

Pericardial heterografts: a comparative study of suture pull-out and tissue strength.

The force required to pull sutures out of glutaraldehyde fixed bovine pericardium, for four different suture bites: 0.5 mm, 1 mm, 1.5 mm and 2.0 mm, was compared with the tissue strength. The mean suture pull-out force was significantly lower than the tissue strength for all bites, with a minimum value of 2.86 +/- 1.02 N for the 0.5 mm bite and a maximum value of 6.32 +/- 0.77 N for the 2.0 mm bite. The mean force which produced failure of the chemically modified pericardium was 15.49 +/- 8.48 N. The mean force at pull-out of the sutures lay on a regression line: force at failure = 1.68 + 2.25 x Bite. A video film of the experiments showed that the suture does not cut through the pericardium. It pulls a V-shaped band of collagen fibre bundles through the stationary pericardium. Eventually this band breaks away from the free edge of the tissue specimen. The specimens under uniaxial load failed by laminate debonding of two layers of tissue, rupture of the serosal surface layer followed by shear and fibre slippage. These results indicate that any suture which bears load, during the normal functioning of a heart valve substitute, will be a source of weakness, compared to the overall tissue strength. As a consequence the alignment/holding suture of the Standard Ionescu-Shiley valve and the modified stitch of the low profile valve are likely to be potential sites of fatigue failure.

Local variation in the tearing strength of chemically modified pericardium.

Forty squares of tissue, 40 mm X 40 mm, were harvested from bovine pericardium fixed in glutaraldehyde free of tension. Two parallel dumb-bell specimens were excised from each square. In 20 pairs of adjacent samples, two 1 mm cuts were introduced into one of the samples at the centre of the dumb-bell. The other 20 pairs were used as controls. There was no significant difference in tensile strength of the paired samples tested without cuts, but there was marked variation in the strength of the tissue in different squares. There was a significant positive correlation between the strength of the paired samples. Introduction of artificial tears produced a significant reduction in the strength of the tissue locally. However, a significant positive correlation between the sample with tears and the sample without tears was still maintained. Failure of the tissue under uniaxial load was observed dynamically by using a Panasonic video camera with zoom and magnification facilities illuminated by an oblique low-power light source placed behind the specimen. All samples, with or without tears, failed by rupture of a layer of tissue, laminate debonding and shear, followed by fibre slippage through the viscoelastic embedding matrix.

Automated haematology: construction of univariate reference ranges for blood cell count and size.

The theory of reference ranges advocated by the International Committee for Standardization in Haematology (ICSH) was tested experimentally for an aperture impedance and a flow cytometric system. The reference sample was drawn from volunteer blood donors and the sampling procedure carefully standardised. Subjects were partitioned for gender and smoking habits, and their ages noted. Reference ranges were constructed from Gaussian statistics, after objective evaluation of the data, based on an assumed occurrence of one false positive measurement in every twenty samples. Different reference ranges were obtained on the two different systems for some haematological parameters, and partitioning also produced differences in calculated reference ranges. We conclude that strict adherence to the ICSH recommendations is almost impossible. Nevertheless, it is important that all laboratories should construct their own local reference ranges for their specific analytical systems before cost effective clinical decisions can be made.