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Biomedical subjects

A M Peters

Publications and source records attributed to A M Peters.

At least 55 records · Page 3Linked to original sources
PubMed2000

SPECT in the management of patients with back pain and spondylolysis.

PURPOSE: Single photon emission computed tomography (SPECT) bone scans of the lumbar spine were evaluated in the management of patients with low back pain and suspected spondylolysis. MATERIALS AND METHODS: Thirty-three patients (mean age, 30 years) with high clinical suspicion of pars interarticularis defects were included in the study. The results of lumbar radiographs and SPECT bone scintigraphy were compared and the influence of these results on patient management was evaluated. RESULTS: Twenty-six of the 33 patients had abnormal results of lumbar radiographs. Of the 21 patients with radiographs indicating spondylolysis, six had abnormal uptake in the pars regions on bone scintigraphy. One patient with normal results of lumbar radiographs had a SPECT bone scan showing uptake in the region of the pars interarticularis. CONCLUSIONS: SPECT bone scanning of the lumbar spine has a role in the treatment of patients with symptomatic spondylolysis.

Adult↗
PubMed2000

Indexed glomerular filtration rate as a function of age and body size.

The conventional way in which to scale or index a measurement of glomerular filtration rate (GFR) is to express it in relation to body surface area (BSA). However, BSA may not be appropriate for infants and children because, as individuals increase in size, their relative BSA decreases. Several other whole-body variables have been suggested as alternatives, including extracellular fluid volume (vECF). The purpose of the present study was to compare BSA and vECF as variables against which to index GFR, and in particular to look at this comparison in children versus adults. A total of 130 patients (age range 1-80 years; 40 patients <12 years) undergoing clinically indicated routine measurement of GFR using the bolus-injection single-compartment technique were included in the study. GFR was measured as the plasma clearance of [(51)Cr]EDTA as assessed from three peripheral venous blood samples taken between 2 and 4 h after injection of [(51)Cr]EDTA. Volume of distribution (V(d)) was obtained by extrapolation of the clearance curve to zero time. GFR was scaled to a BSA of 1.73 m(2). GFR and GFR/1.73 m(2) were corrected to account for the assumption of a single compartment. The rate constant of the exponential between 2 and 4 h was also corrected to give GFR/litre ECF. GFR and GFR/1.73 m(2) were both divided by GFR/litre ECF, to give vECF and vECF/1.73 m(2) respectively. Weight per unit BSA increases as a linear function of BSA. vECF is always less than V(d), on average by about 30%. vECF increased as an exponential function of BSA and as a linear function of body weight. vECF/70 kg body weight was higher in children (16. 2+/-3 litres) than adults (13.4+/-2.3 litres), but vECF/1.73 m(2) was lower in children (9.7+/-1.7 litres) compared with adults (12. 4+/-2 litres). vECV/1.73 m(2) increased as a function of both age and BSA, but vECF/kg decreased. GFR/12.5 litres vECF was higher than GFR/1.73 m(2) in children, but these values were similar in adults, with the ratio of these two forms of indexed GFR falling significantly with both age and BSA. Although this was not a normal population, but one with a wide range of renal function, GFR/vECF showed a strong inverse association with age, whereas for GFR/BSA the association was weak. In conclusion, these data provide further evidence that vECF is more valid physiologically for indexing GFR than is BSA, especially in children. Nevertheless, a GFR measurement in a child should ideally be expressed as a percentage of normal for that child's age. However, such normal values are not yet available.

Adolescent↗
PubMed2000

Pegylated liposome-encapsulated doxorubicin and cisplatin enhance the effect of radiotherapy in a tumor xenograft model.

Concomitant chemotherapy and radiotherapy (CCRT) has recently been shown to improve treatment outcome in a range of solid tumors. Pegylated liposomes have the potential to target drugs directly to tumors and may increase the efficacy and reduce the toxicity of CCRT by selectively delivering radiosensitizing agents to tumor, as opposed to normal, tissues. In these studies, we have assessed CCRT using pegylated liposome encapsulated doxorubicin (PLED) and pegylated liposome encapsulated cisplatin (PLEC) against KB head and neck cancer xenograft tumors in nude mice. The addition of low-dose (2 mg/kg) PLED (P < 0.001) and PLEC (P < 0.001) significantly increased the effect of 4.5 Gy, but not 9 Gy, single-fraction radiotherapy (SFRT). Both PLED and PLEC were significantly more effective than their unencapsulated counterparts in increasing the effect of SFRT. In addition, PLED (P < 0.001) and PLEC (P < 0.05) significantly increased the effect of fractionated radiotherapy (9 Gy in 3 fractions) in two different dosing schedules (2 mg/kg single dose or three sequential doses of 0.67 mg/kg). Unencapsulated diethylenetriaminepentaacetic acid and pegylated liposomal diethylenetriaminepentaacetic acid were used as controls to test the effect of the liposome vehicle and showed no interaction with 4.5 Gy or 9 Gy SFRT (P > 0.1). CCRT was well-tolerated, with no evidence of increased local or systemic toxicity, as compared with radiotherapy alone. This study is the first to demonstrate the value of pegylated liposomes as vehicles for the delivery of radiosensitizing drugs in CCRT strategies.

Animals↗
PubMed1999

Solution-phase and solid-phase synthesis of novel transition state inhibitors of coagulation enzymes incorporating a piperidinyl moiety.

2-Amino-3-piperidin-4-yl-propionic acid containing peptidomimetics are potent protease inhibitors when combined with an appropriate keto-thiazole or keto-carboxylic acid moiety. A novel P1 residue in factor Xa and thrombin inhibitors has been found resulting in IC50 values as low as 0.048 microM, a factor of ten more potent than Argatroban. Starting with non-chiral synthetic routes, a new stereospecific route was developed as well as a new solid-phase method.

Blood Coagulation Factors↗
PubMed1999

Resolution in high field echo planar microscopy.

The application of echo planar imaging to NMR microscopy offers a temporal resolution unparalleled by other techniques. However, a major difficulty in imaging at the high field strengths used for microscopy is the effect of local field inhomogeneities caused by magnetic susceptibility effects. This can give rise to both image distortion and signal loss. In addition, the effect of diffusion in the presence of the large imaging gradients gives rise to a broadening of the point spread function and hence loss of true resolution. We compare the sensitivity of two techniques, MBEST and PEPI, to both of these effects. Analytic expressions for the signal in each echo of the two sequences are developed, and the point spread functions for the two techniques are calculated. Using PEPI, we have been able to produce images with an in-plane resolution of 50 micrometer from a single free induction decay. This technique has been extended to three dimensions allowing the generation of 64(3) images with an isotropic resolution of 80 micrometer.

Diffusion↗
PubMed1999

Measurement of lymphatic function with technetium-99m-labelled polyclonal immunoglobulin.

A reliable method for measuring lymph flow in physiological units would be valuable, especially in conditions in which it is uncertain whether lymph flow is increased or decreased. The requirements of a radiopharmaceutical for such measurement include stable radionuclide labelling and rapid access to lymphatic vessels following tissue injection but no access to blood vessels. A soluble macromolecule is likely to come closest to meeting these requirements. Technetium-99m-labelled human polyclonal immunoglobulin (HIG) was therefore investigated firstly in comparison with 99mTc-labelled human serum albumin (HSA) in patients undergoing routine lymphoscintigraphy and secondly with respect to injection site in a group of volunteers with post-mastectomy oedema (PMO). Subcutaneous injection of 99mTc-HIG into the web space of a distal extremity gave images in which lymphatic vessels were more clearly defined compared with images obtained after injection of 99mTc-HSA. Lymph nodes were also more clearly defined, suggesting specific retention of HIG, possibly through Fc-mediated binding. Peripheral blood sampling showed a delayed arrival in blood of radioactivity after 99mTc-HIG compared with 99mTc-HSA, although ultimately, the blood recovery of 99mTc-HIG was significantly higher (P < 0.05) than that of 99mTc-HSA. Clearance rates of radioactivity from the injection site were not significantly different, however, between the two agents. In patients with PMO, web space injection of 99mTc-HIG gave excellent images of normal lymphatic vessels, of lymph nodes and of abnormal lymph drainage such as dermal backflow in swollen arms. In contrast, neither lymphatic vessels nor lymph nodes were visualised after injection into the skin of the dorsum of the distal forearm. Although there was no difference in clearance rates from the injection sites between normal and swollen arms with either agent in PMO, clearance was significantly faster following injection into the web space (0.11% per minute for normal and swollen arms combined) than into the forearm (0.053% per minute; P < 0.05). These results suggest that (a) 99mTc-HIG is a potentially useful agent for measuring lymph flow and lymph node function; but (b) injection into the dorsum of the forearm is not a useful method of administration for these measurements; and (c) clearance rates from the injection site do not support the notion that PMO is the result of decreased lymph flow. Further studies are warranted to evaluate 99mTc-HIG as an agent for assessment of lymphatic function, especially with respect to measurement of lymph flow and possibly also for the evaluation of lymph node Fc-mediated immunocompetence.

Female↗
PubMed1999

Defective apoptosis due to a point mutation in the death domain of CD95 associated with autoimmune lymphoproliferative syndrome, T-cell lymphoma, and Hodgkin's disease.

Apoptosis via CD95 and its ligand is an important mechanism that prevents uncontrolled proliferation of activated lymphocytes and regulates lymphocyte homeostasis. The apoptosis receptor CD95 is a transmembrane protein with an intracellular domain well conserved between CD95 and tumor necrosis factor receptor I, another apoptosis-inducing protein. Because of its functional importance, this domain was designated the death domain. We describe the molecular analysis of the CD95 death domain in a family with autoimmune lymphoproliferative syndrome (Canale-Smith syndrome), T-cell lymphoma, and Hodgkin's disease. A functional defect in apoptosis was detected in cells from the index patient, a 5-year-old girl suffering from Canale-Smith syndrome and a T-cell lymphoma, as well as in her father, who had a history of splenomegaly and mild hemolysis, and her paternal uncle who had been cured of Hodgkin's disease (HD). Expansion of double-negative T cells (CD4-CD8-) was only seen in the index patient. All family members with a functional defect in apoptosis were heterozygous for a point mutation in the death domain of CD95 (A1009G, E256G). We conclude that, within the same family, a defect in apoptosis due to a mutation in the CD95 death domain can be associated with diverse clinical phenotypes, including mild, reversible symptoms and different malignancies.

Apoptosis↗
PubMed1999

Appropriate corrections to glomerular filtration rate and volume of distribution based on the bolus injection and single-compartment technique.

The bolus injection, single-compartment technique for measuring GFR overestimates the true value. Nevertheless, assuming that for a given indicator the area under the first exponential of the plasma clearance curve is constant from subject to subject, the observed (uncorrected) value can be corrected by multiplication with a 'sliding' factor, the value of which is a nonlinear function of GFR. Several second-order polynomials, based on pre-determined relationships between simultaneously determined two-compartment and one-compartment GFR, have been described for correcting GFR (GFR correction). It is, however, theoretically more rational to use a factor which depends on the rate constant, alpha2, of the terminal exponential of the clearance curve. We have therefore determined a set of linear equations from retrospectively analysed multiple-sample inulin, 99mTc-DTPA and 51Cr-EDTA clearance curves to enable correction of GFR using alpha2. A set of linear equations is also developed to correct the volume of distribution (Vd) of the indicator (close to extracellular fluid volume for these indicators), which is also overestimated by the one-compartment technique. At low levels of GFR, alpha2-corrected GFR is similar to uncorrected GFR for all three indicators. As GFR increases, however, uncorrected GFR progressively overestimates (alpha2-corrected GFR. The overestimation is greater for inulin than for 99mTc-DTPA or 51Cr-EDTA. In the one-compartment approximation, Vd is overestimated more than GFR, and again the greatest overestimation is seen with inulin. In a prospective study of 129 patients undergoing routine measurement of GFR with 51Cr-EDTA, alpha2 correction using a factor based on retrospective EDTA data gave values of GFR which were higher than values obtained from GFR correction using a previously published polynomial (also based on EDTA clearances) by 15% in children and 12.5% in adults when uncorrected GFR was 150 ml/min/1.73 m2. Moreover, the ratio of uncorrected GFR to GFR-corrected GFR was higher in children than adults. We conclude that alpha2 is a more rational variable with which to correct two-sample or three-sample GFR than GFR itself, that the correction formulae are not interchangeable between inulin on the one hand and EDTA and DTPA on the other, and that the relative magnitudes of the corrections given by alpha2 correction versus GFR correction are different for children and adults.

Adult↗
PubMed1999

Clearance kinetics of solutes used to measure glomerular filtration rate.

Agents used to measure glomerular filtration rate (GFR) give a biexponential plasma disappearance curve on multiple peripheral venous sampling between 20 min and 4 h after intravenous injection. These two exponentials are generally regarded to represent equilibration of agent throughout the extracellular fluid (ECF) space and renal clearance, respectively. In seven subjects undergoing diagnostic arteriography, arterial and antecubital venous plasma samples were obtained up to 60 min in five and up to 120 min in two following simultaneous intravenous injection of 99Tcm-diethylene triamine pentaacetate (99Tcm-DTPA) and inulin. The count rate from 99Tcm was simultaneously recorded over the calf with a collimated scintillation probe in five subjects up to 60 min post-injection. The arterial and venous time-concentration curves were interpolated and subtracted to give a curve of the arterio-venous (A-V) concentration difference, which was then integrated. Arterial time-concentration curves display three exponentials, the first of which has the largest amplitude and disappears by about 20 min. The A-V concentration difference becomes zero at about the same time. The integral of the A-V concentration difference, which represents activity in the interstitial space of the forearm, has a time course consistent with the second compartment of a model of two compartments in series (the first being plasma) and a time course that is reciprocally similar to the first exponential of the triexponential arterial plasma curve. The curve externally recorded by scintillation probe has a shape consistent with a signal that is the composite of interstitial 99Tcm-DTPA and plasma 99Tcm-DTPA activities. The arterial plasma clearance curve of GFR agents is triexponential; the first exponential reflects equilibration of agent between plasma and the interstitial space of carcass tissue (mainly muscle and skin). The second exponential is minor compared with the first; it is not clear what it represents. The third exponential reflects renal clearance.

Adult↗
PubMed1999

Sensitivity and specificity of radioisotope right-left shunt measurements and pulse oximetry for the early detection of pulmonary arteriovenous malformations.

STUDY OBJECTIVES: To assess the effectiveness of pulse oximetry and radioisotope measurement of right-to-left (R-L) shunt for the early detection of pulmonary arteriovenous malformations (PAVMs) in patients with hereditary hemorrhagic telangiectasia (HHT). DESIGN: Patients with HHT had serial measurements of the following: (1) arterial oxygen saturation (SaO2) by pulse oximetry in erect and supine positions, and on maximal exercise using cycle ergometry; (2) quantitative radioisotope measurements of R-L shunt using IV 99mTc-labeled macroaggregates of albumin; and (3) routine pulmonary function. After percutaneous transcatheter embolization of all PAVMs with feeding vessel diameters > 3 mm, residual PAVMs were assessed with selective digital subtraction pulmonary angiography. Using postembolization angiography as the "gold standard," SaO2 and radioisotope shunt measurements after embolization were analyzed retrospectively using logistic regression to assess the ability of each test to predict for the presence of residual PAVMs. RESULTS: Of the 66 patients included, 40 had small PAVMs remaining postembolization. Using univariate logistic regression, radioisotope shunt and erect saturation showed a significant relationship with the presence of residual PAVMs (p=0.001, 0.005, respectively). Erect SaO2 < or = 96% had 73% sensitivity and 35% specificity for detecting PAVMs. Radioisotope shunt >3.5% of cardiac output had 87% sensitivity and 61% specificity for detecting PAVMs. CONCLUSIONS: These results confirm that noninvasive measurements are useful in the screening of patients with HHT for the presence of PAVMs without need for angiography and its associated risks, and that radionuclide scanning is better than pulse oximetry.

Angiography, Digital Subtraction↗
PubMed1999

Pulmonary granulocyte kinetics in relation to endothelial and granulocyte activation.

The aim of the study was to measure the peripheral blood levels of soluble E-selectin in patients with systemic inflammation and compare them with in vivo granulocyte activation, pulmonary intravascular granulocyte pooling, pulmonary extravascular granulocyte migration and 99mTc-diethylenetriaminepenta-acetic acid (DTPA) aerosol clearance, an index of lung injury. The level of soluble E-selectin was measured by capture ELISA. Granulocytes were labelled with 111In and 99mTc for quantification of pulmonary granulocyte kinetics. The pulmonary vascular granulocyte pool (PGP) was expressed as a fraction of the total blood granulocyte pool. Pulmonary granulocyte migration was quantified on 24-h images using the 111In signal. Granulocyte activation was quantified as the percentage of circulating cells showing shape change ('primed'). Lung injury was assessed from the clearance rate of inhaled 99mTc-DTPA aerosol. Eighteen patients with systemic inflammation were studied: five with inflammatory bowel disease, eight with systemic vasculitis, four with graft versus host disease and one with a recent renal transplant. The peripheral blood levels of soluble E-selectin were significantly elevated in patients with systemic inflammation. The level of soluble E-selectin showed a significant association with granulocyte migration (Spearman rank correlation coefficient, Rs=0.53; P<0.05) but not with PGP or with the percentage of cells showing shape change (P>0.05 for both). Granulocyte migration was bimodal: patients were therefore subdivided into 'migrators' and 'non-migrators'. Soluble E-selectin level, 99mTc-DTPA clearance and PGP, but not the percentage of cells showing shape change, were significantly higher in migrators than in non-migrators. We conclude that pulmonary intravascular granulocyte pooling is increased in the presence of increased numbers of circulating primed granulocytes but increased pooling does not by itself promote granulocyte migration into the lung interstitium. Insofar as an elevated level of E-selectin in peripheral blood reflects vascular endothelial activation, the data are consistent with the notion that pulmonary endothelial activation is required, in addition to granulocyte activation and an expanded PGP, for granulocyte migration into lung parenchyma and, therefore, for lung injury to occur.

Adult↗
PubMed1999

Nuclear medicine imaging in fever of unknown origin.

Patients presenting with undiagnosed fever generally fall into two broad groups: firstly, those with co-existing disease or recent surgery, and secondly those with pyrexia but who are otherwise more or less well. A pyogenic cause for fever is significantly more likely in the first group as compared with the second. Radionuclide agents which are currently freely available for investigating undiagnosed fever are labelled leukocytes, 67Ga, and radiolabelled human immunoglobulin (HIG). Labelled leukocytes are generally preferable in the group with co-existing disease (occult infection), whereas 67Ga should be used in the second group, which can appropriately be called fever of unknown origin (FUO). The lower specificity of 67G can be perceived as an advantage in this context in view of the wide range of pathologies capable of causing FUO. The role of HIG in undiagnosed fever is unsettled. In general, 67Ga is more helpful than labelled leukocytes when the cause of an FUO is intrathoracic, although the reverse is likely to be true for intra-abdominal causes, partly because of physiological excretion of 67Ga in the gut. Postoperative fever is an indication for a leukocyte scan. Patients with haematological malignancies occasionally present as an FUO, but patients with chronic renal disease should be approached as occult infection. Investigating children with undiagnosed fever is a particularly difficult problem. For the future, we need agents which are particularly effective for localising chronic inflammation and, of secondary importance, agents able to distinguish between infective and non-infective causes of inflammation.

AIDS-Related Opportunistic Infections↗
PubMed1999

Effects of treatment of rheumatoid arthritis patients with an antibody against tumour necrosis factor alpha on reticuloendothelial and intrapulmonary granulocyte traffic.

The therapeutic effects of a monoclonal antibody against tumour necrosis factor alpha (TNFalpha) were evaluated objectively in 10 patients with rheumatoid arthritis by 111In-labelled granulocyte imaging before and after treatment, and compared with changes in granulocyte kinetics with respect to the liver, spleen and lungs. Anti-TNFalpha resulted in a decrease in the size of the whole-body pool of marginating granulocytes, as reflected by a significant increase in the 30 min intravascular recovery of labelled granulocytes from 40% (S.D. 10) to 47% (S.D. 16) of injected activity (P<0.02). The 111In contents of the spleen, liver and lungs were unchanged, so the origin of the increment in recovery was presumed to be a reduction in granulocyte margination in inflamed synovium, although this was not quantifiable. The sizes of the granulocyte pools in the liver and lungs, expressed as the 111In content of the organ per unit of circulating 111In-labelled cells, were not significantly different after treatment, but the splenic granulocyte pool decreased by 16% (S.D. 19) (P<0.05). Individual changes in the size of the splenic pool showed no significant correlation with corresponding changes in 30 min recovery or with corresponding indices of inflammation (24 h 111In-granulocyte joint activity and C-reactive protein). We conclude that anti-TNFalpha produces an obvious resolution in inflammatory joint activity that is accompanied by an increased circulating component of the total blood granulocyte pool, as a result of decreased margination at sites of inflammation. Anti-TNFalpha may also produce a specific decrease in splenic granulocyte pooling, independent of any anti-inflammatory effects, although a similar decrease in the lungs, which might be anticipated as a result of reduced cytokine-induced granulocyte activation, could not be detected.

Aged↗
PubMed1998

Bidirectional transport of iminodiacetic organic anion analogues between plasma and hepatocyte.

The kinetics of organic anions are well described and back-diffusion from hepatocyte to plasma is accepted. Although iminodiacetic (IDA) analogues, as organic anions, should also show bidirectional transport between hepatocyte and plasma, this has not been directly demonstrated heretofore. The aim of this study was to directly demonstrate back-diffusion and to quantify it in terms of its fractional rate constant. Kinetics of diethyl IDA were studied in three anaesthetised dogs in which femoral arterial and hepatic venous samples were obtained after injection of tracer into (a) a peripheral vein or (b) hepatic artery or portal vein. Arterial time-concentration curves were also compared between peripheral venous and either hepatic arterial or portal venous injections. Time-activity curves were recorded from regions of interest over the cardiac blood pool and peripheral hepatic parenchyma in 30 patients undergoing routine IDA hepatobiliary imaging with diethyl IDA or mebrofenin and fractional rate constants of clearance of IDA from the hepatocyte compared between compartmental and deconvolution analyses. After peripheral injection in dogs, there was an early arteriovenous concentration gradient across the liver indicating an hepatocyte extraction fraction in the three animals of 0.9, 0.8 and 0.6. The net extraction fraction decreased exponentially over 40 min. Time-concentration curves from hepatic vein and femoral artery were virtually superimposed following intrahepatic injections. Peripheral arterial curves, however, had different shapes according to whether injections were intrahepatic or peripheral, and were consistent with significant back-diffusion. In clinical studies, the blood disappearance curves were fitted as the sum of two exponentials and the liver curves as the difference of two exponentials (with rate constants denoted alpha1h and alpha2h). Based on compartmental analysis of the blood curves, the sum of the fractional rate constants of tracer movement from hepatocyte to bile canaliculus (k32) and to plasma (k12) was similar to and correlated with the rate constant, alpha, of the hepatocyte impulse response function (r=0.62, n=30, P<0.001). In contrast, alpha1h and alpha2h were respectively clearly greater and smaller than alpha. Moreover, neither of these hepatic rate constants correlated with alpha. Diffusion of IDA from hepatocyte to blood is significant and even in the presence of normal liver function accounts for about 50% of IDA transport out of the hepatocyte. It should be taken into account in pharmacokinetic studies based on either compartmental or deconvolution analysis.

Adult↗
PubMed1998

Analysis of intrapulmonary right to left shunt in the hepatopulmonary syndrome.

BACKGROUND/AIMS: Severe hypoxaemia in patients with chronic liver disease in the absence of intrinsic lung disease, the hepatopulmonary syndrome, is associated with pulmonary vascular dilatation and may be an indication for liver transplantation. Divergence between two methods of measuring right to left shunt (radiolabelled albumin macroaggregates and 100% oxygen breathing) has been described, but the mechanism and reason for the inter-patient variability for this shunt difference are not well understood. METHODS: Eight hepatopulmonary syndrome patients were studied, with characteristic pulmonary diffusion abnormalities (carbon monoxide transfer factor 41+/-5 (mean+/-SE)% predicted) and significant decreases in arterial oxygen saturation (%) on standing vs. supine (-10%+/-3) and on exercise vs. rest (-15%+/-2). All had hypoxaemia at rest (arterial oxygen tension 8.2+/-0.6 kPa), partially corrected by breathing 100% oxygen (48.2+/-8.8 kPa). Pulmonary angiography was performed and right to left shunt measured by two independent methods: (a) 100% oxygen breathing and (b) i.v. injection of radiolabelled microspheres. RESULTS: Measurement of right to left shunt with 99mTc-labelled albumin macroaggregates confirmed significant intrapulmonary microvascular dilatation, i.e. an "anatomical" shunt equalling 32+/-4% of cardiac output. Shunt measurements made simultaneously by the classical 100% oxygen technique were significantly smaller (19+/-3%, p=0.01). For individuals, the difference between the 99mTc-albumin macroaggregate shunt and the 100% oxygen shunt ranged from 2% to 30% absolute, convergence suggesting larger shunt channels (pure anatomical shunt) and divergence representing a combination of anatomical shunt and alveolar-capillary diffusion limitation (smaller microvascular channels). CONCLUSIONS: Hypoxaemia in the hepatopulmonary syndrome may be due functionally either to right to left shunting or to diffusion limitation, depending upon the degree of dilatation of the pulmonary microvessels.

Adult↗
PubMed1998

Bimodal granulocyte transit time through the human lung demonstrated by deconvolution analysis.

The lungs are an important site of granulocyte pooling. The aim of the study is to quantify pulmonary vascular granulocyte transit time using deconvolution analysis, as has previously been performed to measure pulmonary red cell transit time. Granulocyte and red cell studies were performed in separate groups of patients. Both cell types were labelled with Tc-99m, which for granulocyte labelling was complexed with hexamethylpropyleneamine oxime (HMPAO). The red cell impulse response function (IRF) was monoexponential with a median transit time of 4.3 s. The granulocyte IRF was biexponential in 19 of 22 subjects, 18 of whom had systemic inflammation (inflammatory bowel disease, systemic vasculitis or graft-vs-host disease) and four were controls without inflammatory disease. The median transit time of the fast component ranged from 20 to 25 s and of the slow component 120-138 s in the four patient groups. The fraction of cells undergoing slow transit correlated significantly with (a) mean granulocyte transit time and (b) the fraction showing shape change in vitro. We conclude that granulocyte transit time through the pulmonary circulation is bimodal and that shape-changed (activated) cells transit more slowly that non-activated cells. The size of the fraction undergoing slow transit is closely related to mean granulocyte transit time and is an important determinant of the size of the pulmonary vascular granulocyte pool.

Cell Movement↗
PubMed1998

Just how big is the pulmonary granulocyte pool?

1. It is widely believed that a large fraction of the blood granulocyte population is located in the pulmonary circulation. 2. Evidence in favour of this belief is based on several independent and complementary techniques including studies of granulocyte deformability in relation to pulmonary capillary diameter, isolated perfused lungs, direct videomicroscopic observations, cellular and capillary morphometry, physiological studies and labelled blood cell kinetics. 3. Inconsistencies in this body of evidence can be identified and traced in many cases to doubts concerning the physiological integrity of labelled granulocytes. 4. In addition to the lungs, other regions of the body undoubtedly pool granulocytes, and there is good quantitative evidence, based mainly on clinical studies, pointing to the liver, bone marrow and especially the spleen. 5. Clinical studies, furthermore, have generally not supported major granulocyte pooling in the lung, except in association with systemic inflammatory diseases, such as inflammatory bowel disease and systemic vasculitis. 6. Compromises based on technical considerations permit reconciliation of the literature, and an overall whole-body model of granulocyte distribution is proposed with which all the existing data are broadly compatible.

Animals↗