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Elephants were once widely distributed across the Indonesian island of Sumatra but now exist in small, isolated populations. Using the best data available on elephant occurrence, we aimed to (a) predict potential habitat suitability for elephants ( Elephas maximus sumatranus ) across the island of Sumatra and (b) model landscape connectivity among the extant elephant populations. We used direct sightings and indirect observations of elephant signs, as well as six remotely sensed proxies of surface ruggedness, vegetation productivity and structure, and human land use and disturbance, to model habitat suitability in a Google Earth Engine (GEE) environment. We validated the habitat suitability prediction using 10-fold spatial block cross validation and by calculating the area under the precision-recall curve (AUC-PR), sensitivity, and specificity for each model iteration. We also used a geolocation dataset collected from global positioning system (GPS) collars fitted on elephants as an independent validation dataset. Models showed good predictive performance with a mean AUC-PR of 0.73, sensitivity of 0.76, and specificity of 0.68. Greater than 83% of the independent GPS collar geolocations were located in predicted suitable habitat. We found human modification, surface ruggedness, and normalized difference vegetation index to be the most important variables for predicting suitable elephant habitat. Thirty-two percent, or 135,646 km 2 , of Sumatra's land area was predicted to be suitable habitat, with 43 patches of suitable habitat located across Sumatra. Areas with high connectivity were concentrated in the Riau and North Sumatra provinces. Though our analysis highlights the need to improve the quality of data collected on Sumatran elephants, more suitable habitat remains on Sumatra than is used by known populations. Targeted habitat conservation, especially of the suitable habitat in and around the Lamno, Balai Raja, Tesso Tenggara, Tesso Utara, Bukit Tigapuluh, Seblat, Padang Sugihan, and Bukit Barisan Selatan ranges, may improve the long-term viability of this critically endangered species., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Participatory research approaches have brought to the forefront the ethical obligations that researchers have towards underserved communities. We describe how a community-academic partnership used community-based participatory research principles and structure to develop a human subjects research protocol and to address the ethical concerns community stakeholders had regarding maternal mental health research with Black women.

Excited delirium syndrome (ExDS) is defined by marked agitation and confusion with sympathomimetic surge and incessant physical struggle, despite futility, which may lead to profound pathophysiologic changes and sudden death. Severe metabolic derangements, including lactic acidosis, rhabdomyolysis, and hyperthermia, occur. The pathophysiology of excited delirium is a subject of ongoing basic science and clinical research. Positive associations with ExDS include male gender, mental health disorders, and substance abuse (especially sympathomimetics). Excited delirium syndrome patients often exhibit violent, psychotic behavior and have "superhuman" strength which can result in the patient fighting with police and first responders. Continued struggle can cause a patient with ExDS to experience elevated temperature (T) and acidosis which causes enzymes to fail, leading to sudden death from cardiovascular collapse and multi-system organ failure. Therefore, effective early sedation is optimal to stop this fulminant process. Treatment of ExDS must be focused on rapidly, safely, and effectively sedating the patient and providing intensive, supportive care. Benzodiazepines, like midazolam, may not be ideal to sedate ExDS patients since their onset takes several minutes, and their side effects include loss of airway control and respiratory depression. Injectable antipsychotic medications have a relatively slow onset and may cause prolongation of the QTc interval. Ketamine is the ideal medication to sedate patients with ExDS. Ketamine has a rapid, predictable onset within three to four minutes when given by intramuscular (IM) injection. It does not adversely affect airway control, breathing, heart rate, or blood pressure (BP). In this retrospective case series, prehospital scenarios in which ExDS patients received ketamine by paramedics for sedation, and their subsequent treatment in the emergency department (ED) and hospital, are described. It is demonstrated that ketamine administered by paramedics in the prehospital setting of a community hospital based Emergency Medical Services (EMS) system is a safe and effective treatment for ExDS. Scaggs TR , Glass DM , Hutchcraft MG , Weir WB . Prehospital ketamine is a safe and effective treatment for excited delirium in a community hospital based EMS system. Prehosp Disaster Med. 2016;31(5):563-569.

Objective: The objective was to investigate the hypothesis that lymphovenous communications, which allow lymph proteins to access peripheral blood without first entering the thoracic duct, open in patients with abnormal lymphatic function., Methods: Routine lymphoscintigraphy of 182 patients, including 27 without clinical evidence of lymphedema (controls), was performed immediately and 45 and 150 minutes after subcutaneous injection of technetium Tc 99m nanocolloid into both feet. Counts per pixel in a region of interest over the liver (L) were divided by total counts in bilateral ilioinguinal nodes (N) at 45 minutes (L/N45) and 150 minutes (L/N150). If all activity leaving ilioinguinal lymph nodes entered the thoracic duct, these L/N ratios would be similar from patient to patient., Results: Eight patients were excluded because of immediate liver activity suggesting inadvertent intravascular injection of tracer. In controls (group 1), L/N150 displayed a normal distribution with mean (± standard deviation) of 0.16 (0.09) × 10(-4) pixels(-1). Patients with L/N150 >0.34 × 10(-4) pixels(-1) (ie, 0.16 + 2 standard deviations) were assumed to have lymphovenous communications. Of 34 patients with clinical evidence of lymphedema but with normal findings on lymphoscintigraphy (group 2), 3 (9%) had lymphovenous communications; of 114 with abnormalities on lymphoscintigraphy (group 3), 43 (38%) had lymphovenous communications (P = .001). N45/150 was significantly higher than L45/150 in all four groups, indicating arrival of activity in nodes before the liver. Abnormal features of lymphoscintigraphy-lymph transport delay, popliteal node visualization, and diversion of lymph through the skin-showed no association with L/N ratios., Conclusions: Lymphovenous communications exist in about one-third of patients with abnormalities detected on lymphoscintigraphy. The timings of tracer arrival in the liver and lymph nodes is consistent with lymphovenous communication within lymph nodes themselves., (Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Breast cancer-related lymphoedema (BCRL) is a result of interaction between several pathophysiological processes, and is not simply a 'stopcock' effect resulting from removal of axillary lymph nodes. The aim of this study was to test the hypothesis that there is a constitutional 'global' lymphatic dysfunction in patients who develop BCRL., Methods: Lower-limb lymphoscintigraphy was performed in 30 women who had undergone axillary lymph node dissection at least 3 years previously, of whom 15 had BCRL and 15 did not. No patient had any clinical abnormality of the lower limb. The control group comprised 24 women with no history of cancer or lower-limb lymphoedema. (99m) Tc-Nanocoll was injected subcutaneously into the first webspace of each foot, followed by whole-body imaging. Scans were reported as abnormal if there was delay in lymph transport or rerouting through skin or deep system. Quantification was expressed as the percentage injected activity accumulating in ilioinguinal nodes., Results: Mean(s.d.) ilioinguinal nodal accumulation at 150 min was significantly lower in women with BCRL than in those without (2·7(2·5) versus 5·9(4·8) per cent respectively; P = 0·006). Abnormal findings on lower-limb lymphoscintigraphy were observed in 17 of the 30 patients: ten of the 15 women who had BCRL and seven of the 15 who did not. None of the 24 control subjects had abnormal scan findings., Conclusion: Women with BCRL had reduced lower-limb lymph drainage, supporting the hypothesis of a predisposition to BCRL. A surprisingly high proportion of patients with breast cancer also demonstrated lymphatic dysfunction, despite clinically normal lower limbs. Possible explanations could be a systemic effect of breast cancer or its treatment, or an unidentified association between breast cancer and lymphatic dysfunction., Registration Number: ISRCTN84866416 ( http://www.isrctn.com)., (© 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Purpose: To determine how often lymphatic dysfunction is bilateral when, clinically, lymphedema appears unilateral., Methods: Lymphoscintigraphy was performed after subcutaneous Tc-99m-nanocolloid injection in the first webspaces of both feet. The percentage of injected radioactivity accumulating in the ilioinguinal regions was recorded in dedicated images separately acquired at 60 and 180 minutes after injection., Results: Within a consecutive series of 204 patients, 74 had unilateral clinical lymphedema of whom 68 had abnormal scintigraphy. Of these 68 patients, 46 had unilateral abnormal scintigraphy affecting the clinically abnormal limb, but 20 patients had bilateral abnormal scintigraphy and 2 had unilateral abnormal scintigraphy in the clinically unaffected limb. Thus, 32% (22/68) of patients in whom clinical lymphedema appeared to be unilateral, nevertheless, had abnormal scintigraphy in the clinically normal limb. Twenty-nine patients had no clinical evidence of lymphedema in either limb and were scintigraphically normal bilaterally. Mean ilioinguinal nodal accumulation at 180 minutes in the 44 limbs of 22 of these clinically and scintigraphically normal patients (dedicated ilioinguinal imaging was not performed in all patients) was 13.1% (standard deviation, 8.8%), higher (P = 0.02) than the mean value of 9.3% (standard deviation, 5.0%) in the clinically and scintigraphically normal contralateral limbs of 39 patients with unilateral clinical lymphedema., Conclusions: In the presence of unilateral lymphedema, the contralateral limb is often also abnormal. On lymphoscintigraphy, therefore, care should be taken before diagnosing unilateral lymphatic dysfunction. Quantification should be included in routine lymphoscintigraphy, as reduced ilioinguinal nodal accumulation may be the only apparent abnormality.

Objective: The objective of our study was to examine the frequency and significance of visualization of popliteal nodes during lymphoscintigraphy for the investigation of lower extremity swelling., Materials and Methods: Technetium-99m-labeled nanocolloid was injected subcutaneously in the first web spaces of both feet of 204 consecutive patients (69 males, 135 females; age range, 11-79 years) undergoing routine, clinically indicated lymphoscintigraphy; imaging was performed 5, 45, and 150 minutes after injection. The patients were asked not to undertake any vigorous exercise between the injection and completion of imaging., Results: No popliteal nodes were visualized in 29 patients in whom there was no evidence of lymphedema on clinical or lymphoscintigraphic examination (group 1). Unilateral or bilateral popliteal nodes were visualized in 10 of 39 patients (25.6%) with clinical evidence of lymphedema but normal lymphoscintigraphy findings (group 2) (p < 0.005 vs group 1). In 136 patients with clinical evidence of lymphedema and abnormal lymphoscintigraphy findings (group 3), unilateral or bilateral popliteal nodes were visualized in 59 (43.4%) (p < 0.0001 vs group 1). Popliteal nodes were visualized in 40 of 73 limbs with "dermal backflow" (54.8%) and 42 of 335 limbs without dermal backflow (12.5%) (p < 0.0001)., Conclusion: Popliteal node visualization after subcutaneous foot web space injection is an important sign of abnormal lymphatic function in patients with clinical lymphedema of the lower extremities.

Introduction: The slope-only technique for measuring glomerular filtration rate (GFR) relies on extracellular fluid volume (ECV) remaining within narrow limits. Although this requirement is met in healthy individuals, ECV may deviate or vary more in patients with abnormal renal function., Methods: We examined the correlation between surface area-scaled ECV and GFR, and their coefficients of variation (CVs), measured from simultaneous, multisample clearances of 51Cr-EDTA and iohexol in 20 healthy volunteers and 60 patients with a range of renal functions. We also compared scaled GFR and ECV, and their CVs, measured from three-sample, slope-intercept clearance of 51Cr-EDTA in 921 patients routinely referred for GFR measurement., Results: In the 80 participants undergoing multisample, dual-indicator clearance, there was no correlation between GFR measured with one indicator and ECV measured with the other. CVs of GFR in the 60 patients were 48.1 and 44.6% for 51Cr-EDTA and iohexol, respectively, but the CVs of ECV were only 12.3 and 15.4%. These differences were less marked in the healthy participants with corresponding CVs of 13.9 and 14.9% for GFR, and 11.7 and 12.2% for ECV. There was no correlation between scaled GFR and ECV in patients having slope-intercept clearance; CVs of GFR and ECV were 32.4 and 17.8%, respectively., Conclusion: In unselected patient populations, there is no correlation between GFR and ECV. The CV of ECV is slightly higher in patients than healthy individuals but, in both, is less than the CV of GFR. These data do not detract from the use of slope-only GFR.

Background: In adults, dosages of some anaesthetic agents are based on lean body mass (LBM) rather than body weight. Our aim was to derive an equation for estimating LBM in children., Methods: Patients comprised three groups: prospective kidney transplant donors from two separate centres (centres 1 and 3) and children referred to a further centre (centre 2) for the routine clinical measurement of glomerular filtration rate (GFR). GFR and extracellular fluid volume (ECV) were measured using Cr-51-EDTA. LBM was directly estimated (eLBM) in adults using an equation based on height and weight. ECV in children was estimated (eECV) from another equation based on height and weight, converted to eLBM using the relationship between eLBM and ECV determined in the adults from centre 1 and then compared with adult data from centre 3., Results: In children, the ratio of eECV to ECV was 1.04 (SD 0.18). In centre 1, eLBM (kg) was 3.81 (SD 0.55) times greater than ECV (litres) in men (n=50) and 3.77 (0.77) times greater in women (n=51). eLBM in children was therefore derived by multiplying eECV by 3.8. In children, eLBM showed a close linear correlation with measured ECV (eLBM=3.50ECV+2.0; R(2)=0.857), similar to adults (eLBM=2.82ECV+14.5; R(2)=0.582). In all groups, eLBM/weight correlated inversely with weight., Conclusions: In terms of the relationships between eLBM, ECV, and weight, children are similar to adults. Therefore, drug dosage in children should also be based on eLBM rather than weight.

Aims: Cancer patients may have extracellular fluid volume (ECV) abnormalities that potentially invalidate glomerular filtration rate (GFR) measured using the slope-intercept technique. The aim was to test this concern by measuring ECV in cancer patients in comparison with noncancer patients and healthy kidney donors., Methods: GFR was measured with Cr-EDTA and the slope-intercept technique in patients from two hospitals, the first using three samples (540 adults, including 382 with cancer, and 124 children, including 40 with cancer) and the second using four samples (256 adults, including 132 with cancer and 75 donors), scaled to body surface area (BSA) of 1.73 m and corrected using Brochner-Mortensen's equations (GFR/BSA). GFR/ECV was measured from the exponential rate constant with an appropriate one-compartment correction. ECV/BSA was calculated as the quotient, GFR/BSA:GFR/ECV. ECV was also expressed in adults in relation to lean body mass and in children as a fraction of ECV estimated from height and weight (eECV)., Results: In men from both centres, neither ECV/BSA nor ECV/lean body mass showed an increase in cancer patients. In women from both centres, however, they were both significantly higher in cancer patients than in noncancer patients and, in centre 2, than in donors. In children from centre 1, ECV/BSA, but not ECV/eECV, was significantly higher in cancer patients., Conclusion: ECV is expanded in female cancer patients but not male cancer patients. ECV may be expanded in children with cancer but the recorded difference in ECV/BSA is probably related to differences in patient size and a nonproportionate relationship between ECV and BSA.

Aims: The Jacobsson single-sample equation for measuring glomerular filtration rate (GFR) after bolus injection is based on two factors of questionable theoretical validity for correcting the single-compartment assumption. The aims were to redevelop a more transparent equation, show its fundamental similarity with 'slope-only' GFR and compare it with the original equation and with slope-only GFR., Methodology: The modified Jacobsson equation is k = (1/t).ln[V(t)/V(0)], where k is the rate constant of the terminal exponential and V(0) and V(t) are distribution volumes at times 0 and t. V(0) exceeds extracellular fluid volume (ECV): that is k' = (1/t).ln[V(t)/ECV], where k' > k. Moreover, [GFR/ECV] >k (= k + [15.4.k(2)]). The ratio k/k' was determined in 476 patients to calculate single-sample k (3 or 4 h post-injection). Slope-only and single-sample GFR/ECV were measured using Cr-51-EDTA in 105 further studies, multiplied by ECV (estimated from weight), scaled to 1.73 m(2) and compared with GFR/1.73 m(2) from the original Jacobsson equation against reference multi-sample GFR/1.73 m(2) simultaneously and independently measured with iohexol., Results: The relation between k and k' was linear. k/k' was 0.827 at 3 h and 0.864 at 4 h. There was no difference in bias or precision between the original Jacobsson and modified equations. In both, precision was better than slope-only GFR/BSA. When GFR remained scaled to ECV, slope-only GFR showed marginally better precision against reference GFR/ECV., Conclusions: Single-sample and slope-only techniques give GFR as k. Although the theory of the modified Jacobsson equation is more transparent than the original equation, it gives the same result. It is, however, easier to use.

Objective: To examine body surface area (BSA) for scaling extracellular fluid volume (ECV) in obesity. ECV varies less than glomerular filtration rate (GFR) in a clinical population and was therefore used as a surrogate for GFR on the grounds that if BSA is unsuitable for scaling GFR, it will also be unsuitable for ECV., Methods: GFR was measured in 917 patients using (51)Cr-EDTA. GFR scaled to ECV was measured exclusively from the slope rate constant. ECV was calculated as GFR divided by GFR/ECV., Results: BSA correlated strongly with body mass index (BMI). ECV correlated strongly with BSA but the intercept was significantly lower than zero, indicating a disproportionate relation. ECV/BSA correlated with BSA but not with BMI. ECV in obese subjects was significantly less than in non-obese subjects individually matched for BSA. ECV/BSA was similar between obese and lean subjects matched for GFR/ECV and height., Conclusions: For subjects of similar BSA, a high BMI decreases ECV (the 'obesity effect'). Subjects with high BMI generally have high BSA, which tends to increase ECV/BSA because of the disproportionate relation between ECV and BSA (the 'BSA effect'). These opposing effects serendipitously and erroneously create the impression that BSA is suitable for scaling ECV (and by implication, GFR) in obesity., (2009 S. Karger AG, Basel.)

Background/aims: To compare body surface area (BSA) with lean body mass (LBM) for scaling extracellular fluid volume (ECV) and glomerular filtration rate (GFR)., Methods: Phase 1: Total body water (TBW), bromide space and LBM were measured with (3)H-water, (77)Br and dual X-ray absorptiometry, respectively, in 6 healthy adults. Phase 2: ECV and GFR were measured with (51)Cr-EDTA in 95 healthy adults and 56 children (0.5-13 years). ECV was calculated as GFR divided by GFR/ECV, both corrected for the one-compartment assumption. LBM was estimated (eLBM) in adults from height and weight and in children using a height/weight formula for estimating ECV and a constant derived from a separate adult population relating ECV to eLBM., Results: Phase 1: LBM and BSA correlated closely with TBW and bromide space. With LBM, the regressions passed through the origin, but with BSA, the intercepts were significantly below zero. Phase 2: GFR/BSA and ECV/BSA were higher in men than women but no difference was recorded in GFR/eLBM, GFR/ECV or ECV/eLBM. ECV showed a linear relation with eLBM and a non-linear relation with BSA. GFR/BSA and ECV/BSA correlated significantly with BSA but neither GFR/eLBM nor ECV/eLBM correlated with eLBM., Conclusion: eLBM is preferable to BSA for scaling GFR and ECV.

Obesity has been suggested as a risk factor for chronic kidney disease. However, it has also been suggested that the association between obesity and impaired glomerular filtration rate (GFR) arises from the invalid use of body surface area (BSA) for scaling. This study assesses the effect of obesity on GFR by comparing the age-dependent decline in obese (body mass index (BMI) >30 kg/m(2); n=149) and non-obese patients (n=589), aged >30 years, referred for measurement of GFR (Cr-51-EDTA and three blood samples). GFR was scaled to a BSA of 1.73 m(2) (GFR/BSA) and extracellular fluid volume of 13 l (GFR/ECV), both corrected for the one-compartment assumption. When non-obese patients were categorized into 10-year age brackets (from 31 to >70), GFR/BSA and GFR/ECV declined from 92 ml per min per 1.73 m(2) and 95 ml per min per 13 l, respectively, at 31-40 years to 58 and 59 at >70. The declines in obese patients were similar with corresponding values of 88 ml per min per 1.73 m(2) and 97 ml per min per 13 l at 31-40 and 57 and 59 at >70 years. Linear regression analysis of non-categorized data from age 40 years showed rates of decline slightly slower in the obese (0.82 vs 0.95 ml per min per 1.73 m(2) per year and 0.87 vs 1.02 ml per min per 13 l per year). No effect of obesity on renal function was shown. Scaling to BSA did not distort the results.

Unlabelled: Multidrug resistance (MDR) due to expression of a membrane-associated permeability glycoprotein (P-glycoprotein [Pgp]) prevents successful cytotoxic chemotherapy for breast cancer. Identification of MDR would facilitate selection of chemotherapy regimens and MDR modulators. This study aimed to evaluate (99m)Tc-sestamibi imaging for predicting overexpression of Pgp in primary breast cancer and to measure the efficacy of toremifene, the MDR modulator, in vivo., Methods: Twenty patients with untreated breast cancer had (99m)Tc-sestamibi imaging 20 and 120 min after tracer injection before and after a 3-d course of toremifene (780 mg/d). Tumor samples were obtained during surgery for correlation of imaging and Pgp immunohistochemistry., Results: Sixteen of 20 tumors were visualized with sestamibi. Before toremifene, there was a significant inverse correlation (Spearman rank correlation coefficient [R(S)]) between staining intensity, based on the anti-Pgp monoclonal antibodies C494 and C219, and the tumor-to-background ratio (T/B) at 120 min (R(S) = -0.85; P < 0.001 and R(S) = -0.71; P < 0.001, respectively). However, the correlation between the T/B and immunohistochemistry at 20 min was significant only for C494 (R(S) = -0.57; P < 0.01). Similarly, before toremifene, there was an inverse correlation between staining intensity and the change in the T/B between 20 and 120 min (R(S) = -0.77; P < 0.001 and -0.75; P < 0.001 for C494 and C219). After toremifene, an inverse correlation between staining intensity and the T/B was seen only at 120 min and only with C494 (R(S) = -0.68; P < 0.01). However, the change in the T/B between 20 and 120 min correlated significantly with staining intensity for C494 and C219 (R(S) = -0.68; P < 0.01 and -0.7; P < 0.01 for C494 and C219, respectively). Toremifene did not significantly alter the overall T/B at either 20 or 120 min when data were compared before and after toremifene. Nevertheless, at 120 min, 8 of 8 tumors with low Pgp expression showed reduced uptake after toremifene, whereas 5 of 6 tumors with strong expression showed increased uptake (P < 0.003). Moreover, there was a significant correlation between the change in the T/B and staining intensity with C494 (R(S) = 0.59; P < 0.05) and C219 (R(S) = 0.56; P < 0.05) at 120 min but not at 20 min., Conclusion: (99m)Tc-Sestamibi accumulation in breast cancer correlates with Pgp expression. Toremifene has a dual effect on this accumulation, increasing it through an inhibitory effect on Pgp while at the same time reducing it by a direct competition with sestamibi. The latter implies that in response to Pgp modulation the efflux of various agents may be affected differently.

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.

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.

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.

The aim of this study was to evaluate an index of divided renal function based on the quantification of the ureteric jets seen on colour Doppler ultrasound of the bladder. Thirty-one patients attending for scintigraphic renography underwent colour Doppler ultrasound with video recording for 5 min. Divided renal function was calculated as the proportion of jets from the right-sided orifice ('jet index'). This was compared with the corresponding 'scintigraphic index' found using Patlak-Rutland graphical analysis. Absolute discrepancies were calculated. Twenty-eight of thirty-one (90%) of studies were diagnostic for the calculation of jet indices. The mean jet index was 52% (n=28, SEM=5.8%) compared to a mean scintigraphic index of 54% (n = 28, SEM = 4.0%). The two scores were correlated, with a correlation coefficient of 0.72 and the median absolute difference between the two scores was 7.7%. Forty-three per cent (12/28) of subjects had discrepancies in the two scores of 5% or less. The score differences, however, showed a highly skewed distribution with 32% (9/28) subjects showing discrepancies over 20%. This discordant group (> 20% difference) included three patients with functional pelviureteric obstruction, one with a pelvic mass and one with an underfilled bladder. Two patients with very poor quality jets had impaired renal function. In one case, the index improved after angioplasty for renal artery stenosis. This simple test is a useful adjunct to urinary tract ultrasound but should be interpreted alongside evidence of renal obstruction, and complements rather than replaces existing tests.

We have developed and validated a method for imaging inflammation using a monoclonal antibody (1.2B6) against E-selectin, an endothelial-cell specific adhesion molecule. This study was undertaken to compare 111In-1.2B6 with 99Tcm-labelled non-specific IgG (99Tcm-HIG) in the detection of synovitis in 11 patients with rheumatoid arthritis (RA). Imaging was performed 4 h and 20-24 h post-injection (pi) of 555 MBq 99Tcm-HIG and 15 MBq 111In-1.2B6. Scintigraphic results were compared with clinical scores of joint involvement. Joint uptake was semiquantitated. The scintigraphic appearances with both tracers correlated well, although 111In-1.2B6 at 24 h showed the highest detection rate. Taking joint tenderness or swelling as evidence of clinical activity, the sensitivity of 111In-1.2B6 at 4 h and 24 h was 69% and 82%, respectively, compared with 69% and 62% for 99Tcm-HIG. 111In-1.2B6 also displayed abnormal activity over a number of joints that appeared silent on clinical examination. Joint-to-soft tissue ratios were higher for 111In-1.2B6 at 24 h (4.0 +/- 1.9; p < 0.0001 vs all) than at 4 h (2.4 +/- 1.4) or than for 99Tcm-HIG at 4 h and 24 h (1.6 +/- 0.5 and 2.3 +/- 0.7, respectively). Net 111In counts over joints increased significantly between 4 h and 24 h (mean change: 54 +/- 40%). This study demonstrates that 111In-1.2B6 scintigraphy is a sensitive method by which to assess RA activity and that targeting is more intense and specific than using 99Tcm-HIG. However, the optimum time for 111In-1.2B6 scintigraphy is 24 h whereas good results are already obtained with 99Tc-HIG at 4 h pi. Current efforts are directed at developing 99Tcm-labelled 1.2B6 for imaging endothelial activation.

Involvement of the nervous system is an uncommon and underdiagnosed complication of sarcoidosis. We used gallium single photon emission computed tomography (SPECT) to define areas of meningeal involvement in a patient with neurosarcoidosis. This technique may be of value in the assessment of patients with sarcoidosis and suspected central nervous system involvement.

Visual assessment of renal blood flow from renography is usually achieved by comparing the count rate from the kidney with that of the spleen during the first pass of the radiopharmaceutical agent. This is not justifiable if splenic blood flow is abnormal. In nine subjects without evidence of renal or other significant disease, the mean ratio of the slopes of the first pass curves over the left kidney and the spleen was 1.7 (SD 0.32). However, an additional patient, a 67-year-old female with type-II cryoglobulinaemia, illustrated the need for caution when using this approach. Her splenic blood flow was significantly elevated, resulting in a kidney/spleen slope ratio of only 0.66, even though her renal function was thought to be normal.

We have developed a technique for measuring the pulmonary granulocyte pool (PGP) as a fraction of the whole body total blood granulocyte pool (TBGP). The technique "captures" a dose of 99mTc-labeled granulocytes in a region of interest (ROI) over the lung during first pass by integrating an input time-activity curve from an ROI over the pulmonary artery, superior vena cava, or right ventricle. The ratio of the estimated first-pass count rate and the count rate in the same lung ROI after equilibration of the cells between the circulating and pulmonary pools (15-30 min) represents the PGP/TBGP. The technique was validated in eight subjects by using 99mTc-labeled macroaggregated human serum albumin. With corrections for background and injected doses, the ratios of first-pass granulocyte-to-macroaggregated human serum albumin count rates given by the three input ROIs were close to unity [superior vena cava 0.98 +/- 0.079 (SD), right ventricle 1.01 +/- 0.070, and pulmonary artery 0.97 +/- 0.073]. Significant increases in PGP/TBGP were demonstrated in systemic inflammation. Thus, in patients with inflammatory bowel disease, it was 0.22 +/- 0.07 (n = 7) compared with 0.08 +/- 0.01 (n = 5) in control subjects. It was also elevated in patients with systemic vasculitis (0.34 +/- 0.07; n = 5), in transplant recipients (0.33 +/- 0.08; n = 5), and in patients with osteomyelitis (0.15 +/- 0.06; n = 4). We conclude that this is a valid technique for quantifying the PGP that is expanded in several conditions associated with systemic inflammation.