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Peter S Mortimer

Publications and source records attributed to Peter S Mortimer.

16 recordsLinked to original sources
PubMed2006

A quantitative lymphoscintigraphic evaluation of lymphatic function in the swollen hands of women with lymphoedema following breast cancer treatment.

In BCRL (breast cancer-related lymphoedema), arm swelling is unevenly distributed and some regions are partly or entirely spared. In particular, the hand may or not be swollen, but when involved functional impairment can be substantial. We have found previously that, when the ipsilateral hand is spared of swelling (in a limb with swelling proximal to the hand), the local lymph drainage rate constant (k) is at least as high as in the contralateral hand, contrary to the traditional 'stopcock' concept of reduced lymph drainage from the whole limb. In the light of this finding, we have investigated lymph drainage in the hands of eight women with BCRL and moderate-to-severe hand swelling, using gamma-camera quantitative lymphoscintigraphy. Images showed pronounced superficial activity in the ipsilateral swollen arms of most patients, indicating dermal backflow. k for 99mTc-labelled hIgG (human IgG) measured over 5 h in the subcutis of the ipsilateral swollen hand was 34+/-24% less than in the contralateral hand (P=0.013). Activity measured in the ipsilateral swollen forearm increased progressively, but there was very little increase in the contralateral forearm, indicating retention of 99mTc-labelled hIgG in the swollen forearm. It is concluded that lymphatic function in the swollen hand is impaired, and that there appears to be two populations of women with BCRL, i.e. spared-hand and swollen-hand, irrespective of the cancer treatment received.

Aged↗
PubMed2006

Imaging of lymphatic vessels in breast cancer-related lymphedema: intradermal versus subcutaneous injection of 99mTc-immunoglobulin.

OBJECTIVE: The disordered physiology that results from axillary lymph node clearance surgery for breast cancer and that leads to breast cancer-related lymphedema is poorly understood. Rerouting of lymph around the axilla or through new pathways in the axilla may protect women from breast cancer-related lymphedema. The aim of the study was to compare intradermal with subcutaneous injection of technetium-99m ((99m)Tc)-labeled human polyclonal IgG (HIG) with respect to lymphatic vessel imaging. MATERIALS AND METHODS: Six women with breast cancer-related lymphedema underwent unilateral upper limb lymphoscintigraphy, using a web space injection of (99m)Tc-labeled HIG, after intradermal and subcutaneous injections on separate occasions. Multiple sequential images were obtained of the affected upper limb and torso over 3 hr on each occasion. Accumulation of activity in blood was quantified from venous blood samples taken from the opposite arm. RESULTS: Imaging after intradermal injection clearly showed discrete lymphatic vessels in five of six patients, in contrast to imaging after subcutaneous injection, which did not show any discrete vessels in any patient. Intradermal injection resulted in more rapid visualization of cutaneous lymph rerouting than subcutaneous injection in six of six patients. Recovery of injected (99m)Tc-labeled HIG in venous blood was greater after intradermal injection in six of six patients. CONCLUSION: In patients with breast cancer-related lymphedema, lymphatic vessels are more clearly depicted after intradermal than subcutaneous injection as a result of direct access of radiotracer to dermal lymphatics. This finding has implications for imaging lymphatic vessel regeneration and lymph rerouting.

Adult↗
PubMed2005

Regional distribution of epifascial swelling and epifascial lymph drainage rate constants in breast cancer-related lymphedema.

BACKGROUND: The view that breast cancer-related lymphedema (BCRL) is a simple, direct mechanical result of axillary lymphatic obstruction ('stopcock' mechanism) appears incomplete, because parts of the swollen limb (e.g., hand) can remain nonswollen. The lymph drainage rate constant (k) falls in the swollen forearm but not in the spared hand, indicating regional differences in lymphatic function. Here the generality of the hypothesis that regional epifascial lymphatic failure underlies regional swelling was tested. To do so, the regional distribution of epifascial swelling along the forearm was compared with that of epifascial (subcutis) k. METHODS AND RESULTS: Epifascial k (local lymph flow per unit distribution volume) was measured by quantitative lymphoscintigraphy of subcutaneous radiolabeled human immunoglobulin IgG in regions of maximal and minimal % swelling in the ipsilateral swollen forearm, and at matching sites in the contralateral nonswollen arm, in 11 women with BCRL. Swelling was maximal distally in 5 patients and proximally in 6. Proximal k, -0.085 +/- 0.025% min(-1) (mean +/- SD), was 27% bigger than distal k, -0.067 +/- 0.021% min(-1), irrespective of swelling (p = 0.02, two-way repeated measures ANOVA). k fell by 11% from -0.080 +/- 0.028% min(-1) in the nonswollen arm to -0.072 +/- 0.021% min(-1) in the swollen arm (p = 0.17, t test). Local epifascial k was not significantly lower, however, at sites of maximal swelling than minimal swelling, and k correlated positively with arm circumference. CONCLUSIONS: A systematic difference in lymph drainage along the axis of the forearm was demonstrated for the first time. Local differences in epifascial k did not, however, explain the regionality of swelling, in keeping with previous evidence that epifascial k does not correlate with differences in swelling between arms, whereas subfascial k does. The results lead to the rejection of the hypothesis that epifascial (cf. subfascial) lymph drainage rate constants govern epifascial swelling in human forearm.

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PubMed2005

Short-term effects of axillary lymph node clearance surgery on lymphatic physiology of the arm in breast cancer.

It is not known why some women develop breast cancer-related lymphedema (BCRL) of the arm, whereas others having similar treatment do not. We speculated that increased uptake of protein into local blood may protect against BCRL. Sixteen women were given bilateral subcutaneous hand webspace injections of polyclonal immunoglobulin (HIgG), (99m)Tc-HIgG on one side and (111)In-HIgG on the other, before and 3 mo after axillary clearance surgery. The rates of clearance of activity from the depot (k) and accumulation in central blood (b(contra)) were measured using a scintillation probe and bilateral antecubital vein blood sampling, respectively. Activity accumulating in blood ipsilateral to the injected side, in excess of central blood activity (b(ipsi)) was also calculated as a measure of local vascular uptake. The k correlated with b(contra), but neither changed in response to surgery. However, b(ipsi) for injections of (99m)Tc-HIgG into the affected arm increased in all seven patients in whom data were available (0.018 +/- 0.006 to 0.038 +/- 0.007%/min; P < 0.05); indeed, in five of these seven, b(ipsi) paradoxically exceeded b(contra), and none developed BCRL at 3-yr follow-up. We conclude that uptake of protein into local blood and/or proteolysis increases after axillary surgery and may protect against BCRL.

Adult↗
PubMed2004

Finding an optimal method for imaging lymphatic vessels of the upper limb.

Lymphoscintigraphy involves interstitial injection of radiolabelled particulate materials or radioproteins. Although several variations in the technique have been described, their place in clinical practice remains controversial. Traditional diagnostic criteria are based primarily on lymph node appearances but in situations such as breast cancer, where lymph nodes may have been excised, these criteria are of limited use. In these circumstances, lymphatic vessel morphology takes on greater importance as a clinical endpoint, so a method that gives good definition of lymphatic vessels would be useful. In patients with breast cancer, for example, such a method, used before and after lymph node resection, may assist in predicting the development of breast cancer-related lymphoedema. The aim of this study was to optimise a method for the visualisation of lymphatic vessels. Subcutaneous (sc) and intradermal (id) injection sites were compared, and technetium-99m nanocolloid, a particulate material, was compared with (99m)Tc-human immunoglobulin (HIG), which is a soluble macromolecule. Twelve normal volunteers were each studied on two occasions. In three subjects, id (99m)Tc-HIG was compared with sc (99m)Tc-HIG, in three id (99m)Tc-nanocolloid was compared with sc (99m)Tc-nanocolloid, in three id (99m)Tc-HIG was compared with id (99m)Tc-nanocolloid and in three sc (99m)Tc-HIG was compared with sc (99m)Tc-nanocolloid. Endpoints were quality of lymphatic vessel definition, the time after injection at which vessels were most clearly visualised, the rate constant of depot disappearance ( k) and the systemic blood accumulation rate as measured by gamma camera imaging over the liver or cardiac blood pool. Excellent definition of lymphatic vessels was obtained following id injection of either radiopharmaceutical, an injection route that was clearly superior to sc. Differences between radiopharmaceuticals were less clear, although after id injection, (99m)Tc-HIG gave images that were marginally but significantly better than those given by (99m)Tc-nanocolloid. Image quality correlated inversely with time after injection at which the best image was obtained, consistent with the notion that good vessel definition was dependent on a "narrow" bolus width. k was approximately three times higher after id injection than after sc injection but it was not significantly different between radiopharmaceuticals for either injection route. Intradermal (99m)Tc-HIG gave a cardiac blood pool signal that, over the first 60 min, increased about five times faster than that with sc (99m)Tc-HIG, but no clear difference was observed in the rate of increase in hepatic activity between id (99m)Tc-nanocolloid and sc (99m)Tc-nanocolloid. We conclude that id injection provides rapid access of radiotracers to lymphatic vessels, which is ideal for imaging lymphatic vessel morphology. (99m)Tc-HIG is marginally superior to nanocolloid for this purpose and, in drainage basins from which lymph nodes have been excised, is not handicapped by a potentially inferior ability, compared with radiocolloid, to image lymph nodes.

Female↗
PubMed2004

Local vascular access of radioprotein injected subcutaneously in healthy subjects and patients with breast cancer-related lymphedema.

UNLABELLED: The aim of the study was to use dual-isotope lymphoscintigraphy in healthy volunteers and women with breast cancer-related lymphedema (BCRL) to detect and quantify transport of radiolabeled protein from a subcutaneous injection depot to local blood vessels as a potential mechanism of protection against edema resulting from treatment to the axilla. METHODS: A total of 29 subjects and 18 women with a history of BCRL received bilateral subcutaneous injections of human IgG (HIgG) in the second dorsal web space of each hand, (99m)Tc-HIgG on one side and (111)In-HIgG on the other. In 8 further healthy subjects, epinephrine was administered with the labeled HIgG. Radioactivity at each depot was measured at regular intervals for a total of 3 h using a collimated sodium iodide scintillation detector, and radioactivity in venous blood sampled from both arms was measured using an automatic sample counter. Ipsilateral blood time-concentration curves were corrected for recirculating activity by subtraction of the simultaneous contralateral concentration, to define the component of ipsilateral blood resulting from local vascular access of radioprotein. Accumulation of activity in blood was expressed in relation to injected activity and activity that had left the depot and was calculated as a function of time-in systemic blood, by multiplying contralateral concentrations by an estimate of the subject's blood volume, and in ipsilateral blood, by using indicator dilution theory and an assumed forearm blood flow of 20 mL/min. RESULTS: (99m)Tc-HIgG and (111)In-HIgG behave almost identically with respect to depot clearance and accumulation in contralateral venous blood, with or without epinephrine, which reduced both depot clearance and blood accumulation rate. Moreover, a side-to-side correlation with respect to contralateral accumulation was present in healthy subjects, was not abolished by epinephrine, and was maintained in the face of asymmetric accumulation in BCRL. Contralateral accumulation of radioprotein was reduced in BCRL after injection into the affected side only when the hand was involved. In contrast to contralateral sampling, ipsilateral time-concentration and accumulation profiles were consistent with instability of (111)In-HIgG and rapid local vascular access of small amounts of protein-free (111)In. Experiments based on precipitation of protein with trichloroacetic acid confirmed relatively high levels of unbound ipsilateral (111)In, especially in samples obtained early after injection. Substantial accumulation of protein-bound (99m)Tc was observed in ipsilateral blood, with a time course similar to that of contralateral accumulation. Positive correlation between ipsilateral and contralateral blood (99m)Tc activity was observed at all time points, often significantly, in contrast to (111)In, for which it was negative at all time points. Ipsilateral accumulation of (99m)Tc adjusted for activity that had left the depot was unchanged with respect to the affected arm in BCRL patients. CONCLUSION: Whereas (111)In-HIgG and (99m)Tc-HigG are interchangeable for measurement of depot clearance and contralateral venous accumulation rates, ipsilateral sampling is much more sensitive to protein-free radionuclide and detects significant differences resulting from some instability of (111)In-HIgG. On the basis of (99m)Tc data, there appears to be substantial local vascular access of radioprotein within the arm, both in healthy subjects and in patients with BCRL, through either lymphaticovenous communications or direct transendothelial transport.

Arm↗
PubMed2003

Expansion of microvascular bed and increased solute flux in human Basal cell carcinoma in vivo, measured by fluorescein video angiography.

Human basal cell carcinoma (BCC) offers a unique opportunity to assess directly the microvascular abnormalities in a human cancer in vivo. Our objectives were to assess angiogenesis, perfusion, and changes in small solute exchange kinetics. The microcirculation of BCC and a normal (control) skin site was studied in 15 patients by laser Doppler fluximetry and videoangiography after rapid i.v. fluorescein injection. Microvascular morphometry was analyzed off line. Sodium fluorescein accumulation/clearance was recorded for 30 min, and fluorescence intensity (FI) was quantified by computer analysis of videotape image gray levels. In BCCs, the microvascular area fraction was 2.6-fold greater, microvessel length density 2.0-fold greater, average vessel image width 2.1-fold greater, and red cell flux 3.9-fold greater than in control sites (P < 0.01, paired t tests). The initial rate of rise of FI over 10 s was approximately 3-fold greater in BCC than control and correlated with vascular area fraction and red cell flux. Tissue then equilibrated faster in BCC, rate constant -(13.0 +/- 5.6) x 10(-3) s(-1) (mean +/- SD), than controls -(5.3 +/- 1.7) x 10(-3) s(-1), and plasma clearance was 2.6-fold higher in BCC than controls (P < 0.01, paired t test). Similarly, the rate constant of the subsequent clearance phase was approximately 2-fold greater in BCC, -(0.53 +/- 0.19) x 10(-3) s(-1), than controls, -(0.27 +/- 0.22) x 10(-3) s(-1) (P < 0.01). Removal rate constants were an order of magnitude slower than accumulation rate constants. The results demonstrate angiogenesis, increased perfusion, and a more rapid exchange of small solute in human BCC. FI itself is rejected as an index of permeability to small solutes (cf. 29) because it depends also on blood flow, endothelial area, microvascular volume, and interstitial fluid volume.

Aged↗
PubMed2003

Side-to-side symmetry of radioprotein transfer from tissue space to systemic vasculature following subcutaneous injection in normal subjects and patients with breast cancer.

Quantitative lymphoscintigraphy can be used for investigation of unilateral lymphatic disease of the limbs, such as breast cancer-related lymphoedema (BCRL). Previous studies have compared lymphatic function in the affected limb with that in the unaffected contralateral limb. This study aims to confirm that the assumption of pre-morbid symmetry, never previously demonstrated, is valid. A dual-isotope technique, with bilateral subcutaneous hand injection of polyclonal human immunoglobulin G (HIgG) labelled with either technetium-99m or indium-111, was performed on a total of 37 subjects. The use of two different labels, one for each limb, enabled comparison not only of the rate of clearance from the injection depot, but also of the rate of appearance in venous blood. Results demonstrate clear symmetry between the two arms with respect to both depot clearance and blood appearance rates, as well as the coupling between these two variables. In unilateral lymphatic disease, results of quantitative lymphoscintigraphy should be expressed in relation to the normal arm rather than to an independent control population.

Arm↗
PubMed2002

Quantification of lymphatic function for investigation of lymphedema: depot clearance and rate of appearance of soluble macromolecules in blood.

UNLABELLED: The object of this study was to develop a new technique for the quantitative measurement of lymphatic function. The rate of clearance of radiolabeled protein from a subcutaneous depot is supplemented by measurement of the appearance of the protein in venous blood. This initial study was performed on normal arms, with a view to subsequent clinical application such as in the investigation of women with breast cancer--related lymphedema (BCRL). METHODS: Fourteen healthy volunteers (12 women, 2 men) and 8 women awaiting surgery for breast cancer were recruited for the study. Each received subcutaneous depot injection of protein solution in the second dorsal web space of each hand, labeled with (111)In on one side and with (99m)Tc on the other side. Human serum albumin (HSA) was the protein used in the first 8 subjects and human polyclonal immunoglobulin G (HIgG) was used thereafter. The activity at each depot was measured at regular intervals using a collimated sodium iodide scintillation detector, and the activity in venous blood sampled from both arms was measured in an automatic sample counter. RESULTS: (99m)Tc-HSA cleared from the depot consistently faster than (111)In-HSA (P = 0.001). The proportions of radionuclide remaining bound to protein in venous blood were higher for (99m)Tc than for (111)In. HIgG displayed improved labeling stability for both nuclides, reflected in equal rates of clearance. Blood activity rose steadily after an early latent phase and for HIgG correlated strongly with the rate of clearance from the depot (P < 0.001). Marked variation between individuals was observed. CONCLUSION: A dual-isotope technique relies on identical behavior of the 2 radiopharmaceuticals used. This study shows that this is the case with respect to HIgG but not HSA. (99m)Tc-HSA cleared faster than (111)In-HSA and yet displayed better in vivo labeling stability. We conclude that (111)In dissociates from HSA in the depot but then becomes locally bound. Using HIgG, a close correlation was observed between the rates of clearance from the depot and the appearance in venous blood. This finding suggests that HIgG would be a suitable marker for subsequent dual-isotope studies on women with BCRL.

Adult↗
PubMedDate not supplied

The impact on resources of prevalence and nature of skin problems in a modern intensive haemato-oncology practice.

We undertook a randomised prospective observational study to identify the true prevalence of dermatological problems on an acute in-patient haemato-oncology unit treating patients with myeloma and leukaemia (median age 52 years), that could be used to plan for optimum dermatological servicing of such a unit. As a snap-shot, beds were randomly selected each week and the patients in them examined to identify the prevalence and identity of mucocutaneous problems for in-patients. Primary endpoints were the prevalence of integument reactions, prevalence and type of rash. Eighty-four leukaemia and myeloma patients were seen on 200 episodes. Integument changes were seen in 88% of episodes. Predictable changes such as hair loss (74%) and mucositis (38%) were seen commonly. Rashes were seen in 38% of episodes. The most common rash was palm and sole erythema (10% of all episodes) which was associated with allogeneic BMT (20%; p=0.0009). Flexural erythema with subsequent desquamation occurred in 4% of episodes, more commonly in males (p=0.09). Drug allergies were seen in 14 of 200 episodes and were significantly associated with antibiotics (p=0.003). Patients' perceived their skin problems as moderate or severe in 19% of the episodes. The impact on resources in the haematology practice was large; 45% of inpatients were receiving topical or systemic skin treatment, in 5% of patients the oncology treatment was compromised, 11% of patients required extra nursing and 3% of patients stayed longer in hospital. This volume of mucocutaneous problems makes dermatological input to haemato-oncology units vital.

Drug Hypersensitivity↗
PubMedDate not supplied

Dual-frequency ultrasound examination of skin and subcutis thickness in breast cancer-related lymphedema.

Breast cancer-related lymphedema (BCRL) is a chronic swelling of the arm that sometimes follows breast cancer treatment. Clinically, both skin and subcutis are swollen. Edema is considered to be predominantly subcutaneous and of an even distribution. The purpose of this study was to quantify the degree and uniformity of skin and subcutis swelling around the forearms of women with BCRL. Ten women with BCRL were recruited. Both forearms were examined using 20 MHz ultrasound to visualize the skin and 7 MHz ultrasound to visualize the subcutis. Skin thickness was between the bottom of the entry-echo and the skin-subcutis boundary. Subcutis thickness was measured between the skin-subcutis boundary and the subcutis-muscle boundary. Both average skin thickness (1.97 +/- 1.00 mm) and average subcutis thickness (10.32 +/- 5.63 mm) were greater in the ipsilateral arm than in the contralateral arm (skin 1.12 +/- 0.14 mm, subcutis 5.58 +/- 2.04 mm, p < 0.01, t-test). The degree of increase in skin thickness did not vary around the arm (p > 0.05, ANOVA), while the degree of increase in subcutis thickness did vary (p < 0.05). Skin thickness correlated negatively with subcutis thickness in the contralateral arm, but correlated positively in the ipsilateral arm. The skin and subcutis are thickened in the ipsilateral arm of patients with BCRL. Skin thickness is increased uniformly around the arm and correlates strongly with the degree of swelling, while subcutis swelling varies. The measurement of skin thickness using ultrasound may form a useful clinical tool in the diagnosis of lymphedema and also aid further investigation of therapeutic techniques.

Aged↗
PubMedDate not supplied

Assessment of health-related quality of life in patients with lymphedema of the lower limb.

The purpose of this study was to examine the use of a number of tools in the evaluation of health-related quality of life in patients with lower limb lymphedema, and to determine the consequences of cancer history and concurrent leg ulceration. Patients in one health trust having lower limb lymphedema were identified and interviewed at entry and after 24 weeks. The short form-36 (SF-36), modified Barthel scale, McGill short form pain questionnaire, and Euroqol were administered at both time points. Of the 164 (median age=76.9 years, 70.7% women) patients who comprised the study population, 15.2% had a history of cancer and 30.4% had coexisting current leg ulceration. Internal consistencies were high for all scales (Cronbach's alpha >0.80). There were high ceiling effects for a number of SF-36 scores, and high floor effects in these and the McGill short form pain questionnaire, scales. Despite these limitations, there was strong evidence that treatment led to significant improvements in six of eight scores of the SF-36, three of three scores of the McGill short form pain questionnaire and the modified Barthel scale (all p<0.05). The improvement in physical functioning was significantly greater for patients who entered the study with a leg ulcer (mean different=9.1, 95% confidence interval 2.1-16.1, p=0.011). Patients treated with compression bandaging had significantly greater improvements for physical functioning (10.2) than those treated with compression hosiery (-1.5) or no treatment (-2.0), p=0.001. Of the tools assessed, the SF-36, appears to be the most appropriate for use in this patient group.

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