Physician perspectives on chronic pain management: barriers and the use of eHealth in the COVID-19 era.

BACKGROUND: Chronic pain is a highly prevalent and disabling condition which is often undertreated and poorly managed in the community. The emergence of COVID-19 has further complicated pain care, with an increased prevalence of chronic pain and mental health comorbidities, and burnout among physicians. While the pandemic has led to a dramatic increase in virtual health care visits, the uptake of a broader range of eHealth technologies remains unclear. The present study sought to better understand physicians' current needs and barriers in providing effective pain care within the context of COVID-19, as well as gauge current use, interest, and ongoing barriers to eHealth implementation. METHODS: A total of 100 practicing physicians in British Columbia, Canada, completed a brief online survey. RESULTS: The sample was comprised of physicians practicing in rural and urban areas (rural = 48%, urban = 42%; both = 10%), with the majority (72%) working in family practice. The most prominent perceived barriers to providing chronic pain care were a lack of interdisciplinary treatment and allied health care for patients, challenges related to opioid prescribing and management, and a lack of time to manage the complexities of chronic pain. Moreover, despite expressing considerable interest in eHealth for chronic pain management (82%), low adoption rates were observed for several technologies. Specifically, only a small percentage of the sample reported using eHealth for the collection of intake data (21%), patient-reported outcomes (14%), and remote patient monitoring (26%). The most common perceived barriers to implementation were cost, complexity, and unfamiliarity with available options. CONCLUSIONS: Findings provide insight into physicians' ongoing needs and barriers in providing effective pain management during the COVID-19 pandemic. Despite the potential for eHealth technologies to help address barriers in pain care, and strong interest from physicians, enhanced useability, education and training, and funding are likely required to achieve successful implementation of a broader range of eHealth technologies in the future.

The mycotoxin distribution in maize milling fractions under experimental conditions.

Mycotoxin contamination of maize and maize-based food and feed products poses a health risk to humans and animals if not adequately controlled and managed. The current study investigates the effect of dry milling on the reduction of fumonisins (FB), deoxynivalenol (DON) and zearalenone (ZEA) in maize. Five composite samples, constructed to represent different mycotoxin contamination levels were degermed yielding degermed maize and the germ. The degermed maize was milled under laboratory conditions and four major milling fractions (SPECIAL, SUPER, semolina (SEM) and milling hominy feed) collected. The whole maize, degermed maize and total hominy feed (germ+milling hominy feed) were reconstructed to ensure homogenous samples for mycotoxin analyses. For comparison, commercial dry milling fractions (whole maize, SPECIAL, SUPER and total hominy feed), collected from three South African industrial mills, were analysed for the same mycotoxins and hence a more accurate assessment of the distribution between the different milling fractions. The distribution of the mycotoxins during the experimental dry milling of the degermed maize differs, with FB mainly concentrated in the SPECIAL, DON in the SEM whereas ZEA was equally distributed between the two milling fractions. Distribution of mycotoxins between the fractions obtained during commercial dry milling generally provided similar results with the total hominy feed containing the highest and the SUPER milling fractions the lowest mycotoxin levels although variations existed. Although milling is an effective way to reduce mycotoxins in maize, kernel characteristics and resultant fungal colonisation may impact on the distribution of specific mycotoxins among the different milling fractions. Differences in industrial dry milling practices and problems encountered in sampling bulk maize remain a large problem in assessing mycotoxin contamination in milling fractions intended for human consumption.

In vivo measurements of the cerebral perfusion and cardiovascular effects of the novel guanidine ME10092 in the non-human primate, Papio ursinus.

The novel guanidines N-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine (ME 10092) and N-(3,4-dimethoxy-2-chlorobenzylideneamino)-N1-hydroxyguanidine (PR5) were recently reported to exhibit promising cardioprotective activities in myocardial ischaemia and reperfusion in rats. The current study investigated for the first time pharmacological effects of ME10092 in the primate, viz. the Cape baboon Papio ursinus. The effects of ME10092 (1 and 2 mg/kg doses) on the cerebral blood flow, heart rates and the systolic and diastolic blood pressure were investigated after intravenous injection to the baboon under anaesthesia. The cerebral perfusion effects of ME10092 were assessed using Single Photon Emission Computed Tomography according to the split-dose approach and 99mTc-hexamethyl-propylene amine oxime as brain perfusion tracer. The observation that the recovery times from the anaesthesia were unacceptably prolonged excluded doses beyond 2 mg/kg. The data indicate that no cerebral perfusion changes were induced at both the 1 and 2 mg/kg doses of ME10092. Both these doses of ME10092 showed blood pressure and heart rate effects, with the latter being more significant. Decreases in heart rate were seen directly after ME10092 administration reaching levels of about 20% for the 2 mg/kg dose and about 15% for the 1 mg/kg dose at around 6 min post drug administration. A transient decrease in both systolic and diastolic blood pressure was observed for the higher dose. The blood pressure data further suggest an attenuation of the anaesthesia induced increase in pressure usually present in non-intervention studies. ME10092 clearly exhibits mycocardial effects in the non-human primate, similar to the effects previously observed in the ischaemia-reperfusion rat model, where ME10092 showed strong protection.

Measurement of cerebral perfusion after zolpidem administration in the baboon model.

A recent report showed that zolpidem (CAS 82626-48-0) can lead to the arousal of a semi-comatosed patient. Zolpidem is clinically used for the treatment of insomnia. It belongs to the imidazopyridine chemical class and is a non benzodiazepine drug. It illicits its pharmacological action via the GABA receptor system through stimulation of particularly the omega 1 receptors. In this study, the effect of zolpidem on brain perfusion was examined by 99mTc hexamethyl-propylene amine oxime (HMPAO) split dose brain SPECT on four normal baboons and in one baboon with abnormal neurological behaviour. The global and regional brain perfusion was not significantly affected in the normal brains. In some regions of the abnormal baboon brain, however, there was a disproportionate increase in perfusion after zolpidem.

Biodistribution and pharmacokinetics of variously sized molecular radiolabelled polyethyleneiminomethyl phosphonic acid as a selective bone seeker for therapy in the normal primate model.

An ideal radiopharmaceutical for the treatment of neoplastic and inflammatory (benign) bone disease would be a radiolabelled compound that predominantly accumulates in bone lesions with limited access to normal bone and other organs. Neoplastic tissue's abnormal blood supply (increased permeability) and lack of lymphatics will selectively accumulate radiolabelled macromolecules. This enhanced permeability and retention effect forms the basis of this study, using various molecular sizes of the radiolabelled macromolecule polyethyleneiminomethyl phosphonic acid (PEI-MP) for increased selectivity of the bone-seeking radiopharmaceutical. PEI-MP was synthesized by condensation of polyethyleneimine, phosphonic acid and formaldehyde, followed by fractionation into different molecular sizes by membrane ultrafiltration. Labelling efficiency to 99mTc (as radiotracer) was approximately 99% with complexes stable for 24 h. The pharmacokinetics and biodistribution of various 99mTc-PEI-MP fractions were investigated using 4 experimental baboons (Papio ursinus) per fraction. Scintigraphy was performed on the baboons under general anaesthesia of pentobarbital i.v. After an i.v. bolus of 99mTc-PEI-MP (approximately 185 MBq) both dynamic studies (30 x 1 min frames), and static studies (2 min acquisition every hour for 4 h) were done, as well as blood samples and urine collected. From the results macromolecules with sizes ranging between 30-300 kDa were characterized by excessive liver (21%-57% retained activity) and kidney (40% retained activity) uptake and accompanying long residing times (t1/2 up to 24 h). The percentage bone uptake averaged at 8% for these particles excluding sizes 100-300 kDa where very little bone uptake was seen (< 1%). In this case the blood clearance was also slow (t1/2 approximately 2 h). The fraction size 10-30 kDa had comparatively low accumulation and short residence times in the liver and kidneys (resp. 20%, t1/2 = 22 +/- 4 min; 17.5%, t1/2 = 20 +/- 3 min) and although the bone uptake of 18% in this case was high, it is still low for a bone-seeking agent. These particles cleared the blood with t1/2 = 25 +/- 2 min and seemed suitable for labelling with a therapeutic radioisotopic agent.

Metal-ion speciation in blood plasma incorporating the tetraphosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropilydenediphosphonate (APDDMP), in therapeutic radiopharmaceuticals.

In a quest for more effective radiopharmaceuticals for pain palliation of metastatic bone cancer, this paper relates results obtained with 166Ho and 153Sm complexed to the bone seeking phosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropylidenediphosphonate (APDDMP). APDDMP is synthesised from the known bone cancer pain palliation agent 1-hydroxy-3-aminopropylidenediphosphonate (APD) and was complexed to lanthanide trivalent metal ions. This work is performed to utilise the idea that the energetic beta-particle emitter, 166 Ho, coupled with phosphonate ligands such as APD and APDDMP could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants of APDDMP with the important blood plasma metal-ions, Ca2+, Mg2+, and Zn2+ and the trivalent lanthanides Ho3+ and Sm3+ were measured by glass electrode potentiometry at 37 degrees C and I = 150 mM. Blood plasma models were constructed using the computer code ECCLES and the results compared with those gathered from animal tests. The 166Ho-APDDMP complex was found to have little liver or bone uptake while 153Sm-APDDMP had a moderate bone uptake. This was primarily due to the high affinity of APDDMP for Ca(II). Clinical observations could be explained by the blood plasma modelling.

Evaluation in the baboon model of (99m)Tc-biguanide as a tracer for renal imaging.

Studies in various animal species have recently shown that (99m)Tc-BIG has practical and dosimetric benefits for renal imaging that could probably make it a good alternative to (99m)Tc-2, 3-dimercaptosuccinic acid ((99m)Tc-DMSA). In this study, using the baboon experimental model, the biodistribution of (99m)Tc-BIG and (99m)Tc-DMSA are compared. It is demonstrated that early good contrast imaging and more favourable dosimetry is possible with (99m)Tc-BIG compared to (99m)Tc-DMSA, confirming the quoted previous findings with small animals. Time-activity curves for kidneys and other organs support these findings, and MIRDOSE software provided the dosimetry.

Effect of cyclodextrin complexation on the in vivo disposition of the brain imaging radiopharmaceutical 99mTechnetium ethyl cysteinate dimer (99mTc-ECD).

The brain imaging radiopharmaceutical, 99mTechnetium ethyl cysteinate dimer (99mTc-ECD, 99mTc-bicisate) is the most recent addition to the available set of radiopharmaceuticals for measuring cerebral blood flow. Ideally radiotracers should be trapped in the brain long enough so that their distribution can be quantitated and should demonstrate good spatial resolution. Furthermore, the stability (chemical and metabolic) and bioavailability of radiopharmaceuticals have in general proved to be a challenge during development and clinical administration. In view of these challenges and background, this study with 99mTc-ECD is presented. The aims of this research program were to develop novel approaches to improve the chemical and metabolic stability and the bioavailability of 99mTc-ECD across the blood brain barrier for cerebral blood flow determinations, using the well known non-human primate in vivo baboon model. These aims were addressed by investigating the influence of cyclodextrin--99mTc-ECD complexation on normal cerebral blood flow patterns, using two different cyclodextrins, i.e., gamma-cyclodextrin (CAS 17465-86-0) and beta-trimethylcyclodextrin (CAS 55216-11-0). The effect of incubation of 99mTc-ECD (with or without cyclodextrin complexation) in plasma, on metabolic esterase action, was also investigated. Possible protection against plasma esterase by acetylcholine (CAS 51-84-3) of 99mTc-ECD was further determined. The current study has shown that cyclodextrin complexation of 99mTc-ECD indeed offers a useful approach to improve the stability of the radiopharmaceutical against peripheral metabolism. The acetylcholine shows also potential to protect 99mTc-ECD. However, it is clear from the current data that the choice of cyclodextrin is of utmost importance, as has been observed from significantly reduced the bioavailability of 99mTc-ECD when complexed with beta-trimethylcyclodextrin. The plasma incubation procedures showed that gamma-cyclodextrin offers protection with only slightly reduced bioavailability. This study has indicated that novel approaches, such as cyclodextrin technologies, indeed show potential to modify the performance in its currently available 99mTc-ECD form.

Metal-ion speciation in blood plasma incorporating the bisphosphonate, 1-hydroxy-4-aminopropilydenediphosphonate (APD), in therapeutic radiopharmaceuticals.

In the quest for more effective pain palliation radiopharmaceuticals for metastatic bone cancer, this paper relates results obtained with 166Ho complexed to the bone-seeking bisphosphonate, 1-hydroxy-4-aminopropililydenediphosphonate (APD). APD is itself a bone cancer pain palliation agent and this work was therefore driven by the idea that the energetic beta-particle emitter, 166Ho, coupled with APD could afford a highly effective radiopharmaceutical in the treatment of bone cancer. Complex-formation constants for important blood plasma metal-ions were measured by potentiometry or polarography at 37 degrees C and I = 150 mmol dm-3. The latter technique was used for systems where precipitates formed at ligand-to-metal ratios appropriate for potentiometry. For trivalent lanthanides, neither electrochemical technique could be used. Animal tests showed that the 166Ho-APD complex was taken up primarily by the liver due to precipitation or colloid formation.

Quantifying the radiation dosage to individual skeletal lesions treated with samarium-153-EDTMP.

UNLABELLED: Samarium-153ethylenediaminetetramethylenephosphonate (EDTMP) is used in the treatment of painful skeletal lesions. This study attempted to quantify the radiation dosage to individual lesions on both the macroscopic and microscopic level. METHODS: A gamma camera-based quantification technique was adapted and refined for 153Sm. The accuracy of the technique was determined by using a realistic phantom. The activity and volume of lesions as well as normal bone were determined and used to estimate the radiation dosages to these regions. Two patients died of unrelated causes shortly after receiving 153Sm-EDTMP. This made it possible to compare the gamma camera results with direct measurements. It also allowed for autoradiographic examination of the lesions. Finally, the microscopic radiation dosages were estimated. RESULTS: The phantom study indicated that the quantification technique was off, on average, by 4.1% (s.d. = 8.1%). The absolute activity concentration of trabecular bone was found to be approximately 0.22 MBq/g, and that of cortical bone was found to be approximately 0.1 MBq/g, regardless of the dosage administered. The corresponding concentrations for lesions were between 3 and 7 times higher than that of normal bone, with no apparent ceiling. From these results, the macroscopic radiation dosage could be estimated. The dosage to normal bone varied between 0.9 and 3.9 cGy x kg/MBq, and that of the lesions varied between 5.2 and 27.1 cGy x kg/MBq. The autopsy results confirmed that the gamma camera technique was accurate. The autoradiography showed clearly that the activity was associated with the surface of the bone. From these findings, the microscopic radiation dosage distribution was estimated for cortical and trabecular bone as well as osteoblastic lesions. The variation in the microscopic dosage compared to the macroscopic dosage was quite large. Microscopic dosages, when compared to the macroscopic dosages, were as high as 965% and as low as 14.9%. CONCLUSION: The techniques used have been proven to be accurate. The activity in normal bone may be at a ceiling value for all the administered doses, which could explain the small variation. This is not true for the lesions. The large variation in dosages on a microscopic scale, combined with the ceiling in normal bone, may explain the lower than expected toxicity and relatively quick relapse of the patients.

Targeted radiotherapy with Sm-153-EDTMP in nine cases of canine primary bone tumours.

Nine dogs with primary bone tumours were treated with Samarium-153-EDTMP (Sm-153-EDTMP). Conventional treatment protocols were precluded by the size of the dogs and the owners' refusal of limb amputation. All the tumours were of the appendicular skeleton; 4 were confirmed osteosarcomas. The other 5 tumours were radiologically suspect for osteosarcoma. Bone scans were performed on all dogs using Technetium-99m-methylene diphosphonate (Tc-99m-MDP) before administration of Sm-153-EDTMP. Regions of interest were identified over the contralateral limb at the same site as the tumour and counts per pixel were recorded for the tumour and contralateral limb and expressed as a ratio. The dogs were given 1 injection of 37 MBq/kg (1 mCi/kg) of Sm-153-EDTMP intravenously. Thoracic and primary tumour site radiographs were taken at monthly or 2-monthly intervals to monitor progression of the primary tumour and search for evidence of metastasis. Two dogs showed no response to treatment, with an increase in bone pain, and were euthanased within 1 month. In 1 dog, a tumour of the scapula underwent complete involution and the dog is considered free of disease at 20 months post Sm-153-EDTMP treatment. The overall tumourcidal effect of a single dose of Sm-153-EDTMP on primary bone tumours was difficult to evaluate in this group of dogs, as, with one exception, all the primary tumours progressed over time and the dogs were euthanased. Pain control, for which Sm-155-EDTMP is used in man, was not evident, except in the dog that responded completely to treatment.

Uptake of ethylenediamine tetramethylene phosphonic acid in normal bone after multiple applications. A non-human primate study.

Palliation of bone pain in patients with bone metastases has previously been evaluated using 153Sm (samarium) complexed to bone seeking ethylenediamine tetramethylene phosphonic acid (CAS 1429-50-1, EDTMP). Repeated application of the radioligand as needed was found progressively less effective. This study questions whether EDTMP exerts a blocking function, limiting access to bone or osseous tumours with successive administration. The pharmacokinetics and biodistribution of 153Sm-EDTMP in the normal experimental baboon (n = 6) during three successive applications (6 weekly) each with two different concentrations of EDTMP (0.7 and 1.4 mg/kg b.wt.) were investigated using bone scintigraphy. 153Sm-EDTMP (111 MBq) was injected in each case and monitored for 5 h. Curves of tracer kinetics and bone to background uptake were obtained, also blood and cumulative urine curves. Comparisons were statistically assessed in each group between successive applications and between EDTMP concentrations. Partial blocking with the low EDTMP concentration reached statistical significance after the third application. The first application of the high EDTMP concentration yielded lower uptake in the bone than did low EDTMP pointing to blocking by the high concentration, but not seen with repeated applications. Continual application of high concentration EDTMP could lead to a reduced level of calcium in serum and increased parathyroid hormone levels which might trigger osteoblastic activity and bone remodelling. This would partially affect the blocking which was thus more obvious at the low EDTMP concentration.

Dose response relationship and multiple dose efficacy and toxicity of samarium-153-EDTMP in metastatic cancer to bone.

INTRODUCTION: The optimal dose of samarium-153-EDTMP (153Sm-EDTMP) for effective palliation of painful metastases to bone is under investigation. It is not known whether increased doses of 153Sm EDTMP will lead to better and longer pain and tumour control and survival. Multiple dose efficacy and toxicity is of importance as most Patients will require prolonged support for pain. METHODS: Twenty-eight (28) patients were treated with 0.75 mCi/kg, 35 patients with 1.5 mCi/kg and 19 patients with 3 mCi/kg in three sequential Phase I-II trials. Multiple doses were given to patients on the 0.75 mCi/kg and 1.5 mCi/kg dose levels. RESULTS: At all dose levels adequate pain control was achieved in 78-95% of patients. The duration of pain control was 40-56 days with the best results in the 1.5 mCi/kg group (56 days). There is no evidence that increasing dose leads to better and longer pain control, tumour response and survival, but toxicity is increased. Multiple doses can be given with acceptable toxicity and pain control, however, only 38% of patients will qualify for multiple treatments. CONCLUSION: 153Sm-EDTMP provides adequate and safe palliation but multiple doses can only be given in 38% of patients. There is not a clear dose-response relationship. The length of pain control is satisfactory but not ideal and hospitalisation for 4 days every 6-8 weeks is a disadvantage. Further research is required to combine 153Sm-EDTMP with cytostatics and to administer it on an out patient basis.

Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model.

Bone-seeking radiopharmaceuticals such as ethylenediaminetetramethylene phosphonate (EDTMP) complexes of samarium-153 and holmium-166 are receiving considerable attention for therapeutic treatment of bone metastases. In this study, using the baboon experimental model, multicompartmental analysis revealed that with regard to pharmacokinetics, biodistribution, and skeletal localisation, 166Ho-EDTMP was significantly inferior to 153Sm-EDTMP and 99mTc-MDP. A more suitable 166Ho-bone-seeking agent should thus be sought for closer similarity to 153Sm-EDTMP to exploit fully the therapeutic potential of its shorter half-life and more energetic beta radiation.

Samarium-153-EDTMP for palliation of ankylosing spondylitis, Paget's disease and rheumatoid arthritis.

Samarium-153-EDTMP is an effective agent for palliation of widespread skeletal metastases because it concentrates in bone metastases which have an osteoblastic component. Similar concentration in areas of osteoblastic activity in ankylosing spondylitis, Paget's disease and rheumatoid arthritis suggests a possible new treatment approach. Three patients with ankylosing spondylitis, one patient with Paget's disease and one patient with rheumatoid arthritis were treated with 153Sm-EDTMP. Objective and subjective improvement was noted, especially in ankylosing spondylitis patients. Samarium-153-EDTMP has disease-modifying potential in ankylosing spondylitis and Paget's disease and has palliative value in resistant rheumatoid arthritis. Further trials to determine optimal dose, treatment scheduling, long-term disease-modifying potential and toxicity are needed.

Biodistribution and accumulation in inflammatory lesions of different thiol reduction-mediated 99Tcm-IgG preparations in baboon models.

The diagnostic efficacy of 99Tcm-labelled non-specific polyclonal immunoglobulin (IgG) as tracer for abdominal inflammatory lesions is impeded by its unfavourable physiological organ distribution patterns. Modifications to the IgG molecules during preparation and labelling may alter its in vivo behaviour and accumulation in inflammatory foci. This report describes scintigraphic biodistribution studies in the baboon (normal and with inflammatory lesions) of various thiol reduction-mediated 99Tcm-IgG preparations. These are human IgG (Sandoglobulin) where the Fc-mediated complement activity is impaired, human IgG (Gammagard) where the Fc portion is left intact, and baboon IgG isolated from the serum of each animal (autologous): the first two preparations are commercially available. Normal baboon organ distributions were obtained for each tracer over a period of 3 h, commencing 4 h after administration. Similarly, lesion-to-background ratios in thigh and abdominal lesions (bacterial and chemical) were compared. Mean normal organ distributions (n = 6) were relatively constant during this period. Kidney uptake with IgG (Sandoglobulin) was significantly enhanced, as was liver uptake with IgG (Gammagard) and the baboon IgG. Biodistribution pattern changes after lesion induction tended to be similar for IgG (Gammagard) and baboon IgG, where activity washout became more prominent. Lesion-to-background ratios in the thigh far exceeded those in the abdomen, except for the individual animal's own IgG which performed well in this case.

Species and immunoglobulin preparation related effects on the biodistribution of technetium-99m-labelled immunoglobulin G in a baboon model.

Technetium-99m-labelled immunoglobulin G (99mTc-IgG) is a convenient and useful radio-pharmaceutical for the scintigraphic detection of inflammatory foci. However, unfavourable physiological biodistribution patterns such as high activities in the liver and especially in the kidneys impede the efficacy of this agent. This report describes biodistribution studies in the baboon model of various thiol reduction-mediated 99mTc-labelled immunoglobulins, including human IgG preparations (Sandoglobulin and Sigma: gamma-globulins prepared from Cohn fractions II and III) as well as baboon IgG preparations (Sigma: gamma-globulins prepared from Cohn fractions II and III and IgG isolated from the serum obtained from specific animals). The biodistribution studies demonstrated differences in kidney concentration, i.e. human IgG (Sandoglobulin) > baboon IgG (cross-over animal experiments with IgG isolated from the serum of the different animals) > human IgG (Sigma) approximately baboon IgG (Sigma) approximately baboon IgG (own IgG isolated from the serum of a specific animal, labelled with 99mTc and reinjected). Differences in liver concentration were also observed: human IgG (Sandoglobulin) < human IgG (Sigma) approximately baboon IgG (Sigma) approximately baboon IgG (own IgG) approximately IgG (cross-over). Characteristic were the relatively high activities in the liver and kidneys compared to those in other organs with high blood supply, and a relatively high retention in the blood pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Thiol reduction-mediated 99mTc-IgG for scintigraphy of inflammatory lesions in the baboon model.

Radiolabeling procedures may modify the structure of the Fc portion of the immunoglobulin molecule in such a way that its in vivo immunological behavior may be altered and its efficacy as radiopharmaceutical for inflammatory lesions impaired. This study tested the efficacy of thiol reduction-mediated 99mTc human IgG for scintigraphy of focal inflammatory lesions, either bacterially or chemically induced and located either in the abdominal/thoracical region or in the thigh of baboons. Positive images were obtained in the thigh lesions between 4 and 7 hr after i.v. administration of the labeled IgG. The abdominal/thoracic lesions were never very clear, mostly because of very hot kidneys. Late visualization (20 hr) of all lesions was poor and a high background was present. Bacterially induced lesions were better visible, although no neutrophil nor monocyte activity could be established in the mechanism of the IgG localization.

Nucleoid sedimentation analysis of DNA superstructure, gamma-radiation-induced damage and repair in human and chacma baboon (Papia ursinus) peripheral lymphocytes.

The use of the chacma baboon (Papio ursinus) in radiobiological investigations justifies special attention because it answers many of the criteria of parallelism to the human. The present study was undertaken to establish whether in vitro gamma-radiation effects in chacma baboon and human lymphocytes are comparable. The sensitive and rapid nucleoid sedimentation technique was employed to evaluate in vitro DNA superstructure, damage and repair in readily obtainable radiosensitive peripheral lymphocytes. Dose-response curves after 60Co gamma-irradiation were obtained, and by applying single-hit kinetics of the target theory, an estimation of molecular masses of the supercoiled domains was made. The baboon and human lymphocytes produced analogous results, while an ethidium bromide intercalation study also revealed a similarity in average DNA superhelical density. Lymphocyte DNA repair after 0.5-4.0 Gy gamma-irradiation and repair times from 0.5 to 5.0 h were evaluated. The repair data obtained from baboon and human cells after 2.0 Gy irradiation compared favourably in extent of DNA repair as well as the profiles of the kinetic curves. These findings indicate that the chacma baboon would be a useful and relevant model for further in vivo radiobiological studies on lymphocytes. The effects of sedimentation conditions and advantages of using vertical-tube rotors in the nucleoid sedimentation technique are also discussed.