Invited editorial: Gut transfer and doses from environmental technetium.
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Animals↗
Biomedical subjects
J D Harrison
Publications and source records attributed to J D Harrison.
Reliability of the ICRP's dose coefficients for members of the public, II. Uncertainties in the absorption of ingested radionuclides and the effect on dose estimates. International Comission on Radiological Protection.
Data on the gastrointestinal absorption of 12 elements have been reviewed. In each case, absorption is expressed as the fraction of the ingested element absorbed to blood, referred to as the f1 value, applying to intakes of unspecified chemical form by average population groups. The level of confidence in individual absorption values has been estimated in terms of lower and upper bounds, A and B, such that there is judged to be roughly a 90% probability that the true central value is no less than A and no greater than B. Ranges are proposed for intakes by adults, 10-year-old children and 3-month-old infants. Uncertainty in f1 values (B/A) ranged from 10% to factors of 100-400. The lowest uncertainties were for the well absorbed elements, H, I and Cs, for which there are good data, and the greatest uncertainties were for less well absorbed elements for which few data are available, particularly Zr and Sb. Ranges were generally wider for children and infants than for adults because of the need to allow for the likelihood of increased absorption with only limited data in support of the proposed values. The largest ranges were for 3-month-old infants, reflective lack of knowledge on the time-course and magnitude of possible increased absorption in the first few months of life. For each age group, ICRP values of absorption tend towards the upper bound of the ranges, indicating a degree of conservatism in th calculation of ingestion dose coefficients. Examination of the effect of the proposed confidence intervals for f1 values on uncertainties in dose coefficients for ingested radionuclides showed that there was no direct relationship. For some radionuclides, uncertainties in effective dose were small despite large uncertainties in f1 values while for others the uncertainties in effective doses approached the corresponding values for uncertainty in f1 values. These differences reflect the relative contributions to effective dose from cumulative activity in the contents of the alimentary tract, which in many cases is insensitive to uncertainties in f1, and cumulative activity of the absorbed radionuclide in systemic tissues, which is proportional to f1. In general, uncertainties in effective close for children and infants exceeded those in adults as a result of greater uncertainties in f1 values for the younger age groups. However, this effect was reduced in some cases by shorter retention times of absorbed nuclides in body tissues and organs.
Adult↗
A model for the transfer of alkaline earth elements to the fetus.
A biokinetic model has been developed for the transfer of calcium, strontium, barium and radium to the human fetus. For the mother, ICRP models were adapted for pregnancy to include increases in gastrointestinal absorption, urinary excretion and bone turnover rates. The fetus was modelled with blood, soft tissue and bone compartments. Fetal requirements for Ca were determined by skeletal calcification, and recyling between fetal and maternal blood was inlcluded. Daily transfer of Sr, Ba and Ra to the fetus was taken to be lower than for Ca by factors of 0.6 for Sr and 0.4 for Ba and Ra. For acute intakes in late pregnancy at 35 weeks after conception, when maximum transfer occurs, the model predicts whole-body fetus:mother concentration ratios (C(F):C(M)) of 18 for Ca, 8 for Sr and 2 for Ba and Ra, respectively. Estimates of committed equivalent doses to the red bone marrow of offspring, including in utero and postnatal dose, after maternal ingestion in late pregnancy, were greater than corresponding doses in adults by factors of 20-31 for 45Ca, 2-3 for 90Sr and 3-4 for 226Ra but slightly lower (0.8-1.9) for 133Ba.
Barium↗
Lack of detectable transmissible chromosomal instability after in vivo or in vitro exposure of mouse bone marrow cells to 224Ra alpha particles.
Several studies over recent years have highlighted the possibility that radiation can induce transmissible genomic instability. Most of these involve in vitro irradiation and usually in vitro culture. Here it is reported that the short-half-life bone-seeking alpha-particle emitter (224)Ra did not induce excess transmissible chromosomal instability in CBA/H mouse bone marrow cells in a 100-day period after in vivo or in vitro exposure. Similarly, no excess transmissible chromosomal instability could be detected after in vivo whole-body X irradiation. It was noted, however, that short-term culture of murine bone marrow cells elevated yields of aberrations, as did transplantation of untreated marrow into radiation-ablated hosts. These findings emphasize the sensitivity of murine hemopoietic tissue to experimental manipulation and reinforce the importance of appropriate concurrent control experiments in any investigation of transmissible genomic instability.
Alpha Particles↗
The effects of ductal obstruction on the acinar cells of the parotid of cat.
Twenty-nine parotids ligated for between 1 and 365 days were examined by light and electron microscopy. Major changes in the acini were seen at 4 days and included vacuolation, disintegration, extravasation, apoptosis, phagy and a reduction in number and size of secretory granules. There was a further reduction in secretory granules from 7 to 12 days, but acinar cells persisted even up to 365 days, some contained a luminal concentration of small secretory granules and occasionally acinar cells of a similar appearance to normal were found. These findings contrast with a reported absence of acinar cells from the obstructed parotid of rat and show that parotid acinar cells are able to persist and retain an appearance indicative of secretory activity.
Animals↗
Microdistribution and localized dosimetry of the alpha-emitting radionuclides 239Pu, 241Am and 233U in mouse femoral shaft.
PURPOSE: To analyse the temporal change in microdistribution of 239Pu, 241Am and 233U in mouse femur and to compare the calculated radiation doses with regions of the bone marrow thought to contain target cells for osteosarcoma and leukaemia with relative risk for those diseases. MATERIALS AND METHODS: Neutron-induced and alpha-track autoradiographs were prepared from femora of the CBA/H mouse that had been injected with 40 kBq kg(-1) radionuclide between 1 and 448 days previously. Computer-based image analysis of the autoradiographs was performed and dosimetric methods applied to obtain radiation dose-rates to different regions of the marrow cavity. RESULTS: Initially each radionuclide deposited on endosteal and periosteal bone surfaces; 241Am was additionally deposited on vascular canal surfaces. Redistribution resulted in 233U being incorporated into bone, while 239Pu and 241Am showed transfer into both bone volume and marrow. Accumulation in the central marrow peaked at 112-224 days post-injection, but subsequently was cleared by 448 days. Cumulative doses to both osteosarcomagenic and myeloid leukaemogenic target cell regions showed the trend 239Pu > 241Am > 233U. CONCLUSIONS: Calculation of cumulative doses to a 10-microm layer of marrow adjacent to bone surfaces appears to be a suitable predictor for risk of osteosarcoma. Risks of myeloid leukaemia in the mouse are better predicted by considering the central marrow as the target region rather than average dose to all marrow.
Alpha Particles↗
Comparison of cytogenetic damage in cultured cells from cobalt-60 gamma-radiation and the Auger emitter zinc-65.
PURPOSE: To assess the ability of the Auger-emitting nuclide, zinc-65 (65Zn), relative to gamma-irradiation, to cause chromosomal aberrations in cultured rat prostate cells. MATERIALS AND METHODS: Rat prostate adenocarcinoma cells in culture were exposed to doses of 1, 2, 3 or 5 Gy of external gamma-irradiation for 24h or incubated with 0.7, 1.5, 1.8 or 2.8 MBq of 65Zn for 24 h. The uptake by and clearance from cells of 65Zn was measured. Metaphase spreads prepared from washed cells were scored for chromatid- and chromosome-type aberrations. RESULTS: Following exposure to 65Zn or gamma-irradiation, chromatid-type damage was more commonly observed than chromosome-type aberrations. The relationship between induced chromatid damage and gamma dose (to 3 Gy) was best fitted by a second-order polynomial function, while the activity response relationship for chromatid damage caused by 65Zn appeared to be best fitted by a straight line. Measurements of the uptake of 65Zn by cells showed that average concentrations within cells were about 100 times the concentration in the culture medium. Assuming uniform distribution of 65Zn within cells, with 36% in the nucleus, the dose was estimated as 0.70 Gy per MBq added 65Zn, with Auger electrons contributing most (93%) of the dose. Assuming that 20% of cellular zinc was localized in the nucleus, based on previous measurements, the dose to the nucleus was calculated as 0.44 Gy per MBq added 65Zn. RBE values for chromatid damage induced by 65Zn compared to gamma-radiation range from about 1 to 3 based on a uniform dose throughout the cell and from about 2 to 5 based on 20% of 65Zn in the cell nucleus. CONCLUSION: The observed radiotoxicity of 65Zn is consistent with its behaviour as an Auger-emitting radionuclide that is localized to some extent in the nucleus.
Adenocarcinoma↗
Sialadenitis and sialolithiasis.
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Humans↗
Energy storage and cytokine response in patients undergoing liver transplantation.
Overproduction of pro-inflammatory cytokines during surgery has been known to exert tissue-damaging and lethal effects on the host. Hypermetabolism-associated malnutrition, a common feature of patients with end-stage liver diseases, is related to the presence of a systemic inflammatory response, as reflected by enhanced levels of proinflammatory cytokines. The present study was designed to evaluate energy status of 29 liver transplant recipients, and to assess the relation of energy storage to post-operative cytokine response. The glycogen contents of the graft, and the recipient's abdominal muscle and old liver were measured. The plasma concentrations of tumour necrosis factor alpha, interleukin 1beta, interleukin 6, lactate, pyruvate and total ketone bodies were determined during and after surgery. In undernourished patients, ketone bodies seemed to be the major fuel available to muscle. The concentration of ketone bodies decreased rapidly after the incision, and remained at a low level after reperfusion. These patients had higher plasma levels of lactate/pyruvate ratio and aromatic amino acids during the anhepatic phase, followed by an exaggerated response of cytokines. Depletion of energy storage of the recipients may be involved in the deterioration of peri-operative energy metabolism and the exaggerated post-operative cytokine response.
Adolescent↗
Phase II trial of radical surgery for locally advanced pelvic neoplasia.
BACKGROUND: Reported operative mortality and survival rates following total pelvic exenteration (TPE) for recurrent pelvic neoplasia are now as good as those for many primary treatments. The currently accepted primary treatments for these tumours are, however, still either radiotherapy alone or radiotherapy and chemotherapy. The primary aim of this study was to evaluate the safety and tolerability of TPE and secondarily to ascertain survival after TPE. METHODS: This was a phase II study of 50 patients with locally advanced pelvic tumours who underwent TPE. RESULTS: Thirty-two patients (64 per cent) underwent TPE for recurrent carcinoma of the cervix, seven (14 per cent) for rectal cancer, three (6 per cent) for vulval carcinoma, three (6 per cent) for vaginal carcinoma, two (4 per cent) for prostate cancer and three (6 per cent) for other tumours. The 30-day mortality rate was 8 per cent with an in-hospital mortality rate of 16 per cent. The crude morbidity rate was 62 per cent, with 23 patients (46 per cent) having grade III or IV toxicity. A complete response was achieved in 63 per cent and a partial response in 37 per cent of patients. The overall median survival time was 86 weeks; it was 111 weeks in patients in whom a complete response was achieved. CONCLUSION: The survival and operative mortality rates that are now attainable with TPE are comparable to those achieved with chemoradiotherapy in advanced pelvic neoplasia. TPE should no longer be reserved for salvage therapy and should perhaps be compared with chemoradiotherapy as first-line treatment in a phase III randomized trial in patients with these tumours.
Adult↗
Genetic studies of a family with hereditary hyperparathyroidism-jaw tumour syndrome.
BACKGROUND AND OBJECTIVES: Familial hyperparathyroidism may occur as familial isolated hyperparathyroidism (FIHP) or as part of an inherited syndrome, in particular multiple endocrine neoplasia types 1 and 2A (MEN1, MEN2A) and hyperparathyroidism-jaw tumour (HPT-JT) syndrome. The localization of the genes responsible for these syndromes has enabled genetic screening of families with primary hyperparathyroidism (PHPT) to be carried out. This has important clinical implications in terms of individual follow-up and management. We previously reported a large FIHP family with an increased risk of parathyroid cancer and excluded its linkage to MEN1, MEN2 and PTH genes. Here we re-analysed this family and performed genetic linkage to the HPT-JT locus in chromosome 1q21-q32. Loss of heterozygosity studies of 1q21-q32, 11q13 and X chromosome were also performed. PATIENTS AND DESIGN: We studied 19 family members, aged 6-63 years. High molecular weight DNA was isolated from peripheral blood samples from 17 family members. For the two deceased individuals, DNA was extracted from normal paraffin embedded tissues. MEASUREMENTS: All individuals (except two deceased patients) had serum corrected calcium, inorganic phosphate, intact PTH, prolactin and various pancreatic hormones, measured on fasting blood samples. Twenty microsatellite markers were examined for the 1q21-q32 region, the locus for the HPT-JT gene. Genetic polymorphisms were determined by polymerase chain reaction amplification of genomic DNA and genetic linkage analysis was performed. Loss of heterozygosity studies were performed using paraffin-embedded parathyroid tissues from four affected members. RESULTS: Seven of the eight affected family members included in this study had biochemical evidence of PHPT and surgically proven parathyroid tumours. Indication of linkage of the disease to the HPT-JT locus was demonstrated with a maximum lod score of 2.32 by two-points linkage analysis. Linkage data were supported by multi-point analysis which gave a maximum lod score of 2.7. Meiotic recombinations detected in one affected individual narrowed the region to 26 cM. As a result of the genetic findings, we re-screened the living family members by orthopantomograph and renal ultrasound, and identified two jaw lesions in two gene carriers. One affected family member demonstrated polycystic kidney disease, thus establishing the association between the two conditions. A reduced penetrance of HPT in females was evident, in agreement with our previous study. No allelic deletion was detected in any tumour at 1q21-q32, 11q13 or X chromosome. CONCLUSIONS: This study illustrates the usefulness and importance of genetic studies in familial isolated hyperparathyroidism families. Our clinical and genetic findings indicate that this previously reported familial isolated hyperparathyroidism family has hyperparathyroidism-jaw tumour syndrome.
Adolescent↗
Temporal change in microdosimetry to bone marrow and stromal progenitor cells from alpha-particle-emitting radionuclides incorporated in bone.
The microdistributions of the alpha-particle-emitting bone surface-seeking radionuclides (239)Pu, (241)Am and (233)U in the mouse femoral shaft have been studied using computer-based image analysis of neutron-induced and alpha-particle track autoradiographs, prepared from femora of CBA/H mice which had been injected with 40 kBq kg(-1) of radionuclide (as citrate solution) at times from 1 to 448 days previously. Employing dosimetric methods, radiation dose rates and cumulative radiation doses to regions of the bone marrow thought to contain hemopoietic and stromal progenitor cells susceptible to neoplastic transformation to leukemia and osteosarcomas have been calculated. It has been shown that the three radionuclides differ in their relative deposition on the bone surfaces, and that patterns of changing redistribution with time are also varied. For stromal progenitor cells, which are thought to be targets for induction of osteosarcoma and are found in proximity to the bone surfaces, cumulative doses showed the trend (239)Pu > (241)Am > (233)U, correlating well with incidences of osteosarcoma observed in mice. Cumulative doses to the primitive hemopoietic stem cells, concentrated in the central marrow and thought to be susceptible to neoplastic transformation to myeloid leukemia, were considerably lower and also showed the trend plutonium > americium > uranium.
Alpha Particles↗
Dermoid cyst of the parotid gland.
A dermoid cyst occurring within the parotid gland of a 37-year-old Chinese man is reported. The diagnostic difficulties, histopathological features and pathogenesis are considered.
Adult↗
Gut transfer and doses from environmental plutonium and americium.
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Americium↗
Microlithiasis in parotid sialadenosis and chronic submandibular sialadenitis is related to the microenvironment: an ultrastructural and microanalytical investigation.
AIMS: Microlithiasis was investigated in parotid sialadenosis and chronic submandibular sialadenitis to determine if it relates to the glandular microenvironment as has been found experimentally. METHODS AND RESULTS: Semithin sections were stained by a mixture of methylene blue and Azure II followed by basic fuchsin, which stains calcified parts of microliths red and organic parts green, and ultrathin sections were examined electron microscopically and microanalytically. Microliths in sialadenosis were found in periacinar stroma, in which necrotic acinar cells were found, and in parenchyma, and consisted of consolidated organic material with little or no crystalline calcium. Microliths in sialadenitis were found in stroma, particularly around intercalary ducts, in lumina and in parenchyma, and contained much crystalline calcium. Macrophages enclosed some microliths. CONCLUSIONS: The paucity of calcium in microliths in sialadenosis and the abundance in sialadenitis relates to the glandular calcium. The periacinar distribution of microliths in sialadenosis possibly relates to formation in periacinar necrotic debris. The distribution of microliths in sialadenitis around intercalary ducts possibly relates to formation in matrix vesicles formed from atrophic parenchyma, and in lumina to formation in stagnant secretory material. Microliths appear to be scavenged by macrophages. Thus the experimental finding that salivary microlithiasis relates to the microenvironment pertaining in humans.
Calcinosis↗
Role of microliths in the aetiology of chronic submandibular sialadenitis: a clinicopathological investigation of 154 cases.
AIMS: Confusion about the aetiology and pathogenesis of chronic submandibular sialadenitis led to the present investigation of 154 cases in which many clinical and histological features were analysed. METHODS AND RESULTS: By far the greatest number of histological factors, namely liths, atrophy, fibrosis, parenchymal inflammation, lymphoid germinal centres, mucous and ciliary metaplasia, salivary extravasation and glycosaminoglycan accumulation, was related to the degree of inflammation, which appears to be of the greatest importance in the aetiology and pathogenesis. Inflammation, atrophy and fibrosis were related to duration of symptoms, which supports the concept of a chronological progression through increasingly severe histological changes. CONCLUSIONS: Inflammation possibly arises from ascending infection in a normal gland and exerts an obstructive and destructive effect on the parenchyma with the development of the related histological changes and a vicious circle involving further ascending infection. Normal glands contain microliths that possibly by localized obstruction cause atrophic foci that are reservoirs for ascending infection. Microliths and liths were unrelated: microliths were related to age as in normal glands whereas liths were related to duration of symptoms and appeared to be secondary to the sialadenitis. Many glands showed minimal changes, which raises the possibility of conservative treatment.
Adolescent↗
Biokinetics and dosimetry of chromium, cobalt, hydrogen, iron and zinc radionuclides in male reproductive tissues of the rat.
Following intravenous administration to male rats, the uptake and retention by reproductive tissues of chromium-51, cobalt-57, iron-59, zinc-65 and tritium has been studied for up to 28 days. Chromium-51, 57Co, 59Fe and 3H were not or only transiently accumulated in gonads or accessory sex glands at concentrations greater than whole body concentrations. However, 65Zn was concentrated in the dorsolateral region of the prostate gland and autoradiography showed preferential uptake by epithelial cells and lumen of glands. When combined with other information available from the literature, this data would suggest that current models adequately describe the biokinetics of chromium, cobalt, iron and tritium in the prostate and testes and zinc in the testes. Uptake of zinc by the prostate would appear to be best described by an average value of 0.1% and a conservative value of 0.5%. Allowing for greater uptake of zinc (0.5%) by the prostate, after inhalation of 65Zn in a soluble form increases prostate dose by about 3 fold compared to current models. The pessimistic assumptions of a higher relative biological effectiveness (20) for all Auger emissions from 65Zn in cell nuclei and a heterogeneous distribution of 65Zn to sensitive cells in the prostate increases prostate dose by a further factor of 9. Even on the basis of these cautions estimates, occupational exposures to radioisotopes of these elements do not explain the excess of prostate cancer reported amongst some nuclear workers.
Animals↗
Localised oral histoplasmosis lesions associated with HIV infection.
Opportunistic fungal infections account for a significant amount of morbidity associated with HIV disease. We report here a case of localised oral histoplasmosis without evidence of disseminated disease in a patient who lacked stigmata of HIV disease at the time of initial presentation. The diagnosis is based on histology with special stains, complement fixing antibodies in serum, and culture of the organism from fresh tissues. Activation of subclinical disease following an infection in Uganda may explain the development of these exophytic oral lesions in this British resident.
AIDS-Related Opportunistic Infections↗