Biomedical subjects
P Hall
Publications and source records attributed to P Hall.
The death penalty.
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[Low risk of cancer after treatment of hyperthyroidism with iodine-131].
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HIV transmission and the law.
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Leukaemia incidence after iodine-131 exposure.
Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46,988 Swedish patients exposed to iodine-131 (131I) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy (range 0.01-2.226). 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1.09 (95% confidence interval 0.94-1.25). Similar, but again not significantly, increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR = 1.08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR = 1.09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from 131I. One reason for the absence of a radiation effect, other than chance, includes the possible lowering of risk when exposure is protracted over time as occurs with 131I. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to 131I in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident.
In vivo administration of bryostatin 1, a protein kinase C activator, decreases murine resistance to Salmonella typhimurium.
Bryostatin 1, a potent activator of protein kinase C, has antitumor activity against murine lymphoma, leukemia, and melanoma. In vitro, this compound stimulates the release of gamma-interferon, interleukins, and hematopoietic growth factors from accessory cells and activates both T- and B-cells. Bryostatin 1 is also able to stimulate neutrophils to undergo oxidative burst and degranulation. Because of the ability of this compound to stimulate the immune system, cause release of immune mediators, and activate neutrophils, we have examined its effect on bacterial infection by using the gram-negative bacterium Salmonella typhimurium in mice. We find that animals given injections i.v. of S. typhimurium have a shortened life span if they are also given injections i.p. of nonlethal doses of bryostatin 1. There is a dose-response relationship with 100 micrograms/kg bryostatin 1 having a greater effect on survival than 40 micrograms/kg. Below 40 micrograms/kg there are no effects on survival. Analysis of the first 4 h of Salmonella infection demonstrates that bryostatin 1 does not affect the blood clearance of the bacterium. However, by day 2 of infection greater numbers of bacteria are found in the livers and spleens of mice given injections of bryostatin 1. By day 5, 10-fold more S. typhimurium bacteria are found in the livers and spleens of mice receiving 40 micrograms/kg of bryostatin 1. To determine whether bryostatin 1 was affecting growth or causing the death of bacteria, we used a Salmonella carrying a plasmid which has a temperature-sensitive origin of replication and is unable to replicate when the bacteria are in mice. This experiment demonstrates that bryostatin 1 represses bacterial killing but does not affect bacterial growth. Bryostatin 1 given i.p. stimulates a transient syndrome of weight loss and diarrhea from which the mice recover and regain weight, suggesting that bryostatin 1 may release a number of important humoral mediators in vivo. The weight loss is exacerbated by Salmonella infection with mice receiving bryostatin 1 and S. typhimurium, in that they lose approximately 33% of body weight prior to death. Thus, at doses used to treat murine tumors, bryostatin 1 treatment does not affect the clearance of S. typhimurium from the blood but does decrease the killing of bacteria in the liver and spleen, leading to early animal death. Such potential effects of bryostatin 1 on the outcome of bacterial infections should be evaluated in ongoing human trials of this agent.
Cancer mortality after iodine-131 therapy for hyperthyroidism.
Cancer mortality was studied in 10,552 Swedish hyperthyroid patients treated with 131I between 1950 and 1975. The patients were matched with the Swedish Cause-of-Death Register and the cases of 977 patients who died from cancer or leukemia were studied. The patients had been followed up for an average of 15 years (range 0 to 35 years), and the overall standardized mortality ratio (SMR) was 1.09 [95% confidence interval (CI) = 1.03 to 1.16], with a higher risk for women. The highest mortality was seen during the first year after exposure (SMR = 1.15) and decreased for the following 9 years (SMR = 1.04). The risk of dying from a cancer in the digestive tract and respiratory organs was significantly elevated more than 10 years after exposure, as was the overall cancer mortality (SMR = 1.14). No increased risk was seen for leukemia, bladder cancer or breast cancer. Younger patients and those receiving 131I at higher activity had higher SMRs than older patients and those receiving lower activity. Patients with toxic nodular goiter had higher risk than those with Graves' disease. The lack of increasing mortality over time and with increasing activity of 131I administered argues against a carcinogenic effect of 131I. However, in the case of cancers of the stomach, the 131I exposure could have contributed to the excess mortality from these cancers.
Initial experience with the disarticulated (one-half) Palmaz-Schatz stent: a technical report.
We developed an alternative method to stent suitable lesions located in anatomical settings considered to be too complex for regular Palmaz-Schatz stent placement. This method consists of using a disarticulated (one-half) Palmaz-Schatz stent. Eight patients underwent stenting utilizing this method. The left anterior descending was stented in five patients, the right coronary artery in one patient, the proximal and mid shaft of a vein graft in one patient, and a protected left main coronary artery in one patient. In all patients the stents were placed in addition to full stents. In four patients, 1 1/2 stents were placed; two patients had 2 1/2 stents; one patient had 3 1/2 stents and the last patient had a total of 5 stents placed (1 full stent and 8 half stents). One patient had 8 disarticulated stents placed. All half stents prepared for delivery were successfully deployed to the pre-designated angiographic site without complication.
Fine-needle aspiration biopsy for the measurement of hepatic iron concentration.
The potential application of fine-needle aspiration liver biopsy in the documentation of hepatic iron overload has been assessed in iron-loaded rats. Fine-needle aspiration and standard liver biopsy specimens were obtained from three groups of animals supplemented with oral and parenteral iron for 2 to 6 mo. The mean dry weights of standard and fine-needle biopsy specimens were 7.41 +/- 0.77 (+/- S.E.M.) and 0.57 +/- 0.54 mg, respectively. Hepatic iron in fine-needle aspiration biopsy specimens correlated significantly with hepatic iron in standard liver biopsy specimens as measured by biochemical determination, computerized image analysis and histological grading (r greater than 0.9, p less than 0.001). In conclusion, we have shown that fine-needle aspiration biopsy of the liver can obtain sufficient tissue for biochemical measurement of the hepatic iron concentration in an animal model of iron overload. The clinical applications of fine-needle aspiration liver biopsy in human beings with iron overload is currently being investigated.
Radiation-induced thyroid cancer.
Thyroid cancer was the first solid tumor that showed an increased incidence among the Japanese A-bomb survivors and recently published data indicated an increase of thyroid cancer among children in Belarus. The annual thyroid cancer rate between 1986 and 1989 was 4 cases and 2 years later a 14-fold increase was found. That study has several methodological weaknesses but is nevertheless alarming. The present paper reviews the current epidemiological knowledge on radiation-induced thyroid cancer, and discusses the methodological difficulties. It is concluded that low doses of brief gamma radiation induce thyroid cancer in juveniles. No study has yet proven a relationship between protracted low dose exposure and thyroid cancer or an increased thyroid cancer risk among adults after exposure to any form of ionizing radiation. Thyroid cancer seems to have a somewhat shorter latency period than other solid tumors and the dose-response relationship seems to be linear. The most important issues in radiation protection concerning thyroid cancer are the risk of a thyroid cancer following low dose and/or protracted exposure to ionizing radiation and following 131I exposure in childhood.
Intestinal radioprotection by two new agents applied topically.
The purpose of this study was to test two novel antioxidant drugs, each capable of inhibiting membrane peroxidation and of free radical scavenging, as topical radioprotectants for the intestine. A loop of rat midintestine was exteriorized and radiated while the remainder of the animal was protected in a lead box. The intestine was first compartmentalized and each segment filled with a test solution. Radiated segments of intestine were compared, drug filled with vehicle filled, and both with normal unradiated intestine. The animals were killed 5 days after 1100 cGy radiation to the exteriorized loop. Crypt numbers and mucosal height were used as the measures of injury protection. On the basis of crypt numbers, the 21-amino steroid (U-74500A) gave approximately 40% and the vitamin E-like compound (U-78518F) gave 60% reduction in crypt loss. The authors conclude that lumenal antioxidant drugs can provide partial protection of the intestinal mucosa from acute radiation damage and that these two specific agents are effective and potentially useful.
The application of the seven-point check-list in the assessment of benign pigmented lesions.
One hundred consecutive histologically benign lesions seen at a pigmented lesion clinic were studied prospectively to assess the diagnostic accuracy of the seven-point check-list. Lesions were scored by both patient and physician. Thirty per cent of lesions attained a suspicious score. While there was a high level of agreement between patient and clinician regarding the individual characteristics of a lesion as defined in the check-list, final assessments differed. Most patients considered their lesions suspicious, whereas the clinicians correctly recognized that in 94% cases they were benign. The seven-point check-list often fails to exclude common benign pigmented lesions. The revised (1989) check-list is even less specific (70% of lesions achieving a suspicious score). Such check-lists are difficult for the inexperienced to interpret. Clinical familiarity is required in order to provide a confident diagnosis. Future emphasis should be directed towards improving screening in primary care.
'The current literature'--Worcester Development Project.
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Tumors after radiotherapy for thyroid cancer. A case-control study within a cohort of thyroid cancer patients.
A case-control study of Swedish thyroid cancer patients was conducted to evaluate the possible influence of 131I treatment and external radiotherapy on the risk of developing a subsequent cancer. Both cases and controls derived from a cohort of Swedish thyroid cancer patients treated with 131I (n = 834) or by other means (n = 1,121). Thirty-six breast, 13 stomach, 12 kidney, and 5 bladder cancers were found more than 2 years after 131I treatment/thyroid cancer diagnosis. Individual, absorbed dose in the organs was calculated by using ICRP tables, administered activity of 131I, and 24-h 131I uptake. In studying the effect of 131I and external radiotherapy no statistically significant dose-response relationships were found for cancers of the breast, stomach, bladder or kidney. When the absorbed dose from 131I was analyzed separately the risks remained essentially the same. The present follow-up time and the relatively low absorbed dose that the patients received from 131I and external radiotherapy necessitate studies with a longer follow-up time or a larger patient material before more firm conclusions can be made.
Special medical and nursing care needs of people with severe learning difficulties.
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Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer.
Detection of ovarian cancer at an early stage should reduce the mortality associated with this disease. Through the Stockholm Population Registry, 5550 apparently healthy women were enrolled in a study designed in part to define the use of the CA 125 radioimmunoassay (RIA) as an initial test for early detection of ovarian cancer. Women whose CA 125 levels were elevated and an equal number of age-matched controls with normal levels were followed by means of pelvic examinations, transabdominal sonography, and serial CA 125 determinations. Of the 175 women with high CA 125 levels, six were found to have ovarian cancer: two each in stages IA, IIB, and IIIC. Of those with normal-range CA 125 levels, three had ovarian cancer as identified through the Swedish Cancer Registry; all three were under 50 years of age. Ovarian cancer was diagnosed on laparotomy in six of the women age 50 or over. Using thresholds of 30 and 35 U/mL, the rates of specificity for the CA 125 RIA were 97 and 98.5%, respectively, for women age 50 or older, and 91 and 94.5%, respectively, for those younger than 50 years of age. Thus, the specificity of the CA 125 RIA is adequate in postmenopausal women to undertake a larger study to determine whether screening using CA 125 influences survival of patients with ovarian cancer.
Detection of intratumoral aromatase in breast carcinomas. An immunohistochemical study with clinicopathologic correlation.
The expression of aromatase was evaluated in 38 breast carcinomas by an immunohistochemical method (ABC) using an specific polyclonal antibody against human placental aromatase. Fifteen tumors (40%) showed significant immunoreactivity, as defined by cytoplasmic positivity of moderate intensity present in at least 15% of the cells. The results were correlated with the estrogen and progesterone hormone receptor status and several clinicopathologic parameters such as age, tumor size, lymph node status, and stage of the disease. There was a significant, but inverse, correlation between the aromatase activity and the estrogen receptor status (P = 0.04), indicating the likelihood of negative estrogen if substantial aromatase activity was present. No statistically significant correlation was found between the presence of intratumoral aromatase and the rest of the parameters studied (P greater than 0.7). Nor was there a correlation between the aromatase content of the tumors and the menopausal status. The degree of intratumoral heterogeneity of the aromatase content was minimal in six cases where multiple samples from each tumor were analyzed. This is the first study reporting the detection of aromatase in archival material from breast carcinomas using immunohistochemical techniques. The lack of biologic significance of its presence in breast cancer reported here and by others using biochemical assays should be validated in larger series with longer follow-up. The method described can be readily used for that objective.