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Biomedical subjects

A Lindgren

Publications and source records attributed to A Lindgren.

At least 181 records · Page 10Linked to original sources

Prognostic implication of estrogen receptor content in breast cancer.

The cytosolic estrogen receptor (ER) content of the primary tumor was determined by isoelectric focusing in 170 consecutive women with unilateral breast cancer diagnosed in 1977 through 1980. No adjuvant treatment over and above surgery and radiotherapy was given. The overall corrected survival was not significantly (p greater than 0.05) higher in ER-rich (less than 0.1 nmol/g DNA) than in ER-poor tumors, but the median period from recurrence to death was longer in the former (16 months) than in the latter (10 months) group. The difference in disease-free survival (DFS) in favour of the ER-rich tumors achieved its maximum-about 15%-after two years (p less than 0.01). At prolonged follow-up, however, the curves converged and there was no significant difference when the whole six year period of observation was taken into account. In patients without axillary metastases the same pattern emerged, with earlier recurrences in ER-poor tumors and a difference in DFS between the two ER groups at two years (p less than 0.01) which was diminished after five years (p less than 0.05). The ER content provided no significant prognostic information in patients with axillary node metastases or locally advanced disease. We conclude from the present and other available data that the ER content in breast cancer would seem to be an indicator of growth rate rather than of metastatic potential and accordingly a predictor of the pattern of recurrence and length of disease-free survival rather than of long-term survival.

Adult↗

Endometrial polyps and hyperplasia as risk factors for endometrial carcinoma. A case-control study of curettage specimens.

As part of a comprehensive case-control study, the impact of previous endometrial pathology on the risk of developing endometrial carcinoma was investigated. The study comprised 254 consecutive women with histopathologically confirmed cancer of the uterine body in a well-defined population, and their age-matched controls. Ninety-eight (39%) of the patients and 81 (32%) of the controls had previously undergone endometrial curettage. More than one previous curettage was positively associated with endometrial carcinoma (odds ratio = 2.5; 95% CL = 1.4-4.5). Endometrial abnormalities in previous curettage specimens occurred significantly more often among carcinoma patients (57%) than among controls (25%) (odds ratio = 4.0; 95% CL = 2.0-8.0). Twelve patients, but no controls, had adenomatous hyperplasia and this hyperplasia antedated the cancer diagnosis by a mean of 4.6 years. Endometrial polyps were present significantly more often in patients (20%) than in controls (10%) (odds ratio = 3.4; 95% CL = 1.3-9.3). The present results suggest that both of these conditions are risk factors for endometrial carcinoma. Among women who had undergone endometrial curettage more than 4 years after the menopause, 19 out of 30 patients, but none out of 7 controls, showed abnormality in the curettage specimens. Postmenopausal women with endometrial abnormality should thus be regarded as being at risk of developing endometrial carcinoma.

Age Factors↗

Nuclear DNA and endocrine activity in carcinomas of the breast.

In a running study of nuclear DNA profiles of female breast carcinomas, 60 consecutive tumors were collected and stained with the Grimelius argyrophil reaction for the identification of endocrine tumor cells. Four (6.7%) tumors were argyrophilic, and they all displayed diploid nuclear DNA values. The argyrophil tumors constituted 20% of the diploid breast carcinomas. One of the tumors was examined electron microscopically and exhibited an abundance of intracytoplasmatic granules of neurohormonal type. In none of the four carcinomas could the endocrine activity be inferred from the morphologic appearance alone, since all could be grouped in regular histopathologic terms. Since the frequency of endocrine cells in unselected materials of breast adenocarcinomas is very low, a relationship exists between diploid nuclear DNA values and with neurohormonal production in these tumors.

Breast Neoplasms↗

Accumulation of toxic metals in male reproduction organs.

Occupation exposure to metals has been related to impaired reproduction in males. This report summarizes autoradiographic studies on the distribution of cadmium (Cd), chromium (Cr) and arsenic (As) in the testis and epididymis of rodents. Cd and Cr strongly accumulated in the interstitial tissues, indicating an effect on hormone production (Leydig cells) and blood supply or both. Arsenic accumulated in the lumen of the duct of epididymis causing long-term exposure of the semen.

Animals↗

Embryotoxicity of arsenite and arsenate: distribution in pregnant mice and monkeys and effects on embryonic cells in vitro.

The distribution of 74As-labelled arsenate and arsenite in pregnant mice and a monkey has been studied by autoradiography and gamma counting of isolated tissues, and their in vitro toxicity to a chondrogenic system has been investigated. With both arsenic forms, given as single intravenous injections to the mother, the 74As-arsenic appeared to pass the mouse placenta relatively free and approximately to the same extent. The retention time in maternal tissues including the placenta was, however, around three times longer with arsenite than with arsenate. In early gestation, high activity was registered in the embryonic neuroepithelium, which correlates well with reported CNS malformations in rodents. In late gestation, the distribution pattern was more like that in the adults. Accumulation in skin and squamous epithelia of the upper gastrointestinal tract (oral cavity, oesophagus and oesophageal region of stomach) dominated the distribution picture, especially at a long survival interval. Arsenate, but not arsenite, showed affinity for the calcified areas of the skeleton. A marmoset monkey in late gestation receiving arsenite showed a somewhat lower rate of placental transfer than the mice. Skin and liver had the highest concentrations (at 8 hrs), both in mother and foetuses. This species is known not to methylate arsenic, resulting in stronger binding and longer retention times of arsenic as compared with other species. The stronger binding in maternal tissues may possibly explain the lower rate of placental transfer. Arsenite was shown to inhibit cartilage formation in a chick limb bud mesenchymal spot culture system (ED50 approximately 5-10 microM), while arsenate seemed to be without effect at concentrations up to 200 microM (highest tested). Arsenate, however, showed a potentiation of the arsenite toxicity.

Animals↗

Disseminated pulmonary aspergillosis in a previously healthy young woman.

A young woman presented with widespread bilateral infiltrates on chest X-ray and a high fever. Investigations for bacterial, mycobacterial, and fungal infections were negative. A biopsy of the lung showed granulomas, and corticosteroid medication was given on vital indication because of the rapidly progressive disease. There was a dramatic response, with regression of the chest X-ray changes and the fever and the patient was discharged on her own request with a tentative diagnosis of acute sarcoidosis. One month later she was admitted in an alarming state with almost completely consolidated lung and died a few hours later. Autopsy revealed generalized aspergillosis. Renewed extensive investigation of the earlier lung biopsy revealed hyphae. After her death, the case history of an elder brother was traced and revealed that he had died at early age in a generalized granulomatous disease. Although no definite diagnosis can be made, it seems likely that both siblings suffered from a defect in the immune system, probably chronic granulomatous disease of the autosomal recessive type. This disease is sometimes found in young adults without a clear history of earlier infections.

Adult↗

Transplacental movement of inorganic lead in early and late gestation in the mouse.

203Pb(NO3)2 was administered i.v. to pregnant C57BL mice at different stages, from day 8 to day 18 of gestation. The whole animals or excised uteri were subjected to autoradiography or were autopsied for scintillation counting of excised organs. Lead appeared in embryonic and fetal tissues at all stages of gestation. Early (approx. day 8-11) lead was restricted mainly to the embryonic blood, suggesting that free lead was essentially not transferred to the embryo but may have been incorporated in the embryonic hemoglobin when the erythrocytes were formed in the yolk sac placenta (an extraembryonic membrane). From day 12 and later, an uptake was seen in the liver and the cartilaginous skeleton, and from day 14, a strong accumulation was found in calcified bone. This means that the overall fetal concentration increased successively with gestational age of the conceptus. The uptake in fetal liver may be related to the erythropoiesis taking place in the liver in later gestation. While an accumulation of lead was observed in proximal tubuli of the maternal kidney, no corresponding uptake occurred in the fetal kidney. Although lead is teratogenic, causing among others skeletal defects, no effect of inorganic lead in mM concentration was seen on a chondrogenic cell system in vitro. Due to the predominance of lead in hemoglobin, a mechanism of teratogensis based on inhibition of fetal hemoglobin synthesis or function is discussed.

Animals↗

A whole body autoradiographic study on the distribution of 14C-labelled di-(2-ethylhexyl)phthalate in mice.

Di-(2-ethylhexyl)phthalate (DEHP), a plasticizer used for polyvinylchloride polymers, has been reported to leach from blood transfusion bags and the plastic material in hemodialysis units into the blood. Phthalate esters are known to be hepatotoxic and teratogenic in experimental animals. Reports on the distribution and metabolism of DEHP indicate that the compound in largely excreted from the body within a few days. In the present investigation the distribution and tissue retention after administration of [14C]DEHP (carbonyl-14C or 2-ethylhexyl-1-14c) was studied in pregnant and non-pregnant mice with whole body autoradiography. Initially a high activity was observed in the brown fat, liver, gall bladder, intestinal contents, kidney and urinary bladder. Pretreatment with DEHP, phenobarbital sodium or 3-methylcholanthrene caused a relative increase of the activity in the brown fat, indicating that induced metabolic conversion of DEHP leads to an increased deposition of radioactivity in brown fat. After administration of DEHP (carbonyl-14C), but not DEHP (2-ethylhexyl-1-14C),marked retention was observed in the skin, cartilage and tendons. The mechanism responsible for the slow accumulation in these connective tissues is not known. In the early embryo a high concentration was observed in the neuroepithelium. This pronounced uptake may be correlated to the DEHP-induced malformations exencephaly and spina bifida observed in mice.

Animals↗

Autoradiographic studies on the distribution of arsenic in mice and hamsters administered 74As-arsenite or -arsenate.

Whole-body autoradiography in combination with other determinations of tissue levels of 74As-arsenic in mice, 5 min. to 30 days after intravenous injections of 74As-arsenite (As III) or -arsenate (As V), showed higher organ concentrations and whole-body retention of arsenic in the As III mice as compared to the As V mice. Only the kidneys (at short time intervals) and the skeleton had higher levels in the As V mice as compared to the As III mice. The skeletal accumulation of As V is probably due to the resemblance of the arsenate to phosphate, so that arsenate may substitute for phosphate in the apatite crystal. The long-term retention of arsenic was most apparent in hair and skin, squamous epithelium of the upper gastrointestinal tract (oral cavity, oesophagus, and the oesophageal part of the stomach mucosa), the epididymis, thyroid, lens and skeleton. The accumulation in hair, skin and the upper gastrointestinal tract may be ascribed to a binding to keratin, the content of which is high in squamous epithelia. The distribution of arsenic in golden hamsters was similar to that found in mice. The significance of the findings in relation to reported adverse effects of inorganic arsenic is discussed.

Animals↗

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Germany↗

Fluorescence cytophotometric measurements of nuclear DNA in adenocarcinoma of the lung; relation of proliferative activity and DNA ploidy to prognosis.

Nuclear DNA measurements on specimens of adenocarcinomas of the lung obtained at surgery from 22 patients showed that in 8 tumors the cells were near diploid and slowly proliferating. These 8 tumors displayed a higher degree of histopathologic differentiation than did the remaining 14 adenocarcinomas. In 3 of the 14 more poorly differentiated tumors the cells were also near diploid but had more S-phase DNA values, indicating increased proliferative activity. In 11 tumors aneuploid DNA stem line or lines were noted. Among patients with slowly growing near-diploid tumors the frequency of tumor recurrence and/or metastases (1 of 8) was lower than among those with more rapidly proliferating near-diploid tumors and aneuploid tumors (9 of 14). Nuclear DNA histogram patterns yielded information about the tumor proliferation activity, modal DNA value and occurrence of aneuploid DNA values. Furthermore, prognostic information about the likelihood of tumor recurrence after surgical treatment was obtained. This information can be utilized in the choice of therapy and in prognostic evaluation.

Adenocarcinoma↗

Histopathological malignancy grading and familiality in an unselected series of 1303 women with breast carcinoma.

Histopathological characteristics were studied in 1303 women consecutively diagnosed as having breast cancer. They comprised a total material from a defined geographical area. The significance and distribution of malignancy grades according to Ackerman's system were evaluated in this unselected material. Their relationships with other morphological characteristics and with the occurrence of axillary node metastases with or without periglandular growth were appraised. These characteristics were also related to the familial occurrence of breast cancer. The distribution according to the Ackerman grading was: type I 39 cases (3%), type II 75 (6%), type III: 2 95 (7%), type III:1 793 (61%) and type IV 301 cases (23%). The degree of differentiation (partly by definition) correlated highly significantly with the malignancy grading. Axillary lymph nodes were available for histopathological examination in 844 cases. In malignancy types I and II there were no lymph node metastases, in type III:2 2%, in III:I 40% and in type IV 77%. Periglandular growth was found only in type III:I and IV--in 9 and 59%, respectively. Familial occurrence of breast cancer was confirmed in 19% of the patients. Familial and non familial cases did not differ significantly with respect to the distribution of malignancy grades, degree of differentiation, grade of cell polymorphism or frequency of lymph node metastases.

Aged↗

Endometrial patterns in women on chronic luteinizing hormone-releasing hormone agonist treatment for contraception.

Endometrial biopsy specimens were obtained from 12 healthy women under chronic intranasal luteinizing hormone-releasing hormone (LH-RH) agonist treatment for evaluation of the risk of endometrial hyperplasia during long-term inhibition of ovulation. A single daily dose of 400 or 600 microgram of the superactive LH-RH agonist D-Ser(TBU)6-EA10-LH-RH was given for 13 to 55 weeks. Treatment was monitored by clinical examination, basal body temperature (BBT) recordings, and frequently taken venous blood specimens for determination of estradiol and progesterone. Ovulation was inhibited during all but 2 of the 102 treatment cycles. No pregnancy occurred. Six of the women had slight menstrual-like bleeding, and six hac amenorrhea during the treatment period. No dysfunctional uterine bleeding occurred. The dominating histologic picture of the 17 endometrial biopsies, obtained after 78 to 380 days of treatment, was inactive or weak proliferative glands with slightly atrophic stroma. There were no signs of hyperplasia. After discontinuation of treatment ovulatory menstrual cycle rapidly returned.

Administration, Intranasal↗

Foetal distribution and metabolism of N-nitrosodiethylamine in mice.

In pregnant NMRI mice, low-temperature autoradiography was used to study the distribution of N-14C-nitrosodiethylamine in foetal tissues, and autoradiography with heated tape-sections was used to trace nonvolatile metabolites. Autoradiography with 14C-acetate was used to distinguish the part of the radioactivity which upon the degradation of N-14C-nitrosodiethylamine may be incorporated in the normal metabolism of the tissues. The results indicated that the non-metabolized N-nitrosodiethylamine passed to the foetuses with an even distribution in most foetal tissues on all the studied days of gestation (day 12, 14, 16 and 18). The autoradiographic results further indicated a metabolism of the substance in the mucosa of the foetal bronchial tree and in the foetal liver on day 18 of gestation, but not in earlier stages of pregnancy. This was substantiated by studies in vitro, which showed a marked capacity of the 18 day old foetal lung and liver (in contrast to tissues from 16 day old foetuses) to form 14CO2 from the N-14C-nitrodiethylamine. Since the lung and liver are target tissues for the transplacental carcinogenesis of N-nitrosodiethylamine in NMRI mice, a causal relationship between metabolic ability and carcinogenesis may exist in these tissues.

Acetates↗

Bilateral carcinoma of the breast. Epidemiology and histopathology.

A history of previous carcinoma in the contralateral breast was found in 66 of 1351 women (5%) consecutively diagnosed as having breast carcinoma. The mean time interval between the diagnosis of the first and second tumour was 10.0 years (range 0-37 years); 63 of the tumours were metachronous. No significant differences were found between the first and the second carcinoma with respect to the Ackerman malignancy grading or the frequency of axillary node involvement. High risk groups for bilateral disease could not be defined on the basis of information about familial occurrence, parity, age at first birth, or malignancy grade.

Adult↗

Pleural plaques: correlation of autopsy findings to radiographic findings and occupational history.

An investigation was made to correlate autopsy findings of pleural plaques (PP) with the occupational history and findings of such plaques at X-ray before death. A good correlation was found between occupation and occurrence of PP at autopsy. Using strict criteria, 12.5% of all PP observed at autopsy, including small ones, were visible at X-ray. Almost half (3 of 8) of the widespread changes found at autopsy were seen on the X-rays. With more liberal roentgenological criteria 11 of the 24 cases were noted, but there were also 15 false positives.

Adult↗