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Biomedical subjects

J Visfeldt

Publications and source records attributed to J Visfeldt.

At least 37 records · Page 2Linked to original sources

Pathoanatomical aspects of malignant haematological disorders among Danish patients exposed to thorium dioxide.

The Danish Thorotrast Study was recently reestablished and improved. The cohort has been reidentified and followed up, and now comprises 1003 Thorotrast-exposed patients. For all suspected haematological cases, cytological and histological material has been revised and malignant diseases have been reclassified. The numbers of cases of leukemia and other related haematological disorders were as follows: 16 acute myeloid leukemia (AML); 8 myelodysplastic syndrome (MDS); 1 acute lymphatic leukemia (ALL); 3 chronic myeloid leukemia (CML); 4 non-Hodgkin's lymphoma (NHL); 2 multiple myeloma (MM); 2 myelofibrosis (MF); 2 chronic lymphatic leukemia (CLL). Except for CLL, all cases might be Thorotrast-induced. (Expected number of leukemias: < 2.5.) The findings in the German, Japanese, Portuguese and Danish studies are very similar. Some of the characteristic features include a high incidence of AML with several erythroleukemias, many cases of MDS, and a relatively low incidence of CML. In several studies of leukemia induced by alkylating agents, erythroleukemia is also described as a prominent feature. The possibility exists that a phase of relative predominance of erythroid elements in the bone marrow may be a common and not an unusual feature in the pathogenesis of these secondary leukemias. The findings are also compared with histopathological data from a Danish control group of de novo leukemia patients and from atomic bomb survivors with radiation-induced leukemia. The relative frequency of AML is higher among the Thorotrast-exposed patients than among the Danish control group and the A-bomb survivors. In contrast, low relative frequencies are seen for ALL and CML in Thorotrast cases in comparison with de novo leukemia cases and A-bomb survivors. It can be concluded that differences in relative and absolute frequency of leukemias and myelodysplastic syndrome exist not only between the irradiated populations and the unexposed control group, but even between groups exposed to low-LET (linear energy transfer) and high-LET radiation.

Acute Disease↗

Testicular germ cell tumours of childhood in Denmark, 1943-1989: incidence and evaluation of histology using immunohistochemical techniques.

In the Danish Cancer Registry, 72 testicular tumours in boys younger than 15 years of age were recorded during the period 1943-1989 and material from 34 of these was retrieved from Danish departments of pathology. The histological types were evaluated and the role of immunohistochemical staining was analysed. The survival of the patients was correlated with the histological diagnoses, and changes in the incidence of testicular cancers in childhood were analysed. Twenty-nine of the 34 patients had germ cell tumours, which fell into two groups (infantile and pubertal) with distinct differences. The tumours of infancy usually presented before the age of 3 years and were either pure yolk sac tumours or teratomas. The tumours of puberty showed no morphological or immunohistochemical differences from adult germ cell tumours. In the infantile group, immunohistochemical staining confirmed the morphological evaluation but was not necessary for diagnosis. Patients in the infantile group seemed to have a better prognosis than adult patients, only one patient dying from his disease, whereas the pubertal patients seemed to have a prognosis similar to that of adult patients. The incidence of infantile testicular cancer in Denmark appears to have increased at almost the same rate as that observed in adult men, but due to the small numbers in infancy, this cannot be statistically substantiated. We conclude that the testicular germ cell tumours of infancy and puberty may arise from different precursor cells, but both groups seem to arise prenatally.

Adolescent↗

Primary liver tumors among Danish patients exposed to Thorotrast.

The potential carcinogenic effects of internally deposited alpha-particle-emitting nuclides, notably plutonium, in the liver in humans are unknown but are of concern in relation to exposures from the nuclear industry. However, patients injected with the radiographic contrast medium Thorotrast are chronically exposed to alpha-particle radiation from 232ThO2 in the liver. Among 1003 patients injected with Thorotrast, 584 of whom were alive 15 years after the injection and 40 at the end of follow-up, a total of 127 liver cancers were diagnosed, 45 of which were hepatocellular carcinomas, 41 cholangiocarcinomas and 33 hemangiosarcomas. The median time from injection to diagnosis was 35 years (range 18-48) and the cumulative frequency was 55.4% after 48 years. In univariate and multivariate analyses, the cumulative frequency of liver cancer was best described as a function of the estimated mean cumulative alpha-particle radiation dose to the liver 15 years ago, being independent of age, gender and volume of injected Thorotrast. This may be interpreted to mean that the liver cancer rate is not related to the dose rate and that the period from malignant transformation to diagnosis of cancer is 15 years. The risk of liver carcinogenesis induced by alpha-particle radiation, assuming 15 years from induction to diagnosis, was estimated to be 712 cases/10(4) persons per gray. This value is considerably higher than estimated earlier.

Adolescent↗

Human papillomavirus in vulvar squamous-cell carcinoma and in normal vulvar tissues: a search for a possible impact of HPV on vulvar cancer prognosis.

Paraffin-embedded sections of vulvar squamous-cell carcinomas and of normal vulvar tissues were examined for HPV types 6, 11, 16, 18 and 33 by the polymerase chain reaction. Overall, 19 of 62 tumours harboured HPV DNA of types 16, 18 or 33. HPV types 6 and 11 were not detected. HPV DNA was found in 61% of tumours with adjacent intraepithelial neoplasia (VIN III), and in 13% of tumours without associated VIN III. HPV DNA was not detected in any of 101 normal vulvar tissues. HPV DNA was found more often in younger women, in patients with VIN III-associated tumours, and in those with multicentric anogenital neoplasia. This points to the existence of a subset of vulvar carcinomas preceded by intraepithelial neoplasia, with HPV as a major factor in carcinogenesis. HPV also seems to be an important factor in the development of multiprimaries in these patients. The 2 groups of patients with vulvar carcinoma did not differ with regard to prognosis, as estimated by the risk of recurrence after primary surgery.

Adult↗

The significance of histology and morphometry in predicting lymph node metastases in patients with squamous cell carcinoma of the vulva.

The material consists of a series of 73 patients with squamous cell carcinoma of the vulva. The site and the size of the primary tumor and the histological status of the lymph nodes of the groin were known. Two pathologists evaluated nuclear hyperchromatism, nuclear polymorphism, histological differentiation, number of mitoses, inflammatory response, and vascular invasion and graded these parameters from one to three. The reliability of the histopathological grades evaluated by the kappa coefficient showed considerable interobserver variation. Despite this a model which included the subjective parameter nuclear hyperchromatism could predict patients without lymph node metastases. The model consisted of patients with tumors which were not situated on the clitoris, were less than 40 mm in diameter, and exhibited only slight hyperchromatism. The model fitted 19 (26%) and 14 (19%) of the patients with two different pathologists evaluating the nuclear hyperchromatism and none of these patients had lymph node metastases. The quantitative parameter--mean nuclear volume--determined by morphometry was of no diagnostic value for the prediction of patients without groin node metastases at the time of operation.

Adult↗

Relation between bone marrow hemosiderin iron, serum iron status markers, and chemical and histochemical liver iron content in 82 patients with alcoholic and nonalcoholic hepatic disease.

Bone marrow hemosiderin iron was assessed in 48 patients with alcoholic, and in 34 patients with nonalcoholic liver disease (53 men, 29 women, median age 55 years, range 18-84) and correlated to serum (S)-iron status markers (iron, transferrin, ferritin), as well as to histochemical hepatocyte iron and chemical liver iron content. In a control group of 53 healthy subjects (23 men, 30 women, median age 28 years, range 18-90) marrow hemosiderin iron and iron status markers were evaluated as well. Among liver patients, the marrow iron grade was higher in men than in women (p = 0.03). Correlations were found between marrow iron and histochemical liver iron (rho = 0.38, p = 0.0001) as well as chemical liver iron (rho = 0.33, p = 0.01). Marrow iron was correlated to S-ferritin (rho = 0.53, p = 0.0001), mean red cell volume (rho = 0.34, p = 0.003), and S-transferrin (rho = -0.24, p = 0.02). Alcoholics had a higher marrow iron grade than nonalcoholics (p = 0.001) and controls (p = 0.0001). Among controls, the marrow iron grade was likewise higher in men than in women (p = 0.01). Correlations were found between marrow iron and ferritin (rho = 0.64, p = 0.0001), transferrin saturation (rho = 0.56, p = 0.001), transferrin (rho = 0.53, p = 0.001), S-iron (rho = 0.37, p = 0.01), and hemoglobin in women (rho = 0.38, p = 0.05). The results indicate that alcoholics either have increased marrow hemosiderin iron stores, or display a redistribution of iron in reticuloendothelial cells from soluble ferritin-bound iron to insoluble hemosiderin iron. Among patients with absent marrow hemosiderin iron, 81% had absent hepatocyte hemosiderin iron as well. Among patients with absent hepatocyte hemosiderin iron, 23% had absent and 77% normal or increased marrow hemosiderin iron. Therefore, in patients with iron depletion, assessment of marrow hemosiderin iron yields more relevant information of iron status than assessment of hepatocyte hemosiderin iron.

Adolescent↗

Prediction of lymph node metastases in patients with early squamous cell carcinoma of the cervix uteri by histopathological grading and flow cytometry.

The present study comprises a retrospective investigation of 126 patients with stage IB squamous cell carcinoma of the cervix, and a similar prospective investigation of 53 patients with stage IB and 6 patients with stage IIA disease. Tumour biopsies from these patients were analysed by means of flow cytometry and a semiquantitative histological grading system. The study showed that a combination of a low tumour cell DNA index and a low score value of the grading system indicated a very low risk of regional lymph node metastases (0% lymph node metastases in patients with low scores vs. 24-46% metastases in patients with high scores, P < 0.001). In order to study the reproducibility of the histological grading 20 randomly selected cases were studied blindly by three of the participating pathologists and after discussion of the grading criteria. A kappa coefficient of 722 demonstrated a substantial agreement between the observers. These results suggest that by combining flow cytometry with semiquantitative histological grading, a subgroup of patients with early squamous cell cancer of the cervix uteri may be selected that could be sufficiently treated with simple hysterectomy instead of radical hysterectomy including lymphadenectomy, which, in many oncology centres, is the standard treatment of this patient category.

Carcinoma, Squamous Cell↗

Leukemia and other related hematological disorders among Danish patients exposed to Thorotrast.

At least 60 case studies of leukemia among people exposed to chronic low-dose alpha-particle radiation from injections with the radiographic contrast medium Thorotrast and 115 cases from follow-up studies have been described in the literature. In the present study, malignant hematological diseases among 1003 Danish patients injected during 1935-1947 and followed to 1992 accruing 20,433 person-years were assessed and available histopathological specimens revised. The mean cumulative bone marrow alpha-particle radiation dose (1.34 Gy) was estimated from records of the amount of Thorotrast injected (mean 18.7 ml). Sixteen cases of acute myelogenous leukemia (AML) and seven cases of myelodysplastic syndrome (MDS) were diagnosed 8-40 years after injection, the cumulative frequency reaching 7.6%. No significant relationship was seen between the cumulative frequency of AML + MDS and the age at injection, gender, or amount of Thorotrast injected, but a multivariate analysis described data best by a model with the bone marrow dose and the power of the attained age. The risk estimate for AML + MDS was 173 cases/10(4) persons per Gy. If also considering cases of acute lymphocytic leukemia (1), chronic myelogenous leukemia (3), non-Hodgkins lymphoma (4), and multiple myeloma (2), the risk estimate became 248 cases/10(4) persons per Gy. It is suggested that RBE of alpha particles from thorium may be lower than 20.

Adolescent↗

Human papillomavirus types 16 and 18 in adenocarcinoma of the uterine cervix.

Fifty cervical adenocarcinomas and 50 squamous cell carcinomas from age-matched patients were examined for human papillomavirus (HPV) types 16 and 18. The polymerase chain reaction was used to examine formalin-fixed, paraffin-embedded carcinoma tissues for 120 and 113 bp sequences, respectively, of the highly conserved E6/E7 regions of the viral genomes. HPV type 16 was detected more often in squamous cell carcinomas than in adenocarcinomas (60% vs 18%, P less than 0.001). Conversely, HPV type 18 was detected significantly more often in adenocarcinoma tissues (52% vs 12% in squamous cell carcinomas, P less than 0.001). These differences may reflect the fact that different virus receptors exist in cervical cells with different morphologic potential, or they may indicate that the specific HPV infection actually plays a role in directing carcinogenesis.

Adenocarcinoma↗

Mucin-type carbohydrates (type 3 chain antigens) in normal cycling human endometrium.

Carbohydrates related to the ABO, Tn, and T blood group systems are markers of cellular differentiation in many epithelial tissues. Using a panel of specific monoclonal antibodies, we have immunohistochemically investigated the expression of mucin-type (type 3 chain ABO-related) antigens in 64 samples of normal cycling endometria of known ABO and Lewis blood type. Tn and T antigens had a highly restricted expression in normal cycling endometrial tissue. The expression of type 3 chain H and A antigens was always compatible with the ABO blood type of the individual and seems to be regulated by the secretor genes, as secretors [Lewis (a-b+)] expressed more A and H type 3 chains than nonsecretors [Lewis (a+b-)]. The expression of type 3 chain H and A, sialyl-Tn and sialyl-T antigens showed cyclic variations in the glandular epithelium of the functionalis, but not of the basalis layer of cycling endometrium. A hormonal regulation of the enzymes involved in blood group-related carbohydrate chain elongation in human endometrium is thus possible and may participate in the specialized secretory process of human cycling endometrium.

ABO Blood-Group System↗

Monoclonal antibody 43-9F: an immunohistochemical marker of embryonal carcinoma of the testis.

Discrimination between different types of germ cell tumours may be difficult in routine histological preparations. Additionally, none of the established immunohistochemical markers is completely reliable in diagnosis of embryonal carcinoma. A pilot study indicated that monoclonal antibody 43-9F--a marker of carcinoma-in-situ germ cells--may also react with embryonal carcinoma of the testis. In order to elucidate the applicability of 43-9F in diagnosis of embryonal carcinoma, 42 consecutive testicular germ cell tumours were tested immunohistochemically. Among the 42 tumours, 23 were seminomas and 19 were non-seminomas with seminomatous components in seven of them. Embryonal carcinomas were found in 15 tumours, two being of pure type and the remaining 13 a part of mixed tumours. Additionally, the material included 11 teratomas, nine yolk sac tumours and one choriocarcinoma. Immunohistochemical stainings were performed with 43-9F and additionally with antibodies against placental-like alkaline phosphatase, cytokeratins, alpha-foetoprotein and human chorionic gonadotropin. Using 43-9F a strong colour reaction was found in 13 of the embryonal carcinomas, whereas the reaction was moderate in the remaining two cases. A weak positive reaction was found in six seminomas and the remaining 24 did not react at all. 43-9F exhibited a positive reaction in four of 11 teratomas. The reactivity was generally weak with some focal areas with strong staining. In five cases the yolk sac tumour elements did not stain with this monoclonal antibody. The reaction was weak in three cases and in only one case was the staining intensity scored as moderate. Finally, no reaction was found in the choriocarcinoma element. Compared to the other antibodies tested, including the antibody against cytokeratins, in embryonal carcinoma immunohistochemical staining with 43-9F was more specific, stronger and more constantly expressed. The monoclonal antibody 43-9F may be of value in histological diagnosis of germ cell tumours. Additionally, the study confirmed the pathogenetical link between pre-invasive carcinoma in situ and embryonal carcinoma.

Antibodies, Monoclonal↗

Carcinoma in situ, gonadoblastoma, and early invasive neoplasia in a nine-year-old girl with 46,XY gonadal dysgenesis.

Carcinoma in situ (CIS), gonadoblastoma, and early invasive neoplasia were detected in the dysgenetic gonad of a nine-year-old girl with 46,XY gonadal dysgenesis. A close relationship between the three neoplastic components was supported by morphological and immunohistochemical studies. Our findings support the hypothesis that all germ cell tumours, including gonadoblastomas, originate from CIS germ cells formed during early embryonic life.

Carcinoma in Situ↗

[Adrenal cortex function in patients with AIDS and healthy HIV-positive persons].

Adrenal function was estimated by synthetic ACTH test in 18 men with AIDS (or AIDS-related complex) and compared with that of 10 HIV positive but otherwise healthy men. According to this test none fulfilled the criteria for adrenal insufficiency defined as plasma cortisol concentration less than 500 nmol/l 30 minutes after ACTH stimulation. Seven of eighteen AIDS patients had baseline cortisol concentrations above 0.5 mumol/l compared to none in the HIV-positive group. Three of eighteen AIDS patients had a limited response to synthetic ACTH injection compared to none in the HIV-positive group. Two of these three AIDS patients had lowered serum Na+ concentration; they survived for two and three weeks, respectively. Otherwise the basal cortisol level and response to synthetic ACTH was uncorrelated with survival time, other signs of adrenal insufficiency, treatment with ketokonazole, CMV-infection, T-helper cell count or Th/Ts-ratio. The pituitary-adrenal axis was estimated by measuring the diurnal rhythm of serum ACTH and cortisol in eight patients and was found intact and normal in all of them. Thus, absolute adrenal insufficiency is uncommon in AIDS-patients. Relative adrenal insufficiency may occur in severely ill preterminal patients as a result of primary target organ failure, but the pituitary-adrenal axis generally appears to be undisturbed.

AIDS-Related Complex↗

Cytomegalovirus infection in classic, endemic and epidemic Kaposi's sarcoma analyzed by in situ hybridization.

In order to evaluate the association between cytomegalovirus (CMV) infection and Kaposi's sarcoma (KS) at the cellular level, four classic KS, five endemic (African) KS and 55 epidemic KS from 12 patients with AIDS were analyzed by in situ hybridization with a biotinylated specific CMV-DNA probe. CMV-DNA was sparsely demonstrated in the sarcomas in 10 of the patients with AIDS but in none of the classic or endemic sarcomas. The distribution and localization of the CMV-infected cells did not suggest CMV as a major pathogenic stimulus for the development of KS but rather as an opportunistic infection in severely immunosuppressed patients.

Acquired Immunodeficiency Syndrome↗

Value of four models for selecting patients for local excision of invasive squamous cell carcinoma of the vulva.

For 75 women with squamous cell carcinoma of the vulva who underwent radical vulvectomy and inguinofemoral lymphadenectomy, the authors assessed the efficacy of four models for selecting patients who could have been treated adequately with local excision of the tumor. Each of the three models proposed by Andreasson and Nyboe covered 25% of the patients, none of whom had groin metastases or died of cancer. Local recurrence in the vulva occurred in 10%. A model suggested by the International Society for the Study of Vulvar Disease covered almost 10% of the patients. One of seven patients had groin metastases, none died of cancer, and one of seven developed local recurrence in the vulva. The criteria of the clinically best suited model are tumor not situated on the clitoris and less than 4 cm in diameter, with only slight hyperchromasia. This model ought to be tested in a randomized study.

Adult↗

Patho-anatomical studies in patients dying of AIDS.

The incidence of AIDS in Denmark is the highest reported among the countries of Western Europe. This preliminary account is a report of the autopsy findings in 10 patients, 9 homosexual men and 1 woman. Our aim is to provide a detailed description of the patho-anatomical findings, as well as to compare these with corresponding results reported from the United States, with a view to establishing possible geographical differences in the disease picture. The results of the patho-anatomical studies correspond in all essentials to those from the United States. However, it must be stated that no malignant lymphomas were demonstrated in our patients, although the disease can give rise to very pronounced, possibly transitory, lesions in the lymphatic tissue, easily misinterpreted as malignant. Further features that should be emphasized are the often widespread mycobacterial infection found in the intestinal wall in protracted cases, the occurrence of CMV vasculitis, particularly in the adrenal cortex and medulla, and thromboembolic lesions, often demonstrated in a variety of tissues. The studies made so far emphasize the importance of autopsy in AIDS deaths, as it has extended our detailed knowledge of the patho-anatomical lesions associated with certain opportunistic infections. Further, the autopsy findings have been demonstrably significant either for confirming or for rejecting the clinical diagnosis. On the basis of an analysis of the cellular immunological profile in AIDS, parallels can be drawn to the conditions in certain lymphoproliferative diseases. In autopsied AIDS cases, we recommend a standard scheme covering the tissue specimens to be obtained for histological examination. Strict safety precautions should be observed against infection during autopsy.

Acquired Immunodeficiency Syndrome↗