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[Cold nodules of the thyroid. Reevaluation of surgical excision on the basis of a new group of 607 patients(author's transl)].

In a serie of 607 cold nodules developing in normal or apparently normal (on preoperative clinical examination) thyroids, the results of histopathological examination were compared with those in an identical series studied 10 years before. Carcinoma was frequent: 9.7% in the current series and 19% in the first series. Insofar as neither clinical examination nor special investigations at the present time make it possible to affirm that a cold nodule is not malignant, surgical complete lobectomy with frozen section examination remains the required procedure in view of its harmless nature and the good prognosis in differentiated tumours operated upon before any visceral extension has taken place, contrasting with the poor prognosis of others. Recurrences may be prevented by special operative techniques (routine excision of Lalouette's pyramid, division of the contralateral ligament of Grubert) and routine postoperative thyroid extracts in patients with a morphological, familial or biological risk of recurrence.

Adenoma

Novel bacterium infecting an African snail.

Nodules found in the superficial tissues of laboratory-maintained snails (Bulinus jousseaumei) contained a bacterium of two forms. This nonmotile microorganism occurred in intracellular packets as a simple gram-negative rod that appeared to undergo intrapacket transition to a cephalotrichous form. The latter is characterized by a "head" from which emerge long, thick, rigid, flagella-like, helically constituted filamentous organelles with a core and an outer component that is not an extension of the bacterial envelope. Neither form was successfully cultured, but clean snails derived from eggs removed before hatching developed nodules within 1 to 3 months of exposure to infected snails. The infectivity was specific for the host snail, and no transmission occurred to snails of 5 other genera tested. The presence of nodules did not interfere with longevity or reproduction of infected snails. Details of infectivity, transition, and taxonomic position of the bacterium remain to be explored, but it is reported because of unique morphological and ultrastructural features not previously known.

Africa

Granulocytic sarcoma of the cervix as a primary manifestation: case without overt leukemic features for 26 months.

A case of granulocytic sarcoma involving the uterine cervix as primary manifestation without evidence of leukemia is presented. It was followed by neurological symptoms 19 months later and a right breast mass 26 months after the initial cervical lesion, but still with no evidence of leukemia. Two years and four months after onset, soft tissue and skin nodules developed and rare blastic cells appeared on peripheral blood smear. The patient terminally developed acute granulocytic leukemia with a rapidly downhill course. The differential diagnosis of granulocytic sarcoma and histiocytic lymphoma is discussed. The literature is reviewed with emphasis on the clinical and pathological problems that arise when the tumor presents in an unusual location without peripheral blood manifestation of leukemia.

Aged

17beta-oestradiol and Enovid mammary tumorigenesis in C3H/HeJ female mice: counteraction by concurrent 2-bromo-alpha-ergocryptine.

Chronic administration of 17beta-oestradiol (via drinking water) or the oral contraceptive Enovid (norethynodrel and mestranol) (0-1 mg injected s.c. twice weekly) to nulliparous C3H/HeJ female mice, beginning at one month of age and terminating at 20 months (17beta-oestradiol) or 22 months (Enovid), significantly increased the incidence of mammary tumours over solvent-treated controls. Concurrent treatment of the steroid-treated mice with 2-bromo-alpha-ergocryptine (CB-154) (0-1 mg s.c. injected daily) significantly reduced mammary tumour incidence and mammary hyperplastic nodule development to the control level. CB-154 is an efficacious inhibitor of pituitary prolactin secretion. These results demonstrate that steroid-induced mammary gland dysplasias can be sharply reduced by chronic CB-154 treatment, and suggest that some of the mammary tumorigenic activities of oestrogenic steroids in C3H mice are mediated via an increased secretion of pituitary prolactin.

Animals

The steroid alcohol and estrogen sulfotransferases in rodent and human mammary tumors.

Rodent and human mammary tumor systems were investigated to relate the steroid alcohol and estrogen sulfotransferase activities to the hormoanl dependency of the tumor as determined by estrogen receptor content. Unlike the normal mammary gland or the hyperplastic alveolar nodule, rodent mammary neoplasms displayed significant levels of these two sulfotransferases. In the hormone-independent mouse tumors produced from out-growth lines D1, D2, and D8, high dehydroepiandrosterone sulfotransferase activity was characteristic of the rapidity with which hyperplastic alveolar nodules developed into a neoplasms (V-max = 52.8 versus 1.8 fmoles/min/mg protein) while estrone sulfotransferase activity was either not detectable or low (V-max = 5.5 fmoles). After oophorectomy of mice bearing slowly developing tumors, both sulfotransferases in the nonregressing neoplasms showed marked increases in activity (V-max dehydroepiandrosterone = 30.0 fmoles; V-max estrone = 18.5 fmoles). Strain differences not the estrogen receptor content of hormone-dependent rat mammary tumors. In Wistar-Lewis rats the steroid alcohol sulfotransferase activity was at least 35 times higher than in the Sprague-Dawley strain. As was observed in the mouse mammary tumor, Sprague-Dawley rat neoplasms that grew in the absence of ovarian hormones contained significantly greater levels of the steroid alcohol sulfotransferase. Possible correlaion between presence of the steroid alcohol sulfotransferase and the estrogen receptor protein was observed in a limited number of human breast carcinomas.

Alcohols

Effect of sulfated polysaccharides on blood-borne pulmonary metastasis in rats.

The inhibitory effect of sulfated polysaccharides on blood-borne metastasis was examined. As a model of blood-borne metastasis, the ascitic form of hepatoma AH-109A tumor was injected intravenously into Donryu strain rats. Examination of the pulmonary metastatic nodules developed 2 weeks later showed inhibitory effect of the five sulfated polysaccharides tested. Xylan sulfate was the most inhibitory, and exerted its inhibitory effect when the tumor cells were in the pulmonary capillary beds. However, fromthe rapid disappearance of radioactivity from the lungs after injection of 125IUDR-labeled AH-109A cells, tumor cells seemed to be retained in the lungs for only a very short time. Measurement of the anticoagulative and fibrinolytic activities of three sulfated polysaccharides showed that the inhibitory effect of these compounds on blood-borne metastasis was proportional to their anticoagulative and fibrinolytic activities, xylan sulfate showing the highest activities. These results suggest that sulfated polyaccharides may inhibit blood-borne pulmonary metastasis by inhibiting the lodging of tumor cells in the pulmonary capillary beds.

Animals

Angiolymphoid hyperplasia with eosinophilia.

Angiolymphoid hyperplasia with eosinophilia (AHE) is a distinct clinical and pathologic entity that demonstrates proliferation of endothelial cells associated with varying degrees of lymphocytic, histiocytic, and eosinophilic infiltration. Lymphoid hyperplasia with germinal centers often is present in older lesions and the patients may have an associated blood eosinophilia. Multiple deep nodules developed in a young man on the palmar aspect of the left hand, and subsequently the forehead, histologically diagnostic of AHE. Direct immunofluorescence of the tumor removed from the forehead demonstrated granular deposits of IgA, IgM, and C3 associated with small vessels. Cryoglobulins (IgA, IgM, and IgG) were found in the patient's serum. This new information lends support to the hypothesis that AHE is an inflammatory reactive lesion, possibly secondary to an immunologic injury, rather than a true vascular neoplasm with an associated inflammatory reaction.

Adult

Traumatic nodule in surgical scar.

Presented herein is a report on a patient in whom a hyperkeratotic nodule developed in an abdominal surgical scar, ten months after exploratory laparotomy.

Adult

Nodular nonsuppurative panniculitis associated with jejunoileal bypass surgery.

A 32-year-old woman underwent jejunoileal bypass surgery for morbid obesity. Her postoperative course was marked with many of the complications of this type of surgery. In addition, tender, erythematous nodules developed on her legs and abdomen that were grossly and microscopically consistent with nodular nonsuppurative panniculitis. She did not have any condition or disease previously reported to be associated with nodular nonsuppurative inflammation. The nodular panniculitis in this patient appears to be a new complication of small-bowel bypass surgery.

Adult

Plasma cell granulomas in non-lipemic xanthomatosis: apparent induction by indomethacin.

A 71-year-old man with non-lipemic, generalized, plane xanthomas developed nodules and tumors within one month of starting indomethacin therapy. These enlarged and spread during 5 months of daily indomethacin but promptly and spontaneously involuted when the indomethacin was discontinued. Within 4 months, the nodules and tumors were completely gone. The process is viewed as an "indoderma", i.e. a granulomatous drug reaction, analogous to an iododerma.

Aged

Gangliosides of liver tumors induced by N-2-fluorenylacetamide. I. Ganglioside alterations in liver tumorigenesis and normal development.

Hyperplastic nodules and hepatocellular carcinomas were induced in livers of rats by a low-protein diet containing 0.05% of the carcinogen N-2-fluorenylacetamide. Ganglioside amounts and composition were determined for histologically different hepatocellular carcinomas and compared with those for control livers, hyperplastic nodules, and liver tissue surrounding hepatomas and nodules as well as those for livers of fetal, newborn, 1-week-old, weanling, and adult Sprague-Dawley rats. Ganglioside sialic acid levels were elevated above those of normal adult liver in all liver tissues following the carcinogen treatment regimen. Livers of fetal and newborn rats contained nearly twice the amount of ganglioside sialic acid on a protein or DNA basis as did livers of adult rats. Analyses of individual nodules and hepatomas revealed two populations of tumors in which the levels of ganglioside sialic acid were 2.3 and 3.8 times normal. Ganglioside sialic acid content was at hepatoma levels in small nodules. Individual gangliosides were evenly distributed between products of the monosialoganglioside and disialoganglioside pathways in normal liver with a ratio of [N-acetylneuraminic acid (sialic acid)] (NAN)-galactose (Gal)-N-acetylgalactosamine (GalNAc)-(NAN)-Gal-glucose (Glc)-ceramide (Cer) (GD1a) to Gal-GalNAc-(NAN)2-Gal-Glc-Cer (GD1b) of about one. In contrast, the monosialogangliosides predominated in liver tissues following administration of the carcinogen. Increased levels of specific monosialogangliosides were present in nodules, in liver of carcinogen-treated animals prior to the appearance of tumors, and in the liver tissues surrounding nodules and hepatomas. In single hepatomas, ganglioside patterns correlated with tumorigenicity. A well-differentiated hepatoma had a normal complement of most gangliosides but was deficient in trisialogangliosides. In a poorly diferentiated but well-circumscribed hepatoma, the relative levels of all higher gangliosides were reduced. The monosialoganglioside Gal-GalNAc-(NAN)-Gal-Glc-Cer (GM1) accounted for 80% of the total ganglioside in a poorly circumscribed and poorly differentiated hepatoma. The ganglioside pattern of fetal livers most closely resembled that of a poorly differentiated hepatoma. During the first week post natum, levels of all higher monosialogangliosides and disialogangliosides declined, but the decline was most pronounced for gangliosides GM1 and GD1a. The ratio of GM1 + GD1a to GD1b + NAN-Gal-GalNAc-(NAN)2-Gal-Glc-Cer or (NAN)3-Gal-Glc-Cer (GT), used as an index of the relative predominance of the monoslaloganglioside and disialoganglioside pathways, fell from 2.7 for fetal liver to 0.4 for adult liver. Pools of precursor gangliosides increased during development, transiently for GalNAc-(NAN)-Gal-Glc-Cer and for more than 3 weeks for NAN-Gal-Glc-Cer. When hyperplastic nodules and hepatocellular carcinomas were compared, a reverse pattern was observed. The ratio of GM1 + GD1a to GD1b + GT rose steadily to values of 2.7 and 11...

2-Acetylaminofluorene

Mammary nodules in beagle dogs administered investigational oral contraceptive steroids.

Of 172 beagle dogs administered oral contraceptive steroids for 5-7 years, 114 developed 1,156 nodules in the mammary gland region. Most of these nodules arose 2.5-3.5 years after initiation of treatment. Approximately 16% of the nodules were transient and disappeared spontaneously from the mammary gland during the study. A total of 925 nodules were present in 99 dogs at the time of death or necropsy. These nodules were classified as benign mammary dysplasias (7.0%), lobular or intraductal hyperplasias (31.4%), simple adenomas (20.8%), complex adenomas (25.4%), benign mixed tumors (5.3%), malignant tumors (3.6%), or nonmammary lesions (6.5%). Histologically, the mammary nodules were representative primarily of the hyperplasias and tumors that occur spontaneously in the mammary glands of the dog. The only major exception was the presence of 82 simple adenomas that had basaloid features. Most of the contraceptive-related mammary nodules developed in dogs receiving the combination of progestion and mestranol at 10 or 25 times the proposed human dosage. Control dogs and dogs receiving mestrenol alone had few mammary nodules. Combinations of anagestone acetate and mestranol and chloroethynyl norgestrel (WY-4355) and mestranol produced large numbers of nodules at 10 and 25 times the proposed human dosage, whereas ethynerone plus mestranol produced large numbers of nodules only at 25 times the proposed human dosage. Ethynerone, when given alone at 25 times the proposed human dosage, was associated with fewer mammary nodules. Malignant neoplasms were seen in dogs given 10 and 25 times the proposed human dosage of anagestone acetate plus mestranol and 25 times the proposed human dosage of WY-4355 plus mestranol and ethynerone plus mestranol. This study strongly associates certain combinations of progestin and mestranol with mammary neoplasia in dogs.

Adenoma

Inhibition of 3'-methyl-4-dimethylaminoazobenezene-induced hepatocarcinogenesis by portacaval shunt.

Adult male Sprague Dalwey rats on which end-to-side portacaval shunt (PCS) operation was performed did not hyperplastic nodules and hepatoms when they were fed 3'-methyl-4-dimethylaminoazobenzene in semisynthetic basal diet for periods of up to 169 days. In contrast, all the intact rats fed the same diet for only 75 days, developed hyperplastic nodules in the liver. Transferred to normal pellet for another 25 days, hepatomas developed in 100% of these animals. The amount of protein-bond 3'-Me-DAB was found to be much smaller in operated rats than in intact animals. The glutathione (GSH) level in PCS-operated rats was lower than in intact controsl. A single large dose of 3'-Me-DAB led to the increase of only about 30% in the concentration of GSH during the period of 24-48 h, compared to the increase of 50-100% in non-operated rats. No clear tendency to a gradual increase in the activity of gamma-glutamyl transpeptidase was noted in PCS-operated rats during the period of 5 1/2 months of 3'-Me-DAB feeding. The increase in GT-ase activity never exceeded 30% above the level of GT-ase in the livers of PCS-operated rats fed basal diet without the carcinogen. This striking inhibibiton of GT-ase increase induced by 3'Me-DAB in PCS-operated rats contrasted with an increase of GI-ase activity by 5,000% found in livers of non-operated rats with hyperplastic nodules after 75 days of 3'-Me-DAB feeding and the increase by up to 10,000% in developed hepatomas. These effects and the inhibition of 3'Me-DAB-induced hepatocarcinogenesis, manifested by lack preneoplastic morphologic changes and the absecnce of hepatomas in rats after PCS, can best be explained by functional deficiency of the liver to metabolize the procarcinogen 3'-Me-DAB into an activated carcinogen.

Animals

[Nitrogen fixing activity of pea nodule bacteria during different phases of host plant development].

The activity of nitrogenase in nodules of pea plants and the rate of diurnal nitrogen fixation were studied at different phases of the plant growth using the acetylene and isotope techniques. At the same time, the morphology of nodule bacteria was studied by electron and phase-contrast microscopy. About 90% of the bacteria in nodules were found in the form of bacteroids from the early phase of the plant growth (budding) to ripening when gemmated arthrospores could be observed on some bacteroids. The highest activity of nitrogenase and nitrogen fixation was detected at the reproductive stage of growth. Therefore, in order to obtain more active strains of pea nodule bacteria, they should be isolated from nodules at this stage of plant growth.

Fabaceae

Visual scanning, pattern recognition and decision-making in pulmonary nodule detection.

Eye movements were recorded while four subjects searched a set of 60 films, 24 normal and 36 abnormal for pulmonary nodules. Error rates, scanning patterns and the dwell time of fixation clusters on normal and nodule-containing areas of the film were studied. Using the assumption that prolonged dwell time indicates intensive processing of visual data, a model was developed for nodule detection that includes four steps: orientation, scanning, pattern recognition and decision-making. False-negative errors were divided into three classes: scanning errors, recognition errors and decision-making errors. Of 20 false-negative errors, 30% were considered scanning, 25% recognition and 45% decision-making.

Decision Making

Pulmonary necrobiotic nodules without rheumatoid arthritis.

Pulmonary necrobiotic nodules are the least common of the pulmonary lesions associated with rheumatoid arthritis. Histologically they are identical to subcutaneous rheumatoid nodules. Systemic rheumatoid arthritis usually precedes the development of pulmonary nodules. Seven cases where the pulmonary nodule appeared before or without the development of systemic rheumatoid arthritis are described. The typical histological and radiological features of necrobiotic nodules were found in each. In five of the seven the nodules were in more than one site and in five there were cavitating nodules. Spontaneous improvement occurred in one case. Pulmonary nodules preceded systemic rheumatoid arthritis in three cases and in the remaining four cases systemic rheumatoid arthritis has not yet appeared despite prolonged follow-up. In all patients, tests for rheumatoid factor have remained negative. The absence of circulating rheumatoid factor and systemic rheumatoid arthritis cannot exclude the diagnosis in these cases if the histological diagnosis is accepted as conclusive.

Adult

Antineoplastic effects of long-term Trichinella spiralis infection on B-16 melanoma.

Oral infection of mice with Trichinella spiralis has been shown to induce a potentiation of the delayed hypersensitive (DTH) response to BCG. The present investigation was initiated to determine whether nematode-induced potentiation of DTH influenced the induction and progression of a transplantable mouse tumor. B6D2F1/J mice were orally infected with 200 T. spiralis larvae 176 days preceding subcutaneous administration of 5 X 10(5) viable B-16 melanoma cells. The antineoplastic effects of long-term nematode infection were assessed by daily observation of the animals monitoring development and progression of neoplastic nodules. Control mice developed tumors by day 28 following tumor challenge, while none of the corresponding T. spiralis-infected animals demonstrated any signs of neoplasia. All control mice died within 60 days, while none of the nematode-infected animals developed detectable neoplasms. This phenomenon suggested that the presence of well-established larval cysts was capable of stimulating host antineoplastic activity.

Animals

Localization of alpha-fetoprotein by immunofluorescent method during induction of rat liver tumors by 3'-methyl-4-dimethylaminoazobenzene.

Localization of alpha-fetoprotein (alpha-FP) has been followed in hepatal tissue and tumors during induction of primary hepatomas with the aid of 0.12% 3'-Me-DAB (3'-methyl-4-dimethylammoazobenzene) in Wistar rats. The indirect immunofluorescence method was used for the localization of alpha-FP positive cells. During the course of carcinogenesis, alpha-FP in serum was detected by means of the crossing over immunoelectrophoresis. This study has yielded the following results: Alpha FP positive cells resembling small hepatocytes occurred dispersed and in groups beginning with the 5th week of a carcinogenic diet until the appearance of tumors. No alpha-FP positive oval cells have been found. Alpha-FP positive cells were always found in rats with alpha-FP positive serum, but they were rarely present in rats with alpha-FP negative serum. From the 10th week, tumors of the cholangiohepatoma type began to be formed in which variously scattered alpha-FP positive cells of the type of small hepatocytes were present, with the serum being negative. Between week 14 and 21 hepatoma nodules began to be formed. At week 21 frequent alpha-FP positive cells close to normal hepatocytes were observed both singly and in groups. These are considered to be the sites of developing tumor nodules. In all the hepatoma nodules, the number of positive tumorous cells and the intensity of fluorescence proved to be directly proportional to alpha-FP concentration in serum.

Adenoma, Bile Duct