Juvenile cirrhosis in a 16th century Italian mummy. Current technologies in pathology and ancient human tissues.

The natural headless mummy of a young man from the Basilica of Saint Domenico Maggiore in Naples (16th century) showed at autopsy a well-preserved fibrous liver with a nodular surface, suggesting a case of cirrhosis. Stereo and light microscope study confirmed this diagnosis. To identify the possible etiology of this cirrhosis, additional techniques currently used in pathology were performed. Hemochromatosis and alpha1-antitrypsin deficiency were investigated without results. Investigation regarding Wilson's disease gave positive results, since the use of rhodamine staining, which is specific to detect the presence of copper in tissues, resulted in red-brown grains at light microscopy. The positive rhodamine test was invalidated by atomic absorption spectroscopy (AAS), which revealed normal copper levels in the tissues. These negative results and the clear and diffuse macronodularity of the liver suggest a case of post-necrotic cirrhosis.

The "Braids Lady" of Arezzo: a case of rheumatoid arthritis in a 16th century mummy.

OBJECTIVE: To diagnose a probable case of rheumatoid arthritis in a mummified female body from the 16th century and to backdate the first clinical diagnosis, entering the diatribe regarding the ancientness of the disease. METHODS: Image techniques such as normal X-ray, X-ray by mammography, total body CT and high resolution CT were used. Microscopic examination by stereomicroscopy was performed. Samples of tissue were submitted to histology. These data and the review of past literary references, of artistic representations and of paleopathological cases provided an interesting contribution to reconstruct the history of the disease. RESULTS: The body of the "Braids Lady" showed all the "stigmata" of the disease. The left hand revealed large erosions of the metacarpophalangeal joints of both the third and the fourth fingers, volar metacarpophalangeal subluxation of both the third and the fourth fingers and lateral deviation of all the fingers. The carpus showed some minute and marginal erosions of the bones. The bases of the first phalanges were slightly flared. The toes showed partially overlapped fibular deflection. CT evidenced subluxations of the joints. The body showed no involvement of sacroiliac articulation. CONCLUSIONS: The "Braids Lady" was affected by rheumatoid arthritis. A large number of features typical of the disease were recorded. Differential diagnosis supported the findings. The death of the lady was established at the end of 16th century, namely 200 years before the first clinical diagnosis worked out by Landré Beauvais in the early 1800s.

Paleoandrology and prostatic hyperplasia in Italian mummies (XV-XIX century).

Prostatic hyperplasia, a very common condition today, was well known in the past as cause for bladder distension. The difficulty to identify, at autopsy of natural or artificial mummies, even a normal-sized prostate is probably the result of putrefaction processes and its usually dramatic size reduction as well. We report two ancient cases of prostatic hyperplasia recently observed in natural mummies from Italy. The first case regards Pandolfo III Malatesta (1370-1427), a leading figure of the Italian Renaissance. He was a valiant soldier and horseman with a very active life style. The tomb, containing his naturally mummified body, has recently been discovered in Fano (Marche, Central Italy). After careful X-ray and videographic examination, the autopsy showed good preservation of the skeletal muscles, cartilage, internal and external organs, included prostate gland and penis. Macroscopic examination revealed a staghorn calculus (calcium urate) of the left kidney and a severe enlargement of the prostate, with calcifications detectable by X-ray and large nodules protruding in the lumen of an ectatic urethra. Histology shows fibrous brands of connective and muscular tissue surrounding circular and oblong lacunae, with no preservation of epithelial structures. The macroscopic and histological picture allowed us to diagnose prostatic nodular hyperplasia. The second case (XIX century) concerns the natural mummy of an anonymous 50-60 years old man, found in ancient friary near L'Aquila (central Italy), which underwent computed tomography and a complete autopsy. Pelvic CT scans showed distended urinary bladder and a ring of dense tissue at the site of the prostate. At autopsy the bladder measured 7 x 6 x 5 cm and the prostate was 4 x 5 x 3 cm; prostatic urethra had a diameter of x 2 cm. Histology revealed dense fibrous tissue containing muscular fibers and roundish cavities of variable size, filled with eosinophil, PAS-positive material. Concretions were also present in some of these spaces. Strong immunohistochemical reactivy for PSA was observed in this material. The existence of glandular structures containing eosinophil, PAS-positive material, immunoreactive for PSA, confirmed the prostatic nature of the specimen, already suspected after CT scan and gross examination. The presence itself of the prostate, its histological picture, the preserved and distended urinary bladder, in addition to the age of the subject, supported the diagnosis of prostatic hyperplasia.

Prostatic hyperplasia in the mummy of an italian renaissance prince.

BACKGROUND: Pandolfo III Malatesta (1370-1427) was a leading figure of the Italian Renaissance. He was a valiant soldier and horseman with a very active life style. Historical sources report that he died of a fever in 1427. The tomb, containing his mummified body, has recently been discovered in Fano (Marche, Central Italy). METHODS: After careful X-ray and videographic examination, autopsy was performed to diagnose possible pathologies. Samples of different tissues were collected and rehydrated by Sandison's method and submitted to routine histology processes. Sections of treated tissue were fixed on clean slides, stained with hematoxylin-eosin or Gardner's Trichromic and observed at light microscope. RESULTS AND CONCLUSIONS The autopsy showed good preservation of the skeletal muscles, cartilage, internal and external organs included prostate gland and penis. Macroscopic examination revealed stag-horn calculi (calcium urate) of the left kidney and a severe enlargement of the prostate, with calcifications detectable by X-ray and a large nodule protruding in the lumen of an ectatic urethra. Histology shows fibrous bands of connective and muscular tissue surrounding some circular and oblong lacunae, with no preservation of epithelial structures. The macroscopic and histological picture, showing clear prostatic nodular hyperplasia, makes this the first case described in paleopathology.

Goiter in an eighteenth-century Sicilian mummy.

Goiter is still a frequent pathological condition of the thyroid gland. Goiter consists of an enlargement of the gland caused by several physiopathologic events, the most important of which is deficient intake of iodine. A series of eighteenth-century mummies housed in the church of Santa Maria della Grazia in Comiso includes one individual showing a pathological condition, with a very large swelling in the antero-inferior region of the neck. X-rays showed small scattered radiopaque foci. Routine histology showed a large number of circular follicles immersed in fibrous tissue. Finally, immunohistochemistry revealed a strong reactivity for thyroglobulin. The data confirmed the nature of the tissue as thyroid, and the macroscopic diagnosis is that of thyroid goiter.

Vanadium salts induce cytogenetic effects in in vivo treated mice.

Three vanadium salts, vanadyl sulfate (SVO5), sodium orthovanadate (Na3VO4) and ammonium metavanadate (NH4VO3), were tested for induction of genotoxic effects in bone marrow of mice following intragastric treatment. Micronucleus (MN) induction in polychromatic erythrocytes (PCEs), structural (sCA) and numerical (nCA) chromosome aberrations in bone marrow cells were evaluated. The micronucleus test, performed at different harvesting times (0-72 h), was found to be positive for all compounds tested. In contrast, except for vanadyl sulfate, no difference was found between controls and treated animals in the sCA test performed 24 and 36 h after treatment. At the same sampling intervals, second metaphases (M II) were positively scored for nCA induction for all three vanadium salts. In addition, the frequency of hypoploid and hyperploid cells was shown to be statistically different from the control value. Polyploid cells were also induced by all compounds, but their frequency was not statistically significant. The positive results obtained by nCA analysis support the finding of a significant presence of types of micronuclei that are probably aneuploidy-related. This finding was further supported by the successful classification of such micronuclei on the basis of shape and size according to Tinwell and Ashby (1991) during microscope analysis.

Dose-related clastogenic effects induced by benzene in bone marrow cells and in differentiating spermatogonia of Swiss CD1 mice.

Cancer hazard is due to genotoxic events in somatic cells and genetic hazard in the strict sense is due to mutagenic events in germ cells. The investigation of sensitivity differences between somatic and germinal cells is pertinent to the question whether a genotoxic carcinogen is also a germ cell mutagen. Cytogenetic damage induced by benzene in mice was evaluated by determining the frequencies of chromosomal aberrations in bone marrow and spermatogonial cells of male Swiss CD1 mice. First, the analysis was performed by administering 1 ml/kg (880 mg/kg) of benzene as a single oral dose and sampling either cell type after a wide range of times (6, 12, 18, 24, 30, 36, 42 and 48 h) to determine the time of maximum response. At this dose benzene showed high clastogenic activity in bone marrow cells with a peak between 24 and 30 h. In differentiating spermatogonia the frequency of aberrant cells was highest 24 h after treatment. The overall effect in spermatogonia was lower than in bone marrow cells. Second, the dose response was determined 24 h after treatment with two additional doses of benzene: 0.1 ml/kg (88 mg/kg) and 0.5 ml/kg (440 mg/kg) for bone marrow cells; 0.25 ml/kg (220 mg/kg) and 0.5 ml/kg (440 mg/kg) for differentiating spermatogonia. The clastogenic effect was dose dependent in both cell types. The frequencies of aberrant cells increased in a linear-quadratic manner in bone marrow and linearly in differentiating spermatogonia. Furthermore, the per cell damage was higher in bone marrow than in spermatogonial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Clastogenic effects of hydroquinone: induction of chromosomal aberrations in mouse germ cells.

The clastogenic activity of hydroquinone (HQ) in germ cells of male mice was evaluated by analysis of chromosomal aberrations in primary spermatocytes and differentiating spermatogonia. In the first experiment with treated spermatocytes the most sensitive stage of meiotic prophase to aberration induction by HQ was determined. Testicular material was sampled for microscopic analysis of cells in diakinesis-metaphase I at 1, 5, 9, 11, and 12 days after treatment with 80 mg/kg of HQ, corresponding to treated diplotene, pachytene, zygotene, leptotene and preleptotene. The frequencies of cells with structural chromosome aberrations peaked at 12 days after treatment (p less than 0.01). This indicates that the preleptotene when DNA synthesis occurred was the most sensitive stage of meiotic prophase. In the second experiment the dose response was determined 12 days post treatment by applying 2 additional doses of 40 mg/kg and 120 mg/kg. The clastogenic effects induced by 40 and 80 mg/kg were significantly different from the controls (p less than or equal to 0.01) and higher than the results obtained with 120 mg/kg of HQ. A humped dose-effect relationship was observed. In a third experiment the same doses were used to analyse chromosomal aberrations in dividing spermatogonia of mice 24 h after treatment with HQ. All the administered doses gave results statistically different from the control values (p less than or equal to 0.01) and the data were fitted to a linear equation. HQ was found to be clastogenic in male mouse germ cells. It is concluded that the clastogenic effect in male germ cells is of the same order of magnitude as in mouse bone marrow cells.

Benzene and the genotoxicity of its metabolites. II. The effect of the route of administration on the micronuclei and bone marrow depression in mouse bone marrow cells.

Benzene (880 mg/kg) and 4 of its metabolites, i.e., phenol (265 mg/kg), hydroquinone (80 mg/kg), catechol (40 mg/kg), and p-benzoquinone (5-20 mg/kg) have been tested for their capability to induce micronuclei in bone marrow cells of male mice after oral administration or intraperitoneal injection. Oral administration of benzene shows more activity than intraperitoneal injection, whereas the metabolites show more activity if administered by the latter method. The respective genotoxic strengths of the benzene metabolites are the following: hydroquinone much greater than phenol greater than catechol = p-benzoquinone. This last is active when administered orally.

Benzene and the genotoxicity of its metabolites. I. Transplacental activity in mouse fetuses and in their dams.

Benzene and some of its metabolites (hydroquinone, phenol, catechol, 1,2,4-benzenetriol, p-benzoquinone, o,o'-biphenol, p,p'-biphenol) have been tested for their capability to induce micronuclei in bone marrow cells of pregnant mice and, transplacentally, in fetal liver cells. Dams are scarcely sensitive to the genotoxic activity of benzene and its metabolites while the latter are able to produce only evident toxic effects. Benzene and hydroquinone transplacentally induce micronuclei in fetal liver cells while all other metabolites show weak or negative genotoxicity, although they produce severe cellular toxicity.

Experimental model for evaluating the effects of genetic and exogenous factors on transplacental mutagenesis.

Cyclophosphamide (CP)-induced micronuclei were evaluated in females of two strains of mice (C57BL and CD1), in F1 hybrid females and in fetuses (day 13 of gestation) obtained from different crosses. F1 adult hybrids from a cross between the strain with a high level of induced micronuclei (C57BL) and the strain with a low response (CD1) exhibited micronuclei values closer to the latter. CD1/CD1 fetuses showed a higher susceptibility than C57BL/C57BL ones. Heterozygous fetuses from reciprocal crosses, whatever the maternal genotype, showed the same sensitivity, which is very close to that of C57BL/C57BL fetuses. Phenobarbital (PB) pre-treatment modified the mutagenic response to CP depending on the genotype of the treated animal. These results demonstrate that the response to a pro-mutagen requiring metabolic activation depends to a large extent on the genetic background of the target animals, and that mother-fetus interactions in transplacental mutagenesis seem to depend more on the fetal than on the maternal genotype.