Histopathology of the Hematopoietic Bone Marrow in the Temporomandibular Joint of Rats Subjected to Undernutrition and to Mandibular Condyle Fracture

Undernutrition can cause important functional and morphological alterations in the hematopoietic bone marrow (HBM). Degeneration of the HBM in malnourished individuals has been observed in the long bones, but none has been described in the cranial bones. Mandibular condyle fracture can lead to determine nutritional effects due to the high catabolism needed for the bone healing added to the difficulties of mastication. The aim of this study is to describe the histological aspect of HBM in the fractured mandibular condyle and in the temporal bone of malnourished rats. Thirty adult rats suffered unilateral mandibular condyle fracture and were divided into well-nourished (FG) and malnourished (MG) groups. In the MG the animals received a hypoproteic diet during the experiment. Histological sections of the temporomandibular joint were stained to visualize and quantify the HBM in this region at 24h, and 7, 15, 30, and 90 days post-fracture. At 24 hours, FG and MG showed hypocellularity and ischemic degeneration in the mandibular condyle and in the temporal bone. At 7 days, FG exhibited high cellularity in comparison with MG in the condyle; the temporal bone of both groups presented hypocellularity and degeneration. At 30 and 90 days, FG exhibited similar characteristics to those of the control; MG maintained the degeneration level mainly in the temporal bone. Malnutrition prejudices the regeneration of the HBM during a fracture healing in the temporomandibular joint. This fact contributes to a complete modification of the bone structure as well as to an impairment of the healing process.

Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study

The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER-2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC. (C) 2003 Elsevier Science Ltd. All rights reserved.

Genotoxicity biomarkers in occupational exposure to formaldehyde: the case of histopathology laboratories

Formaldehyde, classified by the IARC as carcinogenic in humans and experimental animals, is a chemical agent that is widely used in histopathology laboratories. The exposure to this substance is epidemiologically linked to cancer and to nuclear changes detected by the cytokinesis-block micronucleus test (CBMN). This method is extensively used in molecular epidemiology, since it provides information on several biomarkers of genotoxicity, such as micronuclei (MN), which are biomarkers of chromosomes breakage or loss, nucleoplasmic bridges (NPB), common biomarkers of chromosome rearrangement, poor repair and/or telomere fusion, and nuclear buds (NBUD), biomarkers of elimination of amplified DNA. The aim of this study is to compare the frequency of genotoxicity biomarkers, provided by the CBMN assay in peripheral lymphocytes and the MN test in buccal cells, between individuals occupationally exposed and non-exposed to formaldehyde and other environmental factors, namely tobacco and alcohol consumption. The sample comprised two groups: 56 individuals occupationally exposed to formaldehyde (cases) and 85 unexposed individuals (controls), from whom both peripheral blood and exfoliated epithelial cells of the oral mucosa were collected in order to measure the genetic endpoints proposed in this study. The mean level of TWA8h was 0.16±0.11ppm (

Genotoxicity biomarkers: application in histopathology laboratories

Most cancers results from man-made and natural environmental exposures (such as tobacco smoke; chemical pollutants in air, water, food, drugs; radon; and infectious agents) acting in concert with both genetic and acquired characteristics. It has been estimated that without these environmental factors, cancer incidence would be dramatically reduced, by as much as 80%-90%. The modulation of environmental factors by host susceptibility was rarely evaluated. However, within the past few years, the interaction between environmental factors and host susceptibility factors has become a very active area of research. Molecular biology as a tool for use in epidemiological studies has significant potential in strengthening the identification of cancers associated with environmental exposures related to lifestyle, occupation, or ambient pollution. In molecular epidemiology, laboratory methods are employed to document the molecular basis and preclinical effects of environmental carcinogenesis. Molecular epidemiology has become a major field of research and considerable progress has been made in validation and application of biomarkers and its greatest contribution has been the insights provided into interindividual variation in human cancer risk and the complex interactions between environmental factors and host susceptibility factors, both inherited and acquired, in the multistage process of carcinogenesis.

Histopathology of cutaneous and mucosal lesions in human paracoccidioidomycosis

Biopsies from cutaneous and mucosal lesions from 40 patients with active paracoccidioidomycosis, were studied histopathologically. All cases exhibited chronic granulomatous inflammation and 38 also presented suppuration; this picture corresponded to the mixed mycotic granuloma (MMG). Pseudoepitheliomatous hyperplasia and the transepidermic (or epithelial) elimination of the parasite, were observed in all cases. In paracoccidioidomycosis elimination takes place through formation of progressive edema, accompained by exocytosis. The edema gives rise to spongiosis, microvesicles and microabscesses which not only contain the fungus but also, various cellular elements. Cells in charge of the phagocytic process were essentialy Langhans giant cells; PMN's, epithelioid and foreign body giant cells were poor phagocytes. An additional finding was the presence of fibrosis in most biopsies.

Histopathology and immunocytochemical study of type 3 and type 4 complement receptors in the liver and spleen of dogs naturally and experimentally infected with Leishmania (Leishmania) chagasi

The objective of this study was to compare the histopathological changes and expression of CR3 and CR4 in the liver and spleen of dogs naturally and experimentally infected with L. chagasi. The basic histopathological lesions observed mainly in naturally infected dogs were: epithelioid hepatic granulomas, hyperplasia and hypertrophy of Kupffer cells, Malpigui follicles and mononucleated cells of the red pulp of the spleen. Sections from the liver and spleen by immunocytochemistry technique showed the presence of CD11b,c\CD 18 antigens in the control and infected animals and no qualitative or quantitative differences in the liver. Nevertheless, CD18 was always increased in the spleen of naturally and experimentally infected dogs. These results indicate that there is a difference in the activaton of CD 18 in both experimental and natural cases of canine visceral leishmaniasis that should play an important role in the immunological response to Leishmania chagasi infection.

Carrion's disease (Bartonellosis bacilliformis) confirmed by histopathology in the High Forest of Peru

Bartonellosis or Carrion's disease is endemic in some regions of Peru, classically found in the inter-Andean valleys located between 500 and 3200 meters above sea level. We report the case of a 43 year-old male patient, farmer, who was born in the Pichanaki district (Chanchamayo, Junin), located in the High Forest of Peru. He presented with disseminated, raised, erythematous cutaneous lesions, some of which bled. The distribution of these lesions included the nasal mucosa and penile region. Additionally subcutaneous nodules were distributed over the trunk and extremities. Hematologic exams showed a moderate anemia. Serologic studies for HIV and Treponema pallidum were negative. The histopathologic results of two biopsies were compatible with Peruvian wart. Oral treatment with ciprofloxacin (500 mg BID) was begun. Over 10 days, the patient showed clinical improvement. This is the first report of a confirmed case of bartonellosis in the eruptive phase originating from the Peruvian High Forest, showing the geographical expansion of the Carrion's disease.

The histopathology of cutaneous leishmaniasis due to Leishmania (Leishmania) mexicana in the Yucatan peninsula, Mexico

Localized Cutaneous Leishmaniasis (LCL) known as "chiclero's ulcer" in southeast Mexico, was described by SEIDELIN in 1912. Since then the sylvatic region of the Yucatan peninsula has been documented as an endemic focus of LCL. This study of 73 biopsies from parasitological confirmed lesions of LCL cases of Leishmania (Leishmania) mexicana infection was undertaken: 1) to examine host response at tissue level; and 2) to relate manifestations of this response to some characteristics of clinical presentation. Based on Magalhães' classification we found that the most common pattern in our LCL cases caused by L. (L.) mexicana was predominantly characterized by the presence of unorganized granuloma without necrosis, (43.8%). Another important finding to be highlighted is the fact that in 50/73 (68.5%) parasite identification was positive. There was direct relation between the size of the lesion and time of evolution (r s = 0.3079, p = 0.03), and inverse correlation between size of the lesion and abundance of amastigotes (r s = -0.2467, p = 0.03). In view of the complexity of clinical and histopathological findings, cell-mediated immune response of the disease related to clinical and histopathological features, as so genetic background should be studied.

Histopathology, serology and cultures in the diagnosis of cryptococcosis

Cryptococcosis is one of the most common opportunistic fungal infections in patients with acquired immunodeficiency syndrome (AIDS). We report 13 cases of cryptococcal infection based on histopathology, serology and cultures. Epidemiological analysis, histochemical techniques of hematoxilin and eosin (HE) and Grocot's silver (GMS), as well special histochemical techniques such as Mayer's mucicarmine (MM) and Fontana-Masson (FM), cryptococcal antigen test (CrAg) and isolation on fungal media: Sabouraud's (SAB), brain-heart infusion agar (BHI) and canavanine-glycine-bromothymol blue (CGB) agar were analyzed. Unsatisfactory staining results by MM stain associated to negative titers by CrAg test, which FM stain confirmed that capsule-deficient Cryptococcus infections were observed in four cases. Eight isolated cases were identified as follows: six cases were infection with Cryptococcus neoformans and two cases were Cryptococcus gattii.

The 2009 Pandemic Influenza A (H1N1) Infection: Renal Histopathology Findings in Two Infected Patients

Background: Acute kidney injury in the pandemic swine origin influenza A virus (H1N1) infection has been reported as coursing with severe illness, although renal pathogenic mechanisms and histologic features are still being characterised. Case Report: We present two patients admitted with H1N1 pneumonia, sepsis, acute respiratory distress syndrome and need for invasive mechanical ventilation who developed acute kidney injury and became dialysis-dependent. In both cases a kidney biopsy was performed to establish a definitive diagnosis. Severe acute tubular necrosis was identified, with no further abnormalities. Conclusion: This report seems to confirm that the acute kidney injury in H1N1 infection is focused on the tubular cells. Our cases corroborate the renal histopathologic findings of other studies, highlighting the central role of the tubular cell. We bring new evidence of the histopathology of AKI in H1N1 infection since our data were collected in living patients and not via post-mortem studies.

The un-infectivity of the PF cultivated strain of trypanosoma cruzi to mice. An evaluation through a one year period by blood cultures and histopathology

Trypanosoma cruzi of the cultivated PF strain when injected in mice per subcutaneous route, in adequate doses, is able to induce an efficient sterile immunization in the animais (for at least one year) as determined by whole blood cultures and histopathology.

Rickettsial Infection Caused by Accidental Conjunctival Inoculation

The most common transmission route of tick-borne Rickettsia is through tick bite; nevertheless, other transmission routes should also be considered. We report a case of rickettsial infection in a 15-year-old boy caused by accidental contamination of the conjunctiva through the infected fluid of a crushed engorged tick removed from a dog. Right eye pain, conjunctival hyperaemia with mucopurulent exudate, chemosis and eyelid oedema were the first signs and symptoms. Two days later, the boy developed fever, myalgia, headache, abdominal pain and was vomiting; physical examination showed multiple cervical adenopathies but no rash. He was treated with doxycycline (200 mg/day) for 7 days with progressive resolution of clinical signs. Rickettsial infection was confirmed by immunofluorescence assay with serological seroconversion in two consecutive samples. Rickettsia conorii or Rickettsia massiliae were the possible causal agents since they are the Rickettsia spp found in the Rhipicephalus sanguineus dog tick in Portugal.

Histopathology of human American cutaneous leishmaniasis before and after treatment

Chemical therapy for the treatment of leishmaniasis is still inadequate, and a number of drugs and therapeutic programs are being tested. Besides treatment, the ultimate goal is an effective cure, and histopathological analyses of the lesion cicatrices constitute an important measure of treatment success, or otherwise, in this respect. In this paper, we describe histopathological patterns in cases of American cutaneous leishmaniasis in 32 patients from the municipality of Caratinga, Minas Gerais, Brazil, before and after treatment with the following therapeutic methodos: l) leishvacin + glucantime; 2) leishvacin + BCG associated with glucantime; 3) glucantime; 4) leishvacin + BCG. Lesion fragments were collected from all patients by biopsy prior to, and approximately 30 days after, each treatment which resulted in a clinical diagnosis of cure. Following the analysis of slides, the preparations were described from a histopathological point of view and grouped taking into account the prevalence or significance of the characteristic elements. This process resulted in the following classification: 1. exsudative reaction (ER); 2. exsudative giant cell reaction (EGCR); 3. exsudative productive reaction (EPR); 4. exsudative productive giant cell reaction (EPGCR); 5. exsudative productive necrotic reaction (EPNR); 6. necrotic exsudative reaction (NER); 7. productive exsudative reaction (PER), 8. productive giant cell reaction (PGCR); 9. productive exsudative giant cell reaction (PEGCR); 10. productive exsudative giant cell granulomatous reaction (PEGCGR); 11. productive reaction (PR) and 12. productive cicatricial (cure) reaction (PCR). After this analysis, it was noted that clinical cure did not always coincide with histopathological cure.

Serial heart rate changes in rats inoculated by conjunctival instillation of Trypanosoma cruzi obtained from bug faeces

The cardiac effects of experimentally induced myocarditis, when the parasite is obtained from mouse blood, are well known. However, the consequences of the infection when the parasites are obtained from bug faeces are less well defined. In the present investigation, we have used the "Y" strain of Trypanosoma cruzi, which was maintained in Rhodnius prolixus by repeated passages in mice. The faeces of 30 infected bugs were collected, the number of parasites counted and 4,000 parasites inoculated by the conjunctival route in 60 rats. Twenty-nine other rats received faeces from noninfected bugs (sham-inoculated controls) and 40 were used as normal controls. The heart rate of the three groups of animals was recorded under general anesthesia with ether. The heart rate, at day 0 pre-inoculation, was similar in the three groups of animals (Controls: 379 ± 27 beats/min Mean ± SD; Sham-inoculated: 366 ± 31; Infected: 351 ± 29) (p> 0.05). In the infected animals, the mean heart rate began to increase significantly by day 12 following infection (375 ± 31), reaching the highest values between days 18 (390 ± 33) and 21 (403 ± 33) and returned to baseline by day 30 (359 ± 28) (p< 0.05). The heart rate changes were statistically different from those observed in the sham-inoculated controls and in the control animals. Therefore, these heart rate changes were provoked by the Trypanosoma cruzi-induced infection. Thus, it appears that irrespective of the source of the parasite and route of inoculation Trypanosoma cruziacute infection provokes a transient sinus tachycardia.

Comparison of Trypanosoma cruzi infection in dogs inoculated with blood or metacyclic trypomastigotes of Berenice-62 and Berenice-78 strains via intraperitoneal and conjunctival routes

This paper aimed to verify the influence of the inoculum source (blood or metacyclic trypomastigote) and the route of inoculation (intraperitoneal or conjunctival) on the course of T. cruzi infection in dogs, using comparatively the T. cruzi strains Berenice-62 and Berenice-78. All dogs inoculated intraperitoneally became infected independently of the T. cruzi strain and source of trypomastigotes used. High level of infectivity was also observed when metacyclic trypomastigotes of both strains were inoculated by conjunctival route. However, when blood trypomastigotes were inoculated by conjunctival route the percentages of infectivity were significantly lower in dogs inoculated with both strains. Parasitaemia was significantly higher in animals infected with metacyclic trypomastigotes via the conjunctival route independently of the T. cruzi strain used. All animals infected with Berenice-78 strain showed severe acute myocarditis. On the other hand, animals infected with Berenice-62 showed severe acute myocarditis only when infected with metacyclic trypomastigote, via the intraperitoneal route. The results suggest that the source of the inoculum and the route of inoculation remarkably influence the evolution of the infection for the T. cruzi in the vertebrate host even when the same strain of the parasite is used.