Differential expression of active mitogen-activated protein kinase in cutaneous endothelial neoplasms: implications for biologic behavior and response to therapy.

BACKGROUND: Tumors of endothelium range from benign hemangiomas of infancy to highly malignant angiosarcomas of the elderly. Hemangiomas are the most common tumors in infants and may affect up to 10% of all children. The biologic behavior of these lesions ranges from self-resolving, in the case of hemangiomas and pyogenic granulomas, to lethal metastatic neoplasms in the case of angiosarcoma. Although the clinical outcomes of these diseases are easily distinguished, the biologic basis for these differences is not well understood. Activation of mitogen-activated protein kinase (MAPK) is an important signal transduction mechanism that may predict response of a tumor to chemotherapy. OBJECTIVE: Our purpose was to examine expression of phosphorylated (activated) MAPK in hemangiomas of infancy, pyogenic granulomas, hemangioendotheliomas, and angiosarcomas to determine whether phosphorylated MAPK was expressed in endothelial tumors. In addition, we examined endothelial tumors of infectious origin, Kaposi's sarcoma, and verruga peruana. METHODS: Skin sections from benign and malignant endothelial tumors, including hemangioma of infancy, angiosarcoma, and infectious endothelial lesions (Kaposi's sarcoma, verruga peruana) were stained with an antibody specific for phosphorylated MAPK. RESULTS: We demonstrated strong expression of phosphorylated MAPK in benign endothelial tumors, including capillary hemangioma of infancy and pyogenic granuloma, and greatly decreased expression in angiosarcoma. In addition, infectious endothelial tumors stained strongly with this antibody, similar to benign tumors. The presence of immunoreactive phosphorylated MAPK appears to be inversely correlated with degree of malignancy. CONCLUSION: We demonstrate that the use of antibodies specific for signal transduction pathways is feasible in paraffin-fixed tissue. Thus the activity of a given signal transduction pathway can be ascertained in a biopsy specimen. Immunohistochemistry for phosphorylated MAPK may help the pathologist distinguish benign from malignant endothelial processes and thus guide therapy.

Natural history of infection with Bartonella bacilliformis in a nonendemic population.

An investigation was performed after an outbreak of bartonellosis in a region of Peru nonendemic for this disorder. Symptoms of acute and chronic bartonellosis were recorded. Serological analysis was performed on 55% of the affected population (554 individuals), 77.5% of whom demonstrated previous infection with Bartonella bacilliformis. The attack rate of Oroya fever was 13.8% (123 cases); the case-fatality rate was 0.7%. The attack rate of verruga peruana was 17.6%. A new specific immunostain was developed and used to confirm the presence of B. bacilliformis in the biopsied skin lesions. Most seropositive individuals (56%) were asymptomatic. The symptoms that were associated with prior infection, as determined by Western blot, included fever (37.2% of the seropositive vs. 17.2% of the seronegative population; P<.001), bone and joint pain (27% vs. 9%; P<.001), headache (27% vs. 12.3%; P <.001), and skin lesions described as verruga peruana (26.8% vs. 4.9%; P<.001). Our findings suggest that infection with B. bacilliformis causes a broad spectrum of disease that is significantly milder in severity than that frequently reported.

Helicobacter pylori populations in Peruvian patients.

Helicobacter pylori is an extremely diverse species. The characterization of strains isolated from individual patients should give insights into colonization and disease mechanisms and bacterial evolution. We studied H. pylori isolates from patients in the Japanese-Peruvian Polyclinic in Lima, Peru, by determining metronidazole susceptibility or resistance and by random amplified polymorphic DNA (RAPD) fingerprinting (a measure of overall genotype). Strains isolated from several biopsy specimens from each of 24 patients were studied. Both metronidazole-susceptible and -resistant strains were isolated from 13 patients, whereas strains of more than one RAPD type were isolated from only seven patients. We propose that the homogeneity in RAPD fingerprints for strains isolated from most persons reflects selection for particular H. pylori genotypes during chronic infection in individual hosts and the human diversity in traits that are important to this pathogen. Carriage of related metronidazole-resistant and -susceptible strains could reflect frequent metronidazole use in Peru and alternating selection for resistant and susceptible phenotypes during and after metronidazole therapy.

Algunas características de la infección por Helicobacter pylori en el Perú / Various characteristics of Helicobacter pylori infection in Peru

En la presente serie, compuesta por 2011 pacientes estudiados, nuestras observaciones coinciden con lo reportado en otros países, en relación al porcentaje de hallazgo del H.pylory en los casos de gastritis crónica activa, úlcera p éptica gástrica, úlcera péptica duodenal y en la mucosa gástrica histológicamente normal. En el Perú, en pacientes con síntomas del tracto gastrointestinal superior, la infección por H. pylori se encuentra en porcentajes más elevados (84%) que lo reportado en naciones industrializadas. No observamos incremento de la infección con la edad, debido a que ésta, en nuestro medio, se adquiere en edades muy tempranas como hemos demostrado por la prueba de ELISA. La distribución ecológica de la bacteria, es igual en las tres regiones del Perú y sólo en as mujeres de nivel socioeconómico alto, la prevalencia de la infección es menor. El porcentaje de recurrencia después de tratamiento es superior al descrito en países industrializados

Algunas características de la infección por Helicobacter pylori en el Perú / Various characteristics of Helicobacter pylori infection in Peru

En la presente serie, compuesta por 2011 pacientes estudiados, nuestras observaciones coinciden con lo reportado en otros países, en relación al porcentaje de hallazgo del H.pylory en los casos de gastritis crónica activa, úlcera p éptica gástrica, úlcera péptica duodenal y en la mucosa gástrica histológicamente normal. En el Perú, en pacientes con síntomas del tracto gastrointestinal superior, la infección por H. pylori se encuentra en porcentajes más elevados (84%) que lo reportado en naciones industrializadas. No observamos incremento de la infección con la edad, debido a que ésta, en nuestro medio, se adquiere en edades muy tempranas como hemos demostrado por la prueba de ELISA. La distribución ecológica de la bacteria, es igual en las tres regiones del Perú y sólo en as mujeres de nivel socioeconómico alto, la prevalencia de la infección es menor. El porcentaje de recurrencia después de tratamiento es superior al descrito en países industrializados (AU)

[Various characteristics of Helicobacter pylori infection in Perú]. / Algunas características de la infección por Helicobacter pylori en el Perú.

The rate of infection by Helicobacter pylori in peruvian dyspeptic patients (84%) is higher than that reported in symptomatic patients from developed countries. Helicobacter pylori infection did not increase with age. The ecological distribution is similar in the three different geographical regions of Peru. Only women of high economic status had significantly lower rates of Helicobacter pylori infection compared to all other groups. The recurrence rate after treatment is higher than that reported from developed countries.

Algunas características de la infección por Helicobacter pylori en el Perú. / [Various characteristics of Helicobacter pylori infection in Perú]

The rate of infection by Helicobacter pylori in peruvian dyspeptic patients (84

) is higher than that reported in symptomatic patients from developed countries. Helicobacter pylori infection did not increase with age. The ecological distribution is similar in the three different geographical regions of Peru. Only women of high economic status had significantly lower rates of Helicobacter pylori infection compared to all other groups. The recurrence rate after treatment is higher than that reported from developed countries.

[Detection of pyloric Campylobacter in patients with gastroduodenal diseases]. / Detección del Campylobacter pilórico en pacientes con enfermedades gastroduodenales.

We report a study of 127 patients examined with esophago-gastroduodenoscopy and with a diagnosis of chronic gastritis (by biopsy), and gastric peptic ulcer and duodenal peptic ulcer (endoscopically). Brushing samples and biopsies were taken from the esophagus, stomach, and duodenum. Gram stains of brush-collected samples, culture of brush samples and biopsies were performed in order to detect the presence of PC. In cases of chronic active gastritis, PC was found in 91% of patients. It was found in 73% and 84%, respectively, of cases of gastric and duodenal ulcer. PC was found with equal frequency in the cardia and body as in the antrum of infected individuals, but no confirmed cases of colonization of the esophagus or duodenum were found. The most efficient methods for identifying PC colonization were (in descending order of efficiency), silver stain of biopsies, Gram stain of brushings, hematoxylin-eosin stain of biopsies, culture of biopsies, and culture of brushings. In some cases, we have identified PC in the esophagus and duodenum by gram stain and culture, but no not by silver stain or H&E stain of biopsies, suggesting that contamination from other areas of the stomach may be an occasional problem in sampling these areas for PC.

Detección del Campylobacter pilórico en pacientes con enfermedades gastroduodenales. / [Detection of pyloric Campylobacter in patients with gastroduodenal diseases]

We report a study of 127 patients examined with esophago-gastroduodenoscopy and with a diagnosis of chronic gastritis (by biopsy), and gastric peptic ulcer and duodenal peptic ulcer (endoscopically). Brushing samples and biopsies were taken from the esophagus, stomach, and duodenum. Gram stains of brush-collected samples, culture of brush samples and biopsies were performed in order to detect the presence of PC. In cases of chronic active gastritis, PC was found in 91

of patients. It was found in 73

and 84

, respectively, of cases of gastric and duodenal ulcer. PC was found with equal frequency in the cardia and body as in the antrum of infected individuals, but no confirmed cases of colonization of the esophagus or duodenum were found. The most efficient methods for identifying PC colonization were (in descending order of efficiency), silver stain of biopsies, Gram stain of brushings, hematoxylin-eosin stain of biopsies, culture of biopsies, and culture of brushings. In some cases, we have identified PC in the esophagus and duodenum by gram stain and culture, but no not by silver stain or H&E stain of biopsies, suggesting that contamination from other areas of the stomach may be an occasional problem in sampling these areas for PC.

Immunological survey in high altitude: effect on antibody production and the complement system.

In order to asses the effect of acute exposure to natural high altitude on some immunological mechanisms of mice, the primary response to SRBC was studied by the direct Hemolytic Plaque and Hemagglutination Tests. A control group was studied in Lima, Peru, 150 m. At high altitude (Ticlio, Peru, 4843 m), we found fewer spleen plaque-forming cells (PFC) and the maximal peak of PFC was delayed 1 day, as compared with the response at a lower altitude. Conversely, there was a higher serum concentration of 2-ME sensitive and resistant hemagglutinin antibodies at high altitude and the 19-S (2-ME sensitive) response was predominant during the first days at high altitude while the 7-S response was retarded. These results are interpreted as a stimulating effect of hypoxia on the 19-S antibody production rather than a cellular proliferation as far as the SRBC system is concerned. Serum concentrations of Igs G, M, A and the fraction C'3 of the Complement (B1C/B1A globulin) were determined in normal natives from three cities at different altitude levels: Morococha-Ticlio, 4680 m; La Oroya, 3700 m; and Tarma, 3051 m by the Radial Immunodiffusion Test. The serum concentration of C'3 was correlated with the total hemolytic activity of Complement (C'H50 method) in a group of natives from Morococha. The control group was of normal natives from Lima. No significant differences were found between resum concentration of Igs G, M and A in both groups, but there was a tendency for higher values of IgA at higher altitudes, and most sera in the high altitude group were above the normal IgG values for adults. The resum concentration of C'3 and the hemolytic activity of Complement were wound to be diminished in the high altitude group. These results are interpreted as an inhibitory effect of the altitude on the sequential activation and/or lysing capability rather than a reduction in the C'3 concentration.

Pathogenesis of the verruga of Carrion's disease. Ultrastructural studies.

Five patients having the "eruptive form" of Carrion's disease were found to have bacteria in the fine fibrillar interstitium of the verrugas. Features suggesting phagocytosis of the organisms by the verruga cells were observed. The bacteria are probably Bartonella because they are similar to Bartonella that parasitize red blood cells in the hematic phase of the disease. It is likely that after the hematic phase, unknown mechanisms, probably related to immunity, drive Bartonella organisms to the skin where they are destroyed and eliminated in the verrucous tissue. This suggests that verrucous tissue develops in order to eliminate Bartonella during the tissue phase of the disease.