Incidence, mortality and receptor status of breast cancer in African Caribbean women: Data from the cancer registry of Guadeloupe.

BACKGROUND: Geographical disparities in breast cancer incidence and outcomes are reported worldwide. Women of African descent show lower incidence, higher mortality rates and earlier age of onset. We analyzed data from the cancer registry of Guadeloupe for the period 2008-2013. METHODS: We describe breast cancer characteristics by molecular subtype, as well as estimated observed and net survival. We used Cox proportional hazard models to determine associations between cancer subtypes and death rate, adjusted for variables of interest. RESULTS: Overall, 1275 cases were recorded with a mean age at diagnosis of 57(±14) years. World standardized incidence and mortality were respectively 71.9/100,000 and 14.1/100,000 person-years. Age-specific incidence rates were comparable to European and US populations below the age of 45, and higher in Guadeloupean women aged between 45 and 55 years. Overall, 65.1% of patients were hormone receptor (HR)+ and 20.1% were HR-. Triple negative breast cancers (TNBC) accounted for 14% of all cases, and were more frequent in patients under 40 (21.6% vs. 13.4%, p=0.02). Five-year net survival was 84.9% [81.4-88.6]. It was higher for HR+/Her2+ and HR+/Her2- subtypes, and lower for HR-/Her2+ and TNBC patients. CONCLUSION: We found high age-specific incidence rates of breast cancer in women aged 45 to 55 years, which warrants further investigation in our population. However, this population of mainly African descent had good overall survival rates, and data according to subtypes are consistent with those reported internationally. These results may suggest that poorer survival in other African descent populations may not be an inherent feature of the disease but may be amenable to improvement.

Local production of nitric oxide in patients with tuberculosis.

Nitric oxide (NO), produced by the inducible nitric oxide synthase (iNOS), is important in host defence against Mycobacterium tuberculosis in rodents, but the presence of high-output NO production in human tuberculosis has been controversial. We investigated iNOS and nitrotyrosine (Ntyr) expression in pleural (n = 7), pulmonary (n = 5) and lymph node biopsies (n = 5) from untreated, newly diagnosed tuberculosis patients. Many iNOS and Ntyr reactive macrophages were observed in granulomas, including Langhans giant cells, indicating high-output NO production at the primary site of disease in tuberculosis.

Nitrotyrosine localization to dermal nerves in borderline leprosy.

BACKGROUND: Nerve damage is a common and disabling feature of leprosy, with unclear aetiology. It has been reported that the peroxidizing agents of myelin lipids-nitric oxide (NO) and peroxynitrite-are produced in leprosy skin lesions. OBJECTIVES: To investigate the localization of nitrotyrosine (NT)-a local end-product of peroxynitrite-in leprosy lesions where dermal nerves are affected by a granulomatous reaction. METHODS: We investigated by immunohistochemistry and immunoelectron microscopy the localization of the inducible NO synthase (iNOS) and NT in biopsies exhibiting dermal nerves from patients with untreated leprosy. RESULTS: There were abundant NT-positive and iNOS-positive macrophages in the borderline leprosy granulomas infiltrating peripheral nerves identified by light microscopy, S-100 and neurofilament immunostaining. Immunoelectron microscopy showed NT reactivity in neurofilament aggregates and in the cell wall of Mycobacterium leprae. CONCLUSIONS: Our results suggest that NO and peroxynitrite could be involved in the nerve damage following borderline leprosy.

Expression of inducible nitric oxide synthase and nitrotyrosine in borderline leprosy lesions.

BACKGROUND: In the response to T-helper cell (Th1)-type cytokines and interactions with pathogens, high levels of nitric oxide (NO) are produced by activated macrophages expressing the inducible NO synthase (iNOS). The role and importance of reactive nitrogen intermediates (RNIs) such as NO and peroxynitrite in the host response to diseases caused by intracellular pathogens such as Mycobacterium leprae and M. tuberculosis is unclear. OBJECTIVES: The aim of this study was to investigate the presence of local production of NO and peroxynitrite in borderline leprosy by using antibodies against iNOS and the product of peroxynitrite, nitrotyrosine (NT). METHODS: We detected the presence of iNOS and NT in skin biopsies from borderline leprosy patients, with and without reversal reaction (RR), by immunohistochemistry (n = 26). RESULTS: In general, the granulomas from borderline leprosy lesions with and without RR showed high and specific expression of iNOS and NT. Moreover, strong immunoreactivity to iNOS and NT was observed in granulomas surrounding and infiltrating dermal nerves. The expression of iNOS and NT was also strong in keratinocytes, fibroblasts and endothelial cells in close relation to the granulomatous reaction. In contrast, normal human skin showed no expression of iNOS and NT in these cells. CONCLUSIONS: We conclude that iNOS and NT are expressed in granulomas from borderline leprosy patients with and without RR and propose that RNIs might be involved in the nerve damage following RR in leprosy.

Leishmania aethiopica: experimental infections in non-human primates.

Six Cercopithecus aethiops monkeys, 4 Theropithecus gelada baboons and 2 Papio anubis baboons were infected using Leishmania aethiopica isolates originating either from localized (LCL) or diffuse (DCL) cutaneous leishmaniasis patients. The history of lesions in 4 C. aethiops monkeys infected by LCL strains mimicked the process in human LCL patients. Infection of 2 C. aethiops monkeys using a DCL strain resulted in localized, non-ulcerative, self-healing nodular lesions. Such lesions were also observed in 2 T. gelada baboons infected by LCL strains. Active lesions and healing in C. aethiops and T. gelada, after infection by LCL stains, were accompanied by positive DTH and immunity to challenge by LCL or DCL strains.

Detection of cutaneous Leishmania infection in paraffin-embedded skin biopsies using the polymerase chain reaction.

In this study the polymerase chain reaction (PCR) with previously developed oligonucleotide primers was used to detect Leishmania aethiopica in paraffin-embedded skin biopsy specimens. The Leishmania-specific 120 base pair fragment of the kinetoplast deoxyribonucleic acid (kDNA) minicircles has been amplified from all parasitologically or histologically confirmed cases of cutaneous leishmaniasis (CL), as demonstrated by gel electrophoresis and hybridization with L. aethiopica kDNA. Control specimens from patients with skin diseases other than CL were all negative. Using PCR, Leishmania were demonstrated in the skin lesions of 7 cases in a group of 40 patients in whom the parasites could not be demonstrated by histopathology or culture in vitro although lesions were clinically suggestive of CL. These data indicate that PCR, carried out on DNA extracted from formalin-fixed and paraffin-embedded tissue specimens, is a valuable method for the diagnosis of CL, especially in chronic cases where the parasite load in the lesion is low.

Ethiopian visceral leishmaniasis patients co-infected with human immunodeficiency virus.

This communication reports 7 Ethiopian visceral leishmaniasis (VL) patients co-infected with human immunodeficiency virus (HIV). The clinical and laboratory findings in 6 patients did not differ from classical VL. All patients had highly elevated anti-leishmanial antibody titres, determined by immunoglobulin G-based enzyme-linked immunosorbent assay; they most probably acquired the Leishmania infection before HIV. Amastigotes were identified in the splenic aspirates of 6 patients and in the lymph node aspirate of the 2 patients whose lymph nodes were examined. The CD4:CD8 lymphocyte ratio was depressed in those patients whose ratio was determined. Most patients showed some initial response to pentavalent antimonial therapy.

HIV infection and leprosy: a four-year survey in Ethiopia.

Between 1988 and 1992 three cross-sectional surveys for antibodies to HIV were done in 644 Ethiopian patients with histologically proven leprosy. Whereas the frequency of HIV-1 infection gradually increased from 3.2% to 6.5%, the clinical presentation, number of new patients, and frequency of relapse did not differ between HIV negative and positive patients. Thus HIV appears unlikely to have a significant impact on the incidence of leprosy in sub-Sahelian populations.

In leprosy the presence of mycobacteria in the nerve is an essential factor in the cycle and spectrum of Mycobacterium leprae infection.

A total of 220 untreated leprosy patients who underwent parallel skin and nerve biopsies are included in this study, which is intended to evaluate the extent of previously reported differences in bacillary load between skin and nerve lesions in leprosy and to describe the response of peripheral blood lymphocytes to Mycobacterium leprae antigens in such patients. In 161 patients out of the 220, the skin and nerve biopsies were diagnostic for leprosy. When patients were grouped according their skin and nerve lesions, the 3 groups observed were (1) paucibacillary skin and nerve lesions; (2) multibacillary skin and nerve lesions, and (3) paucibacillary skin and multibacillary nerve lesions. There was no observation of a group of patients with multibacillary skin and paucibacillary nerve lesions. In all patients with multibacillary nerve lesions, regardless of the type of skin lesions, a low response of peripheral blood lymphocytes to M. leprae was consistently noted. These results suggest that the bacillary load in the nerve is certainly one of the factors determining the immunological spectrum observed in leprosy.

Major histocompatibility complex class II antigen expression in nerves in leprosy; an immunoelectronmicroscopical study.

A technique for immunoelectronmicroscopy has been used to investigate major histocompatibility class II expression in leprosy nerves. In normal nerves, endothelial cells and occasional endoneural cells (not Schwann cells) were constitutively class II positive. In both paucibacillary and multibacillary leprosy nerve biopsies, infiltrating leukocytes were positive but class II-positive Schwann cells were not seen. These observations indicate that Schwann cells may not be involved in presenting Mycobacterium leprae antigens to T cells in leprosy. This conflicts with evidence from in vitro studies, but may be explained by the fact that in vivo Schwann cells are surrounded by basement membranes and are closely associated with axons.

Angio-immunoblastic lymphadenopathy with dysproteinaemia in an Ethiopian: case report and literature review.

A thirty year-old man with angio-immunoblastic lymphadenopathy (AILD) is presented. This is the first case recorded from Ethiopia, and few have been reported elsewhere in Africa. The patient presented with generalized lymphadenopathy, fever, weight loss, pruritus, skin rashes, anaemia, hepatomegaly and pulmonary infiltrates. Lymph node histology was typical of AILD. The available literature on this relatively new pathologic entity reveals that little is known about the nature of AILD, and since there is no established therapy, an individualized approach to management is advisable.

Cytomegalovirus colitis in patients with acquired immunodeficiency syndrome.

Twenty-four AIDS patients, who underwent gastrointestinal evaluation, died from their disease and were autopsied. Seven had Cytomegalovirus colitis (group I) and 17 did not (group II). Clinical manifestations, digestive lesions, and infections were compared in the two groups. Chronic watery diarrhea was present in all the patients with colitis but was also present in 65% of the patients without colitis. Hematochezia was present only in the group with colitis (one of seven patients) but appeared late in the diarrheal course, due to necrotizing colitis. No other difference were noted between the two groups (mean duration of diarrhea, frequency and nature of the other infections). As for group I specifically, colonic ulcerations due to Cytomegalovirus were present in all the patients, varying from punctate and superficial erosions to deep ulcerations, with granular and friable intervening mucosa. Severe colonic lesions appeared during the course of Cytomegalovirus colitis in two patients who developed lethal necrotizing colitis. Finally, the clinical and pathologic features of these seven cases were compared to other reports of Cytomegalovirus infection of the colon.

Loiasis: "Calabar" swellings and involvement of deep organs.

The authors report clinical and histopathologic changes in six patients with symptomatic loiasis. One patient had cutaneous swellings, three patients presented with hydrocele, one patient developed bowel obstruction, and one had generalized fatal loiasis. The first five patients had localized lesions provoked by adult worms; all were surgically removed. The sixth patient died of disseminated loiasis that included a severe loal encephalitis. The authors discuss the mechanism of "Calabar" swellings, the reaction to adult Loa loa worms and loal encephalitis.