Search

Sustainable control of human filariasis would benefit enormously from the development of an effective vaccine. The ability to vaccinate experimental animals, with reductions in worm burden of over 70%, suggests this aim is possible. However, in experimental vaccinations the challenge is usually administered 2 weeks after the immunisation phase and thus the protection obtained is likely to be biased by persisting inflammation. Using the murine model Litomosoides sigmodontis, we increased the time between immunisation with irradiated larvae and challenge with fully infective L3 to 5 months. Significant protection was achieved (54-58%) and the reduced worm burden was observed by 10 days p.i. The developmental stage targeted was the L3, since no nematodes died once they reached the pleural cavity of vaccinated mice, as has been previously shown in short-term protocols. However, larval developmental rate was faster in vaccinated than in primary-infected mice. Immunological assessments were made prior to challenge and then from 6 h to 34 days post-challenge. Samples were taken from the subcutaneous tissue where the larvae were inoculated, the lymph nodes through which they migrate and the pleural cavity in which they establish. Eosinophils were still present although scarce in the subcutaneous tissue of vaccinated mice before challenge. Cytokine and specific antibody production of vaccinated and challenged mice were L3-specific and Th2-biased and greatly exceeded the response of primary-infected mice. The heightened Th2 response may explain the faster development of the filarial worms in vaccinated mice. Thus, long-term vaccination protocols generated a strong memory response that led to significant but incomplete protection that was limited to the infective larval stage suggesting alternative vaccination strategies are needed.

Background: Fibromuscular dysplasia (FMD) is a rare non-atherosclerotic and non-inflammatory disease in the arterial system. The purpose of the study was a retrospective analysis of FMD in the renal artery. Patients and methods: A total number of 102 patients (mean age: 36.9 years) who suffered from renovascular hypertension underwent a surgical therapy. The operative specimens of the renal arteries were analysed with the lightmicroscop using histological and immunohistochemical methods. Results: 101 patients (99.02%) presented a medial FMD (extensive-medial subtype in 56 patients, 54.9%, subadventitial subtype in 29 patients, 28.4% and combined subtype in 16 patients, 15.7%). In 1 patient (0.98%) an adventitial FMD was found. We observed the following complications: true and dissecting aneurysms (75 patients, 74.5%), arterio-venous fistulae (2 patients, 1.96%) and chronic thrombosis (10 patients, 9.8%). Conclusions: With the progress in angioplasty, not all patients suffering from FMD undergo a primary surgical therapy and therefore this lesion is less seen in the daily work of the histopathologist.

BALB/c mice of both sexes were infected with a non-virulent strain of Plasmodium chabaudi chabaudi and any pathologies occurring in the urogenital tract and its accessory glands were investigated. Organs and tracts were removed from infected and control mice at 15, 40 and 100 days post-injection, weighed and processed for macroscopical and histological analyses. The relative weights of preputial, clitoral glands and testes were modified in infected mice during the 40 days following infection. The preputial glands show a marked hypotrophy at 15 days post-infection. The bladders of half of the infected female mice and a few infected male mice displayed a conspicuous haemoglobinuria and frequent interstitial cystitis that worsened throughout the experiment. Also, several chronic inflammatory reactions were detected in the prostates, preputial and clitoral glands up to 100 days post-infection. A probable cause of such a divergence in the characteristics of the infection and in the nature of the pathologies identified in infected male and female mice is the interaction between the infection and the immune and endocrine systems of the host. The cause of the pathologies and their consequences on the host condition are discussed.

Background: The goal of our study was to demonstrate the extension of the transitional zone (TZ) between elastic and muscular medial structure in carotid artery tripod. Patients and methods: A histologic study of 56 probes from 8 carotid artery tripods was performed. The probes were obtained from autopsies of 4 adults (mean age: 47.5 years, range 38 to 55 years) and were taken from 7 different topographic sites. Results: At each level of the CCA (at 1 cm and 2 cm proximal to the bifurcation as well as at the bifurcation) we observed an elastic arterial type in 24 (42.8%) probes with 11 to 20 (medium 15.0) elastic fibers per view field (200 ¥ magnification) in the media. In contrast the histologic structure of the ICA and ECA varied as follows: in 8 sections (14.3%) elastic arterial type with 11 to 16 (medium 13.1) elastic fibers, in 11 sections (19.6%) muscular arterial type with 2 to 5 (medium 3.5) elastic fibers and in 9 sections (16.1%) a transitional arterial type with 6 to 8 (medium 6.7) elastic fibers in the media. Atherosclerotic lesions have prevented the assessment of the arterial type in 4 probes (7.1%). The TZ in the medial structure of carotid artery tripods is exclusively localized in the ICA/ECA but not in the CCA. The ICA/ECA presented a TZ with a length up to 0.5 cm (4 probes; 25%), up to 1.5 cm (4 probes; 25%) and longer than 1.5 cm (6 probes; 37.5%). Conclusions: In this study we confirmed that in the carotid artery tripod, a TZ – an arterial segment with transition from elastic to muscular type – does exist, involving a variable length. Furthermore studies on the impact of the biomechanical properties of the TZ as a potential factor in atherosclerotic disease are justified. In addition, the complex biomechanical behavior of the TZ should be considered prior to interventional procedures.

Background: The goal of our study was to demonstrate and to determine the length of the transitional zone in the tunica media in renal arteries. The majority of renal artery atherosclerotic stenotic lesions occurs in this segment. Patients and methods: Anatomical and histological studies were performed on 26 renal arteries from 13 adults at autopsy (mean age 61.6 years, range 33 to 87 years). Results: In the macroscopical examination the right renal arteries (RRA) were longer with a median 53.8 mm (range 38 to 65 mm) than the left renal arteries (LRA) with a median 47.6 mm (range 35 to 63 mm), the circumferences were nearly the same: RRA 10.9 mm (range 5 mm to 15 mm) and LRA 11 mm (range 5 mm to 15 mm). Probes for histological examinations were taken from three different regions of each renal artery (origin, 5 mm and 10 mm distal to the origin). We observed a typical elastic arterial structure at the origin and muscular types at the distal 10 mm region. At the distal 5 mm region variable ratios of elastic tissue (ET) and smooth muscle cells (SMC) were found as follows: 15 arteries presented an equal ratio of EM : SMC, 7 arteries presented ET > SMC and 4 arteries presented ET < SMC ratios. Conclusions: In this study we confirmed that in renal arteries, a transitional zone (TZ) that is an arterial segment with transition from elastic to muscular type, does exist, involving the maximal length of 10 mm. Further studies on the impact of the biomechanical properties of the transitional zone as a potential localizing factor in renal atherosclerotic disease are justified. In addition, the complex biomechanical behavior of the TZ of the arterial wall should be taken into consideration when interventional procedures are planned.

In order to establish the role of eosinophils in destroying parasites, transgenic mice have been used in experimental helminthiases but not in filariasis.Litomosoides sigmodontisoffers a good opportunity for this study because it is the only filarial species that completes its life cycle in mice. Its development was compared in transgenic CBA/Ca mice overexpressing interleukin-5 (IL-5) and in wild-type mice following subcutaneous inoculation of 40 infective larvae. An acceleration of larval growth was observed in the IL-5 transgenic mice. However, the recovery rate of adult worms was considerably reduced in these mice, as evidenced 2 months postinoculation (p.i.). The reduction occurs between days 10 and 30 p.i. in the coelomic cavities. As early as day 10, spherical aggregates of eosinophils and macrophages are seen attached on live developing larvae (always similarly localized on the worm) in both wild-type and transgenic mice. However, on day 60 p.i., granulomas were found in the transgenic mice only, probably because of the higher density of eosinophils. Furthermore, on day 30 p.i., young filariae are seen trapped in granulomas, some of them surrounded by Splendore-Hoeppli deposits, which illustrates the release of the major basic protein by eosinophils. The high protection rate obtained (65%) is similar to that observed previously in BALB/c mice following vaccination with irradiated larvae. Both protocols have a common factor, the high production of IL-5 and eosinophilia. However, protection occurs later in primary infected transgenic mice because specific antibodies are not yet present at the time of challenge.

Coarctation of the aorta usually occurs in the aortic isthmus: however, 2% of all coarctation is localized at atypical sites such as the aortic arch and the thoracic and/or abdominal aorta. Causal therapy involves vascular surgery, and during the procedure, biopsies of the involved vessels should be taken to establish the etiology. This study involved the retrospective analysis of clinical and histopathological findings for seven patients who underwent vascular surgical procedures (age range, 10-37 years; male/female ratio 3:4). Histopathological analysis of specimens revealed two pathological processes taking place with different localization in the aortic wall as the cause of the atypical coarctation of the aorta: (1) fibrosis/scarification in the tunica media and adventitia compatible with chronic lesions of Takayasu's arteritis (four cases); (2) fibromuscular dysplasia in the tunica media (three cases).

Dear Editor: Chronic prolapse of intestinal mucosa appears to be the underlying mechanism behind a number of gastrointestinal conditions. We describe two cases of rectal prolapse in children aged 13 and 14 years presenting as recto-sigmoid polyposis. The underlying rectal prolapse remained undiagnosed for 3 and 4 years respectively. Rectopexy provided complete clinical and endoscopic healing in both cases.

BACKGROUND: Adenoid cystic (cylindromatous) carcinoma is a rare tumor. It accounts for approximately

Une fistule anale d'origine cryptoglandulaire peut-elle etre d'origine sarcoidosique? Si oui, en raison de leur parente sur le plan histologique, quels sont les elements discriminants avec les fistules anales dela maladie de Crohn?

We report an anal metastasis from a lung cancer which was diagnosed on symptoms mimicking an acute anal abcess. The diagnosis was based on specific immunohistochemistry.

An experimental host-parasite association involving BALB/c female mice infected with Plasmodium vinckei petteri was used with the aim of investigating the morphological and physiological alterations induced by the parasite in the genital tract of the host. The vaginal oestrous cycle was monitored as a daily clue to the sexual physiology of the female mice, and a complete histological analysis of the genital tract was performed 36 days following parasite inoculation. The oestrous cycle showed strong transitory alterations during the first 30 days following infection. The occurrence of oestrus days increased during the first 10 days post-infection and then decreased to a subnormal value during the following 20 days. Infected mice also showed a remarkable hypotrophy of their clitoral glands 30 days after the beginning of the malarial infection. A probable cause of such perturbations is a significant hormonal imbalance triggered by the erythrocytic proliferation of the Plasmodium. The relationship between the immune response of the host and these physiological and morphological alterations, as well as the outcomes of these alterations on the sexuality of the rodent host are discussed.

Congenital vascular anomalies can be divided into three groups: those developing during intra-uterine life, those associated with karyotype aberrations, and those arising from the effects of single genes or complex polygenic mutations. There are no good data on the incidence of these lesions; a recent Finnish study on 4346 new-borns showed a 3.8% rate of vascular lesions excluding salmon patches on the head and neck, in general agreement with other studies [1]. Seventy to 80% of lesions are said to regress spontaneously by the age of seven years. In most instances of this type of lesion both blood and lymphatic vessels may be affected.

The cardiovascular system consists of four main types of vessel: arteries, veins, capillaries and the less well defined sinusoids. No vessel (small or large) should be seen as a simple conduit; all have distinct functional characteristics, which, in turn, will affect organ function profoundly, and their structure is modified by the functional demands they must satisfy. As an arbitrary definition we can say that any vessel whose diameter is larger than 250 to 300 lam and visible to the naked eye belongs to the macrocirculation and that the microcirculation is made up of vessels measuring less than 250 μm in diameter [1].

An aneurysm is a localised dilatation of a vessel wall involving all of its coats. Arteries most often become aneurysmal but aneurysms are also found in the mi­crocirculation and, rarely, in veins.

Thrombosis is defined as the formation of a solid mass in the circulatory system from the elements of the blood during life.

In a number of metabolic diseases, involvement of the heart and blood vessels is a central part of the disease process; in some the disease is manifest by virtue of a cardiovascular change or complication [1] It is these conditions which will be considered here.

When vessels are exposed to ionising radiation experimentally there is immediate damage to the endothelium, with increased permeability and necrosis followed by healing with intimal proliferation and vascular stenoses. Smooth muscle cells undergo more subtle damage resulting in loss of cellularity of the media and replacement by fibrosis. Radiation also induces a chronic antiangiogenic effect and contributes to growth abnormality, for example, in limb development [1, 2]. In man, long-term complications of radiation injury are still commonly seen despite advances in radiotherapy. Acute effects are largely time dependent and can be controlled by alteration of therapy schedule. For chronic changes, the age at the time of exposure to radiation does not seem to affect the time of the onset of lesions. No direct correlation has been established between the severity of the injury and the dose of radiation and the true incidence of radiation-induced vascular changes is almost certainly underestimated. The duration of time between exposure and development of post-radiation changes varies from months to 24 years, with a mean of 14 years [3–7], and further complications (tissue necrosis, infection, and ulceration) may occur later. The clinical patterns depend on the role of the organ system involved, and ischaemic syndomes, erectile dysfunction [8], aortic arch syndrome or pulseless disease [9], aneurysms, veno-occlusive liver disease [10] and vascular rupture [11] have all been reported. In children, moyamoya syndrome has been reported following radiation therapy for tumours at the base of the brain [12].

Thrombosis is the formation of a solid mass, derived from the consituents of the blood, within the vascular system during life. As an important part of haemosta-sis, it depends on a normally functioning endothelium and underlying subendothelial layer, platelets, and the coagulation cascade.

Blood vessels and lymphatics play a central role in many infections or infestations. Viruses, bacteria fungi and parasites may all disseminate through vessels or demonstrate a tropism for vessel walls or a capacity to parasitise vessels in the long term, with mechanical complications. Vasculitis (see chapter XI), disseminated intravascular coagulation and thrombosis may occur [1, 2]. There is direct and indirect evidence establishing links between infection and vascu-lopathy, including aortitis, atherosclerosis, Wegener’s granulomatosis and various vasculitic syndromes [3]. However, most complications are caused by the infectious disease itself (via toxins, haemolysis or cross-reacting antigens) or are facilitated by changes in the response of the immune system [4, 5].

First reported by Leadbetter and Burkland in 1938 [1], fibromuscular dysplasia (FMD) is a segmental, non-atheromatous and non-inflammatory disease affecting mostly intermediate size arteries. It is manifest by consistent alterations in the smooth muscle cells of arteries, associated with modifications of the extracellular ground substance. Recent progress in diagnostic imaging allows more precise diagnosis of the location and type of lesions and, in general, pathologists have few opportunities to study fibromuscular dysplasia. X-ray-controlled angioplasty or embolization [2–4] now deals with most of the lesions and operative surgery is carried out only when angioplasty fails. The morphological pattern of fibromuscular dysplasia now seen by the pathologist is a mixture of the primary lesions plus the changes produced by the complications of angioplasty. Many so-called natural complications (dissecting haematoma, aneurysm, AV fistula) result directly from the invasive techniques.

Arterial hypertension is commonly classified as primary (essential) or secondary. Two clinical forms occur; by far the most common is a chronic or slowly developing elevation of the blood pressure leading to structural and functional changes in vessels, mediated primarily by vascular smooth muscle [1]. The aetiology is complex and depends on the interaction of a number of genetic factors and events during development, with environmental factors playing a part in some populations [2]. Information on genetic factors (genes coding for renin, angiotensin converting enzyme, angiotensinogen and the AT1 receptor) is well reviewed by Peters [3] and Morgan et al [4] have investigated the significance of polymorphism in the angiotensinogen gene.

Most angioleiomyomas develop from the smooth muscle cells of the media or adventitia, most frequently in a subcutaneous vein, but larger veins (hepatic, femoral) may be involved. The tumour affects patients between the fourth and sixth decades with a predilection for females. The most frequent locations are in the legs and arms [1–3]. Other sites include the skin, nasal mucosa or the pharyngeal space [4–7]. An angioleiomyoma appears as a circumscribed mass, usually measuring about 2 cm in diameter, rarely larger than 4–5 cm. Pain, present in half of the cases, may be exacerbated by menses, pregnancy, pressure and changes in temperature. Simple excision is adequate treatment.

Bacterial infections in veins may be a complication of local or systemic infections. Infected wounds, superimposed infections in eczema or mycosis or septicaemia may all have a venous component (Fig. 1). Open image in new window (Fig.1) Phlebitis. Haematoxylin, eosin and saffron stain. (HES)

In this area the terminology is often confused, and even misleading. In many conditions, especially with regard to the benign lesions, the clinical and familial history are of great importance in diagnosis.

To establish the role of B cells and antibodies in destroying filariae, mice lacking mature B cells and therefore unable to produce antibodies were used.Litomosoides sigmodontisoffers a good opportunity for this study because it is the only filarial species that completes its life cycle in mice. Its development was compared in B-cell-deficient mice (BALB/c μMT mice) and wild-type BALB/c mice in two different in vivo situations, vaccination with irradiated larvae and primary infection. In all cases, mice were challenged with subcutaneous inoculation of 40 infective larvae. Vaccine-induced protection was suppressed in B-cell-deficient mice. In these mice, eosinophils infiltrated the subcutaneous tissue normally during immunization; however, their morphological state did not change following challenge inoculation, whereas in wild-type mice the percentage of degranulated eosinophils was markedly increased. From this, it may be deduced that the eosinophil–antibody–B-cell complex is the effector mechanism of protection in vaccinated mice and that its action is fast and takes place in the subcutaneous tissue. In primary infection, the filarial survival and growth was not modified by the absence of B cells. However, no female worm had uterine microfilariae, nor did any mice develop a patent infection. In these mice, concentrations of type 1 (gamma interferon) and type 2 (interleukin-4 [IL-4], IL-5 and IL-10) cytokines in serum were lower and pleural neutrophils were more numerous. The effects of the μMT mutation therefore differ from those in B1-cell-deficient mice described on the same BALB/c background, which reveal a higher filarial recovery rate and microfilaremia. This outlines B2-cell-dependent mechanisms as favorable to the late maturation ofL. sigmodontis.

The pathways conferring immunity to human filariases are not well known, in part because human-pathogenic filariae do not complete a full life cycle in laboratory mice. We have used the only fully permissive infection of mice with filariae, i.e., infection of BALB/c mice with the rodent filarial nematode Litomosoides sigmodontis. Our previous results showed that worm development is inversely correlated with Th2 cytokine production and eosinophilia. The scope of the present study was to directly elucidate the role of interleukin-5 (IL-5) and eosinophils in controlling the development of L. sigmodonitis after vaccination and in primary infection. BALB/c mice immunized with irradiated third-stage larvae (L3) were confirmed to have elevated IL-5 levels as well as high subcutaneous eosinophilia and to attack and reduce incoming larvae within the first 2 days, resulting in 70% reduction of worm load. Treatment of vaccinated mice with anti-IL-5 antibody (TRFK-5) suppressed both blood and tissue eosinophilia and completely abolished protection. This demonstrates, for the first time in a fully permissive filarial infection, that IL-5 is essential for protection induced by irradiated L3 larvae. In contrast, in primary-infected mice, anti-IL-5 treatment did not modify filarial infection within the 1st month, most likely because during primary infection IL-5-dependent mechanisms such as subcutaneous eosinophilia are induced too late to disturb worm establishment. However, there is a role for IL-5 late in primary infection where neutrophil-dependent worm encapsulation is also under the control of IL-5.

This study was performed with Litomosoides sigmodontis, the only filarial species which can develop from the infective larvae to the patent phase in immunocompetent laboratory BALB/c mice. Parasitological features and immune responses were analysed up to 3 months before and after challenge inoculation, by comparing 4 groups of mice: vaccinated challenged, challenged only, vaccinated only, and naive mice. Male larvae were very susceptible to irradiation and only female irradiated larvae survived in vivo. Protection, assessed by a lower recovery rate, was confirmed and was established within the first 2 days of challenge. This early reduction of the recovery rate in vaccinated challenged mice was determined by their immune status prior to the challenge inoculation. This was characterized by high specific IgM and IgG subclass (IgG1, IgG2a and IgG3) levels, high specific IL-5 secretion from spleen cells in vitro and a high density of eosinophils in the subcutaneous connective tissue. Six h after the challenge inoculation, most tissue eosinophils were degranulated in vaccinated challenged mice. Thus, in the protocol of vaccination described, protection appeared mainly to result from the stimulation of a Th2 type response and eosinophils seemed to be the main effectors for the increased killing of infective larvae in vaccinated challenged mice. Two months after challenge inoculation, the percentage of microfilaraemic mice was lower in vaccinated challenged mice as a consequence of this overall reduction in the worm load. In both vaccinated challenged and challenged only groups, the in vitro splenocyte proliferative capacity was reduced in microfilaraemic mice.

We report an anal metastasis from a lung cancer which was diagnosed on symptoms mimicking an acute anal abcess. The diagnosis was based on specific immunohistochemistry.

The filaria Monanema martini with skin-dwelling microfilariae induces in its natural murid hosts lesions similar to those in human onchocerciasis. This was demonstrated by histo-pathological studies but it appeared useful to evaluate the model by a clinical investigation. An ophthalmological analysis was performed on the two species of hosts, inoculated by one, two, or multiple doses of larvae, and with infections of at least one year duration. A total of 140 eyes was examined (anterior and posterior segments). We established a system for enumerating the different types and severities of lesions. We prepared a file for each eye and attempted to quantify our observations. The significant lesions were different in the two host species. In Arvicanthis niloticus, in which motile microfilariae were seen in the anterior segment, punctate keratitis was predominant. In Lemniscomys striatus, the posterior segment showed complete chorioretinal atrophy, similar to the final stage of onchocercal chorioretinitis in humans. M. martini represents in its natural hosts two complementary models for the study of the pathogenesis and treatment of human onchocerciasis.

Our aim in this study was to observe the movements of filarial infective larvae following inoculation into the mammalian host and to assess the effect of vaccination on larval migration, in situ. Here we present recordings of larvae progressing through the subcutaneous tissues and inguinal lymph node of primary infected or vaccinated mice. We used the filaria Litomosoides sigmodontis in BALB/c mice that were necropsied 6 hours after the challenge inoculation of 200 larvae. Subcutaneous tissue sections were taken from the inoculation site and larvae were filmed in order to quantify their movements. Our analyses showed that the subcutaneous larvae were less motile in the vaccinated mice than in primary-infected mice and had more leucocytes attached to the cuticle. We propose that this reduced motility may result in the failure of a majority of larvae to evade the inflammatory reaction, thereby being a possible mechanism involved in the early vaccine-induced protection.

Summary The clinical and pathological features of three unusual soft tissue tumors are presented. They occurred in the groin of elderly patients in the subcutaneous tissue. In Case 1, the inguino-crural tumor coexisted with a second mass in the pelvis. The tumors had a tendency to recur locally and to invade the regional lymph nodes. Metastatic dissemination of the disease resulted in the death of the patient in Case 3. Histologically, the tumors appeared composed of small round cells with scanty cytoplasms, arranged in diffuse, poorly cohesive or solid sheets. In places, a trabecular pattern was noted. Mitotic figures were numerous. Some cells exhibited argyrophil granules. The ultrastructural study revealed compact whorls of intermediate filaments and neurosecretory granules. All three cases displayed a paranuclear dot-like positive reaction with antibodies to cytokeratins and neurofilaments. A diffuse cytoplasmic immunostaining for neuron-specific enolase was present in Cases 1 and 2. Protein S-100, vimentin and leucocyte common antigen could not be demonstrated. All these characteristics, except for the subcutaneous location, are shared with neuroendocrine (Merkel cell) tumors of the skin.

A case of acquired myospherulosis of the right gluteal region diagnosed by FNA cytology is reported in a woman who had received a series of intramuscular injections of petrolatum-based hormones. The lesion is characterized by inflammatory pseudocystic nodules containing saccular formations with erythrocytes or "bags of marbles." It results from a physical process similar to the emulsion phenomenon between nonresorbent oily material and plasma. This process gives rise to sequestration of blood corpuscles by oily materials and thus development of foreign body granulomas.

Thirty-nine patients (mean age: 33 years) with Takayasu's disease were observed over the past 8 years. Among these patients, 33 had surgical intervention with a mean follow-up of 4 years. Lesions of the aortic arch were the most common (29 patients, 69 lesions) and frequently were associated with lesions in another site as well. However, in this group of patients, the infrequent presence of signs of cerebral vascular insufficiency limited the number of suitable surgical candidates to 14 patients. Lesions of the renal arteries were noted in 25 patients (37 lesions) and were associated with coarctation of the thoracoabdominal aorta in 12 patients. In contrast to lesions of the aortic arch, the presence of severe hypertension was a frequent indication for surgery in Takayasu's disease. Twenty-one patients had operation. Twenty of 21 patients were considered cured or improved of hypertension. The one patient who received no benefit was the only operative death of the study. In conclusion, although Takayasu's disease is progressive and the life expectancy is foreshortened, hypertension secondary to aortic and renal artery lesions is a frequent and important indication for aggressive operative treatment.