Cicatricial pemphigoid antigen differs from bullous pemphigoid antigen by its exclusive extracellular localization: a study by indirect immunoelectronmicroscopy.

Several components of the dermal-epidermal junction (DEJ) bear the name of the autoimmune bullous disease in which they are involved. The epidermolysis bullosa acquisita (EBA) antigen, a component of anchoring fibrils, and the bullous pemphigoid (BP) antigen, a component of hemidesmosomes (HD) with a molecular weight of 220-240 kD, have been well characterized. In contrast, there is little data known about the cicatricial pemphigoid (CP) antigen. No differences between CP and BP have been reported when sera of patients were studied by Western immunoblotting. Findings of a study of sera from 8 patients with CP by indirect immunoelectron microscopy (IEM) on normal human skin are reported. Saponin (0.1% 10 mn) was used as a permeabilizing agent of cytomembranes and saponin-treated skin samples were compared to saponin-untreated skin samples. Four sera from patients with BP, one from a patient with EBA, and three from healthy donors served as controls. The CP sera produced a similar staining of DEJ on both saponin-treated and saponin-untreated skin samples: immune deposits were localized over the lamina densa and the lower part of the lamina lucida clearly separated from the cytoplasmic membrane of keratinocytes, in regularly spaced clumps. The BP sera produced an intense staining of DEJ only on saponin-treated skin samples: immune deposits were observed on the cytoplasmic attachment plaque of the HD; on saponin-untreated skin samples, BP sera produced only a faint staining of the extracellular part of HD. Finally, as expected the EBA serum appeared on the lower part of the lamina densa and anchoring fibrils, and no DAB deposits were observed with the serum of healthy donors. This data indicated that CP antigen is different than BP antigen by its exclusive extracellular localization. It may be a component of anchoring filaments.

The mechanism of action of synthetic antithyroid drugs: iodine complexation during oxidation of iodide.

A number of compounds of pharmaceutical importance from a variety of chemical families, including thiocyanates, isothiocyanates, thiourea and derivatives, imidazoles, and various amines, were found to form charge transfer complexes with iodine. Parallel studies were carried out to investigate the actions of these drugs on lactoperoxidase and thyroid activity in vivo in the rat (assays of T3 and T4 and histology of the thyroid gland). The results showed that there was a good correlation between the value of Kc (the formation constant of the iodinated complex) and antithyroid activity in vivo. The higher the electron donor power of the compound, the higher the Kc value and the stronger the action on the thyroid. The results indicated that a number of drugs could have secondary antithyroid activity. Some compounds, such as levamisole, tetramethylthiourea, tetrahydrozoline, phenothiazines, and imipramines, with no action on peroxidase had high Kc values (tetramethylthiourea, 13,825 liters/M) and had strong antithyroid activity in the rat. These results suggest that synthetic antithyroid agents may act either on peroxidase and/or the molecular iodine which may be produced by oxidation of iodides (2I(-)----I2----2I+). It has been shown that oxidation of I- can occur in the absence of thyroglobulin. In the absence of a suitable receptor, significant amounts of I2 may, thus, accumulate. The action of such drugs on molecular iodine may have considerable pharmacological significance.

A year-long study of changes induced by thyroidectomy in the plasma lipid and lipoprotein spectrum in the European badger.

Hypothyroidism is associated with hypercholesterolemia and increased risk for atherosclerotic disease. The European badger exhibits large seasonal changes in thyroid activity and the annual minimum of plasma thyroxine level in this species occurs at the same period of the year (i.e. late fall) as a pronounced hypercholesterolemia. We examined the plasma lipid and lipoprotein spectrum in a group of thyroidectomized male badgers every month for a year. Non-operated animals were used as controls. Our analyses included measurement of plasma lipid levels, density gradient ultracentrifugation of lipoproteins, electrophoresis of lipoproteins and apolipoproteins, and histological studies. Maximal differences between the two groups of animals were observed during spring, occurring concomitantly with the annual maximum of plasma thyroxine concentration in control badgers. Comparison with the latter animals revealed a permanent hypercholesterolemia and hyperphospholipidemia in thyroidectomized badgers, while their lipoprotein spectrum was characterized by the continual presence of elevated concentrations of cholesterol-rich lipoproteins of d congruent to 1.015 - 1.027 g/ml. The ratio of triglyceride/cholesteryl ester content in such lipoproteins remained constant throughout the year, resembling that noted in intact animals during late fall. Other features distinguishing the lipoprotein spectrum in thyroidectomized badgers were: (1) higher levels of lipoproteins with d 1.027 - 1.065 g/ml and d 1.065 - 1.100 g/ml, and (2) a cholesteryl ester enrichment of both these lipoprotein subclasses. The two groups of animals shared a heterogeneity of low density lipoprotein subfractions isolated on density gradients, together with the presence of apolipoproteins with molecular weights respectively typical of human apolipoproteins A-I and B throughout the low density range. Arterial walls and heart tissues from intact and thyroidectomized animals were free of atherosclerotic lesions at the end of the experimental period.

Formation of molecular iodine during oxidation of iodide by the peroxidase/H2O2 system. Implications for antithyroid therapy.

The first step in the biogenesis of thyroid hormones is the oxidation of iodides taken up by the thyroid gland. Oxidation of I- by the H2O2/peroxidase system leads to the formation of iodinium ions I+ which bond to thyroglobulin by electrophilic substitution. However, it is not clear whether I- is transformed directly to I+ or whether it passes through a molecular iodine intermediate. This latter possibility is indicated by the oxidation potentials of the reactions. I2 can be detected in vitro from the formation of I3- ions, although this has yet to be confirmed in vivo. The present study was designed to determine, albeit indirectly, whether this reaction occurs in vivo. If I2 is produced, it may form charge transfer complexes with numerous drugs. We also investigated the action of various drugs on lactoperoxidase and assessed their antithyroid activity in the rat by assay of plasma levels of T3, T4, and TSH. We found a good correlation between the value of Kc, the formation constant of the complex of the drug with molecular iodine, and the antithyroid activity in vivo. This correlation was observed in four different classes of compound. The possibility that molecular iodine is produced in the thyroid gland has implications for antithyroid therapy.

Streptococcal cause of erysipelas and cellulitis in adults. A microbiologic study using a direct immunofluorescence technique.

We prospectively studied 42 adult patients with acute dermis and soft-tissue infections (27 with erysipelas and 15 with acute cellulitis) involving the lower limb in all except one case. Streptococcus organisms (groups A, C, D, and G) were researched in skin biopsy specimens by a direct immunofluorescent (DIF) technique using commercially available antibodies. Our results showed that DIF gives a sensitivity of 0.70 for the in situ detection of streptococci in cases of erysipelas and cellulitis. With the obvious contribution of this DIF technique, streptococcal pathogens could be detected in situ and grouped in 19 of 27 cases of erysipelas (group A, 13; group B, 1; group C, 1; and group G, 4) and in ten of 15 cases of cellulitis (group A, 9; group B, 1). Combined data, including conventional cultures, DIF studies, and serologic findings, established that Streptococcus organisms, especially Streptococcus pyogenes (A), were, in nearly all cases, responsible for both erysipelas (26/27 cases) and acute cellulitis (11/15 cases) involving the lower limb in adults.

Cytokeratins expression in paragangliomas of the cauda equina.

BACKGROUND: Paragangliomas rarely involve the cauda equina region. In this location, these tumors can show misleading morphological features such as trabecular or papillary growth patterns and variable expression of cytokeratins. METHODS: We comparatively studied the immunohistochemical and ultrastructural patterns of 3 paragangliomas of the cauda equina (PCE) and of 8 paragangliomas from other sites. RESULTS: All the paragangliomas expressed neuroendocrine markers (neuron-specific enolase, chromogranin A, synaptophysin and neurofilament protein). In PCE, chief cells exhibited a strong positivity with a broad spectrum anti-cytokeratin antibody. The staining was diffuse in the cytoplasm or had a paranuclear dot-like disposition. In other sites, only one paraganglioma showed a focal expression of cytokeratins. At ultrastructural level, chief cells of PCE contained characteristic dense core granules and intermediate-sized filaments sometimes grouped in paranuclear whorls. CONCLUSION: The dual immunophenotype of PCE, paraganglionic and epithelial, must be recognized in order to distinguish these tumors from, for example, a metastasis of a neuroendocrine carcinoma. PCE are slow-growing tumors and have mostly a favorable prognosis after complete surgical excision.

[Giant leiomyoma of the esophagus detected by echocardiography and corroborated by x-ray computed tomography and surgery]. / Léiomyome géant de l'oesophage détecté par échocardiographie et confirmé par tomodensitométrie et chirurgie.

The authors report the case of a 44 year old man with a giant leiomyoma of the lower third of the esophagus. The patient presented with chest pain and the tumour was detected by echocardiography. The diagnosis was confirmed by computerised tomography and histological examination of the surgical specimen weighing 501.5 g. The surgeon performed a large esophago-gastric resection and reestablished the continuity of the digestive track by interposing a section of colon. A good result was obtained with a follow-up of 4 years. The authors underline the potential value of a simple barium swallow during cardiological assessment.

[Report of a case of post-radiation hepatopathy]. / A propos d'un cas d'hépatopathie post-radique.

We report the case of a 65 year-old woman treated by radiation therapy alone for Hodgkin's disease. She developed febricule, nonicteric cholestasis, and inflammatory syndrome two months after irradiation. The clinical record, biological and histological results allowed us to dismiss another etiology especially an hepatic location of Hodgkin's disease. Out come after a twenty months predominance of pathohistological abnormalities in the centrilobular region were in favor of a radiation-induced hepatitis.

[Hepatic involvement in secondary syphilis]. / Atteinte hépatique au cours de la syphilis secondaire.

A case of secondary syphilitic hepatitis is reported. A 49-year old woman was admitted for weight-loss, fever, hepatomegaly and splenomegaly. Diagnosis of syphilitic hepatitis was based on cholestasis associated with positive serologic tests for syphilis without other immunological disturbances. Biopsy of the liver showed a moderate infiltration in and around the portal tracts. Immunofluorescence study for treponema was negative. Rapid improvement was obtained with penicillin initially associated with steroid therapy. Liver involvement in secondary syphilis is characterized by anicteric cholestasis, an inflammatory syndrome, and periportal infiltrate inconstantly associated with centrilobular necrosis, granulomatous reaction and presence of treponemas in the lesions. Due to the increasing frequency of sexually transmitted diseases, this diagnosis could become more frequent.

[Gazeous necrosis of the liver due to hepatic artery thrombosis after liver transplantation]. / Nécrose gazeuse du foie par thrombose de l'artère hépatique après transplantation hépatique.

An emergency liver transplantation was performed in a 22 year-old female for fulminant hepatitis. The donor had had splenectomy with portal vein thrombosis which was diagnosed and removed during portoscopy. Nineteen days later, abdominal pain with shock and hepatic failure occurred. X-rays showed pneumoperitoneum and aeric images in the liver area. Laparotomy disclosed massive liver necrosis with gaz under the Glisson's capsula. The hepatic artery was thrombosed. In spite of emergency retransplantation, the patient died 8 days later, due to systemic aspergillosis. Thrombosis of hepatic artery was particular by the importance of gaz-forming infection, and emphasizes the role of rejection. The discovery of portal thrombosis allows to outline the precautions necessary in case of splenectomized donors. The severeness of aspergillosis is underscored.

[Alithiasic cholecystitis and viral hepatitis B disclosing periarteritis nodosa]. / Cholécystite alithiasique et hépatite viral B révélatrices d'une périartérite noueuse.

The authors report the case of a patient with acute alithiasic cholecystitis associated with viral B hepatitis revealing periarteritis nodosa. Histopathological results showed signs of focal arteritis in the gallbladder and liver. Because of the negativity of the viral DNA in serum and the lack of histopathological necrosis in hepatic specimen, the patient was treated by steroid therapy only with a rapid regression of signs of vasculitis and the disappearance of the hepatitis markers.

[Dysmorphic syndrome and vascular dysplasia: an atypical form of type IV Ehlers-Danlos syndrome]. / Syndrome dysmorphique et dysplasie vasculaire: une forme atypique d'Ehlers-Danlos type IV.

A 29 year old woman was hospitalized for the successive onset of extremely serious vascular accidents: rupture of the gastro-duodenal artery, aneurysm of the posterior tibial artery, discovery of bilateral carotid and vertebral aneurysm with development of a carotid-cavernous fistula. The patient had a very unusual morphotype with dwarfism, white hair and alopecia. Histological investigations failed to reveal atheromatous lesions and by contrast showed involvement of the skin (dermal atrophy) and in the blood vessels fibro-dysplasia of the media. This picture was suggestive of a vascular form of Ehlers-Danlos disease (Sack's syndrome or type IV Ehlers-Danlos disease). This syndrome is characterized by minor skin or joint manifestations replaced by arterial accidents (arterial rupture or development of aneurysms). The etiology is faulty maturation of procollagen III and the diagnosis is based upon fibroblast culture.

[Cysticercosis and neurocysticercosis: epidemiological survey in North Togo]. / Cysticercose et neurocysticercose: enquête épidémiologique dans le nord du Togo.

An epidemiologic survey was carried out by a team of medical doctors working in the Kozah district of North Togo during April 1987. It was designed to evaluate the incidence of epilepsy and cysticercosis, taking a sample population of 5,264 subjects aged over 15 years old. 81.7% of the population feed on pigs which are allowed to roam freely in the vicinity of people's habitations. Cysticercosis (123 cases; incidence 23.3 cases per thousand) was diagnosed when one of the following three tests gave a positive result:--serum sample greater than or equal to 0.400 OD with ELISA test (101 cas),--identification of a cysticercosis cyst on anatomopathological examination of subcutaneous cysts (12 cases),--presence of typical calcification patterns revealed by cranial or muscle X-rays (21 cases in 18 patients). General epilepsy or partial motor fits were entirely clinically diagnosed (88 cases; 16 per thousand of population). Cysticercosis proved to be the cause of 29.5% epileptic sufferers, onset occurring after the age of 50 in 66% of these patients.

[Developmental adrenal tuberculosis. Value of x-ray computed tomography]. / Tuberculose surrénalienne évolutive. Intérêt de la tomodensitométrie.

Two cases of Addison's disease secondary to active adrenal tuberculosis are reported. Computed tomography showed hypertrophy of the adrenal gland, which was bilateral in one case and unilateral in the other. Repeat computed tomography scans during antituberculous chemotherapy demonstrated a progressive change of the adrenals toward atrophy and calcification, while the adrenal function remained impaired. The authors recall that adrenal tuberculosis may be unilateral first, then bilateral, and that the gland is initially hypertrophic before hormonal deficiency appears; later on, adrenal atrophy and calcification develop. Computed tomography seems to be useful in the aetiological diagnosis of Addison's disease. Moreover, it helps in determining whether or not antituberculous therapy is indicated, which is not always easy to decide in the absence of "active" focus. The finding, with or without positive tuberculin skin tests, of an adrenal hypertrophy unexplainable by any other pathology (e.g. metastasis, histoplasmosis) should call for antituberculous treatment, especially since it sometimes results in recovery of adrenal function.

[Immunohistochemical study of lesions in Horton's temporal arteritis before and during corticotherapy]. / Etude immunohistochimique des lésions d'artérite temporale de Horton avant et au cours de la corticothérapie.

The immunohistochemical study was performed on temporal artery biopsies from eight patients with giant cell (temporal) arteritis: three before treatment, four after a short period of corticosteroid therapy (from 1 day to 7 days) and one during relapse occurring after a treatment of 9 years; from four subjects with clinical symptoms but without histological features of giant cell arteritis and from five negative controls. Before treatment, biopsies of patients with temporal arteritis showed an inflammatory infiltrate with macrophages and T cells, essentially CD4+ and memory T cells (CD45 RO+), expressing the markers of activation IL2 receptor and HLA DR. Few B and NK cells were also detected. Adhesion molecules, LFA1 and I-CAM1, were strongly expressed by T cells and macrophages. In contrast, the ligand to the CD2, the CD58 marker, was rarely detected. These immunohistochemical features were also observed after a short corticosteroid treatment (by intravenous methylprednisolone or oral prednisone), with presence of activated T cells, memory T cells, macrophages and I-CAM1 and LFA1 expressing cells in the infiltrate. A temporal biopsy, performed after a long time of corticosteroid therapy, showed activated T cells, macrophages and memory cells in o,ne arteriole. In controls, this study showed some mononuclear cells dispersed in intima and adventia, but without activated or memory T cells. Our results support the presence of immune local response in temporal arteritis, incompletely improved by a short corticosteroid treatment.

[Ovarian pregnancy: its status in 1982. Apropos of 6 cases operated, review of the literature]. / Grossesses ovariennes: le point en 1982. A propos de 6 cas opérés, revue de la littérature.

The authors compare six personal cases of ovarian pregnancy with those in the literature. They point out that there is no specific clinical sign which makes it possible to tell whether one is dealing with an ovarian or a tubal pregnancy. They show the value of laparoscopy and especially of laparotomy and the histo-pathology of the specimen. Finally they show that although ectopic pregnancy rarely occurs in this site it is easy to treat and nearly always can be treated conservatively.

[Distant metastases of cervical cancer. Apropos of an unusual case. Review of the literature]. / Métastases à distance d'un cancer du col utérin. A propos d'un cas exceptionnel. Revue de la littérature.

The authors present a single but unusual case of metastases from a squamous cell cancer of the cervix which had been treated radically 35 months previously; the metastases occurring in the digestive tract as well as the peritoneum. They try to explain the physiopathological mechanisms, which are probably not unequivocal, as to how theses metastases could have occurred. They point out that further studies should be carried out with a view to seeing whether prophylactic chemotherapy should be given even in very early cancers.

[Quinidine-induced lichenoid photodermatitis]. / Eruptions lichénoides photoinduites aux quinidiniques.

Quinidine-induced lichenoid photodermatitis was definitely isolated by Berger and Sesody in 1982. We had an opportunity to observe 4 cases of this striking clinical condition and encountered some particularities. Our patients (2 men and 2 women) were 60, 64, 81 and 68 years old respectively. All had a previous cardiovascular history; diabetes was also present in patient No. 2, and hypertension in patient No. 4. All patients were taking other drugs. The first patient presented with a 4-year old lichenoid eruption on the hands, associated with some degree of follicular keratosis. The second and third patients had a mixture of mainly lichenoid lesions on sun-exposed areas, but eczematous and desquamative lesions were also encountered. The fourth patient had typical lichenoid photodermatitis with occasional bullae on the arms and legs. In all patients the disease appeared or worsened in the Summer. It disappeared rapidly in 3 cases upon withdrawal of quinidine (patients No. 1 and 2) or hydroquinidine (patient No. 3), but it lasted longer in patient No. 4, with pigmented sequelae. Histological examination of the skin was consistent with a lichenoid eruption in all cases. However, an immunopathological study revealed a pemphigoid-like pattern in patients No. 1 and 2, and ovoid bodies more suggestive of lichen planus in patient No. 4. Photobiology was not performed. A review of the literature showed that the terms "lichen planus", "lichenoid", "lichenification" or "violaceus hue" were frequently encountered, and we suggest quinidine as one of the most common agents of lichenoid reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

[Angiolymphoid hyperplasia with eosinophilia. Extensive form associated with thrombopenic purpura]. / Hyperplasie angiolymphoïde avec éosinophilie. Forme profuse associée à un purpura thrombopénique.

The authors report a case, on a 59-year-old female patient, of angiolymphoid hyperplasia with eosinophilia (AHE) associated to a thrombopenic purpura (TP) of which the evolution is parallel. The clinical aspect is made of sub-cutaneous nodules of various sizes (1 or 2 cm on an average) and of more superficial, erythematous, sometimes telangiectatic, pseudo-angiomatous nodules. There are (about) 25 nodules, located on the face, the neck, the arms and the thorax, sometimes pruriginous: the rest of the examination is negative excepting axillary and inguinal small size lymph nodes and of a dermographism. The anatomopathological examination in optical microscopy, shows a dermo-epidermal lymphocytic infiltrate with which mingle numerous eosinophilic leucocytes. The dermal vessels are very altered, with a swelling endothelium and a proliferation of endothelial and perithelial cells filling up in large part the vascular section. The biological investigation show essentially: a slight and altering hypereosinophilia (between 500 and 800/mm3); a low amount of blood-platelets (between 95,000 and 130,000/mm3); an increase of the seroconversion enzyme of angiotensin (75 UI; N less than 52 UI); are normal or negative: ESR, protein electrophoresis, immunological tests. The diagnosis of AHE is held back and the clinical evolution is done in several stages: under general corticotherapy (prednisone 1 mg/kg/j): progressive decrease of the nodules, but stopping of the therapy by the patient after 4 months; testing of treatment by thalidomide (100 mg/day) interrupted after 2 weeks because of the aggravation of the thrombopenia (25,000/mm3); occurrence of a thrombopenic purpura (TP) (amount of platelets 10,000/mm3) without a serious haemorrhagic syndrome, evolving in a parallel way to the outbreak of AHE.(ABSTRACT TRUNCATED AT 250 WORDS)

[Bullous pemphigoid with pemphigus type antibodies in vivo. 2 cases]. / Pemphigoïde bulleuse avec anticorps de type pemphigus in vivo. Deux observations.

Pemphigus vulgaris, whether of the vulgaris or foliaceus variety, and bullous pemphigoid (BP) are two groups of auto-immune bullous diseases which in most cases can easily be differentiated on the basis of clinical, histological and, mainly, immunopathological data. Like cicatricial pemphigoid, BP may be accompanied with circulating pemphigus-like antibodies (PLA) which are not detected in vivo by direct immunofluorescence (IF). However, a true pemphigus-BP association, as reported first by Chorzelski et al., is exceptional. Two cases of BP immunolabelled with pemphigus-like antibodies at direct IF are reported, raising a discussion on this particular association. The first case concerns a 62-year old man presenting with extensive psoriasis treated with salicylated vaseline and topical corticosteroids. The patients was admitted for a disseminated, symmetrical and pruriginous bullous eruption made up of tense bullae on healthy and psoriatic skin or on an urticarial background, without Nikolsky's sign. Pathological examination of a recent bulla showed subepidermal detachment without acantholysis. Direct cutaneous IF revealed linear labelling of the basement membrane zone with IgG, C3 and C1q, and labelling of the inter-cellular substance of the epidermis with IgG. Indirect IF on O+ human skin demonstrated antibodies of the pemphigoid type (1/128) and of the pemphigus type (1/64). Standard laboratory examinations only showed moderate blood eosinophilia (950/mm3) and a rise in total IgE. Under systemic corticosteroid therapy (prednisone 1 mg/kg/day) and azathioprine (2 mg/kg/day) the bullae rapidly disappeared.(ABSTRACT TRUNCATED AT 250 WORDS)