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SARS-CoV-2 Variants of Concern (VOCs) with resistance to neutralizing antibodies are threatening to undermine vaccine efficacy. Vaccination and infection have led to widespread humoral immunity against the pandemic founder (Wu-Hu-1). Against this background, it is critical to assess the outcomes of subsequent immunization with variant antigens. It is not yet clear whether heterotypic boosts would be compromised by original antigenic sin, where pre-existing responses to a prior variant dampen responses to a new one, or whether the memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. We show, in macaques immunized with Wu-Hu-1 spike, that a single dose of adjuvanted beta variant receptor binding domain (RBD) protein broadens neutralizing antibody responses to heterologous VOCs. Passive transfer of plasma sampled after Wu-Hu-1 spike immunization only partially protects K18-hACE2 mice from lethal challenge with a beta variant isolate, whereas plasma sampled following heterotypic RBD boost protects completely against disease., Graphical Abstract, The emergence and spread of antibody-resistant SARS-CoV-2 Variants of Concern (VOCs) threatens to diminish vaccine efficacy. Sheward et al. show, in rhesus macaques and K18-hACE2 mice, that reduced vaccine protection against VOCs can be restored by broadening antibody responses with a third, heterotypic RBD booster immunization.

Rhinovirus (RV) infections are associated with asthma exacerbations. MicroRNA‐146a and microRNA‐146b (miR‐146a/b) are anti‐inflammatory miRNAs that suppress signaling through the nuclear factor kappa B (NF‐κB) pathway and inhibit pro‐inflammatory chemokine production in primary human bronchial epithelial cells (HBECs). In the current study, we aimed to explore whether miR‐146a/b could regulate cellular responses to RVs in HBECs and airways during RV‐induced asthma exacerbation. We demonstrated that expression of miR‐146a/b and pro‐inflammatory chemokines was increased in HBECs and mouse airways during RV infection. However, transfection with cell‐penetrating peptide (CPP)‐miR‐146a nanocomplexes before infection with RV significantly reduced the expression of the pro‐inflammatory chemokines CCL5, IL‐8 and CXCL1, increased interferon‐λ production, and attenuated infection with the green fluorescent protein (GFP)‐expressing RV‐A16 in HBECs. Concordantly, compared to wild‐type (wt) mice, Mir146a/b−/− mice exhibited more severe airway neutrophilia and increased T helper (Th)1 and Th17 cell infiltration in response to RV‐A1b infection and a stronger Th17 response with a less prominent Th2 response in house dust mite extract (HDM)‐induced allergic airway inflammation and RV‐induced exacerbation models. Interestingly, intranasal administration of CPP‐miR‐146a nanocomplexes reduced HDM‐induced allergic airway inflammation without a significant effect on the Th2/Th1/Th17 balance in wild‐type mice. In conclusion, the overexpression of miR‐146a has a strong anti‐inflammatory effect on RV infection in HBECs and a mouse model of allergic airway inflammation, while a lack of miR‐146a/b leads to attenuated type 2 cell responses in mouse models of allergic airway inflammation and RV‐induced exacerbation of allergic airway inflammation. Furthermore, our data indicate that the application of CPP‐miR‐146a nanocomplexes has therapeutic potential for targeting airway inflammation., miR‐146a has anti‐inflammatory properties in human bronchial epithelial cells and mouse airways during rhinovirus infection and in case of allergic inflammation. Particular cell penetrating peptide(CPP)‐miR‐146a nanocomplexes have therapeutic potential for targeting of airway inflammation.

Intestinal nematodes suppress immune responses in the context of allergy, gut inflammation, secondary infection and vaccination. Several mechanisms have been proposed for this suppression including alterations in Th2 cell differentiation and increased Treg cell suppressive function. In this study, we show that chronic nematode infection leads to reduced peripheral responses to vaccination because of a generalized reduction in the available responsive lymphocyte pool. We found that superficial skin-draining lymph nodes (LNs) in mice that are chronically infected with the intestinal nematode Heligmosomides polygyrus, do not reach the same cellularity as worm-free mice upon subsequent BCG infection in the skin. B cells and T cells, all declined in skin-draining LN of H. polygyrus-infected mice, resulting in LNs atrophy and altered lymphocyte composition. Importantly, anti-helminthic treatment improved lymphocyte numbers in skin-draining LN, indicating that time after de-worming is critical to regain full-scale LN cellularity. De-worming, and time for the skin LN to recover cellularity, also mended responses to Bacille Calmette-Guerin (BCG) in the LN draining the footpad injection site. Thus, our findings show that chronic nematode infection leads to a paucity of lymphocytes in peripheral lymph nodes, which acts to reduce the efficacy of immune responses at these sites., Author summary Infections with intestinal nematodes may be one explanation to why BCG vaccination is less effective in areas of high worm burden. In support of this, we recently showed that chronic intestinal nematode infection resulted in reduced immune responses and higher mycobacterial burden at distal sites. How a gut-dwelling nematode modulate immune responses in skin-draining lymph nodes (LN) was not clear. We found a reduced expansion of LN draining the BCG injected footpad in worm-infected animals, but no evidence for a spread of regulatory cells or cytokines to the BCG-draining LN. Interestingly, we found that mice chronically infected with intestinal worms had significantly smaller skin-draining LN. We propose that the expansion of mesenteric lymph nodes (mLN) occur at the cost of other LN, leading to atrophy of skin-draining LN. Expansion of the lymphocyte pool by IL-7, allowed worm-infected animals to maintain larger skin-draining LN while the mLN did not further expand. De-worming treatment of mice eventually restored the cellularity of skin-draining LN. This, however, took time indicating that effect of worms persisted long after the infection cleared. By de-worming and allowing time for the LN to recover, the cellular responses to BCG injection in the footpad were restored in the draining popliteal LN. Thus, paucity of lymphocytes at peripheral sites can explain impaired peripheral immune responses in worm-infected animals.

Asthma, rhinitis, and eczema are complex diseases with multiple genetic and environmental factors interlinked through IgE-associated and non–IgE-associated mechanisms. Mechanisms of the Development of ALLergy (MeDALL; EU FP7-CP-IP; project no: 261357; 2010-2015) studied the complex links of allergic diseases at the clinical and mechanistic levels by linking epidemiologic, clinical, and mechanistic research, including invivo and invitro models. MeDALL integrated 14 European birth cohorts, including 44,010 participants and 160 cohort follow-ups between pregnancy and age 20years. Thirteen thousand children were prospectively followed after puberty by using a newly standardized MeDALL Core Questionnaire. Amicroarray developed for allergen molecules with increased IgE sensitivity was obtained for 3,292 children. Estimates of air pollution exposure from previous studies were available for 10,000 children. Omics data included those from historical genome-wide association studies (23,000 children) and DNA methylation (2,173), targeted multiplex biomarker (1,427), andtranscriptomic (723) studies. Using classical epidemiology and machine-learning methods in 16,147 children aged 4years and 11,080 children aged 8years, MeDALL showed the multimorbidity of eczema, rhinitis, and asthma and estimated that only 38% of multimorbidity was attributable to IgE sensitization. MeDALL has proposed a new vision of multimorbidity independent of IgE sensitization, and has shown that monosensitization and polysensitization represent 2 distinct phenotypes. The translational component of MeDALL is shown by the identification of a novel allergic phenotype characterized by polysensitization and multimorbidity, which is associated with the frequency, persistence, and severity of allergic symptoms. The results of MeDALL will help integrate personalized, predictive, preventative, and participatory approaches in allergic diseases.

Macrophagic myofasciitis (MMF) is an emerging condition of unknown cause, detected in patients with diffuse arthromyalgias and fatigue, and characterized by muscle infiltration by granular periodic acid-Schiff's reagent-positive macrophages and lymphocytes. Intracytoplasmic inclusions have been observed in macrophages of some patients. To assess their significance, electron microscopy was performed in 40 consecutive cases and chemical analysis was done by microanalysis and atomic absorption spectrometry. Inclusions were constantly detected and corresponded to aluminium hydroxide, an immunostimulatory compound frequently used as a vaccine adjuvant. A lymphocytic component was constantly observed in MMF lesions. Serological tests were compatible with exposure to aluminium hydroxide-containing vaccines. History analysis revealed that 50 out of 50 patients had received vaccines against hepatitis B virus (86%), hepatitis A virus (19%) or tetanus toxoid (58%), 3-96 months (median 36 months) before biopsy. Diffuse myalgias were more frequent in patients with than without an MMF lesion at deltoid muscle biopsy (P < 0.0001). Myalgia onset was subsequent to the vaccination (median 11 months) in 94% of patients. MMF lesion was experimentally reproduced in rats. We conclude that the MMF lesion is secondary to intramuscular injection of aluminium hydroxide-containing vaccines, shows both long-term persistence of aluminium hydroxide and an ongoing local immune reaction, and is detected in patients with systemic symptoms which appeared subsequently to vaccination.

We reviewed the cases of 95 children with duplex ureteroceles treated in this department over an 18-year period. There were 101 ureteroceles (6 bilateral). Diagnosis and treatment were analyzed. Special attention was paid to newborns screened in utero. We always strove to preserve functional renal tissue whenever possible. In keeping with this goal, three surgical techniques were used: (1) upper pole heminephrectomy; (2) ureterocele excision, bladder neck reconstruction, and ureter reimplantation with or without cutaneous ureterostomy of the upper pole ureter; and (3) endoscopic ureterocele incision. Follow-up studies using x-ray and radionuclide imaging demonstrated satisfactory renal function in 86.6% of patients. These findings support a conservative approach to ureteroceles using endoscopic ureterocele incision as the primary treatment. Lower urinary tract reconstruction may be associated in cases involving urinary tract infection, obstruction or incontinence. Upper pole heminephrectomy should be performed only after functional evaluation following ureterocele incision or cutaneous ureterostomy.

An inflammatory myopathy, characterised by joint and muscle pain, chronic asthenia, with infiltration of peri-fascicular epimysium, perimysium and endomysium by cells of the macrophagic line, macrophagic myofasciitis is often associated with other, generally auto-immune, affections. However, the coexistence with another inflammatory myopathy is relatively rare.A 29 year-old woman presented with 2 distinct inflammatory myopathies, a macrophagic myofasciitis and a dermatomyositis, which had appeared a few years after.In the rare cases in which 2 inflammatory myopathies are combined, the precise relationship between them is unknown, an individual susceptibility to developing muscle diseases is suggested.

It can be difficult to diagnose focal muscular disease. We report a case of crural biceps focal myositis after an insect bite.We then discuss diagnostics of one or a small number of muscle injury. Focal inflammatory myositis has been described. We emphasize the role of pathology. In our case, pathological examination rules out inflammatory or tumoral disease and access likely toxical etiology. Muscle injury can appear, most frequently around the bite of venomous animal.Hymenopters are often responsible for such stings in France. Venoms are toxic for muscle cells membrane.

We report a case of mitochondrial myopathy (MM), assessed by histological and biochemical studies. This illness was diagnosed in a 69-year-old patient with myocardiopathy revealed by ventricular arrhythmias. The originality of this case lies in the patient's age, the mode of onset and the biochemical features (i.e. normal mitochondrial enzymatic complexes but very low respiration when using glutamate as a substrate).

Inclusion body myositis (IBM) is a severe form of idiopathic inflammatory myopathy. A predominantly T CD8+ lymphocytic infiltrate, with focally non-necrotizing muscular fiber invasion, and rimmed-vacuoles are specific histological signs. A few cases of IBM associated with other dysimmune diseases have been reported, but only once with systemic sarcoidosis. We report three cases of muscular sarcoidosis associated with IBM. This very uncommon observation suggests that major complex of histocompatibility, soluble factors, cytokines and adhesion molecules could be involved. Our cases are a novel example of associated dysimmune diseases.

We describe three patients with macrophagic myofasciitis and inclusion body myositis. All patients fulfilled diagnostic criteria for inclusion body myositis and myopathologic criteria for macrophagic myofasciitis. In the three cases macrophagic myofasciitis complicated the evolution of a known and painless inclusion body myositis and was diagnosed in a repeated deltoid biopsy because of the appearance of myalgia during the course of inclusion body myositis in all cases. The unexpected appearance of myalgia during the course of painless inclusion body myositis must arouse the suspicion of an association of another inflammatory muscle disease, macrophagic myofasciitis.

Macrophagic myofasciitis (MMF), a condition newly recognized in France, is manifested by diffuse myalgias and characterized by highly specific myopathological alterations which have recently been shown to represent an unusually persistent local reaction to intramuscular injections of aluminium-containing vaccines. Among 92 MMF patients recognized so far, eight of them, which included the seven patients reported here, had a symptomatic demyelinating CNS disorder. CNS manifestations included hemisensory or sensorimotor symptoms (four out of seven), bilateral pyramidal signs (six out of seven), cerebellar signs (four out of seven), visual loss (two out of seven), cognitive and behavioural disorders (one out of seven) and bladder dysfunction (one out of seven). Brain T(2)-weighted MRI showed single (two out of seven) or multiple (four out of seven) supratentorial white matter hyperintense signals and corpus callosum atrophy (one out of seven). Evoked potentials were abnormal in four out of six patients and CSF in four out of seven. According to Poser's criteria for multiple sclerosis, the diagnosis was clinically definite (five out of seven) or clinically probable multiple sclerosis (two out of seven). Six out of seven patients had diffuse myalgias. Deltoid muscle biopsy showed stereotypical accumulations of PAS (periodic acid-Schiff)-positive macrophages, sparse CD8+ T cells and minimal myofibre damage. Aluminium-containing vaccines had been administered 3-78 months (median = 33 months) before muscle biopsy (hepatitis B virus: four out of seven, tetanus toxoid: one out of seven, both hepatitis B virus and tetanus toxoid: two out of seven). The association between MMF and multiple sclerosis-like disorders may give new insights into the controversial issues surrounding vaccinations and demyelinating CNS disorders. Deltoid muscle biopsy searching for myopathological alterations of MMF should be performed in multiple sclerosis patients with diffuse myalgias.

X-linked myopathy with excessive autophagy (XMEA, MIM 310440) is a rare inherited mild myopathy. We have used 32 polymorphic markers spanning the entire X chromosome to exclude most of the chromosome except the Xq28 region in a large XMEA family. Using three additional families for linkage analysis, we have obtained a significant two-point lod score with marker DXS1183 (Z = 2.69 at theta = 0). Multipoint linkage analysis confirmed the assignment of the disease locus with a maximal lod score of 2.74 obtained at recombination fraction zero. Linkage of XMEA to the Xq28 region is thus firmly established. In addition, we have ruled out the Emery-Dreifuss muscular dystrophy to be allelic with XMEA by direct sequencing of the emerin gene in three of our families.

A new type of inflammatory myopathy of unknown etiology has recently been described in France. The myopathy, called macrophagic myofasciitis, had never been described in the literature.In December 1998, 35 cases of macrophagic myofasciitis were reported, showing an increase in its incidence since the description of the first case in 1993. The first 22 cases are described.The 22 patients were each referred with a presumptive diagnosis of either polymyositis (11 patients), polymyalgia rheumatica (5 patients), mitochondrial cytopathy (4 patients), or congenital myopathy or muscle dystrophy (1 patient for each). Clinical symptoms included myalgias (91%), arthralgias (68%), marked asthenia (55%), muscle weakness (45%), and fever (32%). Laboratory findings included elevated CK levels (50%) and a marked increased in the erythrocyte sedimentation rate (37%). Electromyographic recordings showed the existence of myopathy (35%). Muscle biopsy showed a unique pattern characterized by: (i) centripetal infiltration of the epimysium, perimysium and perifascicular endomysium by non epitheloid, cells of the monocyte/macrophage lineage (CD68+, CD1a-, S100-) with both large cytoplasm and PAS-positive content; (ii) absence of necrosis, of both epithelioid and giant cells, and of mitotic figures; (iii) occasional CD8+ T-cells; and, (iiii) minimal myocyte suffering. The disease symptoms were easily distinguishable from those of sarcoid myopathy and fasciitis-panniculitis syndromes. Infectious diseases known to be associated with reactive histiocytosis, including Whipple's disease, Mycobacterium avium intracellulare infection and malakoplakia, could not be documented. Patients' condition improved under corticosteroid therapy, associated or not with non-specific antibiotic therapy.A new inflammatory muscle disorder of unknown etiology, characterized by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France. Diagnosis is based on muscular biopsy. Numerous clinical, epidemiological and etiopathologic studies initiated by the GERMMAD (Groupe d'études et de recherche sur les maladies musculaires acquises) are in progress.

An unusual inflammatory myopathy characterised by an infiltration of non-epithelioid histiocytic cells has been recorded with increasing frequency in the past 5 years in France. We reassessed some of these cases.We did a retrospective analysis of 18 such cases seen in five myopathology centres between May, 1993, and December, 1997. The myopathological changes were reassessed at a clinopathology seminar.Detailed clinical information was available for 14 patients. The main presumptive diagnoses were polymyositis and polymyalgia rheumatica. Symptoms included myalgias in 12 patients, arthralgias in nine, muscle weakness in six, pronounced asthenia in five, and fever in four. Abnormal laboratory findings were occasionally observed, and included raised creatine kinase concentrations, increased erythrocyte sedimentation rate, and myopathic electromyography. Muscle biopsy showed infiltration of the subcutaneous tissue, epimysium, perimysium, and perifascicular endomysium by sheets of large macrophages, with a finely granular PAS-positive content. Also present were occasional CD8 T cells, and inconspicuous muscle-fibre damage. Epithelioid and giant cells, necrosis, and mitotic figures were not seen. The images were easily distinguishable from sarcoid myopathy and fasciitis-panniculitis syndromes. Whipple's disease, Mycobacterium avium intracellulare infection, and malakoplakia could not be confirmed. Ten patients were treated with various combinations of steroids and antibiotics; symptoms improved in eight patients, and stabilised in two.A new inflammatory muscle disorder of unknown cause, characterised by a distinctive pathological pattern of macrophagic myofasciitis, is emerging in France.

Pulmonary blastoma is a rare malignant tumor. A new case is reported in a 3 years 6 month-old girl. An apparent clinical remission was first obtained after a surgical treatment followed by a conventional chemotherapy during six months. Afterwards the persistence of a microscopic residual pulmonary disease lead us to deliver successfully an intensive chemotherapy followed by autologous peripheral blood stem cells reinjection. The child remains disease free 12 months after graft. Problems set by the histogenesis of this tumor, its unspecific clinical and paraclinical features and the role of conventional and intensive chemotherapy followed by autologous bone marrow transplantation are discussed on the basis of a review of 50 cases in the literature.

Muscular hypertrophy, rarely reported in muscular sarcoidosis, is usually associated with the myositic, myopathic and nodular types. We report a case with an isolated localised muscular hypertrophy simulating a tumor formation developed after repetitive efforts, in a familial context of sarcoidosis. MRI shows muscular high intensity lesions in the thighs and calves, and after treatment, central areas of low intensity signal. Muscular biopsy confirms diagnosis of sarcoidosis. Gallium-67 scintigraphy shows systemic extension of disease. This case highlights the usefulness of recent imaging techniques in diagnostic strategy and follow up.

A wedge-shaped segment of stomach based on the right gastroepiploic artery was used for bladder augmentation in 11 patients. Initial diagnosis in these 11 patients was bladder exstrophy. Indications for the use of stomach in bladder reconstruction were important bilateral upper tract deterioration in 10 patients, dederivation in 1. A continent appendicostomy (Mitrofanoff) has been performed in all patients. In post-operative follow-up (average 24 months), all patients have stable upper tract X-rays and stable or improved renal function. All patients require intermittent clean catheterization, 8 are totally continent, 2 are partially continent, 1 patient is still incontinent. No serious digestive problem was encountered. The increase in bladder capacity was 300 to 500% after 6 months. Mucus production is reduced relative to other intestinal segments and the patients require no bladder irrigation. The authors recommend the use of stomach for urinary tract reconstruction in compromised patients.

This article reports a new MERRF family. The mother, regarded as suffering from Ramsay-Hunt Syndrome, and her three daughters, had the same clinical pattern: myoclonic epilepsy and ataxia. Two daughters were studied on morphological, biochemical and molecular genetic levels. Muscle biopsies showed ragged-red fibres and mitochondrial vasculopathy. Arterioles were strongly SDH-reactive and COX-negative. By electron microscopy, abnormal mitochondria were observed in skeletal muscle fibres, in smooth muscle fibres of intramuscular vessels and in sweat gland epithelium. The study of the respiratory chain showed complex IV and I + IV deficiency, respectively. Mitochondrial tRNA (lys) mutation at position 8344 was pointed out as previously reported in the MERRF syndrome.

We report a series of 46 patients (32 women and 14 men) with limb-girdle syndrome. After reappraisal, another diagnosis was made in 10 of them. Becker's muscular dystrophy was the most frequent cause among men (near 50 p. 100). A Duchenne muscular dystrophy manifesting carrier was discovered among 13 reevaluated women. Among the 36 cases (29 women and 7 men) without any defined etiology, 29 were without any other known familial history. Fifteen of these women had similar clinical findings: incipient weakness in the pelvic girdle and onset of symptoms most often in the forties. In these cases serum creatine kinase activity was normal or slightly elevated, and muscle biopsy showed non-specific patterns. "Late onset muscular dystrophy in females" should be reevaluated.

Respiratory parameters of skeletal muscle were determined in permeabilized muscle fibers by adapting a technique described by Veksler et al. for cardiac fibers (Biochim Biophys Acta, 892:191-196, 1987). This method consists of the permeabilization of muscle fibers by saponin by allowing respiratory substrates and inhibitors to reach the mitochondria. In this way, the mitochondria may be studied inside the fibers as if they were isolated. We have verified, using various techniques, that the mitochondria remain intact during this procedure. This method has been applied to the study of six newborn infants for whom a diagnosis of a mitochondrial defect was suspected. In all cases, the defect was to be found on the permeabilized fibers, and this was confirmed by an enzymatic study. The advantage of this new method, associated with the measurement of the enzymatic activities on a crude homogenate, is to enable a simple and rapid diagnosis on a small amount of sample without damaging the mitochondria during the isolation procedure.

A 21-year old women with rhizomelic muscular deficit and signs of hypercapnia developed acute respiratory failure. Laboratory tests revealed high creatine kinase activity, and electromyograms showed myogenic patterns with a few myotonic discharges. Biopsy of the quadriceps muscle elicited major vacuolar myopathy with glycogen overload. Acid maltase activity was undetectable in muscular tissue. After 7 months on high-protein diet (1540 calories, 37% proteins) there was no clinical or biochemical improvement. The other published cases of acid maltase deficiency treated with high-protein diet are discussed.

In a family 6 members in 3 generations were affected by centronuclear myopathy (CNM) of autosomal dominant inheritance. The apparent onset was in the early forties and the disease progressed slowly. Limb weakness was predominant. Strabismus was present in 5 cases and calves hypertrophy in 3. Serum creatinine kinase was always within the normal range. In one case myotonic bursts were found at electromyography. In 2 cases brain stem auditory evoked potential studies demonstrated abnormal prolongation of interpeak latencies I-III and favoured subclinical nervous system involvement. Muscular biopsies showed typical features of centronuclear myopathy with 50 to 80% central nuclei. In two cases immunocytochemical labelling of dystrophin showed staining in the sarcoplasm in favour of an arrest in the morphogenesis of developing myofiber. Others families with autosomal dominant CNM in the literature and also some sporadic adult cases had similar clinical features.

Defecography is a useful paraclinical examination to explore disturbances of continence or defecation. The purpose of this study was to present a simplified defecography technique and assess its validity in subjects without defecation problems (n = 10) and in patients complaining of idiopathic chronic constipation (n = 35). The anorectal angle at rest (RAA) and when straining at stool was not significantly different in constipated patients and in controls. Defecography often gave abnormal results. Anterior rectocele was found in almost 50 percent (17/35) of constipated patients and in 20 percent (2/10) of controls (P less than 0.05). None of the patients had posterior rectocele. Persistent imprint of the puborectal muscle during straining was present in 36 percent (9/35) of constipated patients and in 10 percent (1/10) of controls (NS). The imprint was not always associated with closure of the RAA between rest and straining; this closure was never found in controls but was observed in 6 out of 17 constipated patients (35 percent; P less than 0.05). Perineal descent (PD) varied from 0.6 to 3.7 cm (mean +/- s.e.m.: 2.0 +/- 0.63 cm) in controls, as against 0.6 to 7.9 cm (mean +/- s.e.m.: 2.7 +/- 0.45 cm) in constipated patients. In 24 percent of the constipated patients PD was greater than 3.7 cm (the maximum value recorded in controls). All constipated patients with closure of the RAA during defecation had a PD of less than 1 cm, thus confirming the concept of "pelvic floor muscle hypertonia". Disorders of rectal statics are more frequent in subjects with constipation, but their significance is varied. Some abnormalities could be the cause of constipation (e.g. anismus) and others its consequence (anterior rectal prolapse, anterior rectocele, PD).

Ten cases of oculopharyngeal muscular dystrophy (OPMD) were examined ultrastructurally. Two very different types of filamentous inclusions were observed: (1) Nuclear inclusions composed of 8.5 nm external diameter tubular filaments organized in palisades and similar to those described by Tome and Fardeau (1980). They have not yet been reported in other muscle diseases. Their presence in 100% of our cases confirms they are the morphological hallmark of OPMD. (2) 16-18 nm external diameter tubular filaments. These were similar to the inclusions observed in inclusion body myositis (IBM) and morphologically very different from the first type. They were randomly dispersed or arranged in bundles near cytoplasmic debris and whorls of membranes. They were found in cytoplasm. Only once were they observed in a nucleus. These inclusions have been described in IBM but also in other diseases. They were found in 80% of our OPMD cases.

There is currently widespread enthusiasm for abdominal wall reconstruction in patients with the prune belly syndrome. We have devised an operation that appears to offer some advantages over those proposed by Ehrlich and Randolph. The technique preserves the umbilicus, and thickens and strengthens the anterior abdominal wall. By narrowing the waist, it also produces a better cosmetic appearance. After full thickness resection of a varying amount of skin from the central abdomen, the anterior wall is sutured in double-breasted fashion, thus, preserving all vascularization and the umbilicus. Since 1969 we have successfully performed this procedure on 9 prune belly patients including 1 girl. The results were excellent in terms of duration and cosmetic appearance.

Cystoscopic incision for the treatment of ureterocele is a controversial procedure. With the advent of prenatal diagnosis of obstructive uropathy, neonates with asymptomatic ureteroceles are being encountered. We discuss several situations in which transurethral cystoscopic incision of the ureterocele may have merit.

Five cases of mammary carcinoma with osteoclast-like giant cells are reported. This study as well as review of the literature underline characteristic features of this rare histological type of carcinoma: a round well-circumscribed dense nodule of benign appearance on mammograms in half of the cases; brown colour of tumour specimens; stromal hypervascularity; negativity of epithelial, vascular and most histiocytic immunohistochemical markers in giant cells; positivity of leucocyte common antigen and vimentin in giant cells. Giant cells most probably originate from the fusion of histiocytic type mononucleated stromal cells, but results of immunohistochemical stainings cannot actually bring formal arguments to support this hypothesis.

Five cases of uterus didelphys, unilateral imperforate vagina and ipsilateral renal agenesis are reported with a follow-up from 1 to 5 years. Diagnosis included typical revelation at puberty (2 cases) but also in the first months of life (2 cases). One case was only diagnosed at the age of 6 years, and the presence of an ectopic ureter was noted in the imperforate vagina. The authors point out the necessity of precise evaluation and careful management in order to maintain an intact reproductory tract. Simple excision of the septum is recommended which can most of the time be done by the vaginal approach.

We report two cases of giant cell tumor of bone (osteoclastoma) associated with Paget's disease. One appeared on the left cubitus in a 68-year-old male patient while the second involved the right maxillary sinus in a 79-year-old woman. Histopathological study was completed by ultrastructural and immunocytological studies. They were demonstrated to contain intranuclear virus-like filamentous inclusions in the osteoclasts. However, we cannot obtain positive response with antisera against measles virus and respiratory syncitial virus. These data are confronted to the hypothesis for a viral aetiology of Paget's disease and giant cell tumor of bone, associated or not to Paget's disease.

Out of series of 95 ureteroceles in a 15 years period, 17 cases have been treated by simplified method, either endoscopic (7 cases) or polar nephrectomy alone (9 cases). Endoscopic incision alone can be used. In neonates with ureterocele simplex (4 cases cured with no secondary reflux). To assess upper pole function in ureterocele duplex (followed by reconstruction or nephrectomy). To drain some very difficult cases (bilateral, infected). In our experience, the upper heminephrectomy alone as a simplified approach of this pathology has failed in the vast majority of cases, leading to a secondary intervention to cure the intra vesical pathology. It is our opinion that this approach must be restrained to the cases of intra cervical or intra ureteral, the secondary pathology will almost lead to a secondary trans vesical approach with is neither more difficult nor easier that a primary one. Herein is described the present position of the authors concerning rare indication of these simplified approach.

A 54 year-old woman presented with an asymmetrical polyneuropathy, with in addition signs of hepatitis and hypercalcemia. The diagnosis of sarcoidosis was made by hepatic and neuromuscular biopsies. Electrophysiological studies showed an asymmetrical clear neurogenic involvement with an axonal pattern. Ultrastructural study of the nerve showed sarcoid granulomas in epineurium, perineurium and endoneurium, with images of Wallerian degeneration. No features of primary demyelination were found. Granulomas were also present in muscle and liver. Possible etiological mechanisms are discussed: compression of nerve or vessels, or immune angiitis.

A biopsy specimen of an extra-ocular muscle from a brother and sister affected by typical familial Steinert's disease was examined by electron microscopy. Considerable disorganisation of the contractile element was observed with a gross accumulation of abnormal mitochondria. This was a very different appearance to the findings observed in skeletal muscle in Steinert's disease and much closer to the findings in skeletal muscle in certain 'ocular' myopathies. One cannot fail to be impressed by the discordance between the appearance of the muscular disorganisation and the rarity of clinical oculomotor disturbances in this disease.

An X-linked spinal muscular atrophy is reported in one family. Four of the five patients were examined. In three, electromyography, conduction nerve velocities and muscle biopsy were consistent with anterior horn cell disease. Similar families in the literature were reviewed and characteristic data were: 1) adult-onset, 2) proximal, bulbar and facial involvement, 3) prominent perioral fasciculations, 4) frequent association of cramps, tremor and sexual dysfunction (hypogonadism and gynecomastia), 5) very slow progression and favorable prognosis. These characteristics define, among the spinal muscular atrophies, a distinct entity named by several authors Kennedy's disease.

Nuclear inclusions in striated muscle from patients with oculopharyngeal dystrophy have been detected recently. We carried out ultrastructural examinations of biopsy specimens on 5 patients with oculopharyngeal dystrophy and we also reexamined a former case. In these 6 cases we found filamentous inclusions in a few nuclei. These inclusions seem to be characteristic of this disease as they have never been seen elsewhere.

We have been able to examine muscular tissue from two females showing hypothyroid myopathy. Under light microscopy, certain fibres contained basophilic inclusions. Histoenzymology showed that these inclusions were found exclusively in certain type 1 fibres. Ultrastructural examination showed that the inclusions were accumulations without a limiting membrane. These accumulations contained straight fibrils which were randomly distributed. Their mean diameter was 70 A. The neighbouring myofibrils were usually unaltered. We have found similar images described for five cases of hypothyroid myopathies. They are more common in myocardium than in skeletal muscle. These images are similar to those observed in some case of type IV glycogenosis and Lafora's disease.