[Chronic interstitial nephritis and mesalazine: 3 new cases?]. / Néphrite interstitielle chronique et mésalazine: 3 nouveaux cas?

We report three new cases of chronic interstitial nephritis occurring in two patients with Crohn's disease and one patient with ulcerative colitis treated with mesalazine. In the three cases asymptomatic renal disease was revealed by an increase in serum creatinine which was normal before treatment. Renal biopsy showed features of severe chronic interstitial nephritis. Mesalazine withdrawal and administration of steroids in two cases led to partial improvement of renal function. Mechanism of renal toxicity of mesalazine is unknown. These observations stress the need for monitoring renal function in patients with inflammatory bowel disease treated with mesalazine.

Respiratory involvement in relapsing polychondritis. Clinical, functional, endoscopic, and radiographic evaluations.

Although respiratory involvement occurs in 50% of patients with relapsing polychondritis (RP) and augurs a poor prognosis, few previous studies have provided complete descriptions of respiratory tract involvement. For this reason, we investigated the respective role of clinical, functional, endoscopic, and radiographic (computed tomography [CT]) examinations in 9 consecutive patients with RP and lower respiratory tract localization. All exhibited cough, dyspnea, and wheezing. Eight had a nonreversible obstructive pattern with a marked decrease of the maximal flow ratio at 75% and 25% of vital capacity. Rotman functional criteria were evaluated to differentiate upper from lower respiratory tract involvement; they were consistent with the results of other examinations in 4/9 cases. Endoscopic examination showed moderate to severe inflammation in 8/9 patients; tracheal stenosis was present in 6/9 patients, bronchial stenosis in 4/9 patients, and tracheal collapse in 7 cases. CT showed tracheal stenosis in 8/9 patients (diffuse, 7; localized, 1) and bronchial stenosis in 6/9 patients. Tracheobronchial wall thickening and/or calcifications were observed in 7 cases. Clinical symptoms are of poor specificity for defining respiratory involvement precisely, although degree of dyspnea is correlated to the decrease in forced expiratory volume in 1 second (FEV1). Functional criteria were helpful in evaluating the obstructive ventilatory defect but did not differentiate, in most cases, the respective part of lower and upper respiratory involvement when using Rotman criteria. Compared to CT findings, endoscopic examination failed to identify tracheal and bronchial stenosis and tracheal wall alterations at an early stage of the disease. In our series CT appears to be a reliable method to identify tracheal and bronchial involvement and can be repeated safely during the course of the disease.

[Primary pulmonary hypertension: a rare but often fatal complication of Crest syndrome]. / L'hypertension artérielle pulmonaire primitive: une complication rare mais souvent mortelle du Crest syndrome.

In a retrospective study of 194 systemic sclerosis, we selected 37 Crest syndrome patients. Among these 37 patients, five presented a primary pulmonary hypertension. For three of these patients, the evolution of this primary pulmonary hypertension was rapidly fatal, one died of another cause. One died without certitude that death is imputable to HTAP. Diagnosis and management of the evolution of primary pulmonary hypertension may be easily assessed by doppler-echocardiography.

Erythrocyte sedimentation rate, an underestimated tool in chronic renal failure.

BACKGROUND: Erythrocyte sedimentation rate is widely used in the general population. It has seldom been studied in patients with chronic renal failure. The purpose of this study was to assess its usefulness in haemodialysis patients. METHODS: Forty-five haemodialysis patients with no evidence of acute or chronic inflammatory illness were studied. Nine were diabetic, and 12 used a non-biocompatible membrane. Erythrocyte sedimentation rate was determined, using a modified Westergren method. Plasma fibrinogen concentration, complete blood count, and serum chemistries were also studied. RESULTS: Erythrocyte sedimentation rate was normal or mildly elevated in most of our patients, with a median of 30 mm/h. Linear analysis found positive correlation between erythrocyte sedimentation rate and fibrinogen concentration, globulin level, platelet, and white cell counts, and negative correlation with haematocrit. Fibrinogen concentration was normal in 22 patients, and moderately elevated in 14. It was significantly higher in diabetic patients, or those using a non-biocompatible membrane. The same positive correlations were found for fibrinogen concentration as for erythrocyte sedimentation rate. CONCLUSIONS: We conclude that erythrocyte sedimentation rate can be used in haemodialysis patients much in the same way as in the general population, as it is influenced by the same factors, and its baseline value is lower than previously reported. The lower concentration of fibrinogen, an independent predictor of cardiovascular risk, in patients treated with biocompatible membranes may be of clinical relevance.

[Initial manifestations and late diagnosis in chronic atrophic polychondritis: apropos of a series of 15 patients]. / Manifestations révélatrices et retard diagnostique dans la polychondrite chronique atrophiante: à propos d'une série de 15 malades.

An auricular or nasal chondritis or a saddle nose deformity are the initial manifestation in half of cases of relapsing polychondritis; the other initial manifestations are various and less evocative; polyarthritis, laryngo-tracheal symptoms, episcleritis which delay the diagnosis. From 15 cases of relapsing polychondritis, the diagnosis time from the first symptom are studied; this one is long, about 3 years and 6 months (from 3 months to 17 years) in 13/15 of the cases even if the first manifestation is typical (external chondritis). In two cases only, the diagnosis was established after the first attack. This late of diagnosis had socioeconomical impact and exposed to severe complications like tracheal chondritis.

Association of myelodysplastic syndrome and relapsing polychondritis: further evidence.

We report five patients with both a myelodysplastic syndrome (MDS) and relapsing polychondritis (RP), that represented 0.6% of all MDS and 28% of all RP diagnosed over a period of 14 years. Ten other cases had previously been reported (four in detail), supporting a non-fortuitous association between the two disorders, already suggested for MDS and some other immunological disorders.

[Testicular localization of systemic diseases]. / Localisation testiculaire des maladies systémiques.

Acute orchitis or a mass in testis usually evokes a neoplasm, a torsion or infectious disease for the clinician. Rarely, a systemic disease is involved. Nevertheless, testicular involvement occurs during vasculitis, Behçet or granulomatous diseases, but is uncommonly the first manifestation. Histologic changes after biopsy or orchiectomy usually give the diagnosis. Testicular localization of systemic disease does not change the general treatment.

Participation of cryoglobulinaemia in the severe peripheral neuropathies of primary Sjögren's syndrome.

A peripheral neuropathy is encountered in 10 to 50% of patients with primary Sjögren's syndrome (pSS). The pathogenesis of this complication remains unknown, but severe cases of peripheral neuropathies seem to result from a vasculitis. Since about 20% of pSS are associated with a cryoglobulinaemia, we initiated a retrospective study to assess the participation of cryoglobulinaemia in the severe peripheral neuropathies (SPN) of pSS. We found 6 cases of SPN (presence of pain and/or muscle weakness) in a group of 115 pSS (5%): 3 polyneuropathies and 3 mononeuritis multiplex. In all cases, the involvement was sensoromotor and axonal. Four patients had a biopsy-documented cutaneous vasculitis, and 2 of them had also a muscular lymphocytic vasculitis. A cryoglobulinaemia was detected in sera of 5 patients. Although the research was negative in the remaining patient, the presence of an IgM monoclonal gammapathy and of an hypo-complementaemia suggested also the presence of a cryoglobulinaemia. Complement was activated in the 6 cases. Treatment was aggressive: oral corticosteroid (6 cases), methylprednisolone pulses (4 cases), chloraminophen (1 case), plasma exchanges (2 cases), intravenous immunoglobulins (1 case). A stabilization or a partial regression of the neuropathies were observed in 1 case and 5 cases, respectively. This was associated with a reduction of cryoglobulin level and complement activation in 5 cases and 6 cases, respectively. This study suggests that SPN of pSS result from a cryoglobulin-mediated vasculitis.

[Behçet disease. Comparative aspect of diagnostic criteria]. / Maladie de Behçet. Aspect comparatif des critères diagnostiques.

OBJECTIVES: Different diagnostic criteria for Behçet's disease are proposed in the literature. We compared the criteria proposed by Mason and Barnes with those proposed by the International Study Group and with those proposed by the Japanese committee. METHODS: This retrospective study included 41 patients with Behçet's disease according to the criteria set by Mason and Barnes. There were 16 patients of French origin and 25 patients of North African origin. RESULTS: Genital ulcerations were more frequent in the North African population (p < 0.007) and typical Behçet skin lesions were more frequent in the French population (p < 0.021). Comparing the clinical data among the 41 patients with Behçet's disease according to the Mason-Barnes criteria revealed that only 83% met the criteria set by the International Study Group and only 54% the criteria of the Japanese committee. For the International Study Group criteria, the requirement for recurrent buccal ulcerations with at least 3 episodes over a 12 month period (a major criteria) was the most limiting element. Likewise, genital ulcerations were not always recurrent. CONCLUSION: These findings confirm the variability of clinical manifestations of Behçet's disease with ethnic origin. Proposed diagnostic criteria vary depending on the study committee and should be used as diagnostic guidelines rather than as criteria required for positive diagnosis.

[Sensitivity and specificity of antineutrophil cytoplasmic antibodies in systemic vasculitis]. / Sensibilité et spécificité des anticorps anticytoplasme des neutrophiles (c-ANCA) au cours des vascularites systémiques.

The diagnostic value of c-ANCA as a specific marker of systemic vasculitis (particularly Wegener's granulomatosis) is well established. The prognostic value of c-ANCA for determining disease activity is controversial. We have prospectively studied in ten patients with systemic vasculitis over a mean period of 34 months (extreme 2-61 months). All patients had c-ANCA at the moment of the diagnosis: four patients had high titer of c-ANCA all over the period study; three clinical and biological exacerbations of the disease was observed without variation of the c-ANCA titer. In four patients c-ANCA disappeared within 6 months after the beginning of the treatment correlated with disease activity. Sometimes a rise of c-ANCA titer was observed with or without disease activity. In one case c-ANCA titer had a serrated evolution. The sensitivity and the specificity of the c-ANCA for disease activity in the ten studied patients were respectively 1 and 0.28. In patients with systemic vasculitis and c-ANCA at the time of the diagnosis, variation in c-ANCA titer alone is of limited prognostic value for predicting disease course.

[Ultrastructural and immunohistochemical study of the olfactory mucosa in Alzheimer's disease]. / Etude ultrastructurale et immunohistochimique de la muqueuse olfactive dans la maladie d'Alzheimer.

The discovery of reliable peripheral markers would be of great interest for the diagnosis of Alzheimer's disease. Interestingly specific lesions of Alzheimer's disease were found in the olfactory areas of the brain. The loss of the detection and the identification capabilities in olfaction suggest a defect in the olfactory mucosa. The ultrastructural study of biopsy of olfactory mucosa from patients suspected to suffer of Alzheimer's disease revealed a degeneration of sustentacullar and olfactory cells as well as an architectural disorganization. No neuropathological characteristic lesion such as Paired Helicoidal Filaments or amyloid fibrils could be evidenced. Immunohistochemical analysis achieved with a polyclonal antiserum raised against A4 protein (fragment 1-28) showed a specific staining in the sustencellular and of the outer part of the olfactory epithelium corresponding to the mucus area, whereas appropriate controls were negative. Our study raised the question of the amyloid protein origin in the olfactory mucosa. Analysis of some more patients will enable us to determine the diagnostic value of this study in Alzheimer's disease.

[Follow-up study, using dynamic transcutaneous oximetry in 17 patients with stage II Leriche and Fontaine occlusive arterial disease of the lower limbs]. / Suivi par oxymétrie transcutanée dynamique de 17 malades avec artériopathie oblitérante des membres inférieurs au stade II de Leriche et Fontaine.

We evaluated the value of dynamic transcutaneous oxygen pressure measurement (TcPO2) in 17 patients with stage II occlusive arterial disease of the lower limbs treated with exercise only. We studied 17 patients (15 men, two women) with an average age of 63 years (range 39-80 years). Claudication perimeter and dynamic TcPO2 were evaluated before and after 6 month walking exercise and tabac stopping. Four different sites of TcPO2 were studied: precordium (reference probe), thigh, calf and foot in the dorsal recumbent position after 30 minutes rest, during a standardised exercise stress test at 50 watts and during the recovery phase. The results were expressed as ratio of tissue oxygenation (RTO): thigh, calf or foot TcPO2/precordial TcPO2 x 100 in order to take into account the patients cardiorespiratory status and adaptation to exercise. Claudication perimeter was 255 m +/- 221 before 6 months exercise and 835 m +/- 539 after (P < 0.01). The duration of significative ischemia was significantly reduced after 6 months exercise (P = 0.02 calf, P < 0.01 foot). Dynamic transcutaneous oxymetry would therefore seem to be a useful method of assessing stage II occlusive peripheral arterial disease and the topography of tissue hypoxia. It could be valuable in orientating treatment and the first method to provide and objective evaluation of the efficacy of medical or surgical treatment.

[Predictive signs of cancers in dermatomyositis. Study of 29 cases]. / Signes prédictifs de cancers au cours de la dermatomyosite. Etude de 29 observations.

Dermatomyositis (DM) is characterized by an inflammatory myopathy and typical cutaneous lesions. In a retrospective study, 29 adult cases without overlap syndrome were reviewed. Our aim was to define predictive signs of cancer. Ten (four women, six men) of the 29 patients (35%) had DM associated with malignancy. The diagnosis of cancer was made concomitantly in six cases, more than year after (two cases), more than year prior to (two cases) the occurrence of DM. No extensive diagnosis procedures were necessary for identifying the tumors. A paraneoplasic evolution was certain for any patient, probable for six, improbable for fourth. For the group with malignancy: age was higher (P = 0.01), albumin lower (P = 0.04), C reactive protein higher (P = 0.0061). These parameters seem to have predictive value for the presence of malignancy.

[Silicosis and primary Gougerot-Sjögren syndrome]. / Silicose et syndrome de Gougerot-Sjögren primitif.

We report three cases of primary Sjögren's syndrome in silicotic coal miners. All patients fulfilled the diagnostic criteria for Sjögren's syndrome recently established by the European Community study group. One patient had cryoglobulinemia and polynevritis. Another had Raynaud's phenomenon, arthralgia, purpura and polynevritis. Capillary microscopy was normal in all the three patients. Antinuclear antibodies were detected only in one patient, who had also anti-SSa and anti-SSb antibodies. The prevalence of systemic sclerosis, rheumatoid arthritis and probably systemic lupus erythematosus is significantly higher after longstanding occupational exposure to silica. On the contrary, any case of Sjögren's syndrome was till now described in the course of pulmonary silicosis. The physiopathological mechanisms of these associations are misunderstood.

[Vascular manifestations of dermatomyositis and polymyositis. Clinical, capillaroscopic and histological aspects]. / Manifestations vasculaires des dermatomyosites et polymyosites. Aspects cliniques, capillaroscopiques et histologiques.

Polymyositis is characterized by a T-cell-mediated and MHC-I-restricted cytotoxic process, whereas dermatomyositis is a primitively vascular disease with microangiopathy mediated by the complement C5b-9 membranolytic attack complex. We have tried to estimate the frequency of vascular abnormalities in polymyositis as defined by Bohan and Peter. We have retrospectively studied 17 patients with dermatomyositis and 15 patients with polymyositis. Vascular abnormalities have been defined by clinical, capillaroscopic and histologic (muscle biopsy and minor salivary glands biopsy) features. After clinical features, 5/17 dermatomyositis had a Raynaud's phenomenon, against 6/15 polymyositis. Digital necrosis has been observed for 2/17 dermatomyositis and 2/15 polymyositis. In capillaroscopy, 14/17 dermatomyositis had a microangiopathy with or no enlarged capillary loops, against 7/15 polymyositis. None of these polymyositis had enlarged capillary loops. The muscle biopsy showed a predominantly perivascular or perimysial inflammatory infiltrate (vascular process) for 10/16 dermatomyositis against 4/13 polymyositis; a perifascicular atrophy for 3/16 dermatomyositis against 2/13 polymyositis. The histological study of minor salivary glands, showed vascular lesions for 2/11 dermatomyositis and for 1/8 polymyositis. Finally, Bohan and Peter's classification is now inadequate to distinguish between dermatomyositis and polymyositis. Indeed, some dermatomyositis sine dermatitis, may exist and be recognized by their vascular features. To distinguish between dermatomyositis and polymyositis is important, to evaluate the risk of cancer which is more frequent in dermatomyositis.

Prognostic factors in Waldenström's macroglobulinemia: a report of 167 cases.

PURPOSE: A single-center retrospective analysis was conducted in 167 patients with Waldenström's macroglobulinemia (WM) to delineate prognostic factors. PATIENTS AND METHODS: One hundred sixty-seven patients diagnosed between January 1969 and December 1988, fulfilling diagnostic criteria of WM, were entered onto this study. One hundred twenty-eight patients were treated with chlorambucil (0.1 mg/kg/d): 117 at diagnosis and 11 during the disease course. Seventeen variables were analyzed in all patients and in treated patients for their prognostic value on survival using the Kaplan-Meier method and a Cox multivariate regression analysis. RESULTS: Median survival duration for all patients was 60 months. Pretreatment factors associated with shorter survival in the entire population were age > or = 60 years (P = .006), male sex (P = .0001), general symptoms (P = .01), hemoglobin less than 10 g/dL (P = .008), leukocytes less than 4 X 10(9)/L (P = .02), neutrophils less than 1.7 X 10(9)/L (P = .02), and platelets less than 150 X 10(9)/L (P = .0006). Organomegaly, signs of hyperviscosity, renal failure, monoclonal immunoglobulin M (M IgM) level, blood lymphocytosis, and percentage of marrow lymphoid cells were not significantly correlated with survival. In a Cox multivariate regression analysis, the combination of factors that gave the best prognostic value was the association of sex (P = .0002), neutrophils (P = .002), age (P = .008), and hemoglobin (P = .02). CONCLUSION: Our findings suggest that some pretreatment parameters, including older age, male sex, general symptoms, and cytopenias, carry a poor prognosis in WM. By contrast, high initial tumor burden (indicated by organomegaly, high IgM level, and high percentage of marrow lymphoid cells) does not seem to be significantly associated with short survival. Our results help define a high-risk population that could perhaps benefit from newer therapeutic approaches.

Biodegradation and brain tissue reaction to poly(D,L-lactide-co-glycolide) microspheres.

The therapeutic application of neuroactive molecules in neuroscience is limited, due to the problems posed by the administration of these drugs (peripheral metabolism, systemic effect and passage of the blood-brain barrier). One solution is the implantation in the brain of biodegradable polymer devices with controlled release of a neuroactive drug. The biodegradation and tissue reaction of the copolymer poly(D,L-lactide-co-glycolide) microspheres prepared by the solvent evaporation method, radiosterilized and stereotactically implanted in the rat brain were studied by routine staining, immunohistochemistry and transmission electronic microscopy. The brain tissue reaction observed was a non-specific astrocytic proliferation and a macrophagous-microglial cell reaction, typically found following damage to the central nervous system. Some foreign-body giant cells were observed and the inflammatory and macrophagous reaction decreased dramatically after 1 month and almost ended after 2 months when the microspheres were totally biodegraded. The copolymer poly(D,L-lactide-co-glycolide) microspheres may be considered biocompatible to the brain tissue.

[Olfactory mucosa and Alzheimer's disease. Technique for biopsy and ultrastructural study]. / Muqueuse olfactive et maladie d'Alzheimer. Technique biopsique et étude ultrastructurale.

The discovery of a reliable peripheral marker would be of a great interest for the early diagnosis of the Alzheimer's Disease. The olfactory deficit and the major histologic changes of the olfactory-related areas of the brain occurring during this disease raised the possibility that the olfactory epithelia could be one of the way of entry of a possible process that still has to be identified. We have developed an instrument and a technique of biopsy of the human olfactory mucosa to search for the presence of characteristics lesions on patients suffering of an Alzheimer's Disease. These small specimens have been prepared for electronic microscopy. The ultrastructural study of a sample of olfactory mucosa has been realised in 9 cases (5 Alzheimer's-4 controls) revealing in 4 patients suspected of an Alzheimer's Disease a complete architectural disorganisation with a destruction of the dendrite of the olfactory cells and a severe degeneration of the sustentacular cells. We did not find any characteristic changes such as Paired Helicoidal Filaments or amyloid fibrils. These results do not presuppose of their eventual presence at a precocious stage of the disease. Further ultrastructural and immunochemical studies carried out with patients at various stages of the disease are necessary in order to confirm this hypothesis.