[Orofacial manifestations of systemic sclerosis: A study of 30 consecutive patients]. / Les manifestations buccofaciales de la sclérodermie systémique : étude de 30 patients consécutifs.

INTRODUCTION: The face is frequently involved in systemic sclerosis. The main stomatologic manifestations include limited mouth opening, xerostomia, skin atrophy, trigeminal neuralgia. The objective of this study was to describe oral and facial manifestations observed in scleroderma patients from our cohort. METHODS: Between March and October 2006, a stomatologic consultation was included in the follow-up of scleroderma patients seen during consultation or daily hospital in internal medicine or dermatology units. Demographic, clinical and biological data were collected. Stomatologic examination comprised measure of the mouth opening, sugar's and Schirmer's tests, orthopantomogram analysis, and evaluation of the repercussion of symptoms on quality of life using a visual analogical scale (VAS between 0 and 10). RESULTS: This study included 30 patients (women 87 %, mean age 58.6 + or - 13.6 years). Mean duration of systemic sclerosis (n=20 limited cutaneous form, n=10 diffuse form) was eight years. Stomatologic manifestations were: skin atrophy (n=28), peribuccal rhagades (n=25), telangiectasia (n=21), decreased mouth opening (n=20), xerostomia (n=20), xerophtalmia (n=16), periodontal ligament space widening (n=10), bone resorptions (n=2), trigeminal neuralgia (n=1). Xerostomia was considered more discomforting (mean VAS=3.8) than decreased mouth opening (mean VAS=2.6). Xerostomia was the second more discomforting sign of scleroderma and was significantly associated to the limited cutaneous form (p=0.045) and to anticentromeres antibodies expression (p=0.002). Decreased mouth opening was correlated to oesophageal involvement (p=0.025). CONCLUSION: Oral and facial manifestations are frequently observed in scleroderma patients. These manifestations lead to major functional discomfort, mainly due to decreased mouth opening that seems to be frequently associated to oesophageal involvement. Xerostomia is also frequent and is commonly observed in anticentromere antibodies positive cutaneous limited forms of systemic sclerosis. Evolution of radiographic abnormalities like periodontal ligament space widening (33 % of cases), or osteolytic lesions (7 %) is poorly known.

[Orofacial manifestations of systemic sclerosis: a study of 30 consecutive patients]. / Les manifestations buccofaciales de la sclérodermie systémique: étude de 30 patients consécutifs.

INTRODUCTION: The face is frequently involved in systemic sclerosis. The main stomatologic manifestations include limited mouth opening, xerostomia, skin atrophy, trigeminal neuralgia. The objective of this study was to describe oral and facial manifestations observed in scleroderma patients from our cohort. METHODS: Between March and October 2006, a stomatologic consultation was included in the follow-up of scleroderma patients seen during consultation or daily hospital in internal medicine or dermatology units. Demographic, clinical and biological data were collected. Stomatologic examination comprised measure of the mouth opening, sugar's and Schirmer's tests, orthopantomogram analysis, and evaluation of the repercussion of symptoms on quality of life using a visual analogical scale (VAS between 0 and 10). RESULTS: This study included 30 patients (women 87%, mean age 58.6+/-13.6 years). Mean duration of systemic sclerosis (n=20 limited cutaneous form, n=10 diffuse form) was eight years. Stomatologic manifestations were: skin atrophy (n=28), peribuccal rhagades (n=25), telangiectasia (n=21), decreased mouth opening (n=20), xerostomia (n=20), xerophtalmia (n=16), periodontal ligament space widening (n=10), bone resorptions (n=2), trigeminal neuralgia (n=1). Xerostomia was considered more discomforting (mean VAS=3.8) than decreased mouth opening (mean VAS=2.6). Xerostomia was the second more discomforting sign of scleroderma and was significantly associated to the limited cutaneous form (p=0.045) and to anticentromeres antibodies expression (p=0.002). Decreased mouth opening was correlated to oesophageal involvement (p=0.025). CONCLUSION: Oral and facial manifestations are frequently observed in scleroderma patients. These manifestations lead to major functional discomfort, mainly due to decreased mouth opening that seems to be frequently associated to oesophageal involvement. Xerostomia is also frequent and is commonly observed in anticentromere antibodies positive cutaneous limited forms of systemic sclerosis. Evolution of radiographic abnormalities like periodontal ligament space widening (33% of cases), or osteolytic lesions (7%) is poorly known.

Heredity: a prognostic factor for acne.

BACKGROUND: The role of heredity in acne severity and therapeutic response remains unclear. OBJECTIVE: A prospective epidemiologic study was performed to compare clinical and evolutive features of acne and response to treatment in 151 patients with acne with (A+) or without (A-) family history of acne. METHODS: A+ and A- patients were compared on clinical and therapeutic criteria. A+ patients were then distributed into subgroups (M+, F+, M+F+) following the origin of family history (father: F, mother: M). RESULTS: The clinical profile was similar in the A+ and A- populations. Acne occurred earlier and more often before puberty in the A+ population, in which oral treatments and relapse after isotretinoin were more frequent. Retentional lesions (number and extent) were more important in the M+ and M+F+ populations. CONCLUSION: This study confirms the importance of heredity as a prognostic factor for acne. Family history of acne is associated with earlier occurrence of acne, increased number of retentional lesions and therapeutic difficulties.

Prospective study of risk factors of relapse after treatment of acne with oral isotretinoin.

BACKGROUND: The effectiveness of oral isotretinoin against acne is undeniable. However, few data on the maintenance of effect after treatment termination have been published. OBJECTIVE: The purpose of the study was to identify the risk factors of relapse after stopping isotretinoin. METHOD: This prospective open study examined 52 patients with moderate to severe acne at the Dermatological Clinic of the Nantes University Hospital (France). Variables likely to influence relapse were studied using the Cox model. RESULTS: 27 patients (52%) relapsed after stopping treatment. In multivariate analysis, severe seborrhoea and a high score of inflammatory lesions at the end of the treatment, an early age, a family history of acne, prepubertal acne and acne extended to the trunk were the factors increasing significantly the risk of relapse. CONCLUSION: Our data allow to define more precisely the profile of acne patients for whom the risk of relapse is highest and who should therefore be followed up quite regularly after treatment termination.

[Local guidelines and quality of antibiotic treatment in urinary tract infections: a clinical audit in two departments of a university hospital]. / Impact de recommandations locales sur la qualité de l'antibiothérapie dans l'infection urinaire. Audit clinique dans 2 services d'un hôpital universitaire.

AIM: To assess the effect of local guidelines implemented at the Nantes University Hospital regarding antibiotic therapy for urinary tract infections. DESIGN: Before/after study of one medical ward and one urologic surgery ward. Quality was measured by two principal criteria: compliance with guidelines and medical justification in the specific clinical situation. Both criteria considered simultaneously the choice of drug, dose and duration of treatment. Deviations from the guidelines were described. RESULTS: 1086 UTI cases were identified over two 12-month periods, before and after the dissemination of guidelines (for prostatitis, pyelonephritis, indwelling catheter-associated UTIs, and other undefined UTIs). The guidelines were applicable in 313 (30%) cases. Overall, after implementation of the guidelines, the percentage of justified prescriptions did not change significantly (41.8% compared with 38.7%, p=0.299), but the percentage of correct (conforming) prescriptions fell (from 30.4% to 15.7%, p=0.0022). The percentages of correct and justified prescriptions differed in the medical (respectively 45.0% and 46.6%,) and surgical units (13.1% and 36.5%). CONCLUSIONS: Issuing guidelines does not necessarily improve the quality of antibiotic therapy for UTIs in hospitals.

[Adequate prescription of antibiotic therapy for urinary tract infections in hospital: identifying and correcting non-observance of guidelines]. / Bonnes pratiques de prescription des antibiotiques pour la prise en charge des infections urinaires en milieu hospitalier: identification des écarts aux recommandations et actions correctrices.

OBJECTIVE: We analyzed the adequacy of antibiotic therapy prescribed for urinary tract infections (UTI): prostatitis, pyelonephritis, indwelling catheter-associated UTIs, or other undefined UTIs. DESIGN: The adequacy of prescriptions to local guidelines was assessed retrospectively in two wards (Internal Medicine and Surgical Urology) of the Nantes University Hospital. The principal criteria involved simultaneously: choice of the molecule, dose, and treatment duration. Non-observances of guidelines were major (non-adequacy of the molecule, prescription of a non-active molecule according to in vitro susceptibility tests, non-appropriate treatment abstention), or minor (non-justified treatment, non-justified bitherapy, no prescription of bitherapy when requested, no treatment adaptation when requested, too short or too long treatment length, dosage mistakes). RESULTS: One thousand eighty-six infections were collected over a 24-month period. The overall rate of adequate prescriptions was 40.1% (46.6% in Internal Medicine and 36.5% in Surgical Urology). In Internal Medicine (226 non observance among 389 prescriptions), the ratio of major non-observance of guidelines was 9.8%. Among them, 44.7% were non-appropriate treatment abstentions. In Surgical Urology (539 non observance out of 695 prescriptions), non-observance related to treatment length were the most frequent. The ratio of major non-observance was 19.9%. Among them, non-adequacy of the molecule reached 60.7%. Non-justified treatment and non-appropriate bitherapies were frequent. CONCLUSIONS: For both units, indwelling catheter-related UTIs and other UTIs accounted for more than 50% of the infections although not detailed in the local guidelines. Identifying and analyzing Non observance may lead to targeted correcting actions to improve prescription quality.

Human papillomavirus and extragenital in situ carcinoma.

BACKGROUND: The relation between human papillomavirus (HPV) and extragenital Bowen's disease (BD) is controversial. METHODS: This study used in situ hybridisation to evaluate the rate of HPV in extragenital cutaneous BD and investigated possible relations with immune status and exposure of skin to light. RESULTS: HPV DNA was detected in 58% of 69 samples from 50 patients. The percentage of HPV detection was not significantly higher in exposed (55%) than unexposed areas (65%), and no difference in HPV rate was found between immunosuppressed and immunocompetent patients. CONCLUSION: Thus, this study confirms the high rate of HPV detection in extragenital cutaneous BD and suggests that there is no apparent relation concerning exposed areas and immune status.

Prognostic factors in Sézary syndrome: a study of 28 patients.

BACKGROUND: The new European Organization for Research and Treatment of Cancer classification considers Sézary syndrome (SS) among the aggressive epidermotropic cutaneous T-cell lymphomas (ECTLs). Recent technological advances have facilitated the diagnosis of this disease, but it remains practically incurable, with a median survival of about 2.5-5 years. Deaths are due in part to the iatrogenic effects of treatments, which suggests that the management of SS could be improved. OBJECTIVES: Retrospectively to study the prognostic criteria related to disease progression. METHODS: Thirty patients with SS were followed up in the Dermatology Department of the University Hospital in Nantes, France, between January 1989 and May 2000. The diagnosis of SS was based on at least three of the following criteria: erythroderma, histological evidence of ECTL, a level of 20% or more circulating Sézary cells, and loss of My7 antigen expression by basal cells of the epidermis. Two patients not seen again after the initial diagnosis were excluded from the statistical study. RESULTS: The median disease-specific survival of the 28 patients was 64.55 +/- 10.11 months. The prognostic factors found in univariate analysis were age at diagnosis (P = 0.0109), interval before diagnosis (P = 0.0566), lactate dehydrogenase (LDH) level (P = 0.042) and presence of the Epstein-Barr virus (EBV) genome (BHLF in in situ hybridization) in skin (P = 0.0079). The prognostic factors found in multivariate analysis were age, interval before diagnosis and presence of the EBV genome in keratinocytes. A decreased number of Langerhans cells in the epidermis did not appear to be a prognostic factor. CONCLUSIONS: Our study confirms the prognostic value of age and LDH level, and for the first time demonstrates the prognostic value of the identification of the EBV genome in the skin. This seems consistent with a marked immune deficit during severe forms of SS.

Prognostic factors in acute cardiogenic pulmonary edema.

The purpose of this study was to determine the clinical and biological findings at admission in the Department of Emergency Medicine associated with a poor prognosis, and to evaluate early response to treatment as a prognostic factor. It was a prospective cohort study with a 5-month follow-up. One hundred eighty-six patients admitted for acute cardiogenic pulmonary edema were included. Features were analyzed at the admission and on response to initial treatment. The main outcome measure was survival at 2 end-points: hospital discharge, and 5 months of follow-up. Multivariate analysis showed that in-hospital mortality was associated with marbleization (mottling) odd-ratio (OR) = 9.0), low diuresis (OR = 4.0), high breath rate 6 hours after admission (OR = 4.0), and chronic digoxin use (OR = 3.39). Five-month mortality was associated with a bedridden state (OR = 9.0), marbleization (mottling) (OR = 5.5), myocardial infarction (OR = 3), and poor early response to initial treatment (OR = 3.2). In addition to well-known factors, the response to initial treatment evaluated 6 hours after admission was a major determinant of outcome.

Long-term follow-up in 51 patients with mycosis fungoides and Sézary syndrome treated by interferon-alfa.

Although interferon-alfa (IFN-alpha) has proved effective in treating epidermotropic cutaneous T-cell lymphoma (ECTL), few studies have considered the follow-up of treated patients and whether complete remission was maintained. We studied 51 patients (one stage Ia, seven stage Ib, one stage IIa, 30 stage IIb, 11 stage III (Sézary syndrome) and one stage IV) who received low-dose IFN-alpha as monotherapy for ECTL (mean daily dose of IFN-alpha 2.7 x 106 units for 14.9 months), giving special consideration to the significance of My7 (CD13) antigen expression by epidermal basal cells in predicting the maintenance of complete remission. For a mean follow-up period of 43.4 months, the results showed 21 complete remissions, 13 partial remissions and 17 patients with stable or progressive disease. Twelve patients died during the follow-up (3-52 months). IFN-alpha led to an improved response in the early stages, with a greater number of complete remissions (P = 0.03) and partial remissions (P = 0.01). The mean time to complete remission was 4 months, regardless of clinical stage (P = 0.1). Of 21 patients in complete remission, 57% had a relapse within a mean period of 7.5 months. For patients maintained in complete remission, the mean period of response was 31 months. The length of complete remission was independent of clinical stage, and My7 antigen expression was not predictive of complete remission.

Increased pancreatic islet blood flow in 48-hour glucose-infused rats: involvement of central and autonomic nervous systems.

The pancreatic islet blood flow of rats 24 h after a prolonged (48-h) glucose infusion was investigated using a nonradioactive microsphere technique. In the basal state, islet blood flow was significantly increased in previously hyperglycemic rats (HG) compared to that in controls (C). During an i.v. glucose challenge, both plasma insulin and islet blood flow were increased in the two groups, but these increases were significantly higher in HG than in C rats. Although less pronounced, the results were similar when glucose was injected into the carotid artery toward the brain at a dose that did not modify the peripheral glucose level. The effect of this intracarotid injection was abolished after bilateral subdiaphragmatic vagotomy in both C and HG rats. Furthermore, in the latter group, both plasma insulin concentration and islet blood flow returned to values similar to those observed in the basal state in C rats. After pretreatment with the alpha2-adrenoceptor agonist clonidine, the insulin response to the intracarotid glucose load was totally blunted in the two groups of rats. By contrast, whereas such a pretreatment lowered the glucose-induced increase in islet blood flow in C rats, it was without effect in HG rats. These data suggest that a period of hyperglycemia and/or hyperinsulinemia is sufficient to induce a perturbation of pancreatic islet blood flow, which appears to be mainly due to an increased parasympathetic activity, whereas the decrease in sympathetic tone does not play a role. These modifications in autonomic nervous system activity could be due to alterations in some brain areas involved in "glucose sensing."

Replacement fluids in plasmapheresis: cross-over comparative study.

OBJECTIVE: To compare the tolerance and the cost of three replacement fluids in plasmapheresis: albumin 4% alone, albumin 4% + dextran 40, or albumin 4% + hydroxyethylstarch 6%. DESIGN: A one center randomized, cross-over, comparative study designed to explore the tolerance and the colloid oncotic pressure in patients undergoing plasmapheresis. PATIENTS: 225 plasmapheresis procedures were performed in 27 patients. MEASUREMENTS AND RESULTS: Hemodynamic tolerance was good in the three treatment groups. Serum protein concentration after plasmapheresis was significantly lower in the albumin + hydroxyethylstarch group, followed by albumin + dextran 40, versus albumin alone. Colloid oncotic pressure before and after exchange was similar in the three groups. CONCLUSIONS: The clinical use of 25-30% of hydroxyethylstarch 6% or dextran 40 with albumin 4% was clinically well tolerated and associated with a 12% decrease of the cost of substitution solutions.

Increased anti-Epstein-Barr virus antibodies in epidermotropic cutaneous T-cell lymphoma: a study of 64 patients.

Epstein-Barr virus (EBV) is often associated with non-Hodgkin's T-cell lymphomas and has recently been found in the lesions of mycosis fungoides and Sézary syndrome. We sought to determine whether the anti-EBV antibody profile was disturbed in mycosis fungoides and Sézary syndrome and whether there are particular profiles characteristic of disease stage. Anti-EBV antibodies (anti-VCA, -EA and -EBNA) were studied in the sera of 64 patients. An immunoenzymatic technique was used, and the results were compared with the same number of age- and sex-matched healthy controls. Patients with mycosis fungoides and Sézary syndrome developed higher anti-VCA antibody titres (median 1200) than controls (median 320). Thirty-seven patients had anti-VCA > or = 1200 vs. 19 controls (P < 0.01). These elevated anti-VCA antibody titres were associated with positive EA in 19 patients versus three controls. No differences were found between the illness stages. Anti-EBV antibodies were most often found in mycosis fungoides and Sézary syndrome when the serological profile was similar to that of cellular immune deficiencies and EBV-related non-Hodgkin's lymphoma. EBV could be involved, either directly on lymphocytes or, more likely, indirectly by chronic antigenic stimulation.

[Uni- and multivariate analysis of predictive survival factors in hepatocellular carcinoma. A study of a series of 122 patients]. / Analyses uni- et multivariée des facteurs prédictifs de survie des carcinomes hépatocellulaires. Etude d'une série de 122 patients.

The files of 122 patients hospitalized for hepatocellular carcinoma (HCC) were reviewed retrospectively to study survival as a function of treatment and different peri-therapeutic factors. Cirrhosis was certain or probable in 69 cases. Laparotomy was performed 77 times (13 exploratory, 64 excisions). Chemoembolization with Adriamycine was performed 18 times. Median survival was 11.6 months. The factors influencing survival in monovariate analysis were the Child-Pugh stage (p < 0.0001), the Okuda stage (p < 0.0001), ascites (p < 0.001), a post-operative complication (p < 0.0001), gamma-glutamyltransferase level (p < 0.0037), tumor site (p < 0.004), albuminemia (p < 0.008), alkaline phosphatase concentration (p < 0.0087), number of tumors (p < 0.01), portal thrombosis (p < 0.01) and alpha-foetoprotein level (p < 0.01). In multivariate study, the Okuda stage (p < 0.001), age (p < 0.001) and portal thrombosis (p < 0.037) remained significant. The Okuda 1 group was also considered in multivariate study, in which case only patient age and the possibility of therapeutic excision were significant factors. In our opinion, the Okuda classification, which is easy to establish, should be adopted for pretherapeutic evaluation of patients with hepatocellular carcinoma.

Involvement of the autonomic nervous system in the in vivo memory to glucose of pancreatic beta cell in rats.

The fact that the potentiating effect of prolonged hyperglycemia on the subsequent insulin secretion is observed in vivo but not in vitro suggests the involvement of extrapancreatic factors in the in vivo memory of pancreatic beta cells to glucose. We have investigated the possible role of the autonomic nervous system. Rats were made hyperglycemic by a 48-h infusion with glucose (HG rats). At the end of glucose infusion as well as 6 h postinfusion, both parasympathetic and sympathetic nerve activities were profoundly altered: parasympathetic and sympathetic activities, assessed by the firing rate either of the thoracic vagus nerve or the superior cervical ganglion, were dramatically increased and decreased, respectively. Moreover, 6 h after the end of glucose infusion, insulin secretion in response to a glucose load was dramatically increased in HG rats compared to controls. To determine whether these changes could be responsible for the increased sensitivity of the beta cell to glucose, insulin release in response to glucose was measured in HG and control rats, either under subdiaphragmatic vagotomy or after administration of the alpha 2A-adrenergic agonist oxymetazoline. Both treatments partially abolished the hyperresponsiveness of the beta cell to glucose in HG rats. Therefore chronic hyperglycemia brings about changes in the activity of the autonomic nervous system, which in turn are responsible, at least in part, for the generation of enhanced beta cell responsiveness to glucose in vivo.

[Gastric adenocarcinomas (excluding linites). Prognostic factors apropos of a series of 101 cases]. / Adénocarcinomes gastriques (linites exclues). Facteurs pronostiques à propos d'une série de 101 cas.

The incidence of some factors on prognosis of adenocarcinoma of the stomach was evaluated in 101 cases. Linites as well as cancers of the cardia were excluded from the analysis. There were 47 total gastrectomies with more or less extensive node dissection and 54 partial gastrectomies. Overall actuarial survival was 34.5% despite the large number of advanced stage cancers (70% positive lymph nodes, 35 with invasion of neighbouring organs, 13 cases of carcinosis and 13 with liver metastasis). Univariate analysis showed that the following factors were associated with poor prognosis: invasion of the serous layer, nodal involvement, emboli, degree of differentiation. Peritumoural reactional lymphoid infiltration, the presence of a chronic gastritis and intestinal metaplasia were found to be favourable factors. Gastric resection appeared to have less impact than the quality of the nodal dissection. These findings emphasize the importance of extensive dissection of the lymph nodes (survival ranging from 31 to 78% depending on the node score). Extensive dissection, allowing better locoregional control of the disease, improved prognosis whatever the size of the tumour (14.8% survival in case extending to neighbouring organs). The only exceptions were palliative exereses and N4+ cases.

In vivo and in vitro increased pancreatic beta-cell sensitivity to glucose in normal rats submitted to a 48-h hyperglycaemic period.

We investigated the importance of the level and the duration of glucose stimulation on the in vivo and in vitro insulin response to glucose in normal rats previously submitted to hyperglycaemia. Rats were made hyperglycaemic by a 48-h glucose infusion. Glucose-induced insulin secretion was investigated in vivo by a 20-min hyperglycaemic clamp and in vitro by the isolated perfused pancreas technique, 3 h after the end of the in vivo glucose infusion. In glucose-infused rats, as compared to controls, in vivo incremental plasma insulin values above baseline integrated over the 20-min hyperglycaemic clamp (delta I) were five times higher during 8 mmol/l glucose clamp, only two times higher in 11 mmol/l glucose clamp and no different in 16.5 mmol/l. Compared to the controls, in vitro incremental plasma insulin concentration above baseline integrated over a 20-min period (delta I) in glucose-infused rats was 16 times higher in response to 2.8 mmol/l glucose, two times higher in response to 5.5 mmol/l, similar in response to 8.3 mmol/l and significantly lower in response to 16.5 mmol/l. In conclusion, our data suggest that a 48-h hyperglycaemic period results in an increased response of the pancreatic beta cell to low glucose. The response is immediately maximal and can not be increased with higher glucose concentrations. This situation could explain the apparent minimal effect of high concentrations on in vitro insulin secretion in previously hyperglycaemic rats and may provide insights into the sequence of events leading to the impairment of beta-cell function in Type 2 (non-insulin-dependent) diabetes mellitus.

[New aspects of drug hepatotoxicity]. / Nouveautés en hépatotoxicité médicamenteuse.

This article sets out to report the new hepatotoxic drugs identified during the course of 1989 and to describe the state of the art about drugs suspected of hepatotoxicity, such as amoxicillin-a clavulinic or, to a lesser extent, octreotide. In contrast, Exifone, a recently introduced drug, was withdrawn from the market within a year. One is surprised to find drugs such as Buprenorphine and Trimebutine listed, which have never induced clinical cases of hepatitis despite widespread use. The article also reviews the drugs with recognized hepatotoxicity and tries to present the most up-to-date information about them.