[When HbA1c is unreliable : a case report of hereditary spherocytosis]. / Cas clinique. Quand le dosage de l'HbA1c n'est pas fiable : à propos d'un cas de sphérocytose héréditaire.

Glycated haemoglobin (HbA1c) is a biological parameter used in the management of diabetic patients. Independent of the daytime glycaemic variations, but complementary to the measurement of blood glucose or subcutaneous glucose concentrations, it allows both the clinician and the patient to have an appreciation of the glycaemic balance of the last weeks. In this way, anti-diabetic treatment can be adjusted if necessary to achieve the desired goal and hopefully delay or prevent diabetes-related micro- and macroangiopathic complications. Some conditions can alter the glycation of haemoglobin. In this case, the HbA1c level becomes difficult to interpret. Hereditary spherocytosis may be revealed by a dissociation between low HbA1c level and high blood glucose levels. A family history, Coombs-negative haemolytic anaemia, or a finding of spherocytes in the blood smear is suggestive of hereditary spherocytosis. Fructosamine testing may be an alternative. This article will present a patient with hereditary spherocytosis in whom the HbA1c level was not interpretable when compared to the elevated blood glucose measurements.

: L'hémoglobine glyquée (HbA1c) est une valeur biologique utilisée dans le suivi des patients diabétiques. Indépendante de la variation glycémique nycthémérale, mais complémentaire à la mesure de la glycémie ou de la concentration sous-cutanée de glucose, elle permet tant au clinicien qu'au patient d'avoir une appréciation de l'équilibre glycémique des dernières semaines. De cette manière, le traitement anti-diabétique peut être éventuellement adapté pour atteindre l'objectif escompté et espérer retarder, voire prévenir, les complications micro- et macroangiopathiques liées au diabète. Certaines affections peuvent altérer la glycation de l'hémoglobine. Dans ce cas, le taux d'HbA1C devient difficile à interpréter. La sphérocytose héréditaire peut se révéler par un tableau de dissociation entre un taux bas d'HbA1C et des valeurs élevées de glycémie. Des antécédents familiaux, une anémie hémolytique à Coombs négatif, ou une observation de sphérocytes dans le frottis sanguin sont en faveur d'un diagnostic de sphérocytose héréditaire. Le dosage de la fructosamine peut être une alternative. Le présent article abordera le cas d'un patient atteint d'une sphérocytose héréditaire chez qui le taux d'HbA1c n'était pas interprétable en regard des contrôles glycémiques.

[Granulicatella adiacens: an underestimated cause of endocarditis]. / Granulicatella adiacens: une cause sous-estimée d'endocardite.

We report the case of an old man who was affected by an endocarditis related to Granulicatella adiacens, an uncommon bacteria, difficult to isolate and responsible for an important morbidity and mortality. Thus, it is mandatory to seek for endocarditis when this germ is demonstrated in order to start quickly an effective antibiotic treatment. Inversely, in the presence of unexplained endocarditis, further bacteriological investigations are needed to seek for this life nutrition deficient bacteria.

[Hoffmann syndrome presenting to the emergency department]. / Syndrome de Hoffmann aux urgences.

We report a case of hypothyroid myopathy, or Hoffmann syndrome, in a 31-year-old man who presented to the emergency department with asthenia, muscular pain, cramps, and joint pain. Tests revealed increased creatine phosphokinase level (8102 U/L) and severe hypothyroidism (content of T4=3.8 pg/ml, T3=1.3 pg/ml, and thyrotropin stimulating hormone>150 microU/ml). Other causes of myopathy were excluded by anamnestic investigation and paraclinical exam. Treatment was begun with thyroid hormones (from 75 to 175 microg) and good clinical evolution was rapid. The pathophysiology of hypothyroid myopathy, clinical aspects and pathologic anatomic elements are described. The exact etiology of hypothyroidism must be known because some pathologic features are benign and treatment can have good results, whereas others, such as cancer, have worse prognosis.

[Spontaneous coronary artery dissection on the 10th post-partum day: a case report]. / Dissection spontanée d'une artère coronaire au 10e jour post-partum: observation clinique.

Spontaneous coronary artery dissection is a rare cause of myocardial infarction. It most commonly occurs in young women in the peri-partum period. The aetiology remains obscure. The authors describe the case of a 38 year old woman who suffered an inferior wall myocardial infarction on the 10th post-partum day. After failure of thrombolysis, coronary angiography showed dissection of the right coronary artery. An attempted angioplasty was unsuccessful and the patient was treated medically with a favourable clinical outcome. Spontaneous coronary artery dissection should be considered in all young patients without coronary risk factors presenting with acute myocardial ischaemia, especially young women in the peri-partum period. Emergency coronary angiography should be undertaken to establish the diagnosis and orientate appropriate treatment which may be medical, interventional or surgical.

Influence of culture conditions on the alpha 1,2-fucosyltransferase and MUC gene expression of a transformed cell line MM-39 derived from human tracheal gland cells.

Human tracheal glands cells (HTGC) in culture are able to respond to adrenergic, cholinergic and purinergic agonists by increasing their serous and mucin secretions. These secretagogues are also able to maintain an optimal responsiveness of serous cells to stimulation when they are regularly and briefly delivered to the cells, making the HTGC a suitable model to study the serous secretion (Merten, in press). Our interest has been focused on the effects of cholinergic and purinergic secretagogues associated to histamine, on the mucous function of the transformed human tracheal gland cell line MM-39, which has a mixed, both serous and mucous, phenotype. When the cells were exposed to short stimulation every 2 days for 3 weeks with 10 or 100 microM carbachol, UTP and histamine, modifications of their mucous phenotype were observed. The expression of MUC genes appeared dependent on the culture conditions. Transcripts of MUC1, MUC4, and MUC5B genes were observed when the cells were regularly exposed to the mixture of secretagogues at a concentration of 10 microM, in contrast to the unstimulated expression of MUC1 and MUC4 in control cells. MUC1, MUC4, MUC7, MUC6 and MUC11 transcripts were observed when the cells were regularly exposed to the mixture of secretagogues at a concentration of 100 microM. These culture conditions were also able to induce an alpha 1,2-fucosyltransferase activity absent in the MM-39 cells cultivated with standard conditions. There was no marked effect on the alpha 2,3-sialyltransferase activity although the expression pattern of the sialyltransferase genes was reduced to the unique presence of ST3Gal III. In conclusion, MM-39 cells exposed to repeated stimulation by secretagogues at different concentrations express different sero-mucous phenotypes.

In vivo activation of serum complement by contrast media: a clinical study.

The study was designed to confirm complement system activation in vivo in man after intravenous injection of contrast media for brain CT scan enhancement. Four currently available components were tested: C1q, C3 activator, C3c, and C4 after intravenous injection of seven different contrast media: diatrizoate, metrizoate, iothalamate, ioxithalamate, ioxaglate, metrizamide, iopamidol. The complement system was indeed activated by certain control media, but no correlation with clinical reactions or with hypertonicity, ionic or nonionic formulation, or protein binding could be found. However, a correlation was found to some extent between the lipid solubility and the activity on the complement system. Addition of calcium salts definitely inhibited the complement system activation induced by metrizoate and ioxaglate.

Biochemical findings in multiple sclerosis. II. A detailed study of the serum IgA, IgG and IgM levels of 772 MS patients compared with 226 neurological controls.

In the second paper of this series, a detailed study of the three main serum immunoglobulins for a group of 772 MS patients is compared with a group of 226 neurological controls. The results are studied according to sex and different age groups. Except for a slight elevation of the IGM levels in the MS group, especially between 40 and 60 years, no clear cut distinction between the two groups of patients was found.

Biochemical findings in multiple sclerosis IV. Isoelectric focusing of the CSF gamma globulins in multiple sclerosis (262 cases) and other neurological diseases (272 cases).

Despite enormous efforts to find a specific laboratory test for multiple sclerosis, agar gel electrophoresis of the CSF proteins has remained the next to the best one. This study presents evidence that thin layer polyacrylamide isoelectric focusing of the CSF gamma globulins is by far superior for this purpose. In effect, about 91% of the 262 multiple sclerosis patients studied had oligoclonal fractions present in the very alkaline region of the pH gradient. Of the same group of patients only 65% did show pathological results when studied by agar gel electrophoresis. Of the 272 CSF samples from patients suffering from other neurological diseases, only about 7% showed the presence of oligoclonal bands in the same region of the pH gradient, when submitted to isoelectric focusing.

Biochemical findings in multiple sclerosis. III. Immunoglobulins of restricted heterogeneity and light chain distribution in cerebrospinal fluid of patients with multiple sclerosis.

Several biochemical parameters, the most important of which are total IgG, kappa and lambda light chain distribution and thin layer isoelectric focusing, were determined in the cerebrospinal fluid of 36 multiple sclerosis patients. Their ages and the evolution period of their disease are widely spread and no sex differentiation was made.

Clinical parameters and intrathecal IgG synthesis as prognostic features in multiple sclerosis. Part I.

In a search for early prognostic features in multiple sclerosis, the progression rate was calculated in 200 consecutive multiple sclerosis patients who had had a lumbar puncture, and correlated with age at onset, type of disease course, the patient's sex, as well as with indices of blood-brain barrier breakdown and intrathecal IgG synthesis. The present study demonstrates that age at onset plays a role in determining whether the disease will be remitting-relapsing or chronic progressive. Age at onset is also a factor determining the rate of progression of the remitting-relapsing form, but is without influence on the progression of the chronic progressive form. A chronic progressive disease course per se (independent of age at onset) is also associated with a more rapid deterioration. The patient's sex does not appear to be a differentiating factor. Only inconsistent correlations were found between IgG index or number of oligoclonal bands in the CSF and disease progression.

Biochemical findings in multiple sclerosis. V. Transformation of lymphocytes from patients with multiple sclerosis by human basic protein.

Lymphocyte stimulation tests with human basic protein of myelin were performed on patients with multiple sclerosis, with other neurological diseases and on normal subjects. In both MS and OND group, a hypersensitization to basic protein was seen in about one third of the cases. All normal subjects, except one, had negative responses. In the MS group, a positive correlation could be found with some features of the disease: significantly more positive responses were found in independent patients with a short duration of illness and in those with an oligoclonal distribution in the CSF. The authors compare their results with those of the literature. The possible role of BP in pathogeny of MS and OND is discussed.

Intensive immunosuppression with cyclophosphamide in multiple sclerosis. Follow up of 110 patients for 2-6 years.

140 MS patients were treated with intensive I.V. cyclophosphamide immunotherapy and 110 were followed over 2-4 years. Annual relapse rate incidence was calculated over a period of 2 years before and after treatment and repeated neurological scores were made during this period. The conclusions are that 62% of the patients were stabilized during 2-4 years and that clinical improvement of the neurological signs was observed in most of the cases. It is concluded that intensive immunosuppression is able to interfere with the pathological processes involved in the pathogenesis of disseminated sclerosis.

Modulation of immunity in multiple sclerosis: a double-blind levamisole-placebo controlled study in 85 patients.

Levamisole seems to regulate cell-mediated immunity by restoring T-cell function. Since a deficiency of T lymphocytes has been described by various authors in multiple sclerosis patients. Of the 85 patients involved in the trial, evaluation of functional and neurological scores was possible in 54 (32 with placebo and 22 with levamisole). The mean follow-up period was 2 years. This double-blind controlled study indicates that both neurological function and disability significantly deteriorated in the placebo-treated patients, but remained fairly stable in the levamisole-treated group. Since the difference between both groups was not significant, no levamisole effect was demonstrated on progression in multiple sclerosis. With the exception of one case of granulocytopenia (which had no clinical effect), no drug-related changes could be demonstrated. This contrasts with the general impression that this immunomodulator agent might be harmful to patients with multiple sclerosis. The fact that during this blind study both annual relapse rate and disability score remained more stable in treated patients with severe disability suggests that, while waiting for a more effective treatment, long-term levamisole therapy could be useful in patients with multiple sclerosis.

[VEGF and survival of patients with lung cancer: a systematic literature review and meta-analysis]. / VEGF et survie des patients atteints d'un cancer pulmonaire. Revue systématique avec méta-analyse.

The process of angiogenesis is an important factor in tumour development. One of the principal factors implicated in this process is vascular endothelial growth factor (VEGF) which induces, among other things, an increase in vascular permeability. We have undertaken a systematic review of the English and French literature in order to clarify its effect on the survival of patients with small cell (SCLC) and non-small cell (NSCLC) lung cancer. To be eligible studies had to deal with the the evaluation of VEGF or its receptors in lung cancer and describe the relationship of their expression to survival. The survival figures were subject to meta-analysis after a methodological evaluation by means of a specific numerical scale evaluating the design of the study, the methodology (including laboratory techniques), and the analysis of results. Among the 20 studies selected 15 identified VEGF expression, using univariate analysis, as a statistically significant indicator of poor prognosis. 17 reported sufficient data to allow aggregation of the survival figures, of which 15 were devoted to NSCLC (1,549 patients). The median overall methodological score was 48.3% (range 21.8-72.4%), without significant difference (p=0.63) between studies eligible or non-eligible for meta-analysis. The meta-analysis, using the authors' threshold of positivity for VEGF, showed that VEGF is an unfavourable prognostic factor in NSCLC (HR=1.48; 95% confidence interval 1.27-1.72). The data were insufficient to determine the prognostic value of VEGF in SCLC and that of its two receptors Flt-1 and KDR, with 1, 2 and 1 published studies respectively. In conclusion the expression of VEGF in MSCLC is a factor indicating a poor prognosis.

[Is it reasonable to prescribe growth hormones in the elderly?]. / Est-il raisonnable de prescrire de l'hormone de croissance aux personnes âgées?

During normal aging, there is a +/- 60% decrease of the endogenous GH secretion ("somatopause"). However it is safe to prescribe GH therapy only to those people who show a clear cut decrease of GH release as evidenced by low integrated 24 hr secretion and/or low plasma IGF-1. In our view, a complete clinical check up must also show, on the one hand, an abnormal decrease of the optimal quality of life and, on the other hand a willing to maintain a reasonable intellectual and physical activity in the absence of major clinical and biological abnormalities. The benefits are likely to be an increase of muscular strength and of exercise tolerance, a decrease of trabecular osteopenia, a decrease of abdominal obesity, an increase of immunocompetence and a general improvement of the "quality of life". A "pharmacological" prescription is contra-indicated whereas very low dose regimen could induce, through feed back mechanism, a putative decrease of endogenous GH-RH (and GHRPs?) function whose deleterious psychoneuroendocrine effects remain to be demonstrated.