An experimental investigation of the effect of the amount of lubricant on tablet properties.

BACKGROUND: Magnesium stearate (MgSt) is widely used as a lubricant in the production of tablets. However, the amount added to a formulation is often too high or it is poorly mixed, which can lead to the production of tablets whose properties are out of specifications. METHOD: The objective of this work was to investigate by means of a new method based on gamma-ray flux measurement and to study the impact of the amount of MgSt on the mass, thickness, hardness, friability, and disintegration time of tablets containing a 50 : 50 wt.% microcrystalline cellulose and spray-dried lactose pre-blend. Other blends were lubricated with sodium lauryl sulfate (SLS) to compare the performance of the two lubricants in equal amounts. RESULTS: It was observed that, contrary to SLS, a greater amount of MgSt increased the variability of the tablet mass. The tablet hardness decreased with an increasing amount of MgSt, whereas it remained relatively unaffected by the presence of SLS. No solid conclusion could be drawn concerning the relationship between the lubricant concentration and the tablet friability. CONCLUSION: An amount of 0.25 wt.% MgSt and 0.75 wt.% SLS were found to be sufficient amounts of lubricants to obtain a proper compression.

Quality of leucoreduced red blood cell concentrates: 5 years of follow-up in France.

BACKGROUND: Since 1998, prestorage leucoreduction of all cellular blood components has been made mandatory in France. The French blood service needed to follow the data on the quality of the blood components prepared by blood centres. MATERIAL AND METHODS: Quality control (QC) data were submitted to a central data bank by each blood centre. The data were stratified by preparation method for analysis of key performance criteria - residual white blood cell (WBC) and total haemoglobin content. The red blood cell (RBC) preparation processes and the methods for measuring haemoglobin content and residual WBC count were those routinely employed by blood centres. Each year, more than 15,500 RBCs were tested. RESULTS: Red blood cells had a mean haemoglobin content between 53.6 and 54.9 g/unit depending on the year (2001 to 2005). The requirement of 40 g/unit was reached for about 99% of units. The haemoglobin content was influenced by the preparation process: 56.8 +/- 6.9 vs. 50.6 +/- 5.6 g/unit in average for whole blood filtration or RBC filtration, respectively. Apheresis RBCs exhibited a reduced variability (51.8 +/- 3.1 g/unit). The median residual WBC count remained low (0.046 to 0.057 x 10(6) WBCs/unit), and the percentage of RBC units exceeding the 1 x 10(6) WBCs/unit cut-off ranged from 1.5 to 0.6% depending on the year. A seasonal pattern was observed, with a significant increase (P < 0.001) of the median residual WBC count and of the percent of non-conforming units during the summer months. CONCLUSION: Our QC data suggest an overall compliance with the standard. Our data bank is useful to inform on the performance of leucoreduced RBC preparation processes carried out with market available devices.

Lipopolysaccharide-induced diaphragmatic contractile dysfunction and sarcolemmal injury in mice lacking the neuronal nitric oxide synthase.

In this study we evaluated the role of the neuronal nitric oxide synthase (nNOS) in lipopolysaccharide (LPS)-induced diaphragmatic contractile dysfunction and sarcolemmal injury. Wild-type (WT) mice or mice deficient in the nNOS gene (nNOS(-/-)) were injected with either saline (control) or Escherichia coli LPS (LPS groups) and sacrificed 12 h later. The diaphragm was then examined for NOS expression, NOS activity, and in-vitro contractility. We also assessed sarcolemmal injury in isolated muscle strips under resting condition and after 3 min of artificial stimulations. In WT mice, LPS injection reduced maximum force to about 75% of that of control animals and raised total NOS activity significantly due to the induction of the iNOS isoform. Although muscle fiber injury was minimal under resting condition, the percentage of injured fibers in control and LPS-injected mice approached 27% and 40% of total fibers, respectively, in response to artificial stimulation. By comparison, LPS injection in nNOS(-/-) mice elicited a worsening of muscle contractility (maximum force < 60% of control animals) but elicited degrees of sarcolemmal injury similar to those observed in the WT animals. In addition, muscle NOS activity and iNOS protein level in nNOS(-/-) mice injected with LPS reached about 10% and 60% of that of WT animals, respectively (p < 0.05 compared with WT animals). Protein level of endothelial NOS isoform in the diaphragm was not altered by LPS injection in either WT or nNOS(-/-) animals. We conclude that nNOS plays a protective role in attenuating the negative influence of sepsis on diaphragmatic contractility but is not involved in the pathogenesis of sepsis-induced sarcolemmal injury.

[Quality control of labile blood products. Why and howto properly take a specimen? Labile Blood Products Group of the French Blood Transfusion Society]. / Le contrôle de qualité des produits sanguins labiles. Pourquoi et comment bien prélever un échantillon? Groupe de produits sanguins labiles de la Société française de transfusion sanguine.

This article reviews the various techniques of sampling used for the quality control of blood cell products. The importance of this stage for the validity of quality control results is emphasized. Three sampling methods, i.e., stripping, the sterile connection of sampling bag and the destructive method, are described in the form of operating modes and analyzed according to their advantages and drawbacks. The results of a comparative study carried out by the working group 'Blood Cell Products' of the French Society of Blood Transfusion are presented, showing that each method is valid and permits one to obtain a representative sample of the product to be controlled. Thus the diversity of the sampling methods allows us to select the one most adapted to the product to be controlled and to the analyses to be carried out afterward.

Surgical treatment of dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans is a rare dermal tumor that recurs after inadequate primary treatment. In a retrospective study, we analyzed the outcomes of 117 patients (mean age 39 years) treated surgically for a dermatofibrosarcoma protuberans. In most cases (107 patients), surgery was performed according to a protocol of taking wide peripheral resection margins of 5 cm and by resecting a disease-free anatomic zone deep to the lesion. The mean follow-up was 61 months. The results suggest a difference in prognosis between patients treated primarily with wide initial resection and those referred secondarily with recurrent disease following previous treatment by narrow resection margins. There was no recurrent disease in the 66 patients treated primarily by wide peripheral (5 cm) and deep resection of the tumor. Of the 41 patients referred secondarily at the time of recurrence, 2 developed further local disease within a year, despite equally aggressive local treatments. Both patients eventually died of metastatic fibrosarcoma. We emphasize the value of a highly aggressive local resection in the primary treatment of dermatofibrosarcoma protuberans to minimize local recurrence and potential malignant transformation. Modern reconstructive techniques provide satisfactory solutions for defects of almost any size and composition. Our findings suggest that radical primary resection of dermatofibrosarcoma protuberans in conjunction with immediate reconstruction of the primary defect provides the best outcome for the patient.

Monoclonal anti-gamma interferon antibodies enhance experimental allergic encephalomyelitis.

Interferon-gamma (IFN-gamma) is a cytokine with multiple activities on a variety of cells. Under various circumstances, IFN-gamma can exhibit either pro-inflammatory or inhibitory actions. Treatment of SJL/J mice with a monoclonal antibody (Mab) to IFN-gamma during the afferent limb of the immune response to myelin protein produced an enhancement of acute experimental allergic encephalomyelitis (EAE), with increased morbidity, mortality and earlier onset of disease. Systemic administration of IFN-gamma did not improve or worsen clinical outcome, but delayed disease onset. Passive transfer of immune lymph node cells co-activated with MBP and anti-IFN-gamma Mab resulted in more sever disease than that induced by MBP stimulated cells or MBP and IFN-gamma co-stimulated cells. However, in vitro proliferation of an MBP specific T cell line was not influenced by IFN-gamma nor anti-IFN-gamma treatment. Mab to IFN-gamma inhibited suppressor function, in a non-specific assay. These in vivo and in vitro results suggest that systemic IFN-gamma serves as a physiological regulator of a suppressor mechanism in EAE. The abrogation of this regulatory mechanism by anti-IFN-gamma administration contributes to a more severe form of experimental allergic encephalomyelitis.

Histoenzymological study of myocardial ATPase activity in experimental infarction in the rat.

Histoenzymological techniques were used to examine ATPase activity in rat heart muscle fibres after experimental infarction. 25 hours after coronary ligation, ATPase activity in all ventricular section fibres was high, homogeneous at pH 9.4, sections. 48 hours after ligation, necrotic ventricular fibres appeared, leaving only a thin layer of fibres which had apparently preserved their myofibrillar ATPase. These results indicate that, unlike mitochondrial enzyme activity, myofibrillar ATPase activity is relatively resistant to ischaemia.

Closed-chest myocardial ischaemia in dog.

Myocardial ischaemia in dog was induced with releasable material in the distal segment of the anterior descending branch of the left coronary artery. Three releasable materials were tested: gel foam, wax microspheres (120-200 micron) and latex balloons, using different methods of introduction. The left carotid route was selected for introduction of a preformed catheter. The gel foam and wax microspheres caused transitory ischaemia, which was proximal for the foam and distal for the microspheres. The balloons made it possible to standardize the ischaemia as its localization and duration could be selected. This material therefore provided a model for stable chronic ischaemia. Nine dogs were observed by means of precordial mapping (36 electrodes) during the phase following ischaemia or for a period of 4 weeks. The results of these experiments are analysed and correlated with histological results for the post-mortem phase.

[Pulmonary arterial hypertension caused by neoplastic thrombosis of the pulmonary artery]. / Hypertension artérielle pulmonaire par thrombose artérielle pulmonaire néoplasique.

Neoplastic thrombosis of the pulmonary artery is a rare and little known cause of pulmonary arterial hypertension. The clinical picture is one of acute respiratory failure and progressive right ventricular failure caused by pre-capillary pulmonary hypertension. In the living patient there is no way of distinguishing this condition from that of subacute cor pulmonale due to embolism, especially as the primary tumour is not always found either because it is too small or because it has already regressed by the time it has metastasised. The diagnosis usually rests on histological examination of the lungs, and two pathological types can be distinguished: carcinomatous lymphangitis with secondary invasion and thrombosis of the pulmonary arterioles on the one hand, and the neoplastic arterial emboli of a chorio-epithelioma on the other.

[Follow-up study of non-neoplastic Cushing's syndrome followed by paraneoplastic Cushing's syndrome after removal of a malignant pulmonary tumor. Role of the diffuse endocrine system and APUD (amine precursor uptake decarboxylase) cells]. / Syndrome de cushing non tumoral succédant a un cushing paranéoplasique traité avec succès par l'exérèse d'une tumeur pulmonaire maligne. Recul de onze ans. Rôle de la responsabilité du système endocrinien diffus et des cellules dites APUD.

A 27 year old woman had in 1965, a paraneoplastic Cushing's syndrome was cured by removal of a pulmonary tumour. The case was published in June 1968. After a normal pregnancy, a recurrence of the Cushing's syndrome in 1969 led in 1970 to bilateral total adrenalectomy in two stages. Pathology showed hyperplastic adrenal glands. After 11 years follow up, we have not noted any relapse of the tumour nor of the Cushing's syndrome. The pathological appearance of the lung carcinoma removed in 1965 (endocrinoid or neuroid structures) suggests that this was an "apudoma" and that the recurrence of the Cushing's syndrome was perhaps an "apudomatosis" involving the pituitary ACTH cells.

[Biventricular massive infarction with rupture of a mitral papillary muscle and a tricuspid papillary muscle]. / Infarctus massif biventriculaire avec rupture d'un pilier mitral et d'un pilier tricuspidien. Etude anatomique.

The authors report the case of a man of 62 who was admitted with a clinical and electrocardiographic picture of a posterior infarction which was very soon complicated by collapse and anuria. The findings on catheterisation of the right side of the heart were as expected. The cardiac index was very low, and the major abnormality was a type of adiastole with equal pressures in the right ventricle and the auricle of the right atrium. Despite an attempt to assist the circulation by an intra-aortic ballon, the patient died within a few hours. The postmortem examination confirmed the presence of a massive infarction of the left ventricle, but also of the right ventricle, together with rupture of the posterior papillary muscle of the mitral valve, and ischaemic rupture of one papillary muscle of the tricuspid valve.

[Action of bromocriptine on glucose metabolism in diabetics]. / Action de la bromocriptine sur la glycorégulation des diabétiques.

24 diabetics, (9 thin diabetics, 14 cases of maturity onset diabetes, 6 intermediate forms and one case of partial pancreatectomy) received 7.5 to 20 mg of bromocriptine (CB 154) per 24 hours. A definite improvement in glucose metabolism was noted in 6 cases, a definite aggravation in 4 cases; 14 results were not significant (p-0.05). The efficacy of CB 154 did not depend on the clinical type nor on the patient's age. It appeared related to duration of the diabetes (2 years and 3 months in improved patients, 11 years in aggravated patients) and perhaps the degree of retinopathy (more frequent and severe in aggravated patients). The improvement seems to be linked to the existence in certain diabetics of a paradoxical regulation of STH secretion as in acromegaly. The possibility of a peripheral effect of bromocriptine on insulin and glucagon is discussed. The CB 154 test (estimations of STH after a single dose of 2.5 mg) permits one to foresee the efficacy of the drug and perhaps the risk of diabetic retinopathy.

[Hypoglycemic complications of oral drug therapy of diabetes mellitus. 21 cases]. / Les accidents hypoglycémiques des thérapeutiques orales du diabète. 21 cas

The authors present 21 cases of severe hypoglycaemic side effects in diabetics treated with oral sulphonylurea drugs, including two deaths. The medications involved the most frequently were glibenclamide followed by glybutamide and glicalzide. Such side effects often occur early and are unrelated to dose. The classical predisposing factors were noted : old age, renal insufficiency, hepato-cellular insufficiency, drug associations -- in particular oral anticoagulants and salicylates. The indications for such drugs in the treatment of diabetes are discussed. Their use seems doubly illogical in the case of late onset obesity diabetes since the latter is accompanied by cardiovascular complications. It is dangerous in the elderly, particularly sensitive to the risks of hypoglycaemia and in who the diagnosis of "diabetes" is too often made on inadequate grounds.

Tissue-specific synthesis of methotrexate polyglutamates in the rat.

Purified tritium-labeled methotrexate was administered to rats and Sephadex G-15 gel chromatography was used to study the formation of poly-gamma-glutamyl metabolites of methotrexate in different tissues. These metabolities were recognized as tritium-labeled antifolate fractions and were identified by their response to serum pterolypolyglutamate hydrolases and by cochromatography with authentic standards. After doses equivalent to 15 to 20 mg for man, rat liver and kidney were found to contain both 4-amino 10-methylpterolyglutamyl-gamma-glutamic acid and 4-amino-10-methylpterolyglutamyl-gamma-glutamyl-gamma-glutamic acid. With one-third of the dose, only 4-amino 10-methylpteroylglutamyl-gamma-glutamic acid was found. Synthesis of methotrexate polyglutamates in liver and kidney was limited to the interval immediately following methotrexate administration and appeared to occur by sequential addition of single glutamyl residues to so-called "free" intracellular methotrexate. No synthesis of methotrexate polyglutamates was demonstrated in small intestine or thymus. After formation, 4-amino-10-methylpteroyglutamyl-gamma-glutamic acid disappeared from liver and kidney with a half-time of 6.5 days. The effect of these metabolites of methotrexate of cell metabolism is unknown.

[Left ventricular perforation after insertion of a mitral prosthesis. 6 cases]. / Perforation ventriculaire gauche après mise en place d'une prothèse mitrale. Six observations

The external ruptures of the left ventricule occuring in the first twelve postoperative hours and demonstrated by a disastrous haemorrhage or cardiac failure, the other traumatics accidents could be delayed and be observed during the first month, or even later. Essentially two mechanisms are implicated: -- Direct traumatism by a ball valve on the ventricular septrum. -- Sub-annular splitting in connection with the excision of a piece of calcareous valve. Two lines of approch can be offered to avoid these accidents: -- Choose a disc valve when the surgeon finds a small left ventricle below a stenosed and calcified mitral valve. -- Care in the decalcification of the mitral ring and the valvular resection, leaving in case of need a small calcified cuff for safety. The analysis of these findings clarify the main causes of left ventricular rupture after mitral replacement, rare complications, but ones which are very real.