Stability post-licensure: compatibility container content - a practical case study.

Numerous variations to a manufacturing process may take place during the life cycle of a vaccine. To support these variations, the regulator requires providing stability data according to the existing ICH guidelines; these have been designed for documenting the licence of a new vaccine. Comparative studies and adapted stability designs specific to the variation will give far more confidence to the manufacturer and the regulator than the classical model. The following case study applied to a change of a stopper illustrates this approach.

Comparison between different strategies of covalent attachment of DNA to glass surfaces to build DNA microarrays.

DNA microarray is a powerful tool allowing simultaneous detection of many different target molecules present in a sample. The efficiency of the array depends mainly on the sequence of the capture probes and the way they are attached to the support. The coupling procedure must be quick, covalent, and reproducible in order to be compatible with automatic spotting devices dispensing tiny drops of liquids on the surface. We compared several coupling strategies currently used to covalently graft DNA onto a glass surface. The results indicate that fixation of aminated DNA to an aldehyde-modified surface is a choice method to build DNA microarrays. Both the coupling procedure and the hybridization efficiency have been optimized. The detection limit of human cytomegalovirus target DNA amplicons on such DNA microarrays has been estimated to be 0.01 nM by fluorescent detection.

[Jaundice secondary to a metastasis of a malignant melanoma at the level of the common bile duct]. / Ictère secondaire à une métastase de mélanome malin au niveau de la voie biliaire principale.

A patient presenting with a malignant melanoma of the skin developed obstructive jaundice. Ultrasound examination of the upper abdomen revealed dilated bile ducts and the presence of a solid mass at the hilum level. There was no evidence of biliary lithiasis. The intraluminal location of the mass was confirmed by endoscopic cholangiography. Laparoscopy disclosed a 2 cm mass within the wall of the common bile duct. Pathological diagnosis was common bile duct wall metastasis from malignant melanoma.

Cysts of the semilunar cartilages of the knee: a new approach by ultrasound imaging. A study of six cases and review of the literature.

The authors present six cases of cysts of the semilunar cartilages of the knee detected by ultrasonography, all of them confirmed at the time of surgery. Five of these lesions were cysts of the lateral meniscus; one lesion was a cyst of the medial meniscus. Because of ultrasonography, an accurate diagnosis of meniscal cysts is within the reach of the radiologist; it is also possible to visualize the extension of these lesions in a correct way, thereby being of great help to orthopedic surgeons. The main advantages of this technique compared with magnetic resonance imaging (MRI), which is also able to give the same information, are the short time required to perform the examination and the low costs. After outlining their study, the authors give a review of the literature concerning the incidence, clinical features, pathogenesis, and management of the disease.

[Computed tomography aspects of cerebral toxoplasmosis in AIDS]. / Aspects tomodensitométriques de la toxoplasmose cérébrale dans le SIDA.

We followed by CT 19 AIDS patients with cerebral toxoplasmosis. Diagnosis of cerebral toxoplasmosis was assessed on radiological and clinical basis, including the therapeutic response. CT allowed to confirm brain lesions (40 lesions in 19 patients) and to follow the evolution with treatment. Analysis of the CT features of these brain lesions permits to define some characteristic findings, though not pathognomonic. These lesions share common characteristics with other granulomatous diseases or with brain abscesses. The most frequently observed features are: target lesions (74%) with contrast enhancement (95%), frequently multiple (53%), associated with a hypodense area of oedema (100%), and responsible for a mass effect (79%). Under treatment, we observed improvement in 89%, resulting either in complete disappearance of the lesions (16%), disappearance of one or more contrast enhancing (46%) or hypodense (6%) areas, or volumetric regression of the hypodensities (50%). We conclude that CT is a good first-step examination for the detection and follow-up of cerebral toxoplasmosis in AIDS patients. MRI, a method with a higher sensitivity but still less accessible, may be considered at the present time as a second-step examination for those patients with solitary lesions on CT, or for symptomatic patients with normal CT.

[Radiography profile in forced plantar flexion for studying unsteady feet]. / La radiographie de profil en flexion plantaire forcée pour l'étude du pied instable.

We have studied the interest of an original radiological incidence ("Plantar hyperflexion") allowing to demonstrate a possible hyperlaxity of medio-tarsal joints. We discovered a significant difference of mobility between patients with unstable feet and the control group. The existence of a medio-tarsal hyperlaxity should be taken into account before starting any treatment.

[A case of multiple brain calcifications associated with hypoparathyroidism]. / Un cas de calcifications cérébrales multiples associées à une hypoparathyroïdie.

We report a case of extensive cerebral calcifications associated with hypoparathyroidism in a 82-year-old woman who has been thyroidectomized and received an antiepileptic treatment for 26 years after an episode of coma followed by confusion. We discuss the frequent confusion in terminology used for describing such cases, emphasizing the necessary distinction between Fahr's disease (extensive cerebral calcifications without abnormal phosphocalcium metabolism) and cerebral calcinosis associated with hypoparathyroidism.

[Obstruction of the sigmoid colon due to an ovarian metastasis of colonic origin]. / Obstruction du côlon sigmoïde par une métastase ovarienne d'origine colique.

The authors present a case of left ovarian metastasis from colon carcinoma causing sigmoid obstruction. On US and CT the ovarian mass appears as a primary malignant lesion. The lesion caused a regular sigmoid stenosis which mimicked, on barium enema, a volvulus and screened the primary lesion.

Comprehensive and interpretative radiology of middle ear malformations.

Radiological aspects of middle ear malformations based on the study of 31 observations should be correlated with the modalities of normal and abnormal morphogenesis. This is particularly the case for malformations of the ossicles, which can be classified according their precise branchial origin. Facial nerve malformations, dysgenesis of the footplate and atresia of the external auditory meatus is discussed in relation to normal events of middle ear morphogenesis. Standard histochemical procedures and study of radioactive sulphur uptake in the mouse embryo permit to characterize some factors of middle ear ossicles formation. Study of correlations between radiological features and experimental results reveal that the important factors are: the chronology of morphogenesis; the organization of branchial structures; the patterns of neural crest cells migration; the influence of environmental factors. Furthermore, teratologic features obtained in animals models can be correlated with human syndromes.

Prediction of splenic volume by a simple CT measurement: a statistical study.

The width, thickness, and areas of the spleen were obtained by abdominal computed tomography on 50 patients. Several simple linear equations were used to predict the splenic volume and were correlated with a previously published method for volume estimation based on summing areas of multiple contiguous scans. This was used as a standard and demonstrated an excellent linear correlation (r = 0.95) with an estimate based on a product of length and maximal width. Correlation was even better (r = 0.991) with an estimate based on length, maximal width, and thickness.