Evaluation of temperature rise and bonding strength in cements used for permanent head attachments in rats and mice.

In animal models, devices such as indwelling catheters and intracranial cannulae are often fixed on the skull to allow sampling or injection in the freely moving animal. The most commonly used method to fixate these devices is by embedding them in a 'helmet' of cement which is fixed to the skull with screws. Methylmethacrylate cement is commonly used for this purpose. The disadvantages of this cement are the high polymerization temperature, poor bonding to the bone and long hardening time. We have evaluated the use of glass ionomer cement, carboxylat cement and cyanoacrylic glue as alternative for methylmethacrylate cement. Temperature increase during polymerization of methylmethacrylate cement and glass ionomer cement was measured in the cement on the skull and in the brain of 14 rats in an acute model. In a chronic model, 52 rats and 91 mice were equipped with a 'helmet' of one of the cements. The glass ionomer 'helmets' were applied without or with pretreatment of the skull. The attachment of the cement to the skull was checked every day. After four weeks the bonding strengths of the cements were measured. The glass ionomer cement had less temperature increase during polymerization and good bonding capabilities when compared with methylmethacrylate cement. Mechanical pretreatment of the skull resulted in a significant increase in bonding strength of glass ionomer cement in mice and rats as compared with chemical pretreatment. Furthermore, glass ionomer cement had a shorter hardening time than methylmethacrylate cement, and when the glass ionomer cement was used in prepacked capsules, it was possible to apply the cement sterilely and easily. Cyanoacrylic glue had good bonding capabilities to the skull of mice and is also a good substitute for methylmethacrylate cement.

Unmasking of a hemizygous WFS1 gene mutation by a chromosome 4p deletion of 8.3 Mb in a patient with Wolf-Hirschhorn syndrome.

The Wolf-Hirschhorn syndrome (WHS (MIM 194190)), which is characterized by growth delay, mental retardation, epilepsy, facial dysmorphisms, and midline fusion defects, shows extensive phenotypic variability. Several of the proposed mutational and epigenetic mechanisms in this and other chromosomal deletion syndromes fail to explain the observed phenotypic variability. To explain the complex phenotype of a patient with WHS and features reminiscent of Wolfram syndrome (WFS (MIM 222300)), we performed extensive clinical evaluation and classical and molecular cytogenetic (GTG banding, FISH and array-CGH) and WFS1 gene mutation analyses. We detected an 8.3 Mb terminal deletion and an adjacent 2.6 Mb inverted duplication in the short arm of chromosome 4, which encompasses a gene associated with WFS (WFS1). In addition, a nonsense mutation in exon 8 of the WFS1 gene was found on the structurally normal chromosome 4. The combination of the 4p deletion with the WFS1 point mutation explains the complex phenotype presented by our patient. This case further illustrates that unmasking of hemizygous recessive mutations by chromosomal deletions represents an additional explanation for the phenotypic variability observed in chromosomal deletion disorders.