Comorbid disorders and the surgical patient

By understanding the physiologic consequences of select comorbid disorders, we can better anticipate the special needs of surgical patients.     

The frequent and conserved DR3-B8-A1 extended haplotype confers less diabetes risk than other DR3 haplotypes

Aim:  The goal of this study was to develop and implement methodology that would aid in the analysis of extended high-density single nucleotide polymorphism (SNP) major histocompatibility complex (MHC) haplotypes combined with human leucocyte antigen (HLA) alleles in relation to type 1 diabetes risk.
Methods:  High-density SNP genotype data (2918 SNPs) across the MHC from the Type 1 Diabetes Genetics Consortium (1240 families), in addition to HLA data, were processed into haplotypes using P ed C heck and M erlin , and extended DR3 haplotypes were analysed.
Results:  With this large dense set of SNPs, the conservation of DR3-B8-A1 (8.1) haplotypes spanned the MHC (≥99% SNP identity). Forty-seven individuals homozygous for the 8.1 haplotype also shared the same homozygous genotype at four 'sentinel' SNPs (rs2157678 'T', rs3130380 'A', rs3094628 'C' and rs3130352 'T'). Conservation extended from HLA-DQB1 to the telomeric end of the SNP panels (3.4 Mb total). In addition, we found that the 8.1 haplotype is associated with lower risk than other DR3 haplotypes by both haplotypic and genotypic analyses [haplotype: p = 0.009, odds ratio (OR) = 0.65; genotype: p = 6.3 × 10⁻⁵, OR = 0.27]. The 8.1 haplotype (from genotypic analyses) is associated with lower risk than the high-risk DR3-B18-A30 haplotype (p = 0.01, OR = 0.23), but the DR3-B18-A30 haplotype did not differ from other non-8.1 DR3 haplotypes relative to diabetes association.
Conclusion:  The 8.1 haplotype demonstrates extreme conservation (>3.4 Mb) and is associated with significantly lower risk for type 1 diabetes than other DR3 haplotypes.     

CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology.

Cholecystokinin (CCK) is a peptide originally discovered in the gastrointestinal tract but also found in high density in the mammalian brain. The C-terminal sulphated octapeptide fragment of cholecystokinin (CCK8) constitutes one of the major neuropeptides in the brain; CCK8 has been shown to be involved in numerous physiological functions such as feeding behavior, central respiratory control and cardiovascular tonus, vigilance states, memory processes, nociception, emotional and motivational responses. CCK8 interacts with nanomolar affinities with two different receptors designated CCK-A and CCK-B. The functional role of CCK and its binding sites in the brain and periphery has been investigated thanks to the development of potent and selective CCK receptor antagonists and agonists. In this review, the strategies followed to design these probes, and their use to study the anatomy of CCK pathways, the neurochemical and pharmacological properties of this peptide and the clinical perspectives offered by manipulation of the CCK system will be reported. The physiological and pathological implication of CCK-B receptor will be confirmed in CCK-B receptor deficient mice obtained by gene targeting (Nagata el al., 1996. Proc. Natl. Acad. Sci. USA 93, 11825-11830). Moreover, CCK receptor gene structure, deletion and mutagenesis experiments, and signal transduction mechanisms will be discussed.     

Orthodontic reduction of a displaced alveolar fracture: a case study

Abstract –  A 42-year-old woman had sustained a severe dental trauma with an alveolar fracture after an epileptic attack. A tooth block 31, 32, 33 and 34 was dislocated about 7 mm in buccal direction. Panoramic X-rays and CT-scan disclosed the alveolar fracture without total disjunction of the fragment. An orthodontic appliance was used to reduce the fracture with gentle forces during a 5-month period. Normal function was established and the teeth remained vital.