Genetic variation in RYR1 and malignant hyperthermia phenotypes.

BACKGROUND: Malignant hyperthermia (MH) is associated, in the majority of cases, with mutations in RYR1, the gene encoding the skeletal muscle ryanodine receptor. Our primary aim was to assess whether different RYR1 variants are associated with quantitative differences in MH phenotype. METHODS: The degree of in vitro pharmacological muscle contracture response and the baseline serum creatine kinase (CK) concentration were used to generate a series of quantitative phenotypes for MH. We then undertook the most extensive RYR1 genotype-phenotype correlation in MH to date using 504 individuals from 204 MH families and 23 RYR1 variants. We also determined the association between a clinical phenotype and both the laboratory phenotype and RYR1 genotype. RESULTS: We report a novel correlation between the degree of in vitro pharmacological muscle contracture responses and the onset time of the clinical MH response in index cases (P<0.05). There was also a significant correlation between baseline CK concentration and clinical onset time (P=0.039). The specific RYR1 variant was a significant determinant of the severity of each laboratory phenotype (P<0.0001). CONCLUSIONS: The MH phenotype differs significantly with different RYR1 variants. Variants leading to more severe MH phenotype are distributed throughout the gene and tend to lie at relatively conserved sites in the protein. Differences in phenotype severity between RYR1 variants may explain the variability in clinical penetrance of MH during anaesthesia and why some variants have been associated with exercise-induced rhabdomyolysis and heat stroke. They may also inform a mutation screening strategy in cases of idiopathic hyperCKaemia.

Geriatric gynecologic problems increasing.

Over a 3-year period, the percentage of geriatric patients with gynecologic problems treated in one Canadian hospital almost doubled. Pelvic pain, uterine bleeding, and voiding problems were the most common symptoms. Concomitant diseases existed in 60% of the patients, with cardiac and pulmonary problems the most frequent. Uterine fibroids and genital cancer were the most common pathologic diagnoses. Hysterectomy was part of the operative procedure in 37 of 50 patients, and these operations required more time and longer postoperative hospitalization than others. Complications developed in 24% of the patients, with cellulitis, phlebitis, and fever seen most often.

The occurrence of non-tubal ectopic pregnancies in women with an intrauterine device.

The occurrence of intra-ovarian gestation in 2 women and an abdominal pregnancy in a third, all bearing IUDs, is described.

A method of assessing female breast morphometry and its clinical application.

A series of reproducible measurements have been developed with reference to a single midline datum that describe the position of key landmarks on the female breast. Measurements were made on a 'normal' population of 60 subjects content with their breast shape in order to (1) produce 'normal' reference data for breast shape in a population of varying weight and height; and (2) to evaluate factors which may influence the measurements. The findings show that the vertical positions of the measurements migrate inferiorly with increasing age. With increasing weight, the landmarks (except the medial end of the inframammary crease) migrate inferolaterally. Areolar diameter decreases with increasing age and increases with increasing weight. Only one of the 12 bilateral breast measurement parameters shows a significant mean difference between the right and left breast. However, in a proportion of subjects, individual measurements show fluctuating asymmetry. Subsequently, measurements were made of the breasts of women attending with requests for either reduction (n = 25) or augmentation (n = 6) mammaplasty. Compared with the 'normal' population, the group requesting reduction mammaplasty differed significantly in the majority of measurements. The group of patients requesting breast augmentation showed fewer differences compared with the 'normal' population. The average BMI of women requesting augmentation mammaplasty was significantly less and that of women requesting reduction mammaplasty significantly greater than the normal population. In conclusion, a simple and reproducible method of morphometric measurement of the female breast is described. Application of this method suggests that patients requesting reduction or augmentation mammaplasty on the NHS represent a significant deviation from 'normal' morphometry and do not simply have a subjective distortion of their own body image.