Genetic determinants of statin intolerance

Background  

Statin-related skeletal muscle disorders range from benign myalgias – such as non-specific muscle aches or joint pains without elevated serum creatinine kinase (CK) concentration – to true myositis with >10-fold elevation of serum CK, to rhabdomyolysis and myoglobinuria. The genetic basis of statin-related muscle disorders is largely unknown. Because mutations in the COQ2 gene are associated with severe inherited myopathy, we hypothesized that common, mild genetic variation in COQ2 would be associated with inter-individual variation in statin intolerance. We studied 133 subjects who developed myopathy on statin monotherapy and 158 matched controls who tolerated statins without incident or complaint.     

Bilateral versus unilateral sudden sensorineural hearing loss.

OBJECTIVES: To analyze the clinical characteristics and treatment results between bilateral (bi-) and unilateral (uni-) sudden sensorineural hearing loss (SSNHL). STUDY DESIGN AND SETTING: A retrospective study. METHODS: Three hundred twenty-four patients with SSNHL were classified into two groups; simultaneous bi-SSNHL (n = 16) and uni-SSNHL (n = 308). We compared clinical characteristics, medical history, hearing level, and treatment results between the 2 groups. RESULTS: The incidence of bi-SSNHL was 4.9 percent of overall patients with SSNHL. Bi-SSNHL occurs more commonly in patients of older age, with preexisting diabetes mellitus, and lipid panel abnormalities compared with uni-SSNHL. Ten patients (62.5%) in the bi-SSNHL group showed hearing recovery in 1 or both ears compared with 56.5 percent of patients with uni-SSNHL. Only 12 (37.5%) of all 32 ears recovered in bi-SSNHL, which was significantly lower than in uni-SSNHL. CONCLUSION: Bi-SSNHL has a very low incidence and lower recovery rate than uni-SSNHL. Recognition of similarities and differences between bilateral and unilateral SSNHL can help in counseling and managing the patients.     

Disturbances of bone growth and development

"What is growth anyway? Can one talk about positive growth in childhood, neutral growth in maturity, and negative growth in old age?" Our goal is to help promote normal positive growth in infants and children. To achieve this, we must be cognizant of the morphologic changes of both normal and abnormal bone formation as they are reflected in the radiographic image of the skeleton. The knowledge of the various causes and the pathophysiologic mechanisms of the disturbances of bone growth and development allows us to recognize the early radiographic manifestations. Endocrine and metabolic disorders affect the whole skeleton, but the early changes are best seen in the distal ends of the femurs, where growth rate is most rapid. In skeletal infections and in some vascular injuries two-or three-phase bone scintigraphy supercedes radiography early in the course of the disease. MRI has proved to be very helpful in the early detection of avascular bone necrosis, osteomyelitis, and tumor. Some benign bone tumors and many bone dysplasias have distinct and diagnostic radiographic findings that may preclude further studies. In constitutional diseases of bone, including chromosomal aberrations, skeletal surveys of the patient and all family members together with biochemical and cytogenetic studies are essential for both diagnosis and genetic counseling. Our role is to perform the least invasive and most informative diagnostic imaging modalities that corroborate the biochemical and histologic findings to establish the definitive diagnosis. Unrecognized, misdiagnosed, or improperly treated disturbance of bone growth can result in permanent deformity usually associated with disability.     

Desensitization of GABA-induced currents in cultured rat hippocampal neurons.

The basic characteristics of desensitization of the GABAA receptor were investigated in cultured rat hippocampal neurons (three days to four weeks in vitro) using whole cell patch clamp techniques. GABA at 10-500 microM was perfused on to neurons for 30 or 60 s, with 60 s intervals of wash with control bath solution between perfusions. Desensitization, evaluated by peak-to-plateau ratio and time constants of current decay (tau), was dose-dependent and culture age-dependent. Desensitization was observed as early as three days in culture, the earliest time tested. At all ages, higher concentrations of GABA induced both larger and faster desensitization. Desensitization was markedly voltage-dependent and decreased with depolarization; peak-to-plateau ratio went from 6.3 to 1.4 and tau went from 4.6 to 26.8 s when holding potentials were changed from -80 mV to +30 mV. Low concentrations of GABA (1-2 microM) perfused for 2-60 s, which did not induce any current, had no effect on the maximal response nor desensitization produced by a subsequent application of 100 microM GABA. This finding suggests that GABA receptors were not desensitized without first being activated.     

Effects of an Interferon Inducer, Poly I:C, on Acute Ocular Infection Produced by Intracameral Inoculation of Toxoplasma gondii

A potent interferon inducer, synthetic polyinosinic acid-polycytidylic acid complex (poly I:C), was used prophylactically and therapeutically in experimental ocular Toxoplasma infections in rabbits. Daily intravenous injections of poly I:C alone or when combined with daily subconjunctival injections of the inducer delayed the appearance of conjunctivitis, corneal opacity, and iritis in Toxoplasma-infected eyes provided that the treatment was started 1 day before the infection. When the treatment was begun at the same time or 1 day after the infection, no delay in the production of the ocular lesions was noted. In no case was the treatment curative or completely suppressive.     

Spontaneous disruption of mycotic aneurysm involving innominate artery

We report a case of ruptured mycotic aneurysm involving innominate artery requiring an urgent surgical treatment. A 62-yr-old woman presented with fever and dyspnea. Previously, she was diagnosed with colon cancer and received right hemicolectomy and one cycle of adjuvant chemotherapy. On echocardiogram, pericardial effusion was noted and emergency pericardiocentesis was performed. CT scan revealed aortic aneurysm involving ascending aorta and innominate artery, and thrombi surrounding those structures. Patch repair of the defect in the ascending aorta and ringed Goretex graft to bypass the innominate and ascending aorta were performed. We believe that this is the first case of ruptured mycotic aneurysm involving innominate artery.