Risedronate Reduces the Risk of First Vertebral Fracture in Osteoporotic Women

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score =–3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg (n= 328) or placebo (n= 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P= 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P= 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P= 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause. Received: 12 September 2001 / Accepted: 11 December 2001     

The significance of incomplete excision in patients with basal cell carcinoma

Sixty-seven patients with incompletely excised basal cell carcinomas are reviewed. No recurrences were seen in seven patients who had immediate supplementary treatment; 23 of 60 patients submitted to a "wait and see" regimen developed recurrent disease, Recurrence was commoner in those in whom both the lateral and deep margins were involved, and when the incomplete excision was for recurrent disease. The latter recurrences were more difficult to control in patients who had previously had radiotherapy, when the deep margin was involved and when a flap had been used to close the resulting defect. A case is made for immediate re-excision for all patients with incompletely excised basal cell carcinomas.     

Ultrasound Densitometry of the Os Calcis in Patients with Hemiparesis Following a Cerebrovascular Accident

Ultrasound densitometry has been measured in the os calcis of 31 stroke patients (14 women, 17 men), ages 46–87 years, to determine whether bone density is lower than expected for normal subjects at this site, and to investigate whether or not the stroke side has lower values than the nonstroke side. We have also measured a large control group of 268(39 men, 228 women) subjects who showed similar values to other published data. Immobility is a known precursor to bone loss and so we also compared ultrasound Stiffness Index with an index of mobility in 22 of the stroke patients. In healthy subjects, ultrasound densitometry (measured as Stiffness) fell by 25% in females from 48–52 to 68–72 years. Stiffness (expressed as z-score) in patients with stroke was low in females (P < 0.02) but not in males, but both stroke side and nonstroke side were equally low. Stiffness did not decline with time since stroke, but did correlate with mobility after stroke, on the stroke (r = 0.73) and nonstroke (r = 0.62) side. The data suggest that stroke patients, particularly females, have low bone density before the stroke event. The greater ultrasound Stiffness with increasing mobility after stroke may suggest that active rehabilitation after stroke may produce denser bone. Received: 30 July 1997 / Accepted: 10 June 1999     

Effect of vitamin C on glycosylation of proteins.

Twelve nondiabetic subjects consumed 1 g/day vitamin C for 3 mo. A fasting blood sample was taken at the start of the study and at the end of each month for the measurement of plasma and intraerythrocyte glucose, vitamin C, glycosylated hemoglobin (affinity chromatography and electrophoresis), and glycosylated albumin (affinity chromatography). Although there were no significant changes in fasting glycemia, glycosylated hemoglobin (affinity chromatography) decreased 18%, from 6.18 +/- 0.48% (mean +/- SD) at the start to 5.05 +/- 0.50% (P less than 0.0001) after 3 mo, whereas, HbA1 measured by electrophoresis increased 16%, from 6.17 +/- 0.61 to 7.16 +/- 0.59% (P less than 0.0001) in this period. Glycosylated albumin decreased 33%, from 1.56 +/- 0.24 to 1.04 +/- 1.01% (P less than 0.0001) after 3 mo. This discrepancy between glycosylated hemoglobin measured by electrophoresis and affinity chromatography was due to methodological differences between the two techniques, with affinity chromatography measuring "true" glycosylated hemoglobin. The greater decrease found with glycosylated albumin was probably due to the different distribution of vitamin C between plasma and within the erythrocyte, levels after 1 mo of supplementation being 109 +/- 19 and 59 +/- 9 microM, respectively (P less than 0.001). This indicates that administration of oral vitamin C may inhibit the glycosylation of proteins in vivo by a competitive mechanism.     

Effect of Paget's disease of bone on areal lumbar spine bone mineral density measured by DXA, and density of cortical and trabecular bone measured by quantitative CT

Although bone density may be increased in bone that is affected by Paget's disease, density changes in cortical and trabecular bone and the effect on bone that is apparently unaffected by Paget's disease are relatively unexplored. We have investigated 81 vertebrae (28 affected, 53 unaffected) in 27 patients with Paget's disease, by dual X-ray absorptiometry (DXA) and by quantitative CT (QCT) bone density measurements of trabecular and cortical bone. DXA bone density was high (mean z-score = 1.62, p < 0.001) in vertebrae affected by Paget's disease, but not significantly different from normal in unaffected vertebrae (mean z-score = 0.07, ns). Mean QCT z-score in Paget's vertebrae was 2.07 (p = 0.009) for cortical bone and 1.37 (p = 0.008) for trabecular bone. DXA correlated with QCT cortical values in affected and unaffected bone (r = 0.8 and 0.56, respectively), and with QCT trabecular values (r = 0.72 and 0.48, respectively). There was no significant difference in the slopes for the correlations in affected or unaffected bone. Cortical QCT values are underestimated in Paget's disease compared with physical measurements of density, owing to the computer algorithm used. High DXA values may alert to the possibility of Paget's disease, especially if the value deviates from the expected normal sequence in lumbar vertebrae. Osteoporotic vertebrae may be overlooked if the average value of bone mineral density is taken in the lumbar spine without reviewing each vertebra.     

Lesion heterogeneity in multiple sclerosis: a study of the relations between appearances on T1 weighted images, T1 relaxation times, and metabolite concentrations

OBJECTIVES: Multiple sclerosis lesions appear as areas of high signal on T2 weighted MRI. A proportion of these lesions, when viewed on T1 weighted MRI, appear hypointense compared with surrounding white matter. These hypointense T1 lesions are thought to represent areas of greater tissue damage compared with the more non-specific, total T2 lesion load. This study aimed to better characterise the properties of high signal T2 lesions with differing appearances on T1 weighted MRI using quantitative MR techniques. METHODS: Eleven patients with secondary progressive multiple sclerosis were studied. Two high signal T2 lesions were selected from each patient-one of which appeared hypointense and one isointense on a T1 weighted image. A voxel was positioned around each lesion and for this volume of brain the metabolite concentrations were estimated using proton MR spectroscopy ((1)H-MRS) and the T1 relaxation time within each voxel calculated from a T1 map generated using a multislice technique. RESULTS: Compared with isointense T1 lesions, hypointense T1 lesions exhibited a significantly lower absolute concentration of N-acetyl derived metabolites (tNAA) and a significantly higher absolute concentration of myo-inositol (Ins). T1 relaxation time correlated significantly with both tNAA (r=-0.8, p < 0.001) and Ins (r=0.5, p=0. 012). There was no correlation between T1 relaxation times and creatine/phosphocreatine or choline containing compounds. CONCLUSIONS: Prolonged T1 relaxation times seem to reflect the severity of axonal damage or dysfunction (inferred by a low tNAA) and possibly also gliosis (inferred by a high Ins) in chronic multiple sclerosis lesions.     

Case Report and Cohort Analysis of Drug-Induced Liver Injury Associated with Daptomycin

A patient receiving daptomycin developed asymptomatic transaminitis and hyperbilirubinemia without concurrent multiorgan dysfunction or elevation of his creatinine kinase level. After ruling out other etiologies, the liver injury was attributed to daptomycin and was subsequently resolved. A single-center retrospective cohort analysis of baseline and follow-up liver function panels (n = 614) from all admissions from 2008 to 2013 during which daptomycin was administered did not reveal any other cases of probable or definite drug-induced liver injury associated with daptomycin.     

The nucleotide sequence of the gene for human protein C.

A human genomic DNA library was screened for the gene for protein C by using a cDNA probe coding for the human protein. Three different overlapping lambda Charon 4A phage were isolated that contain inserts for the gene for protein C. The complete sequence of the gene was determined by the dideoxy method and shown to span about 11 kilobases of DNA. The coding and 3' noncoding portion of the gene consists of eight exons and seven introns. The eight exons code for a preproleader sequence of 42 amino acids, a light chain of 155 amino acids, a connecting dipeptide of Lys-Arg, and a heavy chain of 262 amino acids. The preproleader sequence and the connecting dipeptide are removed during processing, resulting in the mature protein composed of a heavy and a light chain held together by a disulfide bond. The heavy chain also contains the catalytic region for the serine protease. Two Alu sequences and two homologous repeats of about 160 nucleotides were found in intron E. The seven introns in the gene for protein C are located in essentially the same positions in the amino acid sequence as the seven introns in the gene for human factor IX, while the first three introns in protein C are located in the same positions as the first three in the gene for human prothrombin.     

Use of alcohol intoxication codes for serious non-fatal hospitalised injury

Aim

To determine the extent to which ICD-10 alcohol intoxication codes are used for serious hospitalised injury and the distribution of these codes according to gender, age, injury mechanism and intent, severity of injury, and whether the patient was treated in an Intensive Care Unit.

Design

Cross-sectional study.

Setting

New Zealand.

Participants

All injury hospital discharges in 2010 that met specified severity criteria.

Measurements

Cases which had a measurement of BAC (Y90) coded, or only a subjective assessment of alcohol intoxication (F10.0).

Findings

2.5% had a blood alcohol recorded (Y90) and a further 3% were coded as being intoxicated but there was no blood alcohol code. All factors investigated were shown to be independently associated with the assignation of codes. Notable findings were the elevated odds of an alcohol code for males, assault and the more severe injuries.

Conclusions

Assessment of alcohol intoxication among seriously injured persons appears to be very uncommon. The development of a standardised instrument for clinical judgement of intoxication would be highly desirable.