Familial hypercholesterolemia (FH) is seen with high frequency in the province of Québec, Canada. A large deletion (> 10 kb) of the 5'-end of the low density lipoprotein receptor (LDL-R) gene is the major mutation of the LDL-R in FH subjects in Québec (approximately 60% of FH subjects). No mRNA is produced from the allele bearing the mutation, and cellular cholesterol obtained by receptor-mediated endocytosis is under the control of the non-deletion allele. We have previously reported that some patients with the 10-kb deletion (approximately 9%) fail to respond to the hydroxymethylglutaryl coenzyme A reductase (HMG CoA reductase) inhibitor class of medications. We studied mRNA levels of the LDL-R and HMG CoA reductase genes in response to the HMG CoA reductase inhibitor lovastatin in a time- and dose-dependent fashion in cultured human skin fibroblasts and we devised an in vitro model to study the response to drug therapy in subjects with FH. We determined mRNA levels by RNase protection assay in skin fibroblasts obtained from controls (n = 3) and FH subjects with the > 10-kb deletion (responders, n = 3; non responders, n = 3; to drug therapy). We measured 125I-LDL binding on skin fibroblasts grown in the presence of lipoprotein-deficient serum with or without 1 microM lovastatin, using 10 micrograms/mL of 125I-LDL protein. Control subjects exhibited coordinate regulation of the LDL-R and HMG CoA reductase genes in response to lovastatin, 0.1-25 microM, for 0-24 h. Correlation coefficients between mRNA levels of both genes were > 0.9 in controls and FH subjects. However, by linear regression analysis, the corresponding slopes for the correlation between both genes were 0.98 (controls), 3.36 and 3.63 (FH responders and non-responders), indicating a pattern of dissociated but still coordinate regulation in FH subjects. The magnitude of increase of mRNA levels of the LDL-R gene was approximately five-fold over LPDS in controls, two-fold in FH responders and two-fold in non-responders. Binding studies using 125I-LDL reveal that a control subject and all responders had a 2-2.5-fold increase in binding to cell surface receptors but two out of three FH non-responders showed no increase in binding in response to 1 microM lovastatin. The LDL-R and HMG CoA reductase genes are expressed in coordinate regulation in fibroblasts from subjects with FH due to the > 10-kb deletion, but with a proportionately greater up-regulation of the HMG CoA reductase gene. Some subjects, with FH caused by the > 10-kb deletion of the LDL-R gene, who fail to respond to HMG CoA reductase inhibitors have abnormal LDL receptor binding activity at the cell surface in response to lovastatin in vitro.
Acute tubular necrosis (ATN) represents a serious problem in kidney transplantation. We have reviewed the causes and effects of ATN on kidney transplant patients treated in our hospital between June 1981 and December 1992. We analyzed 359 consecutive kidney transplants performed in 338 patients (213 male and 125 female). There were 311 first grafts. The actuarial functional graft survival (AFGS) was 85% at 1 year and 58.2% at 10 years. The incidence of long-term chronic rejection, the 1-year creatinine blood level (CBL) and the AFGS are summarized: [table: see text] The donor age and the PRA level were significantly correlated with ATN occurrence. ATN after transplantation was associated with a poorer function and survival of the kidney graft. Better donor and patient selection could decrease the occurrence of ATN, thus improving the graft outcome.
Adalimumab (Humira) restores clinical response in patients with secondary loss of efficacy from infliximab (Remicade) or etanercept (Enbrel): results from the STURE registry at Karolinska University Hospital.
OBJECTIVES: To determine whether the tumour necrosis factor-alpha (TNF-alpha) antagonist adalimumab (Humira) can be efficacious after secondary loss of efficacy (i.e. loss of clinical response in patients who had initially demonstrated clinical response) to infliximab (Remicade) or etanercept (Enbrel). PATIENTS AND METHODS: We studied 36 patients from the Stockholm TNF-alpha follow-up registry (STURE) who received adalimumab after secondary loss of efficacy to infliximab (group A, n = 27) or etanercept (group B, n = 9), and 26 patients who were started on adalimumab as the first TNF-alpha antagonist (group C). RESULTS: In group A, the baseline disease activity score 28 (DAS28) at infliximab institution was 5.5+/-0.2. During infliximab treatment, the mean best DAS28 was 3.7+/-0.2 (p
OBJECTIVE: To evaluate the efficacy of adenoidectomy compared with long term chemoprophylaxis and placebo in the prevention of recurrent acute otitis media in children aged between 10 months and 2 years. DESIGN: Randomised, double blind, controlled trial. SETTING: Oulu University Hospital, a tertiary centre in Finland. PARTICIPANTS: 180 children aged 10 months to 2 years with recurrent acute otitis media. INTERVENTION: Adenoidectomy, sulfafurazole (sulphisoxazole) 50 mg/kg body weight, given once a day for six months or placebo. Follow up lasted for two years, during which time all symptoms and episodes of acute otitis media were recorded. MAIN OUTCOME MEASURES: Intervention failure (two episodes in two months or three in six months or persistent effusion) during follow up, number of episodes of acute otitis media, number of visits to a doctor because of any infection, and antibiotic prescriptions Number of prescriptions, and days with symptoms of respiratory infection. RESULTS: Compared with placebo, interventions failed during both the first six months and the rest of the follow up period of 24 months similarly in the adenoidectomy and chemoprophylaxis groups (at six months the differences in risk were 10% (95% confidence interval -9% to 29%) and 18% (-2% to 38%), respectively). No significant differences were observed between the groups in the numbers of episodes of acute otitis media, visits to a doctor, antibiotic prescriptions, and days with symptoms of respiratory infection. CONCLUSIONS: Adenoidectomy, as the first surgical treatment of children aged 10 to 24 months with recurrent acute otitis media, is not effective in preventing further episodes. It cannot be recommended as the primary method of prophylaxis.
Although a majority of patients with hypertension require a multidrug therapy, this is rarely considered when measuring adherence from refill data. Moreover, investigating the association between refill non-adherence to antihypertensive therapy (AHT) and elevated blood pressure (BP) has been advocated.
Identify factors associated with non-adherence to AHT, considering the multidrug therapy, and investigate the association between non-adherence to AHT and elevated BP.
A retrospective cohort study including patients with hypertension, identified from a random sample of 5025 Swedish adults. Two measures of adherence were estimated by the proportion of days covered method (PDC=80%): (1) Adherence to any antihypertensive medication and, (2) adherence to the full AHT regimen. Multiple logistic regressions were performed to investigate the association between sociodemographic factors (age, sex, education, income), clinical factors (user profile, number of antihypertensive medications, healthcare use, cardiovascular comorbidities) and non-adherence. Moreover, the association between non-adherence (long-term and a month prior to BP measurement) and elevated BP was investigated.
Non-adherence to any antihypertensive medication was higher among persons
Cites: Am Heart J. 2014 Jan;167(1):51-58.e524332142
The authors conducted a retrospective review of the clinical and treatment characteristics and outcomes in 28 pediatric patients with anaplastic ependymoma treated with radiation therapy since the advent of computerized tomography (CT) (1978-1994). Twelve patients received craniospinal irradiation followed by a boost to the primary site, two received whole-brain radiation therapy followed by a boost to the primary site, and the remaining 14 were treated with focal radiation therapy. The mean dose to the primary site was 5486 cGy. With a median follow-up period of 86 months for the 14 surviving patients (range 31-201 months), the median disease-free survival, measured from the date of diagnosis to the time of recurrence after radiation therapy, was 40 months. The median disease-free survival measured from the start of radiation therapy was 32 months. The median overall survival rate has not been reached and the actuarial estimates of overall survival rates at 5 and 10 years were 56% and 38%, respectively. According to univariate analysis, the disease-free survival rate was significantly improved (p
To compare antibiotic treatment failure evaluated as switch from one type of antibiotics to another in ambulatory care.
Data on all dispensed doxycycline, amoxicillin, phenoxymethylpenicillin and macrolides in Norway June 2013 - May 2015, was retrieved from the Norwegian Prescription Database. We computed switch rates for the selected antibiotics on day 1-28 after initial dispensing, and the corresponding odds-ratios, adjusted for patients´ age and gender, and prescribers´ specialty.
Of 1.860.036 dispensed antibiotics, 103.076 (5.5%) were switched within 28 days. Within 10 days after the index date, the switch rate was highest for phenoxymethylpenicillin (4.1%), followed by amoxicillin (2.5%), macrolides and doxycycline (2.2%).
The switch rate after initial dispensing of phenoxymethylpenicillin is higher than that of more broad-spectrum antibiotics. However, it is still low, supporting the recommendation of phenoxymethylpenicillin as first line treatment when an antibiotic is indicated for a respiratory tract infection in primary care.
Fermented milk (FM) with putative antihypertensive effect in humans could be an easy applicable lifestyle intervention against hypertension. The mode of action is supposed to be through active milk peptides, shown to possess in vitro ACE-inhibitory effect. Blood pressure (BP) reductions upto 23?mm?Hg have been reported in spontaneously hypertensive rats fed FM. Results from human studies of the antihypertensive effect are inconsistent. However, many studies suffer from methodological weaknesses, as insufficient blinding and the use of office BP measurements. We conducted a randomised, double-blind placebo-controlled study of the antihypertensive effect of Lactobacillus helveticus FM in 94 prehypertensive and borderline hypertensive subjects. The participants were randomised into three treatment groups with a daily intake of 150?ml of FM, 300?ml of FM or placebo (chemically acidified milk). The primary outcome was repeated 24-h ambulatory BP measurements. There were no statistically significant differences in the outcome between the groups (systolic BP (SBP), P=0.9; diastolic BP (DBP), P=0.2). However, the group receiving 300?ml FM had reduced BP across the 8-week period in several readings, which could be compatible with a minor antihypertensive effect. Heart rate and lipids remained unchanged between groups. Hence, our study does not support earlier studies measuring office BP-measurements, reporting antihypertensive effect of FM. Based on straight performed 24-h ambulatory BP measurements, milk fermented with Lactobacillus helveticus does not posses significant antihypertensive effect.