Multicentre survey on compliance with growth hormone therapy: what can be improved?

A survey was undertaken to evaluate compliance in Spanish patients receiving growth hormone treatment. The 28-item structured questionnaire was designed to collect data on compliance, treatment schedule, device used and instruction received. In total, 473 questionnaires were completed in 17 paediatric endocrine units. Compliance was divided into four categories based on percentage of doses omitted, classified as excellent if 0%, good <5%, fair 5–10% and poor >10%. The level of compliance was excellent in 74.0%, good in 20.1%, fair in 3.4% and poor in 2.5%. Compliance was better in those who injected themselves (p < 0:01), were trained by hospital staff (p < 0:01) and used automatic pens (p < 0:05). Patients using conventional syringes were less likely to comply (p < 0:05). More information on growth hormone treatment was requested by 57.6% of patients. The results indicate that the specialist nurse should spend sufficient time with the patients and relatives to ensure a higher compliance rate.     

Validation of a prioritization tool for patients on the waiting list for total hip and knee replacements

Rationale and aims Total hip and knee replacements, usually, have long waiting lists. There are several prioritization tools for these kind of patients. A new tool should undergo a standardized validation process. The aim of the present study was to validate a new prioritization tool for primary hip and knee replacements. Methods We carried out a prospective study. Consecutive patients placed on the waiting list were eligible for the study. Patients included were mailed a questionnaire which included, among other questions, the seven items of the priority tool and the Western Ontario and McMasters Universities Arthritis Index (WOMAC) specific questionnaire. The priority tool gives a score from 0 to 100 points, and three categories (urgent, preferent and ordinary). We studied the content and construct validity. We used Student's t‐test or one‐way analysis of variance. Correlational analysis was used to evaluate convergent and discriminate validity. Results The sample consisted of 838 patients (62.3% were female), with mean age of 70.2 years (SD 8.4). A total of 55.5% patients underwent knee replacement. Given that the tool was elaborated by patients and orthopaedic surgeons, it shows a good content validity. The priority score was statistically different (P < 0.001) among the three urgency categories created. The scores of the three WOMAC dimensions showed differences (P < 0.001) by the three urgency categories created. The correlations between the priority score and WOMAC dimensions were 0.79 (function), 0.69 (pain) and 0.51 (stiffness). The correlations between WOMAC items and items from priority tool were greater (0.47–0.69) between items measuring similar constructs than those measuring different constructs (0.27–0.49). These data are similar in both joints. Conclusions Results support the validity of the prioritization tool to be used with patients waiting for hip or knee replacement.     

Restless legs syndrome in Parkinson's disease.

The present study explores the frequency of RLS in PD and focuses on the clinical differences between patients with and without restless legs syndrome (RLS). A cross-sectional study was designed, comprising 114 patients diagnosed with PD. Those patients positive for RLS were assessed for intensity of the syndrome (IRLS). We compared the clinical characteristics of the patients with and without RLS, using specific scales: Unified Parkinson's Disease Rating Scale (UPDRS I-IV), quality of life (Parkinson's Disease Questionnaire, PDQ 39), sleep symptoms (Parkinson's Disease Sleep Scale, PDSS), and diurnal hypersomnia (Epworth Sleepiness Scale). Twenty-five patients (21.9%) out of a total of 114 subjects diagnosed with PD met the RLS diagnostic criteria. RLS was more frequent in women (68%). The patients with RLS showed poorer scores on the PDSS (PD-RLS+: 102.4 +/- 15.1 vs PD-RLS-: 113.2 +/- 16.4) (P = 0.005) and in the bodily discomfort dimension of the PDQ-39 (PD-RLS+ 6.1 +/- 3.4 vs PD-RLS- 3.8 +/- 2.6) (P = 0.002). Analysis of the subscales of the PDSS showed significant differences (P < 0.001) between both groups of patients in items 4 and 10, and to a lesser degree in items 5 (P = 0.01) and 11 (P = 0.02) There was no increased incidence of diurnal hypersomnia in the group of patients with RLS. There were no differences in the rest of the variables. RLS is frequent in patients with PD, though this condition doesn't apparently affect quality of life or lead to an increased presence of diurnal hypersomnia. It would be advisable to validate the diagnostic criteria of RLS in this specific group of patients.     

Carcinoma de mama: metástasis en cuero cabelludo

We report a case of metastatic lesion to the scalp and the right and left parietal bones 15 years after the development of the primary breast lesion and 7 years after axillary lymph node metastasis and uterine adenocarcinoma probably related to tamoxifen.     

Gene duplications in 21-hydroxylase deficiency: the importance of accurate molecular diagnosis in carrier detection and prenatal diagnosis

BACKGROUND: The detection of 21-OH deficiency (21OHD) carriers in the general population requires that misinterpretations of apparently severe mutations in alleles carrying duplicated genes be avoided. Prenatal treatment prevents virilization in female fetuses and genetic counseling may be offered to couples in which one partner is either a patient or a carrier. This paper proposes a semiquantitative PCR method involving primer extension that distinguishes the severe point mutation Q318X in single gene copy alleles from the normal/nondeficient variant in gene-duplicated alleles. SAMPLES AND METHODS: DNA from 65 individuals carrying Q318X variants, that of 85 partners of 21OHD carriers or patients, and one fetal sample (as well as the DNA of his family) were analyzed. 21OHD alleles were studied by gene-specific PCR/allele-specific oligonucleotides hybridization for common mutations, Southern analysis, complementary direct sequencing and microsatellite typing. Primer extension analysis of the Q318X variants using fluorescent dideoxynucleotides was performed on CYP21A2 gene-specific PCR-amplified DNA samples from controls, patients, potential carriers and prenatal samples. RESULTS: Different fluorescence patterns were seen for the severe mutation (single gene copy) and the nondeficient (gene-duplicated) alleles carrying Q318X. The normal/mutant fluorescence peak (N/M) ratio was < 1 in all heterozygous carriers (mean 0.83; min. 0.70; max. 0.95). In all normal individuals carrying the gene-duplicated Q318X normal variant, the N/M ratio was > 1 (mean 1.69; min. 1.44; max. 2.02). CONCLUSION: The proposed method discriminated between the severe Q318X mutation and the normal Q318X variant in gene duplication, and could be a useful complementary tool in prenatal diagnosis and carrier detection.     

Familial hyperinsulinism-hyperammonemia syndrome in a family with seizures: case report

Hyperinsulinism-hyperammonemia (HI/HA) syndrome is the second most frequent cause of congenital hyperinsulinism (CHI) and it is characterized by recurrent symptomatic hypoglycemia and persistent hyperammonemia. We describe the familial case of a 2-year-old child and her 32-year-old mother who, having suffered from tonic-clonic seizures since infancy, had both been diagnosed with epilepsy and treated with sodium valproate. Hypoglycemia was identified in the child in routine analysis. Six days after admission, a complete study of hypoglycemia showed test results compatible with hyperinsulinemic hypoglycemia and hyperammonemia. A mutation in the GDH gene (Arg269His) confirmed the diagnosis in both the mother and the child. An important peculiarity of this case is the diagnosis of a 32-year-old woman, previously diagnosed with epilepsy through her daughter's diagnosis at a Pediatric Endocrinology Department and subsequently treated ineffectively with sodium valproate. We conclude that, as hypoglycemia may be subtle, the diagnosis of HI/HA should be considered in children or adults with seizures/epilepsy and hyperammonemia, serum ammonia being a simple screening test for the disease.     

The cytoskeletal protein septin 11 is associated with human obesity and is involved in adipocyte lipid storage and metabolism

Aims/hypothesis

Septins are newly identified members of the cytoskeleton that have been proposed as biomarkers of a number of diseases. However, septins have not been characterised in adipose tissue and their relationship with obesity and insulin resistance remains unknown. Herein, we characterised a member of this family, septin 11 (SEPT11), in human adipose tissue and analysed its potential involvement in the regulation of adipocyte metabolism.

Methods

Gene and protein expression levels of SEPT11 were analysed in human adipose tissue. SEPT11 distribution was evaluated by immunocytochemistry, electron microscopy and subcellular fractionation techniques. Glutathione S-transferase (GST) pull-down, immunoprecipitation and yeast two-hybrid screening were used to identify the SEPT11 interactome. Gene silencing was used to assess the role of SEPT11 in the regulation of insulin signalling and lipid metabolism in adipocytes.

Results

We demonstrate the expression of SEPT11 in human adipocytes and its upregulation in obese individuals, with SEPT11 mRNA content positively correlating with variables of insulin resistance in subcutaneous adipose tissue. SEPT11 content was regulated by lipogenic, lipolytic and proinflammatory stimuli in human adipocytes. SEPT11 associated with caveolae in mature adipocytes and interacted with both caveolin-1 and the intracellular fatty acid chaperone, fatty acid binding protein 5 (FABP5). Lipid loading of adipocytes caused the association of the three proteins with the surface of lipid droplets. SEPT11 silencing impaired insulin signalling and insulin-induced lipid accumulation in adipocytes.

Conclusions/interpretation

Our findings support a role for SEPT11 in lipid traffic and metabolism in adipocytes and open new avenues for research on the control of lipid storage in obesity and insulin resistance.

     

Prevention of Recurrent Thrombosis in Antiphospholipid Syndrome: Different from the General Population?

Antiphospholipid syndrome (APS) is characterized by arterial and/or venous thrombosis with or without pregnancy morbidity in the presence of autoantibodies targeting proteins that associate with membrane phospholipids, termed “antiphospholipid antibodies” (aPL). Management of arterial and venous thromboses shares some similarities with management of arterial and venous thromboses in the general population; however, there are key differences. The majority of studies addressing management of thrombotic APS focus on secondary prevention. Vitamin K antagonists (VKA) are typically used for secondary prevention of venous thromboembolism in APS. Optimal management of isolated arterial thrombosis, in particular ischemic stroke, in patients with APS is controversial, and proposed therapeutic options have included antiplatelet agents and VKA. Primary prophylaxis in aPL-positive patients should be an individualized decision taking into account patient-specific risks. There may be a role for adjuvant therapies such as hydroxychloroquine, vitamin D, statins, or novel therapeutics in specific patient populations.     

Effect of hospital on variation in visual acuity and vision‐specific quality of life after cataract surgery

Objective To evaluate the contribution of hospital‐to‐hospital variability in changes in clinical and health‐related quality of life outcomes among patients undergoing cataract extraction by phacoemulsification. Methods Prospective observational study of 14 public hospitals. We recruited consecutive patients on waiting lists for cataract extraction. Clinical data were collected prior to the intervention and 6 weeks afterward. Subjects completed the visual function index (VF‐14) prior to the procedure and 3 months afterward. Univariate and multivariate analysis were performed for visual acuity and VF‐14 scores. Results Substantial differences were observed across the 14 hospitals. At baseline, mean visual acuity ranged from 0.16 to 0.34, and mean VF‐14 scores ranged from 48.06 to 75.89. Following cataract extraction, the mean improvement in visual acuity ranged from 0.35 to 0.57 and in VF‐14 scores from 10.94 to 41.70. The ranges were even more pronounced among patients with low visual acuity or low VF‐14 scores prior to the intervention. Significant differences remained in multivariate analysis. Within the multivariate analysis, the variable ‘hospitals’ had an R² of 0.069 for the visual acuity model and of 0.073 for the VF‐14 model, 20% and 13%, respectively, of the total variability explained. Variation was also observed within geographic regions. Conclusions Outcomes of patients undergoing cataract extractions vary widely from hospital to hospital, even within the same geographic region, explaining an important part of the results. Quality improvement efforts should concentrate on patients with low pre‐intervention visual acuity or vision‐related disability to reduce this variability in outcomes.     

Peroxisome proliferation and antioxidant enzymes in transplanted mussels of four basque estuaries with different levels of polycyclic aromatic hydrocarbon and polychlorinated biphenyl pollution

We aimed to determine the effects of changes in polycyclic aromatic hydrocarbon (PAH) and polychlorinated biphenyl (PCB) bioavailability on peroxisome proliferation and antioxidant enzymes to assess their potential use as pollution biomarkers. For this, mussels (Mytilus galloprovincialis) were sampled in Txatxarramendi and transplanted to Arriluze, Muskiz, and Plentzia (northern Spain), and vice versa. Arriluze was the most heavily polluted site, followed by Plentzia, Txatxarramendi, and Muskiz. Animals transplanted from a polluted station to a cleaner station lost contaminant load in three to six weeks, and when transplanted to a more polluted station, they accumulated PAHs and PCBs accordingly. Peroxisomal acyl-A oxidase (AOX) activity was the highest in animals from Arriluze, and animals transplanted to Arriluze showed increased AOX activity, reaching the levels of native mussels. Mussels from Txatxarramendi showed the lowest peroxisomal volume density (Vvp). Among mussels from Txatxarramendi, only those transplanted to Plentzia showed increased Vvp, whereas animals from Arriluze and Muskiz transplanted to Txatxarramendi after 2 d and six weeks, respectively, had decreased Vvp. Two days after transplant, superoxide dismutase and glutathione peroxidase activities were significantly lower in mussels from Arriluze and Muskiz, respectively, than in those from Txatxarramendi and than in animals transplanted to Txatxarramendi from these stations. In conclusion, transplant experiments with mussels are useful to assess the effects of pollution. Peroxisome proliferation, measured as induction of AOX or increased Vvp, shows great potential as a biomarker of pollution to be included in pollution monitoring programs. In the present work, we have demonstrated that peroxisome proliferation is a reversible phenomenon in mussels.