Identification of 32 novel mutations in the factor VIII gene in Indian patients with hemophilia A

Seventy-five unrelated hemophilia A patients from India were analyzed for factor VIII gene defects. Intron 22 inversion was identified in 22 patients and intron 1 inversion in 2 patients. In the remaining 51 patients without inversions screening the FVIII gene by denaturing high performance liquid chromatography (DHPLC) revealed 42 different mutations in 44 unrelated subjects. These included 14 missense, 7 nonsense, 9 splice site, 8 deletional, 3 insertional mutations and one indel mutation. Of these, 32 were novel gene alterations. The hotspots included intron 22 inversion, CpG and adenine runs.     

Facilitating the WHO expanded program of immunization: the clinical profile of a combined diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine.

BACKGROUND: Vaccines are important weapons in the fight against infectious diseases. The World Health Organization (WHO) Expanded Program on Immunization (EPI) has been extended to include recommendations for hepatitis B and Haemophilus influenzae type b (Hib) vaccinations. The WHO has recommended that combined vaccines be used where possible, to reduce the logistic costs of vaccine delivery. This paper reviews the efficacy, safety and cost-effectiveness of Tritanrix-HB/Hib, the only commercially available combined diphtheria, tetanus, whole cell pertussis, hepatitis B and conjugated Hib vaccine. METHODS: The immunogenicity and reactogenicity results of five published clinical trials involving Tritanrix-HB/Hib in a variety of immunization schedules and countries were reviewed. Based on these data and cost-effectiveness studies, an assessment of its suitability for use in national immunization programs was made. RESULTS: Tritanrix-HB/Hib has shown excellent immunogenicity in clinical trials using a variety of schedules, with no reduced immunogenicity observed for any of the components of the combined vaccine. It has similar reactogenicity to DTPw vaccines alone. Pharmacoeconomic analyses have shown combined DTP-HB/Hib vaccines to be cost-effective compared to separate vaccines. CONCLUSIONS: Replacement of DTPw vaccination by Tritanrix-HB/Hib can be done without modifying the existing national immunization programs. This should facilitate widespread coverage of hepatitis B and Hib vaccinations and their rapid incorporation into the EPI.     

Delirium: Its historical evolution and current interpretation

Delirium was one of the first mental disorders ever to be described, though it remains an elusive concept to this day. Historically, delirium has developed from the prototype of acute confusion with psychomotor agitation. It was thought to be caused by the withdrawal of substance dependence or severe somatic diseases accompanying by fever; however only in the 20th century, it was concluded that delirium and similar states manifest themselves as a consciousness disorder, and is not a specific state of somatic diseases. Four core features defines delirium at present: a disturbance of consciousness, a disturbance of cognition, limited course and external causation. However, these features do not include common manifestations of delirium in elderly patients with dementia; therefore the concept of delirium should be revised and corrected.     

Exercise training after coronary angioplasty improves cardiorespiratory function

Aim. The aim of this prospective randomized study was to evaluate the impact of long-term aerobic exercise training on respiratory function, left ventricular systolic function and remodeling in patients with coronary heart disease and ischemic heart failure after successful angioplasty. Design. Patients (n=185) have undergone Doppler echocardiography and ergospirometry. Ninety-five patients practiced 6 month-term aerobic exercise training, less by 10% to their anaerobic threshold. Ninety patients were studied as controls. They were given only drug treatment without training. Measurements were repeated after 6 and 12 months. Results. Training group patients after 6 months showed significant (p<0.05) improvement in exercise capacity, oxygen consumption and ventilating equivalents. The Doppler echocardiographic findings revealed significant (p<0.05) improvement in ejection fraction, left ventricular and atria morphometric data. Improved ergospirometric and echocardiographic data were established after 12 months, too. Conclusions. Long-term aerobic exercise training is an effective and workable measure improving respiratory efficiency, left ventricular systolic function, attenuating negative remodeling and stopping further progression in patients with coronary heart disease and chronic heart failure after successful angioplasty.     

Eight novel F13A1 gene missense mutations in patients with mild FXIII deficiency: in silico analysis suggests changes in FXIII-A subunit structure/function

Mild FXIII deficiency is an under-diagnosed disorder because the carriers of this deficiency are often asymptomatic and reveal a phenotype only under special circumstances like surgery or induced trauma. Mutational reports from this type of deficiency have been rare. In this study, we present the phenotypic and genotypic data of nine patients showing mild FXIII-A deficiency caused by eight novel heterozygous missense mutations (Pro166Leu, Arg171Gln, His342Tyr, Gln415Arg, Leu529Pro, Gln601Lys, Arg703Gln and Arg715Gly) in the F13A1 gene. None of these variants were seen in 200 healthy controls. In silico structural analysis of the local wild-type protein structures (activated and non-activated) from X-ray crystallographic models downloaded from the protein databank identified potential structural/functional effects for the identified mutations. The missense mutations in the core domain are suggested to be directly influencing the catalytic triad. Mutations on other domains might influence other critical factors such as activation peptide cleavage or the barrel domain integrity. In vitro expression and subsequent biochemical studies in the future will be able to confirm the pathophysiological mechanisms proposed for the mutations in this article.     

Current management of late onset neonatal bacterial sepsis in five European countries

Late onset neonatal sepsis (LOS) has a high mortality and the optimal management is poorly defined. We aimed to evaluate new expert panel-derived criteria to define LOS and characterize the current management and antibiotic susceptibility of LOS-causing organisms in Europe. A prospective observational study enrolled infants aged 4 to 90 days in five European countries. Clinical and laboratory findings as well as empiric treatment were recorded and patients were followed until the end of antibiotic therapy. Failure was defined as a change of primary antibiotic, no resolution of clinical signs, appearance of new signs/pathogens or death. Antibiotic therapy was considered appropriate if the organism was susceptible to at least one empiric antibiotic. 113 infants (median age 14 days, 62 % ≤1500 g) were recruited; 61 % were culture proven cases (28 CoNS, 24 Enterobacteriaceae, 11 other Gram-positives and 6 Gram-negative non-fermentative organisms). The predictive value of the expert-panel criteria to identify patients with a culture proven LOS was 61 % (95 % CI 52 % to 70 %). Around one third of Enterobacteriaceae were resistant to ampicillin + or cefotaxime + gentamicin but only 10 % to meropenem. Empiric treatment contained a total of 43 different antibiotic regimens. All-cause mortality was 8 % with an additional 45 % classified as failure of empiric therapy, mainly due to change of primary antibiotics (42/60). Conclusions: The expert panel—derived diagnostic criteria performed well identifying a high rate of culture proven sepsis. Current management of LOS in Europe is extremely variable suggesting an urgent need of evidence-based guidelines.     

Clinical outcomes of patients with lumbar disc herniation, selected for one-level open-discectomy and microdiscectomy

The aim of our study was twofold: firstly, to compare the preoperative and postoperative results at mid-term follow-up periods along with the data of the control group. Secondly, to evaluate the effectiveness among open-discectomy and microdiscectomy surgical groups. In the present study, we investigated a cohort of 100 patients with the lumbar disc herniation causing low back pain compared to 100 subjects of the control group with the non-specific low back pain by applying physical activity, pain scale, Short Form 36 General Health Questionnaire and additional postoperative records of patient’s satisfaction and complications level, consumption of analgesics, and return to work status. The quantitative analysis of all questionnaires showed substantial differences in the preoperative and postoperative groups. The best results were achieved at the second year follow-up period. However, there were no statistically significant differences in both the examined surgical subgroups (p > 0.05). In addition, we estimated from moderate to great statistical significance (p < 0.01–0.05) among preoperative and overall postoperative results: PHC and MHC in the SF-36, Oswestry and VAS. The total increased satisfaction, reherniation rate and return to work frequency comprised 40, 9 and 64%, respectively. The analgesics were still indicated for 21% of the patients. The results of the present study suggest of sufficient decompression in both surgical groups, as the health-related quality of life parameters (Oswestry, VAS and SF-36) were defined as clinically improved. Regardless of persisted minor pain in both areas, it remained greater in the low back than in the leg, which should be held for beneficial to decompressive surgery.     

Management of acute traumatic atlas fractures

OBJECTIVE: A prospective review of a clinical series was performed. The treatment features of atlas fractures with and without associated axis injuries were investigated. METHODS: Twenty-nine patients were investigated. RESULTS: No displaced fractures were treated with a cervical orthosis. Patients with displaced fractures were managed with a halo vest immobilization; 96.4% patients had a solid fusion at their last follow-up evaluations. CONCLUSIONS: Isolated not displaced or combined with not displaced axis fractures atlas fractures can be treated effectively with a rigid cervical collar alone. Isolated displaced fractures or not displaced but with concurrent displaced axis fractures require immobilization by the halo vest.