The Apex polyester fibre anterior cruciate ligament implant: operative procedure and early results

This paper describes the surgical method and instruments for placing and anchoring the Apex polyester fibre anterior cruciate ligament (ACL) reconstruction. It then reviews the early clinical findings and describes recent developments. At the time of review, 172 Apex replacements had been implanted in the UK in arthroscopically proven chronic ACL-deficient knees. These had been inserted at eight centres since 1987, and follow up was by a single observer assessing patients by questionnaire, clinical examination, stress X-ray and KT 1000 arthrometer. Patients less than 12 months from surgery were excluded, leaving 95 with a mean follow up of 27 months (range 13 to 66 months) on whom results are based. Assessment showed improved stability after operation and the Apex implant appears to provide a reliable method of stabilizing the ACL deficient knee within the confines of this short-term review. The authors feel that further trials are justified.     

NON-IgE-MEDIATED ASTHMA IN CHILDREN

ABSTRACT. Among 586 children with asthma, 484 (82 %) were found to have IgE-mediated ("extrinsic") asthma, and seventy-two (12 %) non-IgE ("intrinsic") asthma. The remaining 30 patients (6%) were classified as "intermediate", as they had serum IgE within or above serum IgE levels of healthy children but no allergy to common allergens. During a three-year study period, the seventy-two patients with intrinsic asthma as opposed to 84 patients with extrinsic asthma had significantly 1) more hyperinflation of the lungs, 2) more episodes of acute hospital admissions due to asthma and/or pneumonia, 3) more elevated serum IgG and IgM, and 4) more cultures from secretions of lower airways of Haemophilus influenzae and pneumococci. Further, although treated with corticosteroids, eleven of the children with intrinsic asthma showed progressive disease, judged from fixed and/or declining forced vital capacity followed by signs of lung fibrosis on repeated pulmonary X-rays. It is emphasized that children with intrinsic asthma may represent an entity of childhood asthma, in some cases with severe progression of disease within a few years.     

Genetic and physical mapping of the McKusick-Kaufman syndrome

McKusick-Kaufman syndrome is a human developmental anomaly syndrome comprising mesoaxial or postaxial polydactyly, congenital heart disease and hydrometrocolpos. This syndrome is diagnosed most frequently in the Old Order Amish population and is inherited in an autosomal recessive pattern with reduced penetrance and variable expressivity. Homozygosity mapping and linkage analyses were conducted using two pedigrees derived from a larger pedigree published in 1978. The PedHunter software query system was used on the Amish Genealogy Database to correct the previous pedigree, derive a minimal pedigree connecting those affected sibships that are in the database and determine the most recent common ancestors of the affected persons. Whole genome short tandem repeat polymorphism (STRP) screening showed homozygosity in 20p12, between D20S162 and D20S894 , an area that includes the Alagille syndrome critical region. The peak two-point LOD score was 3.33, and the peak three-point LOD score was 5.21. The physical map of this region has been defined, and additional polymorphic markers have been isolated. The region includes several genes and expressed sequence tags (ESTs), including the jagged1 gene that recently has been shown to be haploinsufficient in the Alagille syndrome. Sequencing of jagged1 in two unrelated individuals affected with McKusick-Kaufman syndrome has not revealed any disease- causing mutations.      

Urinary miRNA-377 and miRNA-216a as biomarkers of nephropathy and subclinical atherosclerotic risk in pediatric patients with type 1 diabetes

Background

Urinary microRNAs (miRNAs) play a role in the pathogenesis of chronic kidney disease (CKD).

A randomised,controlled, double-blind,cross-over pilot study assessing the effects of spironolactone,losartan and their combination on heart rate variability and QT dispersion in patients with chronic heart failure

Background and objective

The blocking of aldosterone or angiotensin II receptors improves mortality in patients with chronic heart failure. We explored whether combining losartan and spironolactone would have any added benefit on the known surrogate of mortality by using heart rate variability (HRV) and QT dispersion as our endpoints.

Methods

We designed a three-phase, consecutive, randomised, controlled, double-blind, cross-over pilot study to assess the effects of losartan alone (50 mg/day), spironolactone (25 mg/day) with angiotensin converting enzyme (ACE) inhibitor and, finally, losartan with spironolactone, on HRV and QT dispersion. We enrolled eight patients (aged 47 to 72 years, mean = 63.7 years), with New York Heart Association (NYHA) class II–III heart failure and ejection fraction (EF) < 35%, in the study at a university-affiliated hospital in Dundee, Scotland. Digital 24-hour Holter recordings were analysed for time-domain HRV and the 12-lead ECG was optically scanned and digitised for analysis of QT dispersion. Evaluations were done at baseline, and at six, 12 and 18 weeks from baseline.

Results

Losartan and spironolactone showed statistically significant, favourable effects on HRV, QT dispersion and mean heart rate (p < 0.05).

Conclusion

The data showed that in these patients with heart failure, the addition of spironolactone to an ACE inhibitor, or the use of losartan on its own, or the combination of losartan plus spironolactone induced a favourable sympathovagal balance. The drugs significantly improved HRV indices and QT dispersion further, and the combination appeared to be safe. However, no significant differences were seen between the effects of each of these regimes on HRV and QT dispersion.     

Fibrinogen potentiates the effect of interleukin-3 on early human hematopoietic progenitors

The effect of human fibrinogen on the proliferation of purified SBA- CD34+ human bone marrow progenitors was investigated in clonal cultures. Fibrinogen alone or in combination with erythropoietin had no significant effect. However, in the presence of recombinant human interleukin-3 (IL-3), fibrinogen increased significantly in a dose- dependent manner the number of mixed and burst-forming unit-ethrocyte-- derived colonies, whereas the number of other colonies did not significantly change. In the presence of fibrinogen, low concentrations of IL-3 (0.17 U/mL) produced three times more mixed colonies than without fibrinogen, reaching the number of colonies obtained with optimal concentrations of IL-3 (1.67 U/mL). Fibrinogen fragment D had the same effect in the presence of IL-3 as intact fibrinogen, whereas fibrinogen fragment E and human collagen IV did not. This effect was not mediated by integrins, because peptides or monoclonal antibodies that block fibrinogen binding on integrins alpha IIb beta 3, alpha v beta 3 (RGD-peptides), alpha m beta 2 (OKM-1), and alpha x beta 2 (HC1/1) did not affect the observed mitogenic effect. The mitogenic effect of fibrinogen and its D fragment was not mediated by induction of IL-6 or granulocyte--colony-stimulating factor secretion, because it was not inhibited by blocking antisera against these two growth factors. Our results indicate that fibrinogen potentiates the effect of IL-3 on primitive hematopoietic progenitors and suggest that the mitogenic effect of fibrinogen could be mediated via a specific mitogenic receptor that does not belong to the integrin family.