Whole body vibration in cystic fibrosis--a pilot study.

INTRODUCTION: In cystic fibrosis (CF), bone mass deficits as well as a lack of muscle mass and force have been described. The bone mass deficits are thought to be at least in part secondary to the reduced muscle mass. Whole body vibration has recently been suggested as an effective technique to increase muscle force and power. The aim of this pilot study was to evaluate the compliance and safety of a side-alternating, whole body vibration platform in patients with CF and to assess its effects on muscle force, muscle power, bone mass and lung function. PATIENTS AND METHODS: Eleven adult CF patients participated in a six-months home-based training programme on a whole body vibration platform. Muscle force and power were assessed with three standard manoeuvres on a ground reaction force plate at regular intervals. Bone densitometry was performed at the spine, the radius and the tibia using quantitative computerized tomography. RESULTS: Regular cardiovascular monitoring did not show any critical drop in oxygen saturation or blood pressure. Lung function remained relatively constant with a median FEV1 change [% of norm] of -3.1% (range -7-20). Trabecular density at the spine and parameters of bone density and geometry at the radius and tibia did not show consistent changes. A median decrease of -0.3% (-31.0-17.9) for muscle force and a median increase of 4.7% (-16.4-74.5) for muscle power and 6.6% (-0.9-48.3) for velocity was noted in the two-leg jump. In the one-leg jump, a median increase of 6.7% (-8.5-24.3) for muscle force was measured. CONCLUSIONS: Whole body vibration was well tolerated in the majority of the study participants. Most patients were able to increase peak force in the one-leg jump. In the two-leg jump, velocity and muscle power increased with equal or decreased muscle force. This may indicate an improvement in neuromuscular and intramuscular co-ordination (and therefore efficiency) with less muscle force necessary to generate the same power.

Effect of growth hormone therapy on nitric oxide formation in cystic fibrosis patients.

Airway nitric oxide production is decreased in cystic fibrosis. As growth hormone therapy has been shown to increase nitric oxide production in growth hormone-deficient patients, it may also affect nitric oxide production in patients with cystic fibrosis. The objective of the present study was to investigate the effect of growth hormone therapy on systemic and airway nitric oxide formation in patients with cystic fibrosis. Nitric oxide metabolites in serum and urine, amino acid concentrations in serum and sputum, as well as exhaled nitric oxide, were measured in children with cystic fibrosis before, during and after 1 yr of treatment with human growth hormone. Nitric oxide metabolite concentrations increased significantly in serum and urine during the treatment period. Serum amino acid concentrations (including l-arginine, the substrate for nitric oxide synthases) also increased during treatment. The systemic bioavailability of l-arginine for nitric oxide synthases, expressed as ratio of l-arginine/l-ornithine+lysine, remained unchanged. In contrast, l-arginine concentrations in sputum decreased significantly during growth hormone treatment, as did exhaled nitric oxide levels. Treatment with growth hormone in children with cystic fibrosis decreases exhaled nitric oxide by reducing the concentration of l-arginine in the airways.

Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency.

Combined pituitary hormone deficiency (CPHD) has been linked with rare abnormalities in genes encoding transcription factors necessary for pituitary development. We have isolated LHX3, a gene involved in a new syndrome, using a candidate-gene approach developed on the basis of documented pituitary abnormalities of a recessive lethal mutation in mice generated by targeted disruption of Lhx3 (ref. 2). LHX3, encoding a member of the LIM class of homeodomain proteins, consists of at least six exons located at 9q34. We identified a homozygous LHX3 defect in patients of two unrelated consanguineous families displaying a complete deficit in all but one (adrenocorticotropin) anterior pituitary hormone and a rigid cervical spine leading to limited head rotation. Two of these patients also displayed a severe pituitary hypoplasia, whereas one patient presented secondarily with an enlarged anterior pituitary. These LHX3 mutations consist of a missense mutation (Y116C) in the LIM2 domain at a phylogenetically conserved residue and an intragenic deletion predicting a severely truncated protein lacking the entire homeodomain. These data are consistent with function of LHX3 in the proper development of all anterior pituitary cell types, except corticotropes, and extrapituitary structures.

Functional activity of CD44 isoforms in haemopoiesis of the rat.

Expression of CD44 is involved in the maturation as well as the homing of haemopoietic progenitor cells. Whether these processes are mediated by CD44 standard (CD44s) or variant (CD44v) isoforms is unknown. To assign functional activities of CD44 in haemopoiesis of the rat to distinct isoforms, ligand binding of haemopoietic progenitor cells was inhibited by monoclonal antibodies recognizing an epitope on CD44s (Ox50) or CD44 exon v6, (1.1ASML). The vast majority of rat bone marrow cells (BMC) as well as stromal cells and non-adherent cells in long-term bone marrown culture (LTBMC) expressed CD44s. Bone marrow cells and non-adherent cells in LTBMC, but not the stromal cells, also contained a population of large and granulated cells, which stained with anti-CD44v6. In vivo and in vitro reconstitution experiments revealed that homing of BMC as well as settlement on stromal elements was influenced exclusively by anti-CD44s, which also inhibited proliferation of progenitor cells. Anti-CD44v6 had no influence on homing and seeding, but interfered with stroma formation and progenitor maturation. Finally, restoration of functional activity of T-lineage cells was impaired in the presence of anti-CD44v6. The data indicate that CD44s and CD44v6 fulfilled distinct functions in haemopoiesis of the rat. Although CD44s facilitated homing and expansion of stem cells, progenitor cells, CD44v6 was involved in differentiation processes, particularly of lymphoid progenitor cells.

Phenotypic classification of male pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency.

Conversion of testosterone (T) to dihydrotestosterone (DHT) in genital tissue is catalysed by the enzyme 5 alpha-reductase 2, which is encoded by the SRD5A2 gene. The potent androgen DHT is required for full masculinization of the external genitalia. Mutations of the SRD5A2 gene inhibit enzyme activity, diminish DHT formation, and hence cause masculinization defects of varying degree. The classical syndrome, formerly described as pseudovaginal perineoscrotal hypospadias, is characterized by a predominantly female phenotype at birth and significant virilization without gynecomastia at puberty. We investigated nine patients with steroid 5 alpha-reductase 2 deficiency (SRD). Phenotypes, which were classified according to the severity of the masculinization defect, varied between completely female (SRD type 5), predominantly female (SRD type 4), ambiguous (SRD type 3), predominantly male with micropenis and hypospadias (SRD type 2), and completely male without overt signs of undermasculinization (SRD type 1). T/DHT-ratios were highly increased ( > 50) in the classical syndrome (SRD type 5), but variable in the less severe affected patients (SRD types 1-4) (14-35). Mutations in the SRD5A2 gene had been characterized using PCR-SSCP analysis and direct DNA sequencing. A small deletion was encountered in two patients, while all other patients had single base mutations which result in amino acid substitutions. We conclude that phenotypes may vary widely in patients with SRD5A2 gene mutations spanning the whole range from completely female to normal male without distinctive clinical signs of the disease. Hence, steroid 5 alpha-reductase deficiency should be considered not only in sex reversed patients with female or ambiguous phenotypes, but also in those with mild symptoms of undermasculinization as encountered in patients with hypospadias and/or micropenis. A classification based on the severity of the masculinization defect may be used for correlation of phenotypes with enzyme activities and genotypes, and for comparisons of phenotypes between different patients as the basis for clinical decisions to be made in patients with pseudohermaphroditism due to steroid 5 alpha-reductase 2 deficiency.

[Thoracoscopic treatment of spontaneous pneumothorax using fibrin pleurodesis]. / Thorakoskopische Behandlung des Spontanpneumothorax mittels Fibrinpleurodese.

In 33 patients with a recurrent spontaneous pneumothorax, a thoracoscopic pleurodesis with fibrin glue was performed under local anesthesia. During an average postoperative observation period of 4 years the relapse frequency was 39% (13 cases). In these cases thoracotomy was performed and a new relapse of pneumothorax occurred in 3 patients (23%): Application of thoracoscopy with fibrin glue pleurodesis should only be applied in those patients without large emphysema vesicles and without large coalescences. Under these conditions the relapse frequency could be reduced to 26%. The thoracoscopic treatment of recurrent pneumothorax by using fibrin glue and local anesthesia in well selected patients is an alternative procedure to thoracotomy.