Search PubMed⌕ Search

Biomedical subjects

J Harle

Publications and source records attributed to J Harle.

13 recordsLinked to original sources

Effects of ultrasound on transforming growth factor-beta genes in bone cells.

Therapeutic ultrasound (US) is a widely used form of biophysical stimulation that is increasingly applied to promote fracture healing. Transforming growth factor-beta (TGF-beta), which is encoded by three related but different genes, is known to play a major part in bone growth and repair. However, the effects of US on the expression of the TGF-beta genes and the physical acoustic mechanisms involved in initiating changes in gene expression in vitro, are not yet known. The present study demonstrates that US had a differential effect on these TGF-beta isoforms in a human osteoblast cell line, with the highest dose eliciting the most pronounced up-regulation of both TGF-beta1 and TGF-beta3 at 1 hour after treatment and thereafter declining. In contrast, US had no effect on TGF-beta2 expression. Fluid streaming rather than thermal effects or cavitation was found to be the most likely explanation for the gene responses observed in vitro.

Acoustics↗

Gene expression profiling of bone cells on smooth and rough titanium surfaces.

Titanium (Ti) and Ti alloys are widely used as dental and orthopaedic implants, but the effects of the surface characteristics of these materials on the response of cells and target tissues is not well understood. The present study has therefore examined the effects of a rough Ti (RT) and a smooth Ti (ST) surface on human bone cells in vitro. Scanning electron microscopy showed attachment and spreading of cells on both surfaces. Expression profiling using ATLAS gene arrays showed marked differences in gene responses after 3 h of culture. A number of osteoblast genes were identified as "roughness response" genes on the basis of changes in expression on the RT compared with the ST surfaces. The surface roughness of Ti was thus found to have a profound effect on the profile of genes expressed by the bone cells, and suggests that improvements in the biological activity and possibly the clinical efficacy of these materials could be achieved by selective regulation of gene expression mediated by controlled modification of Ti surface.

Adult↗

Roughness response genes in osteoblasts.

Titanium (Ti) and Ti alloys are widely used as dental and orthopedic implants, but the effects of the surface characteristics of these materials, including roughness, on the response of target tissues in vivo are not well understood. The present study has therefore examined the effects of a moderately rough (sand-blasted, acid-etched; SLA) Ti surface, a highly rough (plasma-sprayed; TPS) surface, and a smooth surface (SMO) on bone cells in vitro. X-ray photoelectron spectroscopy showed that these surfaces had similar surface chemistry, while scanning electron microscopy suggested that the SLA provided a transiently less biocompatible surface, with initially less well-attached cells. SLA also delayed bone cell growth compared with SMO, whereas the TPS surface elicited the greatest increase in cell numbers. In addition, expression profiling using the ATLAS gene array showed marked differences in gene responses after 3 h of incubation; this increased further after 24 h, with TPS generating the largest number of up- and down-regulated genes compared with SLA and SMO. A number of osteoblast genes were also identified as 'roughness' genes on the basis of their similar response on SLA and TPS, compared with SMO. These findings show, for the first time, that the surface roughness of Ti has a profound effect on the profile of genes expressed by bone cells and suggest that improvements in the biological activity and possibly the clinical efficacy of these materials could be achieved by selective regulation of gene expression mediated via modification of surface roughness.

Adult↗

Effects of ultrasound on the growth and function of bone and periodontal ligament cells in vitro.

The effects of therapeutic ultrasound (US) on tissue healing processes in vivo are likely to involve US-induced changes in key cellular functions. However, these have not yet been clearly delineated and the present study has, therefore, examined the effects of a single 5-min CW exposure of 3.00-MHz US on the growth and functional activity of a human osteoblast-like cell line (MG63 cells) and human periodontal ligament (PDL) cells in vitro. Although cell proliferation was found to be largely unaffected by spatial average intensity (I(SA)) values of between 140-990 mW/cm(2), flow cytometry (FCM) analysis showed that there were pronounced and differential effects on cell function. Thus, bone-associated proteins were down-regulated, whereas collagen type I (COL I) was unaffected and fibronectin (FN) was up-regulated at low intensities in MG63 cells. In contrast, bone protein expression was found to be dose-dependent, and FN and COL I were down-regulated in PDL cells. These results show that US has potentially important effects on the functional activities of connective tissue cells in vitro, which could markedly influence tissue repair and regeneration processes in vivo.

Cell Division↗

Lack of efficacy of riluzole in the treatment of peripheral neuropathic pain conditions.

OBJECTIVE: To assess the efficacy, tolerability, and safety of riluzole in the treatment of peripheral neuropathic pain conditions. BACKGROUND: Both basic and clinical research has demonstrated that drugs with sodium channel and NMDA antagonism can be effective in alleviating neuropathic pain. Riluzole, a drug currently used for treatment of ALS, possesses these properties. It was hypothesized that riluzole would be effective in reducing the pain in subjects with peripheral neuropathic pain. METHODS: Two randomized, placebo-controlled, crossover studies were performed at two sites. Study 1 compared 100 mg/day of riluzole (the currently recommended dosage for treatment of ALS) versus placebo, and Study 2 compared 200 mg/day of riluzole versus placebo. Each treatment phase (both studies) was 2 weeks long, separated by 2-week wash-out periods. Outcome measures included change in the score on a 100-mm pain intensity visual analog scale, the Neuropathic Pain Scale, allodynia, hyperalgesia, and preference for study treatment phase. RESULTS: Twenty-two subjects completed Study 1, and 21 subjects completed Study 2. Four subjects (two from each study) discontinued the study because of intolerable side effects. No statistical difference was found for any study outcome measure between riluzole and placebo for either study. In Study 1, pain intensity was more likely to increase than decrease with riluzole (mean treatment difference 8.7 mm; 95% CI -19.5 to +2.1 mm). In Study 2, very slight pain reduction was observed with riluzole compared with placebo (mean treatment difference 1.4 mm; 95% CI -5.1 to +8.0 mm). In both studies, the majority of subjects chose "no change" in pain on the category relief scale after placebo and riluzole treatment phases. On study completion, no treatment preference was reported by 76% of the subjects in Study 1 and by 61% of the subjects in Study 2. CONCLUSIONS: Doses of riluzole at (100 mg) or above (200 mg) those used for the treatment of ALS were not effective in alleviating peripheral neuropathic pain.

Adult↗

Response to intravenous lidocaine infusion predicts subsequent response to oral mexiletine: a prospective study.

The local anesthetic sodium-channel blockers lidocaine and mexiletine reduce spontaneous and evoked activity in experimental neuroma models and have been reported to relieve a variety of clinical neuropathic pain conditions. The predictive value of relief from an intravenous lidocaine infusion (IVL) for subsequent relief from a 4-week trial of oral mexiletine was assessed in a prospective study of nine subjects with chronic neuropathic pain of peripheral origin. Subjects received IVL, 2 mg/kg and 5 mg/kg, over 45 min during separate sessions in random order under double-blind conditions. One week later, a 4-week titrating trial of oral mexiletine was initiated. Both doses of IVL significantly reduced pain visual analogue scores (VAS) scores. Although IVL 5 mg/kg produced significantly higher pain relief scores than IVL 2 mg/kg, subjects responded in a highly consistent manner to the two IVL. Subsequent response to oral mexiletine was significantly correlated with the average response to the two IVL. Mexiletine dose and blood levels were not correlated with pain relief. The results suggest that IVL may be a valuable tool in selecting patients for oral therapy with analogous drugs.

Administration, Oral↗

[Prognostic value of bad distal irrigation incides, revealed by irrigraphy in arteritis of the lower limbs (author's transl)].

A study is made in this paper of the prognostic significance of a very low distal index (index 6), revealed by irrigraphy. On the basis of examination of 55 case histories, the patients were divided into two groups A and B as a function of the distal indices at the root of the limb. The amputation rate was very high in both groups, but the prognosis was better in group A where the situation could be improved by restorative surgery at a high level. Analysis of the surgical possibilities has indicated that restorative surgery at a high level is a promising procedure, especially in group A. Surgery at the femoro-popliteal level yielded less satisfactory results because of the often considerable degradation of the arterial bed further downstream. Sympathectomy appears to be a useful supplement to restorative surgery in appropriate cases. The concept of the reduced distal index is also valuable for detecting cases of arteritis which are still well compensated but are in danger of vascular failure (dangerous claudications).

Arteries↗

Effects of therapeutic ultrasound on osteoblast gene expression.

Ultrasound (US) is commonly used as a physiotherapy aid for a number of types of injury to soft connective tissues and for fracture healing. However, the precise effects of therapeutic US on tissue healing processes are not clearly understood, although they are likely to involve changes in key cellular functions. The present study has therefore examined the effects of several US intensity levels on the activity of two bone-associated proteins, alkaline phosphatase (ALP) and osteopontin (OP) in a human cell line, MG63, using RT-PCR. ALP showed progressively higher expression with increasing US intensities, whereas OP responded differently, showing down-regulation at 120 mW/cm2, the lowest US exposure. OP expression was considerably less affected overall compared with the relative response of ALP to the same US doses. The results show that there is a differential response to therapeutic levels of US, since ALP and OP clearly exhibited gene-specific response profiles. These findings suggest that modifying the parameters of US exposure could be used to improve repair and regeneration processes and enhance the clinical efficacy of implanted biomaterials for tissue engineering.

Journal Article↗

The mechanisms of venous stasis in post-phlebitic syndromes.

Venous stasis in post-phlebitic syndromes may be caused by several physiopathological processes. Phlebography and functional investigations (Doppler, occlusive rheoplethysmography) enables us to make a fairly precise analysis of the causal factors: --The obstruction of a large venous collector defines the obstructive syndromes. The size of the stasis depends on the functional value of the substitutional channels; distinction may be made between compensated obstructive syndromes (with efficient substitutional circulation) and poorly or non-compensated obstructive syndromes. --Orthostatic reflux in devalvulated deep veins constitutes another factor of stasis. Distinction to be made between minor reflux, and major reflux with massive reflux in the great trunks and associated insufficiency of the tibial communicators. --Post-phlebitic superficial venous insufficiency is often observed. Its physiopathology is basically no different to that of primary varices, the functioning of the tibial communicators is often perturbed. --The restrictive syndrome, result of functional investigations, corresponds to a reduction of the venous distensibility whose effects are superadded to those of the syndromes described above.

Blood Flow Velocity↗

[Value of rheoplethysmography with venous occlusion in the detection of venous thrombosis].

The study of the correlations between occlusive rheoplethysmography (RPO) and phlebography, carried out in 170 explorations, shows an over-all rate of 78.3% correct correlations. This correlations is more accurate for negative RPOs (91.8%) than for positive ones (59.6%). There are in fact few inaccurate negatives (i.e. venous thrombosis with negative RPO) but there are a certain number of erroneous positives, linked basically with states of cardiac insufficiency and phlebitic after-effects. The RPO examination is a useful complement to the clinical data; it means that the number of necessary phlebographical examinations can be cut down, and it provides a useful guide to treatment options.

Diagnosis, Differential↗

[Study of venous distensibility using plethysmography with venous occlusion in post-phlebitic syndromes].

Venous distensibility has been studied in the cases of twelve patients presenting a post-phlebitic syndrome, compared with five patients with primary varicose veins. In the post-phlebitic syndromes we note far fewer symptoms of venous distensibility, whereas in the cases of varicose veins there is an increase of venous distensibility. Statistics of the delta V max. 50 and the symptoms of distensibility are given in a recapitulatory table, and a diagram.

Humans↗

[The clinical problem of false phlebitis].

This is a study of some of the problems presented by "false phlebitis". This problem arises when patients are wrongly considered as post-phlebitis when the venous system is intact. There is also the problem of false diagnoses of venous thrombosis leading to anticoagulant treatment which is not indicated or to surgical measures, equally unjustified for the prevention of possible pulmonary embolism. Finally there is the problem of venous compression simulating thrombosis where the diagnosis of thrombosis leads to delay in the institution of specific treatment. The current means of diagnosis, phlebography and functional investigations, should permit a significant reduction in the number of these errors of diagnosis which may be of great disadvantage to the patients.

Diagnostic Errors↗