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Biomedical subjects

S Hellem

Publications and source records attributed to S Hellem.

At least 19 recordsLinked to original sources

Non-submerged implants in the treatment of the edentulous lower jar. A 2-year longitudinal study.

Non-submerged ITI Bonefit implants (ITI Dental Implant System) were inserted in edentulous lower jaws of 46 patients. The patients were provided with either a fixed prosthesis or an overdenture, and has been followed during a 2-year-period. At the 1-year examination, the suprastructures were removed permitting test of the individual implant stability. Radiographic examinations were performed in connection with the loading of the implants and at the 1-year examination. In total 216 implants were inserted. 4 implants were lost before loading and 4 during the 2nd year of function, which gives a survival rate after 1 year 98% and after 2 years of 96%. The mean marginal bone loss during the first year of function was 0.1 mm. However, the marginal bone changes had a high degree of variation and four implants showed a severe bone loss. The intention is to follow this patient group with annual examinations during 5 years.

Adult

A bone tissue integrated single fibre laser Doppler flowmeter probe.

Laser Doppler Flowmetry was developed and evaluated mainly for measuring blood flow in exposed or superficial tissue layers like skin. Results showed large variation coefficients between juxtaposed skin sites with apparently homogeneous blood perfusion. Spatial differences in blood flow as well as anatomical differences probably explain the obtained results. Vasomotion, hereto only discovered with a microscopic technique, was recorded and evaluated for the first time. Similar results had been obtained in previous bone perfusion studies. The LDF technique has also been used extensively for skin irritancy tests and microvascular effects of vasoactive substances and drugs. An in vivo model in calibrating LDF quantitatively showed a linear relationship between LDF output signal and total blood flow in the range 0-300 ml min-1 100 g-1. This quantitative calibration is however tissue specific. Most tissues of interest are not superficial. The single fibre LDF provides additional power in studying deep tissue physiology and trauma-induced changes in regulation of microvascular perfusion. Furthermore long-term studies require implantable and biocompatible probes and this could be fulfilled using the SFLDF technique in combination with a tissue-integrated titanium probe. Implantation of the titanium probes initially creates some trauma to the vascular bed in the bone marrow but almost none in the opposite cortical bone layer. The healing process enhances the blood perfusion during the first weeks. The increased perfusion can be due to different parameters such as angiogenesis. The histological findings support this hypothesis. This gives preference to the tissue-integrated probe where interference with the tissue should be avoided. The integrated probe technique has only been evaluated in bone tissue. Modification of the probe shape and dimension, however, would make it suitable for other tissues as well.

Animals

Protein phosphorylation substrates in normal and neoplastic squamous epithelia of the human upper aero-digestive tract.

Protein phosphorylation was studied in crude and in protein kinase C (Pk-C)-enriched preparations from squamous cell carcinomas and normal mucosa of the human upper aero-digestive tract. In crude soluble preparations from neoplastic mucosa we found a 5-fold higher basal endogenous phosphorylation when compared to normal mucosa. In particulate fractions the increase was 3-fold. SDS-PAGE and autoradiography of phosphorylated proteins in crude soluble tumor extracts showed bands corresponding to proteins with apparent molecular weights of 18, 37, 40-42, 52, 60, 62 and 90 kDa. In normal mucosa the phosphorylation of these proteins was very low or absent, except for the proteins with molecular weights of 40-42 and 52-55 kDa. Addition of Ca2+ or Ca2+/phospholipids to the reaction mixture caused phosphorylation of additional proteins with apparent molecular weight of 45-50 kDa in soluble preparations of tumors. Cyclic AMP or cGMP had no significant effect on the phosphorylation of endogenous proteins. In the partially purified, Pk-C-enriched fractions the phosphorylation in the presence of Ca2+/phospholipids was distinctly higher in tumors when compared to the phosphorylation observed in normal mucosa, and some phosphorylation substrates were detected only in tumor tissue. In order to find out whether the elevated basal phosphorylation was due to an endogenous activation of protein kinases, different inhibitors of serine/threonine protein kinases were tested. These inhibitors included: heat-stable cyclic AMP-dependent protein kinase (Pk-A) inhibitor, Pk-A inhibitor peptide (Wiptide), heparin and the Pk-C inhibitors peptide 19-36 and H-7. None of these inhibitors had any significant effect on the basal phosphorylation. In conclusion, our results show the existence of endogenous phosphorylation substrates in human squamous cell carcinomas from the upper aerodigestive tract, and indicates that there is a significantly higher basal and Pk-C specific phosphorylation of endogenous substrates in tumors compared to normal mucosa. This may be of importance for the transformation and altered growth regulation in epithelial tumors.

Aged

Tyrosine kinase activities in normal and neoplastic epithelia tissue of the human upper aero-digestive tract.

Tyrosine kinase activity was studied in the crude cytosolic and particulate fraction of normal mucosa and squamous cell carcinomas of the upper aero-digestive tract. In the presence of exogenously added phosphorylation substrate (Glu,Tyr4:1), the cytosolic tyrosine kinase activity was 6-fold higher in tumors compared to normal mucosa (p = 0.001), and in the particulate fraction the increase was 8-fold in tumors compared to normal mucosa. Different proposed tyrosine kinase inhibitors, including genistein, quercetin and the alpha-cyanocinnamide ST 638, were tested for their ability to inhibit phosphorylation of the synthetic tyrosine phosphorylation substrate. Phosphorylation of Glu,Tyr4:1 in tumors (cytosolic fraction) was reduced to 77.8 +/- 8.7% of the control value by 10 microM ST 638 (p less than 0.05), and to 50.7 +/- 10.4% by 100 microM quercetin (p less than 0.01). In normal mucosa (cytosolic fraction) the corresponding values were 41.7 +/- 16.6% in the presence of 10 microM ST 638 (p less than 0.05) and 32.1 +/- 5.8% in the presence of 100 microM quercetin (p less than 0.05). These inhibitors had no effect on the tyrosine kinase activity in the particulate fractions. Phosphorylation of endogenous proteins in the crude cytosolic fraction was evaluated by SDS-polyacrylamide gel electrophoresis after alkali treatment of the gels. Autoradiography of the gels treated in this manner revealed bands corresponding to phosphorylated proteins with apparent molecular weight of 18, 23, 37-38, 42-44 (double band), 53-55 (double band), 61 and 92-94 (double band) kD. Quercetin (100 microM) markedly reduced the phosphorylation of these proteins, while no effect of ST 638 could be seen. Heparin (20 micrograms/ml) stimulated the phosphorylation of three proteins with apparent molecular weight of 39 and about 72 kD, respectively, and inhibited the phosphorylation of 2 proteins with molecular weight of 92 and 53 kD in tumors. These features were observed in both tumors and normal tissue, with the exception that heparin only stimulated the 72 kD band in normal mucosa and that the phosphorylation was markedly higher in tumors. In summary, our results show an increased tyrosine phosphorylation in squamous cell carcinomas of the upper aero-digestive tract compared to normal oral mucosa. These differences and their origin might be of vital importance in the regulation of events leading to malignant transformation.

Aged

Protein kinase activities in neoplastic squamous epithelia and normal epithelia from the upper aero-digestive tract.

In the present study the activities of three different protein kinase were determined in squamous cell carcinoma from the upper aero-digestive tract, and compared with the activities in normal oral mucosa. The protein kinases investigated are: a) cAMP-dependent protein kinase; b) cGMP-dependent protein kinase, and c) casein kinase II. The basal protein kinase activity, when histone IIa was used as substrate, was about 3-fold higher in tumors, as compared to normal mucosa, in the soluble fraction (32.0 +/- 4.2 and 10.9 +/- 2.4 pmol 32P/mg prot. X min, respectively). In the particulate fraction the basal protein kinase activity was about 9 times higher in tumors as compared to normal mucosa (19.4 +/- 5.2 and 2.1 +/- 0.3 pmol 32P/mg prot X min, respectively). The protein kinase activity in the presence of cyclic nucleotide (cAMP/cGMP) minus the basal protein kinase activity was taken as the cAMP- and the cGMP-dependent protein kinase activity, respectively. Maximal protein kinase activity was obtained in the presence of 0.5 microM of cyclic nucleotide both in squamous cell carcinoma and normal mucosa. In the cytosolic fraction the cAMP-dependent protein kinase activity was 33.9 +/- 13.0 pmol 32P/mg prot. X min in tumors, and 28.2 +/- 5.8 pmol 32P/mg prot. X min in normal tissue, after stimulation with 0.5 microM cAMP. The cGMP-dependent protein kinase activity was 5-10% of the cAMP-dependent protein kinase activity, and no concentration-dependent stimulation with cGMP was seen. The cGMP-dependent protein kinase activity in the presence of 0.5 microM cGMP was 2.4 +/- 1.3 and 1.8 +/- 0.6 pmol 32P/mg prot. X min in tumors and normal mucosa, respectively. Casein kinase II activity was determined only in the cytosolic fraction and was found to be 3-fold higher in tumors as compared to normal mucosa (31.8 +/- 5.2 and 8.6 +/- 3.5 pmol 32P/mg prot X min, respectively). This study shows a general increase in histone phosphorylation and casein kinase activity in neoplastic squamous epithelia compared to normal epithelia. No evidence for an increase in cyclic nucleotide dependent protein kinase activities in neoplastic squamous epithelia was found. This study thus supports the idea that phosphorylation/dephosphorylation reactions may play an important role in the control of cell growth, differentiation and proliferation.

Aged

Titanium-coated hollow screw and reconstruction plate system (THORP) in mandibular reconstruction.

Clinical results are presented which have been obtained from mandibular reconstruction with the Titanium-coated Hollow Screw and Reconstruction-Plate system (THORP) in 7 selected patients. In 3 of the patients primary bone grafting was performed with simultaneous implantation of titanium fixtures for dental reconstruction. The reconstruction-plates have shown excellent functional stability with no failures, such as loosening of screws, within an observation period up to 2 1/2 years. The system was submitted to immediate full functional loading despite the limited number of 2-3 fixation screws for each end of the plate. Among several technical advantages of the system are the possibility of lingual plate application and reconstruction with a three-dimensionally free, adjustable condylar prosthesis.

Adult

Bone-plates for stabilizing Le Fort I osteotomies.

16 adults were treated by inferior repositioning of the maxilla. Miniaturized plates were used for stabilizing the jaw in its new position. No interpositional bone grafts were used but the osteotomy spaces were covered by strips of cancellous iliac bone. Healing was uncomplicated. Retrospective cephalometric study of the results of treatment showed a mean frontal vertical relapse of about 20% (range 0-100%). The relapse occurred during the early postoperative period. No linear correlation was found between the amount of vertical repositioning and the anterior vertical relapse. We consider that the mini-plate technique is more advantageous than previous methods.

Adolescent

Measurement of microvascular blood flow in cancellous bone using laser Doppler flowmetry and 133Xe-clearance.

Blood flow in cancellous bone with varying vascular density was investigated simultaneously with Laser Doppler Flowmetry (LDF) and 133Xe-clearance. The cancellous bone subapical to 2 contralateral incisors in the mandibles of 17 young pigs was used as an experimental model. Light from a 2 mW He-Ne-laser was guided through an optical fibre to a flowmeter probe. Stainless steel probe-holders firmly inserted in the pulpal canals of the two incisors served as the probe entrance to cancellous bone for blood flow recording. Due to the Doppler effect, the light scattered by circulating blood cells undergoes a frequency shift. The back-scattered light picked up by optical fibres in the probe, was guided to a photosensitive device, where it was demodulated. After signal processing, a signal referred to as the Blood Flow Value (BFV) was recorded on a pen recorder. Rhythmical variations (vasomotion) in BFV with frequencies from 2-11 cycles/min were observed in 6% of recordings made initially after probe-holder implantation, and in 34% of the recordings made 5 weeks later. On this occasion, a marked increase in BFV was recorded. Histological examination showed increased vascularity in the bone tissue. The reproducibility error of LDF was 7.4% and temporal changes in BFV, apart from vasomotion, were 8.3%, provided no injections or manipulations of the probe were made. Spatial variations in BFV were found to be related to the vascular density. 2 successive recordings by LDF from the same bone area were highly correlated (r = 0.98). The corresponding figure for 2 logarithmic decay rates of locally injected 133Xe was 0.76. No correlation between BFV and 133Xe-clearance could be demonstrated.

Animals

Microvascular response in cancellous bone to halothane-induced hypotension in pigs.

The microvascular response in cancellous bone to halothane-induced hypotension was studied simultaneously using Laser Doppler Flowmetry (LDF) and clearance of locally injected 133Xe in the subapical mandibular bone of 16 young pigs. During halothane inhalation, a significant reduction in mean blood pressure to values ranging from 22 to 60 mm Hg was observed. The blood flow, as measured with LDF, increased in more than 60% of the animals with hypotension levels above 30 mm Hg. At hypotension levels below 30 mm Hg, blood flow decreased in all cases. The individual regional vascular resistance, calculated as the quotient between blood pressure and recorded blood flow value, was significantly reduced (p less than 0.001) during hypotension. Rhythmical flow variations, observed in some animals at normotension, disappeared immediately following the start of halothane inhalation, but returned when blood pressure was stabilized at a lower level. For recordings made with 133Xe-clearance, a significant reduction (p less than 0.001) in the logarithmic decay of the washout curves was observed during hypotension. This logarithmic decay was correlated to the reduced blood pressure levels (r = 0.73). No average change in regional vascular resistance could, however, be demonstrated. The lack of correlation between results obtained by the 2 methods may be due to the fact that LDF is sensitive to the total blood flow in a limited tissue volume, while the 133Xe isotope seems to be washed out mainly by the capillary blood flow. It can be further concluded that halothane-induced hypotension levels, applicable to clinical routines, may produce an increase rather than a decrease in total blood flow in cancellous bone tissue.

Animals

Paracetamol plus supplementary doses of codeine. An analgesic study of repeated doses.

A double-blind, multicentre analgesic trial was carried out in patients suffering from pain after removal of an impacted lower wisdom tooth. 266 patients were evaluated after random allocation to treatment with paracetamol 500 mg, paracetamol 500 mg plus codeine 20 mg, paracetamol 500 mg plus codeine 30 mg, or paracetamol 500 mg plus codeine 40 mg. On the day of surgery the patients assessed their own pain intensity hourly on a visual analogue scale. The analysis of the results was carried out according to the method which considered repeated dose intake. A statiscally significant dose-response relationship was obtained between the supplementary doses of codeine and analgesic efficacy. In the comparison of side effects, their frequency increased with increasing amounts of codeine. In clinical practice codeine 30 mg appeared to be the optimal supplement for paracetamol 500 mg.

Acetaminophen

Normal and retrograde blood supply to the body of the mandible in the dog. I. A new method for selective multicolor arterial perfusion, combined with microangiography and histology.

An experimental study was performed to evaluate a method for selective, multicolor arterial perfusion. In seven adult beagle dogs the lingual, facial and mandibular arteries on one side were cannulated and perfused selectively with different colored perfusates (Microfil and Colorpaque). Identification of the perfusates was achieved using a clearing technique combined with microradiography and histology. With this method, the vascular territories of the body of the mandible and its adjacent tissue could then be identified separately.

Angiography