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Biomedical subjects

R Kissling

Publications and source records attributed to R Kissling.

At least 19 recordsLinked to original sources

Natural history of individuals with asymptomatic disc abnormalities in magnetic resonance imaging: predictors of low back pain-related medical consultation and work incapacity.

STUDY DESIGN: Prospective study on individuals with asymptomatic lumbar disc abnormalities detected in magnetic resonance imaging. OBJECTIVES: To determine the natural history of asymptomatic disc abnormalities in magnetic resonance imaging and to identify predictors of future low back pain-related medical consultation and work incapacity. SUMMARY OF BACKGROUND DATA: The natural history of individuals with asymptomatic disc herniations has not been well established, but the high rate of lumbar disc alterations recently detected in asymptomatic individuals by magnetic resonance imaging demands reconsideration of a pathomorphology-based explanation of low back pain and sciatica. METHODS: Forty-six asymptomatic individuals who had a high rate of disc herniations (73%) were observed for an average of 5 years (range, 54-72 months). Four classes of variables (medical data including magnetic resonance imaging-identified disc abnormalities, general psychological factors, physical job characteristics, and psychosocial aspects of work) were assessed at baseline and follow-up. RESULTS: Disc herniations and neural compromise did not significantly worsen at follow-up, whereas disc degeneration progressed in 17 individuals (41.5%). Minor episodes of low back pain occurred in 19 individuals (41.3%), 6 of whom had to seek medical treatment and 5 of whom had to stop work temporarily. The requirement for low back pain-related medical consultation was predicted with high accuracy by listlessness, job satisfaction, and working in shifts (P < 0.001). Work incapacity was best predicted by physical job characteristics, job disaffection, and working in shifts (P < 0.01). CONCLUSION: Physical job characteristics and psychological aspects of work were more powerful than magnetic resonance imaging-identified disc abnormalities in predicting the need for low back pain-related medical consultation and the resultant work incapacity. However,the conclusions are still preliminary, and replication of the findings in larger and more representative study samples is needed.

Adult↗

Docosahexaenoic acid reverses cyclosporin A-induced changes in membrane structure and function.

The use of a fish oil vehicle for cyclosporin A (CsA) can decrease the toxic effects of CsA but the mechanism is unclear. Here we examine the mechanism by which docosahexaenoic acid (DHA), a fish oil-derived polyunsaturated fatty acid, can alter the toxic effects of CsA on mouse organ function, endothelial macromolecular permeability, and membrane bilayer function. Mice given CsA and fish oil showed increased liver toxicity, kidney toxicity, incorporation of DHA, and evidence of oxidized fatty acids compared to control animals. We hypothesized that the toxic effects of CsA were primarily a result of membrane perturbation, which could be decreased if DHA were not oxidized. The presence of CsA (10 mol%) alone increased dipalmitoylphosphatidylcholine membrane permeability by seven fold over control (no CsA, no DHA). However, if non-oxidized DHA (15 mol%) and CsA were added to the membrane, the permeability returned to control levels. Interestingly, if the DHA was oxidized, the antagonistic effect of DHA on CsA was completely lost. While CsA alone increased endothelial permeability to albumin, the combination of non-oxidized DHA and CsA had no effect on endothelial macromolecular permeability. However the combination of oxidized DHA and CsA was no different than the effects of CsA only. CsA increased the fluorescence anisotropy of DPH in the liquid crystalline state of DPPC, while DHA decreased fluorescence anisotropy. However the combination of CsA and DHA was no different than DHA alone. We conclude that non-oxidized DHA can reverse the membrane perturbing effects of CsA, and the increases in endothelial macromolecular permeability, which may explain how fish oil is capable of decreasing the toxicity of CsA.

Animals↗

Is the amount of trabecular bone-loss dependent on bone mineral Density? A study performed by three centres of osteoporosis using high resolution peripheral quantitative computed tomography.

For the risk getting osteoporosis as well as for diagnosis of osteoporosis 3 facts are highly important: bone-mass, the amount of bone-loss and bone-structures (microarchitecture of bone). All three parameters can be validated today with high precision but the amount of bone-loss seems to be the most important one, even for the decision of either antiresorptive or bone-stimulating therapy. But to calculate the amount of bone-loss until now at least two measurements of bone mineral density (BMD) are necessary which have to be performed within a certain period of time, depending on the reproducibility of the method to be used. If on the other hand the amount of bone-loss would be dependent on actual base-line bone-mass the right therapy could be started already after only one measurement of BMD. The aim of this study was therefore to investigate if there is any relation between the amount of bone-loss and base-line volumetric BMD. For this we separately measured trabecular and cortical bone densities of 135 women in three independent centres of osteoporosis in Zurich and Munich using the method of high resolution quantitative computed tomography - pQCT - with the Densiscan 1000, Scanco Medical, Zurich. We did this at least twice and then compared absolute volumetric BMD in the first step before we calculated trabecular and cortical bone loss per year for each woman. We could not only confirm again that bone loss in trabecular bone was significantly higher than in cortical bone and that the non-weight-bearing trabecular bone as could be found in the distal radius seems to be the skeletal site of maximum bone-loss, but moreover - and this is the more important finding - we could show that the amount of relative bone-loss was the higher the lower trabecular base-line volumetric BMD was. According to this the rate of fast-loser (more than 3.5% per year) increased the lower trabecular base-line volumetric BMD was. These results may lead to a new screening-test for the assessment of the individual risk of osteoporosis and for the individual risk of fast bone-loss which now can be evaluated with only one single measurement of BMD, to treat the so classified patients not only earlier but even more rational, dependent if either antiresorptive therapy or stimulation of bone-formation seems to be more important.

Adult↗

[Diagnostic assessment in lumbar back pain. I. Anamnesis and clinical examination].

The diagnostic assessment of the low back pain patient is often unsatisfactory because a clear morphological alteration explaining the patient's symptoms can only be found in 10-20% of the cases. The majority of the patients is suffering from non-specific low back pain. However, the high incidence of benign, self-limiting low back pain leads to the risk of overlooking specific causes such as tumor or infection. Similarly, relevant paresis and bladder and bowel dysfunction must be diagnosed in time. Furthermore, the aim of the diagnostic work-up is to diagnose and treat specific causes of back and leg pain (e.g. disc herniation and spinal stenosis) to avoid chronicity. In the majority of the cases, history and clinical examination alone allow to differentiate between specific and non-specific low back pain and may lead to a further diagnostic work-up by imaging studies.

Diagnosis, Differential↗

Spondylodiscitis caused by viridans streptococci: three cases and a review of the literature.

Three cases of spondylodiscitis caused by viridans streptococci were observed within the course of 1 month. Although streptococci have been reported as the third most frequent cause of spondylodiscitis after staphylococci and gram-negative bacteria, alpha-haemolytic streptococci are rarely seen. The three patients presented with symptoms of low back pain; they felt well and did not have a fever or chills. Laboratory examinations revealed inflammation. Further examinations such as scintigraphy, computed tomography or magnetic resonance imaging were done. Bacteriological diagnosis was established by blood cultures in two cases and by needle biopsy of the disco-vertebral space in one. In one patient endocarditis was also documented. Because the prevalence of endocarditis was found to be higher in our cases of spondylodiscitis due to Streptococcus viridans than for other bacteria, the exclusion of this diagnosis must be pursued aggressively. These observations lead us to question if the spectrum of bacteria causing spondylodiscitis is undergoing a change. an aetiological agent could be isolated in 1168 patients (85.4%): in 48% a staphylococcus, in 28% a gram-negative bacterium and in only 10% a streptococcus. There were two cases of viridans streptococci (0.2%). These two cases together with other single case reports [14-22] account for 15 cases of spondylodiscitis due to alpha-haemolytic streptococci. Differentiation of the organisms to the species level was accomplished in six cases: S. mitis (3), S. sanguis (2) and S. anginosus (1). Although a multitude of organisms, bacterial as well as fungal, causing spondylodiscitis has been reported in recent years, almost all were single cases [23-42]. The unusual observation of three cases of spondylodiscitis due to alpha-haemolytic streptococci within 1 month prompted us to review the clinical and laboratory findings and to compare these cases with those caused by Staphylococcus aureus.

Adult↗

Highly precise peripheral quantitative computed tomography for the evaluation of bone density, loss of bone density and structures. Consequences for prophylaxis and treatment.

The importance of serial examinations over time with peripheral quantitative computed tomography (pQCT) is that they enable the detection of patients at high risk of osteoporosis, and the individualisation of prophylaxis and treatment. We have shown that postmenopausal patients with high bone turnover evaluated by biochemical markers are identical to fast bone losers as determined by pQCT. As a consequence, we use agents that inhibit bone resorption in patients who are fast bone losers and agents that stimulate bone formation in patients who are slow bone losers. To visualise bone microarchitecture, and to evaluate bone density and the rate of bone loss, we used a highly sensitive pQCT system (DENSISCAN 1000, reproducibility of 0.3% in a mixed population of normal individuals and patients with osteopenia or osteoporosis). This system enabled us to separately assess trabecular and cortical bone density in the radius and tibia, and to differentiate between fast and slow bone losers within a few months (threshold: 3% loss of trabecular bone density in the radius per year). We have shown that the lower the trabecular bone density in the distal radius, the higher the relative bone loss. To classify patients as slow and fast losers in the future, we may need only one measurement. With this highly precise measurement method, we have shown that calcitonin and etidronate are more effective in fast than in slow bone losers, and that vitamin D metabolites (calcitriol or 1 alpha-calcidol) and estrogens can halt fast bone loss. In conclusion, highly sensitive pQCT enables us to adapt the treatment to different forms of osteoporosis and bone turnover, resulting in an increase in the number of patients successfully treated and also in patient compliance. Because our treatment is based on precise, objective measurements, treatment modifications--especially in those who change from a slow to a fast bone-loser state--can be easily justified.

Adult↗

[Prevention of osteoporosis].

The European Parliament presented June 10th in Brussels the 'Osteoporosis Report in EU--Means for Prevention'. It was emphasized that in the EU more than 3500 million Ecu have to be spent for hospitalization and that more than 500,000 hospitals beds are being used by osteoporotic patients. According to some calculations this number will double within the next 50 years. The EU has set up eight steps to be considered, e.g. have densitometric measurements available for persons with high risk and have these measurement paid by the insurances to further finance and support research for the very important areas of prevention and treatment. One distinguishes between primary, secondary and tertiary prevention of osteoporosis. Primary prevention aims at reaching at adolescent age a peak bone mass as high as possible. Secondary prevention aims at reducing bone loss peri- and postmenopausal. The tertiary prevention with manifest osteoporosis aims at preventing fractures. Emphasis of the primary prevention is, besides a sufficient calcium intake, to omit risk factors; with secondary prevention the use of medical treatments such as estrogens/gestagens, bisphosphonates, and recently also SERMs is applied. The tertiary prevention tries mostly to reduce the femur fractures. In addition to drugs such as vitamin D/calcium, vitamin D metabolites and bisphosphonates it is very important to create 'a fall-proof home'. Also very useful are hip protectors.

Adolescent↗

Spondylodiscitis caused by Tropheryma whippelii.

We describe the first case of spondylodiscitis caused by Tropheryma whippelii in which this so far unculturable organism was shown to be present at the site of infection in a patient without significant gastrointestinal symptoms. The methods used included broad-range PCR amplification with universal primers complementary to constant sequences of the gene coding for 16S rRNA, direct sequencing of the amplified fragment, and comparison of the sequence determined with those deposited in sequence databases. In addition to demonstrating the presence of this organism in the affected vertebral body, we found in our patient that the specific PCR is more sensitive than histology for detecting Whipple's bacilli in bowel biopsy specimens. Because histology of small bowel biopsies from the duodenum were-in contrast to PCR from the same site-not diagnostic for Whipple's disease in our patient, we recommend PCR whenever Whipple's disease has to be excluded.

Actinobacteria↗

Comparison of chondroitin sulphate composition of femoral head articular cartilage from patients with femoral neck fractures and osteoarthritis and controls.

The glycosaminoglycan (GAG) and uronic acid (UA) composition of human hip articular cartilage from patients with femoral neck fractures [assumed osteoporosis (OP); n = 12], from patients with osteoarthritis (OA; n = 12) and from normal controls (n = 9) was determined. Full depth tissue samples from the control and OP groups were analysed from the superior, inferior, anterior and posterior regions, while the OA tissue was from cystic (tissue growing on top of cystic bone lesions) and osteophytic regions, from normal and fibrillated resident cartilage and from regions immediately adjacent to eburnated bone. The total sulphated GAG and UA content was reduced in the inferior region of control cartilage compared to the other regions and the values of all regions of the assumed OP group. Cystic regions and OA cartilage adjacent to the bone also showed lower GAG and UA levels than the other regions. The ratios of chondroitin 6-sulphate (C6S) to chondroitin 4-sulphate (C4S) indicated a similar pattern in the different regions of controls and the patient group with femoral neck fracture (OP group). The cystic and osteophytic cartilage of the OA group exhibited lower C6S/C4S ratios than any other region. The levels of dermatan sulphate (DS) in the cartilage of all regions of the OP and control groups were very similar and low, while the tissues of the OA group contained significantly higher amounts, particularly the cartilage from osteophytes. The previously presumed compositional similarity between normal aged and osteoporotic articular hip cartilage was essentially confirmed in a comparative analysis. Significant changes in GAG and UA composition of OA cartilage from distinct regions was also recorded.

Aged↗

Cathepsin B in osteoarthritis: zonal variation of enzyme activity in human femoral head cartilage.

OBJECTIVES: To determine the quantitative topographical distribution of cathepsin B in human femoral head cartilage by measuring the zonal variation of enzyme activity in specimens taken from various anatomical regions of normal and osteoarthritic (OA) tissues, and to correlate this parameter with the severity of the OA lesions. METHODS: OA articular cartilage was obtained at surgery for total hip replacement and control cartilage obtained at postmortem. Cylinders of full thickness cartilage with underlying bone were retrieved with a biopsy trephine. Sections of cartilage were produced by cryocutting the tissue as slices parallel to the articular surface and assayed for cathepsin B with a specific, highly sensitive fluorogenic substrate. The severity of the OA lesions was graded according to the histopathological-histochemical method of Mankin. RESULTS: Zonal cathepsin B activity of normal cartilage was uniform and low in all regions of the femoral head. In apparently intact OA cartilage and in severely degraded tissue the zonal distribution and the amounts of enzyme were similar to control values. At sites with active disease, cathepsin B activity was much greater than in controls and its irregular zonal distribution correlated with tissue degeneration, hypercellularity, or cloning of chondrocytes as determined histochemically. Particularly high enzyme levels were observed at sites with regenerating cartilage, where some zonal peaks attained 20-fold activity with respect to controls. CONCLUSION: Cathepsin B may play a role in sustaining the chronicity of OA, not as an initiator, but rather as a perpetuator of the disease and as an antagonist of regeneration.

Adult↗

Cathepsin B in osteoarthritis: cytochemical and histochemical analysis of human femoral head cartilage.

OBJECTIVE: To localise the cysteine endopeptidase cathepsin B in chondrocytes and cartilage from normal and osteoarthritic (OA) human femoral heads in order to provide qualitative information on its cellular expression and distribution at possible sites of action. METHODS: OA articular cartilage was obtained at surgery for total hip replacement; control cartilage was obtained at postmortem. Chondrocytes were isolated by sequential enzymatic digestion and cathepsin B analysed by immunocytochemistry and activity staining with a fluorogenic substrate. Lysosomes were visualised by fluorescence microscopy after staining of living cells with acridine orange. Using a histochemical reaction, enzyme activity was measured in cryosections of full thickness cartilage. RESULTS: Chondrocytes from normal cartilage contained very few lysosomes and only a minor cell population was cathepsin B positive. A high proportion of chondrocytes from active OA cartilage contained a large number of lysosomes and an excess of cathepsin B in intracellular organelles; the enzyme was stored in an active form. In this respect, OA chondrocytes closely resembled normal cells that had been phenotypically modulated by serial subcultures. No cathepsin B activity could be detected by histochemistry in either chondrocytes or matrix of normal cartilage. While apparently intact and severely degraded OA cartilage was also cathepsin B negative, tissue at sites of active destruction and, particularly, at repair sites was highly positive. CONCLUSION: The presence and the particular distribution of active cathepsin B in OA cartilage at 'more involved' sites suggest a pathological role for this enzyme in sustaining and perpetuating cartilage degradation. While other stimuli may also be responsible for cathepsin B expression in OA chondrocytes, the similarity with artificially modulated cells indicates fibroblastic metaplasia as a plausible mechanism.

Adult↗

[Spinal syndromes. On the clinical aspects and possibilities of conservative therapeutic approaches].

The great socio-economic importance of back pain is undisputed. A precise definition and nomenclature of the multiple clinical syndromes aids in a clearer assessment of the individual problems of the patient and subsequently the selection of suitable conservative therapeutical measures. It is stressed that each treatment has to be selected with care and in consideration of the individual situation. The lack of generally applicable recommendations and patented recipes is emphasized. Therapeutical possibilities are essentially based on three columns: active and passive physical treatment both supported by the third mean, pharmacotherapy. Secondary prophylaxis following the acute phase of the disease should not be forgotten.

Diagnosis, Differential↗

Glycosylation of alpha 1-acid glycoprotein in relation to duration of disease in acute and chronic infection and inflammation.

Microheterogeneity of acute phase proteins frequently differs in acute and chronic types of inflammation. However, it is unknown whether these changes depend on the duration of the inflammation in a given disease. We therefore investigated the microheterogeneity of alpha 1-acid glycoprotein (AGP) in sera from patients with acute and chronic bacterial infection in comparison to rheumatoid arthritis and ankylosing spondylitis. In acute bacterial infection Con A-reactivity of AGP was significantly elevated. By contrast, AGP in chronic bacterial infection showed the same glycosylation pattern as rheumatoid arthritis and ankylosing spondylitis being characterized by a decreased reactivity to Con A. Serial measurements in individual patients with bacterial infections showed a transition from the initially elevated to decreased reactivity to Con A as the disease became chronic.

Acute Disease↗

[Physical therapy aspects of treatment following total hip prosthesis].

Our physiotherapy program after total hip arthroplasty is presented, and certain modifications in relation to cemented or cementless implantations are discussed. Three different stages must be considered: preoperative instructions of the patient, mobilization of the patient and his joints, water gymnastics to enable the patient to obtain total independence. During the first three months only partial weight should be put on the operated leg. In comparison to the cemented system, the biomechanical properties of the cementless prosthesis permit only a careful and delayed mobilization and charge of the operated leg, as long as a secondary stability of the implant has not been reached. In more complicated cases it is of importance that the whole planning of postoperative physiotherapy should be discussed individually and in detail with the surgeon concerned.

Bone Cements↗

The effects of morphology and histopathologic findings on the mobility of the sacroiliac joint.

The sacroiliac joints of seven pelvic specimens were examined to determine functional, morphologic, and histopathologic aspects. The movements were measured in four intact pelvises (from two men and two women). The joint surfaces of all pelvises (from three men and four women) then were examined topographically by means of a photogrammetric method. After this, they were examined histologically to characterize any effects on function. The morphologic investigation revealed sex-specific differences. All joint surfaces from the female pelvises showed circular contours, the centers of which coincided with the iliac tuberosities. These morphologic characteristics were not discernible in the joint surfaces from the male pelvises; these had interlocking irregularities without a topographic pattern. As expected, this configuration involved distinct differences in mobility. Rotation of the sacrum was markedly less in the sacroiliac joints of men than in those of women.

Cadaver↗