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Biomedical subjects

R Theiler

Publications and source records attributed to R Theiler.

At least 37 records · Page 2Linked to original sources
PubMed2000

Determination of the origin of charge heterogeneity in a murine monoclonal antibody.

PURPOSE: The aim of this study was to elucidate the molecular basis of charge heterogeneity found in a purified monoclonal IgG1 antibody, MMA383. METHODS: Cation exchange chromatography (CEX) and isoelectric focusing (IEF) were used to monitor charge heterogeneity. CEX in conjunction with carboxypeptidase B digests of the antibody was used to determine the contribution of C-terminal lysines to MMA383 charge heterogeneity. Potential chemical degradation sites were identified by peptide mapping of individual chains, with peptide identification by mass spectrometry (MALDI-TOF MS). Peptide sequencing was used to determine specific deamidation sites. Binding constants of predominant isoforms were compared by surface plasmon resonance (SPR). RESULTS: Extensive charge heterogeneity of purified MMA383 was detected by CEX and IEF. Removal of C-terminal lysines simplified the IEF pattern to nine predominant isoforms. Quantitation of isoaspartate in each of the isoforms indicated deamidation of MMA383 as a major cause of charge heterogeneity. CEX of the individual isoform chains suggested the presence of one deamidation site on each of the heavy and light chains. The two sites of deamidation were identified using peptide mapping, sequencing and mass spectrometry. SPR results showed no significant difference in the binding parameters among the isoforms. CONCLUSIONS: C-terminal lysine microheterogeneity and deamidation of Asn141 in the heavy chain and Asn161 in the light chain are the major causes of MMA383 charge heterogeneity. Identification of the two deamidation sites will allow replacement of these amino acids in order to create a product less susceptible to degradation.

Antibodies, Monoclonal↗
PubMed2000

No influence of osteoarthritis of the hand on phalangeal osteography in elderly women.

We investigate the influence of hand osteoarthritis on skeletal quantitative ultrasound (QUS) measurement through the proximal phalanges in female geriatric inpatients. In a cross-sectional study, bone status was assessed with QUS at the distal metaphysis of the first phalanges of fingers II-V. Thirty-three of 101 female geriatric inpatients met the clinical criteria of the American College of Rheumatology for osteoarthritis of the hands (median age: 85 years) and were compared to 68 female inpatients without swellings of the small finger joints (median age: 88 years). Amplitude-dependent speed of sound at the distal metaphysis, the electronic signal of the ultrasonic wave after crossing the phalanx (graphic trace), and the thickness of the each phalanx were measured and compared between the two groups by a phalangeal QUS device (DBM-Sonic 1200). There were no significant differences between the phalangeal QUS readings of both groups. The only statistically significant difference was observed in the comparison of the small finger thickness with a lower value in the osteoarthritis group (p = 0.02). These findings suggest that at the metaphyseal level of phalanges, the degenerative process of osteoarthritis doesn't influence the QUS assessment. This could be explained by the finger thickness at metaphyseal level, which was not increased in patients with osteoarthritis compared with control subjects, at least as detected by the applied finger ultrasound method.

Aged↗
PubMed2000

Influence of physical mobility and season on 25-hydroxyvitamin D-parathyroid hormone interaction and bone remodelling in the elderly.

OBJECTIVE: To investigate influences of physical mobility and season on 25-hydroxyvitamin D-intact parathyroid hormone (iPTH) interaction in the elderly. DESIGN: We examined 188 frail institutionalized elderly at the expected nadir of their serum vitamin D concentrations (winter). This group was compared with 309 healthy ambulatory elderly at the expected time of maximum vitamin D repletion (summer), to accentuate the influences of season and physical activity. METHODS: Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, iPTH and urinary deoxypyridinoline (DPD) were measured. RESULTS: Vitamin D metabolites were significantly lower in the institutionalized elderly (P<0.0001), with an 82.5% prevalence of vitamin D deficiency (25-hydroxyvitamin D <12ng/ml) in institutionalized elderly in wintertime and 15.5% in ambulatory elderly in summertime. Overall, median iPTH did not differ between groups. However, median iPTH secretion in the presence of low vitamin D serum concentrations (5-30ng/ml) was greater in ambulatory elderly. This could be explained by lower mobility status being correlated with greater serum calcium concentrations (r=0.24, P=0.02 in women; r=0.35, P=0. 001 in men) and greater urinary excretion of DPD (r=0.41, P=0.0001 in women; r=0.42, P=0.0002 in men), independent of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and iPTH. CONCLUSIONS: These data support the hypothesis that immobility, even in the presence of vitamin D deficiency, acts as an overriding influence on bone metabolism by promoting bone resorption (measured as urinary DPD) and increasing serum calcium independent of iPTH. Therefore mobility status may substantially affect 25-hydroxyvitamin D threshold values and the degree to which patients benefit from vitamin supplementation.

Aged↗
PubMed1999

Immobility as a major cause of bone remodeling in residents of a long-stay geriatric ward.

Residents of a long-stay geriatric ward at the University Hospital Basel were included in a study to investigate the effects of hypovitaminosis D and immobility. All 91 women (mean age 82.5 years) and 92 men (mean age 78.7 years) were enrolled in the study. Measurements included bone resorption, as measured by urinary deoxypyridinoline (dpd), serum 25-hydroxyvitamin D (25OHD), serum intact parathyroid hormone (iPTH), and their correlations with a four grade mobility score. Mobility score reflected the degree of weight bearing, ranging from walking independently to primarily bed bound. In 86% of all residents, serum 25OHD levels were below the normal limit of 12 ng/ml. Secondary hyperparathyroidism (HPT) was detected in 24% of all patients, using 55 pg/ml as the upper limit for serum iPTH. No significant correlation was found between urinary dpd and serum 25OHD or serum iPTH. Mobility index and both urinary dpd (f: P = 0.001, r = 0.37; m: P < 0.0001, r = 0.47) and serum calcium (female: P = 0.007, r = 0.28; male: P = 0.02, r = 0.24) were positively related. In institutionalized elderly people with a high prevalence of vitamin D deficiency serum intact PTH levels did not correlate with bone resorption as measured by urinary deoxypyridinolin. However, more immobile subjects had significantly higher excretion rates for urinary dpd and higher serum calcium levels. Our results suggest that in elderly people immobility may contribute to bone loss that might preempt the development of secondary HPT through elevation of serum calcium.

Activities of Daily Living↗
PubMed1999

Type I osteogenesis imperfecta: diagnostic difficulties.

A 65-year-old woman presented with vertebral fractures of the lumbar spine and a history of pathological fractures following minor trauma, which had occurred before the onset of menopause. Her past medical history was significant for intermittent low back pain since childhood, which was attributed to thoracolumbar scoliosis. A diagnosis of unclassifiable osteoporosis was made until invasive diagnostic procedures suggested a mild form of type I osteogenesis imperfecta (OI). In unclear or atypical perimenopausal osteoporosis and diagnosis of OI should be considered.

Absorptiometry, Photon↗
PubMed1999

High bone turnover in the elderly.

OBJECTIVES: To document lifestyle-associated variations in biochemical markers of bone metabolism in advanced age. STUDY DESIGN: Cross-sectional study. SETTING: Department of Geriatrics, University Hospital, Basel, Switzerland. SUBJECTS: Three hundred twelve ambulatory and 193 institutionalized men and women, aged 54 to 99 yrs. OUTCOME MEASUREMENTS: Biochemical markers of bone resorption (urinary deoxypyridinolin and N-telopeptides), serum vitamin D metabolites, and serum intact parathyroid hormone (iPTH) concentrations were assessed. Mean values of all parameters were correlated with a six-grade activity score. Physical activity score reflected the degree of weight bearing, ranging from walking independently to primarily bed-bound. Ambulatory subjects were measured in summertime and institutionalized subjects in wintertime to accentuate seasonality of vitamin D hormone levels. RESULTS: Excretion of bone resorption markers was significantly higher in the institutionalized and physically inactive patients compared with those who were ambulatory and physically active (p = .0001). Vitamin D deficiency (25-hydroxyvitamin D of <12 ng/mL) was present in 86% of institutionalized and 15% of ambulatory subjects, and 1,25-dihydroxyvitamin D serum concentrations were lower in institutionalized than in ambulatory subjects (p = .0001). Mean serum concentrations for iPTH were similar for both the institutionalized and ambulatory groups. When subjects were arranged according to activity score, mean excretion of urinary bone resorption markers increased with degree of inactivity. CONCLUSION: Despite the difference in vitamin D metabolites, iPTH serum concentrations did not differ significantly between the institutionalized and ambulatory groups. However, institutionalized and physically inactive participants had markedly elevated excretion of urinary bone resorption markers compared with ambulatory and physically active subjects. These results suggest that high bone turnover in the elderly may be caused by physical inactivity related to low mechanical loading rather than secondary hyperparathyroidism.

Aged↗
PubMed1999

Muscle strength in the elderly: its relation to vitamin D metabolites.

OBJECTIVE: To identify a relation between loss of muscle strength and vitamin D deficiency in ambulatory elderly persons not receiving vitamin D supplementation. DESIGN: Cross-sectional study. SETTING: All measurements were taken at the Department of Geriatrics, University Hospital, Basel, Switzerland. SUBJECTS: Three hundred nineteen patients (103 women, 216 men) selected by random sampling from participants in an ongoing interdisciplinary study on aging (mean age for women, 74.2 yrs; for men, 76.7 yrs). OUTCOME MEASURES: Leg extension power (LEP) and body mass index (BMI); serum values of 25-hydroxyvitamin D [calcidiol, 25(OH)D], 1,25-hydroxyvitamin D [calcitriol, 1,25(OH)2D], and intact parathyroid hormone (iPHT). RESULTS: Twelve percent of women and 18% of men had 25(OH)D values below the normal range (<12 ng/mL). Muscle strength was lower in older subjects (female: r = -.35; p = .0005/male: r = -.48; p < .0001) and was lower in women than in men (p < .0001). In men both 25(OH)D and 1,25(OH)2D was significantly correlated with LEP (r = 0.24; p = .0004/r = .14; p = .045). In women, only 1,25(OH)2D was significantly correlated with LEP (r = 0.22; p = .034). In an ANCOVA including all participants and explaining LEP by sex, age, BMI, 1,25(OH)2D, 25(OH)D, and iPTH, all factors showed significant effects except 25(OH)D and iPTH (r2 = .41). CONCLUSION: Muscle strength declined with age in ambulatory elderly people and showed modest, but significant, positive correlation with 1,25(OH)2 vitamin D in both sexes and with 25(OH)D in male subjects. Therefore vitamin D deficiency appears to contribute to the age-related loss of muscle strength, which might be more pronounced in institutionalized elderly people with a high prevalence of vitamin D deficiency.

Aged↗
PubMed1999

Calcidiol, calcitriol and parathyroid hormone serum concentrations in institutionalized and ambulatory elderly in Switzerland.

AIM: The aim of the present study was to measure concentrations of vitamin D metabolites and intact parathyroid hormone (iPTH) serum concentrations and an urinary bone resorption marker in two groups of elderly subjects, who differed markedly in their sedentary status and seasonality. DESIGN: 193 institutionalized elderly people of a long-stay geriatric ward (106 women: mean age 82; 87 men: mean age 78) were studied during wintertime. 312 ambulatory elderly people (109 women: mean age 74; 203 men: mean age 76) were studied during summertime. Concentrations of calcidiol (25(OH)D), calcitriol (1,25(OH)2D) and serum iPTH, as well as urinary N-telopeptides (NTX) were measured. RESULTS: Vitamin D deficiency (defined as serum 25(OH)D < 12 ng/ml) was present in 86% of institutionalized at the expected nadir (wintertime), compared to 15% of the ambulatory elderly subjects at the expected maximum (summertime). Serum calcitriol concentrations were significantly lower in institutionalized subjects (p = .0001). However intact PTH concentrations did not differ significantly between institutionalized and ambulatory elderly. Institutionalized and female subjects showed higher urinary NTX excretion (female institutionalized: 131.9; female ambulatory: 66.8/male institutionalized: 76.3 male ambulatory: 45.8 nmol/mmol). CONCLUSION: This cross-sectional study documented very low serum calcidiol and calcitriol concentrations and high urinary N-telopeptide excretion in institutionalized elderly people. There was no difference in serum iPTH concentrations between institutionalized and ambulatory elderly. This finding could not be explained by the differences in calcidiol and calcitriol concentration, nor urinary NTX excretion. These results suggest that other factors than vitamin D deficiency, such as lower mobility status and sedentary life style, might have an important role in the regulation of iPTH and mechanisms of bone loss in the elderly.

Aged↗
PubMed1999

Superior responsiveness of the pain and function sections of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as compared to the Lequesne-Algofunctional Index in patients with osteoarthritis of the lower extremities.

OBJECTIVE: To compare the responsiveness of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and a questionnaire format of the Lequesne-Algofunctional Index in patients with OA of the lower extremities. METHODS: Longitudinal analysis of the instruments' responsiveness [standardized response mean (SRM), effect size (ES)] in ambulatory patients undergoing hip or knee arthroplasty. RESULTS: At six months 36, and at one year 40 out of 43 patients undergoing hip (N=30) or knee arthroplasty (N=13) could be examined. Both responsiveness statistics revealed the same order of responsiveness. For both indices and for both locations, the pain sections were more responsive than the function sections. However, the WOMAC scales and the WOMAC global index (hip at 12 months: SRM=2.4; knee at 12 months: SRM=2.0 ) were more responsive than the comparable Lequesne sections and Lequesne index (hip at 12 months: SRM=2.1; knee at 12 months: SRM=1.5). CONCLUSIONS: Although our results are based on a German version using a self-report format, the WOMAC scales appear to be more responsive than the Lequesne index in patients with OA of the lower extremities.

Adult↗
PubMed1998

[Bone ultrasound and diagnosis of osteoporosis: correlation of 2 quantitative ultrasound methods with bone density].

In this study, 96 women (mean +/- SD, 65.3 +/- 13.2 years) were investigated by bone mineral densitometry (DXA, Hologic QDR 2000) and quantitative ultrasound (QUS) of the tibia (n = 96; Sound-Scan2000, Myriad) and phalanges (n = 84: DBM Sonic 1200, IGEA). We observed a good correlation of QUS measurement with bone mineral content (BMD) on lumbar spine and both hips (Ward and Neck). Correlation of the two QUS-techniques measuring at different skeletal sites within the same patient was good. QUS instruments measuring at the various skeletal sites and their suitability for screening patients at risk of osteoporosis are discussed. The usefulness of the different QUS methods and the best measuring site for the assessment of fracture risk in osteoporotic patients still have to be established.

Absorptiometry, Photon↗
PubMed1998

Interfemur variation of bone mineral density in patients receiving high-dose thyroxin therapy.

In order to evaluate the interfemoral variability of bone mineral density (BMD) in patients receiving thyroxin (T4) replacement therapy, dual-energy X-ray absorptiometry (DXA) was performed on both hips and the lumbar spine of 114 individuals. BMD was measured in 47 patients under T4 therapy in suppressive doses because of histologically proven thyroid cancer and 67 age-matched controls free of any known local or generalized disorder that would affect the bones and joints. Variation in BMD between both hips was determined for four different regions of interest, i.e., Ward's triangle, intertrochanteric region, trochanter, and femoral neck. No significant difference in hip BMD was found between patients and controls. Even though some individuals had large interfemoral BMD variation, no significant difference in hip BMD variability between the groups was observed. In patients under suppressive T4 replacement therapy, BMD measurement in one hip is suitable to predict BMD of the other hip and therefore unilateral hip measurement may be adequate.

Absorptiometry, Photon↗
PubMed1998

Comparison of the WOMAC (Western Ontario and McMaster Universities) osteoarthritis index and a self-report format of the self-administered Lequesne-Algofunctional index in patients with knee and hip osteoarthritis.

OBJECTIVE: To compare the metric properties and validity of German versions of the WOMAC (Western Ontario and McMaster Universities) and a self-administered questionnaire-format of the Lequesne-Algofunctional-Index in patients with osteoarthritis (OA) of the lower extremities. DESIGN: Cross-sectional analysis of the instruments' internal consistency (Cronbach's coefficient alpha) and construct validity (correlation with radiological OA-severity and limitation in range-of-motion) in ambulatory patients and patients before hip arthroplasty. Test-retest reliability was assessed on a subsample after 10 days. RESULTS: Data from 51 patients out of 91 contacted could be analyzed. Twenty-nine patients had knee and 22 patients had hip OA. Both the WOMAC and Lequesne OA-indices and their scales or sections had a satisfactory test-retest reliability (Intraclass correlation coefficient 0.43-0.96). All scales of the WOMAC were internally consistent (Cronbach's coefficient alpha 0.81-0.96) and associated with radiological OA-severity and joint range of motion. However, only the function but not the symptom sections (Cronbach's coefficient alpha knee: 0.55; hip: 0.63) of the self-administered Lequesne OA index were internally consistent for both, patients with knee and hip OA. Also, the symptom components were not or only weakly associated with radiological OA-severity and joint range of motion. CONCLUSIONS: Although our results are based on a German version using a self-report format we may caution using the self-administered Lequesne OA index without prior testing of its metric properties and validity.

Aged↗
PubMed1998

Elevated PTH levels in hypovitaminosis D are more rapidly suppressed by the administration of 1,25-dihydroxy-vitamin D3 than by vitamin D3.

OBJECTIVE: To assess markers of bone metabolism in two groups of inpatients with hypovitaminosis D and elevated PTH levels receiving two different vitamin D medications. METHODS: 26 patients with secondary hyperparathyroidism (2 degrees HP) were treated either with 800 IU cholecalciferol and 1000 mg calcium or 0.5 microgram calcitriol plus 500 mg calcium daily for 6 months. 25-OH-vitamin D3, 1,25-dihydroxy-vitamin D3, intact PTH, calcium and urinary N-telopeptides of bone collagen I were measured at baseline, 3 and 6 months. RESULTS: PTH levels decreased earlier in the calcitriol group than in the cholecalciferol group. After six month no difference could be documented. Lowering of urinary N-telopeptides excretion was observed in both groups. CONCLUSION: The use of both forms of vitamin D supplementation appears to be useful for patients with hypovitaminosis D, elevated PTH levels and high telopeptide excretion.

Administration, Oral↗
PubMed1996

Parametric and non-parametric measures in the assessment of knee and hip osteoarthritis: interobserver reliability and correlation with radiology.

The aim of this study was to evaluate the interobserver reliability of parametric and non-parametric variables in the clinical assessment of hip and knee osteoarthritis (OA). Three rheumatologists examined 49 patients with different radiological stages of OA using different assessment tools such as a tape measure, a goniometer, a plurimeter and a hand-held pull gauge. The reliabilities of parametric variables calculated by analysis of variance (ANOVA) showed much higher values than the non-parametric ones calculated by Kendall's tau beta. The highest levels of correlation in hip OA between clinical functional tests and radiological changes were found for hip extension (r = 0.57; P < 0.01) and the Patrick sign (r = 0.54; P < 0.01) while in knee OA the highest correlations were found for knee circumference (r = 0.5; P < 0.01) and knee flexion (r = 0.035; P < 0.02). Knee muscle strength, as measured with a hand-held pull gauge, showed a high level of interobserver agreement (r = 0.79), but correlated poorly with radiological changes. In conclusion parametric variables of joint morphology as knee circumference of parametric variables of function as the Patrick sign should be preferred for assessing secondary endpoints in OA clinical trials.

Aged↗
PubMed1996

Hyperostotic and destructive osteoarthritis in a patient with vitamin A intoxication syndrome: a case report.

The authors present a case report of a 59-year-old female suffering from hyperlipidemia who developed chronic vitamin A intoxication syndrome after ingestion of 30,000 IU retinol/daily over a period of six years. The patient's main complaints included severe headaches, morning nausea, myalgias and disability around the hip, knee, and ankle joints. Radiologically, hyperostosis of the acetabular circumference and the spine was demonstrated. Because of rapidly increasing pain, total hip replacement was performed. Histology of cross sections from the femoral head revealed destructive osteoarthritis. Since no other causative reason was found, retinol may not only be responsible for hyperostotic bone and soft tissue formations but may perhaps also account for rapid progressing of degenerative joint disease. Despite the cessation of vitamin A intake the clinical symptoms persisted due to hyperlipidemia. The enlarged number of chylomicrons and the higher fraction of very low density lipoproteins may represent a second retinyl ester pool in case of overloaded fat storing Ito-cells in the liver. Therefore, rheumatological treatment reducing risk factors such as hyperlipidemia is mandatory.

Chronic Disease↗
PubMed1995

The role of motor evoked potentials in psychogenic paralysis.

STUDY DESIGN: This prospective clinical study identified patients in whom paralysis developed after lumbar surgery. OBJECTIVE: To determine whether patients with psychogenic paralysis could be identified using noninvasive techniques. SUMMARY OF BACKGROUND DATA: Before the advent of transcranial magnetic stimulation, no clinically applicable, noninvasive technique was available to confirm the integrity of the corticospinal tract. METHODS: Patients with suspected postoperative psychogenic paralysis were evaluated by clinical examination and neurophysiologic work-up, including transcranial magnetic stimulation. RESULTS: Six patients with psychogenic paralysis were identified in a 15-month period. In each case, motor evoked potentials could be demonstrated from the affected muscle(s), thus obviating the need for further invasive imaging or surgical exploration. CONCLUSIONS: Transcranial magnetic stimulation is a reliable, painless, and noninvasive technique for demonstrating structural integrity of the corticospinal tracts.

Adult↗
PubMed1995

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↗