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Biomedical subjects

R Valkema

Publications and source records attributed to R Valkema.

At least 55 records · Page 3Linked to original sources
PubMed1995

Prednisone treatment of elderly-onset rheumatoid arthritis. Disease activity and bone mass in comparison with chloroquine treatment.

OBJECTIVE: Prednisone is frequently used in the treatment of elderly-onset rheumatoid arthritis (RA), but the balance between efficacy and toxicity, including the effect on bone mass, has not been investigated in long-term studies. This prospective, randomized study was undertaken to compare disease activity and bone mass during long-term treatment with prednisone versus chloroquine in this patient population. METHODS: Patients with active RA diagnosed at age > or = 60 were randomized to receive prednisone (15 mg/day for 1 month, with the dosage tapered as low as possible thereafter) (n = 28) or chloroquine (n = 28). Patients who did not show a response received other second-line drugs as an adjunct to prednisone or as a replacement for chloroquine. Bone mass was measured by dual-energy x-ray absorptiometry. The study duration was 2 years. RESULTS: During the 2 years, treatment with other second-line drugs was needed for 12 patients in the prednisone group (43%) and 8 in the chloroquine group (29%). Functional capacity and disease activity improved significantly in both groups and did not differ significantly between the groups, except for a greater improvement in the prednisone group at 1 month. Radiographic scores for joint destruction progressed similarly in both groups. There was a nonsignificant excess bone loss of 1.8% in the spine and 1.5% in the hip in the prednisone group, compared with the chloroquine group. CONCLUSION: Neither treatment was entirely satisfactory since a significant number of patients needed an additional second-line drug over the 2-year period.

Aged↗
PubMed1995

The G protein beta subunit is essential for multiple responses to chemoattractants in Dictyostelium.

Increasing evidence suggests that the beta gamma-subunit dimers of heterotrimeric G proteins play a pivotal role in transducing extracellular signals. The recent construction of G beta null mutants (g beta-) in Dictyostelium provides a unique opportunity to study the role of beta gamma dimers in signaling processes mediated by chemoattractant receptors. We have shown previously that g beta- cells fail to aggregate; in this study, we report the detailed characterization of these cells. The g beta- cells display normal motility but do not move towards chemattractants. The typical GTP-regulated high affinity chemoattractant-binding sites are lost in g beta- cells and membranes. The g beta- cells do not display chemoattractant-stimulated adenylyl cyclase or guanylyl cyclase activity. These results show that in vivo G beta links chemoattractant receptors to effectors and is therefore essential in many chemoattractant-mediated processes. In addition, we find that G beta is required for GTP gamma S stimulation of adenylyl cyclase activity, suggesting that the beta gamma-dimer activates the enzyme directly. Interestingly, the g beta- cells grow at the same rate as wild-type cells in axenic medium but grow more slowly on bacterial lawns and, therefore, may be defective in phagocytosis.

Adenylyl Cyclases↗
PubMed1995

The intramedullary hydraulic pressure tolerance of the human femur.

A new range of clinically used, biodegradable, bone-bonding copolymers has hydrogel properties. With intramedullary press fit, these polymers generate considerable pressure through swelling caused by water absorption. In total hip arthroplasty, high intramedullary pressures can be attained by insertion of the prosthesis into femora by using methylmethacrylate cement and a cement plug. Because the effects of such intramedullary pressures are not fully known, 10-cm-long segments of the proximal diaphysis of fresh femoral bones from 22 human cadavers were tested for their intramedullary pressure resistance. The intramedullary pressure resistance, calculated burst forces, and stress on the bone were correlated to age, gender, bone mineral content per unit length, and bone mineral density. In most bone segments, a burst fracture occurred just opposite the linea aspera. The hydraulic bursting pressures ranged from 2.3 to 13.4 MPa (age adjusted gender effect [male-female], 2.2 MPa [p = 0.05]). The forces at fracture were calculated to be between 265 and 1361 N (regression coefficient: 247/unit bone mineral content per unit length). The tangential stress appeared to be between 7.54 and 27.54 MPa (regression coefficient: 11.6/unit bone mineral density; bone mineral density adjusted gender difference [male-female], 4.5 MPa [p < 0.05]). Biochemical examination of the bones did not show any abnormalities. The results of this study show that the human femora can resist mechanically an intramedullary pressure of at least 2 MPa. From a mechanical point of view, intramedullary pressures generated by swelling polymers should remain below 2 MPa for safe use.

Aged↗
PubMed1994

A model for cAMP-mediated cGMP response in Dictyostelium discoideum.

In Dictyostelium discoideum extracellular cyclic AMP (cAMP), as shown by previous studies, induces a transient accumulation of intracellular cyclic guanosine-5'-monophosphate (cGMP), which peaks at 10 s and recovers basal levels at 30 s after stimulation, even with persistent cAMP stimulation. Additional investigations have shown that the cAMP-mediated cGMP response is built up from surface cAMP receptor-mediated activation of guanylyl cyclase and hydrolysis of cGMP by phosphodiesterase. The regulation of these activities was measured in detail on a seconds time-scale, demonstrating complex adaptation of the receptor, allosteric activation of cGMP-phosphodiesterase by cGMP, and potent inhibition of guanylyl cyclase by Ca2+. In this paper we present a computer model that combines all experimental data on the cGMP response. The model is used to investigate the contribution of each structural and regulatory component in the final cGMP response. Four models for the activation and adaptation of the receptor are compared with experimental observations. Only one model describes the magnitude and kinetics of the response accurately. The effect of Ca2+ on the cGMP response is simulated by changing the Ca2+ concentrations outside the cell (Ca2+ influx) and in stores (IP3-mediated release) and changing phospholipase C activity. The simulations show that Ca2+ mainly determines the magnitude of the cGMP accumulation; simulations are in good agreement with experiments on the effect of Ca2+ in electropermeabilized cells. Finally, when cGMP-phosphodiesterase activity is deleted from the model, the simulated cGMP response is elevated and prolonged, which is in close agreement with the experimental observations in mutant stmF that lacks this enzyme activity. We conclude that the computer model provides a good description of the observed response, suggesting that the main structural and regulatory components have been identified.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

Dual photon absorptiometry for bone mineral measurements using a gamma camera.

A gamma camera was equipped with a special collimator and arm assembly for bone mineral measurements with dual photon absorptiometry (DPA). The system was evaluated in vitro and in vivo and compared both with a rectilinear DPA and a dual energy X-ray (DEXA) system. All 3 systems showed a linear response in measurements of 4 vials, containing different amounts of hydroxyapatite. Phantom measurements with the gamma camera system showed a precision of 1.6% to 2.8%. Results obtained in 8 healthy volunteers with rectilinear and gamma camera systems were well correlated (R2 = 0.78). With the photon beam directed from posterior to anterior, the separation of vertebrae was easy with the gamma camera system. We conclude that bone mineral measurements can be made with a gamma camera for assessment of fracture risk and in the decision process whether a patient needs treatment or not. For follow-up, the precision of DPA with a gamma camera is inadequate.

Absorptiometry, Photon↗
PubMed1992

Inhibition of receptor-stimulated guanylyl cyclase by intracellular calcium ions in Dictyostelium cells.

In Dictyostelium discoideum extracellular cAMP stimulates guanylyl cyclase and phospholipase C; the latter enzyme produces Ins(1,4,5)P3 which releases Ca2+ from internal stores. The following data indicate that intracellular Ca2+ ions inhibit guanylyl cyclase activity. 1) In vitro, Ca2+ inhibits guanylyl cyclase with IC50 = 41 nM Ca2+ and Hill-coefficient of 2.1. 2) Extracellular Ca2+ does not affect basal cGMP levels of intact cells. In electro-permeabilized cells, however, cGMP levels are reduced by 85% within 45 s after addition of 10(-6) M Ca2+ to the medium; halfmaximal reduction occurs at 200 nM extracellular Ca2+. 3) Receptor-stimulated activation of guanylyl cyclase in electro-permeabilized cells is also inhibited by extracellular Ca2+ with half-maximal effect at 200 nM Ca2+. 4) In several mutants an inverse correlation exists between receptor-stimulated Ins(1,4,5)P3 production and cGMP formation. We conclude that receptor-stimulated cytosolic Ca2+ elevation is a negative regulator of receptor-stimulated guanylyl cyclase.

Animals↗
PubMed1992

The use of bisphosphonates in the treatment of osteoporosis.

The efficacy of bisphosphonates in the treatment of conditions characterized by increased osteoclastic bone resorption has been established. Recent evidence indicates that these compounds are also effective in the treatment of patients with osteoporosis. Two main protocols have been tried. One is based on the intermittent administration of the bisphosphonate, which is expected to decrease bone resorption, and give a drug-free period during which bone formation may proceed at a normal rate, leading to a positive calcium balance. The other argues that the resetting of the equilibrium in a cyclical process is, as a rule, incomplete and continuous low-grade suppression of resorption will result in a continuing positive bone balance. Intermittent administration of the first generation bisphosphonate, etidronate, for up to three years increases trabecular bone density, stabilizes it after two years, and appears to reduce the rate of new vertebral fractures in women with postmenopausal osteoporosis. Longer follow-up studies are needed before this beneficial effect is unequivocally established. Continuous administration of the second-generation bisphosphonate, pamidronate, increases spinal bone density in patients with osteoporosis linearly for up to four years, and is associated with a low rate of new vertebral fractures. These results need to be confirmed in controlled studies involving more patients. There are indications that pamidronate given continuously can prevent glucocorticoid-induced bone loss. There is no information about the effects of bisphosphonates on non-vertebral fractures. There are limited data about the use of bisphosphonates in the prevention of postmenopausal bone loss. Extensive studies on efficacy and safety are needed before this treatment is offered as an alternative to hormone replacement therapy.

Bone Resorption↗
PubMed1990

Limited precision of lumbar spine dual-photon absorptiometry by variations in the soft-tissue background.

The estimation error due to variations in soft-tissue baseline in lumbar bone mineral content (BMC) measured by dual-photon absorptiometry (DPA) was calculated with a new method of automatic baseline subtraction. In water phantom measurements, the s.d. of the soft-tissue (ST) baseline matched closely (r = 0.98) to the random error, calculated using 44 keV and 100 keV count rates and the directly determined baseline variations. In 21 volunteers and in 70 patients with osteoporosis, the ST variations were larger than the expected random error, revealing a source of error related to the inhomogeneity of soft tissue. The estimation error in BMC caused by ST variations was 0.7% in healthy subjects (mean BMC 40.5 gHA) and 1.5% in patients (mean BMC = 26.4 gHA). These results indicate that ST-related errors are an important limit to the precision of lumbar DPA measurements.

Absorptiometry, Photon↗
PubMed1989

Precision of dual photon absorptiometry measurements: comparison of three different methods of selection of the region of interest.

To determine the short-term reproducibility of bone mass calculations with dual photon absorptiometry of the lumbar spine (L2-L4), duplicate measurements in healthy subjects were used. Three different methods for selection of region of interest were compared: a rectangular region with variable height and width, an irregular region to be drawn freely by the operator and the standard calculation software supplied with the bone densitometer. Contributions of changes in size and location of the region of interest on calculated bone mineral mass were also investigated. An increase in height of the region by 2 scan lines caused an increase in bone mineral content (BMC) of 8.4% +/- 1.8%. Enlargement in width by 2 pixels in each scan line caused an increase in BMC of 2.5% +/- 1.3%. The difference between these region of interest changes was significant (P less than 0.0005). The use of a rectangular region, optimized to enclose L2-L4 in each person but of the same size in both measurements, resulted in a reproducibility of 1.4% and 0.7% respectively for 2 observers, with an inter observer variation of 1.2%. The reproducibility of the duplicate measurements was worse for the other methods of region of interest selection. A further series of duplicate DPA measurements in normal subjects, but with a standard meal between the measurements, showed a larger variation in the results. Again the reproducibility of the calculations using the rectangular region was better than with the other methods, with much less inter observer variation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

The reproducibility of single photon absorptiometry in a clinical setting.

The reproducibility of single photon absorptiometry (SPA) results for detection of changes in bone mineral content (BMC) was evaluated in a clinical setting. During a period of 18 months with 4 different sources, the calibration scans of an aluminium standard had a variation of less than 1% unless the activity of the 125I source was low. The calibration procedure was performed weekly and this was sufficient to correct for drift of the system. The short term reproducibility in patients was assessed with 119 duplicate measurements made in direct succession. The best reproducibility (CV = 1.35%) was found for fat corrected BMC results expressed in g/cm, obtained at the site proximal to the 8 mm space between the radius and ulna. Analysis of all SPA scans made during 1 year (487 scans) showed a failure of the automatic procedure to detect the space of 8 mm between the forearm bones in 19 scans (3.9%). A space adjacent to the ulnar styloid was taken as the site for the first scan in these examinations. This problem may be recognized and corrected relatively easy. A significant correlation was found between BMC of the lower arm and BMC of the lumbar spine assessed with dual photon absorptiometry. However, the error of estimation of proximal BMC (SEE = 20.0%) and distal BMC (SEE = 19.4%) made these measurements of little value to predict BMC at the lumbar spine in individuals. The short term reproducibility in patients combined with the long term stability of the equipment in our clinical setting showed that SPA is a reliable technique to assess changes in bone mass at the lower arm of 4% between 2 measurements with a confidence level of 95%.

Bone and Bones↗
PubMed1989

Maintained improvement in calcium balance and bone mineral content in patients with osteoporosis treated with the bisphosphonate APD.

The effects of the (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in osteoporosis were investigated in a series of open studies. Seven patients received a high dose of 600 mg/day of APD orally and showed an increase in calcium balance of 5.5 mmol/day (P less than 0.01) within a period of 10 days. In a group of 14 patients with osteoporosis, receiving a low dose of 150 mg/day of APD continuously, the mean calcium balance rose from -0.72 +/- 0.59 mmol/day before treatment to 1.33 +/- 0.87 mmol/day (P less than 0.005) after 1 year. In 24 patients treated with APD 150 mg/day for a mean period of 3.7 years (range 1.4-6.2) repeated dual photon absorptiometry measurements of the lumbar spine showed a mean rate of increase in bone mineral content of 3.1 +/- 1.0% per year (P less than 0.005). This yearly gain in bone mineral content appeared continuous for several years of treatment. In a comparable group of 19 patients with osteoporosis who also received conventional care and treatment but no APD, no significant changes in bone mineral content were found. Addition of a low dose of APD to conventional treatment of osteoporosis does not only prevent bone loss but induces a continuous gain in bone mass. These results justify long-term prospective studies with uninterrupted low dose APD treatment in osteoporosis.

Adult↗
PubMedDate not supplied

Cardiac metabolism: a technical spectrum of modalities including positron emission tomography, single-photon emission computed tomography, and magnetic resonance spectroscopy.

Noninvasive techniques for the assessment of cardiac metabolism are important for the detection of potentially salvageable tissue in jeopardized areas of the myocardium. The correct identification of hibernating and stunned myocardium in patients with severely depressed cardiac function can have vital therapeutic consequences for the patient. Changes in myocardial fatty acid and glucose metabolism during acute and prolonged ischemia can be traced by positron-emitting or gamma-emitting radiopharmaceuticals. Alternatively, 31P-labeled magnetic resonance spectroscopy can be used for the assessment of high-energy phosphate metabolism. It is not yet clear which modality will emerge as the most useful in the clinical setting. Positron emission tomography (PET) that uses combinations of flow tracers and metabolic tracers offers unique opportunities for quantification and high-resolution static and rapid dynamic studies. Currently, assessment of glucose metabolism with 18F-fluorodeoxyglucose is regarded as the gold standard for myocardial viability and prediction of improvement of impaired contractile function after revascularization. However, preserved oxidative metabolism may be required for potential functional improvement, and therefore assessment of residual oxidative metabolism by 11C-labeled acetate PET may prove to be more accurate than 18F-fluorodeoxyglucose PET, which reflects both anaerobic and oxidative metabolism. Moreover, because fatty acids are metabolized only aerobically, they are excellent candidates for the clinical assessment of myocardial viability and prediction of functional improvement after revascularization. Especially derivatives of fatty acids that are not metabolized but accumulate in the myocyte are attractive for myocardial imaging. Examples are 123I-beta-methyl-p-iodophenyl pentadecanoic acid and 15-(o-123I-phenyl)-pentadecanoic acid. These tracers can be detected by planar scintigraphy and single-photon emission computed tomography, which are more economical and widely available than PET. In addition, 511 keV collimators have been developed recently, making the detection of positron emitters by planar scintigraphy and single-photon emission computed tomography feasible. The experience with 31P-labeled magnetic resonance spectroscopy in humans is still limited. With current magnetic resonance spectroscopic techniques, insufficient spatial resolution is achieved for clinical purposes, but the possibility of serial measurements to monitor rapid changes of phosphate-containing molecules in time makes magnetic resonance spectroscopy very valuable for the research of myocardial metabolism.

Acetic Acid↗
PubMedDate not supplied

Dobutamine-atropine stress myocardial perfusion SPECT imaging in the diagnosis of graft stenosis after coronary artery bypass grafting.

OBJECTIVE: To assess the accuracy of dobutamine stress myocardial perfusion single photon emission computed tomographic imaging (SPECT) for the diagnosis of vascular stenosis after coronary artery bypass grafting (CABG). BACKGROUND: Exercise thallium scintigraphy is a clinically useful method for the diagnosis of graft stenosis after CABG. Although dobutamine perfusion scintigraphy is an alternative method for the evaluation of patients with limited exercise capacity, its value in the diagnosis of vascular stenosis after CABG has not been studied. METHODS: Dobutamine (up to 40 lg/kg/min)-atropine (up to 1 mg) stress test in conjunction with myocardial perfusion SPECT imaging (201T1 or 99m technetium sestamibi [MIBII) was performed in 71 patients (mean age 58 9 years, 57 men) with limited exercise capacity referred for evaluation of myocardial ischemia 3.7 3.5 years after CABG. Significant vascular stenosis was defined as >50% luminal diameter stenosis of a graft or a native nongrafted coronary artery and was predicted on the basis of reversible perfusion abnormalities. RESULTS: Significant vascular stenosis was detected in 52 patients. Sensitivity, specificity, and accuracy of reversible perfusion defects at dobutamine SPECT for the overall diagnosis of vascular stenosis were 81%, confidence interval (CI) 72 to 90, 79%, CI 69 to 88, and 80%, CI 71 to 90, respectively. Significant vascular stenosis was detected in 73 arterial regions. Sensitivity, specificity, and accuracy of dobutamine SPECT for the diagnosis of regional vascular stenosis were 66%, CI 58 to 74, 83%, CI 76 to 89, and 74%, CI 67 to 81, respectively. Patients with multivessel stenosis had a higher number of ischemic segments (1.6 + 1.3 vs 1 + 1, P < .05) and ischemic perfusion score (3.2 2.7 vs 2.2 + 2.3, P < .05) than patients with single-vessel stenosis, respectively. Significant graft stenosis was detected in 67 graft regions. Sensitivity, specificity, and accuracy of dobutamine SPECT for the diagnosis of regional graft stenosis were 64%, CI 56 to 73, 85%, CI 78 to 91, and 74%, CI 66 to 82, respectively. CONCLUSION: Dobutamine stress myocardial perfusion SPECT imaging is a useful method for the diagnosis of significant vascular stenosis after CABG in patients with limited exercise capacity.

Adult↗