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Biomedical subjects

C Egsmose

Publications and source records attributed to C Egsmose.

32 records · Page 2Linked to original sources

Metronidazole elimination is preserved in the elderly.

1 The disposition of metronidazole and its major metabolites was compared in 11 subjects aged 86 +/- 6 years and 8 aged 30 +/- 6 years. 2 The plasma clearance of metronidazole was 1.20 +/- 0.53 and 1.25 +/- 0.22 ml min-1 kg-1, the volume of distribution 0.77 +/- 0.27 and 0.77 +/- 0.09 1 kg-1 and the half-life 7.8 +/- 1.9 and 7.2 +/- 0.9 h in elderly and young subjects, respectively (P less than 0.05). 3 The area under the plasma concentration-time curve of the hydroxy metabolite was 32 +/- 14 and 21 +/- 3 mM min-1 (P less than 0.05) whereas its half-life was 21 +/- 14 and 12 +/- 2 h (P less than 0.05) in the elderly and young subjects, respectively. 4 The recovery in the urine of metronidazole and its metabolites was 42 +/- 21% and 87 +/- 6% of dose in elderly and young subjects, respectively (P less than 0.05). With this reservation the only elimination pathways of metronidazole affected by old age were the renal excretion of unchanged compound and the hydroxy metabolite. 5 It is concluded that the ability to eliminate metronidazole is preserved in old age and that age-related dose adjustments are not necessary.

Adult↗

Determination of bone Gla protein (osteocalcin) by enzyme-linked immunosorbent assay.

Bone Gla protein (BGP, osteocalcin) is a marker of bone formation. We present a novel enzyme-linked immunosorbent assay for measuring BGP in plasma and serum. The antibody used was raised in rabbits following immunisation with highly purified bovine BGP conjugated with keyhole limpet hemocyanin. The binding of the antibody to BGP was calcium-dependent. The sensitivity, inaccuracy, and imprecision of the assay equal or exceed existing radioimmunoassays, and the present assay is less tedious. Plasma BGP in 249 healthy adults, aged from 20 to 93 yr, was 8.3 +/- 6.6 micrograms/l (mean +/- 2 SD). A significant decrease was seen in both sexes from the third to the forth decade of life. A subsequent significant increase was seen with age in women. but not in men. Plasma BGP was significantly higher in young men than in young women, and significantly higher in elderly women than in elderly men. Values were in the same range as those found with existing radioimmunoassays.

Adult↗

Steady state pharmacokinetics of naproxen in elderly rheumatics compared with young volunteers.

The elderly rheumatic patients and 7 healthy young persons received naproxen (Naprosyn, Syntex) 500 mg orally twice a day for 4 weeks. The serum concentrations were determined using mass fragmentography. After an initial 1,000-mg dose, no significant differences were found between the two groups in peak serum concentration, time to peak serum concentration, area below the serum concentration-time curve, volume of distribution, elimination half-life, or total body clearance of naproxen. At steady state, the median total through naproxen concentration was 50.5 mg/l in the elderly and 62.7 in the young (p = 0.08); the unbound concentration was 58 micrograms/l and 44 micrograms/l, respectively (p = 0.06). There was a significant inverse correlation between serum albumin and the free fraction of naproxen (R = -0.58, p = 0.01). The hepatic extraction ratio of naproxen is relatively low and it is suggested that the reduced protein binding in the elderly may conceal the age-related reduction in cellular activity. An estimated value of intrinsic clearance was reduced by 37% in the elderly patients. It is suggested to start naproxen at the lower end of its dose range in the elderly.

Adult↗

Timegadine: more than a non-steroidal for the treatment of rheumatoid arthritis. A controlled, double-blind study.

Timegadine is a tri-substituted guanidine derivative which inhibits both arachidonate cyclo-oxygenase and lipoxygenase activity. In a 24-week randomized double-blind controlled trial, timegadine 500 mg/day was compared with naproxen 750 mg/day in two groups of 20 patients with active rheumatoid arthritis. In the timegadine group, significant improvements were seen in both biochemical and clinical markers of disease activity, i.e. ESR, serum IgG and IgM, leukocyte and platelet counts, duration of morning stiffness, Ritchie index, number of swollen joints, pain, and general condition. In the naproxen group, only the Ritchie index improved. Differences between treatments, when present, were always in favour of timegadine. Serum alkaline phosphatase rose during the first 8 weeks of treatment in the timegadine group. A transient rise was also seen in the naproxen group. The side effects reported were mainly gastrointestinal and allergic, the latter being more frequently found in the timegadine group. Timegadine is superior to naproxen in controlling disease activity in rheumatoid arthritis, and appears to possess disease-modifying properties.

Adult↗

Establishment of the relative antiinflammatory potency of deflazacort and prednisone in polymyalgia rheumatica.

Conventional glucocorticoids exert a negative influence on calcium balance, and long-term treatment with these agents leads to osteopenia. Deflazacort is an oxazoline derivative of prednisolone with documented calcium-sparing properties when compared to prednisone on a weight basis. The purpose of the present study was to determine the relative antiinflammatory potency of deflazacort and prednisone. In a randomized, cross-over, double-blind trial, 11 patients, all suffering from polymyalgia rheumatica, and all on a stable maintenance dose of prednisone, were treated with equimolar doses of prednisone and deflazacort (i.e., weight ratio 1:1.2) for two consecutive 2-week periods. Following deflazacort treatment, significant rises compared with initial values were seen in erythrocyte sedimentation rate (ESR), plasma fibrinogen, serum alkaline phosphatase, and general pain and tenderness. No changes were seen following prednisone treatment. Subsequently, in a similar regimen, prednisone was compared with deflazacort at a weight ratio of 1:1.2 in 10 patients, 1:1.5 in another 10 patients, and 1:1.8 in still another 10 patients for purposes of dose titration. Again, significant rises were seen in ESR, plasma fibrinogen, and serum alkaline phosphatase following the lowest dose of deflazacort, whereas no changes were seen following the higher doses of deflazacort or prednisone. In conclusion, the relative antiinflammatory potency of deflazacort and prednisone lies between 0.83 and 0.66 on a weight basis (1.02 and 0.82 on a molar basis) as evaluated by clinical and biochemical parameters reflecting disease activity in polymyalgia. This disease appears to represent a sensitive, reliable and reproducible clinical model for assessment of the relative antiinflammatory potency of glucocorticoids.

Aged↗

Low serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D in institutionalized old people: influence of solar exposure and vitamin D supplementation.

The vitamin D status was investigated in 94 geriatric patients in a Danish long-stay ward. The influence of mobility and thus possibility of outdoor activity was studied as well as the influence of regular vitamin D intake. Serum levels of 25-hydroxyvitamin D (25-OHD) were significantly reduced in all groups compared with age-matched controls. In 50% of the patients hypocalcaemia and elevated levels of alkaline phosphatase and immunoreactive parathyroid hormone (iPTH) were found in combination with severely reduced serum 25-OHD values (less than 5 ng/ml) indicating the presence of osteomalacia. Supplementation with 400 IU vitamin D daily in the winter months resulted in significantly higher 25-OHD levels and normocalcaemia while slightly elevated levels of alkaline phosphatase and iPTH persisted. The serum concentrations of 25-OHD were highest in the subjects who were not confined to bed. In these patients the biochemical parameters reflecting osteomalacia were normal. Low serum 1,25-dihydroxyvitamin D levels were found in the patients with low 25-OHD while 24,25-dihydroxyvitamin D levels were within the normal range in all groups and correlated with 25-OHD. Daily vitamin D supplementation appears to be indicated for geriatric patients, especially when bedridden, even in countries where the nutritional vitamin D intake is high.

Aged↗

Pharmacokinetic profile of indoprofen in elderly subjects.

Multiple dosing four times daily for 7 days of indoprofen 200 mg, a non-steroidal anti-inflammatory drug with a short half-life (t1/2), revealed drug accumulation in eight elderly subjects. This indicates a substantially longer t1/2 (11 h) than that reported in young persons (3 h). A reduction in dose compared to younger subjects is recommended in elderly patients with osteoarthritis.

Aged↗

Immunocytochemical demonstration of calmodulin in cells secreting by exocytosis.

Calmodulin is a regulator of several calcium-dependent cellular processes. It has been suggested that it plays a role in the mechanism of secretion. Employing an indirect immunoperoxidase technique at the light microscope level, this study demonstrates the presence of calmodulin in several exocytotic cells (mast cells, thyroid follicular cells, neurohypophyseal neurosecretory terminals, pancreatic beta-cells and pancreatic acinus cells) in rat and man. The positive staining reaction for calmodulin was granular and at least in the case of rat mast cells it appeared to be associated with the granule membrane.

Animals↗

Changes in vitamin D metabolites and bone histology in rats during recovery from rickets.

The relative roles of 25-hydroxyvitamin D (25-OHD), 1,25-dihydroxyvitamin D (1,25-(OH)2D) and 24,25-dihydroxyvitamin D (24,25-(OH)2D) in bone mineralization are largely unknown. Young vitamin D depleted rats were fed increasing amounts of vitamin D and grouped radiologically in accordance with the rat line test. They ranged from severely rachitic to normal. Radiology was correlated with serum levels of 25-OHD, 1,25-(OH)2D, 24,25-(OH)2D, ionized calcium, magnesium, and phosphate, with bone histology, and with the total mineral content of the animals. Serum 1,25-(OH)2D rose in a linear fashion to supranormal values during bone healing and correlated with the radiological degree of rickets. Serum 25-OHD was below detection limit in the most rachitic and low in the radiologically normal rats, whereas 24,25-(OH)2D was low in all groups. These two metabolites showed no correlation with the radiologic, histologic or biochemical parameters. In rachitic rats, 1,25-(OH)2D appears to play a major role in bone healing and possibly exerts a direct effect on bone cells. It cannot be ruled out, however, that the effect is mediated through a rise in serum levels of calcium and phosphorus, although signs of bone healing were seen in the presence of a subnormal calcium X phosphorus product. Initiation of mineralization can take place with unmeasurable 25-OHD, and 24,25-(OH)2D seems to be without importance.

Animals↗

Hip joint distension in osteoarthrosis. A triple-blind controlled study comparing the effect of intra-articular indoprofen with placebo.

In a triple-blind controlled study, significant pain alleviation (p less than 0.01) was registered in patients with osteoarthrosis (OA) of the hip in the first 24 h after hip joint distension. There was no significant difference between treatment with indoprofen (a new non-steroidal anti-inflammatory drug for intra-articular use) and placebo. Pain relief lasted for at least 12 weeks in approximately half of the patients, in whom a significant increase in joint mobility was registered. Intra-articular indoprofen was not superior to placebo as regards pain relief or increased joint mobility. These findings indicate that the effect of a single hip joint distension in OA is due to a mechanical distension of the joint capsule, perhaps involving disruption of local agglutinations, and not due to suppression of inflammation.

Adult↗

Soft tissue composition, quadriceps strength, bone quality and bone mass in rheumatoid arthritis.

OBJECTIVES: To examine differences in soft tissue composition, bone quality, bone mass and quadriceps strength between women with rheumatoid arthritis (RA) and healthy controls. METHODS: 79 women with RA (median disease duration 10 yrs) were studied. Most were or had been on steroids. 67 healthy age-matched women served as controls. The lean tissue mass (LTM) and fat mass (FM) of the total body and of the major body subregions, as well as the bone mineral density (BMD, g/cm2) of the femoral neck, spine (L2-L4) and distal forearm were measured by dual energy x-ray absorptiometry (DXA). Bone quality expressed as the speed of sound (SOS m/sec), broadband ultrasound attenuation (BUA, dB/MHz) and stiffness was assessed by an Achilles ultrasound device, and isometric quadriceps strength by an isokinetic dynamometer. RESULTS: No between-group differences were found for the body mass index (BMI, weight/height2), total or regional percentage fat, LTM and FM. However, women with RA had 20% lower quadriceps strength than controls. BMD at the femoral neck and distal forearm, and SOS, BUA and stiffness were significantly lower in patients than in controls. No difference was found for spine BMD. In the RA group, z-scores for SOS and stiffness were significantly more reduced than those for BMD. Multiple regression analyses indicated negative associations between ultrasound parameters and the cumulative steroid dose. CONCLUSIONS: Reductions in BMD and muscle strength in RA were not accompanied by changes in soft tissue composition, Bone quality assessed by ultrasonography was compromised in RA and may be modified by steroids.

Absorptiometry, Photon↗