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Biomedical subjects

E Lesaffre

Publications and source records attributed to E Lesaffre.

At least 55 records · Page 3Linked to original sources

Factors associated with cortical and trabecular bone loss as quantified by peripheral computed tomography (pQCT) at the ultradistal radius in aging women.

Peripheral quantitative computed tomography (pQCT) allows the separate determination of cortical and trabecular bone mineral density in the peripheral skeleton. This cross-sectional study was designed to examine the effects of healthy aging on pQCT measurements at the ultradistal radius. In a well-defined sample of 129 community-based women, aged 70-87 years, the differences in cortical and trabecular density over the age range were equivalent to losses of -0.41% and -0.65% per year, respectively. To investigate the mechanism of this age-related decline, we assessed relationships between both parameters and height, weight, body mass index, dietary calcium intake, grip strength, and serum concentrations of insulin-like growth factor-I (IGF-I), calcidiol (25(OH)D3), calcitriol (1,25(OH)2D3), parathyroid hormone (PTH), and sex hormone binding globulin (SHBG). Multiple regression was used to adjust for potential confounders. Age was not significant after controlling for other covariables. Body mass index, grip strength, serum IGF-I, 25(OH)D3, and PTH (1-84) were found to be independent predictors of total bone density. Including (total or free) 1,25(OH)2D3 did not improve the model precision. These findings provide evidence that, among other factors, the activity of the growth hormone-IGF-I-axis is of importance for skeletal integrity. Grip strength, serum IGF-I, and PTH (1-84) were discovered to be significantly related to cortical but not to trabecular density, suggesting that different mechanisms may be involved in compact and cancellous bone loss.

Aged↗

Determinants of age-associated changes in os calcis ultrasonic indices in elderly women: potential involvement of geriatric hyposomatotropism in bone fragility.

OBJECTIVE: ultrasound measures a clinically relevant property of bone strength in addition to and distinct from bone mass. The aim of the present study was to examine the effects of healthy ageing on ultrasound measurements of the calcaneus. DESIGN: cross-sectional study. STUDY PARTICIPANTS: a sample of 177 community-dwelling healthy women aged 70-87 years. Exclusion criteria were diseases or medications known to affect the musculoskeletal system or the somatotrophic axis. MEASUREMENTS: serum levels of 1,25-dihydroxyvitamin D3 and insulin-like growth factor-I (IGF-I) were measured by radioimmunoassay, serum 25-hydroxyvitamin D3 (25(OH)D3) was determined by competitive binding assay and serum parathyroid hormone was assessed immunochemically. Isometric and isokinetic quadriceps strength were evaluated using a Cybex II system. Calcaneal ultrasound indices--broadband ultrasound attenuation (BUA) and speed of sound (SOS)--were measured with an Achilles system. RESULTS: we found a significant decrease with ageing in BUA and SOS (-0.5 and -1.3% per year, respectively), suggesting a continuing loss of bone quality. Quadriceps strength, serum IGF-I and 25(OH)D3 constituted the best predictors of BUA, while IGF-I was the only parameter found to be independently associated with SOS. CONCLUSION: these findings suggest that, among other factors, the activity of the growth hormone-IGF-I axis is of importance for skeletal integrity. Age-related bone fragility may, in part, be related to geriatric hyposomatotropism.

Aged↗

Is metabolic evidence for vitamin B-12 and folate deficiency more frequent in elderly patients with Alzheimer's disease?

BACKGROUND: It is still unclear whether there is an association between Alzheimer's disease and vitamin B-12 or folate deficiency. This study was designed to investigate whether patients with Alzheimer's disease are particularly prone to metabolically significant cobalamin or folate deficiency as compared to nondemented hospitalized controls and healthy elderly controls living at home. METHODS: Evaluation for the diagnosis of Alzheimer's disease, routine laboratory tests, serum folate and vitamin B-12, serum methylmalonic acid (MMA), total homocysteine (tHcy), and radiological tests was performed in 52 patients with Alzheimer's disease (AD), 50 nondemented hospitalized controls, and 49 healthy elderly subjects living at home. RESULTS: Serum vitamin B-12 and folate levels are comparable between patients with AD, hospitalized control patients, and subjects living at home. Patients with AD have the highest serum MMA and tHcy levels. The MMA levels of patients with AD and hospitalized controls are not different, but the mean tHcy level is significantly higher in patients with AD as compared to nondemented patients or subjects living at home. CONCLUSION: The interpretation of the vitamin B-12 and folate status in patients with AD depends largely on the methodology (i.e., serum vitamin vs metabolite levels) and the selection of the control group. Although patients with AD have the highest tHcy and MMA levels, metabolically significant vitamin B-12 and folate deficiency is also a substantial problem in nondemented elderly patients.

Aged↗

Short-term reproducibility of pressure pain thresholds in masseter and temporalis muscles of symptom-free subjects.

Pressure pain thresholds (PPTs) of the bilateral masseter and temporalis muscles were assessed over a single day and in between 2 days with the aid of an electronic algometer in 11 males and 11 females. Using a mixed model approach, covariance results were controlled for confounding of gender, day, time of the day and the within-session replications of the measurements. For every jaw muscle, the first PPT measurement of a session was markedly higher than the last one of that same session. Except for the right temporalis muscles, no significant systematic PPT differences could be observed between male and female subjects. The differences between morning and afternoon sessions were not significant for any of the muscles tested. Although the PPTs measured on the 1st day were systematically lower than those on the 2nd day for the left masseter and temporalis muscles, no significant difference between the time of the day could be observed when the values of the different muscles were grouped within a subject. Analysis of variance showed that the variability induced by the day or the time of the day was similar to the variability of the measurement itself. The inter-individual variability of PPTs was 2.3 to 9 x higher than the variability observed between trials, sessions or days. The results indicate that the PPT measurement will not be systematically influenced by the time of registration (morning/afternoon) or inbetween consecutive days. In addition, the important inter-individual differences favor the use of longitudinal within-subject studies.

Adult↗

Time course of serum lipids and apolipoproteins after acute myocardial infarction: modification by pravastatin.

Pravastatin was administered to patients suffering an acute myocardial infarction starting with a dose of 10 mg/day at day 3 and continuing with a dose of 20 mg/day up to a period of 3 months. The study was performed on the basis of a randomized placebo-controlled double-blind trial. At the dosage used pravastatin significantly lowered the total cholesterol and LDL-cholesterol levels and increased the HDL-cholesterol levels compared to placebo. A prospective clinical trial in order to examine the possible clinical relevance of these findings is recommended.

Anticholesteremic Agents↗

Effect of dropouts in a longitudinal study: an application of a repeated ordinal model.

An analysis is presented of a longitudinal study of fluvoxamine, an antidepressant drug, with ordinal responses, regressed on a combination of discrete and continuous covariates and with a substantial proportion of dropouts. Classical methods, such as weighted least squares (SAS procedure CATMOD) and logistic regression, are not suitable for the analysis of such data. Instead, we illustrate how a recently introduced model can be used to solve most of the problems posed. The method is likelihood-based and is an extension of the bivariate Dale model to an arbitrary number of outcomes. The method is suitable for several types of designs commonly employed in clinical trials.

Antidepressive Agents, Second-Generation↗

Dietary salt, nitrate and stomach cancer mortality in 24 countries. European Cancer Prevention (ECP) and the INTERSALT Cooperative Research Group.

BACKGROUND: High salt and nitrate intake are considered as risk factors for stomach cancer, but little is known about possible interactions. This ecological study examines the respective importance of both factors for stomach cancer mortality at the population level using data obtained under standardized conditions and with biochemical analyses performed in the same laboratories. METHODS: Randomly selected 24-hour urine samples from 39 populations, sampled from 24 countries (N = 5756 people for sodium, 3303 for nitrate) were obtained from the INTERSALT study. Median sodium and nitrate levels were age- and sex-standardized between ages 20-49 years and averaged per country. Ecological correlation-regression analyses were done in relation to national stomach cancer mortality rates. RESULTS: The Pearson correlation of stomach cancer mortality with sodium for the 24 countries was: 0.70 in men and 0.74 in women (both P < 0.001) and with nitrate: 0.63 (P = 0.001) in men and (P < 0.005) in women. In multiple regression of stomach cancer mortality, using sodium and nitrate as independent variables the adjusted R2 was 0.61 in men and 0.54 in women (both P < 0.001). Addition of the interaction term (sodium x nitrate) to the previous model increased the adjusted R2 to 0.77 in men, and to 0.63 in women. The analysis of this model showed that the importance of nitrate as risk factor for stomach cancer mortality increased markedly with higher sodium levels. However, the relationship of stomach cancer mortality with sodium was always stronger than with nitrate. CONCLUSIONS: Salt intake, measured as 24-hour urine sodium excretion, is likely the rate-limiting factor of stomach cancer mortality at the population level.

Adult↗

A 12-week treatment for dermatophyte toe onychomycosis: terbinafine 250 mg/day vs. itraconazole 200 mg/day--a double-blind comparative trial.

Lamisil (terbinafine) 250 mg daily and itraconazole 200 mg daily were compared in the treatment of dermatophyte toe onychomycosis over 12 weeks in a double-blind randomized clinical trial. At the end of follow-up (week 48) treatment with Lamisil led to negative mycology in 73% of patients compared with 45.8% in the itraconazole group (P < 0.0001). Globally the clinical symptoms of the target nail improved, a response which was in favour of Lamisil (P = 0.001). The percentages of patients who were clinically totally cured or who presented with only minimal symptoms were 76.3% for the Lamisil-treated group compared with 58.1% in the itraconazole group. The unaffected nail length for big toes was significantly higher in the Lamisil-treated group (9.1 mm vs. 7.7 mm; P = 0.0298). Onycholysis was also less in the Lamisil group (P = 0.001). We conclude that 12 weeks' continuous oral therapy leads to higher cure rates with Lamisil than with itraconazole and that both drugs are equally well tolerated.

Administration, Oral↗

Relationship between baseline insulin-like growth factor-I (IGF-I) and femoral bone density in women aged over 70 years: potential implications for the prevention of age-related bone loss.

OBJECTIVE: To test the hypothesis that the decline in femoral bone mass associated with healthy aging is partially accounted for by deficiency of the growth hormone-insulin-like growth factor-I (IGF-I) axis. DESIGN: Cross-sectional study. STUDY PARTICIPANTS: A sample of 245 community-dwelling healthy women aged 70 and older. Exclusion criteria were diseases or medications known to affect the musculoskeletal system or the somatotrophic axis. MEASUREMENTS: Serum levels of IGF-I, calcitriol, and osteocalcin were determined by radioimmunoassay; serum calcidiol was measured by competitive binding assay, and serum parathyroid hormone (PTH) was assessed immunochemically. Urinary pyridinium crosslinks were measured by fluorescent detection after high-pressure liquid chromatography. Isometric and isokinetic quadriceps strength was evaluated using an isokinetic dynamometer. Bone density (BMD) was assessed by dual-energy X-ray absorptiometry at the proximal femur. Multiple regression was used to adjust for potential confounders. RESULTS: At the proximal femur, BMD declined by 0.59-0.84% per year. In addition to body mass index and muscle strength, serum IGF-I was found to be an independent predictor of BMD at all femoral sites. CONCLUSION: The data support the hypothesis that circulating IGF-I not only reflects the integrated growth hormone secretion but also has a direct role in the endocrine regulation of bone remodeling. The present findings support the need for further studies to assess the potential of IGF-I in attenuating age-related femoral bone loss.

Age Factors↗

Are different reference intervals for methylmalonic acid and total homocysteine necessary in elderly people?

To determine whether age-adjusted reference intervals for methymalonic acid (MMA) and total homocysteine (tHcy) are necessary, data from 2 previous studies were used. First, the reference intervals for serum vitamin B12, folate, methylmalonic acid and total homocysteine were determined in 2 reference sample groups: 99 healthy adults and 64 selected healthy elderly subjects living at home. Secondly, health-related reference limits were estimated in 143 elderly subjects after supplementing the nutritional status with a combination of vitamin B12, vitamin B6 and folate during a 3-wk period. In the latter group, the adjusted reference intervals for MMA (46-288 nmol/L) as well as for tHcy (5-13.6 mumol/L) are different with considerably lower upper reference limits than that estimated with the original reference values (72-476 nmol/L for MMA; 6.8-21 mumol/L for tHcy) in the elderly subjects. Our data suggest that the MMA and tHcy levels increase with age. Moreover, the upper reference limit for MMA and tHcy, conventionally defined as the mean +2 SD in healthy elderly reference sample group without supplementing the nutritional status, might result in falsely high values due to a high prevalence of an inadequate vitamin B12, vitamin B6 and folate status.

Adult↗

Tauroconjugation of cholic acid stimulates 7 alpha-dehydroxylation by fecal bacteria.

We examined the effect of the type of cholic acid conjugation (taurine-conjugated, glycine-conjugated, or unconjugated cholic acid) on cholic acid 7 alpha-dehydroxylation by intestinal flora. Cholic acid 7 alpha-dehydroxylation in fecal cultures, in cultures of a defined limited flora consisting of a mixture of seven bacterial species isolated from the intestinal tract, and in a binary culture of a 7 alpha-dehydroxylating Clostridium species plus a cholic acid-deconjugating Bacteroides species was studied. We found that tauroconjugation of cholic acid significantly (P < 0.05) increased bacterial 7 alpha-dehydroxylation of cholic acid into deoxycholic acid from 34 to 55% in fecal cultures, from 45 to 60% in defined limited fecal cultures, and from 75 to 100% in binary cultures. Equimolar concentrations of free taurine did not stimulate 7 alpha-dehydroxylation in fecal cultures or in the defined limited flora, but free taurine did stimulate 7 alpha-dehydroxylation in the binary culture. In the binary culture of Clostridium species strain 9/1 plus Bacteroides species strain R1, the minimal flora capable of increased 7 alpha-dehydroxylation of taurocholic acid, strain R1 deconjugated taurine and rapidly reduced it to H2S. Bacteroides species strain R1 did not grow unless taurine or another appropriate reducible sulfur source was present. Clostridium species strain 9/1 did not grow or 7 alpha-dehydroxylate unless H2S or another source of reduced sulfur was present. We conclude that the increased 7 alpha-dehydroxylation of tauroconjugated cholic acid depends on the reduction of taurine to H2S, which is a necessary growth factor for the 7 alpha-dehydroxylating bacteria.

Bacteria↗

Deficiency of the growth hormone-insulin-like growth factor-I axis potentially involved in age-related alterations in body composition.

Because the body composition effects of growth hormone and insulin-like growth factor-I (IGF-I) are opposite to those of advancing age, it has been hypothesized that the decreased activity of the growth hormone-IGF-I axis is partly responsible for the loss of bone and muscle mass that characterizes normal human aging. The aim of the present cross-sectional analysis was to test this hypothesis in a well-defined community-based sample of 245 healthy elderly women. Dual-energy X-ray absorptiometry was used to measure body composition. To establish the major determinants of total bone mineral content (TBBMC), we assessed the relationships between TBBMC and age, height, weight, body mass index, muscle strength and serum concentrations of IGF-I, calcidiol, calcitriol, parathyroid hormone and sex hormone-binding globulin. Total body lean mass (TBLM), an indication of muscle mass, was related to the following potential determinants: age, habitual physical activity and serum IGF-I. Multiple regression was used to adjust for potential confounders. A significant relationship between circulating IGF-I and TBLM was not apparent in this study. On the other hand, serum IGF-I was found to be an independent predictor of TBBMC, despite the inclusion of established determinants of bone mass. These findings suggest that the demineralization of the skeleton in aging women is in part due to a deficiency of the somatotrophic axis.

Absorptiometry, Photon↗

Correlation between oxidized low density lipoproteins and von Willebrand factor in chronic renal failure.

An ELISA specific for a wide spectrum of oxidized apo B-100 in OxLDL was developed and applied to blood samples from 27 control subjects, 20 mild chronic renal failure (MCRF) patients, 21 severe chronic renal failure patients on conservative treatment (SCRF) and 56 severe chronic renal failure patients on maintenance hemodialysis (HEMO). Mean levels of OxLDL were 0.59 mg/dl in controls (95% CI, 0.52-0.66 mg/dl), and were 2.7-fold (p < 0.01), 3.1-fold (p < 0.001) and 5.4-fold (p < 0.001) higher in MCRF, SCRF and HEMO patients, respectively. Levels of von Willebrand factor, a marker of endothelial injury, were 100 percent in controls (95% CI, 90-110 percent), and were 1.5-fold (p = NS), 1.6-fold (p < 0.01) and 2.1-fold (p < 0.001) higher in MCRF, SCRF and HEMO patients, respectively. Multiple regression analysis revealed that the extent of renal failure (F = 14; p = 0.0004) accounted for a significant fraction of the variation in OxLDL levels, also after exclusion of patients with evidence of ischemic atherosclerotic disease (F = 21; p = 0.0001). After adjustment for the extent of renal failure, hemodialysis (F = 5.6; p = 0.021) and LDL cholesterol levels (F = 7.1, p = 0.0095) contributed significantly to the variation in OxLDL levels. Whereas the extent of renal failure contributed only marginally to the individual variations in vWF levels (F = 4.1; p = 0.048), these levels correlated significantly with plasma levels of OxLDL (F = 26; p = 0.0001). In conclusion, OxLDL increase progressively during the development of renal failure suggesting that the oxidation of LDL may be associated with endothelial injury and atherogenesis in these patients.

Aged↗

Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS)

OBJECTIVE: To evaluate the efficacy and safety of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke. DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. SETTING: A total of 75 hospitals in 14 European countries. PATIENTS: A total of 620 patients with acute ischemic hemispheric stroke and moderate to severe neurologic deficit and without major early infarct signs on initial computed tomography (CT). INTERVENTION: Patients were randomized to treatment with 1.1 mg per kilogram of body weight of rt-PA (alteplase) or placebo within 6 hours from the onset of symptoms. OUTCOME MEASURES: Primary end points included Barthel Index (BI) and modified Rankin Scale (RS) at 90 days. Secondary end points included combined BI and RS, Scandinavian Stroke Scale (SSS) at 90 days, and 30-day mortality. Tertiary end points included early neurologic recovery (SSS) and duration of in-hospital stay. Safety parameters included mortality and incidence of intracranial or extracranial hemorrhage. RESULTS: The distribution of demographic variables was similar among patients in the rt-PA and placebo treatment arms in both the intention-to-treat (ITT) analysis and the explanatory analysis for the target population (TP). A total of 109 patients (17.4%) were included in the trial despite major protocol violations but excluded from the TP. There was no difference in the primary end points in the ITT analysis, while the TP analysis revealed a significant difference in the RS in favor of rt-PA-treated patients (P = .035). Of the secondary end points, the combined BI and RS showed a difference in favor of rt-PA-treated patients in both analyses (P < .001). Neurologic recovery at 90 days was significantly better for rt-PA-treated patients in the TP (P = .03). The speed of neurologic recovery assessed by the SSS was significantly better up to 7 days in the ITT analysis and up to 30 days for the TP in the rt-PA treatment arm. In-hospital stay was significantly shorter in the rt-PA treatment arm in both analyses. There were no statistically significant differences in the mortality rate at 30 days or in the overall incidence of intracerebral hemorrhages among the rt-PA and placebo treatment arms in either analysis. However, the occurrence of large parenchymal hemorrhages was significantly more frequent in the rt-PA-treated patients. CONCLUSIONS: Intravenous thrombolysis in acute ischemic stroke is effective in improving some functional measures and neurologic outcome in a defined subgroup of stroke patients with moderate to severe neurologic deficit and without extended infarct signs on the initial CT scan. However, the identification of this subgroup is difficult and depends on recognition of early major CT signs of early infarction. Therefore, since treating ineligible patients is associated with an unacceptable increase of hemorrhagic complications and death, intravenous thrombolysis cannot currently be recommended for use in an unselected population of acute ischemic stroke patients.

Acute Disease↗

Measurement of femoral geometry in type I and type II osteoporosis: differences in hip axis length consistent with heterogeneity in the pathogenesis of osteoporotic fractures.

The epidemiologic patterns of vertebral and femoral fractures are sufficiently different to suggest that they represent distinct disorders (type I versus type II osteoporosis) although osteopenia is common in both. To determine whether differences in femoral geometry, one of the main determinants of bone quality, might contribute to the heterogeneity in osteoporotic fractures, we obtained dual energy X-ray absorptiometry scans on 210 women age 60 or older, including 105 type I fracture cases, 30 type II patients, and 75 controls. Hip axis length, measured on the scan printout, was significantly increased (p < 0.01) in hip fracture patients compared with women with postmenopausal osteoporosis, whereas femoral neck density (BMD) was equal in both groups. The best discrimination between both fracture types was obtained by a logistic regression model based on age and axis length. Adding BMD to the model did not improve the discriminative power (p = 0.67). These data provide further evidence that geometric characteristics may be implicated in hip fracture risk. Furthermore, these findings suggest that an increase in hip axis length may predispose osteopenic subjects to a femoral localization of fragility fractures, consistent with the postulated heterogeneity in the pathogenesis of osteoporotic fractures.

Absorptiometry, Photon↗

The use of Sandimmun (cyclosporin A) in severe refractory rheumatoid arthritis: the Belgian experience.

OBJECTIVE: To investigate practicability, efficacy and tolerability of low starting doses of Sandimmun (cyclosporin A) (2.5 mg/kg daily) in patients with severe refractory rheumatoid arthritis in the short (6 months) and middle (12 months) term. METHODS: Fifty-nine patients, presenting with active and severe rheumatoid arthritis unresponding to conventional DMRADs were allowed to start Sandimmun at the dose of 2.5 mg/kg daily. This dose was progressively increased by steps of 25 mg daily up to a maximum of 5 mg/kg daily according to the renal function and blood pressure. RESULTS: A mean maintenance dose of 3.9 mg/kg daily was reached after 5 months and maintained throughout the study. Twenty-one patients (36%) completed the one year study. The reasons for discontinuation were: inefficacy (13), adverse events (17), both inefficacy and adverse events (5) and non-compliance (3). For those patients who completed the trial, clinical relevant improvements were observed within 3 months of treatment and were maintained until the end of the study for the Lee functional and the Ritchie articular index, as well as for the number of tender and swollen joints. No changes for the grip strength, the biological and immunological parameters were observed. Mean serum creatinine values rose from 0.81 mg/dl at start to 1.1 mg/dl after 5 months of therapy and remained at that level throughout the study. In patients who discontinued, the serum creatinine level nearly normalized after one month of Sandimmun withdrawal. One hundred and sixty-two side effects were reported of which most were minor and known to occur with Sandimmun. Twenty-two cases (37% of patients) dropped out for adverse events before 1 year treatment. The criteria to withdraw the patients from the study differed greatly from centre to centre. CONCLUSIONS: Managing RA patients presenting with very long and severe disease remains difficult. Therefore low dose Sandimmun (2.5-5 mg/kg daily) appears to be a valuable therapeutic opportunity in RA patients refractory to various other conventional drugs, including methotrexate.

Adolescent↗

Maxillofacial growth after neck burn injury at a young age: an experimental study in the rabbit.

An experimental model was designed to define alterations in the normal mandibular growth process under the influence of postburn neck contractures. Additionally, this craniofacial growth model was used to compare two early treatment modalities of neck burns in their capability to minimize contracture and hence allow for normal mandibular growth and development. Growth implies increase in size as well as change in shape and position. These three aspects of growth were defined accordingly to Björk as rotations. The intramatrix rotation expresses the change in mandibular shape, and the matrix rotation expresses the change in mandibular position relative to surrounding structures. The total rotation expresses both, and together with the measurement of the mandibular length, they represent the increase in mandibular size. Thirty-two 7-week-old rabbits were divided at random in four groups of eight rabbits each and randomized for selection for the 14 operation days defined as t = 0: Group A: controls to define normal mandibular growth Group B: untreated third-degree neck burns Group C: third-degree neck burns treated by a full-thickness skin graft Group D: third-degree neck burns treated by a myocutaneous flap All animals underwent placement of two bone markers in the maxilla. With biweekly intervals, standardized lateral skull roentgenographs were taken until the rabbits reached the age of 21 weeks. In this time period, major growth accelerations including the pubertal growth spurt took place. By the use of 13 reference points and 7 reference lines, rotations and distances were calculated. Statistical analysis of the data was performed. The results show that the normal mandibular length was unaffected in all groups. There were no statistically significant changes in matrix, intramatrix, and total rotations of the mandible and the maxilla. There was a statistically significant difference in the displacement of the mandibular reference point between all groups, suggesting a variable degree of normal backward skull rotation, namely, due to group B. Explanations to be considered concerning the fact that the only minor differences were found in group B: 1. Drawbacks of the animal model: differences in skin texture, postnatal mandibular growth, and head position compared with those of humans. 2. Other functional adaptation mechanisms such as changes in head position, which are recruited at first in adapting to disturbances of homeostasis, were not measured. Soft-tissue compensation probably has overcome major bony deformations. Nevertheless, some drawbacks of the model can be viewed as ideal concerning treatment of neck burns.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Influence of age, sex, and insulin on osteoblast function: osteoblast dysfunction in diabetes mellitus.

The osteoblast function was evaluated in normal and diabetic children and adults by measurements of the serum concentration of the carboxy-terminal extension peptide of procollagen (PICP), total and skeletal alkaline phosphatase (ALP), and osteocalcin. Moreover, the osteoblast-stimulating growth factor, insulin-like growth factor I (IGF-I), was measured in the same samples. In normal children (n = 420; age, 5-20 yr), a marked pubertal increase of serum IGF-I (peak values at age 14-16 yr in both sexes), osteocalcin, and total and skeletal ALP (peak values earlier in girls than in boys) and a small increase in PICP were observed. All osteoblast markers and IGF-I were markedly lower in normal adults (n = 229; age, 21-69 yr) than in children. All osteoblast parameters showed a high degree of correlation (P < 0.001) with each other. In adolescents (n = 104) treated for insulin-dependent diabetes mellitus (IDDM), serum IGF-I (-19%), osteocalcin (-28%), and skeletal ALP (-28%) were markedly decreased, whereas total ALP was significantly increased (29%), and serum PICP remained normal. In adult IDDM (n = 125), both serum IGF-I (-41%) and osteocalcin (-24%) were decreased, but skeletal ALP and PICP remained normal. A similar abnormality in serum IGF-I and osteocalcin was observed in white (n = 61) and Pima Indian (n = 16) non-IDDM patients. The concentration of skeletal ALP was highly significantly correlated (r > or = 0.9) with total ALP in both normal and diabetic subjects, but the slope of the regression was significantly different, indicating the presence of other, probably intestinal, ALP in all types of diabetes. In conclusion, the osteoblast function is significantly decreased in diabetic patients, which can best be characterized as a maturation defect, since the early osteoblast marker, PICP, remained normal in all types of diabetes, whereas a later marker, skeletal ALP, is frankly abnormal only in diabetic children. The most mature osteoblast marker, osteocalcin, is decreased in all types of diabetes irrespective of age.

Adolescent↗