Biomedical subjects

K Weber

Publications and source records attributed to K Weber.

At least 55 records · Page 3Linked to original sources

PubMed2001

Prevalent vertebral deformity predicts incident hip though not distal forearm fracture: results from the European Prospective Osteoporosis Study.

The presence of a vertebral deformity increases the risk of subsequent spinal deformities. The aim of this analysis was to determine whether the presence of vertebral deformity predicts incident hip and other limb fractures. Six thousand three hundred and forty-four men and 6788 women aged 50 years and over were recruited from population registers in 31 European centers and followed prospectively for a median of 3 years. All subjects had radiographs performed at baseline and the presence of vertebral deformity was assessed using established morphometric methods. Incident limb fractures which occurred during the follow- up period were ascertained by annual postal questionnaire and confirmed by radiographs, review of medical records and personal interview. During a total of 40348 person-years of follow-up, 138 men and 391 women sustained a limb fracture. Amongst the women, after adjustment for age, prevalent vertebral deformity was a strong predictor of incident hip fracture, (rate ratio (RR) = 4.5; 95% CI 2.1-9.4) and a weak predictor of 'other' limb fractures (RR = 1.6; 95% CI 1.1-2.4), though not distal forearm fracture (RR = 1.0; 95% CI 0.6-1.6). The predictive risk increased with increasing number of prevalent deformities, particularly for subsequent hip fracture: for two or more deformities, RR = 7.2 (95% CI 3.0-17.3). Amongst men, vertebral deformity was not associated with an increased risk of incident limb fracture though there was a nonsignificant trend toward an increased risk of hip fracture with increasing number of deformities. In summary, prevalent radiographic vertebral deformities in women are a strong predictor of hip fracture, and to a lesser extent humerus and 'other' limb fractures; however, they do not predict distal forearm fractures.

Aged↗

PubMed2001

Physiological responses in tennis and running with similar oxygen uptake.

The purpose of the study was to compare selected physiological responses during singles tennis match play and continuous running at a similar mean oxygen uptake (VO2). The study consisted of two main parts, which were separated by 1 week. In the first part, 12 nationally ranked senior tennis players [six females and six males; 47.2 (6.6) years old and 47.0 (5.4) years old, respectively] each completed a 2-h singles tennis match (TE). Mean VO2 during TE [23.1 (3.1) ml.kg(-1). min(-1) for the women and 25.6 (2.8) ml.kg(-1).min(-1) for the men] was measured by a portable spirometry-telemetry system and corresponded to 56% (women) or 54% (men) of their respective maximum VO2. In the second part, the relative VO2 data measured during TE were used to set a similar workload during a 2-h treadmill run at a constant level (RU). At the measured time points, heart rate [140.1 (15.5) beats.min(-1) vs 126.4 (15.1) beats. min(-1)], lactate concentration [1.53 (0.65) mmol.l(-1) vs 1.01 (0.38) mmol.l(-1)] and glucose concentration [5.45 (0.84) mmol.l(-1) vs 4.34 (0.56) mmol.l(-1)] in capillary blood, as well as the respiratory exchange ratio [0.93 (0.03) vs 0.88 (0.03)], were higher (P<0.05) in TE compared to RU. Serum concentrations of free fatty acids increased (P < 0.05) during both work loads [from 0.25 (0.15) mmol.l(-1) to 1.31 (0.44) mmol.l(-1) in TE and from 0.22 (0.17) mmol.l(-1) to 1.24 (0.35) mmol.l(-1) in RU]. Post-exercise urine concentrations of epinephrine [0.17 (0.14) micromol.l(-1) vs 0.08 (0.04) micromol.l(-1)] and norepinephrine [1.27 (0.59) micromol.l(-1) vs. 0.55 (0.33) micromol.l(-1)] were higher in TE (P<0.05). These results indicate a stronger metabolic emphasis on glycolysis and glycogenolysis and an overall enhanced sympathoadrenal activity during tennis match play compared to continuous running exercise at a similar mean VO2.

Adult↗

PubMed2001

Aspects of Lyme borreliosis in Europe.

Lyme borreliosis in Europe is somewhat different from that encountered in the USA. The aim of this review is to present historical, ecological, epidemiological, clinical, and therapeutic aspects associated with Lyme borreliosis in Europe. It becomes apparent that a considerable body of information about European Lyme borreliosis exists, which has been accumulated for more than 100 years.

Animals↗

PubMed2001

Incidence and prevalence of infection with human granulocytic ehrlichiosis agent in Germany. A prospective study in young healthy subjects.

BACKGROUND: Only limited data are available on incidence and prevalence of infection with the human granulocytic ehrlichiosis (HGE) agent in a healthy population. MATERIALS AND METHODS: In a prospective study, we tested 361 male soldiers (age 18-29 years) from southwestern Germany for the HGE agent immunoglobulin G (IgG) using an indirect immunofluorescence antibody assay and for Borrelia burgdorferi IgG with an ELISA at the beginning and the end of their 10-month military service. Using a standardized questionnaire, the subjects were asked about clinical symptoms at the beginning and the end of the observation period. RESULTS: Of these 361 subjects, 14.9% were HGE agent IgG positive at study entry. 19 participants (5.3%) seroconverted from IgG negative to positive during the observation period resulting in an incidence rate of 6.4% per year. 20 subjects converted from initially HGE agent IgG positive to negative resulting in a reconversion rate of 6.6% per year. Concurrence of Borrelia IgG and HGE agent IgG was observed in 21.1%, whereas 13.7% were HGE agent IgG positive but Borrelia IgG negative (not significant). Clinical symptoms associated with HGE were not present in seroconverting subjects. CONCLUSION: Infection with the HGE agent occurs frequently in southwestern Germany but was asymptomatic in these young subjects.

Adolescent↗

PubMed2001

Species-specific elimination of polychlorinated biphenyls in estuarine animals and its impact on residue patterns.

Elimination kinetics of tetra-, penta- and hexachlorobiphenyls (IUPAC Nos. 44, 52, 87, 95, 101, 153) were investigated by laboratory experiments in three species of different phyla: Nereis diversicolor (Polychaeta), Palaemon longirostris (Crustacea) and Platichthys flesus (Pisces). Half-lives were species-specific and structure-dependent. Palaemon longirostris eliminated all components fastest. N. diversicolor was faster than Platichthys flesus except for components 95 and 153. Contrary to the fish species, the two invertebrates contained significant amounts of polar transformation products of No. 52, which had been applied as 14C labelled. Therefore, the faster elimination by Palaemon longirostris and N. diversicolor was assumed to be generally due to increased biotransformation. Elimination was in accordance with polychlorinated biphenyl (PCB) residue patterns obtained from field samples of the species. Congeners with vicinal H atoms in m,p positions were under-represented in Palaemon longirostris and so were congeners with > or = 7 Cl in N. diversicolor, while the PCB residue pattern in Platichthys flesus was similar to that of Clophen A60. By comparing percentages of the experimental congeners in sigma PCB and their elimination half-lives in the three species, it was revealed that residue patterns were also influenced by species-dependent uptake, e.g. feeding habits. Extractable organic matter-based sigma PCB levels increased with trophic levels of the three species.

Animals↗

PubMed2001

Effects of endocrine modulating substances on reproduction in the hermaphroditic snail Lymnaea stagnalis L.

Various man-made agents like pesticides, industrial chemicals and some natural substances have the potential to alter hormonal pathways that regulate reproductive processes in certain species of wildlife. Until now, only a few investigations have been undertaken to determine the effects of these substances on reproductive capacities (fecundity and fertility) in exposed invertebrate aquatic species. In this study one of the most abundant mollusc of European limnic systems, the hermaphroditic gastropod Lymnaea stagnalis was investigated to determine the effects of endocrine modulating substances on reproductive parameters. Known endocrine modulating substances were tested using the following nominal concentrations; Tributyltin (TBT in ng Sn/l) and beta-sitosterol at 1, 10 and 100 ng/l, respectively, and 4-nonylphenol (4-NP) at 1, 10 and 100 microg/l. In addition, experiments were carried out with 1, 10 and 100 ng/l of t-methyltestosterone. All the testing was carried out on recently matured adults of Lymnaea. Fifteen to twenty snails per treatment were exposed for between 7 and 12 weeks in a semi-static test with a weekly exchange of testwater. Shell height and weight and mortality of the adults, egg production, hatching rate of the eggs, and histopathology of the adult snails were analysed. The same parameters were investigated on F(1) generation snails from exposed parents at two dates (1 week after exposure and at the end of the exposure duration). Treatments with TBT and 4-NP had only slight effects on the egg production of the adults and hatching rate of the eggs. However, increased histopathological changes were observed in epithelial tissues of the adult snails, e.g. lung and foot also characterised by extreme inflammatory processes. While beta-sitosterol and t-methyltestosterone had no effect on the shell height and weight or the mortality of adult snails nor on the egg production or ensuing egg hatching rate, beta-sitosterol treated snails presented a distinct atrophy of the albumen gland and so did t-methyltestosterone, albeit with a lower degree of atrophy. The observed histopathological effects due to exposure to tributyltin or 4-NP are suggested to lead to long-term adverse reproductive effects mediated by an impairment of the fitness of the snails. In the experiments the steroid-dependant (beta-sitosterol and t-methyltestosterone) degeneration of the albumen gland caused no obvious adverse effects on the fecundity nor fertility of the adults or on F(1)-generation. However, the impact on fertility following a prolonged exposure to high concentrations of the phytoestrogen cannot be predicted.

Animals↗

PubMed2001

Marginal quality and microleakage of adhesive class V restorations.

OBJECTIVES: The aim of this in vitro study was to determine the marginal quality and microleakage of composite resin class V restorations. METHODS: Standardized mixed class V cavities (diameter: 4mm, depth: 2mm) with half of the finish lines limited within dentin were cut in 90 freshly extracted human molars and randomly assigned to nine groups (n=10). After etching enamel and dentin, the cavities were restored with nine different restorative systems (Syntac Sprint/Tetric Ceram=SS, Syntac Single-Component/Tetric Ceram=SC, Onestep/Aeliteflo=OS, Aquaprep+Onestep/Aeliteflo=OA, Prime & Bond 2.1/TPH=PB, Optibond Solo/Prodigy=OP, Singlebond/Z100=SB, Tenure Quik/Marathon=TQ, Solobond M/Arabesk=SM) using a wet-bonding procedure. After finishing and polishing, the teeth were stored for 24h in distilled water at 37 degrees C before they were subjected to thermocycling (5/55 degrees C, 1000x). Epoxy replicas were made for margin analysis in the SEM. Specimens were stained in methylene blue, sectioned, and evaluated for microleakage. Dye penetration was scored on a 0-3 ordinal scale. RESULTS: Statistical analysis (Kruskal-Wallis H-test, Mann-Whitney U-test) revealed significant differences (P<0.05) among the groups at dentin and enamel margins for the microleakage scores as well as for the results of the quantitative SEM margin analysis. SC revealed a significantly higher percentage of perfect margins in the SEM than OS and SM in enamel and dentin, respectively. OA exhibited significantly more leakage in enamel than all other groups. CONCLUSIONS: None of the tested restorative systems achieved a perfect seal in dentin and enamel of mixed class V cavities. Marginal quality and sealing ability of adhesive systems to dentin, using a wet-bonding procedure, is still inferior compared with enamel margins.

Barium Compounds↗

PubMed2001

Developmentally controlled expression patterns of intermediate filament proteins in the cephalochordate Branchiostoma.

Expression of cytoplasmic intermediate filament (IF) proteins starts in the gastrula with three keratins (k1, Y1, D1) and protein X1. The number of IF proteins expressed increases at the neurula and early larval stages to seven and 11, respectively, and reaches 13 in the adult. Using antibodies specific for a single IF protein the expression patterns of nine of the 13 IF proteins were analyzed at different developmental stages. Keratin k1 of the larval epidermis is replaced in the juvenile by keratin E1. Protein C1 of the larval epidermis persists only weakly and only in the most ventral part of the adult. While down-regulated in the adult epidermis k1 and C1 are major proteins in the atrial epithelium which forms in the later larva. B1 is currently the only IF protein expressed in mesodermally derived tissues such as the muscle tails and some coelomic epithelia. Two-dimensional gels confirm that keratins are the major IF proteins in the nerve cord. Immunogold electronmicroscopy shows that proteins X1 and C2 are present in epidermis and nerve cord in keratin IF.

Animals↗

PubMed2001

Immune reconstitution and production of intracellular cytokines in T lymphocyte populations following autologous peripheral blood stem cell transplantation.

For the better understanding of engraftment properties after autologous peripheral blood stem cell transplantation (PBSCT), hematopoietic recovery, immune reconstitution and functional capacity of cytokine production in different lymphocyte populations were examined. In a prospective study, we examined 24 patients suffering from different malignancies after autologous PBSCT. The examination intervals were 1, 3, 6 and 12 months after PBSCT. T cells, B cells and NK cells were analyzed using flow cytometry. The expression and kinetics of cytokines in T lymphocytes were evaluated in 10 patients by intracellular staining of cytokines after PMA/ionomycin stimulation. We observed rapid hematopoietic engraftment proceeding to stable long-term reconstitution. For CD3(+) lymphocytes, a consistent reconstitution associated with an increase in CD3(+)CD8(+) cytotoxic T cells was observed, whereas the CD3(+)CD4(+) helper/inducer T cells remained low (< 200/microl). Impaired B lymphopoiesis with severe depression (<1%) was detected 1 month after PBSCT but recovered thereafter (12.8% after 3 months). The percentages of cytokine-producing T cells and the mean fluorescence intensity (MFI) shifts suggested an insufficient capacity for producing IFNgamma, in particular for CD3(+)CD4(+) T cells, compared to healthy volunteers early after PBSCT. Rapid hematopoietic recovery and partly impaired immune reconstitution, especially regarding the regeneration of B lymphocytes and T helper cells, was observed. The CD4(+) subpopulation remained low throughout the period of examination, whereas the B cells showed a delayed recovery after 3 months. Cytokine production proved to be sufficient after in vitro stimulation in T cell populations with the exception of IFNgamma synthesis.

Adult↗

PubMed2001

Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in nondiabetic, morbidly obese subjects with body mass index greater than 30.

We studied 31 nondiabetic, habitually (> or =5 years) morbidly obese subjects (mean +/- SD body mass index [BMI] 43 +/- 8.7, median 43). Our specific aim was to determine whether metformin (2.55 g/d for 28 weeks) would ameliorate morbid obesity and reduce centripetal obesity; lipid and lipoprotein cholesterol, insulin, and leptin levels; and plasminogen activator inhibitor activity (PAI-Fx), risk factors for coronary heart disease (CHD). The patients were instructed to continue their prestudy dietary and exercise regimens without change. After 2 baseline visits 1 week apart, the 27 women and 4 men began receiving metformin, 2.55 g/d, which was continued for 28 weeks with follow-up visits at study weeks 5, 13, 21, and 29. Daily food intake was recorded by patients for 7 days before visits then reviewed with a dietitian. Kilocalories per day and per week were calculated. At each visit, fasting blood was obtained for measurement of lipid profile, insulin, leptin, and PAI-Fx. The mean +/- SD kilocalories consumed per day, 1,951 +/- 661 at entry, fell by week 29 to 1,719 +/- 493 (P =.014) but did not differ at weeks 5, 13, and 21 from that at week 29 (P >.2). Weight fell from 258 +/- 62 pounds at entry to 245 +/- 54 pounds at week 29 (P =.0001). Girth was reduced from 51.8 +/- 6.2 to 49.2 +/- 4.5 inches (P =.0001). Waist circumference fell from 44.0 +/- 6.4 inches to 41.3 +/- 5.9 (P =.0001). The waist/hip ratio fell from 0.85 +/- 0.09 to 0.84 +/- 0.09 (P =.04). Fasting serum insulin, 28 +/- 15 microU/mL at entry, fell to 21 +/- 11 microU/mL at week 29 (P =.0001), and leptin fell from 79 +/- 33 ng/mL to 55 +/- 27 ng/mL (P =.0001). On metformin, there were linear trends in decrements in weight, girth, waist circumference, waist/hip ratio, insulin, and leptin throughout the study period (P <.007). Low-density lipoprotein (LDL) cholesterol, 126 +/- 34 mg/dL at study entry, fell to 112 +/- 43 mg/dL at week 29 (P =.001), with a linear trend toward decreasing levels throughout (P =.036). By stepwise linear regression, the higher the entry weight, the larger the reduction in weight on metformin therapy (partial R(2) = 31%, P =.001). The greater the reduction in kilocalories consumed per day, the greater the decrease in weight on metformin therapy (partial R(2) = 15%, P =.011). The higher the waist/hip ratio at entry, the greater its reduction on metformin therapy (partial R(2) = 11%, P =.004). The higher the entry serum leptin, the greater its reduction on metformin therapy (partial R(2) = 29%, P =.002). The greater the reduction in insulin on metformin, the greater the reduction in leptin (partial R(2) = 8%, P =.03). The higher the entry PAI-Fx, the greater the reduction in PAI-Fx on metformin (partial R(2) = 43%, P =.0001). Metformin safely and effectively reduces CHD risk factors (weight, fasting insulin, leptin, LDL cholesterol, centripetal obesity) in morbidly obese, nondiabetic subjects with BMI > 30, probably by virtue of its insulin-sensitizing action.

Adult↗

PubMed2001

The effect of recovery duration on running speed and stroke quality during intermittent training drills in elite tennis players.

The aim of this study was to assess the effect of the recovery duration in intermittent training drills on metabolism and coordination in sport games. Ten nationally ranked male tennis players (age 25.3+/-3.7 years, height 1.83+/-0.8 m, body mass 77.8+/-7.7 kg; mean +/- sx) participated in a passing-shot drill (baseline sprint with subsequent passing shot) that aimed to improve both starting speed and stroke quality (speed and precision). Time pressure for stroke preparation was individually adjusted by a ball-machine and corresponded to 80% of maximum running speed. In two trials (T10, T15) separated by 2 weeks, the players completed 30 strokes and sprints subdivided into 6 x 5 repetitions with a 1 min rest between series. The rest between each stroke-and-sprint lasted either 10 s (T10) or 15 s (T15). The sequence of both conditions was randomized between participants. Post-exercise blood lactate concentration was significantly elevated in T10 (9.04+/-3.06 vs 5.01+/-1.35 mmol x l(-1), P < 0.01). Running time for stroke preparation (1.405+/-0.044 vs 1.376+/-0.045 s, P < 0.05) and stroke speed (106+/-12 vs 114+/-8 km x h(-1), P < 0.05) were significantly decreased in T10, while stroke precision - that is, more target hits (P < 0.1) and fewer errors (P < 0.05) - tended to be higher. We conclude that running speed and stroke quality during intermittent tennis drills are highly dependent on the duration of recovery time. Optimization of training efficacy in sport games (e.g. combined improvement of conditional and technical skills) requires skilful fine-tuning of monitoring guidelines.

Adult↗

PubMed2001

An analysis of polygenes affecting wing shape on chromosome 2 in Drosophila melanogaster.

Genetic effects on an index of wing shape on chromosome 2 of Drosophila melanogaster were mapped using isogenic recombinants with transposable element markers. At least 10 genes with small additive effects are dispersed evenly along the chromosome. Many interactions exist, with only small net effects in homozygous recombinants and little effect on phenotypic variance. Heterozygous chromosome segments show almost no dominance. Pleiotropic effects on leg shape are only minor. At first view, wing shape genes form a rather homogeneous class, but certain complexities remain unresolved.

Alleles↗

PubMed2001

Relevance of IGF-I, IGFBP-3, and IGFBP-2 measurements during GH treatment of GH-deficient and non-GH-deficient children and adolescents.

BACKGROUND: Little information is available on the relevance of parameters representing the insulin-like growth factor (IGF) system with regard to growth hormone (GH) treatment during childhood. In adults, high IGF-I levels were found to be associated with side effects and long-term risks. AIM/METHOD: Our aim was to monitor the serum levels of IGF-I, IGF-binding protein (IGFBP) 3, and IGFBP-2 during long-term GH treatment of 156 patients with GH deficiency (GHD) and of 153 non-GHD patients. We determined the extent to which the IGF parameters exceed the normal ranges and identified those parameters which are predictive of 1st-year growth. RESULTS: In prepubertal GHD children, the levels of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 exceeded the 95th centile of the reference values for this age group in 2.3, 0.3, and 7.9% of the cases, respectively, whereas in prepubertal non-GHD children, the same parameters exceeded the 95th reference centile in 20.1, 3.5, and 32.2%, respectively. In pubertal GHD children IGF-I, IGFBP-3, and IGF-I/IGFBP-3 levels exceeded the 95th reference centile in 11.1, 1.5, and 15.4%, respectively. In pubertal non-GHD children, these levels also exceeded the 95th centile in 26.7, 7.0, and 41.4%, respectively. In both GHD and non-GHD groups, however, some patients had IGF parameters which were below the reference values. Our analysis showed that, in both groups, in addition to maximum GH, all IGF parameters (IGF-I, IGFBP-3, IGF-I/IGFBP-3 ratio, IGFBP-2 or derivatives) significantly extend the scope of a calculated model for predicting 1st-year height velocity. CONCLUSION: For reasons of safety and optimization of GH therapy, it is essential to follow up IGF-I, IGFBP-3, and IGFBP-2 levels regularly during childhood.

Adolescent↗

PubMed2001

Genes for intermediate filament proteins and the draft sequence of the human genome: novel keratin genes and a surprisingly high number of pseudogenes related to keratin genes 8 and 18.

We screened the draft sequence of the human genome for genes that encode intermediate filament (IF) proteins in general, and keratins in particular. The draft covers nearly all previously established IF genes including the recent cDNA and gene additions, such as pancreatic keratin 23, synemin and the novel muscle protein syncoilin. In the draft, seven novel type II keratins were identified, presumably expressed in the hair follicle/epidermal appendages. In summary, 65 IF genes were detected, placing IF among the 100 largest gene families in humans. All functional keratin genes map to the two known keratin clusters on chromosomes 12 (type II plus keratin 18) and 17 (type I), whereas other IF genes are not clustered. Of the 208 keratin-related DNA sequences, only 49 reflect true keratin genes, whereas the majority describe inactive gene fragments and processed pseudogenes. Surprisingly, nearly 90% of these inactive genes relate specifically to the genes of keratins 8 and 18. Other keratin genes, as well as those that encode non-keratin IF proteins, lack either gene fragments/pseudogenes or have only a few derivatives. As parasitic derivatives of mature mRNAs, the processed pseudogenes of keratins 8 and 18 have invaded most chromosomes, often at several positions. We describe the limits of our analysis and discuss the striking unevenness of pseudogene derivation in the IF multigene family. Finally, we propose to extend the nomenclature of Moll and colleagues to any novel keratin.

Amino Acid Sequence↗

PubMed2001

Identification of essential genes in cultured mammalian cells using small interfering RNAs.

We report the first RNAi-induced phenotypes in mammalian cultured cells using RNA interference mediated by duplexes of 21-nt RNAs. The 21 gene products studied have different functions and subcellular localizations. Knockdown experiments monitored by immunofluorescence and immunoblotting show that even major cellular proteins such as actin and vimentin can be silenced efficiently. Genes were classified as essential or nonessential depending on impaired cell growth after RNA silencing. Phenotypes also involved altered cell morphology and aberrant mitotic arrest. Among the essential genes identified by RNAi for which such information was previously not available are lamin B1, lamin B2, NUP153, GAS41, ARC21, cytoplasmic dynein, the protein kinase cdk1 and both beta- and gamma-actin. Newly defined nonessential genes are emerin and zyxin. Several genes previously characterized by other methods such as knockout of murine genes are included as internal controls and gave identical results when RNAi was used. In the case of two nonessential genes (lamin A/C and zyxin) RNAi provides a recognizable phenotype. Our results complete the characterization of the mammalian nuclear lamins. While lamins A/C appear as nonessential proteins in the mouse embryo and in RNAi treated cultured cells, the two other lamins, B1 and B2, are now identified as essential proteins. Interestingly the inner nuclear membrane protein emerin, thought to be a ligand of lamin A/C, is also a nonessential protein in tissue culture cells.

Animals↗

PubMed2001

1alpha-hydroxyvitamin D2 is less toxic but not bone selective relative to 1alpha-hydroxyvitamin D3 in ovariectomized rats.

Identification of bone selective vitamin D analogues would provide an interesting substance class for the treatment of osteoporosis. The synthetic prodrug 1alpha-hydroxyvitamin D2 [1alpha(OH)D2] has been shown to combine equal bone-preserving activity with distinctly reduced calcemic effects relative to 1alpha-hydroxyvitamin D3 [1alpha(OH)D3] in 3-month-old ovariectomized (OVX) rats. Therefore, 1alpha(OH)D2 may be a bone-selective compound. The aim of this study was to compare the bone protective and the calcemic activities of chronically administered 1alpha(OH)D2 and 1alpha(OH)D3 in 6-month-old OVX rats over a broad dose range from ineffective to toxic doses. Ninety-six female 6-month-old Fischer-344 rats were used for this experiment. Eighty rats were bilaterally OVX, 8 rats were sham-operated (SHAM), and 8 rats were killed at the time of surgery as a baseline control. Groups of OVX rats received vehicle alone (n = 16) or daily doses in the diet of 0.025, 0.05, 0.1, and 0.2 microg of 1alpha(OH)D2 or 1alpha(OH)D3 per kg body weight (BW) per day (n = 8 each). After calcein double-labeling, all animals were killed 3 months post-OVX. Orally administered 1alpha(OH)D2 was significantly less toxic compared with 1alpha(OH)D3 in terms of BW gain and kidney calcium content. The effects of 1alpha(OH)D2 and 1alpha(OH)D3 on serum calcium and urinary calcium excretion were generally similar at all doses in this study. Both 1alpha(OH)D2 and 1alpha(OH)D3 prevented the estrogen deficiency-induced bone loss in OVX rats, and induced profound bone anabolic effects at high dosages. 1alpha(OH)D3 and 1alpha(OH)D2 also dose-dependently increased total bone mineral density (BMD), cortical area, and cortical thickness in the tibial diaphysis of OVX rats. Bone resorption as assessed by osteoclast numbers (Oc.Ns) in vertebral cancellous bone and urinary excretion of deoxypyridinoline (DPD) was dose-dependently suppressed by 1alpha(OH)D2 and 1alpha(OH)D3. These data show that although 1alpha(OH)D2 was slightly but significantly less toxic compared with 1alpha(OH)D3, it did not have increased skeletal effects at any dose. Taken together, our findings argue against selective metabolic activation of 1alpha(OH)D2 in bone.

Animals↗

PubMed2001

The clavicle: a vulnerable bone in pediatric oncology.

The clavicle is frequently incorporated into the radiation field in the treatment of malignant tumors located in the head and neck. From 1954 to 1995, 499 pediatric patients were treated with moderate to high-dose radiation therapy to the head and neck at the University of Texas M.D. Anderson Cancer Center. The medical records of 312 of these patients were available and were reviewed. The period of observation ranged from 5 to 30 years. Five late radiation-induced abnormalities of the clavicle were encountered: osteosarcoma; osteochondroma; malignant fibrous histiocytoma; radionecrosis and impaired healing following trauma and radionecrosis and lysis. The doses of radiation therapy which induced the abnormalities varied from 35 to 60.5 Gy (median 34.75 Gy). The interval from radiation therapy to discovery of the complications varied from 6 to 11 years. Two patients died: one from malignant fibrous histiocytoma and another from a radiation-induced meningioma of the brain (which accompanied radionecrosis of the clavicle). We conclude that the incidence of radiation-induced abnormalities of the clavicle in pediatric long-term survivors is low (1.5%). However, some of the late sequela are potentially fatal. The clavicle should be considered a vulnerable bone to radiation therapy and should be monitored in long-term survivors of childhood cancer. The experience is compared to radiation-induced abnormalities recorded in the literature.

Adolescent↗

PubMed2001

[Influence of stable iodine on the uptake of the thyroid--model versus experiment].

AIM: The influence of physiological and pharmacological amounts of iodine on the uptake of radioiodine in the thyroid was examined in a 4-compartment model. This model allows equations to be derived describing the distribution of tracer iodine as a function of time. The aim of the study was to compare the predictions of the model with experimental data. METHODS: Five euthyroid persons received stable iodine (200 micrograms, 10 mg). I-123-uptake into the thyroid was measured with the Nal(Tl)-detector of a body counter under physiological conditions and after application of each dose of additional iodine. Actual measurements and predicted values were compared, taking into account the individual iodine supply as estimated from the thyroid uptake under physiological conditions and data from the literature. RESULTS: Thyroid iodine uptake decreased from 80% under physiological conditions to 50% in individuals with very low iodine supply (15 micrograms/d) (n = 2). The uptake calculated from the model was 36%. Iodine uptake into the thyroid did not decrease in individuals with typical iodine supply, i.e. for Cologne 65-85 micrograms/d (n = 3). After application of 10 mg of stable iodine, uptake into the thyroid decreased in all individuals to about 5%, in accordance with the model calculations. CONCLUSION: Comparison of theoretical predictions with the measured values demonstrated that the model tested is well suited for describing the time course of iodine distribution and uptake within the body. It can now be used to study aspects of iodine metabolism relevant to the pharmacological administration of iodine which cannot be investigated experimentally in humans for ethical and technical reasons.

Biological Transport↗