Comparison of quantitative ultrasound in the human calcaneus with mechanical failure loads of the hip and spine.

OBJECTIVE: Quantitative ultrasound of the calcaneus is used clinically for evaluating bone fracture risk, but its association with the mechanical properties at other skeletal sites is not well characterized. The objective was therefore to determine its predictive ability of the mechanical failure loads of the proximal femur and lumbar spine. METHOD: In 45 human cadavers (29 males and 16 females, aged 82.5 +/- 9.6 years), we determined the speed of sound, broadband ultrasonic attenuation (BUA) and the empirical stiffness index, using a commercial quantitative ultrasound scanner. The proximal femora and the fourth vertebral body were excised and loaded to failure in a testing machine. RESULTS: Femoral failure loads ranged from 933 to 7000 N and those of the vertebrae from 1000 to 7867 N, their correlation being 0.51 in females and -0.08 in males. Forty percent of the variability of femoral, but only 24% of the variability of the vertebral fracture loads could be predicted with calcaneal speed of sound. In the femur, a combination of speed of sound and BUA improved the prediction (r2 = 50-60%), but not in the spine. CONCLUSIONS: The study provides experimental evidence that calcaneal quantitative ultrasound is capable of predicting mechanical failure at other skeletal sites and has potential to identify patients at risk from osteoporotic fracture. The different association of quantitative ultrasound with femoral and vertebral failure may result from the influence of the cortical bone and a higher microstructure-related similarity of the calcaneus and the femur.

Prediction of vertebral failure loads from spinal and femoral dual-energy X-ray absorptiometry, and calcaneal ultrasound: an in situ analysis with intact soft tissues.

The objective of the current study was to determine the correlation of spinal and femoral dual-energy X-ray absorptiometry (DXA) and calcaneal ultrasound, measured in situ with intact soft tissues, with the in vitro failure loads of lumbar vertebral bodies. Forty-nine cadavers with intact skin and soft tissues (32 men aged 82.1 +/- 9.0 years, 17 women aged 83.1 +/- 10.1 years) were examined. The bone mineral content (BMC), the projectional area, and the bone mineral density (BMD) of the lumbar spine and proximal femur were determined with DXA, and the ultrasonic properties of the calcaneus with quantitative calcaneal ultrasound. The fourth lumbar vertebra was then excised with adjacent intervertebral disks and its mechanical failure load determined, using a materials testing machine. Absolute fracture loads were significantly higher in men than in women, but they were similar after adjusting for body weight and height. Spinal DXA was significantly associated with vertebral failure load (r = 0.62 combined; r = 0.54 men; r = 0.58 women). Femoral DXA (r = 0.46) and calcaneal ultrasound (r = 0.48) showed somewhat lower correlation coefficients, with the speed of sound (SOS) being able to add predictive information in a stepwise regression model. Normalizing the vertebral failure loads to body weight and height reduced the correlations, with only spinal DXA yielding a significant relationship. Our data suggest that previous in vitro studies may have overestimated the association between spinal DXA and vertebral failure loads, presumably because measurements were performed on excised bones, but not in situ in the presence of soft tissue inhomogeneity. The results indicate that, even in a population of old age and under in situ conditions, spinal DXA may still be somewhat better than femoral DXA and calcaneal ultrasound in predicting vertebral failure loads.

Correlation of femoral and lumbar DXA and calcaneal ultrasound, measured in situ with intact soft tissues, with the in vitro failure loads of the proximal femur.

The objective of this study was to determine experimentally the sex-specific correlation of femoral and lumbar DXA and calcaneal ultrasound, measured in situ, with the in vitro failure loads of the proximal femur. Fifty-eight cadavers with intact skin and soft tissues (34 male, aged 81.2 +/- 8.7 years; 24 female, aged 83.7 +/- 10.6 years) were examined. The bone mass of the proximal femur and the lumbar spine were determined using dual-energy X-ray absorptiometry and the ultrasonic properties of the calcaneus with quantitative ultrasound. Afterwards, the right femora were excised 18 cm distal to the minor trochanter, and their load to failure determined with a material testing machine. Femoral fracture loads were significantly higher in males than in females, both before and after correcting for body height and weight. Femoral neck bone mineral density (BMD) was significantly correlated with femoral failure loads (r = 0.65 all specimens, 0.57 males (0.64 after excluding trochanteric fractures) and 0.77 females; p < 0.001). The correlations with the ultrasonic Stiffness Index of the calcaneus were in a similar range (r = 0.67 all specimens, 0.48 males (0.64 after excluding trochanteric fractures) and 0.65 females; p < 0.001). The correlations between femoral failure loads and the spinal BMD were lower (r = 0.40, p < 0.01), particularly in males (r = 0.30, not significant). In contrast to previous experimental investigations on excised bones, our results are consistent with clinical studies that have reported that ultrasound and femoral DXA have a similar ability to predict the risk of hip fracture.

Continuous ambulatory peritoneal dialysis impairs T lymphocyte selection in the peritoneum.

Peritoneal lymphocytes (PCL) of 45 healthy individuals, four uremic patients with end-stage renal disease (ESRD) and 25 long-term continuous ambulatory peritoneal dialysis (CAPD) patients were characterized by flow cytometry to investigate whether CAPD alters the phenotype of PCL. B lineage cells constitute a minority of PCL (2.5% of cells). Although the majority of peritoneal T cells expressed alpha beta T cell receptor (TcR), 7% expressed gamma delta TcR, a proportion which was significantly higher than that in peripheral blood (PBMC) (approximately 4%). The majority of PCL T cells exhibited markers of the thymus-dependent lineage (CD2, CD3, TcR alpha beta, CD8 alpha beta or CD4) and surface antigens associated with memory and activation (CD45RO, CD11a, CD18, CD49d, HLA-DR). An average of 75% of both CD4+ and CD8+ PCL T cells of healthy subjects and CAPD patients were CDw60+, thus characterizing the T cell subset containing the helper activity for the mitogen-driven B cell differentiation. CD44s was abundantly expressed on PCL T cells. In contrast to PCL T cells of healthy subjects peritoneal T lymphocytes of CAPD patients exhibited CD44 splice variants containing products of exon-v9 and the proportion of CD44v9+ cells correlated with the frequency of peritonitis episodes the patients had gone through. The majority of PCL T cells of both healthy subjects and CAPD patients were CD8+. A large proportion of CD8+ PCL T cells from healthy subjects expressed the homodimeric CD8 alpha alpha isoform; however, such cells were not found in CAPD patients. In healthy subjects mRNA for the recombination activating gene 1 (RAG-1) was detectable in a PCL population containing CD7-CD34+ and CD7+CD34+ cells. In contrast, neither mRNA transcripts of the RAG-1 gene nor CD34+ cells were detectable in PCL of CAPD patients.

[Premature rupture of fetal membranes at term: an indication for induced labor with prostaglandins?]. / Vorzeitiger Blasensprung am Termin: Eine Indikation zur Geburtseinleitung mit Prostaglandinen?

Premature rupture of membranes (PROM) at term is thought to be related to an increased infection risk for mother and child. A prospective study was conducted to evaluate the efficacy of prostaglandins for induction of labour in 433 cases of PROM presenting after 35 completed weeks of gestation. Intracervical gel or vaginal pessaries were given in dependence on the Bishop-score. Course of delivery and fetal outcome were analysed. In 57.3% single application was sufficient to induce the delivery. Only 1.8% of cases did not respond. 21% of patients were delivered within six hours of the first application and 89.6% during the first 24 hours. The rate of cesarean section was 15.5%. Fetal distress caused by uterine hyperstimulation was observed in 9.9% and required intrapartum tocolysis. A fetal acidosis (pH < 7.15) was present in 4.1%. The neonatal infective morbidity was 0.4%. Severe maternal complications were not observed. We conclude that use of prostaglandins for induction of labour in case of PROM at term seems to be a recommendable measure. In primiparous women or in the presence of an unfavorable cervix-score shorter duration to delivery diminishes the risk of fetal infection.

Fetal growth, major malformations, and minor anomalies in infants born to women receiving valproic acid.

The association of fetal and neonatal distress, birth measurements, major malformations, and minor anomalies was studied prospectively in 14 infants of women with epilepsy who were receiving valproic acid (VPA) monotherapy and in 12 infants of women with epilepsy who were receiving VPA in combination with other anticonvulsant drugs. Comparison was made with 26 matched-pair controls and 116 controls from a larger study of antiepileptic drugs. During the first trimester, total VPA serum concentrations were well above therapeutic levels (100 to 184 micrograms/ml) in two women receiving high VPA doses (2000 and 1500 mg daily). Although dosage remained the same, serum concentrations decreased during pregnancy to therapeutic levels (33.9 to 57.0 micrograms/ml). The VPA percent free fraction increased in the third trimester and was threefold higher at birth. Almost half of the infants exposed to VPA monotherapy were distressed during labor, and 28% had low Apgar scores. Fetal and neonatal distress may be caused by the high VPA percent free fraction during labor and at birth. Mean body measurements at birth after VPA monotherapy were comparable to those in the matched control group, but were reduced in the group of infants receiving VPA combination therapy. Four infants exposed to VPA monotherapy were born with major malformations. The median number of minor anomalies was four times higher in infants whose mothers received VPA alone or VPA combination therapy than in controls. Seven infants had a pattern of craniofacial and digital anomalies that was distinctly different from that observed after in utero exposure to other anticonvulsant medications. The occurrence of major malformations and the number of minor anomalies may be dose related.

Extent of nicotine and cotinine transfer to the human fetus, placenta and amniotic fluid of smoking mothers.

Nicotine and cotinine concentrations were measured in placental tissue during the first trimester, in amniotic fluid during the second trimester and in placental tissue and fetal serum at birth. These values were compared to the corresponding serum concentrations of the smoking mothers. Nicotine concentrations in the placentas (range 3.3-28 ng/g), in amniotic fluid (range 1.5-23 ng/ml) and in fetal serum (range 0.5-25 ng/ml) were all higher than the corresponding maternal serum values: amniotic fluid/maternal vein serum concentration ratio 1.54 +/- (SD) 0.27 (n = 23; week 16-24 of gestation), umbilical vein serum/maternal vein serum ratio 1.12 +/- 0.30 (n = 26; at birth); placental tissue/maternal vein serum ratio 2.58 +/- 1.30 (n = 17; at birth); these ratios were between 1.2 and 5 during week 10 of gestation (n = 3). The ratios did not depend on the time between the last cigarette smoked and sampling. Significant correlations were found between nicotine concentrations in amniotic fluid and maternal serum (r = 0.88), between fetal and maternal serum levels (r = 0.88) and between placental and maternal serum levels (r = 0.52). Cotinine concentrations in placental tissue (range 10-131 ng/g), amniotic fluid (range 5-188 ng/ml) and fetal serum (range 15-233 ng/ml) were lower than or similar to corresponding maternal serum levels. Our results indicate that the human fetus is exposed to higher nicotine concentrations that the smoking mothers.

Protein binding of carbamazepine and its epoxide in maternal and fetal plasma at delivery: comparison to other anticonvulsants.

A detailed investigation of the plasma protein binding of carbamazepine (CBZ) and its major metabolite carbamazepine epoxide (CBZE) revealed that both compounds are more extensively bound to plasma proteins in the mother (% free fraction CBZ, 28.4 +/- 3.0; CBZE, 55.1 +/- 5.0) than in the fetus (% free fraction CBZ, 31.5 +/- 2.2; CBZE, 61.5 +/- 3.1) at the time of birth. Fetal and maternal protein binding is reduced compared to controls (% free fraction CBZ, 26.5 +/- 2.1; CBZE, 49.1 +/- 5.7). A correlation of the unbound fraction with various biochemical parameters suggested that among other factors, high bilirubin concentrations in the fetus could be responsible for the relatively increased free fraction of CBZ and CBZE compared to maternal values. As free fraction values of CBZ and CBZE are either the same (CBZ) or slightly higher (CBZE) in women at term compared to nonpregnant controls, a regular monitoring of maternal free fraction values seems unnecessary. For other anticonvulsive drugs, however, like diazepam and valproic acid, monitoring of both total plasma concentrations and free fractions is strongly recommended.

Placental transfer of etozolin and ozolinone during the first half of gestation in man.

The placental transfer of etozolin and its pharmacologically active metabolite ozolinone was studied in 48 patients during the first (44 patients) and second (4 patients) trimester. 24 patients received a single oral dose of etozolin 400 mg 2-20 h prior to interruption of pregnancy by curettage or prostaglandin infusion. 24 other patients received 3 oral doses of etozolin 400 mg (11 patients) or 800 mg (13 patients) on 3 consecutive days, and pregnancy was terminated 2-10 h after the last dose. The fetal tissue/maternal serum and placental tissue/maternal serum ratios of etozolin and ozolinone were found to lie between 0.3 and 0.6. The serum levels were lower in pregnant than in non-pregnant patients. The low placental and fetal concentrations of etozolin and ozolinone suggest that these drugs may prove useful when a diuretic is indicated in the treatment of oedema and hypertension during pregnancy.

Effect of 1,25(OH)2D3 and 24,25(OH)2D3 on experimental rickets.

The vitamin D3 metabolite 1,25(OH)2D3 alone may not be able to reverse defective bone mineralization, while a combination with another metabolite, 24,25(OH)2D3 might be necessary to display the known effect of vitamin D on bone. Growing rachitic rats were treated with 25 ng vitamin D3/d, 10 ng 1,25(OH)2D3/d, 10 ng 24,25(OH)2D3/d, 5 ng 1,25(OH)2D3/d and 5 ng 24,25(OH)2D3/d in combination and 10 ng 1,25(OH)2D3/d and 10 ng 24,25(OH)2D3/d in combination. After 10 days of treatment the epiphyseal plate width of femura and the distance of tetracycline fluorescence bands were measured microscopically on undecalcified sections of the bone. The calcium content of femur epiphysis was measured by neutron activation analysis. Neither parameter showed on greater effect of the combination of 1,25(OH)2D3 and 24,25(OH)2D3 than of 1,25(OH)2D3 alone.

[Coronary vessel anomaly: fistula between the right coronary artery and the left ventricle clinically presenting as aortic valve insufficiency (author's transl)]. / Koronargefässanomalie: Fistel zwischen rechter Koronararterie und linkem Ventrikel mit dem klinischen Bild einer Aorteninsuffizienz.

Under more than 200 cases of coronary vessel anomalies only 33 are fistulas from the right or left coronary artery into the left ventricle. The case presented here of a fistula from the right coronary artery into the left ventricle featured the clinical picture of an aortic valve insufficiency. The histologic findings support the theory that these fistulas are embryological anomalies: transient communications between the ventricular trabeculas and the coronary vessels may be lined with endothelium and become then persisting as fistulas.

[Coincidence of two carcinomata with excessive high level of serumestrogen (author's transl)]. / Koinzidenz zweier Karzinome mit ungewöhnlich hohem Serumöstrogenspiegel

A case of an unusual combination of a metastasing bronchus cancer, a non-metastasing cancer of prostata and an excessive high level of serum-estrogen is described. This casuistic gives rise to some more general discussion of the pathogenesis and differential diagnosis of paraneoplastic endocrinopathies.

PIP: Breast cancer was discovered in a 78-year-old man, which came from a metastasizing bronchus cancer. Investigation showed a level of serum estrogen 20 times higher than normal. This was probably due to a nonmetastasizing prostate cancer, spironalactone therapy for heart trouble, paraneoplactic endocrinopathy, and the Pierre-Marie-Bamberger syndrome.