Cartilage decisively shapes the glenoid concavity and contributes significantly to shoulder stability.

PURPOSE: Glenohumeral joint injuries frequently result in shoulder instability. However, the biomechanical effect of cartilage loss on shoulder stability remains unknown. The aim of the current study was to investigate biomechanically the effect of two severity stages of cartilage loss in different dislocation directions on shoulder stability. METHODS: Joint dislocation was provoked in 11 human cadaveric glenoids for 7 different directions between 3 o'clock (anterior) and 9 o'clock (posterior). Shoulder stability ratio (SSR) and concavity gradient were assessed in three states: intact, 3 mm and 6 mm simulated cartilage loss. The influence of cartilage loss on SSR and concavity gradient was statistically evaluated. RESULTS: Both SSR and concavity gradient decreased significantly between intact state and 6 mm cartilage loss in every dislocation direction (p ≤ 0.038), except concavity gradient in 4 o'clock direction. Thereby, anterior-inferior dislocation directions were associated with the highest decrease in both SSR and concavity gradient of up to 59.0% and 49.4%, respectively, being significantly bigger for SSR compared with all other dislocation directions (p ≤ 0.040). Correlations between concavity gradient and SSR for pooled dislocation directions were significant in each separate specimen's state (p < 0.001). CONCLUSION: From a biomechanical perspective, articular cartilage of the glenoid contributes significantly to the concavity gradient, correlating strongly with the associated loss in glenohumeral joint stability. The biggest effect of cartilage loss is observed in the most frequently occurring anterior-inferior dislocation directions, suggesting that surgical interventions to restore cartilage's surface and concavity should be considered for recurrent shoulder dislocations in presence of cartilage loss.

Helical plating - a novel technique to increase stiffness in defect fractures.

Single-plate fixation bridging bone defects provokes nonunion and risks plate-fatigue failure due to under- dimensioned implants. Adding a helical plate to bridge the fracture increases stiffness and balances load sharing. This study compares the stiffness and plate surface strain of different constructs in a transverse contact and gap femoral shaft fracture model. Eight groups of six synthetic femora each were formed: intact femora; intact femora with lateral locking plate; contact and gap transverse shaft osteotomies each with lateral locking plate, lateral locking plate and helical locking plate, and long proximal femoral nail. Constructs underwent non-destructive quasi-static axial and torsional loading. Plate surface strain evaluation was performed under 200 N axial loading. Constructs with both lateral and helical plates demonstrated similar axial and torsional stiffness- independent of the contact or gap situations - being significantly higher compared to lateral plating (p < 0.01). Torsional stiffness of the constructs, with both lateral and helical plates in the gap situation, was significantly higher compared to this situation stabilised by a nail (p < 0.01). Plate surface strain dropped from 0.3 % in the gap situation with a lateral plate to < 0.1 % in this situation with both a lateral and a helical plate. Additional helical plating increases axial and torsional construct stiffness in synthetic bone and seems to provide well-balanced load sharing. Its use should be considered in very demanding situations for gap or defect fractures, where single-plate osteosynthesis provides inadequate stiffness for fracture healing and induces nonunion.

Comparison of different theories for focusing through a plane interface: reply.

The correction pointed out by Kim et al. [J. Opt. Soc. Am. A35, 591 (2018)JOAOD60740-323210.1364/JOSAA.35.000591] to our paper [J. Opt. Soc. Am. A14, 1482 (1997)JOAOD60740-323210.1364/JOSAA.14.001482] is welcome. A few additional remarks are included in this reply.

Characterizing microcrack orientation distribution functions in osteonal bone samples.

Prefailure microdamage in bone tissue is considered to be the most detrimental factor in defining its strength and toughness with respect to age and disease. To understand the influence of microcracks on bone mechanics it is necessary to assess their morphology and three-dimensional distribution. This requirement reaches beyond classic histology and stereology, and methods to obtain such information are currently missing. Therefore, the aim of the study was to develop a methodology that allows to characterize three-dimensional microcrack distributions in bulk bone samples. Four dumbbell-shaped specimens of human cortical bone of a 77-year-old female donor were loaded beyond yield in either tension, compression or torsion (one control). Subsequently, synchrotron radiation micro-computed tomography (SRµCT) was used to obtain phase-contrast images of the damaged samples. A microcrack segmentation algorithm was developed and used to segment microcrack families for which microcrack orientation distribution functions were determined. Distinct microcrack families were observed for each load case that resulted in distinct orientation distribution functions. Microcracks had median areas of approximately 4.7 µm2 , 33.3 µm2 and 64.0 µm2 for tension, compression and torsion. Verifying the segmentation algorithm against a manually segmented ground truth showed good results when comparing the microcrack orientation distribution functions. A size dependence was noted when investigating the orientation distribution functions with respect to the size of the volume of interest used for their determination. Furthermore, a scale separation between tensile, compressive and torsional microcracks was noticeable. Visual comparison to classic histology indicated that microcrack families were successfully distinguished. We propose a methodology to analyse three-dimensional microcrack distributions in overloaded cortical bone. Such information could improve our understanding of bone microdamage and its impact on bone failure in relation to tissue age and disease.

[Experiences with PMMA cement as a stand-alone intervertebral spacer. Percutaneous cement discoplasty in the case of vacuum phenomenon within lumbar intervertebral discs]. / Erfahrungen mit PMMA-Zement als intervertebraler Stand-alone-Platzhalter. Perkutane Zement-Diskoplastie bei Vakuumphänomen der lumbalen Bandscheiben.

BACKGROUND: The treatment of symptomatic degenerative disc disease of the lumbar spine in elderly patients by standard surgical methods is often limited due to severe comorbidities (e.g., cardiopulmonary disease, hypertonia, diabetes). Minimally invasive procedures are more acceptable in this population, since they reduce surgical morbidity and the risk of complications. The percutaneous cement discoplasty (PCD) technique was introduced by the authors to treat dynamic (and angular) instability of the symptomatic lumbar segment by injecting bone cement (polymethylmethacrylate, PMMA) into the disc spaces showing vacuum phenomena via a posterolaterally positioned Jamshidi needle. The aim of this article is to describe the indication, method, and clinical results of PCD. METHOD: A total of 81 patients were treated with PCD in a tertiary care referral center over a 6-year period. The current study includes the first group of 47 consecutive patients to complete a pre- and postoperative questionnaire booklet regarding leg and back pain using the visual analog scale (VAS) and the Oswestry disability index (ODI) questionnaire. RESULTS: A total of 130 discs in these 47 patients were treated with PCD. The majority of patients reported a reduction in their lower back and leg pain (69 and 66 %, respectively; p < 0.02) postoperatively. At 6-month follow-up, 61 % of patients had a minimum 10-point reduction in their ODI scores (p < 0.01). CONCLUSION: Elderly patients with symptomatic dynamic foraminal stenosis and vacuum phenomenon in the intervertebral disc are suitable candidates for PCD, particularly if they represent high-risk patients for open surgery.

Experiences with PMMA cement as a stand-alone intervertebral spacer: Percutaneous cement discoplasty in the case of vacuum phenomenon within lumbar intervertebral discs.

BACKGROUND: The treatment of symptomatic degenerative disc disease of the lumbar spine in elderly patients by standard surgical methods is often limited due to severe comorbidities (e.g., cardiopulmonary disease, hypertonia, diabetes). Minimally invasive procedures are more acceptable in this population, since they reduce surgical morbidity and the risk of complications. The percutaneous cement discoplasty (PCD) technique was introduced by the authors to treat dynamic (and angular) instability of the symptomatic lumbar segment by injecting bone cement (polymethylmethacrylate, PMMA) into the disc spaces showing vacuum phenomena via a posterolaterally positioned Jamshidi needle. The aim of this article is to describe the indication, method, and clinical results of PCD. METHOD: A total of 81 patients were treated with PCD in a tertiary care referral center over a 6-year period. The current study includes the first group of 47 consecutive patients to complete a pre- and postoperative questionnaire booklet regarding leg and back pain using the visual analog scale (VAS) and the Oswestry disability index (ODI) questionnaire. RESULTS: A total of 130 discs in these 47 patients were treated with PCD. The majority of patients reported a reduction in their lower back and leg pain (69% and 66%, respectively; p < 0.02) postoperatively. At 6-month follow-up, 61% of patients had a minimum 10-point reduction in their ODI scores (p < 0.01). CONCLUSION: Elderly patients with symptomatic dynamic foraminal stenosis and vacuum phenomenon in the intervertebral disc are suitable candidates for PCD, particularly if they represent high-risk patients for open surgery.

Clinical management and innovation in fracture non-union.

INTRODUCTION: With the introduction and continuous improvement in operative fracture fixation, even the most severe bone fractures can be treated with a high rate of successful healing. However, healing complications can occur and when healing fails over prolonged time, the outcome is termed a fracture non-union. Non-union is generally believed to develop due to inadequate fixation, underlying host-related factors, or infection. Despite the advancements in fracture fixation and infection management, there is still a clear need for earlier diagnosis, improved prediction of healing outcomes and innovation in the treatment of non-union. AREAS COVERED: This review provides a detailed description of non-union from a clinical perspective, including the state of the art in diagnosis, treatment, and currently available biomaterials and orthobiologics.Subsequently, recent translational development from the biological, mechanical, and infection research fields are presented, including the latest in smart implants, osteoinductive materials, and in silico modeling. EXPERT OPINION: The first challenge for future innovations is to refine and to identify new clinical factors for the proper definition, diagnosis, and treatment of non-union. However, integration of in vitro, in vivo, and in silico research will enable a comprehensive understanding of non-union causes and correlations, leading to the development of more effective treatments.

QCT-based finite element models predict human vertebral strength in vitro significantly better than simulated DEXA.

SUMMARY: While dual energy X-ray absorptiometry (DXA) is considered the gold standard to evaluate fracture risk in vivo, in the present study, the quantitative computed tomography (QCT)-based finite element modeling has been found to provide a quantitative and significantly improved prediction of vertebral strength in vitro. This technique might be used in vivo considering however the much larger doses of radiation needed for QCT. INTRODUCTION: Vertebral fracture is a common medical problem in osteoporotic individuals. Bone mineral density (BMD) is the gold standard measure to evaluate fracture risk in vivo. QCT-based finite element (FE) modeling is an engineering method to predict vertebral strength. The aim of this study was to compare the ability of FE and clinical diagnostic tools to predict vertebral strength in vitro using an improved testing protocol. METHODS: Thirty-seven vertebral sections were scanned with QCT and high resolution peripheral QCT (HR-pQCT). Bone mineral content (BMC), total BMD (tBMD), areal BMD from lateral (aBMD-lat), and anterior-posterior (aBMD-ap) projections were evaluated for both resolutions. Wedge-shaped fractures were then induced in each specimen with a novel testing setup. Nonlinear homogenized FE models (hFE) and linear micro-FE (µFE) were generated from QCT and HR-pQCT images, respectively. For experiments and models, both structural properties (stiffness, ultimate load) and material properties (apparent modulus and strength) were computed and compared. RESULTS: Both hFE and µFE models predicted material properties better than structural ones and predicted strength significantly better than aBMD computed from QCT and HR-pQCT (hFE: R² = 0.79, µFE: R² = 0.88, aBMD-ap: R² = 0.48-0.47, aBMD-lat: R² = 0.41-0.43). Moreover, the hFE provided reasonable quantitative estimations of the experimental mechanical properties without fitting the model parameters. CONCLUSIONS: The QCT-based hFE method provides a quantitative and significantly improved prediction of vertebral strength in vitro when compared to simulated DXA. This superior predictive power needs to be verified for loading conditions that simulate even more the in vivo case for human vertebrae.

Bone and cellular immune system of multiparous sows are insensitive to ovariectomy and nutritive calcium shortage.

Research in osteoporosis, which is a complex systemic disease, demands suitable large animal models. In pigs, most research has been done in growing minipigs, which probably are not ideal models for postmenopausal osteoporosis. Therefore, our aim was to analyze the effects of ovariectomy (OVX) and nutritive calcium shortage on multiparous Large White sows. 32 animals were randomly assigned to 4 groups in a cross design with OVX vs. sham and physiological calcium supplementation (0.75% calcium) vs. dietary calcium shortage (0.3% calcium). The observation period was 10 months with blood sampling every 2 months for hematological, immunological, and biochemical bone marker measurements. At the termination of the experiment, animals were sacrificed. Samples of trabecular bone of distal radius, proximal tibia, and sixth lumbar vertebra were subjected to micro-computed tomography imaging and ashed afterwards. Dual X-ray absorptiometry scans of the proximal femora were performed with prepared bones being placed in a water bath for mimicking soft tissue. Analyses of bone marker and cytokine profile kinetics, distribution of leukocyte subpopulations, and morphometrical and densitometrical analyses showed no evidence of any impact of OVX or calcium shortage. In conclusion, the skeleton of adult sows of a conventional breed is seemingly protected from effects of OVX and calcium shortage.

OPG-Fc treatment in growing pigs leads to rapid reductions in bone resorption markers, serum calcium, and bone formation markers.

Inhibition of the receptor activator of NF-κB ligand (RANKL) is a novel therapeutic option in the treatment of osteoporosis and related diseases. The aim of this study was to evaluate bone metabolism and structure in pigs after RANKL inhibition. 12 growing pigs were assigned to 2 groups with 6 animals each. The OPG group received recombinant human OPG-Fc (5 mg/kg IV) at day 0, the control group was given 0.9% NaCl solution. Serum levels of OPG-Fc, calcium (Ca), phosphorus (P), and bone turnover markers were evaluated every 5 days, and pigs were euthanized on day 20. Serum OPG-Fc concentration peaked at day 5 and coincided with significantly decreased Ca, P, and bone turnover markers. By day 15, measureable OPG-Fc serum levels could only be detected in 2/6 animals. With OPG-Fc clearance starting at day 10, serum Ca and P concentrations were not different between the 2 groups. TRACP5b, P1CP, and BAP levels significantly decreased by 40-70% relative to vehicle controls in the OPG-Fc group between days 5 and 10, indicating that pharmacologic concentration of OPG-Fc led to systemic concomitant inhibition of bone formation and resorption in young growing pigs. Dual X-ray absorptiometry data derived from the proximal femur did not differ between the 2 groups. µCT analysis of selected bone sites demonstrated an OPG-Fc-induced improvement of specific bone architectural indices and bone mineralization.

A calibration methodology of QCT BMD for human vertebral body with registered micro-CT images.

PURPOSE: The accuracy of QCT-based homogenized finite element (FE) models is strongly related to the accuracy of the prediction of bone volume fraction (BV/TV) from bone mineral density (BMD). The goal of this study was to establish a calibration methodology to relate the BMD computed with QCT with the BV/TV computed with micro-CT (microCT) over a wide range of bone mineral densities and to investigate the effect of region size in which BMD and BV/TV are computed. METHODS: Six human vertebral bodies were dissected from the spine of six donors and scanned submerged in water with QCT (voxel size: 0.391 x 0.391 x 0.450 mm3) and microCT (isotropic voxel size: 0.018(3) mm3). The microCT images were segmented with a single level threshold. Afterward, QCT-grayscale, microCT-grayscale, and microCT-segmented images were registered. Two isotropic grids of 1.230 mm (small) and 4.920 mm (large) were superimposed on every image, and QCT(BMD) was compared both with microCT(BMD) and microCT(BV/TV) for each grid cell. RESULTS: The ranges of QCT(BMD) for large and small regions were 9-559 mg/cm3 and -90 to 1006 mg/cm3, respectively. QCT(BMD) was found to overestimate microCT(BMD). No significant differences were found between the QCT(BMD)-microCT(BV/TV) regression parameters of the two grid sizes. However, the R2 was higher, and the standard error of the estimate (SEE) was lower for large regions when compared to small regions. For the pooled data, an extrapolated QCTBMD value equal to 1062 mg/ cm3 was found to correspond to 100% microCT(BV/TV). CONCLUSIONS: A calibration method was defined to evaluate BV/TV from QCTBMD values for cortical and trabecular bone in vitro. The QCT(BMD-microCT(BV/TV) calibration was found to be dependent on the scanned vertebral section but not on the size of the regions. However, the higher SEE computed for small regions suggests that the deleterious effect of QCT image noise on FE modelling increases with decreasing voxel size.

Biomechanical assessment of vertebrae with lytic metastases with subject-specific finite element models.

The assessment of risk of vertebral fracture in patients with lytic metastases is challenging, due to the complexity in modelling the mechanical properties of this heterogeneous material. Currently clinical assessment of patients at high risk of fracture is based on the Spinal Instability Neoplastic Score (SINS), which however in many cases does not provide clear guidelines. The goal of this study was to develop a computational approach to provide a comparative biomechanical assessment of vertebrae with lytic lesions with respect to the adjacent controls and highlight the critical vertebrae. The computed tomography images of the thoracolumbar spine of eight patients suffering of vertebral lytic metastases with SINS between 7 and 12 (indeterminate unstable) were analysed. For each patient one or two vertebrae with lytic lesions were modelled and the closest vertebrae without lesions were considered as control. Metastatic vertebrae (N = 12) and controls (N = 18) were converted to subject-specific, heterogeneous, isotropic, nonlinear finite element models for simulating uniaxial compression. Densitometric and mechanical properties were computed for each vertebra. In average, similar mechanical properties were found for vertebrae with lytic lesions and controls (e.g. ultimate force equal to 6.2 ±â€¯2.7 kN for vertebrae with lytic lesions and to 6.2 ±â€¯3.0 kN for control vertebrae). Only in three patients the vertebrae with lytic lesions were found to be mechanically weaker (-19% to -75% difference for ultimate stress) than the controls. In conclusion, in this study we presented an approach to estimate the mechanical competence of vertebrae with lytic metastases. It remains to be investigated in a clinical study if this method, together with the SINS, can better classify patients with vertebrae with lytic lesions at high risk of fracture.

Time-of-flight spectroscopy of the energy distribution of laser-ablated atoms and ions.

The growth of ultrathin films, deposited by laser ablation, crucially depends on the energy of the ablated species. Therefore, a time-of-flight (TOF) spectrometer has been constructed and measurements have been carried out in order to determine the energy distribution of laser-ablated Fe and Pt atoms and ions in the plasma created by nanosecond pulses of a frequency-doubled neodymium doped yttrium aluminum garnet laser. The experiments have been performed in ultrahigh vacuum at relatively low laser power. For measuring the spectra of the neutrals, a cross-beam electron source for postionization and electric as well as magnetic fields for repelling the ions are employed. Nevertheless, measurements of neutral particles are restricted to low plasma densities due to electrostatic shielding within the plasma, leading to an inefficient deflection of charged particles by electrostatic and magnetic fields. Test measurements have been performed by utilizing the TOF spectrometer as a pressure gauge and also by chopping the electron beam, running the TOF spectrometer as a residual gas mass spectrometer. The spectra of the laser-ablated plasmas have shown plasma conditions with a Debye length of approximately 10(-4) m, densities of 10(15)-10(16) m(-3) and ion energies up to 150 eV. Neutral spectra have shown an unexpectedly low fraction of neutrals (10(-3)-10(-4)) and hyperthermal energies up to several 10 eV, possibly contributed by recombination of ions and electrons in the plasma. Even though gas spectra had demonstrated the expected sensitivity of the TOF spectrometer for low-energy neutrals, no thermally evaporated neutral atoms could be found.

Ultrasound palpation for fast in-situ quantification of articular cartilage stiffness, thickness and relaxation capacity.

Most current cartilage testing devices require the preparation of excised samples and therefore do not allow intra-operative application for diagnostic purposes. The gold standard during open or arthroscopic surgery is still the subjective perception of manual palpation. This work presents a new diagnostic method of ultrasound palpation (USP) to acquire applied stress and strain data during manual palpation of articular cartilage. With the proposed method, we obtain cartilage thickness and stiffness. Moreover, repeated palpations allow the quantification of relaxation effects. USP measurements on elastomer phantoms demonstrated very good repeatability for both, stage-guided (97.2%) and handheld (96.0%) applications. The USP measurements were compared with conventional indentation experiments and revealed very good agreement on elastomer phantoms ([Formula: see text]) and good agreement on porcine cartilage samples ([Formula: see text]). Artificially degenerated cartilage samples showed reduced stiffness, weak capacity to relax after palpation and an increase of stiffness of approximately 50% with each single palpation. Intact cartilage was measured by USP directly at the patella (in situ) and after excision and removal of the subchondral bone (ex situ), leading to stiffness values of [Formula: see text] and [Formula: see text] ([Formula: see text]), respectively. The results demonstrate the potential of the USP system for cartilage testing, its sensitivity to degenerative changes and as a method for quantifying relaxation processes by means of repeated palpations. Furthermore, the differences in the results of in-situ and ex-situ measurements are of general interest, since such comparison has not been reported previously. We point out the limited comparability of ex-situ cartilage with its in-situ biomechanical behavior.

Mortality and the relationship of somatic comorbidities to mortality in schizophrenia. A nationwide matched-cohort study.

AIM: We conducted a matched-cohort study to assess mortality in schizophrenia and the relationship of mortality with comorbid somatic conditions and suicide attempts. METHOD: A full-population register-based prospective matched-cohort study was performed including all eligible patients with schizophrenia in Hungary between 01/01/2005 and 31/12/2013. Control subjects were individually matched to patients with schizophrenia at a 5:1 ratio. The principal outcome measure was death due to any reason. A non-parametric approach was used for descriptive statistical purposes, the Kaplan-Meier model for survival analysis, and the Cox proportional-hazards regression model for inferential statistics. RESULTS: Patients with schizophrenia (n=65,169) had substantially higher risk of all-cause mortality than the control subjects (n=325,435) (RR=2.4; P<0.0001). Comorbidities and suicide attempts were associated with significantly increased mortality in both groups. As compared to the controls, 20-year old males with schizophrenia had a shorter life expectancy by 11.5years, and females by 13.7years; the analogous numbers for 45-year old schizophrenics were 8.1 and 9.6years, respectively. CONCLUSIONS: A significant mortality gap - mainly associated with somatic comorbidities - was detected between patients with schizophrenia and individually matched controls. Improved medical training to address the disparity in mortality, and many other factors including lack of resources, access to and model of medical care, lifestyle, medication side effects, smoking, stigma, need for early intervention and adequate health care organization could help to better address the physical health needs of patients with schizophrenia.

Kinetics of the reduction of the Rh(111) surface oxide: linking spectroscopy and atomic-scale information.

The reduction of the surface oxide on Rh(111) by H(2) was observed in situ by scanning tunneling microscopy (STM) and high-resolution core level spectroscopy (HRCLS). At room temperature, H(2) does not adsorb on the oxide, only in reduced areas. Reduction starts in very few sites, almost exclusively in stepped areas. One can also initiate the reduction process by deliberately creating defects with the STM tip allowing us to examine the reduction kinetics in detail. Depending on the size of the reduced area and the hydrogen pressure, two growth regimes were found. At low H(2) pressures or small reduced areas, the reduction rate is limited by hydrogen adsorption on the reduced area. For large reduced areas, the reduction rate is limited by the processes at the border of the reduced area. Since a near-random distribution of the reduction nuclei was found and the reduction process at defects starts at a random time, one can use Johnson-Mehl-Avrami-Kolmogoroff (JMAK) theory to describe the process of reduction. The microscopic data from STM agree well with spatially averaged data from HRCLS measurements.

Unusual process of water formation on RuO2(110) by hydrogen exposure at room temperature.

The reduction mechanism of the RuO(2)(110) surface by molecular hydrogen exposure is unraveled to an unprecedented level by a combination of temperature programmed reaction, scanning tunneling microscopy, high-resolution core level shift spectroscopy, and density functional theory calculations. We demonstrate that even at room temperature hydrogen exposure to the RuO(2)(110) surface leads to the formation of water. In a two-step process, hydrogen saturates first the bridging oxygen atoms to form (O(br)-H) species and subsequently part of these O(br)-H groups move to the undercoordinated Ru atoms where they form adsorbed water. This latter process is driven by thermodynamics leaving vacancies in the bridging O rows.

Progesterone-dependent immunomodulation.

The biological effects of progesterone are mediated by a 34-kDa protein named the progesterone-induced blocking factor (PIBF). PIBF, synthesized by lymphocytes of healthy pregnant women in the presence of progesterone, inhibits arachidonic acid release as well as NK activity, and modifies the cytokine balance. Within the cell the full-length PIBF is associated with the centrosome, while secretion of shorter forms is induced by activation of the cell. PIBF induces nuclear translocation of STAT6 as well as PKC phosphorylation and exerts a negative effect on STAT4 phosphorylation. The concentration of PIBF in pregnancy urine is related to the positive or negative outcome of pregnancy; furthermore, premature pregnancy termination is predictable by lower than normal pregnancy PIBF values. In vivo data suggest the biological importance of the above findings. Treatment of pregnant Balb/c mice with the antiprogesterone RU 486 results in an increased resorption rate, which is associated with the inability of spleen cells to produce PIBF. High resorption rates induced by progesterone receptor block as well as those due to high NK activity are corrected by simultaneous PIBF treatment.

ELISA test for the detection of an immunological blocking factor in human pregnancy serum.

We have previously shown that progesterone-treated lymphocytes of healthy pregnant women can produce a 34 kDa protein, progesterone-induced blocking factor (PIBF) capable of blocking lymphocyte function in vitro. Lymphocytes of women with idiopathic threatened pre-term delivery failed to produce this factor. On the assumption that the PIBF appears in the serum of healthy pregnant women but not in that of women at risk for immunologically based abortion of pre-term delivery, an ELISA has been designed for detecting the blocking factor in serum samples. Sera obtained at the time of delivery, as well as those from women with pre-term deliveries or miscarriages, contained significantly less PIBF than sera of 209 healthy pregnant women. Data obtained by testing sera of women at 16 weeks gestation whose pregnancies ended in spontaneous abortion showed that the predictive value of the test depended on the time interval between blood sampling and the onset of abortion. In 11 of 13 women with uterine contractions the outcome of pregnancy was predictable by normal or lower than normal levels of PIBF in the sera taken at the time the symptoms were presented. The data suggest that determination of PIBF in pregnancy serum might contribute to the diagnosis of immunologically bases pre-term disruption of pregnancy.

Lymphocytic progesterone receptors in normal and pathological human pregnancy.

The progesterone receptor-specific monoclonal antibody (MoAb) mPRI was tested for its reactivity towards peripheral blood lymphocytes (PBL) of 49 healthy pregnant women, nine pregnant women with clinical symptoms of threatened preterm delivery, seven women with recurrent spontaneous abortion, ten women in labour and ten women with spontaneous abortion. Lymphocytes of 12 healthy age-matched non-pregnant volunteers were used as controls. Lymphocytes of nine healthy pregnant women at the 1st trimester of pregnancy and those of two non-pregnant donors were tested for the presence of estrogen and progesterone receptors by enzyme immunoassay. PBL of healthy pregnant women contained significantly more positive cells than those of non-pregnant controls. Furthermore, the number of receptor-containing cells increased in parallel with gestational age. In blood samples drawn during labour, as well as in those obtained from women with spontaneous abortion or clinical symptoms of threatened pre-term delivery, the percentage of positively stained lymphocytes was significantly lower than normal pregnancy values. This was also the case in peripheral blood of pregnant women with a history of recurrent spontaneous abortions.