Sliding contact accelerates solute transport into the cartilage surface compared to axial loading.

OBJECTIVE: The objectives of this study were: first, to compare solute uptake driven by sliding to cyclic uniaxial compression. And secondly, to evaluate the role of the superficial region on passive diffusion to determine if mechanical action is merely overcoming the low permeability of the superficial region or exceeding equilibrium capacity of the tissue. DESIGN: Tests were performed on osteochondral plugs under two types of conditions: cyclic loading (sliding vs axial compression) and unloaded passive diffusion (intact vs superficial zone removed). The articular surfaces were exposed to a fluorescent bath and uptake was quantified from the surface to the subchondral bone using fluorescent microscopy. Primary outcome measures were total mass transfer, mass transfer rate, and surface partition factor. RESULTS: Mass transfer was 2.1-fold higher at 0.5 h for sliding compared to uniaxial compression (p = 0.004). This increased to 4.4-fold at 2 h (p = 0.002). Solute transport for both loading conditions at 2 h had reached or exceeded intact passive diffusion at 12 h. Total mass transport and mass transport per hour was higher in samples without the superficial region compared to intact samples at equilibrium. Rate of mass transfer was not declining for samples subject to sliding indicating solute uptake induced by sliding would exceed passive tissue capacity. CONCLUSIONS: These results are the first to quantify solute uptake between two components of joint articulation. The study demonstrates that sliding is a larger driver of solute transport compared to cyclic uniaxial compression. This has implications for cell nutrition, tissue engineering and biochemical signaling.

Bone density changes following surgical correction of femoroacetabular impingement deformities.

OBJECTIVE: Femoroacetabular impingement (FAI) involves abnormal hip biomechanics due to deformities and is associated with osteoarthritis. Bone mineral density (BMD) in the acetabulum is higher in subjects with convex femoral (cam) FAI deformities compared to control subjects. The objective of this study was to assess post-operative changes of BMD with and without surgical correction of the cam deformity. DESIGN: Thirteen patients with bilateral cam deformities but unilateral symptoms underwent pre-operative and follow-up computed tomography (CT) scans of both hips. The deformity was surgically removed from the symptomatic hip. BMD was measured in regions of interest (ROI) around the superior acetabulum from CT scans at both time points. The contralateral untreated hip was used as a within-patient control. Changes in BMD were assessed by two-way repeated measures ANOVA (side, time) and paired t-tests. RESULTS: A greater BMD decrease was seen in the treated compared to the untreated hip (P < 0.0018). BMD within the superior acetabulum decreased by 39 mg/cc on the treated side (P < 0.0001) but only 9 mg/cc (P = 0.15) in the untreated contralateral hip. These changes represent 7.1% and 1.7% of the pre-operative BMD on the respective sides. CONCLUSIONS: BMD decreased in the treated hip, suggesting a positive effect of surgical correction in relieving stresses within the hip joint. Longer term follow-up is required to assess the ultimate fate of the articular cartilage within the joint. This study showed that surgical correction of the cam deformity in patients with FAI may alter the pathological biomechanics within the joint.

Femoral subchondral bone properties of patients with cam-type femoroacetabular impingement.

OBJECTIVE: Morphological deformities of the hip, such as femoroacetabular impingement (FAI) may be responsible for up to 80% of hip osteoarthritis. In cam type FAI, the pathomechanism has been attributed to repeated abnormal contact between the femur and the antero-superior acetabular rim, resulting in cartilage and labrum degeneration. Subchondral bone stiffness likely plays a major role in the process, but little is known of the mechanical properties of the cam deformity. The purpose of this study was to determine tissue modulus and the trabecular micro-architecture of the subchondral bone of the cam deformity of patients undergoing resection surgery as well as comparing these parameters to healthy aged matched controls. DESIGN: Twelve osteochondral bone biopsies were obtained from symptomatic FAI patients and ten osteochondral control specimens were harvested from cadaveric femurs. A combination of mechanical testing, micro-CT and finite element (FE) analysis were used to determine tissue modulus, bone volume fraction, trabecular thickness, trabecular and spacing, and trabecular number. RESULTS: The mean tissue modulus of the cam-type FAI deformities (E = 5.4 GPa) was significantly higher than normal controls (E = 2.75 GPa, P = 0.038), but no statistically significant differences were found in bone micro-architectural parameters. CONCLUSIONS: The data suggests that subchondral bone of the cam deformity consists of older secondary mineralized bone. This supports the notion that the cam deformity is a primary malformation with intrinsic biomechanical abnormalities rather than a secondary deformity as part of the degenerative process of the covering cartilage or remodeling due to repeated impingement.

Genicular Artery embolisation in Patients with Osteoarthritis of the Knee (GENESIS) Using Permanent Microspheres: Long-Term Results.

PURPOSE: To report the 2-year follow-up of patients with mild-to-moderate knee osteoarthritis (OA) treated with genicular artery embolisation (GAE) as part of the GENESIS study. MATERIALS AND METHODS: Forty-six patients, median age = 60 (45-83) underwent GAE using permanent microspheres (100-300 µm). Technical success was defined as embolisation of the targeted genicular arteries. Knee Injury and Osteoarthritis Outcome Score (KOOS) and Visual Analogue Scale (VAS) (0-100 mm) were recorded at baseline, 6 weeks, 3 months, 1, 2 years. Contrast-enhanced MRI knee scans were acquired at baseline and 1 year, and evaluated with the Whole-Organ Magnetic Resonance Imaging Score (WORMS). Functional MRI brain imaging and psychometric assessments were undertaken to investigate correlation between neuropsychological phenotypes and clinical outcome. Adverse events were recorded prospectively. RESULTS: Technical success was achieved in forty patients (87%). Mean VAS improved from 58.63 (SD = 20.57, 95% CI 52.7-65.5) at baselines to 37.7 at 2-years (SD = 26.3, 95% CI 27.0-47.5). Whole and subgroup KOOS were significantly improved at each timepoint with associated reductions in analgesia usage. WORMS analysis demonstrated significant reduction in synovitis (p < 0.05) with no cases of osteonecrosis. Self-limiting skin discolouration occurred in four patients. A self-limiting groin haematoma and single case of deep-vein thrombosis due to immobilisation were also recorded. Nine patients subsequently underwent knee arthroplasty with no additional operational complexities identified. Neuropsychometric assessment elucidated a correlation between baseline catastrophising and greater reduction in pain post GAE. CONCLUSION: GAE is a safe intervention for mild-moderate knee osteoarthritis, with sustained efficacy at 2 years. These results are promising and justify ongoing controlled trials.

Increased acetabular subchondral bone density is associated with cam-type femoroacetabular impingement.

OBJECTIVE: Femoroacetabular impingement (FAI) has been associated with significant acetabular cartilage damage and subsequent degenerative arthritis. Subchondral bone, often neglected in osteoarthritis studies, may play an important role in the degenerative cascade. Hence the goal of this study was to assess acetabular subchondral bone mineral density (BMD) in subjects with asymptomatic or symptomatic cam deformities compared to normal control subjects. The relationship between BMD and the alpha angle, a quantitative measure of the deformity, was also analyzed. METHODS: Patients diagnosed with symptomatic cam FAI were recruited ('Surgical') as well as subjects from the general asymptomatic population, classified from CT imaging as normal ('Control') or having a cam deformity ('Bump') based on their alpha angle measurement. There were 12 subjects in each group. All subjects underwent a CT scan with a calibration phantom. BMD was calculated in regions of interest around the acetabulum from CT image intensity and the phantom calibration. BMD was compared between groups using spine BMD as a covariate. The relationship between BMD and alpha angle was assessed by linear regression. RESULTS: In the antero-superior regions bone density was 15-34% higher in the Bump group (P < 0.05) and 14-38% higher in the Surgical group (P < 0.05) compared to Controls. BMD correlated positively with the alpha angle measurements (R(2) = 0.44, P < 0.001). CONCLUSION: BMD was elevated in subjects with cam-type deformities, with the severity of the deformity more correlative than symptom status. Similarities to the symptomatic group suggest that hips with an asymptomatic deformity may already be in early stages of joint degeneration.

Bone density is higher in cam-type femoroacetabular impingement deformities compared to normal subchondral bone.

OBJECTIVE: Cam-type femoroacetabular impingement (FAI) deformities have been associated with early osteoarthritic degeneration of the hip. Degeneration depends on many factors such as joint morphology and dynamics of motion. Bone mineral density (BMD) appears to be a manifestation of the above, and may be a potentiator. Thus the goal of this study was to assess subchondral BMD of cam deformities in symptomatic and asymptomatic FAI subjects, and to compare to normal controls. METHODS: Subjects undergoing surgical correction of a symptomatic cam-type deformity were recruited ("Surgical"). Asymptomatic volunteers were also recruited and classified as normal ("Control") or having a deformity ("Bump") based on their alpha angle measurement. All subjects (n = 12 per group) underwent computed tomography (CT) with a calibration phantom. BMD was determined in volumes of interest around the femoral head and neck to a depth of 5 mm. BMD was compared between groups in each section using spine BMD as a covariate. RESULTS: No differences were seen between groups in the peripheral bearing surface. The Bump group exhibited higher BMD than Controls within the head/neck junction (P < 0.05). When compared to normal subchondral bone in the peripheral level of Controls, BMD in the deformity was up to 78% higher in Bump subjects and up to 47% higher in Surgical subjects (P < 0.05). CONCLUSION: Subchondral BMD of cam deformities is higher than that of normal subchondral bone in the peripheral region of the femoral head, regardless of symptom status. The expected increased subchondral stiffness may increase contact stresses in the joint tissues leading to accelerated degeneration.

The effect of skin tension, needle diameter and insertion velocity on the fracture properties of porcine tissue.

Using metal needles to penetrate skin tissue is common in medical treatments for the delivery of medication or minimally invasive surgery. In most applications the fracture properties of skin tissue is not important as the human surgeon has full control over the needle. Given that robotically controlled surgeries and self applied medical devices have become increasingly popular, a better understanding of the fracture properties and how to mathematically model the fracture process is needed. Experiments measuring the force required to fracture porcine skin tissue were done while varying the applied skin tension, needle insertion speed and needle diameter. The applied skin tension was found to have the greatest influence on the fracture properties, while the insertion speed was found to have a negligible impact. The variance in experimental results was not well explained by the three independent variables alone, suggesting that additional parameters influence the fracture process.

Genicular artEry embolizatioN in patiEnts with oSteoarthrItiS of the Knee (GENESIS) Using Permanent Microspheres: Interim Analysis.

PURPOSE: Planned interim analysis of GENESIS; a prospective pilot study investigating the role of genicular artery embolization (GAE) in patients with mild to moderate osteoarthritis of the knee using permanent microspheres. METHODS: Thirty-eight patients, median age = 60 (45-83), attended for GAE using 100-300 µm permanent microspheres. All patients had mild to moderate knee OA, resistant to conservative treatments over 6 months. Knee MRI was performed at baseline, and 12 months, enabling semi-quantitative analysis using Whole-Organ Magnetic Resonance Imaging Score (WORMS). Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS) (0-100 mm) were completed at baseline, 6 weeks, 3 months (n = 32), and 1-year (n = 16). Adverse events were recorded prospectively. RESULTS: Technical success of accessing and embolizing the target genicular arteries was 84%. Six patients were not embolized: four due to a presumed risk of non-target embolization, and two due to a lack of hyperaemic target. Mean VAS improved from 60 (SD = 20, 95% CI 53-66) at baseline to 36 (SD = 24, 95% CI 28-44) at 3 months (p < 0.001) and 45 (SD = 30, 95% CI 30-60) at 1-year (p < 0.05). All KOOS subscales showed a significant improvement at 6-weeks, 3-months, and 1-year follow-up, except function in daily living, which reached borderline significance (p = 0.06) at 1-year. Four patients experienced mild self-limiting skin discoloration over the embolized territory. One patient experienced a small self-limiting groin haematoma. WORMS scores at 1-year follow-up showed significant improvement in synovitis (p < 0.05). There were no cases of osteonecrosis. CONCLUSION: GAE using permanent microspheres in patients with mild to moderate knee OA is safe, with potential efficacy at early follow-up.

Persistent hypertension following inhibition of nitric oxide formation in the young Wistar rat: role of renin and vascular hypertrophy.

OBJECTIVE: To determine whether induction of arterial hypertension in young normotensive Wistar rats by chronic inhibition of nitric oxide production with NG-nitro-L-arginine methyl ester (L-NAME) produced a form of self-sustained hypertension, and to investigate the role of the renin-angiotensin system and vascular hypertrophy in the hypertensive process. METHODS: Three-week-old Wistar rats were given 100 or 40 mg/kg per day L-NAME or 40 mg/kg per day L-NAME plus 100 mg/kg per day captopril in their drinking water for between 4 and 7 weeks. Systolic blood pressure was measured by tail-cuff plethysmography both during treatment and after the treatment had been stopped. The effect of treatment on plasma renin was measured and the effect of treatment on mesenteric resistance artery structure was determined using a small-vessel myograph. RESULTS: L-NAME produced a progressive and marked increase in blood pressure during the period of treatment. Hypertension was sustained for 14 weeks after stopping treatment. L-NAME resulted in a fourfold increase in plasma renin which remained elevated after treatment was stopped. Blood pressure was correlated with plasma renin levels. Treatment with L-NAME plus captopril markedly attenuated the rise in blood pressure and captopril also produced a marked fall in blood pressure in rats that developed persistent hypertension. Rats with self-sustained hypertension exhibited both cardiac and mesenteric resistance vessel hypertrophy. The induction of vascular hypertrophy with low-dose L-NAME did not result in the development of self-sustained hypertension. CONCLUSIONS: Chronic L-NAME treatment in young rats can produce a form of persistent hypertension which is renin-dependent and which does not seem to involve a vascular amplifier mechanism.

Aspects of multiple embryo transfer.

Three hundred seventy-two patients underwent laparoscopy for in vitro fertilization and embryo transfer. Of these, 156 were treated with clomiphene citrate alone, 203 with clomiphene citrate and hMG, and 13 with hMG alone. Two-hundred seventy-two of these patients underwent embryo transfer, and 55 pregnancies resulted. Of these, 30 were ongoing, 14 biochemical, 6 ectopic, and 5 aborted. Where four embryos were transferred, the pregnancy rate was found to be significantly higher than when a lesser number were transferred. When the embryos transferred were analyzed, however, it was found that fewer than 10% of all transferred embryos implanted and it was largely a function of multiple embryo transfer per patient that led to success. When the type of hyperstimulation was compared, clomiphene citrate cycles were found to be less successful in that they produced fewer oocytes and embryos than did cycles in which hyperstimulation was achieved by supplementary hMG. It is conceded that this is an overall analysis and that individuals, especially those producing twins, had more than one good embryo transferred into a receptive uterus. The data suggest that unsuccessful cycles had somewhat poorer quality embryos, nonreceptive endometria, or a combination of these factors when compared with those of the successful embryo transfer cycles. The only predictive factor as to outcome relates to the multiplicity of embryos transferred. The fact that some IVF cycles produce multiple pregnancies indicates that a predictor of embryo health is urgently required. However, until such a reliable predictor is obtained, multiple embryo transfer remains a major advance in the success of IVF and ET.

Patient selection for in vitro fertilization: physical and psychological aspects.

The impact of maternal age, previous childbearing, and the type of underlying pathology on the success rate of an IVF program is explored. There is no difference in the pregnancy rate or in the abortion rate with increasing maternal age, and a similar result is seen in relation to previous childbearing. A reduced fertilization rate is seen in couples classified as having unexplained infertility, dyspermia, and male immobilizing sperm antibodies. The pregnancy rates in the first two groups are satisfactory once fertilization has occurred, but there have been no ongoing pregnancies if there are circulating sperm immobilizing antibodies present in either the male or the female. The psychological problems facing the infertile patient are discussed with special reference to in vitro fertilization.

Betamethasone, albuterol, and threatened premature delivery: benefits and risks. Study of 469 pregnancies.

This report details the outcome of pregnancy in 469 patients admitted before 34 weeks' gestation with premature labor with intact membranes (253 patients) or premature rupture of the membranes (PROM) but no labor (216 patients). Betamethasone significantly reduced the incidence of severe respiratory distress syndrome (RDS) both in patients with intact membranes and in those with PROM. PROM had a significant beneficial effect on the incidence of RDS in both groups of patients, those who had received betamethasone and those who had not. Fetal sex did not significantly influence the respiratory response to either PROM or betamethasone administration, except that betamethasone treated female fetuses showed a significantly better response to PROM than similarly treated males. Except in patients with PROM associated with a cervical suture, betamethasone administration did not increase the risk of perinatal or maternal infection.

Pregnancies after intracytoplasmic injection of sperm collected by fine needle biopsy of the testis.

OBJECTIVE: To investigate the use of intracytoplasmic sperm injection with sperm collected by fine needle biopsy of the testis as a treatment for male genital tract obstruction. DESIGN: Sperm isolated from a fine needle biopsy of the testis were used to inseminate oocytes by intracytoplasmic sperm injection. SETTING: A hospital-based tertiary referral infertility service. PATIENTS: Case studies of two couples in whom the male partner had a genital tract obstruction. MAIN OUTCOME MEASURES: Fertilization and pregnancy. RESULTS: In the first case, 9 oocytes fertilized normally out of 13 injected. After the transfer of fresh (one cycle) and frozen (four cycles) embryos, a single intrauterine fetal heart pregnancy was achieved. In the second case, five oocytes fertilized normally from nine oocytes injected; two embryos were transferred fresh and three were frozen. A single fetal heart intrauterine gestation was obtained after the initial transfer of two fresh embryos. CONCLUSIONS: A high normal fertilization rate and pregnancies are possible with intracytoplasmic sperm injection using sperm collected directly from the testis. Sperm retrieval by fine needle biopsy offers a viable alternative to microsurgical aspiration and is also suitable for treating patients with intratesticular blockage.

Pregnancy following intrauterine implantation of an embryo obtained by in vitro fertilization of a preovulatory egg.

A normally progressing pregnancy has been established by implanting an eight-cell embryo into the uterine cavity of an infertile woman. The embryo was obtained by in vitro fertilization of preovulatory egg aspirated at laparoscopy 28 hours after the beginning of the luteinizing hormone surge during the patient's natural menstrual cycle. Elevated levels of serum human chorionic gonadotropin and progressively increasing levels of total urinary estrogens and pregnanediol confirmed the presence of an early pregnancy. Ultrasound examination revealed an intrauterine gestational sac at 5 weeks, a 1-cm fetus with fetal heartbeat at 7 weeks, and an active, normally growing fetus at 13 and 16 weeks. Chromosome analysis at this time revealed no abnormality, and the alpha-fetoprotein level was within normal limits. The patient is due to be delivered on or about June 28.

A laparoscopic approach to a program of gamete intrafallopian transfer.

Gamete intrafallopian transfer (GIFT) provides an effective method of achieving pregnancy in infertile women with normal fallopian tubes. Laparoscopic approach to ovum pickup and tubal catheterization provides a simple and rapid means of performing the operation. Equipment used to facilitate this process is described, and techniques of tubal catheterization are discussed. A clinical pregnancy rate of 27% is reported in a series of 71 treatment cycles. The application of GIFT in conjunction with in vitro fertilization is discussed, especially the use of excess gametes to provide embryos for freezing. The use of GIFT as a research and investigative tool may provide further insight into the causes for idiopathic infertility.

Human chorionic gonadotropin to oocyte retrieval interval in in vitro fertilization--how critical is it ?

This study shows that modification of the hCG-oocyte retrieval interval from 34 1/2 hours to 37 hours in patients having IVF had no significant effect on the number or quality of oocytes retrieved or on the ultimate pregnancy rate. More consideration can therefore be given to other factors such as patient convenience when scheduling the timing of hCG administration.

Increasing the human menopausal gonadotropin dose--does the response really improve?

This study assesses the effects of attempts to optimize human menopausal gonadotropin (hMG) dosage in 271 patients who had at least two hyperstimulation cycles for in vitro fertilization or gamete intrafallopian transfer. In the first cycle, all patients received clomiphene citrate and hMG 150 IU/d. In the second cycle, the hMG dose was increased in 45% of patients to try to increase the egg yield. In spite of the increase, the population response was practically identical in both cycles. Median numbers of eggs retrieved (6 versus 6), no eggs retrieved (0.4% versus 1%), only one or two eggs retrieved (10% versus 10%), and canceled cycles (10% versus 10.7%). This suggests that increasing the hMG dosage above 150 IU does not increase the number of eggs retrieved. A poor response may be due to inherent differences in follicular development that cannot be overcome by increases in hMG dosage.

The ultrastructure of the preovulatory human egg fertilized in vitro.

Preovulatory eggs in cumulus were inseminated in vitro with washed spermatozoa which had been preincubated for 1.5 hours. After 3 hours, three eggs were processed for electron microscopy and each was sectioned serially from pole to pole. In the two eggs which had been fertilized, the expanded chromatin of the fertilizing sperm head and the chromatin of the ovum were almost completely surrounded by a developing pronuclear envelope. In one of the penetrated eggs the developing male pronucleus and associated midpiece and sperm tail were located within an incorporation cone. The surface of the cone was free of microvilli but contained a zone of microfilaments immediately beneath the plasma membrane. A similar zone of microfilaments was present beneath the advancing surface of the extruding second polar body (PB2) which was connected to the ovum by an interbody and microtubules of the meiotic spindle. Cortical granules were completely absent from the fertilized eggs but were present in the unfertilized egg. PB2 contained a nucleus at a stage of development similar to that of the early pronuclei.