Alternative and complementary therapies in osteoarthritis and cartilage repair.

Osteoarthritis (OA) is the most common joint condition and, with a burgeoning ageing population, is due to increase in prevalence. Beyond conventional medical and surgical interventions, there are an increasing number of 'alternative' therapies. These alternative therapies may have a limited evidence base and, for this reason, are often only afforded brief reference (or completely excluded) from current OA guidelines. Thus, the aim of this review was to synthesize the current evidence regarding autologous chondrocyte implantation (ACI), mesenchymal stem cell (MSC) therapy, platelet-rich plasma (PRP), vitamin D and other alternative therapies. The majority of studies were in knee OA or chondral defects. Matrix-assisted ACI has demonstrated exceedingly limited, symptomatic improvements in the treatment of cartilage defects of the knee and is not supported for the treatment of knee OA. There is some evidence to suggest symptomatic improvement with MSC injection in knee OA, with the suggestion of minimal structural improvement demonstrated on MRI and there are positive signals that PRP may also lead to symptomatic improvement, though variation in preparation makes inter-study comparison difficult. There is variability in findings with vitamin D supplementation in OA, and the only recommendation which can be made, at this time, is for replacement when vitamin D is deplete. Other alternative therapies reviewed have some evidence (though from small, poor-quality studies) to support improvement in symptoms and again there is often a wide variation in dosage and regimens. For all these therapeutic modalities, although controlled studies have been undertaken to evaluate effectiveness in OA, these have often been of small size, limited statistical power, uncertain blindness and using various methodologies. These deficiencies must leave the question as to whether they have been validated as effective therapies in OA (or chondral defects). The conclusions of this review are that all alternative interventions definitely require clinical trials with robust methodology, to assess their efficacy and safety in the treatment of OA beyond contextual and placebo effects.

[Does Routine Pathology Evaluation of Uterine Content Following Evacuation for Abnormal Early Pregnancy Influence Further Management?]

The aim was to determine usefulness of routine pathologic evaluation of uterine content after uterine evacuation following the diagnosis of abnormal early pregnancy. This retrospective descriptive study performed during a one-year period included all patients diagnosed with abnormal early pregnancy clinically or by ultrasound in the first trimester. All patients had uterine evacuation. During the study period, 335 women were diagnosed with abnormal early pregnancy and referred for uterine evacuation. Pathology results were available for 312 women included in the analysis. In 272 (87.2%) women, trophoblast tissue was found on examination and therefore intrauterine pregnancy was confirmed. In the remaining 40 patients, trophoblast was not found. In 10 (3.2%) patients, gestational trophoblastic disease was diagnosed, not being suspected on pre-evacuation assessment. In one patient, suspected molar pregnancy was excluded by pathology evaluation. Based on 51/312 (16.3 %) patients where pathology examination of uterine content influenced further management and treatment, we believe that routine pathology examination of uterine content after uterine evacuation in the fi rst trimester following abnormal early pregnancy is justifiable in clinical practice.

The impact of 5-azacytidine on placental weight, glycoprotein pattern and proliferating cell nuclear antigen expression in rat placenta.

During the placentation process, the expression of various glycoproteins plays an important role in embryonal development. Alterations in DNA methylation caused by 5-azacytidine (5azaC) can disturb normal glycoprotein expression as well as the proliferative ability of trophoblast cells. In order to assess this, a single dose of 5azaC was injected intraperitoneally into pregnant rats during days 1-19 of gestation. Animals were euthanised on day 20 and placental weight, as well as glycoprotein composition, was analysed together with immunohistological assessment of the degree of proliferation of the trophoblast cells. The placental weight was found to be significantly smaller in animals treated by 5azaC during days 4 to 14 of gestation (p<0.01, Student's t-test). The treatment on days 4, 5, and 6 resulted in a lack of labyrinth with the strong proliferative activity of the cells in the basal layer. Expression of glycoproteins with molecular mass smaller than 60 kDa was reduced with treatment on day 6. The 5azaC administered from days 7 to 10 completely disturbed the placental structure and the proliferation of trophoblast cells was poor. During these days GP70 exhibited stronger expression in treated animals, contrary to GP40, which was stronger in controls. A natural border between the labyrinth and the basal layer was established on days 11 and 12. The basal layer was dominant with a lower proliferation of trophoblast cells compared with the controls. With the establishment of the labyrinth on day 13, the expression of GP40 was restored. Proliferation of the trophoblast cells from days 13 to 15 was higher compared with the controls. The changes in placental mass and the proliferative ability of trophoblast cells in rat placenta exposed to 5azaC represent more proof of the importance of epigenetics in the regulation of placental development.

Antenatal detection of mosaic trisomy 9 by ultrasound: a case report and literature review.

This paper presents a fetus with mosaic trisomy 9 diagnosed by chorionic villus sampling and confirmed by cordocentesis, and compares this case with published cases in order better to define the ultrasound markers confined to trisomy 9 syndrome. Detailed fetal ultrasound examination was carried out, revealing shortened femur, placental cysts and oligohydramnios. All published trisomy 9 cases with abnormal ultrasound findings were extracted from the MEDLINE database in the period from 1973 to 2002. We found 12 non-mosaic and 13 mosaic cases, including our case. The most frequent ultrasound abnormalities included characteristic cardiac, skeletal, craniofacial and central nervous system malformations. Intrauterine growth restriction and single umbilical artery were prevalent non-specific findings in both non-mosaic and mosaic groups. Parental chromosomal variations, as in our case, were not uncommon findings. When a fetus shows structural anomalies suggesting the presence of trisomy 9, karyotyping should be performed on both chorionic villi or amniocytes and fetal blood lymphocytes to enable a correct diagnosis to be made.

Non-invasive method of evaluation of trophoblast invasion of spiral arteries in monochorionic twins with discordant birthweight.

To test the hypothesis that variation in birthweight between twin pairs is due to discordant placental development, we determined spiral arterial blood flow by colour pulsed Doppler ultrasound scan. We prospectively studied 24 twin pregnancies in the late second trimester with (n=12) and without (n=12) inter-pair difference in estimated birthweight of > or = 20 per cent. In the discordant growth group, there were seven cases with chronic twin-twin transfusion syndrome (TTTS) and five without. The blood flow in spiral artery of each twin's portion of the placenta was assessed by resistance index (RI) by colour flow pulsed Doppler within a 5 cm radius of cord insertion. In twins with discordant weight, RI was increased in the growth restricted (FGR) twin than the appropriate for gestational age (AGA) co-twin (0.46 +/- 0.02 vs 0.3 +/- 0.01; P< 0.001) and the control group (P< 0.001). However, delta RI was comparable between twins with and without TTTS (0.13 +/- 0.01 vs 0.19 +/- 0.02; P=NS). No such differences were found between concordant twin pairs (0.28 +/- 0.01 vs 0.29 +/- 0.1; P=NS) and AGA twins of the discordant growth group. This study indicates that growth restricted twins have increased resistance to blood flow in the spiral arteries than the AGA co-twins. This observation, therefore, suggests non-physiological remodelling of the maternal spiral arteries in response to migrating trophoblast in placental bed of FGR MC twins.

Post-partum hysterectomies: revisited.

This retrospective case analysis is performed in order to analyze post-partum hysterectomies in St. Mary's Hospital, Manchester during the last thirteen years and to compare it with the published results twenty years ago. We wanted to determine any possible changes in trends as well as to discuss the place of post-partum hysterectomy in modern obstetric practice. The main outcome measurements were incidence, maternal mortality and morbidity, indications and risk factors for post-partum hysterectomy in our hospital today and twenty years ago. Obtained results were compared to the same data and trends world-wide. There has been a fall in the incidence of both, elective and emergency post-partum hysterectomies in St. Mary's Hospital. All together, 28 women underwent post-partum hysterectomy electively or as an emergency in the period between 1985 and 1997. Mortality rate was 1 in 28 cases and morbidity rate was 65% in emergency group and 37.5% in elective group. The most common indication for elective post-partum hysterectomy is cervical intraepithelial neoplasia. The most important risk factor for emergency post-partum hysterectomy is previous cesarean section especially related to placenta accreta. There was no significant changes in trends, maternal mortality and morbidity and indications related to emergency post-partum hysterectomies today and twenty years ago, while the indications for elective cases were changed.

Cervical incompetence: the use of selective and emergency cerclage.

OBJECTIVE: This prospective case series was performed in order to assess pregnancy outcome of women with tentative diagnosis of cervical incompetence undergoing selective and emergency cervical cerclage. METHODS: Women recruited in this case series were divided into two groups. The selective group (n = 13) was chosen among pregnant women with a history suggestive of cervical incompetence, but no clinical evidence of threatened miscarriage. The definition of cervical incompetence was dilatation of internal cervical os with shortening of the cervix less than 25 mm and "funnelling" of 25% and more, found on the ultrasound examination of the cervix. The emergency group (n = 12) had clinical symptoms of threatened miscarriage. After exclusion of infection and in the absence of uterine activity they were counseled and offered cerclage. RESULTS: After cervical cerclage all women were treated in the same way as per our clinical protocol and monitored until delivery. The median gestational age at delivery was 36 weeks (19-39) in the selective group and 33 weeks (22-38) in the emergency group. This difference is not statistically significant. There was 1 miscarriage (8%), 5 pre-term deliveries (38%) and 7 term deliveries (54%) in the selective group; and 4 miscarriages (33%), 3 pre-term deliveries (25%) and 5 term deliveries (42%) in the emergency group. Total neonatal survival was 19/20 (95%) if pregnancy exceeded 24 weeks, making perinatal mortality 5%. There was no differences between selective and emergency groups (1 of 12 in selective vs. 0 of 8 in emergency). CONCLUSION: Overall, it can be concluded that both selective and emergency cerclage may have some benefits in patients with cervical incompetence. However, in the absence of a randomized-controlled study, these beneficial effects described cannot be considered as proved.

First trimester malformation screening.

First trimester fetal malformation screening still represents a diagnostic challenge in modem obstetrics. Being solely dependent on ultrasound instrumentation, and the skill and experience of the operator, recently improved by introducing high frequency transvaginal approach and digital image processing. This opens a new field of ultrasound in obstetrics called sonoembriology. Until now sonoembriology in routine clinical practice resulted in numerous reports about early detection of rare anomalies and uncommon syndromes. The reported sensitivity of sonoembriology with a respect to a final pregnancy outcome was more than 60% of all malformations in total, while in combination with ultrasound screening in second trimester, increases to in excess of 80%. The commonest anomalies detected by sonoembriology are anomalies of the head and brain, heart, abdominal wall, unbilical cord, urinary tract and skeleton. There is an important role of sonoembriology in the assessment of the nuchal translucency in the screening programme for chromosomal anomalies. This changes the well-known concept "fetus as a patient" to "embryo as a patient" and opens new frontiers in fetal diagnosis and therapy.

In vivo assessment of failed trophoblastic invasion of the spiral arteries in pre-eclampsia.

OBJECTIVE: To assess the ability of colour/pulsed Doppler ultrasound to detect failed physiologic change of the spiral arteries in pregnancies complicated by pre-eclampsia. DESIGN: Prospective matched-pairs case controlled study. SETTING: Tertiary referral teaching hospital. SAMPLE: Sixteen women with severe pre-eclampsia and 16 normotensive controls. METHODS: Colour/pulsed Doppler assessment of blood flow in the uterine arteries and spiral arteries in central and peripheral parts of the placental bed. MAIN OUTCOME MEASURES: Impedance to blood flow in the spiral arteries in pre-eclamptic group compared with normotensive controls. RESULTS: In women with pre-eclampsia there is significantly higher impedance to blood flow in spiral arteries compared with normotensive women. CONCLUSIONS: Ultrasound colour/pulsed Doppler based investigation of blood flow in the spiral arteries in ongoing pregnancy can detect failed physiological change of these vessels in pre-eclampsia. This is in concordance with histologic data.

Outcome of post-term pregnancy: a matched-pair case-control study.

AIM: Matched-case control study was performed to assess perinatal mortality and feto-maternal morbidity related to the post-term pregnancy. METHODS: 124 patients who delivered after 42 weeks of pregnancy were matched by age and parity with a control group of patients who delivered at term. Perinatal mortality and neonatal morbidity, as well as maternal morbidity were analyzed in both groups and differences tested for statistical significance. RESULTS: There was no statistically significant difference in perinatal mortality between the two groups (1 vs. 0; p>0.05). A statistically significant difference was found in the umbilical cord blood sample base excess after delivery in the post-term group. Cesarean section rate was higher in the post-term group (-6.1 vs. -4.9, p<0.05). If spontaneous labor occurred, there were no statistically significant differences in any of the analyzed parameters between the groups (p>0.05). CONCLUSION: Post-term pregnancy was related to higher maternal and neonatal morbidity, but the risks were biased by higher induction of labor rate and more frequent monitoring resulting in a higher intervention rate.

Exaggerated effects of progestogen on uterine artery pulsatility index in Turner's syndrome patients receiving hormone replacement therapy.

OBJECTIVE: To investigate the effect of estrogen and progestogen on the resistance to blood flow in the uterine arteries of Turner's syndrome patients. DESIGN: Prospective clinical study. SETTING: A tertiary infertility clinic. PATIENTS: Five Turner's syndrome patients, six patients who had surgical castration, and five patients with idiopathic primary ovarian failure. INTERVENTIONS: The patients were treated with 2 mg E2 valerate to which 500 micrograms norgesterel was added for 10 days in a 28-day cycle. Transvaginal color Doppler was used to measure pulsatility index in the uterine arteries at eight regular intervals during a single cycle. MAIN OUTCOME MEASURE: Pulsatility index of the uterine arteries. RESULTS: The administration of norgesterel to Turner's syndrome patients resulted in an increase in pulsatility index that was significantly higher than in patients who had surgical castration (confidence interval = 0.17 to 2.42). CONCLUSION: The uterine arteries of Turner's syndrome patients are more sensitive to the tonic effect of progestogen. If manifest in cardiac arteries also this phenomenon may be partly responsible for the increased incidence of cardiovascular disease and shorter life expectancy in Turner's syndrome patients. To achieve optimal protection from cardiovascular disease, Turner's syndrome patients may benefit from hormone replacement treatment containing altered doses of estrogen and progestogen.

Spiral artery blood flow in the central and peripheral areas of the placental bed in the second trimester.

OBJECTIVE: To assess impedance to blood flow through spiral arteries in the central and peripheral areas of the placental bed, to determine if in vivo findings are in concordance with histologic observations of cytotrophoblast invasion. METHODS: This study was cross-sectional, using transabdominal color flow and pulsed Doppler imaging in 64 women with normal, singleton pregnancies at 17-20 weeks' gestation. Spiral arteries were visualized by color Doppler in the central and peripheral parts of the placental bed, and blood flow was analyzed using pulsed Doppler to calculate the resistance index (RI) and the pulsatility index (PI). RESULTS: Visualization of flow in the spiral arteries was achieved in 100% of cases in the central area and in 95% in the periphery. Both the RI and PI were significantly lower in the center compared with the periphery (P < .001). There was no significant difference in the peak systolic velocities between the two areas. Regression analysis showed no significant difference in RI or PI at the different weeks of gestation in the central and peripheral areas of the placental bed. CONCLUSION: Impedance to blood flow through spiral arteries in the second trimester is lower in the central area of the placental bed, and is in agreement with previous histologic data. Physiologic change of the spiral arteries is functionally complete around 17 weeks' gestation.

Stage I ovarian cancer by transvaginal color Doppler sonography: a report of 18 cases.

A total of 18 cases with ovarian carcinoma stage I (15 stage Ia and three stage Ib) were studied retrospectively to evaluate the efficiency of transvaginal color Doppler sonography in detecting the disease in its early stages. Four asymptomatic women (two cases with morphologically normal ovaries, and two with simple unilocular cysts) were found during the screening program. These cases would have been missed without the use of transvaginal color Doppler sonography. One ovary with stage Ia, and another ovary in a case with stage Ib ovarian cancer were missed. These data show the ability of transvaginal color Doppler sonography to detect ovarian cancer as early as stage I even in asymptomatic women as well as in the morphologically normal ovary.

Transvaginal color Doppler in the assessment of abnormal early pregnancy.

The study groups comprised 61 pregnant women whose gestational age ranged from 7 to 12 weeks from the last menstrual period. All patients apparently had a normal developing pregnancy; there were no clinical symptoms of pathology e.g. bleeding in early pregnancy. Eighty-two patients with a clinically and ultrasonographically normal pregnancy whose gestational age ranged from 7 to 12 weeks, served as a control group. When the anatomical position of investigated area have been obtained clearly, pulsed wave Doppler sample volume was placed on the structures of interest: the both uterine arteries and intervillous space. There is no statistically significant difference between the Resistance Index (RI) in the left or right uterine artery (P greater than 0.01) and among investigated groups of patients (P greater than 0.01). The intervillous blood flow RI in the case of molar pregnancy was 0.38 with SD +/- 0.03; in blighted ovum 0.43 with SD +/- 0.03, and in missed abortion 0.43 with SD +/- 0.02. It should be stressed that in nine (31%) cases of blighted ova and in five (26%) cases of missed abortion, intervillous space flow could not be detected. In the control group, intervillous blood flow was always visualized and the mean RI was 0.45 with SD - 0.04. Statistical analysis showed significantly higher RI in control group in comparison with other groups of patients (P less than 0.01), and significantly lower RI in molar pregnancy in comparison with other groups of patients (P less than 0.01). There was no difference in RI between blighted ova and missed abortions (P greater than 0.01).