Persistent functional and social benefit 5 years after a multidisciplinary arthritis training program.

OBJECTIVE: To assess the sustainable benefits of a professional, multidisciplinary training program for patients with rheumatoid arthritis. DESIGN: Two studies with different observation periods. Study I was a prospective, randomized trial for 1 year. Study II was a noncontrolled observation over 5 years. SETTING: The 9-day program for eight patient groups encompassed a multidisciplinary cooperation between rheumatologists, orthopedists, physicotherapists, psychologists and social workers. PATIENTS: Sixty-eight consecutive patients with rheumatoid arthritis participated in an arthritis training program either immediately after enrollment in the program or after 1 year. INTERVENTIONS: The program covered the following fields: pathogenesis of rheumatoid arthritis, drug therapy, physicotherapy, practical exercise in remedial gymnastics, use of joint protection devices, orthopedic perspectives, psychological counseling, dietetics, information about unproven cures and social assistance. MAIN OUTCOME MEASURES: Clinical outcome was assessed by self-report questionnaires: (1) Stanford Health Assessment Questionnaire, (2) Freiburg Questionnaire of Coping with Illness, (3) Beck Depression Inventory, and (4) a 21-point scale to evaluate cognitive-behavioral and environmental impact. RESULTS: A significant and persistent improvement of all investigated parameters was demonstrated in the 1-year controlled trial. Between the end-point of the 1-year study and the 5-year evaluation, this improvement increased even more for functional status and coping with illness, whereas depression returned to baseline values. These effects were seen even without reinforcement of the training. CONCLUSION: A professional, multidisciplinary approach to educate patients with rheumatoid arthritis leads to a significant and sustained improvement of the clinical outcome and is an approach that should be established as a part of conventional therapy.

Increased natural killer cell activity correlates with low or negative expression of the HER-2/neu oncogene in patients with breast cancer.

BACKGROUND: Increased expression of the HER-2/neu oncogene in breast cancer correlates with decreased estrogen receptor concentration and seems to be an important prognostic factor. The authors investigated whether there is a correlation between HER-2/neu expression and immunologic parameters representing tumor defense in patients with breast cancer. METHOD: A Western blot analysis was used to investigate HER-2/neu expression, whereas a chromium-release assay using the K562 cell line as target was used to measure natural killer (NK) cell activity. RESULTS: In patients with breast cancer, NK cell activity was significantly higher compared with patients with benign tumors (P = 0.006) or healthy control subjects (P = 0.002). Moreover, 23.3% of patients with breast cancer showed an overexpression of HER-2/neu protein. Within this group of patients, NK cell activity was significantly lower (45.6 +/- 16.1%) compared with the group with no HER-2/neu overexpression (57.3 +/- 11.0%). NK cell activity did not increase in patients with HER-2/neu overexpression. Thus, there was a statistically significant correlation of cytolytic effector cell function with HER-2/neu expression of the tumor (P = 0.003), and HER-2/neu overexpression correlated with a negative estrogen receptor status (P = 0.005). CONCLUSION: These data add further evidence to previous observations from the authors' laboratory that certain tumor characteristics may be associated with reactions of the host with breast cancer.

Clinical evaluation of new assays for determination of serum calcitonin concentrations.

In order to test the clinical usefulness of new commercially available kits for determination of calcitonin serum concentrations, we investigated the family (N = 10) of a patient with medullary thyroid carcinoma and bilateral pheochromocytoma including his affected son, 10 athyreotic patients, totally thyroidectomized for non-medullary thyroid cancer, and 4 normal volunteers. Pentagastrin tests were performed in all subjects. Serum calcitonin levels before and after pentagastrin were determined by 4 kits. Kits A and B are immunoradiometric assays of the sandwich-type, kits C and D are radioimmunoassays, D being the one hitherto routinely used. Our results show that the new assays (kits A, B and C) have a better diagnostic accuracy in screening for medullary thyroid cancer than the RIA (kit D), hitherto used, where basal values overlapped with normals. Although basal values of normals were mostly near the detection limit of all 4 kits, kits A and B were sensitive enough to detect stimulation of calcitonin secretion by pentagastrin in all subjects with intact thyroid glands and kit C in most of them. The lack of increase in calcitonin after pentagastrin observed by kits A, B and C in athyreotic patients suggests deficiency of secretion of this hormone. Only kit D was unable to show this deficiency.

[Cryopreservation of human embryos. A new dimension of in-vitro fertilization]. / Die Kryokonservierung humaner Embryonen. Eine neue Dimension bei der in-vitro-Fertilisierung.

The use of multiple embryo-transfers during the procedure of in-vitro fertilization increases the clinical pregnancy rate but also the rate of multiple gestation. To reduce this risk cryopreservation techniques can be used for storing excess embryos. These can be used for replacement in spontaneous ovulatory cycles or could be used for transfer to a woman who cannot produce her own gametes. Reservations concerning the use of cryopreservation techniques are the risk of cryo-injury, the unknown risk of birth defects, the fear of failure in the mechanical support systems and the legal status of the embryo. Several committee considerations and recommendations are cited.

[Delivery of quadruplets after in vitro fertilization: perinatologic and ethical aspects]. / Entbindung von Vierlingen nach In-vitro-Fertilisierung: Perinatologische und ethische Aspekte.

Progress in modern reproductive medicine has brought much success to infertile couples. A side effect of IVF procedure are multiple pregnancies with clinical, ethical, perinatal and social problems. We report about the first case of quadruplets after IVF born in Austria and try to illustrate the perinatal, social and ethical problems. The 34 year old woman was treated in our sterility outpatient clinic because of secondary sterility. In 1988 finally she underwent IVF procedure. Four oocytes were retrieved by means of vaginal follicle puncture. 4 embryos were transferred, and after 3 weeks 4 viable embryos were seen at an ultrasound investigation. Due to placental insufficiency a cesarean section had to be performed in the 31st week of gestation. The weights of the premature infants were 1280 g, 1340 g, 1260 g and 1250 g. Two years after birth two infants show neurologic defects and need permanent care.

Impaired production of tumor necrosis factor in breast cancer.

Spontaneous and lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF) by peripheral blood macrophages was investigated in breast cancer. Whereas spontaneous TNF production by macrophages derived from patients with breast cancer was comparable with the one found in healthy controls (P greater than 0.1), LPS-stimulated macrophages derived from patients in the disease-free interval as well as with metastatic breast cancer were found to produce significantly lower amounts of TNF, as compared with macrophages derived from healthy control individuals (P less than 0.0005). However, the production of TNF did not significantly differ between the two patient populations (P greater than 0.05). The impairment of LPS-induced TNF production did not depend upon such characteristics of the primary tumor as size, axillary lymph node and estrogen receptor status, or upon the fact of administration of adjuvant chemotherapy and, in patients with metastatic disease, hormone treatment. To further investigate cytokine production by macrophages, spontaneous and LPS-induced interleukin-1 (IL-1) production was investigated also. However, no difference was found between patients and controls concerning IL-1 generation. The authors thus conclude that LPS-induced TNF production was impaired in breast cancer independent of the presence of detectable metastatic disease, whereas IL-1 production remained unimpaired.

In vitro fertilization with spermatozoa from alloplastic spermatocele.

This case report describes successful IVF of oocytes of a 22-year-old female with epididymal spermatozoa aspirated from alloplastic spermatocele of the husband presenting with bilateral congenital absence of the vas deferens. Motile spermatozoa were aspirated from the reservoir 3 months after implantation. Abortion occurred 22 days after embryo replacement.

Is trisomy 22 in acute myeloid leukemia a primary abnormality or only a secondary change associated with inversion 16?

In an attempt to confirm the existence of acute myeloid leukemia (AML) with trisomy 22, we studied three patients in whom trisomy 22 imposed as the sole karyotype abnormality. After revision of the karyotypes, however, we were able to identify an inv(16) as the important primary abnormality in all of them. Based on this experience, we investigated whether at least some of the 17 AML cases with trisomy 22 reported so far might possibly have been misinterpreted. Interestingly, ten out of 16 evaluable cases were classified as M4, some of them with bone marrow eosinophilia. As in cases with inv(16), only few metaphases contained trisomy 22. Furthermore, in at least two out of the only four published karyotypes of cases with trisomy 22, an inv(16) is evident and in the other two cases it cannot be ruled out. We therefore believe that at least some of the trisomy 22 cases mentioned in the literature are in fact only secondary changes occurring in AML with an inv(16) and suggest that future reports of AML with trisomy 22 as a specific primary abnormality can only be accepted as such if inv(16) has been excluded with appropriate methods.

[Hypophyseal suppression and subsequent cycle stimulation: experiences in an in vitro fertilization program]. / Hypophysäre Suppression und anschliessende Zyklusstimulation: Erfahrungen in einem IVF-Programm.

Gonadotropin releasing hormone (GnRH) agonists can induce a hypogonadotropic state. We studied the effect of a long acting GnRH agonist on pituitary gonadotropin levels, the pattern of serum steroid levels in subsequent cycle stimulation, and whether such a protocol can improve the results of an in-vitro fertilization (IVF) program. 29 patients with tubal factor from our IVF program received 4 mg Decapeptyl CR intramuscularly and were subsequently stimulated with FSH/HMG/HCG (Group I). 35 patients were stimulated according to our standard protocol with HMG/HCG (Group II). After a single injection of Decapeptyl CR, serum levels of LH, FSH and E2 fell to more than half of pretreatment levels. In the subsequent cycle stimulation the gonadotropin dosage was increased threefold compared with the control group. In group I, progesterone levels were significantly higher. Though more oocytes were retrieved in group I, fertilization rates were significantly lower. After Decapeptyl and the subsequent stimulation, we observed short rises in urinary LH in 22/29 patients. In our experience, a single intramuscular injection of Decapeptyl resulted in sufficient pituitary suppression, however, we could not see an improvement in the results after IVF.

Follicular aspiration for in vitro fertilization: sonographically guided transvaginal versus laparoscopic approach.

Laparoscopy is the most commonly used procedure for oocyte retrieval in an in-vitro fertilization (IVF) program. In this study we compared the results of 21 laparoscopic and 21 sonographically guided transvaginal oocyte retrievals using a vaginal probe. Laparoscopically 3.7 and transvaginally 4.8 oocytes per patient were recovered. Overall 6 pregnancies were achieved, giving a pregnancy rate of 14.1% per patient. Vaginal follicular aspiration resulted in a higher oocyte recovery rate. The advantages of the method were a shorter operation time, a superficial anesthesia and, compared to laparoscopy, a less invasive and simpler technique. Therefore this method is now commonly used for routine IVF procedures in our institution.

Relationship between the steroid and prolactin concentration in follicular fluid and the maturation and fertilization of human oocytes.

Seventy-eight follicles and their follicular fluid were aspirated from 46 women undergoing in vitro fertilization (IVF) procedures after stimulation of the ovaries with a low-dose human menopausal gonadotropin/human chorionic gonadotropin stimulation regimen. The concentrations of estradiol (E2), progesterone (P), testosterone (T), and prolactin (PRL) were measured in follicular fluid and related to the maturation of the oocyte-corona-cumulus complex (OCCC) and the fertilization of oocytes. Follicles containing mature oocytes had significantly higher follicular fluid E2 and P levels than follicles with intermediate and immature oocytes. A constant decrease in PRL and T values with advancing follicular maturation was observed. Similar results were obtained when the fertilizing ability of the oocytes was examined. The gradual decline in follicular fluid PRL and T levels during follicular development was connected with increasing E2 and P biosynthesis and therefore seems to be an important precondition for normal follicular and oocyte maturation.

[Effect of serum prolactin on cycle stimulation and fertilization of human oocytes]. / Der Einfluss des Serum-Prolaktins auf Zyklusstimulation und Fertilisierung menschlicher Eizellen.

During cycle stimulation for in-vitro fertilisation (IVF) some patients develop hyperprolactinaemia. Since prolactin (PRL), being an aromatase inhibitor, can interfere with follicular fluid steroid metabolism, we examined the influence of high serum PRL levels on the endocrine response and fertilisation rate of oocytes. 33 consecutive patients stimulated by hMG/hCG for IVF were included in this study. Two groups of patients were established: Group 1 consisting of 18 patients with serum PRL levels less than or equal to 25 ng/ml, and group 2 containing 15 patients, who developed PRL levels greater than 25 ng/ml during cycle stimulation. The serum oestradiol (E2), progesterone (P) and PRL levels 3, 2 and 1 day before and at the day of follicle puncture were evaluated. The decrease of E2 levels at the day of oocyte retrieval was significantly steeper in group 1. The P levels 2 days before oocyte retrieval were significantly higher in group 1 indicating the onset of preovulatory luteinization. Luteinization after the hCG injection was more effective in group 1 resulting in significantly higher P levels. Fertilisation and cleavage rates were significantly higher in patients with normal PRL levels. High serum PRL levels therefore might indicate an interference in follicular and oocyte development leading to oocytes of inferior quality.

[Comparison of vaginosonographic, transabdominal sonographic and laparoscopic follicle puncture for the retrieval of oocytes within the scope of an in vitro fertilization program]. / Vergleich von vaginosonographischer, transabdomineller sonographischer und laparoskopischer Follikelpunktion zur Gewinnung von Eizellen im Rahmen eines In-vitro-Fertilisierungsprogrammes.

For follicular aspiration and oocyte retrieval for in-vitro-fertilization (IVF) laparoscopy, laparotomy and different ultrasound guided methods like transvesical and transvaginal puncture can be used. Sonographically guided follicular aspiration has become more important because this procedure is less invasive. In this study we compared the results of 28 laparoscopical, 35 transabdominal and 21 transvaginal follicle puncture after successful cycle stimulation. Performing transvaginal puncture 4.7, using laparoscopy 3.4 and performing transvesical puncture 2.0 oocytes per attempt were retrieved. The advantages of transvaginal follicle aspiration were a shorter operation time, a superficial anesthesia and compared to laparoscopy a less invasive and simple technique. Therefore this method is now commonly used for routine IVF procedures in our institution.

Comparison of the results of vaginal and abdominal follicle scans.

The hormonal profile and sonographical assessing of the number and size of the follicles are important in hyperstimulated cycles. Follicular imaging obtained by abdominal scanning may be distorted by echoes from the intestine or by unfavourable location of the ovaries and patients must have a full bladder. We compared the number and size of the follicles at abdominal sonography with the results obtained by vaginal sonography in 37 patients. Vaginal sonography showed more follicles than abdominal sonography because of improved imaging of small follicles on early days of cycle. This might help one to tailor the hyperstimulation to an individual's endocrine response.

Hormonal parameters in follicular fluid and the fertilization rate of in vitro cultured oocytes.

Oocytes and matched samples of follicular fluid were obtained from 52 preovulatory follicles aspirated laparoscopically for in vitro fertilization (IVF). Follicular fluid concentrations of estradiol (E2), progesterone (P), testosterone (T), prolactin (HPRL), prostaglandin F2 alpha (PGF2 alpha), prostaglandin E (PGE), protein content, and collagenolytic activity were measured and related to the fertilization rate of oocytes cultured in vitro. High concentrations of P and low levels of T and HPRL were associated with mature, fertilizable oocytes. Levels of PGF2 alpha, PGE, and follicular fluid protein concentrations were similar in both groups. Mean collagenolytic activity was increased in the fertilized oocytes, although no significant difference could be observed. Our data demonstrate a close association between follicular fluid steroid and HPRL concentrations and successful fertilization of oocytes.

[Intrauterine pregnancy following intratubal gamete transfer--a case report]. / Intrauterine Schwangerschaft nach intratubarem Gametentransfer--ein Fallbericht.

Since the beginning of 1986 gamete intrafallopian transfer (GIFT) has been used in the treatment of infertile couples. Only patients in whom tubal patency has been ascertained are included in the programme. After hormonal stimulation of the ovaries and laparoscopic follicular aspiration oocytes and semen are transferred by means of catheterisation into the fallopian tubes. The first pregnancy in our department established by gamete intrafallopian transfer--and the first in Austria to our knowledge--is reported.