Postmarketing experience with auranofin in the Federal Republic of Germany.

Data about adverse events can be particularly useful when assessing newly marketed drugs. However, spontaneous reporting of adverse events does not generally provide sufficient or highly accurate data on incidence and prevalence. In order to provide the most complete and accurate data, a postmarketing surveillance program (PMSP) for auranofin (AF) oral gold therapy for rheumatoid arthritis (RA) was conducted in the Federal Republic of Germany (FRG) from December 1982 through December 1985. The objectives of the program were to observe a large population treated with AF for more than a year; to compare the safety profile of AF with experience from clinical trials; and to register rare or previously unknown adverse events. The program included 2,777 patients with RA from 928 test centers. Disease duration was less than 2 years in 29%. 2-5 in 23.2%, 5-10 in 32.5%, and more than 10 in 13.3% (no data for 2%); disease was mild or moderate in 67.4% and severe in 29.9% (no data for 2.7%). Auranofin was given 6 mg/day as either two 3-mg tablets at breakfast or 1 tablet at breakfast and 1 at the evening meal. Laboratory studies and efficacy, as indicated by increase in grip strength and decrease in number of tender and swollen joints, were monitored regularly. A total of 1,595 patients completed 1 year of treatment with AF. Withdrawals included 12.9% for adverse events, 4.2% for insufficient therapeutic effect, and 33.1% for a variety of administrative or technical reasons. The most common adverse event was alteration in stool pattern, which occurred in 22.5% of patients, compared with 46.6% in worldwide AF clinical trials. Other gastrointestinal symptoms occurred in 17.4%, compared with 22.4% worldwide. The occurrence of most adverse events in the PMSP was much less than in worldwide studies, for example: skin rash 7.3% vs. 24.2% worldwide, pruritus 4.2% vs. 16.6%, proteinuria 1.0% vs. 5.0%, and leukopenia 0.7% vs. 1.9%. These discrepancies may be explained by the method of monitoring employed in the postmarketing study, which favored the reporting of only clinically relevant adverse events. The pattern of occurrence of adverse events was similar to that seen during other AF trials, indicating that any intolerance to AF occurs primarily within the first 6 months of treatment. However, hematologic or nephrologic adverse events appear to be independent of time on therapy, with a constant monthly prevalence of about 0.1-0.2%.(ABSTRACT TRUNCATED AT 400 WORDS)

[Ultrasound computer tomography--new image-producing possibilities]. / Ultraschall-Computertomographie--neue bildgebende Möglichkeiten?

A new technique using ultrasound computed tomography is explained. Reconstruction of pictures follows basically the algorithm of radiology CT in one plane. The computed data of several scan planes with different angles of the same subject are used for image reconstruction. In this manner, poor lateral resolution of reflections is eliminated. The improved quality of the CT ultrasound images is shown.

[3-dimensional sonography--technical concept and image-producing possibilities]. / Dreidimensionale Sonographie--technisches Konzept und bildgebende Möglichkeiten.

An ultrasound-system realizing 3-D-technique is described. Its handling and depicting possibilities are mentioned. This ultrasound equipment gives additional imaging possibilities. These are combinable planes of cuts, adding-up-techniques, corner-like ultrasound cuts and the possibility to trace a process even out of the straight plane and visualize it. Whole 3-dimensional-technique is available through full stereometric pre- and postprocessing of 3-D pictures which are separately depicted and viewed via stereometric optics.

Hormonal and ultrasonic characteristics of 23 clomiphene citrate stimulated cycles resulting in pregnancies after in vitro fertilization and embryo transfer.

In vitro fertilization (IVF) and embryo transfer (ET) were successful in 24 clomiphene citrate stimulated cycles in 22 patients. Ovarian follicular growth was monitored by ultrasound (US) and serum estradiol (E2) concentrations in order to determine the most favorable time for the induction of ovulation by administration of human chorionic gonadotropin (hCG). The day of the hCG injection was considered day 0. After an almost linear growth the mean diameter of the dominant follicle reached 19.3 +/- 2 mm on day 0. Serum E2 concentrations also increased in almost linear fashion up to a maximum of 1,037 +/- 322 pg/ml on day +1. On day 0 the mean serum E2 concentration was 862 +/- 279 pg/ml. A mean serum E2 concentration per dominant and codominant follicle of 328 +/- 100 pg/ml was found on day 0. There was no linear correlation between the follicular diameters and the serum E2-values on the same day. The time of ovum recovery was often different to the time at which ovulation would have been expected in a normal cycle.

[Duchenne muscular dystrophy: detection of carriers using ultrasound]. / Muskeldystrophie Duchenne: Konduktorinnenerfassung mit Ultraschall.

For detection of carriers of Duchenne muscular dystrophy the calf musculature was investigated for increased fat and connective tissue content using ultrasound. The investigation was done blind in 24 females without prior information on family history and creatine kinase (CK-)values. In 5 out of 6 carriers and in 5 out of 7 controls the correct diagnosis was made. One carrier was assumed to be unaffected and in two controls findings were inconclusive. Out of 11 potential carriers with normal CK-values 4 were considered to be carriers. One borderline case could not be assigned clearly. For the present problem ultrasound diagnostics have been proven to be useful particularly in older females in whom enzyme assessment will not produce pathological data.

Luteal phase following oocyte aspiration, in vitro fertilization, and embryo transfer in clomid/HCG-stimulated cycles.

Using basal body temperature and repeated radioimmunological plasma progesterone estimations we monitored the luteal phase in seven patients after the administration of Clomid/hCG, oocyte recovery, in vitro fertilization and embryo transfer. In six of these women, the transferred embryos did not implant, and they bled 13--16 days after oocyte recovery. Neither the basal body temperature charts nor the plasma progesterone levels provided any indication of a luteal phase defect, being indistinguishable from those obtained in a control group of healthy women during the natural cycle. In the seventh woman, transfer of an eight-cell stage embryo resulted in implantation and a pregnancy which, to date (37th week) is developing normally.

[Possibilities of ultrasonic examination of the mammae (author's transl)]. / Möglichkeiten der Ultraschalluntersuchung der Mammae.

1,344 women were examined in the course of 3 years by means of the ultrasonic system Multiplanar MS 3 which was coupled direct to the skin. This direct coupling to the skin of the breast and the freely mobile sound head enable immediate puncture of tumours of the breast in direct ultrasonic vision. In multiple cysts it will be possible to puncture all cysts--including the occult ones--in one session. In the first 229 examined tumours, the rate of accuracy of the diagnosis "cyst" was 98%. Successful punctures, including the non-palpable cysts, were effected down to a minimum volume of 0.1 ml. The problem of the nonpalpable cysts can be considered as solved from the sonographic angle. In our case, this entailed omission, and hence saving in cost, of every third biopsy of the mammae (approximately 200 out of 600 biopsies per annum).

[On-target accuracy of tumour punctures in the breast. Possible sources of error in puncture cytology (author's transl)]. / Zur Treffsicherheit von Tumorpunktionen in der Brust. Mögliche Fehlerquellen zur Punktionszytologie.

Puncture cytology can yield false results if the tumour to be explored is not definitely located by the puncture needle. The risk of missing the tumour is particularly great if the tumour is small. We do not know of any safe method to control and ensure on-target accuracy. In the course of 3 years we punctured in 203 women 665 palpable and also non-palpable cysts, using compound scanner Multiplanar-MS-3. 38 further individual punctures failed despite repeated attempts under visual control of this device which supplies a spatial impression of the target during puncture. Some of the small tumours will evade the advancing needle time and again.

[Microcalcifications in mammography and visualization by ultrasound (author's transl)]. / Mikrokalk im Mammogramm und Darstellungsmöglichkeit im Ultraschall.

Sonography can yield indirect visualization only of microcalcifications in the female breast. In order to obtain an image of the echo pattern of the grouped microcalcifications, it is essential that the device employed possesses suitable dynamic characteristics, and it is also necessary to employ the technique of additive tomography. The investigator must familiarize himself with the proper interpretation of reflex patterns. Microcalcifications cannot be detected via sonography with the same degree of accuracy as with the help of mammography. However, sonographic detection is easier if the microcalcifications are more closely grouped. Nevertheless, the authors were able to show in a small comparative series that grouped calcifications can be detected even without previous information of their presence.