High-dose chemotherapy with autologous hematopoietic stem-cell support compared with standard-dose chemotherapy in breast cancer patients with 10 or more positive lymph nodes: first results of a randomized trial.

PURPOSE: Investigation of high-dose chemotherapy (HD-CT) followed by autologous hematopoietic stem-cell support compared with standard-dose chemotherapy (SD-CT) as adjuvant treatment in patients with primary breast cancer and 10 or more positive axillary lymph nodes. PATIENTS AND METHODS: Between November 1993 and September 2000, 307 patients were randomized to receive (following four cycles of epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2), intravenously every 21 days) either HD-CT of cyclophosphamide 1500 mg/m(2), thiotepa 150 mg/m(2), and mitoxantrone 10 mg/m(2), intravenously for 4 consecutive days followed by stem-cell support; or SD-CT in three cycles of cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), and fluorouracil 600 mg/m(2) intravenously on days 1 and 8, every 28 days. The primary end point was event-free survival. RESULTS: After a median follow-up of 3.8 years, 144 events with respect to event-free survival have been observed (HD-CT: 63 events; SD-CT: 81 events). The first event of failure (HD-CT v SD-CT) was an isolated locoregional recurrence (nine v 11), a distant failure (52 v 68), and death without recurrence (two v two). The estimated relative risk of HD-CT versus SD-CT was 0.75 (95% CI, 0.54 to 1.06; P =.095). Overall survival showed no difference (HD-CT: 40 deaths; SD-CT: 49 deaths). CONCLUSION: There was a trend in favor of HD-CT with respect to event-free survival, but without statistical significance. Further follow-up and a meta-analysis of all randomized studies will reveal the effect of HD-CT as compared with SD-CT as adjuvant treatment in high-risk primary breast cancer.

Characterization by Scatchard plots of monoclonal antibody enzyme conjugates directed against alpha-1-foetoprotein.

A radioimmunoassay was used to investigate the affinity of 2 monoclonal antibodies against human alpha-1-foetoprotein before and after conjugation with horseradish peroxidase. The equilibrium constant of the high-affinity antibody was reduced 10-fold whereas it remained unaffected in the low-affinity antibody. With the Scatchard diagram, quantification of unlabelled antibodies in the unpurified conjugate mixture is also possible if antibody affinity is changed by the coupling procedure.

Effects of castration, exogenous testosterone and estrogen on endotoxin response in male rats.

Using an experimental model of continuous endotoxin infusion, the effects of castration, testosterone and estrogen substitution on disseminated intravascular coagulation in male rats were investigated. Male rats which are not pretreated react in the same way to an endotoxin infusion as female animals, with an increase in free plasma hemoglobin, decrease of fibrinogen level, decrease of hematocrit and platelets and glomerular fibrin depositions. Different experimental groups of testectomized rats were pretreated with (i) 0.3 micrograms (pregnancy-conserving dose) or (ii) 30 micrograms ethinylestradiol (ovulation-suppression dose) or (iii) 250 mg testosterone. They were then compared to groups of animals treated with sesame oil as well as untreated group of rats. The pretreatment with testosterone and estrogens in the small-dose group had only an insignificant effect on the shock sequence. Only those animals which were treated with a high dose of estrogens showed a dramatic enhancement of their endotoxin sensitivity. It was also shown that in male animals an increased estrogen level might mediate a state of 'preparation', but testosterone does not 'prepare' castrated rats for the generalized Schwartzman reaction. The possible significance of enhancement of endotoxin toxicity by estrogens in explaining some pathophysiological characteristics of disseminated intravascular coagulation in pregnancy is discussed.

The identification of IUDs by ultrasound in the uterine cavity.

PIP: More than 80 patients were examined by parallel B-scan ultrasonic equipment (Vidoson 635, Siemens). 30 have been followed in time sequences up to 8 months. It is important that the patient have a full bladder which elevates the uterus out of the small pelvis. Loops are easily identifiable if the uterus is in the anteverted-fected position, difficult to visualize in the retroflected position, and outlined only if the uterus is extremely retroflected. The middle position can allow for misinterpretation. The IUD may be in the uterus, cervix, or vagina and the ultrasonic echo of the string may cause further error. Proper localization can be accomplished if the applicator is placed in a longitudinal position. If this fails the uterus can be lifted out of the pelvis and tipped anteriorly by digital elevation from the vagina. This requires an additional investigator. Proper localization of an IUD failed in about 10% of examinations. Obesity and intraabdominal adhesions provided for many errors. In more than 90% the technique is qualified for follow-up controls. The authors use it routinely to check proper insertion. In 3 cases early partial expulsion was diagnosed, which prompted extraction of the IUD.^ieng

The uterotubal junction. A proposal for classifying its morphology as assessed with hysteroscopy.

Hysteroscopy was used to characterize the morphology of the uterotubal ostium (UTO). A comparison was made with the laparoscopic assessment of the tube in 86 infertile women. In addition, histology was performed on the UTO from women undergoing hysterectomy for cervical dysplasia. These comparisons revealed that the incidence of mucosal damage to the UTO is not related to that of adnexal adhesions unless the postinflammatory changes are severe. Most notable was the correlation between endosalpingeal hyperplasia and salpingitis isthmica nodosa.

Therapeutic laparoscopy. An update on the instrumentation.

The ancillary instruments in therapeutic laparoscopy can be divided into passive ones, which stabilize or manipulate, and active ones, which "treat" the tissue. Eight new instruments have been developed. In the passive category are oviduct, mesoovary, adhesion and pin forceps. In the active category are a dividing spatula, bipolar microforceps, self-tying suture and swab carrier. This diversification of instrumentation ensued from the restricted number of instruments that may be used simultaneously at laparoscopy, and the new designs help reduce the duration of laparoscopic operations.

Recovery of ovarian function after laparoscopic treatment of acute adnexal torsion. A case report.

Adnexal torsion due to an ovarian cyst was treated laparoscopically by fenestration of the cyst and shortening of the ovarian ligament. Serial ultrasound examinations three months later demonstrated recovery of follicular growth.

Standardizing microcolposcopy. Assessing the criteria for evaluating the presence and degree of cervical intraepithelial neoplasia.

We established criteria for the detection and grading of cervical intraepithelial neoplasia with microcolposcopy. These criteria were assessed for their accuracy through comparison with the histologic evaluation of cone biopsy or hysterectomy specimens in 26 highly selected cases. There was a positive correlation of 88.5% and no false-negative cases. Microcolposcopy, performed in a standardized manner, may be a valuable adjuvant to colposcopy.

[Contraindications for the use of copper T intrauterine pessaries]. / Kontraindikationen für die Anwendung von Kupfer-T-Intrauterinpessaren

PIP: The Copper-T IUD is a highly effective, relatively safe method that offers a real alternative to other contraceptives. Lest the device be unjustly discredited by erroneous use, it is imperative to determine its limitations. Clinical observation and review of the literature reveal several contraindications, including pregnancy, structural anomalies of the uterus, myomas of the uterus, hypoplastic uterus, uterus auctus, inflammations of the inner genitals, recurrent menstrual difficulties, dysmenorrhea, and certain illnesses. As a case history shows, an IUD is occasionally inserted in a pregnant woman, despite precautions. Bleeding in early pregnancy may be mistaken for the regular menstrual period; timing of the insertion is especially difficult with women whose periods are still unstable following discontinuation of ovulation inhibitors. Other cases illustrate the danger of perforation posed by slippage, bending, or misplacement of the Cooper-T IUD in an abnormal uterus, e.g., double uterus. Particularly where the uterus is abnormally large - e.g., in postabortum or postpartum cases the danger of cervical perforation by the vertical arm of the device makes choice of another method advisable. Supersonic diagnosis to check position of IUDs is very useful, but not completely error-proof. As for other contraindications, pelvic inflammations must be treated before inserting the IUD, especially if gonorrhea is suspected. The Copper-T IUD, with its known tendency to induce menstrual disturbances, is not the method of choice where dysmenorrhea or recurrent abnormal bleeding already exist. Diseases accompanied by a heightened tendency to bleed are contraindications, as are disturbances of the clotting function and the von Willerbrand syndrome. Caution should be observed in prescribing the device to women allergic to copper; a case of probable allergic reaction to the device has been observed at the authors' clinic. Given these limitations, the Copper-T IUD is nevertheless a relatively dependable, complication-free method.^ieng

Preparation for disseminated intravascular coagulation by Yoshida sarcoma in rats.

Five days following implantation of a Yoshida sarcoma, female rats developed an increase in plasma fibrinogen concentration and a decrease in the number of platelets. The endotoxin induced fibrinisation of the microcirculation, as measured in percent involvement of glomerula, was found to be five to ten times higher than in control animals. A single injection of endotoxin without infusion was sufficient in tumor bearing animals to induce glomerular capillary thrombosis. The Yoshida sarcoma induced pathophysiological changes with a "preparative" effect on the endotoxin-induced disseminated intravascular coagulation.

Portal venous thrombosis in ulcerative colitis: CT diagnosis with angiographic correlation.

A case of portal venous thrombosis in a patient with chronic ulcerative colitis is presented. Computed tomography correctly diagnosed the abnormality as confirmed by angiography.

[Cervical perforation due to a copper-T device placed following abortion (author's transl)].

Report on a patient who had a Copper-T intrauterine device placed following abortion. The vertical arm of the device perforated the cervix and resulted in cervicitis and endometritis.

[Partusisten as a possible cause for renal colics (author's transl)]. / Partusistengabe als mögliche Ursache für Nierenkoliken in der Schwangerschaft

Two patients were treated with Partusisten and Isoptin to inhibit uterine contractions. One patient was in the 36th and the other in the 32th week of pregnancy. Both developed colic like complaints related to the urogenital system, which disappeared after disruption of treatment and reoccured after restarting. The case description seemed to indicate an as yet not described side reaction of Partusisten.

[Long term experience with the IUD copper-T-200 (author's transl)]. / Langzeiterfahrungen mit dem Intrauterinpessar Cu-T-200.

During a period of seven years pregnancy-, expulsion- and extraction-rates of the copper-T-200 were determined for two different groups of patients in a university hospital. The first group were patients of the ambulatory care service representing an heterogenous composition. The other group were patients from a private practice representing a more homogenous population. In the first group insertions and controls were done by different physicians at various stages of their training, in the second group they were performed by an experienced clinician. In the first group there were 1397 primary IUD-insertions and 22,203 months of use, in the second group the corresponding data were 272 primary insertions an 5127 months of use. The pregnancy rates calculated according to the Pearl-index were 1.0 and 0.24, respectively. The expulsion rates were calculated as 0.8 and 0.2, respectively. The extraction rates because of unwanted side-effects were 4.4 in the first and 1.6 in the second group of patients. There seems to be an advantage in having the care of the IUD-patient being taken by an experienced physician, especially regarding the extraction rates because of unwanted side effects.

PIP: During a period of 7 years, pregnancy, expulsion, and extraction rates for the Copper T-200 were determined for 2 different groups of patients in a university hospital. The 1st group were patients on an ambulatory service care representing a heterogenous composition; the other group were patients from a private practice representing a more homogenous population. In the 1st group, insertions and controls were done by different physicians at various stages of their training; in the 2nd group they were performed by an experienced clinician. In the 1st group, there were 1397 primary IUD-insertions and 22,203 months of use, and in the 2nd group, the corresponding data were 272 primary insertions and 5127 months of use. The pregnancy rates calculated according to the Pearl index were 1.0 and 0.24 respectively. The expulsion rates were calculated as 0.8 and 0.2 and the extraction rates due to unwanted side effects were 4.4 in the 1st and 1.6 in the 2nd group. There seems to be an advantage in having the care of the IUD patient being taken on by an experienced physician, especially regarding the extraction rates due to side effects. (author's)

[Results of the follow-up of the position of intra-uterine device by ultra-sonography (author's transl)]. / Ergebnisse der Lageüberwachung von Intrauterinpessaren durch Ultraschall.

The position of the intra-uterine device copper-T in 1372 women was followed up by ultrasound for four years. During this time 2565 ultrasound studies for the position of the intra-uterine device were carried out. The intra-uterine device was found in the cervix in 81 ultrasound investigations and removed or exchanged. In 12 cases the device was pushed back into the uterine cavity. 12 women became pregnant. This corresponds to a Pearl index 0.72 with a mean insertion time of 14.6 months and 20.000 patient-months of wearing of an intra-uterine device. In 9 of the 12 pregnant cases the device was found in the cervix. 6 of these patients reported only once instead of the projected four times for ultra-sound follow-up and the last normal ultrasound follow-up was usually nine months or longer ago. Our findings suggest that the contraceptive effectiveness of an intra-uterine device can be improved by regular ultra-sonic control of the position and can by approximated to the effectiveness of hormonal contraception.

PIP: A report of 2565 ultrasonic examinations of 1372 women to determine the position of a Copper T IUD is presented. The mean length of IUD use was 14.6 months. In 139 cases the IUD was found in an intracervical position; in 93 of these cases the position of the IUD in the cervix was verified by pelvic examination and reinserted or replaced in 81 cases. The pregnancy rate was 12 for 20,031 use-months, corresponding to a Pearl index of .72. In 9 of these 12 pregnancies, the IUD was found in the intracervical position, and in the majority of these cases the most recent ultrasonic examination had been done more than 6 months previously. A large number of IUDs were found in an intracervical position in the first 2 months after insertion. It is recommended that an ultrasonic examination to determine the position of an IUD be given a few days following the insertion, after each of the first 2 months following insertion, and every 3-6 months afterwards.