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Biomedical subjects

H Ochs

Publications and source records attributed to H Ochs.

At least 37 records · Page 2Linked to original sources

[Treatment of endometriosis with the GnRH agonist buserelin (Suprecur): a multicenter study].

A phase III multicentre study was carried out with the GnRH agonist buserelin (Suprecur) at five university institutions (Dept. of Obstetrics and Gynaecology of Essen, Kiel, Tübingen, Münster and Erlangen) to evaluate the effect of Buserelin (3 x 300 micrograms daily intranasal) on endometriosis for a period of 6 months. Endometriosis was verified by light microscopy in all cases. The data of 430 patients could be evaluated. The extent of the endometriotic lesions was studied before the start and at the end of therapy. The mean age of the patients was 30 +/- 5 years. For 300 patients (66.4%) sterility was a main problem. Previous treatment for endometriosis consisted of operation in 20.5%, treatment with danazol in 16.8% and treatment with gestagens in 11.6% of the patients. Under treatment FSH changed from 11.0 +/- 31.4 mIU/ml to 7.0 +/- 5.6 mIU/ml at the end of therapy; LH from 11.1 +/- 12.9 mIU/ml to 7.4 +/- 7.3 mIU/ml; estradiol from 113.9 +/- 89.0 to 35.9 +/- 60.3 pg/ml and progesterone from 7.2 +/- 11.2 ng/ml to 0.8 +/- 1.4 ng/ml. The effect on endometriosis was judged according to the revised American Fertility Society score (rAFS 1985). The changes of the rAFS-score stages were as follows (before/after therapy): Stage 0: 0%/42.8%; stage I: 43.5%/38.5%; stage II: 31.1%/11.2%; stage III: 18.1%/2.2%; stage IV: 6.3%/0.2%. The total mean AFS-stage changed from 1.9 to 0.7. The frequency of clinical symptoms improved (before/after therapy): dysmenorrhoea 65.0%/11.2%; pelvic pain 48.2%/14.1%; pain at the time of gynaelogical examination 40.0%/9.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

Estrogen and progesterone receptor content of enucleated uterine myomata after luteinizing hormone-releasing hormone. Analogue depot therapy.

We wanted to correlate the degree of myoma shrinkage after luteinizing hormone-releasing hormone (LHRH)-analogue depot therapy to the estrogen and progesterone receptor content of the enucleated fibroids. Twenty premenopausal, regularly menstruating women wishing to preserve their childbearing capacity were treated for three to six months with 3.75 mg of leuprorelin acetate depot subcutaneously. Four weeks after the last injection, all fibroids were enucleated and investigated immunohistochemically by using monoclonal (rat) antibodies to human estrogen and progesterone receptors. The localization and distribution of nuclear staining was visualized through a light microscope and scored semiquantitatively by multiplying the staining intensity with the percentage of positive cells. Although LHRH-analogue depot therapy led to almost the same degree of ovarian suppression in all of the women, extent of myoma shrinkage varied from 0% to 87%. On the other hand the extent of myoma regression correlated significantly to the estrogen receptor content of the enucleated fibroid, while diminution of myoma size seemed to be independent of the progesterone receptor. This indicates an association between myoma shrinkage and the estrogen receptor status of the enucleated fibroid. It remains to be proved that pretreatment receptor analysis may predict the myomata that are sensitive to endocrine treatment.

Adult↗

Inflammatory reaction in endometriotic tissue: an immunohistochemical study.

A panel of monoclonal antibodies specific for macrophage subtypes appearing in early (27E10), down-regulatory (RM3/1) and late (25F9) stages of inflammation had been applied to 20 endometriotic implants of 14 women. Of those patients 9 were in the follicular phase of the cycle, two on danazol, one on LHRH-analogue (buserelin) and another two on oral contraceptives. Beside the macrophage subsets, antibodies against T4, T8 lymphocytes as well as proliferating cells (EN7/44 and Ki67) were examined. In all specimens immunologically competent cells could be detected to a varying degree and within the same implant different stages of inflammation were discernible. Endometriosis presented with signs of early inflammation indicated by 27E10+ macrophages and CD4+ lymphocytes (15 specimens) and with down-regulatory, late inflammatory reactions as shown by RM3/1+, 25F9+ macrophages and CD8+ lymphocytes (19 biopsies). Additionally, in 14 specimens cells of the EN7/44+ and Ki67+ type was detected. These preliminary results showed no significant correlation to either extension of endometriotic implants or adhesions or concomitant therapy and clearly indicate, that there is an immunological dynamic process within the lesion itself in addition to that one of the peritoneal fluid.

Adult↗

Narcotic receptor blockade and its effect on the analgesic response to placebo and ibuprofen after oral surgery.

The purpose of this study was to evaluate the contribution of endogenous opiates to the analgesic response after treatment with placebo, codeine, and ibuprofen after oral surgery. Eighty-one patients undergoing complicated dental extractions were pretreated with either a placebo or the narcotic antagonist naltrexone 50 mg, 30 minutes before surgery. After surgery, patients self administered one of three possible postsurgical medications, which included placebo, codeine 60 mg, and ibuprofen 400 mg, when their pain reached a moderate or severe intensity. The study was double-blind with the three postsurgical treatments being randomly allocated within each presurgical treatment block. Pain intensity, pain relief, pain half gone, and overall evaluations were assessed for up to 6 hours. Ibuprofen was significantly more efficacious (p < .05) than codeine or placebo for most analgesic measures. The administration of naltrexone before surgery reduced the analgesic response to both placebo and codeine. Pretreatment with naltrexone did not diminish the peak analgesic response to ibuprofen, but surprisingly prolonged (p < .05) the duration of its action. The results suggest that a blockade of endogenous opiates by naltrexone diminished the placebo response, but that naltrexone may prolong ibuprofen analgesia by some unknown mechanism.

Adult↗

Experience with leuprorelin acetate depot in the treatment of fibroids: a German multicentre study.

Between October 1988 and October 1990 in a noncomparative multicentre study, 114 patients were treated for uterine fibroids with the gonadotrophin-releasing hormone (Gn-RH) agonist, leuprorelin acetate depot. The mean age of the women was 33 years and 55.3% of them had a history of infertility. After confirmation of the diagnosis by ultrasound and/or operation, treatment began between day 1 and 3 of the cycle with leuprorelin acetate depot 3.75 mg subcutaneously. Therapy was carried out for a total of 6 months with one injection every 4 weeks. Treatment was paralleled by measurements of endocrine and metabolic parameters, estimation of myoma and uterine size by ultrasound and self-reporting of the patients of drug-related complaints. Four of the 114 women did not complete the whole treatment, two of them because of general side effects, one because of carcinophobia and unsatisfactory regression of the myoma and the last one for unspecified reasons. During treatment, a mean reduction of the uterine volume of about 67% was observed, in conjunction with shrinkage of the myoma in 92.1% of cases (mean decrease of 56% of the fibroids) with a large interindividual difference. Maximal diminution of uterine and fibroid size had been nearly completely reached within the first 12 weeks of therapy. After 4 weeks of the Gn-RH agonist depot most of the patients had achieved postmenopausal status, which continued throughout the remaining 20 weeks of treatment. In accordance with this finding, the majority of general side effects was due to the hypo-oestrogenic endocrine status. Liver and lipid metabolism was almost unaffected, although increasing calcium and alkaline phosphatase serum levels as well as an increased urinary calcium/creatinine ratio demonstrated an increased metabolic turnover of the bone. Haemoglobin concentrations, however, increased in those cases with fibroid-related anaemia. Thus the slow-release form of leuprorelin acetate is an adjunct to myomectomy especially in those women in whom family planning is not yet completed.

Adult↗

Localization of the gene for the Wiskott-Aldrich syndrome between two flanking markers, TIMP and DXS255, on Xp11.22-Xp11.3.

The Wiskott-Aldrich syndrome (WAS) is an X-linked recessive genetic disease in which the basic molecular defect is unknown. We previously located the WAS gene between two DNA markers, DXS7 (Xp11.3) and DXS14 (Xp11), and mapped it to the proximal short arm of the human X chromosome (Kwan et al., 1988, Genomics 3:39-43). In this study, further mapping was performed on 17 WAS families with two additional RFLP markers, TIMP and DXS255. Our data suggest that DXS255 is closer to the WAS locus than any other markers that have been previously described, with a multipoint maximum lod score of Z = 8.59 at 1.2 cM distal to DXS255 and thus further refine the position of the WAS gene on the short arm of the X chromosome. Possible locations for the WAS gene are entirely confined between TIMP (Xp11.3) and DXS255 (Xp11.22). Use of these markers thus represents a major improvement in genetic prediction in WAS families.

Chromosome Mapping↗

[Value of the tumor markers CA 125, Ca 19-9, CA 15-3 and CEA in endometriosis].

CA 125, CA 19-9, CA 15-3 and CEA were measured in 42 patients with histologically verified endometriosis, who had been treated for six months by the LHRH-analogue buserelin (900 mcg/d intranasally). Before therapy, for all of the markers tested the sensitivity was as follows: CA 125 49%, CA 19-9 19%, CA 15-3 19% and CEA 0%. Pretherapeutically the correlation coefficient between CA 125 and the AFS stages was r = 0.40, indicating no significant relation. Following therapy the correlation between the tested glycoproteins and the AFS stages was less indicative. Only CA 125 showed a significant decrease during treatment (p less than 0.05), which paralleled the therapeutic hypo-oestrogenism. According to our results measurement of CA 125, CA 19-9, CA 15-3 and CEA is not sufficient to replace surgical procedures of monitoring endometriosis. The significant reduction of CA 125 apparently represents loss of ovarian function rather than regression of the disease.

Adult↗

The pharmacokinetics of total IgG, IgG subclasses, and type specific antibodies in immunodeficient patients.

The advent of immunoglobulin concentrates suitable for intravenous administration has greatly improved the clinical management of patients with a primary immunodeficiency syndrome. However, proper treatment requires understanding of the pharmacokinetics of the infused IgG and its components. We review here the work that has been conducted in this area. In particular, two studies have shown that these concentrates have adequate catabolic properties with regards to total IgG, IgG subclasses, and specific antibodies. We conclude that careful evaluation of the pharmacokinetics of a given IgG preparation is necessary in order to determine an appropriate treatment regimen.

Female↗

Identification of a closely linked DNA marker, DXS178, to further refine the X-linked agammaglobulinemia locus.

X-linked agammaglobulinemia (XLA) is an inherited recessive disorder in which the primary defect is not known and the gene product has yet to be identified. Utilizing genetic linkage analysis, we previously localized the XLA gene to the map region of Xq21.3-Xq22 with DNA markers DXS3 and DXS17. In this study, further mapping was performed with two additional DNA probes, DXS94 and DXS178, by means of multipoint analysis of 20 families in which XLA is segregating. Thirteen of these families had been previously analyzed with DXS3 and DXS17. Three crossovers were detected with DXS94 and no recombinations were found between DXS178 and the XLA locus in 9 informative families. Our results show that XLA is closely linked to DXS178 with a two-point lod score of 4.82 and a multipoint lod score of 10.24. Thus, the most likely gene order is DXS3-(XLA,DXS178)-DXS94-DXS17, with the confidence interval for location of XLA lying entirely between DXS3 and DXS94. In 2 of these families, we identified recombinants with DXS17, a locus with which recombination had not previously been detected by others in as many as 40 meiotic events. Furthermore, DXS178 is informative in both of these families and does not show recombination with the disease locus. Therefore, our results indicate that DXS178 is linked tightly to the XLA gene.

Agammaglobulinemia↗

[Residual endometriosis following LHRH analog therapy].

LHRH analogue therapy has proved effective in the treatment of endometriosis. Although in the majority of patients a marked reduction in AFS implant score is observed, in some cases residual endometriotic foci are macroscopically suspected and can be confirmed by histological examination during a second check operation at the end of treatment. In the study presented, 34 patients from 69 showed residual endometriosis after a 6 months' treatment with the LHRH analogue buserelin (900 mcg/d intranasally). According to light microscopical criteria regressive changes were seen in 52% of the implanted patients, nevertheless 29% presented with proliferative elements of the disease. In 19% proliferation and regression were seen in the same biopsy or even in the same gland. Histology did not relate to either the degree of ovarian suppression by LHRH analogue therapy, or to the location of the residual endometriotic foci. These results add another piece of evidence to the fact, that endometriosis presents itself as a heterogenic disorder. In addition, susceptibility to a hormonal ablative therapy rather depends on the degree of dysontogenetic differentiation, than on the completeness of induced ovarian suppression.

Adult↗

LH-RH agonist (buserelin): treatment of endometriosis. Clinical, laparoscopic, endocrine and metabolic evaluation.

To investigate the effects of the LH-RH agonist Buserelin [D-Ser (But)6 des-Gly10-LHRH ethylamide] on endometriosis, 64 patients were treated with 900 micrograms/d Buserelin intranasally over 6 months after histological verification of the disease. As shown by the follow-up operation at the end of treatment, 73% of cases showed regression of implants, whereas adhesions seemed to be unaffected. The uncorrected pregnancy rate of the 45 patients with a history of infertility was 40%, while the overall recurrence rate--confirmed by histological examination--was 9.4%. The endocrine parameters demonstrated a highly significant suppression of estradiol (E2) and a sharp decline of progesterone (Prog), indicating anovulatory cycles. Follicle-stimulating hormone (FSH) was unchanged, while luteinizing hormone (LH) and prolactin (Prl) decreased significantly. The androgenic parameters testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), and sex-hormone-binding globulin (SHBG) revealed no relevant changes. Influence on bone metabolism could not be detected by measuring calcitonin and parathyroid hormone fragments (PTH-C and PTH-MM). Negative metabolic effects were absent in terms of hematology, clotting system, liver enzymes, renal parameters and lipid metabolism. Remarkable was a significant increase of high-density-lipoprotein cholesterol (HDL). Subjective complaints were mostly attributed to the therapy-induced hypoestrogenism. We consider Buserelin to be an effective drug in the treatment of endometriosis, with a low incidence of relevant side effects.

Buserelin↗

Detection of X-linked lymphoproliferative disease using molecular and immunovirologic markers.

PURPOSE, PATIENTS, AND METHODS: Detection of males affected with the X-linked lymphoproliferative disease (XLP) was sought using immunovirologic and molecular genetic linkage techniques. The study population consisted of 20 males in six families with XLP. RESULTS: Concordance for detection of affected males was 100% when linkage analysis using DXS42 and DXS37 DNA probes and antibody responses to challenge with bacteriophage phi X174 were both determined. Most affected males showing IgG subclass immune deficiency could not produce antibodies to Epstein-Barr virus nuclear antigen and had deficient responses to challenge with bacteriophage phi X174. CONCLUSION: Use of only one of the techniques described can fail to lead to the diagnosis of XLP, because problems can prevail with each individual determination.

Adolescent↗

Quantitative structure-activity studies on effects of sixteen different steroids on growth and monooxygenases of rat liver.

Sixteen steroids with different endocrine activities were administered to female rats for 6 or 7 days, in a broad range of doses. Liver growth was recorded by measuring weight and DNA contents and monooxygenase activity by assaying the turnover of five different substrates. According to their effects on these parameters steroids were assigned into one of the following three groups: (a) Estrogens estradiol and ethinylestradiol, as well as the progestins norethynodrel and norethisterone (norethindrone) which have estrogenic activity in rats. These agents induced pronounced liver growth and excessive DNA increase which was not associated with major monooxygenase induction. (b) A different type of response consisted of liver growth and DNA increase associated with a pronounced induction of monooxygenase(s) in a characteristic pattern. This response was elicited by pregnenolone-16 alpha-carbonitril, by progestins progesterone, cyproterone acetate, and medroxyprogesterone (but not gestoden and levonorgestrel), by the antimineralocorticoid spironolactone and by the glucocorticoids cortisol and dexamethasone. Apparently, this response pattern was not related to any specific endocrine action but to certain structural features, in particular to the presence of a saturated, at least two-membered alkyl substituent at C17 of the steroid ring system. (c) No or small effects were observed after gestoden, levonorgestrel and the androgens testosterone and methyltestosterone. Dose-response stuides revealed that estrogens estradiol and EE2 induced hepatic effects more potently by four orders of magnitude than progestins. The response patterns observed may be relevant to the tumor-promoting activity of some of the steroids tested.

Animals↗

Umbilical cord separation in the normal newborn.

During a 13-month period, 363 infants were followed up through the first six weeks to determine the effect of perinatal factors (birth weight, gestational age, type of delivery, and pregnancy and neonatal complications) on umbilical cord separation. Also, breast-feedings and umbilical cord care were studied. Except for cesarean section deliveries, study infants were similar to all infants (N = 1474) admitted to the same nursery during the study period. Cord separation occurred from days three to 45, with a mean of 13.9 days. Infants born by cesarean section were found to have an increased interval for cord separation when compared with infants born vaginally (mean +/- SD, 15.9 +/- 5.0 days vs 12.9 +/- 4.2 days). In this study, delays in separation of the umbilical cord beyond 3 weeks of age was not associated with an increased risk of infection.

Birth Weight↗

[Metabolic effects and general side effects in the treatment of endometriosis with an LHRH agonist].

Between 1983 and 1986 40 patients were treated for external genital endometriosis with the LHRH agonist buserelin. Ovarian suppression was achieved for a period of six months with a dose of 900 to 1,800 mcg per day. In addition to gynecological findings, liver and kidney function and lipid metabolism were checked prior to treatment and at regular intervals during treatment. No deviations from normal ranges were found. The general side effects observed during treatment were as a rule attributable to the buserelin-induced relative estrogen deficiency. The efficacy of the medication in the treatment of endometriosis was demonstrated by control pelviscopy. Since no undesirable metabolic side effects have so far been observed with buserelin, it may be considered an effective new alternative treatment for endometriosis.

Adult↗

Induction of monooxygenases and growth in rat liver by progesterone.

Female Wistar rats were treated with various doses of progesterone orally via the diet or via the SC route. Oral treatment resulted in enhanced progesterone levels in the liver as measured by radioimmunoassay. There were up to 3-fold increases in activity of ethylmorphine demethylation by isolated microsomes; metabolism of aminopyrine and benzphetamine was less enhanced, that of aniline and p-nitroanisol showed no distinct increases. Progesterone also caused increases in liver size and total liver protein by up to 50%; total liver DNA showed only slight, insignificant increments. These studies suggest that hepatic effects of progesterone are similar to those previously described with synthetic steroids such as pregnenolone-16 alpha-carbonitrile (PCN) and cyproterone acetate.

Animals↗