Sutureless cartilage graft laryngotracheal reconstruction using fibrin sealant

BACKGROUND: To estimate the value of CA-125 for the diagnosis of endometriosis in women with dysmenorrhea, as well as its significance in monitoring therapy and follow-up. METHODS: One hundred and fifty-seven women undergoing laparoscopy for dysmenorrhea were prospectively studied for serum CA-125 concentration. For those with advanced endometriosis receiving danazol treatment after conservative surgery, CA-125 was also determined every month during medication and once every 12 months after treatment. RESULTS: The sensitivity and specificity of serum CA-125 for the diagnosis of endometriosis were 61.1% and 87.5% respectively. Elevated CA-125 (>35 U/ml) was noted in 65/75 cases (86.70%) with advanced endometriosis, but in only 15/56 patients (26.8%) with minimal and mild endometriosis. Although there were significantly higher CA-125 levels in unmarried women, and a negative correlation (r=-0.1970, p=0.0284) between CA-125 and parity, there was no statistical difference in incidence of endometriosis by the status of marriage or parity. Ten women with advanced endometriosis were found with persistent endometriosis by laparoscopy during danazol treatment, even though they tested with normal CA-125 levels (<35 U/ml) at that time. Fifteen patients had elevated CA-125 levels before and one year after therapy, and were confirmed with recurrence of endometriosis by laparoscopy. Nine women with elevated CA-125 levels before treatment, were found without recurrence of endometriosis and had normal CA-125 levels one year after therapy. CONCLUSION: For endometriosis, CA-125 is a valuable adjuvant in the follow-up of recurrence in patients with advanced endometriosis and initially elevated CA-125 levels. It is not an effective screening tool for patients with dysmenorrhea, or for monitoring therapy. There was no significant correlation between the development of endometriosis and reproductive factors.     

Unexpected increase of the CA 19-9 tumour marker in patients with endometriosis

The purpose of this study was to investigate whether the ovarian function of women with endometriosis could be identified by serologic concentration of the oncofetal antigen CA 19-9 before, during and after treatment for 6 months with danazol. A total of 15 women with endometriosis, 20-40 years old, were studied. The serum CA 19-9 antigen was measured by immunoradiometric assay. The measurement of CA 19-9 was repeated during the last 15 days of a 6-month therapy period with danazol and after 3 months from the end of the therapy in only seven women. It was found that: 1) Eight out of 15 women (53.3%) showed higher CA 19-9 values than the upper normal limit. 2) Danazol caused a significant decrease in the antigen values which remained stable after the cessation of therapy. This data suggests that endometriosis should be classified among other diseases which cause an increase in the serum levels of CA 19-9 and that ovarian function is related to antigen levels.     

Endometriosis in adolescent women

With the aim of determining an effective therapy for adolescent women with endometriosis, the authors analyzed the results of laparotomy performed on 16 cases of female teenagers over a seven-year period. All patients, whose average age of menarche is 12.8, were diagnosed with endometriosis between two months and nine years after the menarche, with an average interval of 5.2 years. The chief symptoms are dysmenorrhea, pelvic pain and abdominal fullness. Of the three patients of unicornuate uterus with rudimentary horn, endometriosis was found only involving the adnexa on the side of the rudimentary horn, two of the three patients had absence of affected side kidney. Conservative operation including six cases of salpingo-oophorectomy and 10 cases of ovarian cystectomy were chosen followed by danazol treatment. One year to seven years after surgical treatment, two patients required subsequent conservative operation for recurrence of endometriosis and two other patients resumed dysmenorrhea. Two married women became pregnant 5 and 10 months after surgical and medical therapy respectively. In conclusion, adolescent endometriosis may occur around five years after menarche and an obstructive uterine anomaly, enhancing retrograde menstruation, increases the occurrence rate. The symptoms and treatment of endometriosis in teenage group do not really differ from that in the older women. In the treatment of endometriosis and for the prevention of recurrence, it is recommended to give three to six months of danazol after surgical treatment.     

Novel vaginal danazol ring therapy for pelvic endometriosis, in particular deeply infiltrating endometriosis

Danazol is routinely administered orally to inhibit ovulation and to treat pelvic endometriosis. However, recent evidence suggests that danazol can act directly on endometriotic tissue in vitro to inhibit DNA synthesis and induce apoptosis. Danazol was administered via the vagina in this study, using a vaginal ring drug delivery system containing 1500 mg of danazol. This therapy was effective for treatment of pelvic endometriosis, especially for deeply infiltrating endometriosis, resulting in a cure of dysmenorrhoea and tenderness in the cul-de-sac within 3 months, and of induration or nodularity in the cul-de-sac within 7 months. Moreover, conception was possible during insertion of the vaginal ring in 17 out of 31 infertile women with deeply infiltrating endometriosis, and in two out of eight infertile women with ovarian endometriotic cysts not adhering to the cul-de-sac and without deeply infiltrating endometriosis. Serum danazol concentrations, high during oral daily 400 mg danazol therapy, but undetectable during vaginal danazol ring therapy, explain why ovulation and conception could occur during insertion of the vaginal danazol ring, and why general side-effects, which are often observed during oral danazol therapy, were not observed during vaginal danazol ring therapy. Danazol seems to be absorbed through the vaginal mucosa and reaches the deeply infiltrating endometriosis via diffusion.     

A practical guide to topical therapy in children

OBJECTIVE: To determine the duration of time to the recurrence of pain attributable to endometriosis after the discontinuation of treatment with danazol or a GnRH agonist (GnRH-a) in patients who have had a satisfactory response to the treatment. DESIGN: Retrospective study. SETTING: Nine academic medical centers in three countries. PATIENT(S): Three hundred twenty-seven women with diagnosed and staged endometriosis who were treated with at least 6 months of danazol or a GnRH-a and who experienced significant pain relief with therapy. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Duration of pain relief after completion of treatment as determined by a patient-initiated report of pain recurrence or increase in pain severity requiring intervention. RESULT(S): The median time to the recurrence of pain was 6.1 months for patients treated with danazol and 5.2 months for patients treated with a GnRH-a. CONCLUSION(S): Although there was a lack of uniformity in treatment effects across sites, the analyses have taken into account major covariant effects. The time to the recurrence of endometriosis-associated pain after danazol treatment was slightly longer than that after GnRH-a treatment.     

The efficacy of drugs in the management of endometriosis

STUDY OBJECTIVE: To establish the crude effects of danazol and gonadotropin-releasing hormone (GnRH) analogs in the management of endometriosis. DESIGN: Prospective case-control study. SETTING: Unit of the Pathophysiology of Reproduction outpatient department. PATIENTS: Two groups of 110 women each with endometriosis (American Fertility Society score 1-3) who received danazol and GnRH analogs, and a control group who did not receive any drugs. INTERVENTIONS: Women in the treatment groups received danazol 200 mg every 8 hours for 6 months, or a different GnRH agonist at standard dosages for 6 months. Laparoscopy was performed twice, at the time of diagnosis and just before the end of treatment (or no therapy for controls). Surgical treatment of the implants was performed at the second laparoscopy. MEASUREMENTS AND MAIN RESULTS: Samples of both eutopic and ectopic endometrium were collected during both laparoscopies. Both danazol and GnRH agonists were useful in reducing the AFS scores to inactive endometriotic implants, and there were no significant differences between the effects (p <0.001). Fibrosis was found after 6 months of observation in the implants in one control woman (0.9%), in 20 patients (18.2%) treated with danazol (p <0.001 vs controls), and in 4 patients (3.6%) treated with GnRH agonists (NS vs controls). A correlation between a clinical diagnosis of AFS score zero and histologic features of fibrosis in the ectopic specimens after therapies was observed in 28% of women, with poor agreement (k = 0.07). CONCLUSIONS: Fibrosis, which represent the absence of endometrial cells within the specimens of endometriotic lesions or eutopic endometrium, did not appear in eutopic endometria but it was found in some endometriotic implants. Danazol and GnRH agonists reduced the clinical AFS scores of endometriosis, but their histologic effects in completely and permanently eliminating endometriotic implants were unacceptable.     

The effect of regular exercise on women receiving danazol for treatment of endometriosis

OBJECTIVE: To determine the effects of regular exercise on women receiving danazol for the treatment of endometriosis. METHODS: Thirty-nine patients were randomized to a danazol-only or a danazol/exercise regimen in a prospective clinical trial carried out at tertiary care institutions. Patients in the danazol/exercise group were instructed to exercise four times per week, for 40 min per session, at an intensity of 20 metabolic units. Side effect profiles, pelvic symptoms, aerobic fitness, strength and hormone levels were compared for all subjects. The number of side effects of danazol was analyzed by the method of generalized estimating equations. RESULTS: The number of side effects reported during a 4-week period was 1.09-2.17 times greater for the danazol-only than for the danazol/exercise group. All patients had improvement of symptoms during treatment. The danazol/exercise group had significantly lower testosterone levels during treatment. The time to recurrence of endometriosis was not different between groups. CONCLUSIONS: Exercise during danazol therapy reduces the number of androgenic side effects. Relief of pain and time to recurrence are unaffected.     

Elevated antitoxin titers in a man with generalized tetanus

STUDY OBJECTIVE: To compare the outcome of in vitro fertilization and embryo transfer (IVF-ET) after laparoscopic surgery in women with endometriosis with that of patients with tubal factor infertility. DESIGN: Retrospective survey of hospital and office charts using a computerized worksheet. SETTING: Lin-Kou medical center of Chang Gung Memorial Hospital. PATIENTS: Sixty-seven women with minimal to mild or moderate to severe endometriosis. Women with tubal factor infertility without other associated disorders (60 cycles) made up the control group. INTERVENTIONS: Seventy-five consecutive cycles of IVF-ET were performed in these patients who failed to conceive after laparoscopic conservative surgery. MEASUREMENTS AND MAIN RESULTS: The concentration of serum estradiol on the day of human chorionic gonadotropin (hCG) injection, the day of hCG injection, clinical pregnancy rates per transfer, number of follicles larger than 14 mm, number of embryos transferred, and implantation rate were not significantly different between women with endometriosis and those with tubal factor infertility. The number of oocytes retrieved and number fertilized were decreased, and the basal level of follicle-stimulating hormone on cycle day 3 was higher in women with both degrees of endometriosis. Women in both endometriosis groups received more follicle-stimulating hormone and human menopausal gonadotropin than those with tubal factor infertility. CONCLUSIONS: The outcome of IVF-ET in patients with endometriosis after laparoscopic surgery did not differ from that in the group with tubal factor infertility, but the former required more ampules of gonadotropin to achieve the same response. The advantages of laparoscopic surgery in women with endometriosis should be probably correlated with success of IVF-ET.     

Cytotoxicity versus antibacterial activity of some antiseptics in vitro

The relationship between endometriosis and infertility is observed frequently. Patients with both conditions require a conservative approach to their management. Since hormonal therapy is one of those approaches, we sought to compare the efficacy of Danazol and Gestrinone in 80 infertile patients (48 and 32, respectively). Therapy lasted 6 months in both treatment groups, and all patients studied had laboratory tests performed and were clinically evaluated and classified through laparoscopy before and after therapy. The improvement of symptoms and favorable follow-up were similar with both treatments. The reestablishment of menstrual patterns and fertility were also nearly alike in both groups. However, Gestrinone was associated with fewer secondary effects and is easier to administer than Danazol. We conclude that Gestrinone is a useful medication in the management of the infertile patient with endometriosis.     

Excretion of urinary N-telopeptides reflects changes in bone turnover during ovarian suppression and indicates individually variable estradiol threshold for bone loss

OBJECTIVE: To evaluate the effectiveness of N-telopeptides and E2 in monitoring bone turnover during GnRH agonist- (GnRH-a) or danazol-induced hypoestrogenism. DESIGN: Comparative, nonrandomized prospective study. SETTING: Institute for the Study and Treatment of Endometriosis. PATIENT(S): Premenopausal women undergoing ovarian suppression with GnRH-a (n = 16) or danazol (n = 9). INTERVENTION(S): Serum and urine samples were collected and bone mineral density was measured before, during, and after treatment. MAIN OUTCOME MEASURE(S): N-telopeptide excretion, serum E2, and bone mineral density at L1 to L4 and femoral neck. RESULT(S): During treatment in the GnRH-a group, mean E2 levels were 53% below and N-telopeptides were 38% above the mean baseline. At 1 month post-treatment, L1 to L4 bone mineral density decreased by 3.85%. In the danazol group, E2, N-telopeptides and L1 to L4 bone mineral density changed nonsignificantly in the opposite direction with the mean 1.25% increase in L1 to L4 at 1 month post-treatment. In combined groups, L1 to L4 bone mineral density better correlated with other measures than femoral neck bone mineral density. N-telopeptide excretion was more predictive of L1 to L4 change, with correlation the highest between N-telopeptides at month 4 and bone mineral density at month 1 afterward, while E2 appeared more predictive of the less reliable femoral neck bone mineral density. Individual exceptions to the model of an E2 threshold for bone loss were observed. Also noted were high correlation between on-therapy levels of E2 and N-telopeptides, as well as the presence of a 1-month time lag between E2 and N-telopeptide changes. CONCLUSION(S): Bone density decreases during GnRH-a and may slightly increase during danazol treatment. However, E2 threshold for bone loss varies individually. N-telopeptides predict changes in bone mineral density at L1 to L4 better than E2.     

Inhibition of omeprazole induced hypergastrinaemia by SMS 201-995, a long acting somatostatin analogue in man

Whether the long acting somatostatin analogue SMS 201-995 (octreotide, Sandostatin) could inhibit the basal and meal stimulated hypergastrinaemia and hyperpepsinogenaemia induced by omeprazole was investigated. Eight healthy subjects were randomised to receive five day courses of SMS 201-995 (25 micrograms subcutaneously three times daily), omeprazole (40 mg once a day), a combination of both drugs, or placebo. Basal and meal stimulated serum gastrin and basal serum pepsinogen A and C values were measured the day before treatment, on day five of treatment, and the day after each course of treatment. Omeprazole caused significant increases in basal and meal stimulated peak and integrated serum gastrin values and pepsinogen A and C levels, which were still significantly raised the day after stopping omeprazole treatment. Giving SMS 201-995 with omeprazole significantly reduced any omeprazole induced increases in basal and meal stimulated peak and integrated serum gastrin levels; serum pepsinogen A and C values were significantly inhibited too. Serum gastrin values during combined therapy were not significantly different from those during placebo treatment, whereas pepsinogen A and C levels were still significantly raised. On the day after stopping combined therapy, basal and meal stimulated peak and integrated serum gastrin and serum pepsinogen C (but not pepsinogen A) levels were not significantly different from values obtained on the day after stopping omeprazole alone. SMS 201-995 without omeprazole significantly inhibited basal and meal stimulated peak and integrated serum gastrin levels. Pepsinogen A was also significantly inhibited by SMS 210-995, but the reduction in pepsinogen C failed to reach statistical significance. In conclusion, SMS 201-995 prevents basal and meal stimulated increases in serum gastrin during omeprazole therapy. This finding may have clinical importance in the few patients who have pronounced hypergastrinaemia because of profound long acting acid inhibition.     

Massive ascites associated wth endometriosis

Massive ascites associated with pelvic endometriosis is an unusual occurrence. Two cases recently encountered by the authors are presented, and 7 additional cases from the literature are reviewed. Clinical courses and operative findings are described, and the management of the cases is presented. The etiology of ascites is explored and the possibility of conservative surgery and hormonal control with danazol is discussed.     

Modulation of plant plasma membrane H+-ATPase by phytotoxic lipodepsipeptides produced by the plant pathogen Pseudomonas fuscovaginae

OBJECTIVE: Dienogest, a synthetic steroid with progestational activity, is used as a component of oral contraceptives and is currently being evaluated clinically for the treatment of endometriosis. The present study was conducted to confirm the effects of dienogest on experimental endometriosis in rats and to elucidate its mechanism of action. DESIGN: Experimental endometriosis induced by autotransplantation of endometrium in rats. METHODS: Endometrial implants, immune system, and bone mineral were investigated after 3 weeks of medication. RESULTS: Dienogest (0.1-1 mg/kg per day, p.o.) reduced the endometrial implant volume to the same extent as danazol (100 mg/kg per day, p.o.). Simultaneously, dienogest ameliorated the endometrial implant-induced alterations of the immune system: i.e. it increased the natural killer activity of peritoneal fluid cells and splenic cells, decreased the number of peritoneal fluid cells, and decreased interleukin-1beta production by peritoneal macrophages. In contrast, danazol (100 mg/kg per day, p.o.) and buserelin (30 microg/kg per day, s.c.) had none of these immunologic effects. Additionally, combined administration of dienogest (0.1 mg/kg per day) plus buserelin (0.3 microg/kg per day) suppressed the bone mineral loss induced by buserelin alone, with no reduction of the effect on endometrial implants. In vitro studies on dienogest revealed an antiproliferative effect on rat endometrial cells due to inhibition of protein kinase C activity plus a partial progestational effect. CONCLUSIONS: Dienogest appears to be a potent agent with mechanisms of action different from those of danazol and GnRH agonists currently available for the treatment of endometriosis.     

Technique and rationale of lymph node dissection in bronchial carcinoma

BACKGROUND: Psoriasis is a chronic T-cell-mediated inflammatory skin disease which can be treated with topical medication, phototherapy or systemic medication. A subgroup of psoriatic patients does not respond to monotherapy and needs combination therapy. We used low-dose narrow-band UVB phototherapy, combined with balneotherapy, short-contact anthralin, liquor carbonis detergens and calcipotriol for treatment of psoriatic patients in our day care centre. OBJECTIVE: Our purpose was to study the efficacy, induction of erythema and effect on systemic T-cell activation of this combination therapy. METHODS: Skin reflectance spectrophotometry was used to measure skin erythema. The Psoriasis Area and Severity Index (PASI) was used to evaluate psoriatic patients. Serum soluble IL-2 receptor (sIL2-R) levels were measured by an ELISA. RESULTS: The possible erythematogenic effect of low-dose narrow-band UVB irradiation was studied (skin reflectance spectrophotometer) in a control group of psoriatic patients (n = 11). No induction of skin erythema was seen. Subsequently, this low-dose irradiation regimen was used in combination with topical medication in 26 psoriatic patients. A 90% decrease in the PASI was seen after a mean number of 35 treatment sessions. Seventeen patients (65%) remained in remission during the following 6 months. Serum sIL-2R levels were elevated in all patients (mean 913 U/ml) and did not change during treatment. CONCLUSION: Our data indicate that low-dose narrow-band UVB can be used successfully, in combination with topical treatment, in a day care setting to treat psoriatic patients. Since sIL-2R serum levels were not decreased, it can be speculated that this treatment does not induce systemic immunosuppression.     

The role of scientific societies

Ectopic pregnancy is one of the most common and dangerous complications of the early pregnancy period. Until now diagnosis has been late because major symptoms occur after tubal rupture and so only demolitive surgery has been possible. At present, with the appearance of ultrasound in obstetrics an earlier diagnosis of this pathology can be made before tubal rupture so medical treatment has become possible. We treated a series of twelve patients with early ectopic pregnancy (9 tubal and 3 with no localized site of implantation) with intramuscular 0.5 mg/kg methotrexate and oral 0.1 mg/kg of folic acid (Citrovorum Factor) on alternate days, in the attempt to reduce hospitalization and obtain more effective and safer medical management. We observed a fall in serum beta-HCG levels after one cycle of treatment in 11 out of 12 patients and after two cycles of therapy in the remaining case. Minimal side-effects were observed in four cases. Three pregnancies occurred after treatment before the advised interval time and ended in blighted ovum. Methotrexate systemic therapy can be considered an elective treatment and a sufficiently safe management in early unruptured ectopic pregnancy when a good clinical selection of patients is performed.     

Fertility after conservative and radical surgery for tubal pregnancy

A retrospective cohort study was set up to evaluate the effectiveness of conservative and radical surgery for tubal pregnancy towards subsequent fertility. Consecutive patients undergoing conservative or radical surgery for tubal pregnancy between January 1990 and August 1993 in two university hospitals were included in the study. Outcome measures were spontaneous intrauterine pregnancy (IUP) and repeat ectopic pregnancy (EP). Of the 135 patients analysed, 56 underwent conservative surgery and 79 underwent radical surgery. Patients treated with conservative surgery achieved a higher 3-year cumulative pregnancy rate than those treated radically (P < 0.001, log-rank test). In patients treated conservatively, there was only one spontaneous IUP in the period between 18 months and 3 years after the tubal pregnancy. In contrast, patients treated radically continued to conceive in this period. Multivariate analysis showed a fecundity rate ratio (FRR) of 1.9 [95% confidence interval (CI): 0.91 to 3.8] for IUP after conservative surgery in the first 18 months of follow-up. In patients with a history of bilateral tubal disease the FRR was 3.1 (95% CI: 0.76 to 12), whereas in patients without a history of bilateral tubal disease the FRR was 1.4 (95% CI: 0.13 to 16). The FRR for repeat EP was 2.4 (95% CI: 0.57 to 11). Our data indicate a beneficial effect of conservative surgery towards subsequent fertility that was not, however, statistically significant in the multivariate analysis. In view of these inconclusive data and the importance of this major health problem, randomized studies are required to assess whether conservative surgery really improves the fertility prospects of patients with tubal pregnancy.     

Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin

AIMS: To evaluate absorption of protein-bound and unbound cyanocobalamin before and during treatment with omeprazole, and cobalamin levels in patients on long-term treatment with omeprazole. METHODS: In eight former duodenal ulcer patients absorption of unbound and protein-bound cobalamin was determined by measuring 24-h urinary excretion of unbound 58Co-cyancobalamin or protein-bound 57Co-cyanocobalamin during a modified Schilling test. Tests were performed before and during treatment with 20 mg and 40 mg omeprazole daily for 9 days. Serum cobalamin levels were assessed in 25 patients with gastro-oesophageal reflux disease (GERD) before and during long-term maintenance therapy with omeprazole. Mean treatment duration was 56 months (range 36-81 months). RESULTS: Urinary excretion of unbound cobalamin was unchanged with both dosages of omeprazole. Excretion of 57Co-cyanocobalamin, however, decreased significantly during treatment with both 20 mg omeprazole (mean +/- S.E.M.: 1.31 +/- 0.20 vs. 0.54 +/- 0.17%; P < 0.02) and 40 mg omeprazole (1.25 +/- 0.26 vs. 0.29 +/- 0.06%; P < 0.02). Mean serum cobalamin levels (+/- S.E.M.) before and during therapy with omeprazole in GERD patients were 298 +/- 27 and 261 +/- 16 pg/mL (normal range 180-900 pg/mL), respectively (P = N.S.). CONCLUSIONS: Absorption of protein-bound, but not unbound, cyanocobalamin is decreased when measured by a modified Schilling test during treatment with omeprazole. However, no change in serum cobalamin levels was observed in patients with GERD after treatment with omeprazole for up to 7 years.     

Scrotal ulcer occurring in patients with acute promyelocytic leukemia during treatment with all-trans retinoic acid

STUDY OBJECTIVE: To evaluate the efficacy of conservative laparoscopic surgery in a series of patients with stage III-IV endometriosis. DESIGN: Prospective study (Canadian Task Force classification II-1). SETTING: University-affiliated hospital. PATIENTS: All 141 women who underwent conservative operative laparoscopy for stage III-IV endometriosis between January 1993 and December 1996 and were followed for a minimum of 6 months. INTERVENTIONS: Laparoscopic procedures performed with scissors, bipolar coagulation, and hydrodissection. MEASUREMENTS AND MAIN RESULTS: Clinical examination, transvaginal ultrasonography, and pain questionnaire were scheduled every 6 months postoperatively. The cumulative proportion of pregnant patients and cumulative recurrence rate were calculated by Kaplan-Meier method. Twenty-five women (44%) with infertility became pregnant. Twenty-three (51%) had stage III and two (16.7%, p <0.05) had stage IV endometriosis. The 24-month cumulative pregnancy rate was 57.5%. Thirty-one women (22%) reported pain recurrence during follow-up. Five (3.5%) recurrences were confirmed by histologic examination and eight (5.7%) were documented only by clinical and ultrasonographic findings. No recurrence occurred in the first 6 months of follow-up. CONCLUSION: Operative laparoscopy seems to be effective treatment for stage III endometriosis. A larger series with longer follow-up is necessary to clarify its role in the management of stage IV disease. (J Am Assoc Gynecol Laparosc 6(1):55-58, 1999)     

Extended clomiphene citrate (CC) and prednisone for the treatment of chronic anovulation resistant to CC alone

OBJECTIVE: To evaluate effectiveness and safety of a regimen of extended clomiphene citrate (CC) and prednisone for patients who fail treatment with CC alone. DESIGN: Retrospective observational analysis. SETTING: University-based tertiary infertility center. PATIENT(S): Twenty-four anovulatory patients who failed to ovulate after CC 150 mg administered for 5 days. INTERVENTION(S): Treatment consisted of CC given on cycle days 3 through 9 (extended) at a starting dose of 100 to 150 mg/d. Additionally, patients were given prednisone 5 mg orally each night throughout the cycle. MAIN OUTCOME MEASURE(S): Ovulation was confirmed by luteal serum P. Pregnancy was confirmed by rising hCG levels and transvaginal ultrasound. RESULT(S): A total of 60 cycles were available for review. Forty-four of these cycles were ovulatory (73%) and 11 patients (46%) conceived on this therapy. Logistic (two-parameter) pregnancy occurrence over time (cycles) revealed a maximum pregnancy probability of 0.66 and a cycle fecundity of 0.36. No complications of therapy were noted. CONCLUSION(S): Clomiphene citrate-resistant anovulatory patients have high rates of ovulation and pregnancy after treatment with extended CC and prednisone. This therapy offers a potential reduction in cost and risk and should be considered in this group of patients before gonadotropin stimulation or surgery.     

Danazol for systemic lupus erythematosus with refractory autoimmune thrombocytopenia or Evans' syndrome

OBJECTIVE: To determine the efficacy of danazol for refractory autoimmune thrombocytopenia or Evans' syndrome complicating systemic lupus erythematosus (SLE). METHODS: We studied 16 consecutive patients with SLE and corticosteroid refractory autoimmune thrombocytopenia; 3 patients had coexisting autoimmune hemolysis (Evans' syndrome). Five patients had undergone splenectomy. Danazol was commenced at 200 mg/day, and increased stepwise (maximum 1200 mg/day) until benefit or toxicity was observed. After remission the danazol dose was gradually reduced to 200-400 mg/day. RESULTS: All 16 patients achieved a complete remission (platelet count >100 x 10(9)/l, hematocrit >39%) 2 months after starting danazol (range 6 weeks-8 months). Remission persisted during continued danazol therapy (mean followup 18.2 months, range 2-49 months). One patient with Evans' syndrome required discontinuation of danazol because of jaundice and biopsy proven minimal hepatic necrosis: hemolysis recurred after discontinuation of danazol. CONCLUSION: Danazol is effective for the treatment of autoimmune thrombocytopenia or Evans' syndrome complicating SLE irrespective of splenectomy status. Longer followup will be needed to determine whether the remission persists after withdrawal of danazol.