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The article reports on the pathogenesis and management of primary dysmenorrhea. Evidence-based data support the efficacy of cyclooxygenase inhibitors. They reduce the amount of menstrual prostanoids (MP)released with concomitant reduction in uterine hypercontractility. Oral contraceptive pills inhibit endometrial development and decrease MP.

Dystrophic epidermolysis bullosa is a major form of epidermolysis bullosa and may be inherited as an autosomal dominant or recessive trait, with associated mutations in the COL7A1 gene. Here, we describe a consanguineous Pakistani family with four affected individuals suffering from recessive dystrophic epidermolysis bullosa. Exome sequencing of the proband's DNA revealed a homozygous missense variant (c.8038G>A:p.Gly2680Ser) in COL7A1 which cosegregated with disease in the family. The emergence of this particular glycine substitution in patients from diverse ethnic backgrounds such as China, United Kingdom, Poland, Iran, and Pakistan indicates that this variant most likely constitutes a recurrent mutational hotspot in the COL7A1 gene, rather than a germline mutation present at low levels in the general population.

Black and hispanic patients sustained on maintenance hemodialysis have better survival than their white counterparts. It is speculated that this is partly because of delayed initiation of dialysis in whites. We retrospectively analyzed 220 patients with chronic renal failure started on hemodialysis at our institution from 1987 to 1994 to detect any racial differences in uremia severity at initiation of dialysis. The 220 study subjects (120 women, 100 men) included 139 blacks (63%), 61 whites (28%), 16 hispanics (7%), and 4 asians (2%) of mean (+/- SD) age 53.5 +/- 15.6 years at referral. At initiation of dialysis, nonwhites had a higher mean serum creatinine concentration (sCr) than whites (12 +/- 5.1 vs 8.8 +/- 3.7 mg/dl; p = 0.001). Mean hematocrit was lower in nonwhites (24% +/- 5.8%) than whites (28% +/- 4.8%; p = 0.001). Logistic regression analysis with adjustment for potential confounders showed that nonwhites were three times more likely than whites to have a hematocrit value of less than 22% at initiation of dialysis (odds ratio, 3.0; 95% confidence interval [CI], 1.11-7.6; p = 0.02). Furthermore, the higher the sCr at initiation of dialysis, the higher the odds of having a hematocrit value of less than 22% (odds ratio, 1.1; 95% CI, 1.03-1.12; p = 0.005). We conclude that at initiation of dialysis, nonwhites have higher sCr as well as more severe anemia than whites, which suggests that initiation of dialysis is not delayed in whites relative to nonwhites.

The corpus luteum is controlled by luteinizing hormone (LH) and intraovarian morphofunctional specialization and autocrine/paracrine mechanisms. Corpus luteal insufficiency produces luteal phase defects (LPD). The poor precision and validation of endometrial histologic dating and single or random multiple serum progesterone measurements produce widely variable diagnoses. The true prevalence rate of LPD may be only 3-5% similar to that due to chance. The role of LPD in causing infertility can be challenged because the diagnosis is not predictive of recurrence in subsequent cycles, and other causes of infertility are not controlled for. Intraobserver and interobserver variability, uterine site of biopsy, luteal phase length, time of ovulation, and luteal phase timing of biopsy have been examined and have confirmed the imprecision of dating as a sensitive and reliable assessment of luteal insufficiency. There is support for either early or late luteal phase biopsy. Endometrial dating using LH timing as a reference point is relatively more reliable. Integrated luteal progesterone is the only currently accurate assessment of luteal sufficiency. Clomiphene does not increase LPD but increases serum progesterone, integrated progesterone, corpus luteum LH/human chorionic gonadotropin (hCG), and insulin-like growth factor-1 (IGF-1) receptors, all of which promote increased progesterone production and do not affect endometrial estrogen and progesterone receptors. hCG is more likely to stimulate progesterone production if given at the mid rather than early luteal phase corresponding to the phase with highest total and available (unoccupied) corpus luteal LH receptors. Careful analysis of published studies on treatment of LPD revealed only one randomized controlled study, and, statistically, all studies revealed no better outcome with progesterone treatment.

In a randomized four-way crossover study, 32 women with primary dysmenorrhea were treated with transcutaneous electrical nerve stimulation (TENS) for two cycles, placebo (sham) TENS for one cycle, or ibuprofen 400 mg four times a day for one cycle. The TENS setting used was 100 pulses per second with 100-microsecond pulse widths. The subjects were allowed to adjust the amplitude to a comfortable level. The pain rescue medication was ibuprofen 400 mg as needed, up to 1600 mg/day. Significantly more subjects who had TENS treatment did not require rescue medication or required less backup ibuprofen at 0-4, 4-8, and 8-12 hours after the onset of dysmenorrhea and starting treatment, as well as during the first 24 hours and for the duration of the menstrual flow, when compared with placebo TENS or ibuprofen-treated cycles (Tukey multiple comparison, P less than .01). Transcutaneous electrical nerve stimulation significantly delayed the need for ibuprofen by an average of 5.9 hours, compared with 0.7 hours when using ibuprofen alone (P less than .05, paired t test). Transcutaneous electrical nerve stimulation alone provided good to excellent subjective pain relief in 42.4% of subjects, compared with 3.2% with placebo TENS, and significantly reduced diarrhea, menstrual flow, clot formation, and fatigue compared with placebo TENS. Transcutaneous electrical nerve stimulation plus less ibuprofen provided pain relief equivalent to that obtained with ibuprofen alone (71 and 75% of the subjects, respectively). We conclude that TENS is a safe, effective, non-medication method for managing primary dysmenorrhea and that TENS plus ibuprofen was the best overall treatment, as indicated by pain relief.

Fetal oxytocin contribution to the mother during spontaneous labor was investigated using a specific and sensitive radioimmunoassay to measure oxytocin in blood, amniotic fluid, and urine. In 26 subjects with spontaneous labor and vaginal delivery (Group I) and 18 subjects with cesarean section after labor (Group II), umbilical arterial plasma (UA) oxytocin concentrations were significantly higher than umbilical venous plasma (UV) ocytocin concentrations. With elective cesarean section (Group III), UA oxytocin concentration was 29.8 +/- 7.5 pg/ml and UV oxytocin concentration was 16.1 +/- 5.9 pg/ml (n = 14). In contrast, the mean UV oxytocin concentration was higher than the mean UA oxytocin concentration, when oxytocin was given to the mothen concentration in Groups I and II was significantly higher than in Group III. Amniotic fluid oxytocin concentrations in Group I and II patients were higher than in Group III. Oxytocin was also present in fetal urine. The findings indicate that during spontaneous labor, oxytocin is produced by the fetus and flows toward the maternal circulation.

Serum human chorionic gonadotropin (hCG) was measured by a radioreceptorassay (RRA) and radioimmunoassay (RIA) and serum hCG-beta and hCG-alpha by RIA in 10 patients with intact mole, 3 patients with choriocarcinoma, and 4 patients with hydatidiform mole during treatment. hCG levels by RRA were higher in 5 of 10 molar pregnancies and ranged from 20,900 to 100,000 ng/ml and from 30,000 to 100,000 ng/ml by RIA. hCG levels by RRA and RIA paralleled one another closely during treatment of hydatidiform mole. hCG-alpha was higher than hCG by RRA and RIA and hCG-beta in molar pregnancies, in the uterine venous blood draining a uterine choriocarcinoma, and during chemotherapy of choriocarcinoma. In 2 of 3 choriocarcinoma patients who eventually developed cerebral metastases, hCG-alpha increased while hCG and hCG-beta were declining or negative. hCG-beta was usually lower than hCG or hCG-alpha in all the cases studied. These results demonstrate the production of free alpha and beta subunits in trophoblastic disease. Further, due to the biospecificity, simplicity, and rapidity, the RRA of hCG is a sueful diagnostic aid during treatment of trophoblastic neoplasia until the levels fall to within the sensitivity range of the assay. Finally, the RIA of hCG, hCG-beta, and hCG-alpha, which requires several days, should be performed until they become negative or fall within normal range.

In a randomized study, 94 patients with term pregnancies underwent augmentation of labor with either continuous or pulsed (every 8 minutes) intravenous oxytocin infusion. There were no significant differences with respect to the maternal characteristics, cervical dilatation and effacement, induction-to-labor interval, induction-to-delivery interval, cesarean section rate, analgesia for labor, or low Apgar scores. No hyperstimulation was noted in either group. In each group, 20% of the patients had dysfunctional labor patterns, with coupling and tripling of the uterine contractions. The mean +/- SEM oxytocin administered in the pulsed-infusion group was significantly lower than that in the continuous-infusion group (2.1 +/- 0.4 versus 4.1 +/- 0.4 mU/minute; P less than .001). The mean +/- SEM total amount of oxytocin administered was 1300 +/- 332 mU for the pulsed group and 1803 +/- 302 mU for the continuous group, indicating that lower amounts of oxytocin were required for pulsed administration. Our study demonstrates that pulsatile administration of oxytocin is similar in efficacy to our standard continuous oxytocin infusion and requires a lower total amount and rate of oxytocin administered, which may afford a greater margin of safety.

Serum progesterone was measured by competitive protein binding assay at regular intervals up to 24 hours after delivery in 4 normal pregnancies. In 6 cases of hydatidiform mole, serum progesterone was assayed before and at regular intervals up to 48 hours after uterine evacuation or hysterectomy. Serum progesterone dropped rapidly by more than 50% during the first hour postpartum, and it was less than 25% of the predelivery levels 24 hours after parturition. In all 6 cases of molar pregnancies, serum progesterone fell rapidly within the first few hours after uterine evacuation. In the presence of theca lutein cysts (2 cases), serum progesterone fell much more slowly than in the absence of theca lutein cysts after removal of the mole tissue. Serum progesterone was less than 5mg/ml after total hysterectomy of uterine evacuation in moles without theca lutein cysts. These findings suggest that while the placenta is the principal source of elevated serum progesterone in normal pregnancy, the molar trophoblast is the principal source of elevated serum progesterone in hydatidiform mole, with the theca lutein cysts making a contribution when they are present.

Serum or plasma total unconjugated estriol and total estriol glucuronide fractions were measured in 14 patients with unaborted hydatidiform mole between 11 and 25 weeks of gestation and in 20 normal pregnant patients between 8 and 17 weeks of gestation. The estriol fractions were separated by solvent partition, and the estriol was measured by radioimmunoassay using antiserum against estriol-16-17-dihemisuccinate conjugated to bovine serum albumin. The values (means and ranges) found in normal pregnant patients were as follows: estriol 1.3 ng/ml (0.3-2.9); estriol glucuronide, 11.1 ng/ml (4.7-24.8). Wide ranges of values were found in patients with molar pregnancies compared to those with normal pregnancies of equivalent gestation, some values being within the upper range of normal and others being well below the normal range. Of the 14 molar pregnancies studied, 9 (64%) were associated with serum estriol values which were below the ranges for normal pregnancy, and 8 (57%) were associated with similarly low estriol glucuronide values. The incidences of low estriol and estriol glucuronide values were less than those reported for low urinary estriol excretion in hydatidiform moles. No correlation was found between any of the serum estriol fractions and the serum hCG values or with the presence of theca lutein cysts in the ovaries. It was suggested that the trophoblast was the principal source of estriol in these molar pregnancies.