Elastin degradation by cathepsin V requires two exosites.

Cathepsin V is a highly effective elastase and has been implicated in physiological and pathological extracellular matrix degradation. However, its mechanism of action remains elusive. Whereas human cathepsin V exhibits a potent elastolytic activity, the structurally homologous cathepsin L, which shares a 78% amino acid sequence, has only a minimal proteolytic activity toward insoluble elastin. This suggests that there are distinct structural domains that play an important role in elastinolysis. In this study, a total of 11 chimeras of cathepsins V and L were generated to identify elastin-binding domains in cathepsin V. Evaluation of these chimeras revealed two exosites contributing to the elastolytic activity of cathepsin V that are distant from the active cleft of the protease and are located in surface loop regions. Replacement of exosite 1 or 2 with analogous residues from cathepsin L led to a 75 and 43% loss in the elastolytic activity, respectively. Replacement of both exosites yielded a non-elastase variant similar to that of cathepsin L. Identification of these exosites may contribute to the design of inhibitors that will only affect the elastolytic activity of cysteine cathepsins without interfering with other physiological protease functions.

A Quantification of the Injury-Induced Changes in Central Aromatase, Oestrogenic Milieu and Steroid Receptor Expression in the Zebra Finch.

In songbirds and mammals, brain injury results in the up-regulation of aromatase (oestrogen synthase) expression in astroglia. The resulting presumed synthesis of neural oestradiol (E2 ) has neuroprotective effects including a decrease in neurodegeneration, neuroinflammation and apoptosis. The development of therapeutic tools that exploit oestrogenic neuroprotection in the treatment of neurotrauma requires a precise quantification of the endogenous changes in neural aromatase and E2 following brain injury. Surprisingly, the expected increase in neural oestrogens following brain injury has not been demonstrated. Furthermore, we are just beginning to unravel the mechanisms behind the protective effects of centrally synthesised E2 . In the present study, levels of aromatase immunoprotein, neural E2 and steroid receptor mRNA were quantified in adult male and female zebra finches 48 h following a unilateral penetrating brain injury. Both aromatase and E2 were up-regulated in the injured hemisphere of the brain compared to the uninjured hemisphere, demonstrating for the first time a robust increase in neural E2 levels following injury. We did not detect an effect of injury on mRNA expression of the oestrogen receptors (ER)-α, ER-ß or GPER-1, but observed a significant decrease in androgen receptor transcription in the injured lobe relative to the contralateral uninjured hemisphere. We conclude that mechanical damage causes a dramatic increase in local aromatisation, and the resultant high levels of central E2 are available to modulate steroid sensitive targets. Studies using alternate methods of receptor detection and/or time points may be necessary to understand the complete suite of mechanisms underlying the neuroprotective effects of induced oestrogen synthesis in this animal model.

First report of management and outcome of pregnancies associated with hereditary orotic aciduria.

Two pregnancies in a 25-year-old woman with hereditary orotic aciduria who was managed prenatally on uridine therapy are described. The first pregnancy resulted in an infant with multiple congenital anomalies and a 47,xx,inv(4)(p12q25), +der(22)t(11;22)(p23;q11) karyotype. The proposita was found to be a carrier of a de novo 11;22 translocation and a pericentric inversion of chromosome 4. Subsequently, several carriers of orotic aciduria in this family were identified with the inverted chromosome 4. The second pregnancy resulted in a normal male with an inverted chromosome 4.

Use of professional patients in teaching pelvic examinations.

Learning proper techniques in physical examinations is mandatory for a physician. Although students may examine each other in early training, examination of the female pelvis does not readily conform to this reciprocity. A randomized study was conducted, comparing teaching methods utilizing professional patients or plastic models. Training on a professional patient significantly increased a student's chance of palpating one or both ovaries, reduced the student's anxiety about performing a pelvic examination, and may have improved the student's gentleness. Costs of the professional patient method were minimal. It is recommended that teaching pelvic examinations with the professional patient replace teaching on the plastic model.

Management of Landry-Guillain-Barré syndrome in pregnancy.

The criteria for Landry-Guillain-Barré syndrome are reviewed and a case of a patient requiring respirator support during pregnancy is presented. Based on a current review of the literature, a total of 29 cases have been reported with an estimated fetal survival rate of 96% (26 of 27). The syndrome is not affected by pregnancy or pregnancy termination. Respirator support has the highest risk of maternal morbidity and mortality but should be minimized with modern pulmonary treatment. Additional management considerations are discussed.

Real-time ultrasound in locating intrauterine contraceptive devices.

Roentgenography and ultrasonography have been recommended for location of an intrauterine contraceptive device (IUCD) when the strings are not visible at the cervical os. Real-time ultrasound may have limited application compared to gray-scale B-scanning in certain clinical applications. Because of previous difficulty in locating an IUCD in 2 gravid and 2 nongravid patients, a blind study of 68 women was conducted. Seven patients were eliminated from the study because of inadequately filled bladders and failure to return for follow-up visits. There were 37 patients with IUCDs and 24 patients in the control group who used other forms of contraception. An incorrect diagnosis was made in 12 of 61 patients. Ten of 37 patients with an IUCD were identified as having no IUCD and 2 of 24 patients without an IUCD were identified as having an IUCD present. The accuracy of correctly identifying the presence or absence of an IUCD appears to be related to the type of device used. All of the 20 patients with a Copper-7 were correctly identified as having an IUCD, although the type was in error in 11 of the 20. Five of 7 patients with a Lippes Loop and none of the patients with a Saf-T-Coil were correctly identified as having an IUCD. Prior literature is reviewed, and possible sources of error are discussed.

Diagnosis of vasa previa with transvaginal and color flow Doppler ultrasound.

Vasa previa, which is associated with high fetal mortality, is present when fetal vessels cross the internal cervical os as a velamentous insertion of the umbilical cord with or without a succenturiate lobe or bilobate placenta. This is the first case report of vasa previa not associated with a succenturiate lobe or bilobate placenta and in which the diagnosis was made using a combination of transvaginal ultrasonography and color flow Doppler ultrasound. The infant was delivered by elective cesarean, and the ultrasound findings were confirmed. Color flow Doppler and transvaginal ultrasound facilitate this diagnosis because the internal os and surrounding structures are easier to visualize; in addition, vascular flow and Doppler patterns characteristic of the umbilical cord can be demonstrated in structures suspected to be vessels.

False-positive acetylcholinesterase with early amniocentesis.

Among 93 acetylcholinesterase determinations performed on amniotic fluid samples from pregnancies at 11-14 weeks' gestation, five unexplained false-positive results were observed. In four of the five cases, the ratio of acetylcholinesterase to pseudocholinesterase was compatible with that observed in association with open neural tube defects in later gestation. In contrast, no false-positive results were noted among 951 acetylcholinesterase determinations performed on samples from women at 15-20 weeks' gestation. Repeat amniocentesis was performed several weeks after the first procedure in four of the five cases of early amniocentesis and false-positive results; in each case, the acetylcholinesterase was negative on the second sample. All four pregnancies had a normal outcome. In the remaining case, trisomy 21 was diagnosed in the fetus and the pregnancy was terminated. Positive acetylcholinesterase results should be interpreted cautiously in samples from early amniocentesis, especially when the amniotic fluid alpha-fetoprotein level is not markedly elevated. The acetylcholinesterase-to-pseudocholinesterase ratio is not useful in identifying fetal neural tube defects before 15 weeks' gestation. Repeat amniocentesis may help in determining the significance of a positive acetylcholinesterase result from early amniocentesis when no fetal defect is identified by ultrasonography.

Ultrasonographic description of succenturiate placenta.

Postpartum hemorrhage may occur in cases of a retained succenturiate lobe. More catastrophic is rupture of the fetal vessels connecting the lobe to the placenta. A case is presented demonstrating the sonographic description of a large succenturiate lobe.

Ultrasonography preceding diagnostic amniocentesis and its effect on amniotic fluid cell growth.

Experience with 107 consecutive patients with and without ultrasonography preceding diagnostic amniocentesis is presented. Cell cultures and alpha-fetoprotein levels were obtained on all specimens. Adequate cell growth was found in both groups. The frequency of bloody taps was reduced from 15 to 6.9% and of repeat taps from 6.3 to 0%. Possible complications of amniocentesis which might be avoided by prior ultrasonography are discussed. The use of gray scale or real time ultrasonography prior to diagnostic amniocentesis is stressed.

Value of serial sonography in the in utero detection of duodenal atresia.

Duodenal atresia can be fatal unless promptly diagnosed and treated surgically. Death occurs in the newborn secondary to emesis, aspiration, and electrolyte imbalance. Serial ultrasound scans were obtained for 2 patients, but duodenal atresia was not detected until 29 and 32 weeks' gestation, respectively. With prior knowledge of an infant with Down syndrome and duodenal atresia, management of fetal distress with subsequent operative delivery can be altered. Early prenatal diagnosis by ultrasonography and subsequent amniocentesis plays an important role in the antenatal and postpartum counseling and management of these patients and neonates.

Efficacy of combined administration of magnesium sulfate and ritodrine in the treatment of premature labor.

Seventy-four patients in preterm labor at 20-35 weeks' gestation were randomly assigned to receive ritodrine (N = 36) or ritodrine plus magnesium sulfate treatment (N = 38) for tocolysis. Ten did not complete therapy and were excluded from analysis. Nineteen of 32 patients (59%) in the ritodrine plus magnesium sulfate group were successfully treated, compared with only 11 of 32 patients (34%) in the ritodrine-only group (P less than .05). Of the 21 patients who failed to respond to the initial ritodrine treatment, 16 received intravenous magnesium sulfate supplemental therapy; 75% of this group were treated successfully. The frequency of adverse maternal and fetal side effects did not differ between the treatment groups. In the combined group compared with the ritodrine group, the dose requirements for ritodrine therapy as well as the total duration of treatment for both ritodrine and magnesium sulfate were reduced significantly. We conclude that concurrent administration of ritodrine and magnesium sulfate is more efficacious than ritodrine alone and does not appear to increase the frequency of adverse side effects.

Premature rupture of membranes: a prospective, randomized evaluation of steroids, latent phase, and expectant management.

A prospective, randomized study was conducted comparing the use of betamethasone and early delivery, early delivery alone, and expectant management in patients in the 28th to 34th week of pregnancy with premature rupture of the membranes (PROM). Tocolytic drugs were used to delay delivery until 24 hours had elapsed after the first dose of steroid or 24 to 48 hours of latent period had elapsed in the second group. There were no significant differences in maternal age, gestation at PROM, maximum maternal temperature, birth weights, maternal hospital days, respiratory distress, maternal sepsis, or delivery routes in the three groups. Comparisons with one other similar prospective, randomized study support the concept that expectant management offers less risk from tocolytic side effects.

Sonolucencies in fetal and infant abdomen: implications for management.

The increased use of prenatal and antenatal ultrasonography will detect predictably abnormalities of fetal and infant anatomy not assessed or suspected previously. Three cases are presented illustrating similar ultrasonographic findings with different diagnoses and prognoses, and comparisons are made with other cases reported in the literature. Caution should be used in interpreting sonolucencies in fetal and infant abdomen to be diagnostic of a particular defect since further studies are required to define properly the specific abnormality so that proper treatment can be instituted.

Diet composition related to body fat in a multivariate study of 203 men.

OBJECTIVE: To assess whether usual diet (especially intake of dietary fat, carbohydrate, and fiber) was related to body fat percentage in healthy men. DESIGN: A written questionnaire provided data on demographic and lifestyle characteristics. Dietary fat, carbohydrate, protein, and fiber intakes were analyzed using the National Cancer Institute food frequency questionnaire. Percentage of body fat was determined using three-site skinfold measurements, and a submaximal treadmill test was used to estimate aerobic fitness. SUBJECTS: Subjects were 203 healthy men (14.0 +/- 5.3% mean body fat) aged 21 to 71 years. The subjects were chosen from randomly selected districts within Utah County and volunteered for free diet and fitness evaluations. STATISTICAL ANALYSIS: Multiple regression analysis determined the extent to which the individual diet components predicted body composition before and after controlling for energy intake, fitness level, body weight, and age. Multivariate analysis of variance was used to compare relative body fat groups in regard to dietary variables. RESULTS: Reported intakes of carbohydrate (P = .0085, R2 = .022), complex carbohydrate (P = .0127, R2 = .024), and fiber (P = .002, R2 = .03) were inversely associated with body fat after controlling for age, energy intake, and fitness level. Energy intake was positively related to body fat after controlling for age, fitness level, and body weight. When subjects were separated into low-, moderate-, and high-body-fat groups, the fattest subjects reported eating significantly more dietary fat (P = .05) and less carbohydrate (P = .01), complex carbohydrate (P = .01), and fiber (P = .005) than the leanest subjects. No significant difference in reported energy intake was noted across body fat groups. APPLICATIONS: Composition of the diet may play a role in obesity beyond energy intake in men over the long-term. Lifestyle changes for men should probably include modifications in diet composition, especially increased consumption of foods high in complex carbohydrate and fiber.

Introduction to transvaginal imaging.

Transvaginal sonography provides improved resolution and avoidance of intervening anatomic structures that can degrade the image. In this article, transvaginal transducers are described and compared with transabdominal transducers. The sagittal and coronal views used in transvaginal sonography are described. Advantages and disadvantages of transvaginal sonography are considered. Safety considerations of the decreased attenuation path to the fetus are dealt with.

The role of antepartum surveillance in the management of gastroschisis.

OBJECTIVE: To evaluate the perinatal morbidity and mortality of fetuses diagnosed with gastroschisis at our Fetal Diagnosis and Treatment Center. METHODS: A retrospective review of a regional prenatal diagnostic center. Twenty-nine cases of gastroschisis which were diagnosed, managed, delivered and had corrective surgeries through the Fetal Diagnosis and Treatment Center were identified from 1985 to 1994. Perinatal morbidity and mortality were reviewed. Antepartum testing schemes were reviewed when available to determine whether morbidity or mortality could have potentially been prevented. RESULTS: Meconium occurrence, intrauterine growth retardation (IUGR) and oligohydramnios complicated 79%, 41% and 36% of the cases, respectively. The perinatal mortality of this series was 241/1000. Significant differences in perinatal mortality were noted when fetal testing was incorporated (200/1000 vs. 286/1000, P < or = 0.001). CONCLUSION: Gastroschisis is associated with a high incidence of IUGR, meconium, oligohydramnios and high perinatal mortality. Antenatal testing appears to significantly lower perinatal mortality in pregnancies complicated by gastroschisis.

Effectiveness of the Isaacs cell sampler for endometrial cultures.

Because of encouraging results from a preliminary clinical investigation, a practical method of obtaining uncontaminated endometrial cultures using an endometrial sampling device developed for aspiration of cytologic specimens was investigated. Four groups of patients were studied: 8 nonpregnant women, 22 nonpregnant women having a total abdominal hysterectomy, 6 afebrile postpartum women and 8 women with postpartum clinical endometritis. The cervical flora obtained with a swab and the endometrial flora obtained with the sampling device and by direct culture at hysterectomy were compared. The data showed some degree of cervical contamination with the Isaacs method, suggesting that while the technique may be simple, design modifications of the device are needed for it to be dependable.

Obstetric and anesthetic considerations in the May-Hegglin anomaly. A case report.

The obstetric and anesthetic considerations in the management of a patient with the May-Hegglin anomaly, an autosomal dominant platelet deficiency, are discussed. A review of the medical literature notes three previous case reports of May-Hegglin anomaly in pregnancy. In addition to the two successful pregnancies reported in this paper, there are four infant survivors among the five reported pregnancies. Anesthetic managements included general and spinal anesthesia: the latter employed following platelet transfusion. A successful pregnancy should be anticipated when management includes a well-informed patient and coordinated obstetric and anesthetic care.