A comparison of ventricular function during high right ventricular septal and apical pacing after his-bundle ablation for refractory atrial fibrillation.

This study compares LV performance during high right ventricular septal (RVS) and apical (RVA) pacing in patients with LV dysfunction who underwent His-bundle ablation for chronic AF. We inserted a passive fixation pacing electrode into the RVA and an active fixation electrode in the RVS. A dual chamber, rate responsive pulse generator stimulated the RVA through the ventricular port and the RVS via the atrial port. Patients were randomized to initial RVA (VVIR) or RVS (AAIR) pacing for 2 months. The pacing site was reversed during the next 2 months. At the 2 and 4 month follow-up visit, each patient underwent a transthoracic echocardiographical study and a rest/exercise first pass radionuclide ventriculogram. We studied nine men and three women (mean age of 68 +/- 7 years) with congestive heart failure functional Class (NYHA Classification): I (3 patients), II (7 patients), and III (2 patients). The QRS duration was shorter during RVS stimulation (158 +/- 10 vs 170 +/- 11 ms, P < 0.001). Chronic capture threshold and lead impedance did not significantly differ. LV fractional shortening improved during RVS pacing (0.31 +/- 0.05 vs 0.26 +/- 0.07, P < 0.01). RVS activation increased the resting first pass LV ejection fraction (0.51 +/- 0.14 vs 0.43 +/- 0.10, P < 0.01). No significant difference was observed during RVS and RVA pacing in the exercise time (5.6 +/- 3.2 vs 5.4 +/- 3.1, P = 0.6) or the exercise first pass LV ejection fraction (0.58 +/- 0.15 vs 0.55 +/- 0.16, P = 0.2). The relative changes in QRS duration and LV ejection fraction at both pacing sites showed a significant correlation (P < 0.01). We conclude that RVS pacing produces shorter QRS duration and better chronic LV function than RVA pacing in patients with mild to moderate LV dysfunction and chronic AF after His-bundle ablation.

Exercise and beta-adrenergic regulation of rat cardiac myosin isoforms.

BACKGROUND: The purpose of this experiment was to examine the effects of both exercise and beta-adrenergic receptor blockade on the expression of native cardiac myosin isoforms. Specifically, this experiment tested two hypotheses: 1) treatment of sedentary rats with the beta blocker, propranolol, will promote increased ventricular V3 (slow) native myosin content with a concomitant reduction of V1 (fast) myosin isoforms; and 2) endurance exercise training will result in an increased sympathetic drive and therefore will retard the propranolol-induced shift in cardiac myosin isoform expression. METHODS: Adult, male Sprauge-Dawley rats (120 days old) were randomly divided into 4 groups: 1) exercise-sham (ES); 2) exercise-propranolol (EP); 3) sedentary-sham (SS); and 4) sedentary-propranolol (SP). Propranolol (30 mg drug/kg body wt) and sham (saline) injections (i.p.) were administered 30 minutes prior to daily exercise. Both ES and EP groups completed six weeks (5 day/wk) of treadmill running at approximately 65-70% VO2max. RESULTS: Data analysis revealed that exercise training did not alter (p > 0.05) ventricular myosin isoforms in the sham injected animals. In contrast, propranolol treatment resulted in a significant (p < 0.05) increase in the slow (V3) myosin isoform and a concomitant decrease in the V1 isoform in both sedentary and exercise trained animals. CONCLUSIONS: The observed increase in V3 myosin isoform in propranolol treated rats supports the notion that beta-adrenergic stimulation is an important regulator of cardiac myosin isoform expression. However, our hypothesis that exercise training would retard the propranolol-induced shift in cardiac myosin was not supported.

Photodynamic therapy of choriocarcinoma transplanted to the hamster cheek pouch. I. Intraperitoneal photosensitization.

Human choriocarcinoma (JEG-3) cells were transplanted into the cheek pouch of hamsters and treated with photodynamic therapy. Twenty-four hours after intraperitoneal injection of the photosensitizer dihematoporphyrin ether (DHE), 20 tumors were illuminated with 100 J/cm2 of 630-nm light from an argon pumped dye laser. Contralateral tumors served as controls. Dihematoporphyrin ether alone had no effect on tumor growth, while laser light in the absence of DHE resulted in complete regression in 3 tumors (17%), and partial regression in 4 of 18 tumors (22%), possibly due to hyperthermia, P greater than 0.10. Using the combination of DHE plus light (photodynamic therapy) complete tumor regression was noted after a single treatment in 11 of 20 tumors (55%, mean tumor volume 279 mm3) and in 7 of 7 tumors (100%) after a second treatment. Two of 20 tumors were not retreated. Therefore, 18 of 20 tumors (90%) were grossly destroyed by one or two photodynamic treatments. Contralateral control tumors continued to grow to a median volume of 990 mm3 (chi 2 = 26.30, P less than 0.0001). Choriocarcinoma transplanted into the hamster cheek pouch is highly responsive to photodynamic therapy.

Resection of fixed pelvic tumors using the Nd:YAG laser.

Clinical experience using the Nd:YAG laser to resect intra-abdominal malignancies is limited. Presented are two cases of recurrent gynecologic cancers, one ovarian carcinoma of low malignant potential and one fallopian tube carcinoma grade 1, in which the Nd:YAG laser allowed removal of recurrent tumor fixed to sacral bone and pelvic sidewall. The ability to accomplish laser vaporization of the tumor bed along with periosteum may reduce the risk of local recurrence. Further investigation of laser treatment of tumors fixed to sacral or pubic bone, pelvic sidewall tissues or other structures should lead to the evolution of the Nd:YAG laser as a useful tool to the cancer surgeon.

Early third-trimester ultrasound screening in gestational diabetes to determine the risk of macrosomia and labor dystocia at term.

The purpose of this study was to determine whether an early third-trimester fetal abdominal circumference measurement can be used in patients with gestational diabetes to predict the presence or absence of macrosomia and labor dystocia at term. The predictive accuracy of a 30- to 33-week abdominal circumference measurement was tested, using the ninetieth percentile as the discriminant point. The study consisted of 201 patients with gestational diabetes who maintained weekly fasting glucose levels less than 100 mg/dl and 2-hour postprandial glucose levels less than 120 mg/dl with dietary management alone. The predictive accuracy of a 30- to 33-week fetal abdominal circumference measurement was 96.4% for ruling out macrosomia and 56.3% for predicting macrosomia. Patients with fetal abdominal circumference measurements greater than the ninetieth percentile at 30 to 33 weeks had a significantly increased incidence of cesarean section for failure to progress, shoulder dystocia, and birth trauma, whereas patients with abdominal circumference measurements less than or equal to the ninetieth percentile were at no greater risk than the general population. These results suggest that patients with non-insulin-dependent gestational diabetes with fetal abdominal circumference measurements less than or equal to the ninetieth percentile at 30 to 33 weeks are not at increased risk for macrosomia, cesarean section, or birth trauma at term, as long as their weekly glucose testing remains within normal limits. Efforts to decrease the incidence of macrosomia and its attendant risks should focus on those gestational diabetic patients whose fetal abdominal circumference greater than the ninetieth percentile at 30 to 33 weeks.

Antepartum predictors of fetal distress in postterm pregnancy.

The purpose of this study was to determine the efficacy of combining nonstress testing with ultrasound assessment of amniotic fluid volume for the antenatal evaluation of the postterm fetus. Postterm patients (884) were managed with amniotic fluid assessments and nonstress tests (including evaluation for variable and late decelerations) twice a week. There were no perinatal deaths or major neonatal morbidity. However, the antenatal testing sensitivity, specificity, negative, or positive predictive values were not improved by combining the two tests. Individually, amniotic fluid assessment was just as accurate a predictor of fetal well-being and was a significantly more sensitive test than the nonstress test. In addition, antenatal predictors of fetal distress and intrapartum signs of fetal distress were almost exclusively those reflective of umbilical cord compromise. These findings stress the importance of antenatal screening for signs of umbilical cord compromise as an early indication of potential fetal compromise. Although the results also suggest that amniotic fluid assessment is superior to the nonstress test, they do not conclusively support the use of amniotic fluid assessment as the sole parameter for postterm antenatal surveillance.

The role of antepartum testing in the management of postterm pregnancies with heavy meconium in early labor.

The documented association between heavy meconium in early labor and increased perinatal morbidity and mortality has alerted physicians to the presence of a potential high-risk fetal condition and to the possible need for immediate fetal blood pH determination. The purpose of this study was to determine whether antepartum fetal assessment can predict whether a postterm fetus with heavy meconium in early labor is at low or high risk for an adverse perinatal outcome. Eight hundred thirty-nine postterm patients were followed with antepartum testing, consisting of twice-weekly fetal heart rate (FHR) testing and ultrasonic amniotic fluid volume estimation. Overall, patients with heavy meconium in early labor had a significantly greater frequency of fetal distress. However, when women with heavy meconium in early labor were separated according to their antepartum testing results, those with normal results were found to have no greater risk for fetal distress or perinatal morbidity than women with normal testing and subsequently clear amniotic fluid. These findings suggest that postterm patients with heavy meconium in early labor and normal antepartum testing can be managed in labor in the same manner as low-risk patients without meconium.

Treatment of vulvar carcinoma in situ with the CO2 laser.

Between January 1960 and December 1982, 142 patients with carcinoma in situ of the vulva were treated at Cedars-Sinai Medical Center and UCLA Medical Center. Primary treatment consisted of wide excision in 45 patients; vulvectomy in 23 patients; topical chemotherapy in 9 patients; and CO2 laser therapy in 42 patients. Twenty-three patients were also treated with the CO2 laser for recurrent disease. Multifocal disease was present in 59% of the cases. Lesions involving the posterior vulva recurred most commonly, for both initial and recurrent disease. Results utilizing the CO2 are compared with the other methods of treating carcinoma in situ of the vulva. The CO2 laser is well suited for treatment of both multifocal and unifocal vulvar lesions, as it allows for maximal retention of vulvar integrity with no decrease in therapeutic efficacy.

A pilot study of lorazepam-induced amnesia with cis-platinum-containing chemotherapy.

Eighteen patients with advanced epithelial ovarian cancer were given 36 courses of cis-platinum-containing chemotherapy at Cedars-Sinai Medical Center. Patients were given lorazepam (Ativan) prior to chemotherapy. Amnesia for the day of chemotherapy was reported in 29 courses. Lack of recall for the chemotherapy infusion and the subsequent 8 hr or greater was reported in 33 of the 36 courses. In two courses, no amnesia effects were noted. No serious side effects of lorazepam therapy occurred and all patients believed that the amnesic effect was beneficial during chemotherapy. Lorazepam (Ativan) appears to be a safe medication to induce amnesia for cis-platinum chemotherapy and deserves further study to determine its effect on anticipatory vomiting, nausea and vomiting, and patient compliance with continued chemotherapy.

Varying bioactive to immunoactive ratios of the human chorionic gonadotropin-like substance present in normal human tissues.

To further characterize the hCG-like substance found in normal nonpregnant human tissues, we compared the biological (B) and immunological (I) activities of the substance in extracts of 40 nontrophoblastic tissues and 7 placentas. B was measured in an in vitro mouse testicular interstitial cell bioassay, and I was measured in the beta hCG RIA. Highly purified hCG (CR 119) was used as a standard. B was detected in 92% of the nontrophoblastic nonpituitary tissues. Parallelism between serial dilutions of extracts and the hCG standard was found for 75% of the pituitary extracts, 86% of the placental extracts, and 53% of the other tissues. The correlation between B and I activities in the nontrophoblastic nonpituitary tissues was good (r = 0.8; P less than 0.001). Preincubation of the tissue extracts with anti-hCG serum before bioassay significantly reduced the B activity. There was wide variation in the B to I ratio between tissues and within the same tissues from different individuals. A B to I ratio less than 1 was found in 50% of the tissues, excluding placenta and pituitary, and may have been due to the presence of incomplete or altered hCG molecules, which are immunologically active but have reduced B activity.

Modulation of ectopic secretion of human chorionic gonadotropin by cultured ovarian adenocarcinoma cells.

Modulation of ectopic human chorionic gonadotropin (hCG) secretion by a human nontrophoblastic ovarian papillary cystadenocarcinoma cell line maintained in monolayer culture was studied. Exposure of cells to methotrexate (MTX, 0.1 microM) significantly enhanced hormone secretion while actual cell replication was decreased. In contrast, exposure of cells to actinomycin D (25 pM) for 24 hr completely abolished hormone secretion and resulted in death of all cells. Exposure of the cells to hypothalamic peptides (thyrotropin-releasing hormone, gonadotropin-releasing hormone, and somatostatin) did not alter hCG production. hCG secretion was stimulated after 24-hr incubation with dibutyryl cAMP (100 microM) and by prostaglandin F1 alpha (10 microM). Two separate mechanisms of modulation of ectopic hCG by these cells are possible: a cAMP-mediated stimulation independent of cell-growth kinetics after exposure to dibutyryl cAMP and prostaglandin F1 alpha, and a selective inhibition of DNA synthesis which results in slowing of cell replication and concomitant increase in hCG production per cell.

Comparison of antepartum testing schemes for the management of the postdate pregnancy.

We analyzed the outcome results of 583 postdate pregnancies managed prospectively by one of three antepartum testing schemes, each predicated on the nonstress test. In scheme 1, we relied upon the contraction stress test for evaluation of the nonreactive nonstress test. In scheme 2, we used a modified biophysical profile to evaluate the nonreactive nonstress test. In addition, patients were tested semiweekly. In scheme 3, we added routine weekly ultrasound evaluation of amniotic fluid volume to scheme 2. Only in scheme 3 did we induce labor for decreased amniotic fluid volume or fetal cardiac decelerations irrespective of reactivity. The incidence of fetal distress, perinatal mortality, and perinatal morbidity was increased in babies with decelerations or decreased amniotic fluid volume. Nevertheless, outcome results in scheme 2 were improved over those with scheme 1 and were best with scheme 3. These results suggest a benefit to both semiweekly testing and liberalized criteria for intervention in postdate pregnancies. We also compared the outcome results of scheme 3 with those reported for schemes in which the weekly contraction stress test was used as the primary form of surveillance. We found the outcome results comparable in that both schemes showed minimal mortality and morbidity statistics but high intervention rates (25% to 30%). Differences in methodology and test criteria, however, make such comparisons less than ideal.

A randomized prospective study of the use-effectiveness of two methods of natural family planning.

The final results of a prospective comparative study of two methods of natural family planning indicate a significant difference in the 12 month net cumulative pregnancy rates between the ovulation and symptothermal methods. These differences are on the order of two to one in favor of the symptothermal method. Pearl pregnancy rates confirm similar differentials between the two methods. Dropout rates for both methods were high. Lack of interest or dissatisfaction with the method was the major reason for dropout training while pregnancy or desire for pregnancy were the major reasons for dropout during the formal phase of the study.

PIP: In a prospective, comparative study in Los Angeles, California (1976-1978), 1247 volunteer couples were randomly assigned to either the ovulation method (OM) or the symptothermal method (STM) of natural family planning (NFP). 12-month Pearl pregnancy rates for both phases of the clinical trial (3-5 month training phase plus formal study phase) showed STM to be more effective (16.6 pregnancies/100 women-years) in preventing pregnancy than OM (34.9 pregnancies/100 women-years). For the formal study phase excluding training, Pearl rates were 13.7 for STM and 39.7 for OM. Both methods showed high dropout rates at 12 months (including training) 74% for OM and 64% for STM. Reasons given during the training phase were lack of interest or method dissatisfaction and during the study phase unplanned pregnancy. Of the 90 pregnancies that occurred during training (59 OM and 31 STM) and 62 during the study phase (42 OM and 20 STM), only 6 OM and none of the STM pregnancies were considered strictly method failures. Other pregnancies were due to inaccurate interpretation of mucus symptoms and failure to follow rules. The unexpected difficulty in recruiting couples is attributed to lack of public awareness of NFP, user satisfaction with and acceptance of other contraception methods, and an unwillingness to adhere to the formal requirements of the study protocol. Two-thirds of the 1247 volunteer couples responded to follow-up 1 year after the study. One-half were still using the NFP method they were taught. The other half had stopped because of desired pregnancy or inconvenience or dislike of the abstinence required.

Clinical pharmacists' contribution to patient care on a gynecological unit.

A retrospective study of the contributions of clinical pharmacists on a gynecological unit was undertaken, based on an examination of the clinical pharmacists' interventions in and recommendations for drug therapy. Intervention or recommendations were classified as to type and as to probable result had the pharmacist not intervened or made recommendations. Over an eight-month period, the clinical pharmacist intervened in or made recommendation in 227 instances (0.8% of all medication orders). It was considered that two of the orders would probably have caused death had they been carried out, six could have caused toxicity and possible death, and 39 could have led to serious toxicity. The quality of patient care seemed to have been positively affected by having the clinical pharmacist in the patient care area.

Interrelationships of human chorionic gonadotropin, human placental lactogen, and pregnancy-specific beta 1-glycoprotein throughout normal human gestation.

Human chorionic gonadotropin (hCG), human placental lactogen (hPL), and pregnancy-specific beta 1-glycoprotein (PSBG) were measured by radioimmunoassay in 270 samples of serum from women with uncomplicated pregnancies. All three proteins were significantly correlated with each other in individual samples of serum and with the estimated trophoblastic mass during the first trimester. No significant correlation could be demonstrated between the concentrations of hCG and PSBG in maternal serum during the second or third trimesters or between the concentrations of hCG and hPL during the second trimester. Levels of PSBG and hPL in serum were significantly correlated throughout all three trimesters. These findings suggest that the secretion of hCG, hPL, and PSBG may be regulated by similar control mechanisms during the first trimester of pregnancy. However, after this period, the factors that modulate the production of hCG differ from those that regulate the production of hPL and PSBG.

Comparative evaluation of two methods of natural family planning in Columbia.

Results of a comparative study of the ovulation method (OM) and symptothermal method (STM) of natural family planning in Colombia are presented. Recruitment of volunteer couples began in August, 1976, and continued through December, 1978, during which time 566 couples were randomly assigned to one or the other of the two methods. The study included 3 to 5 months of training in the method assigned, after which the couples entered the follow-up phase of the study. They remained in follow-up until (1) they dropped out or (2) the study closed in June, 1979. Total dropout rates were high for both methods of natural family planning. One year after entry into the follow-up phase of the study, net pregnancy rates were 24.2% for OM users and 19.8% for STM users. Gross pregnancy rates were 29.2% for OM and 26.1% for STM. Differences in pregnancy rates between the two methods were not statistically significant.

PIP: A comparative study of the use-effectiveness of the OM (ovulation method) and the STM (symptothermal method) of natural family planning was conducted in Bogota and Palmira, Colombia. The pregnancy rates obtained in the study were high for both methods and no significant difference was observed in the pregnancy rates for couples using the OM and for couples using the STM. The study was initiated by the government and the Javeriana University, sponsored by the World Health Organization, and designed and analyzed by the Department of Biostatistics of the University of North Carolina. The planned study was widely publicized and couples were urged to volunteer as study participants. 544 couples, who meet specified requirements, were recruited and randomly assigned to receive training in either the OM or the STM. Training lasted from 3-5 months. 57% of the participants dropped out during the training phase. The remaining 241 couples were then included in the formal follow-up phase of the study and were followed-up monthly for 1 year. Pregnancy rates were computed using both the life table method and the Pearl method. The net cumulative drop-out rate after 1 year of follow up for the 241 couples was 60.1% for OM users and 53.0% for STM users. Net cumulative rate of voluntary withdrawal was 30.3% for OM users and 26.0% for STM users, and the net cumulative pregnancy rate was 24.2% for OM users and 19.8% for STM users. The Pearl pregnancy rate was 33.8/100 users for the OM and 26.0/100 users for the STM users. There were no significant differences in the characteristics of OM and STM participants who took part in the follow-up phase nor between OM and STM drop-outs. The high drop-out and pregnancy rates observed in this study suggested that natural family planning was probably not an effective form of contraception for a large proportion of the Colombian population.

Maternal serum human chorionic gonadotropin concentrations and fetal sex prediction.

The feasibility of using maternal serum human chorionic gonadotropin (hCG) concentrations for prenatal sex prediction was examined. hCG was mesured in 822 serum samples from 560 women with uncomplicated pregnancies. Significantly higher hCG concentrations were found in the serum of women bearing female fetuses than in the serum of women bearing male fetuses during the third trimester, especially during the 10th lunar month. The data were utilized to construct probability graphs for fetal sex prediction based upon a single maternal serum hCG determination during the third trimester and during the 10th lunar month. However, the utility of these graphs is limited by the small proportion of pregnant women with serum hCG concentrations that were high or low enough to allow a prediction with high probability.