Bedform alignment in directionally varying flows.

Many kinds of sediment bedforms are presumed to trend either normal or parallel to the direction of sediment transport. For this reason, the trend of bedforms observed by remote sensing or by field observations is commonly used as an indicator of the direction of sediment transport. Such presumptions regarding bedform trend were tested experimentally in bidirectional flows by rotating a sand-covered board in steady winds. Transverse, oblique, and longitudinal bedforms were created by changing only two parameters: the angle between the two winds and the proportions of sand transported in the two directions. Regardless of whether the experimental bedforms were transverse, oblique, or longitudinal (as defined by the bedform trend relative to the resultant transport direction), they all had trends that yielded the maximum gross transport across the bedforms. The fact that many of the experimental bedforms were neither transverse nor parallel to the resultant transport direction suggests that transport directions cannot be accurately determined by presuming such alignment.

Pharmacokinetics of 111In-labeled OC-125 antibody in cancer patients compared with the 19-9 antibody.

We recently reported on the pharmacokinetics in 14 cancer patients of the 19-9 antibody radiolabeled with 111In. We have now repeated this investigation in 18 cancer patients using the OC-125 antibody, in part to compare the in vivo behavior of two murine monoclonal antibodies of the same subclass administered as the F(ab')2 fragments, by the same route and at the same dose. As in the earlier investigation, 1 mg of fragments was infused i.v., and organ quantitation was obtained for up to 72 h along with frequent blood and urine samples for chromatographic evaluation. Analysis of urine showed that activity clearance by this route amounted to 0.29%/h and consisted of labeled DTPA only in early samples and metabolic products thereafter. Analysis of serum samples often showed the presence of a high-molecular-weight species appearing within 24 h. This species is probably due to antibody binding to circulating antigen, although the percentage of circulating activity present as this species did not correlate well with circulating antigen levels. As before, organ accumulation was greatest in the liver, although levels were significantly reduced (12% compared to 20% of administered dose at 24 h, P less than 0.01). Plasma clearance was also significantly different: whereas the label in the case of the OC-125 antibody showed one-compartment clearance kinetics and remained in the plasma compartment, in the 19-9 case the label diffused to a second, unidentified compartment.

Human antibody response to the intravenous and intraperitoneal administration of the F(ab')2 fragment of the OC125 murine monoclonal antibody.

We have characterized the human immune response against murine monoclonal antibodies (HAMA) in 18 patients following administration of the F(ab')2 fragment of the murine monoclonal antibody OC125. OC125 is directed against the CA125 antigen, present on the surface of many human ovarian cancers. An affinity matrix was used to separate serum into immunoglobulin-containing and immunoglobulin-free fractions. HAMA titer was determined on the immunoglobulin fraction with an OC125 sandwich enzyme-linked immunosorbent assay (ELISA). All patients developed an HAMA response, despite the use of F(ab')2 fragments and small amounts (1-4 mg) of antibody. It may be that the intraperitoneal (i.p.) route provides a more marked HAMA response. Enzyme-linked sandwich immunoassays were also used to determine anti-isotype and anti-idiotype titers. Anti-isotype titers were analyzed with antigen irrelevant, isotype-matched murine antibodies and OC125-HRPO. Anti-idiotypes titers were assessed in a sandwich assay that utilized F(ab')2 and F(ab') fragments of OC125. The anti-isotype response tended to be of low titer and short duration, while the anti-idiotype response was of high titer and remarkably persistent. HAMA interfered in an unpredictable manner with the correct measurement of serum levels of CA125 in an enzyme immunoassay using OC125. Corrected values of CA125 could be obtained by measurement of antigen in the immunoglobulin-free fraction of serum. The response of one patient, who developed a markedly elevated anti-idiotype titer after serial i.v./i.p. injections, was further characterized and found to contain an antibody consistent with an anti-anti-idiotype to the CA125 antigen.

Radiation therapy for surgically proven para-aortic node metastasis in endometrial carcinoma.

The impact of para-aortic field radiation therapy upon survival was studied among 26 patients with para-aortic nodal metastases from carcinoma of the endometrium. Seventeen of these 26 patients received postoperative radiation therapy to the para-aortic field as a part of their primary therapy. Sixteen of the 17 also received adjuvant hormonal therapy. Nine of 17 patients (53%) are alive without evidence of disease (18-55 months) with a median survival time of 27 months. Of the remaining eight patients, six (35%) died of endometrial cancer at 6-38 months, with a median survival time of 14.5 months. Five of these patients had distant disease. Two of the 17 patients (12%) died of intestinal obstruction felt to be secondary to radiation enteritis, one of whom was disease free. No difference in survival was detected in patients treated with radiation therapy with microscopic versus macroscopic nodal involvement. Of the nine patients who did not receive para-aortic radiation, eight were treated with hormonal therapy (n = 6) or chemotherapy (n = 2). Seven patients died of disease from 5-28 months, with a median survival time of 13 months. One patient is alive at 12 months. Survival in the 17 patients treated with para-aortic radiation was better than the eight patients not treated with para-aortic radiation (p = 0.004). This survival difference remained significant for patients with microscopic but not macroscopic nodal disease. Para-aortic field radiation appears to improve survival, but has a significant complication rate, and should be reserved for patients with histologic evidence of para-aortic metastases.

Primary radiation therapy for endometrial carcinoma: a case controlled study.

PURPOSE: Primary radiation therapy is generally considered inferior to a surgical approach for patients with endometrial carcinoma and is reserved for patients with a high operative risk. These patients are usually elderly, have multiple medical problems and frequently die of intercurrent disease. To evaluate the efficacy of primary radiation therapy a case controlled analysis comparing corrected survival of patients treated with primary radiation to patients treated with surgical therapy with or without radiation therapy was performed. METHODS AND MATERIALS: Sixty-four patients treated with primary radiation therapy were retrospectively studied. A Kaplan-Meier product limit survival analysis was used to estimate survival among patients treated with primary radiation therapy. A case control study matched by clinical stage, tumor grade, and time of diagnosis was performed. The Mantel-Cox statistic was used to evaluated the equality of the survival curves. RESULTS: Primary radiation therapy was used to treat 9.0% of the patients with endometrial carcinoma during the study period. Cardiovascular disease, diabetes, age greater than 80 and morbid obesity were the most common indications. Ninety percent of patients had either Stage I or II disease. Forty-eight of the 64 patients (75%) completed treatment which included both teletherapy and brachytherapy. Ten patients received brachytherapy only. Twelve complications, both acute and chronic, occurred in eleven patients (17%). Intercurrent disease accounted for 13 of the 36 (36%) of the deaths. Clinical stage of disease and histologic grade of the tumor were significant predictors of survival, p = 0.0001 and p = 0.013, respectively. The case controlled study of Stage I and II patients treated by primary radiation therapy matched to surgically treated controls showed no statistical difference in survival. Dilatation and curettage after the completion of radiation therapy was predictive of local control, p = 0.003. CONCLUSION: Although surgery followed by tailored radiation therapy has become widely accepted therapy for Stage I and II endometrial carcinoma, even in patients who are a poor operative risk, the survival with primary radiation therapy is not statistically different.

The absorption of iron as supplements in infant cereal and infant formulas.

The absorption of iron was measured from isotopically tagged salts used in supplementing infant cereals and as the iron supplement in cow's milk and soy-based formulas. Iron as sodium iron pryophosphate and ferric orthophosphate were poorly absorbed from infant cereal (mean, smaller than 1.0%) and thus are not dependable sources of iron to meet the nutritional needs of infants. Reduced iron of very small particle size and ferrous sulfate when added to cereal was absorbed to a greater extent (mean, 4.0% and 2.7% respectively). For technical reasons, these two forms of iron had not been added to commercial cereal products because of discoloration, distribution problems of the iron in the product, and shortened shelf life. Therefore, at the present time, iron supplementation of infant cereals with sodium iron pyrophosphate, ferric orthophosphate, and reduced iron of large particle size does not provide a predictable and available source of iron to meet the needs of infants. Supplemental iron as ferrous sulfate in milk- and soy-based formulas gave a mean absorption of 3.4% and 5.4%. The iron supplements in these formulas can essentially meet the needs for dietary iron of healthy infants.

Use of ultrasonography in the difficult postmenopausal dilation and curettage.

Six patients from our series of 21 cases are presented to illustrate the use of real-time ultrasound to complete the D&C. Thirteen of the 21 had concomitant ultrasound because of stenosis of the cervix or vagina, three because of previous vaginal procedures that distorted the anatomy, and five because of concern regarding perforation.

Appendectomy in primary and secondary staging operations for ovarian malignancy.

Appendectomy was performed at primary or secondary staging operations in 100 patients with ovarian malignancies. Of 80 patients who underwent appendectomy at the time of their primary surgery, 25 (31.2%) had appendiceal metastases. Among 47 patients who were believed to have disease limited to the pelvis at the time of surgery--stage I (N = 34), II (N = 7), IIIA (N = 5), and those designated stage IIIC solely on the basis of microscopic para-aortic nodal metastasis (N = 1)--the appendix was involved with disease in only two patients (4.3%). However, among 33 patients with advanced disease--stage IIIB (N = 6), IIIC except those designated IIIC solely on the basis of microscopic paraaortic nodal metastasis (N = 19), and IV (N = 8)--the appendix was involved with disease in 23 patients (69.7%) (P less than .001). Poorly differentiated tumors and serous histologic cell types more frequently metastasized to the appendix (64, 15, 6, and 8% for grades 3, 2, and 1 and borderline histology, respectively; P less than .001; and 48, 13, and 8% for serous, endometrioid, and mucinous; P less than .001). Of 20 patients who underwent appendectomy at their secondary staging procedure, two had metastases. Metastatic disease in the appendix was microscopic in nine of 27 patients. Because the frequency of appendiceal metastasis is similar to that of other metastatic sites in stages I and II ovarian cancer, it should be removed at primary staging procedures. Appendectomy should also be performed in patients with advanced ovarian malignancies if it contributes to cytoreduction or at the time of secondary staging procedures.

Prognostic significance of estrogen and progesterone receptors in epithelial ovarian cancer.

Estrogen and progesterone receptor assays were analyzed from epithelial ovarian cancer in 123 patients to determine the prognostic significance of receptor results. In 110 (89%), assays were performed at diagnosis and in 13, assays were performed after previous therapy. Estrogen receptor determinations were positive (above 10 fmol/mg) in 75 cases (61%), progesterone receptor determinations were positive (above 3 fmol/mg) in 35 (28%), and both were positive in 20 (16%). Progesterone receptors were more frequently positive (53%) in tumors of endometrioid histology than with other histologic types (P = .01). Thirty-one subjects had a second assay; estrogen receptors were positive in 16 cases (52%), progesterone receptors were positive in five (17%), and both were positive in five (17%). Synchronous and metachronous assays were in agreement in 60-79% of the cases. By multivariate analysis, positive estrogen receptor, progesterone receptor, or both did not predict response to chemotherapy, negative second-look findings, or survival. Thirty-one women received hormonal therapy; one of 26 evaluable subjects had a partial response and four (13%) maintained stable disease for at least 6 months (6-21 months). Positive receptors did not predict hormonal response or disease stabilization.

Primary adenocarcinoma of the breast arising in the vulva.

Primary adenocarcinoma of ectopic breast tissue in the vulva has been reported in only four instances. A fifth case, in which estrogen and progesterone receptors were present, is described. Estrogen and progesterone receptor studies may be helpful in identifying adenocarcinoma of uncertain origin.

Serial serum CA 125 measurements for evaluation of recurrence in patients with endometrial carcinoma.

OBJECTIVE: To evaluate the usefulness of serum assays for CA 125 to detect recurrent endometrial carcinoma. METHODS: Two hundred sixty-six patients were studied with 1101 post-treatment assays. Patients were categorized as low, medium, or high risk based on surgical-pathologic findings. CA 125 values were analyzed with respect to each patient's disease status. RESULTS: Serial CA 125 levels were elevated (greater than 35 U/mL) in 19 of 33 patients (58%) with recurrent disease. Among 236 surgically treated patients, 97 (41.1%), 42 (17.8%), and 97 (41.1%) were considered low, medium, and high risk, respectively. None of the low-risk and only two (4.7%) of the medium-risk patients developed recurrent disease. One of the latter patients was detected based on an elevated CA 125 level alone. Twenty-seven (27.8%) of the high-risk patients developed recurrent disease, 23 of whom had elevated pre-treatment CA 125. Fifteen of 16 (94%) with recurrent disease had an elevated CA 125 level. Nine of 12 patients with papillary serous carcinoma experienced recurrence; eight of these nine had elevated CA 125 levels at diagnosis and recurrence, in contrast to only one patient with a normal pre-treatment level (P = .018). False elevations were noted in 13 patients, 12 of whom had received radiation therapy. CONCLUSIONS: CA 125, if elevated at diagnosis of endometrial carcinoma, is an important marker for recurrent disease. The use of serial CA 125 assays is most beneficial in diagnosing recurrence in a high-risk population, including patients with papillary serous carcinomas. False elevations may occur following radiation therapy.

Factors affecting graft force in surgical reconstruction of the anterior cruciate ligament.

The effect of the maximum unloaded graft length (Lo) and femoral fixation hole location on graft force with the knee under anteriorly directed tibial loads was measured in five fresh cadaver knees with a reconstruction of the anterior cruciate ligament (ACL). The reconstruction was performed using a composite graft consisting of the semitendinosus and gracilis tendons augmented with the Kennedy ligament augmentation device (LAD). Buckle transducers were used to measure ligament and graft forces. The total graft force was adjusted to match the intact ACL at 30 degrees flexion using a force-setting method so that a standardized reference configuration could be repeatedly obtained. The graft force was highly sensitive to Lo, typically changing by 50% with a change in Lo of 3 mm. Variation in femoral hole location of 5 mm anterior, posterior, proximal, and distal to the anatomic position produced changes in graft force, particularly at 60 degrees and 90 degrees flexion; however, these changes were not statistically significant. The effect of femoral hole location varied considerably between knees. This variability makes predicting proper hole placement difficult, and suggests the need to adjust each knee at surgery to account for this variable femoral hole position sensitivity.

Method for setting total graft force and load sharing in augmented ACL grafts.

The objective of this study was to develop a method for obtaining a controllable and reproducible immediate postoperative mechanical state in a knee with an anterior cruciate ligament (ACL) reconstruction. This method, called the force-setting technique, was demonstrated using a composite graft consisting of the middle third of the patellar tendon with bone blocks (PT) and the ligament augmentation device (LAD). The total graft force was set to match the force in the intact ACL at 30 degrees flexion with the knee under the same standardized external load, while at the same time the load sharing between the biologic and augmentation components was controlled. The total graft force was set to match the ACL force three separate times in each knee, with ratios of load sharing set at the following levels: 50% PT-50% LAD, 25% PT-75% LAD, and 75% PT-25% LAD. ACL, PT, LAD, and collateral forces were measured using buckle transducers, and three-dimensional knee motion was measured using an instrumented spatial linkage as 90 N anteriorly directed tibial loads were applied to eight specimens at 0 degree, 30 degrees, 60 degrees, and 90 degrees flexion with an intact ACL, an excised ACL, and the three load-sharing reconstruction states. The total graft force could be consistently set to within an average of 2% of the intact ACL force at 30 degrees flexion, and load sharing between the graft segments could be set to within an average of 5.1% of the desired ratio at 30 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)

Cochlear polyamines: markers of otitis media-induced cochlear damage.

High-performance liquid chromatography (HPLC) set to the femtomole [corrected] sensitivity level was used to identify and quantify the polyamines spermidine and spermine as well as the diamine putrescine in the different tissues of the inner ears of guinea pigs with experimentally induced otitis media. The tissues examined were the lateral wall (stria vascularis and the spiral ligament), the organ of Corti, and the cochlear nerve. The difference in polyamine profile in the different tissues of the control noninfected guinea pigs suggests a relation to the particular function of each of these tissues [see erratum notice re: preceding sentence]. The difference in polyamine profile in infected different inner ear tissues compared to controls encourages the assumption that the polyamines may be involved in a repair process of the inner ear after injury and that they may be considered as biochemical markers for inner ear damage secondary to acute otitis media.

Hyperuricemia and locomotor activity in developing rats.

This research was motivated by the previous finding that serum uric acid levels correlate with symptoms of hyperactivity in normal children. We attempted, therefore, to investigate this relationship in an animal model. Dose and time relationships between allantoxanamide-induced heightened serum uric acid and locomotor activity were investigated. A dose- and time-dependent relationship was shown between serum uric acid levels and allantoxanamide. Those doses of allantoxanamide which elevated serum uric acid produced time-dependent changes in locomotor activity. In the first two hours following injection, activity increased relative to controls, in the next two-hour block activity decreased, only to rise again above control levels in the third two-hour period. The possible role of uric acid and allantoxanamide are discussed in relation to these complex changes in activity.

Effects of uric acid and caffeine on A1 adenosine receptor binding in developing rat brain.

Previous studies have demonstrated that elevated levels of serum uric acid or caffeine are associated with increased locomotor activity in rats and humans. Since uric acid and caffeine are structurally similar, it was hypothesized that these compounds alter locomotor activity through a common neural mechanism, specifically by acting as receptor antagonists at adenosine A1 binding sites. In vitro competition of caffeine and uric acid against the A1 agonist, [3H] cyclohexyladenosine ([3H]CHA), was conducted using homogenates of adult rat forebrain. Caffeine effectively competed for the A1 binding site as previously reported (IC50 = 107 microM), but uric acid failed to compete with [3H]CHA binding at concentrations within a relevant physiological range. Nevertheless, in vivo experiments indicated that chronic elevation of uric acid following allantoxanamide treatment of male rats on days 4-27 of life significantly decreased A1 receptor binding in the striatum, a region traditionally implicated in mammalian locomotion. In contrast, chronic caffeine treatment on days 4-27 of life caused an increase in A1 receptor binding in the cortex similar to increases reported previously in whole brain. These changes in A1 receptor binding following chronic elevation of uric acid or caffeine did not persist in rats that had been withdrawn from allantoxanamide or caffeine treatment for 14 days. Results from in vitro and in vivo experiments indicate that despite a similar molecular structure uric acid does not act by the same mechanism as caffeine to increase locomotor activity in rats.

Preoperative CA-125 levels predict poor prognostic pathologic features in early stage, FIGO grade 1 and 2 endometrial adenocarcinoma.

Preoperative CA-125 levels were studied in patients with favorable histology and early clinical stage endometrial adenocarcinoma to determine its ability to predict the presence of poor pathologic prognostic features on final pathology. One hundred and one patients with clinical stage I (N = 65) or II (N = 19) or diagnosed by endometrial curettage (EMC) only (N-17) with grade 1 or 2 endometrial adenocarcinoma without gross cervical involvement underwent preoperative CA-125 levels. Final pathology was reviewed for five poor prognostic pathologic features: FIGO grade 3 histology, unfavorable histologic type (sarcoma, clear cell, or papillary serous), invasion into the outer third of the myometrium, extension to the cervix, and extra-uterine metastases. Fifteen patients (14.9%) had CA-125 levels greater than 30 IU ml-1. Of these 15 patients, 12 had one or more of the five poor prognostic pathologic features (positive predictive value 80.0%, specificity 95.8%, P < 0.0001). However, since 30 of the 101 patients were found to have one or more of these poor prognostic pathologic features the sensitivity was only 40.0%. When clinical stage I patients were analyzed separately three patients (4.6%) had CA-125 levels greater than 30 IU ml -1 (positive predictive value 100%, specificity of 100%, sensitivity of 21.4%, P = 0.008). For patients with clinical stage II carcinoma, CA-125 was not predictive of pathologic findings except as a negative predictor of disease in a subgroup of patients whose endocervical curettage (ECC) demonstrated carcinoma unattached to endocervical tissue. In patients diagnosed by EMC only, an elevated CA-125 level was associated with poor prognostic pathologic features (P = 0.001). An elevated preoperative CA-125 reliably predicts advanced disease even in patients with apparently favorable histology and clinical stage, however the sensitivity of this method remains low.

Brachytherapy for early endometrial carcinoma: a comparative study with long-term follow-up.

The current study was undertaken to evaluate the effect of preoperative uterine or postoperative vaginal brachytherapy compared to no adjuvant therapy on the disease-free interval, sites of recurrence, and survival in favorable stage IB endometrial carcinoma. One hundred and forty-six patients with FIGO grade 1 and 2 endometrial carcinoma and 1-33% myometrial invasion treated between 1974 and 1992 were retrospectively studied. The use of brachytherapy varied among the treating physicians during the study period. A Kaplan-Meier survival analysis was used to estimate disease-free survival and differences between treatment groups were evaluated with the Mantel-Cox statistic. Recurrent disease occurred in 7 patients (5.3%). Vaginal recurrences accounted for 6 of the 7 sites of recurrences. Recurrences occurred in 1.3% of grade 1 vs. 8.7% of grade 2 tumors (P = 0.04). Among 69 grade 2 tumors, recurrences occurred in 7.5% of those treated with brachytherapy vs. 10.3% of those not treated (P = 0.68). Brachytherapy did not affect the disease-free or overall survival. No serious complications directly related to therapy occurred. Vaginal recurrences occur even in early endometrial carcinoma. This study demonstrates no apparent benefit to brachytherapy. A larger study would be required to see a recurrence or survival difference.

Comparison of the biochemistry of proteoglycans isolated from normal, idiopathic scoliotic and cerebral palsy spines.

Six levels of anulus and nucleus were obtained from each of three spines: one with idiopathic scoliosis, one with cerebral palsy, and one age-matched control. Proteoglycans from all spines had the same extractability and distribution in the associative and dissociative cesium chloride density gradients. In all cases, the anulus differed from the nucleus samples in terms of all the parameters studied. There was no difference between the cerebral palsy and idiopathic scoliotic values. However, they both differed from the control values, having significantly higher levels of aggregate and larger nonaggregating monomers, but no significant differences in proteoglycan monomer chemistry. Results indicate that idiopathic scoliosis may not be the result of a biochemical alteration in proteoglycan but that curvature per se may lead to an alteration in the proteoglycan composition, particularly in the nucleus pulposis.

Skiing injuries.

Skiing is a winter sport enjoyed by approximately 200 million people worldwide. An overall injury rate of approximately 3 per 1000 skier-days means that skiing certainly is the riskiest sport undertaken by adults on a routine basis. However, the data suggest that one can anticipate years of enjoyable recreation free from injury. Many troubling injuries, particularly to the lower leg, have shown a steady decline over the past 20 to 30 years because of advances in boot design and binding capabilities. In addition, as information has been gathered regarding the importance of proper maintenance and adjustments, equipment now available can protect a skier more effectively than at any time in the past. Nevertheless, skiing continues to present inherent risks that can be minimized through the following strategies: 1. Enroll in a conditioning program before skiing that focuses on strength and endurance components particularly of the legs and back. 2. Have equipment that is compatible with the skier both from the standpoint of size and expertise. 3. Have equipment adjusted professionally. 4. Do routine testing of binding releases each day before beginning to ski. 5. Ski under control at speeds that are consistent with ability. 6. Stop skiing before fatigue becomes the limiting factor.