Enhanced survival in Pseudomonas aeruginosa septicemia associated with high levels of circulating antibody to Escherichia coli endotoxin core.

We studied the relationship between serum antibodies to the cross-reactive endotoxin core of Escherichia coli and survival following Pseudomonas aeruginosa septicemia. Core glycolipid was purified from the outer cell membrane of a uridine diphosphate galactose 4-epimerase-deficient rough mutant E. coli (J5 strain), characterized, and used as the antigen in a quantitative enzyme-linked immunosorbent assay (ELISA) to measure core-specific IgG and IgM antibodies. 43 patients with Pseudomonas septicemia, among whom there was a mortality of 42%, were evaluated. Core-specific antibody concentrations in acute sera ranged from 1 to 49 micrograms/ml in the case of IgG and from 1 to 200 micrograms/ml for IgM. Core-specific antibodies of both isotypes were higher in patients who survived compared with those who succumbed to their septicemias (mean, microgram/ml +/- SEM, 26 +/- 3 vs. 14 +/- 4, P = 0.005 for IgG, and 55 +/- 12 vs. 18 +/- 5, P = 0.009 for IgM). Although total IgG levels were also higher in acute sera from survivors compared with nonsurvivors (mean, mg/dl +/- SEM, 1,120 +/- 99 vs. 694 +/- 119, P = 0.004), total IgM levels were virtually identical in the two groups (146 +/- 23 vs. 148 +/- 48, P = 0.52). Conversely, patients with core-specific IgG levels greater than 10 micrograms/ml at the onset of septicemia had better survival than those with levels less than 10 micrograms/ml (79 vs. 14%, P less than 0.001), and patients with core-specific IgM levels greater than 30 micrograms/ml had better survival than those with levels less than 30 micrograms/ml (81 vs. 44%, P = 0.01). In comparison, patients with total IgG levels greater than 1,000 mg/dl also had better survival than those with levels less than 1,000 mg/dl (82 vs. 42%, P = 0.01), while those with total IgM levels greater than 150 mg/dl showed somewhat less improvement in survival compared with those with levels less than 150 mg/dl (71 vs. 50%, P = 0.12). Core-specific IgM was highly correlated with core-specific IgG (r = 0.52), but not with type-specific anti-lipopolysaccharide (r = 0.13) or anti-toxin A (r = 0.12) antibodies, or with total IgG (r = 0.28) or IgM (r = 0.31). In contrast, core-specific IgG correlated somewhat more closely with type-specific antibodies (r = 0.36), and with total IgG (r = 0.51) and IgM (r = 0.52). Stepwise linear discriminant analysis indicated that type-specific antibody levels were the best predictor of outcome, among those antibodies examined, followed by anti-core IgM. Although anti-core IgG, anti-toxin A, and total IgG levels all correlated individually with survival, none augmented the prognostic power of type-specific antibodies in combination with anti-core IgM, which together predicted outcome accurately 73.5% of the time. Host factors not significantly associated with anti-core antibody levels included rapidly fatal underlying disease, age, sex, leukopenia, and prior treatment with cytotoxic drugs. In contrast, prior steroid therapy was associated with low levels of both core-specific IgG and IgM (P < 0.05). These data suggest cross-protective activity against P. aeruginosa septicemia of naturally occurring antibodies to the endotoxin core of E. coli. Anti-core antibodies, particularly of the IgM isotype appear to augment the more specific protective immunity engendered by antibodies to the O-specific side chains of Pseudomonas lipopolysaccharides. This cross-protective immunity likely applies to other Gram-negative pathogens as well.

Epidemiology of human immunodeficiency virus in families in Lusaka, Zambia.

Persons living in the same household as index patients with AIDS or ARC in Lusaka, Zambia were clinically and serologically evaluated for HIV-1 infection. In the 150 households of male index cases, 92 (61.3%) of their spouses were infected, compared with 57 (73.1%) of the spouses of the 78 female index cases. The more advanced the clinical stage of illness in the index cases, the greater the probability of HIV infection in the spouse (RR = 4.44), and the more likely the spouse was symptomatic. Four of the 11 spouses who seroconverted to HIV had also had sexual intercourse at a time when their HIV-infected partner had genital ulcers (RR = 7.45). Of 144 children under 5 years of age, 36 (25.0%) were infected, all had infected mothers and were the last to be borne in all but one household. Three of 120 children 5 to 10 years of age were also infected, presumably through perinatal transmission. Forty-six of 52 discordantly infected couples followed for 1 year continued to have unprotected vaginal intercourse, and 11 (21.2%) of these seroconverted to HIV. There were no HIV infections that could be attributed to transmission by other means than heterosexual intercourse between spouses or by perinatal infection in children borne of infected mothers. The study suggests that there is an increasing risk of HIV heterosexual transmission as infection progresses in the infected partner, and that more effective counseling is needed to prevent it.

PIP: An investigation of members of households of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) in Lusaka, Zambia, revealed a high rate of human immunodeficiency virus (HIV) infection in marital partners, regardless of the sex of the index case. The study, conducted in August 1985-June 1987, involved individuals in 244 households of index patients diagnosed with AIDS or ARC. 92 (61.3%) of the 150 male index cases and 57 (73.1%) of the 71 female index cases had an HIV-infected marital partner, and the severity of HIV disease (AIDS or ARC) in the index partner was linearly associated with the severity of HIV disease in the spouse. 10 (25.6%) of 39 uninfected wives of HIV-positive men compared with only 1 (7.7%) of 13 uninfected husbands seroconverted during the 1st year of follow- up. 4 of the 11 spouses who seroconverted during this period reported sexual intercourse at a time when their HIV-infected partner had genital ulcers. Of the 264 children under 10 years of age from 154 households with an HIV-positive adult who were also evaluated as part of this study, 39 (14.8%) were infected--26 had ARC and 13 had asymptomatic infection. Only 3 of the infected children were older than 5 years of age; the mean was 24.9 months. In all cases, transmission in children was attributable to HIV infection in the mother. These findings suggest a need for more aggressive counseling to reduce the sexual transmission of HIV infection to uninfected partners. 46 of 52 discordantly infected couples followed for 1 year continued to have unprotected vaginal intercourse--a factor that certainly contributed to the high concordance of HIV infection among the couples in this study.

Effect of IL-1alpha on the release of norepinephrine in rat hypothalamus.

The increased release of norepinephrine (NE) in the brain as part of the 'acute phase response' has been postulated to result from a direct action of IL-1 on the hypothalamus. To test whether the effects of IL-1alpha were direct, we carried out in vivo experiments using microdialysis and measured NE release in the hypothalamus using high pressure liquid chromatography (HPLC). Two groups of male Sprague Dawley rats were either injected intraperitoneally with 1 ml of IL-1alpha (2 microg/ml) or had IL-1alpha 2 microl (100 ng/ml) infused directly into the medial hypothalamus. A significant increase in extracellular hypothalamic NE was observed in the animal group treated with IL-1alpha intraperitoneally and not in the controls or the group treated with IL-1alpha intracerebrally. One-way ANOVA showed a significant effect of drug and route of administration with the ip IL-1alpha treated group, differing from all other groups (vehicle ip, IL-1alpha ic, and vehicle ic). Therefore these findings suggest that some aspects of IL-1alpha actions on the HPA may be indirect requiring other intermediate steps or mediators outside the central nervous system.

Opsonic activity of commercially available standard intravenous immunoglobulin preparations.

Several standard intravenous immunoglobulin G (IVIG) products are available in the United States and have been used with the intent to treat or prevent infections in neonates. We evaluated more than 100 lots of IVIG, from 6 products, to determine the amount of opsonic antibody against neonatal pathogens. Neutrophil-mediated opsonophagocytosis was used to determine opsonic activity in these preparations for Staphylococcus epidermidis; Haemophilus influenzae type b; Streptococcus pneumoniae serotypes 3, 14 and 19; Group B Streptococcus serotypes Ia, Ib, Ia/c, II and III; and Escherichia coli (K1). Pathogen-specific opsonic activity of the lots tested ranged from undetectable to 1:80 and was detectable in < 10% to > 90% of lots tested depending on the organism and manufacturer. Within an IVIG lot there was variable opsonic activity against different strains or serotypes of the same organism. Opsonic activity was significantly (P < or = 0.05) affected by the manufacturer's donor pool and less so by the manufacturing method. We conclude that the pathogen-specific opsonic antibody activity of an IVIG lot is: (1) highly variable for several common neonatal pathogens; (2) predominantly dependent on the donor pool and not the manufacturing method. Clinicians may more appropriately select therapy if the pathogen-specific antibody content of IVIG products by lot are known. In the future neonatal IVIG research should focus on using preparations with known pathogen-specific antibody activity.

Normal erect swallowing. Normal function and incidence of variations.

Of 871 candidates presenting for upper gastrointestinal examinations, 16 met the rigorous criteria established for selecting asymptomatic normal volunteers. Frame-by-frame evaluation of their videorecorded pharyngeal swallow confirmed many observations made previously utilizing cine recording at much higher radiation dosages. In addition, new observations were made: the nasopharynx may not occlude until the bolus is entirely within the pharynx; air mixes with the bolus if the swallow is an "open" type; the epiglottis always inverts in normal individuals regardless of the type of swallow ("open," air filled oro-and hypopharynx into which the swallowed bolus is dropped; "closed," airless oropharynx into which the swallowed bolus is pushed by a continuous peristaltic drive of the tongue and palate, thus reconstituting the pharyngeal space); laryngeal descent may aid in stripping the bolus from the pharynx; the vestibule may not completely close during the swallow and the larynx can still be impervious to the bolus; the peristaltic wave does not begin until the bolus has breeched the cricopharyngeus; the cricopharyngeus may be seen frequently in normal individuals, but does not delay the passage of the bolus; asymmetric flow of the bolus around the larynx is common and may not be the result of epiglottic tilt or head positioning.

Timing in the normal pharyngeal swallow. Prospective selection and evaluation of 16 normal asymptomatic patients.

A review of timing of pharyngeal events with radiography has been made. A prospective selection of normal asymptomatic patients presenting for a gastrointestinal evaluation was made and timing of 55 events in the videorecorded pharyngeal swallow in these patients was performed. Only 16 normal asymptomatic patients as defined for selection were found among 870 patients presenting for gastroesophageal examination. A detailed description of their timing observations is presented. The timing data were used to temporally order events in the pharyngeal swallow. This ordering of events in the pharyngeal swallow and the data upon which it is based are reported here in detail.

Ranking: a year three follow-up in a different institution.

Ranking residents as a means of semiobjective evaluation of their overall performance was described in 1985. The predictive nature of pooled faculty ranking of residents was stressed. Ranking of resident total scores on The American College In-training Examination and American Board of Radiology written examination was noted to be statistically related to the pooled faculty ranking. Similarly, the faculty ranking was predictive of itself in subsequent rankings. A cohesiveness of faculty consensus was present such that small numbers (five minimum) were predictive of larger groups of participating faculty. All reported observations persist in the new institution. Exceptions to expected residency level of training stratification (eg, third-year residents ranking in the midst of first-year residents, second-year residents ranking above many third-year residents) continue to be the most useful observation in counseling residents. Additional information reported includes sensitivity of the ranking to improvement or nonimprovement of probated residents.

Evaluation of radiology resident cognitive performance.

Using radiographs and slides in three formats, we objectively tested the cognitive performance of 16 residents during an 8-month period. One format tested individual residents with radiographs and required only that a list of findings be provided within a week. For the second method, radiographs were projected to a small group of residents and a single diagnosis for each of ten cases was required. The third format required a larger group of competing residents to view projected slides of ten loosely defined but thematically connected cases and develop one diagnosis. Two of the test formats correlated significantly with a Spearmen rank, r = .50 or better (P less than .025) with a ranking based upon total score on the American College of Radiology Inservice Examination. All three test formats had a Spearmen rank r = .50 or better (P less than .05) when compared with pooled ranking performed by the staff radiologists.

Ranking: a reproducible semiobjective means of evaluating overall resident performance.

Eleven staff radiologists evaluated resident performance by independent subjective ranking regardless of residency year. A pooled ranking correlated with a ranking obtained from the total raw score of the American College of Radiology (ACR) Inservice Examination (P less than .005). The staff pooled ranking had a Spearman rank correlation, r = .70, with resident overall performance upon the ACR Inservice Examination. The pooled ranking had a Spearman rank correlation, r = .90, with a subsequent pooled ranking obtained six months later (P less than .0001). This method of ranking accurately predicts ACR Inservice Examination performance and appears to evaluate the objectivity of the staff radiologists involved.

Selecting radiology resident candidates.

Radiology resident candidate selection has become a burdensome, subjective, and somewhat arbitrary process. Because the luxury of many well-qualified candidates exists, there is an obligation to select them as honestly, equitably, and objectively as possible. Two years were spent in revising and modifying the resident selection process to make it more uniform and more efficacious. An application scoring form was devised to extract uniform pertinent information from the original application form. Candidates could then be ranked according to a numerical score derived from the form. This allowed easy selection of top candidates to be interviewed. A new interviewing scoring form was developed to include desirable characteristics of resident candidate performance. This form was also devised in such a way as to be easily scored and to allow selection of the top 20 to 25 candidates. These candidates were then ranked by participating faculty members while reviewing their application score forms and their interview forms. Positions for the residency training program were offered according to the ranking. The usefulness of both new forms was evaluated and confirmed by correlating form scores with faculty ranking of academic performance of current residents in the training program.

Teaching concepts of clinical measurement variation to medical students.

An exercise in clinical epidemiology was developed for medical students to demonstrate the process and limitations of scientific measurement using models that simulate common clinical experiences. All scales of measurement (nominal, ordinal and interval) were used to illustrate concepts of intra- and interobserver variation, systematic error, recording error, and procedural error. In a laboratory, students a) determined blood pressures on six videotaped subjects, b) graded sugar content of unknown solutions from 0 to 4+ using Clinitest tablets, c) measured papules that simulated PPD reactions, d) measured heart and kidney size on X-rays and, e) described a model skin lesion (melanoma). Traditionally, measurement variation is taught in biostatistics or epidemiology courses using previously collected data. Use of these models enables students to produce their own data using measurements commonly employed by the clinician. The exercise provided material for a meaningful discussion of the implications of measurement error in clinical decision-making.

Effects of aspirin, dipyridamole, and dibutyryl cyclic adenosine monophosphate on platelet-derived growth factor A chain mRNA levels in human saphenous vein endothelial cells and smooth muscle cells.

Aspirin and dipyridamole have frequently failed to control intimal hyperplasia in vascular grafts in animal and clinical trials. These trials were based on the concept that the smooth muscle mitogen, platelet-derived growth factor (PDGF) released from platelets, was a major cause of intimal hyperplasia. Both endothelial and smooth muscle cells (ECs and SMCs), however, can also release PDGF-like SMC mitogens that might cause intimal hyperplasia. We therefore tested whether aspirin and dipyridamole alone or together can affect PDGF-A chain mRNA levels in cultured human saphenous vein ECs and SMCs. Cultures were exposed for 72 hours to 3 x 10(-5) mol/L aspirin and/or 5 x 10(-6) mol/L dipyridamole. Cellular RNA was then extracted, and PDGF-A chain mRNA signal levels were measured by a reverse transcription/polymerase chain reaction method. mRNA for glyceraldehyde-3-phosphate dehydrogenase was used as a constitutively expressed control RNA species. Signal strength on Southern blots of amplified polymerase chain reaction products was measured by densitometry. Neither aspirin nor dipyridamole alone or together reduced the ratio (PDGF-A chain signal/glyceraldehyde-3-phosphate dehydrogenase signal) below that of control cultures. PDGF-A chain expression was not a constitutive artifact of culture because dibutyryl cyclic AMP (5 x 10(-4) mol/L) reduced PDGF-A chain signal from a control index of 1.0 to 0.5 +/- 0.1 (mean +/- SE) (n = 3; p less than 0.05) in EC cultures and to 0.2 (mean) (n = 2) in SMC cultures. These data may explain why aspirin and dipyridamole fail to reduce intimal hyperplasia in some animal and clinical trials despite effective inhibition of platelet aggregation.

Distant metastasis from a carcinoid tumor of the appendix less than one centimeter in size.

The presentation and management of a patient with liver metastasis from a 0.6 cm carcinoid tumor of the appendix is presented. This is the first documented case of distant metastasis from a carcinoid of the appendix less than 1 cm in size. Histopathologic, immunohistochemical, and electron microscopic studies support the appendiceal carcinoid as being the primary neoplasm. Invasion of the mesoappendix was the only finding to suggest potentially aggressive behavior. We reviewed the literature and found 414 previously reported cases that provided complete information regarding tumor size, mesoappendiceal invasion, and presence of metastasis. For the entire group the frequency of metastasis was related to tumor size greater than 2 cm (p less than 0.0001) and invasion of the mesoappendix (p less than 0.0001). After dividing the group based on size, mesoappendiceal invasion was related to metastasis in those tumors less than 2 cm in size (p less than 0.0001) but not in tumors larger than 2 cm (p = 0.1538).

Both lisinopril and verapamil reduced platelet-derived growth factor-A chain mRNA levels in human saphenous vein endothelial cells stimulated by thrombin.

BACKGROUND: Both angiotensin-converting enzyme inhibitors and calcium channel blockers decrease postinjury intimal thickening in vivo, but their mechanisms of inhibitory action are unclear. Expression of the gene for platelet-derived growth factor (PDGF), a smooth-muscle mitogen, in endothelial cells (ECs) after vessel injury has been postulated to cause intimal thickening. In this study, we tested whether lisinopril, an angiotensin-converting enzyme inhibitor, or verapamil, a calcium channel blocker, would suppress the PDGF gene expression in stimulated human saphenous vein ECs. METHODS: Drugs were added to replicate EC cultures 30 minutes before adding 10 units/ml alpha-thrombin. Changes in PDGF-A chain mRNA levels were measured by Northern blot analysis or reverse transcription-polymerase chain reaction method. PDGF-AA homodimer in conditioned media was measured by ELISA: RESULTS: Lisinopril attenuated the induction by thrombin of PDGF-A chain mRNA levels significantly in human ECs at doses of 10(-6) mol/L and 10(-5) mol/L (p < 0.05) and appeared to decrease PDGF-AA homodimer released in conditioned medium. Verapamil also reduced thrombin induction of PDGF-A chain mRNA levels significantly at a dose of 10(-5) mol/L (p < 0.05) and appeared to reduce PDGF-AA homodimer secretion. CONCLUSIONS: These data suggest that one means by which lisinopril and verapamil both suppress intimal thickening might be inhibition of PDGF-A chain gene expression in ECs regrowing over vessel injury areas that are sites of thrombin generation.

Primary and preventive care services provided by obstetrician-gynecologists.

OBJECTIVE: To determine the level and types of primary and preventive care services delivered by obstetrician-gynecologists. METHODS: A self-administered questionnaire was mailed to a random sample of 1250 obstetrician-gynecologists practicing in the United States. The response rate was 71%. RESULTS: Fifty-three percent of the respondents indicated that they provide primary and preventive care during more than half of their practice time. Although obstetrician-gynecologists provide a wide range of preventive services, the proportion of doctors providing any specific service varies. Whereas virtually all (92% or more) obstetrician-gynecologists provide or order blood pressure screening, breast examinations, mammography, and Papanicolaou tests, only six of ten report regular cholesterol screening for most of their patients. A higher percentage of female obstetrician-gynecologists, who are on average younger than their male counterparts, report that they provide primary preventive services to most of their patients. CONCLUSION: The majority of obstetrician-gynecologists provide a wide range of primary and preventive care services to their patients, although there is variability in the proportion of doctors providing any specific service to most (60% or more) of their patients.

Antepartum screening in the office-based practice: findings from the collaborative Ambulatory Research Network.

OBJECTIVE: To examine utilization patterns of four antepartum screening tests by office-based obstetricians. METHODS: The population surveyed was the Collaborative Ambulatory Research Network, a voluntary subset of 550 ACOG fellows from 130 practices participating in data collection regarding ambulatory practices. Responses from self-administered questionnaires concerning screening for hepatitis B, gestational diabetes, neural tube defects, and trisomy 21 were analyzed. RESULTS: Hepatitis screening was performed by all practices with 95% (2750 of 2886) of women tested; however, only 55% (six of 11) of at-risk newborns received treatment. For gestational diabetes screening, 94% (116 of 124) administer a 50-g glucose load to all parturients, regardless of risk factors, two-thirds initiate further testing for a 1-hour post-load glucose of 140 mg/dL or greater, and 34% do so at lower glucose levels (130-135 mg/dL). For neural tube defect screening, 92% (95 of 103) offer maternal serum alpha-fetoprotein (MSAFP) screening although when results are elevated, further recommendations are varied. For women under 35 years of age, 84% (87 of 103) offer serum screening for trisomy 21 risk, most (68%) with double or triple (MSAFP, hCG, and estriol) markers. For women over 35 years, a majority (87%) offer serum screening, although half do so only if amniocentesis is declined for age risk alone. The relatively high initial positive rate and poor specificity of serum screening were underappreciated by a large number of respondents. CONCLUSION: Increased initial and continuing education of antenatal care providers is warranted if these screening tools are to perform optimally within office practices.

Patient satisfaction with collaborative practice.

OBJECTIVE: To gather information on women's perceptions of the services delivered in collaborative obstetrics and gynecology practices and to determine whether patients perceive a difference in the delivery of services in a variety of practice settings. METHODS: A cross-sectional patient satisfaction survey was developed by the Collaborative Practice Advisory Group of ACOG. Ten collaborative practices were selected to participate: five in private offices, two in clinics, two in health maintenance organizations, and one in the military. Between April 15 and May 15, 1994, 3257 completed surveys were obtained for analysis. RESULTS: Between 71% and 92% of women, depending upon the practice setting, agreed with statements regarding the possible benefits from being cared for in a collaborative practice. The majority (75-92%) expected services provided in a collaborative practice to differ from those provided in a noncollaborative practice. Women making their first visit to a collaborative practice expected quicker appointments, more time with the provider, more health information, and more specific diet information than did women who had previously been seen in such a practice. There were minimal differences in comfort levels when discussing issues of sexuality and physical and sexual abuse in either public or private settings with physicians or non-physicians. CONCLUSIONS: Patients in this survey were accepting of the concept of collaborative practice and felt that it offered quicker appointments, more time with the provider, more health information, and more specific diet information than did physician-only practices.

Review of use of statistics in The American Journal of Tropical Medicine and Hygiene for January-December 1988.

A statistical review of all 201 scientific articles published during the calendar year 1988 in The American Journal of Tropical Medicine and Hygiene was made to determine the type of study published by the journal, the level of statistics that was employed by the published articles, and the extent of common statistical errors. Sixty-five (32%) of the articles were classified as experimental, with most of the remaining observational studies classified as cross-sectional in design. A reader with the knowledge of only simple descriptive statistics would be able to understand 60% of the statistical procedures used in the published papers. Knowledge of the usual components of a single semester course in introductory statistics increases understanding to 91% of the techniques used. It was determined that 148 (73.5%) of the 201 articles had at least 1 detectable statistical error; most of these errors involved improper documentation or application of statistical hypothesis testing. The most common descriptive statistical error was the misuse of the concepts of "standard deviation" and "standard error" which was found in greater than 20% of the articles. Examples of each of the common statistical errors seen are given with suggestions for improvement.

Standard versus hyperimmune intravenous immunoglobulin in preventing or treating neonatal bacterial infections.

Although current studies suggest that IVIg is safe, larger controlled trials will soon be published and will be important to confirm this observation. In addition, the current studies do not establish the efficacy of IVIg for either treating or preventing neonatal bacterial infections. Some studies with small numbers of infants suggest benefit of IVIg therapy and prophylaxis; however, the studies reviewed do not, individually or combined, prove efficacy. Clinicians and investigators must not confuse studies that prevent infection with those that treat infection because different therapeutic regimens may be necessary. Many questions remain concerning IVIg therapy, such as is IVIg efficacious in preventing or treating neonatal sepsis, what is the appropriate immunoglobulin dosage, and how variable is the pathogen-specific antibody activity of standard IVIg products. To determine the appropriate use of IVIg in neonates effectively, well-designed and carefully controlled trials are needed to address these issues using sufficiently large numbers of infants to arrive at valid scientific conclusions. Although many questions will be answered with the trials currently in progress, we must continue to base further recommendations for immunoglobulin therapy on solid scientific data.

Murine immunization by cesium-137 irradiation attenuated Schistosoma mansoni cercariae.

Cesium-137, becoming a more readily available ionizing gamma radiation source for laboratory use, was shown to effectively attenuate Schistosoma mansoni cercariae for vaccine production. In parallel comparison studies with the murine model, cesium-137 attenuated cercariae consistently afforded better (P greater than 0.05) protection than did the cobalt-60 prepared vaccine. Dose-response data indicated that the optimal total irradiation with cesium-137 was between 45 and 50 Krad.