Effect of PGG-glucan on the rate of serious postoperative infection or death observed after high-risk gastrointestinal operations. Betafectin Gastrointestinal Study Group.

BACKGROUND: Postoperative infections remain common after high-risk gastrointestinal procedures. PGG-glucan (Betafectin; Alpha Beta Technology Inc, Worcester, Mass), derived from yeast cell walls, promotes phagocytosis and intracellular killing of bacterial pathogens by leukocytes, prevents infection in an animal model of wound infection, and acts synergistically with antibiotics to reduce mortality in rat peritonitis. HYPOTHESIS: We hypothesized that infectious complications in these patients might be reduced by the administration of a nonspecific immune-enhancing agent. DESIGN: Multicenter, prospective, randomized, double-blind, placebo-controlled trial of 1249 patients prospectively stratified into colorectal or noncolorectal strata. SETTING: Thirty-nine medical centers throughout the United States. PATIENTS: Aged 18 years or older, scheduled for gastrointestinal procedure lasting 2 to 8 hours, with 2 or more defined risk factors. INTERVENTIONS: PGG-glucan, 0.5 mg/kg or 1.0 mg/kg, or placebo once preoperatively and 3 times postoperatively. All patients received standardized antibiotic prophylaxis. MAIN OUTCOME MEASURES: Serious infection or death within 30 days. RESULTS: All randomized patients revealed no difference in serious infections and deaths in the treated groups compared with placebo groups (15% vs 14%, P>.90). In the prospectively defined noncolorectal stratum (n = 391), PGG-glucan administration was associated with a statistically significant relative reduction (39%) in serious infections and death (placebo, 46 [36%] of 129 vs either PGG-glucan group, 29 [21%] of 132 and 28 [22%] of 130, P<.02). PGG-glucan reduced postoperative infection or death in malnourished patients having noncolorectal procedures (31 [44%] of 70, placebo group; 16 [24%] of 68, 0.5-mg/kg PGG-glucan group; 12 [17%] of 72, 1.0-mg/kg PGG-glucan group; P<.001). Study drug was stopped owing to adverse effects more frequently for patients receiving PGG-glucan than placebo (2%, 4%, and 7% for the placebo group, 0.5-mg/kg PGG-glucan group, and 1.0-mg/kg PGG-glucan group, respectively, P<.003). CONCLUSION: Perioperative administration of PGG-glucan reduced serious postoperative infections or death by 39% after high-risk noncolorectal operations.

Left ventricular coordinate systems.

Three-dimensional kinematics of radiopaque markers in anterior, posterior, septal, and lateral regions of a major equatorial plane were evaluated in anesthetized dogs by biplane fluoroscopy. Stationary coordinate systems measured marker locations recorded during diastole and systole from a contractile origin at the center of contraction at end systole and from a geometric origin at the intersection with the equatorial plane of the ventricular long axis at end diastole. A time-indexed system measured marker locations at end diastole and at end systole, respectively, from the locations of the geometric origin at end diastole and end systole. Compared to the stationary system with the geometric origin, both the stationary system with the contractile origin and the time-indexed system reduced the variability of the radial components of the contractile displacements between ventricular regions. In contrast to the other two systems, the system with the contractile origin reduced circumferential components to values not significantly different from zero. These results indicate that 1) abnormally contracting regions of the ventricle may be located and their size measured by determining the region where the radial component differs from that in the rest of the equatorial plane and 2) rotation in a major equatorial plane of the ventricle is significant, but the influence of rotation can be minimized by referencing ventricular dimensions to a coordinate system with an origin at the center of contraction.

Intracranial arteriovenous malformation: contralateral steal phenomena.

Sixty-two patients with radiographically proven intracranial arteriovenous malformations underwent preoperative regional cerebral blood flow measurement with 133Xe single-photon emission computed tomography. Contralateral regions of hypoperfusion were detected in all cases. Steal severity was assessed according to the contralateral steal index [ISteal(c)]. ISteal(c) was greater than 0.7 (severe) in 22 (35%), 0.7-0.8 (intermediate) in 18 (29%), and greater than 0.8 (mild) in 22 (35%). ISteal(c) was more frequently severe or mild in females and more often intermediate in males (p less than 0.05). Hyperemic complications were encountered more frequently in patients with intermediate ISteal(c) (p = 0.086). An unfavorable outcome was associated with less severe contralateral steal (p = 0.12). A detailed clinical, radiographic, and hemodynamic profile may help to preoperatively identify patients at high risk for a poor surgical outcome.

Intracranial arteriovenous malformation: relationships between clinical and radiographic factors and cerebral blood flow.

Arteriovenous malformations (AVMs) dramatically alter normal cerebral circulatory dynamics. Clinical and radiographic data from 62 patients were analyzed to determine their impact on total brain blood flow (TBF) measured by single-photon emission computed tomography. 48% of patients presented with hemorrhage and 34% with progressive deficits. 37% had angiographic steal and 21% developed postoperative hyperemic complications. 40% were under 30 years old, 45% were between 30 and 50 years of age, and 15% were over 50. TBF was less than 70 ml/100 gm/min in 32% of patients, between 70 and 84 ml/100 gm/min in 40%, and greater than 84 ml/100 gm/min in 27%. Female patients had higher TBF than males; 42% of females but only 17% of males had values greater than 84 ml/100 gm/min (p less than 0.05). A trend toward decreased TBF with advancing age was noted. Intracranial hemorrhage was associated with lower TBF; 47% of patients with hemorrhage and 19% of those without had TBF of less than 70 ml/100 gm/min (p less than 0.05). 89% of patients with AVMs less than 5 cm in diameter had TBF of less than or equal to 84 ml/100 gm/min, and 65% of those with larger AVMs had similarly low flows (p less than 0.05). A trend toward lower TBF was observed in patients with unfavorable outcomes.

Intracranial arteriovenous malformation: relationship between clinical factors and surgical complications.

Serious morbidity and hyperemic states continue to complicate the treatment of certain intracranial arteriovenous malformations (AVMs). Clinical and radiographic characteristics of 62 patients treated over 3 years were analyzed to determine if hyperemic complications (HCs) (defined as unusual perioperative edema or hemorrhage) and outcome could be predicted. Twenty-five (40%) of the patients were less than 30 years old, 28 (45%) were between 30 and 50, and 9 (15%) were more than 50. A history of hemorrhage was found in 48%, and 34% presented with progressive deficits. Thirteen (21%) developed evidence of HCs; 51 (82%) ultimately had a good outcome, 4 (6%) had a poor outcome, and 7 (11%) died. The incidence of HCs was higher in patients whose AVMs recruited perforating vessels (53%) than those without (7%) (P less than 0.001). The presence of preoperative angiographic steal carried a 35% risk of HCs whereas its absence carried a 13% risk (P less than 0.05). The sum of the diameters of the feeding vessels was also predictive (P less than 0.05). Outcome was clearly age-related: good outcome was achieved in 92% of the patients less than 30 years old, 86% of those 30 to 50, and 44% of patients older than 50 (P less than 0.05). Left hemispheric AVMs showed less morbidity than right (P less than 0.05) as did those without perforating vessel recruitment (P less than 0.07). HCs had a dramatic impact on outcome with 92% of patients without HCs having good outcome and 46% of those with HCs recovering well (P less than 0.001).

Interaction of irradiation and microwave-induced hyperthermia in the Dunning R3327G prostatic adenocarcinoma model.

The interaction of radiation and hyperthermia was systematically studied in the Dunning R3327G prostatic adenocarcinoma, the preeminent animal model for human prostatic cancer. Subcutaneous tumors (produced by injection of 10(7) cells) were treated when they had reached a volume of about 1 cm3, which occurred about 3 weeks after implantation. With the use of a randomized complete factorial design, four factors were examined. Each agent was used at one of three dose levels. For radiation, these were 5, 15, and 25 Gy; for hyperthermia, 42 degrees C for 15 minutes, 43 degrees C for 30 minutes, and 44 degrees C for 60 minutes. Two sequences (hyperthermia plus irradiation and irradiation plus hyperthermia) and five time delays between agents (0, 12, 24, 48, and 120 hours) were used. The growth delay (the time it took for the initial tumor volume to double) of subcutaneously implanted tumor served to quantitate treatment effect. Significant (P less than .05) statistical interactions were observed for several combinations of factors and individual factors. Hyperthermia plus irradiation was more effective than irradiation plus hyperthermia except at the delay time between treatments of 0 hours. Peak growth delay occurred when the time between treatments was 0-24 hours and depended on agent doses. Many combinations produced therapeutic synergy.

Intracranial arteriovenous malformation: relationships between clinical and radiographic factors and ipsilateral steal severity.

Intracranial arteriovenous malformations (AVMs) are high flow shunts that may jeopardize the perfusion of adjacent tissue. Clinical and radiographic data from 62 patients were analyzed to determine their relationship to the severity of steal measured by single photon emission computed tomography (SPECT). The ipsilateral steal index [ISteal(i)] was determined by dividing regional cerebral blood flow (rCBF) values within hand-drawn regions of hypoperfusion in the ipsilateral hemisphere by total brain flow, which was calculated as the average rCBF of each hemisphere. Of the patients, 40% were less than 30 years of age, 45% were 30 to 50 years old, and 15% were over 50. Forty-eight per cent presented with hemorrhage and 34% presented with progressive deficits. There was angiographic steal in 37%, and postoperative hyperemic complications developed in 21%. All patients had ipsilateral regions of hypoperfusion. The ISteal(i) was less than 0.7 in 23 (37%), 0.7 to 0.8 in 20 (32%), and greater than 0.8 in 19 (31%). The ISteal(i) was significantly less severe in the patients over 50; 78% of these patients had an ISteal(i) of greater than 0.8 (P less than 0.01). A history of hemorrhage was associated with less severe steal than that in patients who had not bled (P = 0.088). Patients presenting with a history of progressive deficits had increased severity of steal compared with those without progressive deficits (P less than 0.05). A trend toward decreased severity of steal was noted in patients with unfavorable outcomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Ventricular ejection fractions of linear transformation and ellipsoid models.

Eigenvolumes calculated from a linear transformation model were found previously to be linearly related to balloon volumes in excised hearts. The present study analyzed endocardial marker kinematics in intact, contracting left ventricles by biplane cinefluorography. Ejection fractions of the linear transformation model were compared by linear regression analysis with those of an ellipsoidal model, whose ejection fractions had been documented previously in closed and open-chest dog preparations. Data from 10 dogs indicated a correlation coefficient of 0.98 and a regression equation with close similarity to the line of identity. Ejection fractions calculated from the linear transformation model are concluded to be proportional to actual ejection fractions in intact, beating left ventricles.

Systematic investigation into interaction of ionizing radiation and doxorubicin in the Dunning R3327G prostatic adenocarcinoma model.

The interaction of doxorubicin and radiation has been systematically studied in the Dunning R3327G prostatic adenocarcinoma, the preeminent animal model for human prostatic cancer. Subcutaneous tumors (produced by injection of 10(7) cells) were treated when about 1 cm3 in volume (19-22 days postimplant). Each modality was used at 1 of 3 dose levels; 2, 4, and 9 mg/kg for doxorubicin; and 5, 15, and 25 Gy for radiation. Single treatment with each agent was combined, in both sequences and five delay times (0.5, 12, 24, 48, and 120 hr) between agents. Growth of individual tumors was fit to a quadratic exponential growth model which was solved for the growth delay and growth rate at twice initial volume. Analysis of variance identified significant interactions for doxorubicin and radiation (due to drug toxicity), sequence and delay, and sequence and radiation, in addition to the four factors individually. The effect on the tumor of combined doxorubicin and radiation is basically additive. Sequence and delay are important in overall tumor control.

Acoustic analysis of affective prosody during right-sided Wada Test: a within-subjects verification of the right hemisphere's role in language.

A within-subjects study of the affective characteristics of voice was carried out in patients undergoing a Wada Test (WT). All patients became densely aphasic after the left-sided WT and lost the ability to impart affect into speech after the right-sided WT. The affective changes in voice induced by the Wada test were acoustically analyzed by computer-assisted techniques and compared to data obtained pre-Wada and post-Wada. The statistical results, using a one-way analysis of variance for repeated measures, confirmed robustly the current view that the right hemisphere modulates dominantly the affective components of language. The results are also evaluated in light of recent clinical and acoustical data regarding the organization of language in speakers of tone languages, thus, allowing the authors to address issues concerning universal principles of brain-language-behavioral relationships.

Changes in left ventricular geometry during spontaneous breathing.

The purpose of these experiments was to determine the effects of a spontaneously generated inspiration on the size and shape of the left ventricle (LV) in anesthetized supine dogs. We implanted markers in the LV to establish three perpendicular axes and recorded the motion of these markers using biplane cinefluoroscopy at 60 Hz. The primary changes in LV size that accompanied inspiration occurred at end diastole (ED). The largest change in LVED dimension was a 2.46-mm narrowing of the septal-lateral wall dimension, but the apex-base dimension decreased also, by 0.74 mm. The anteroposterior dimension actually widened by 1.07 mm. The septal-lateral narrowing was caused by both a 1.0-mm narrowing of the distance between the septal marker and the apex-base axis, as well as by a 1.4-mm narrowing between the apex-base axis and the lateral wall marker. Narrowing of the septal portion seemed expected because of presumed enhanced right ventricular filling during inspiration. Narrowing of the lateral portion of the LV, while the anteroposterior dimension widened, was surprising because a change in LVEDV shape is implied. Assuming ventricular homogeneity, this change in LVED shape implies that the forces applied to the epicardial surface were not uniform. There must have been a retraction on the anterior and posterior surface that was not experienced by the lateral LV wall. The net effect of these dimensional changes of the LV at end diastole (estimated from the product of the three ED axes) was a 3.5-cm3 reduction in LVED volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Prospective surveillance of Haemophilus influenzae type b disease in Dallas County, Texas, and in Minnesota.

Among children less than 12 years of age residing in Dallas County, Texas, and in the state of Minnesota we conducted prospective, active surveillance of invasive Haemophilus influenzae disease. During 18 months, 616 cases were identified, of which 600 were caused by type b organisms. The annual incidence of disease was significantly greater in Dallas than in Minnesota (109 v 68/100,000 children younger than 5 years of age, P less than .001) and was greater in Dallas, even when rates for white children in the two regions were compared (P less than .001). Other regional differences were observed. In Dallas, a larger proportion of cases were in children attending day-care centers (27% compared with 12% in Minnesota, P less than .001) and more patients attended day care for greater than 40 h/wk (56% compared with 30% in Minnesota, P less than .001). Outer membrane protein subtyping of isolates revealed that in Dallas 6U isolates were associated significantly with cases in black children who attended day care. In Minnesota, but not in Dallas, isolates with subtype 1H were associated significantly with cases in children in day care. These data indicate that there are regional differences in the epidemiology of type b Haemophilus disease that may relate to differences in strains, day-care practices, or other unknown cultural or environmental factors. Finally, because only 15% of systemic Haemophilus disease in these regions occurred in children in the age groups recommended for vaccination (24 to 59 months), the new Haemophilus type b polysaccharide vaccine is expected to have a limited impact on the overall incidence of disease.

Risk of subsequent disease among day-care contacts of patients with systemic Hemophilus influenzae type B disease.

There is controversy about whether to provide rifampin prophylaxis routinely to contacts in day-care facilities of a patient with a primary case of Hemophilus influenzae type b disease. We prospectively investigated primary cases of H. influenzae type b disease in day-care facilities in Dallas County, Texas, to determine the rate of subsequent disease among contacts. Ninety-one children with primary cases of H. influenzae type b disease who were attending day-care facilities were enrolled from October 1982 to October 1984. A total of 587 classroom contacts of these children under four years of age were not given rifampin. During 60 days of follow-up, there was one subsequent case in a classroom contact. Untreated children under two years of age who were directly exposed to a patient with a primary case were considered to be at highest risk of disease, but there were no subsequent cases in this group of 361 children. However, there were two cases in new enrollees who started attending day-care facilities during the 60-day follow-up period but who were not exposed to a patient with a primary case. At day-care centers in which there was a second case during the follow-up period, there was a high prevalence of colonization with H. influenzae type b in both patient and nonpatient groups of preschool children. These data indicate that the rate of subsequent disease in classroom contacts of patients in day-care facilities is lower than that reported in households (1 of 587 vs. 20 of 829, P = 0.001) and that this rate may be similar to the base rate of primary disease in day-care facilities. We conclude that rifampin prophylaxis may not be appropriate after the occurrence of a primary case of H. influenzae type b disease in a day-care facility in Dallas County.

Formaldehyde-induced acentric chromosome fragments and chromosome stickiness in Chortophaga neuroblasts.

Embryos of the grasshopper Chortophaga viridifasciata were exposed in vitro to formaldehyde (FA), as formalin, at concentrations ranging from 10(-8)M (0.0003 ppm) to 10(-3) M (30 ppm) at 38 degrees C. A low frequency of distinct acentric chromosome fragments (0.02-0.04/cell) was observed in the neuroblasts after 1 hr exposure to 7.5 X 10(-4) or 10(-3) M FA plus 3 hr recovery, but not at lower concentrations, even with 4 hr exposure. There was no obvious relation between distinct fragment frequency and concentration of FA. Neuroblasts with sticky chromosomes were observed at 10(-4), 7.5 X 10(-4), and 10(-3) M FA, the percent of cells with slight, moderate, or severe stickiness varying with FA concentrations. Fragments were associated with the sticky chromosomes. The frequency of these sticky fragments at the two higher concentrations (0.15-0.30/cell) was greater than the frequency of distinct fragments. It is concluded that the distinct acentric fragments induced by FA result from breakage at a single sticky point (slight stickiness) between separating sister chromatids. The chromosome effects observed probably result from the action of daughter products that are formed by the interaction of FA with culture medium components, especially the fetal calf serum.

Incidence of adult respiratory distress syndrome in patients with multiple musculoskeletal injuries: effect of early operative stabilization of fractures.

Records of 132 consecutive patients with multiple musculoskeletal injuries were examined for the purpose of assessing the relationship between the length of time from injury to the operative stabilization of major fractures and the incidence of adult respiratory distress syndrome (ARDS). To be included in the study patients had to have had at least two major long-bone fractures and a Hospital Trauma Index-Injury Severity Score (ISS) of 18 or higher. Early operative fracture stabilization (STAB) is defined as an operation in the first 24 hours postinjury at which the majority of fractures were stabilized without leaving a spine, pelvis, or femur fracture unstable. A stepwise logistic regression was performed on the data. The dependent variable was the presence or absence of ARDS. The independent variables were age, sex, number of injuries, days to first surgery, early operative fracture stabilization (STAB), units of blood the first week, and ISS and its major components: RESP, ABD, CV, EXT, NS, and SSQ. The two independent variables selected as significant by this procedure were STAB and ISS. For the overall data set, a delay in orthopedic surgery (greater than 24 hours) is associated with a five-fold increase in the incidence of ARDS (p less than 0.001). For the more severely injured patients (ISS greater than 40), the comparable rates are 17% with early surgery and 75% with delayed surgery (p less than 0.001). A Chi-square test for association between ARDS and STAB adjusting for changes due to ISS grouping is significant (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Mitomycin C effects on cell cycle progression, including inhibition of very late prophase, as seen in living neuroblasts of Chortophaga viridifasciata, with some observations on mitomycin C purity.

Observations were made on living neuroblasts (Nbs) of the grasshopper (Chortophaga viridifasciata) embryo during a 4-h recovery period following 1-h in vitro exposure to 10(-8), 10(-6), and 10(-4) M mitomycin C (MMC). None of these concentrations affected the duration of mid-mitosis (prometaphase, metaphase, anaphase), but one as low as 10(-8) M causes a small reduction in the rate at which Nbs move through the remainder of the cell cycle, primarily by retarding their progress through S. As the concentration is increased there is slower movement through S and also prophase (there are no true G1 and G2 periods in the rapidly dividing Nb: 4-h cell cycle at 38 degrees C). A significant proportion of the cells exposed to 10(-4) M are blocked for 1 or more h at very late prophase, i.e., just before nuclear membrane breakdown. In such retarded prophases the chromosomes resemble c-metaphase chromosomes even though the nuclear membrane remains intact. Mass spectrometry data revealed that one lot of the MMC used contained one or more impurities.

Chromosome fragments and other abnormalities induced by mitomycin C in the neuroblast of Chortophaga viridifasciata.

Mitomycin C (MMC) induces acentric chromosome fragments in the neuroblast (Nb) of the grasshopper embryo (Chortophaga viridifasciata) after acute and chronic exposure to concentrations ranging from 10(-8) to 10(-4) M, the dose response being essentially linear up to 10(-5) M. Because Colcemid is not used in the Nb assay, it was possible to detect two additional effects of MMC: (1) Prolonged retardation of many cells occurs when they reach very late prophase; the chromosomes continue condensing and lose their orderly prophase orientation, and the nuclear envelope becomes increasingly fragile. Such cells, which were observed after both acute and chronic exposure, give the false impression of being c-metaphases when they are fixed and squashed. The frequency of retarded very late prophases and the duration of retardation are related to MMC concentration and time of exposure. A rationale is presented supporting the idea that the events associated with retarded very late prophase result from MMC effects on the nuclear envelope. (2) MMC significantly increases the frequency of Nb's with attenuated centromeres at the beginning of early anaphase, an effect that appears to be caused by a delay in the repulsion of sister chromatids that usually occurs immediately after centromere separation begins.