Antibiotics for the acute abdomen.

Antibiotics are only an adjunct to proper surgical therapy for the treatment of the acute abdomen associated with bacterial secondary peritonitis. Upon presentation, all patients require a preoperative dose of antibiotics for prophylaxis against infection of remaining sterile tissues. Patients found intraoperatively to have an established peritoneal infection benefit from an immediate postoperative course of therapeutic antibiotics. A regimen that adequately covers facultative and aerobic gram-negative bacilli and anaerobic organisms is essential. The duration of therapeutic antibiotics is probably best decided on an individual patient basis. The goal of antibiotics is to reduce the concentration of bacteria invading tissues. The pathogens of bacterial peritonitis are influenced by such factors as the patient's pre-existing chronic diseases, state of acute physiologic debilitation, immunocompetence, recent antibiotic use, recent hospitalization, and neutralization of gastric acidity. Intraoperative peritoneal cultures are most useful in patients suspected of having impaired local host defenses. In these patients, all identified organisms, such as Enterococcus or Candida, may be potential pathogens. The common practice of administering empiric and prolonged courses of broad-spectrum antibiotics in patients who manifest persistent signs of inflammation may be more harmful than beneficial. These patients warrant an exhaustive search for extra-abdominal and intraperitoneal sources of new infection. Otherwise, such use of antibiotics may continue to promote the selection of bacteria that are highly resistant to conventional antibiotics and permit the overgrowth of organisms commonly seen with tertiary peritonitis. The best chance of resolving bacterial peritonitis is through early, aggressive surgical management complemented by short courses of potent antibiotics and appropriate physiologic support. Through these efforts, the clinician tries to help the systemic inflammatory response to benefit the host and not become unregulated, result in MOFS, and produce a high mortality.

Lymphocyte-derived cytokines augment macrophage tumor necrosis factor-alpha and interleukin-6 secretion during experimental gram-negative bacterial sepsis.

Although lymphocyte-derived cytokines are known to augment macrophage cytokine production in vitro, their effect on macrophage tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) secretion during gram-negative bacterial sepsis has not been characterized. The purpose of this study was to examine the effect of lymphocyte-derived cytokines on macrophage TNF-alpha and IL-6 secretion during gram-negative bacterial peritonitis. To examine this problem, uninfected and infected mice were studied. Mice were infected with Escherichia coli O111:B4 and two subgroups were examined consisting of those pretreated iv 1 hr prior to bacterial challenge with either (1) saline or (2) anti-E. coli O111:B4 LPS mAb 2A3, the latter administered to abrogate the effects of LPS in vivo. Thus, three groups of mice were studied in relation to pretreatment and infectious challenges: (1) saline/saline (control); (2) saline/E. coli (saline); and (3) mAb 2A3/E. coli (mAb 2A3). Nonadherent splenocytes (> 95% lymphocytes by histologic staining criteria) harvested 16 hr later from mice in each group were incubated in culture ex vivo for 3 hr to obtain supernatants containing lymphocyte-derived cytokines. These supernatants containing lymphocyte-derived cytokines then were incubated in vitro with naive splenic macrophages with or without E. coli O111:B4 LPS. Macrophage TNF-alpha and IL-6 levels were determined using L929 and B9 bioassays.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis and treatment of cytomegalovirus disease in pediatric renal transplant recipients.

The purpose of this study was to identify factors associated with the development of cytomegalovirus (CMV) disease and to assess the morbidity of this illness in pediatric renal transplant patients. The authors retrospectively reviewed the records of 135 patients (< 18 years of age) who underwent a total of 151 transplants (146 kidney transplants, five kidney/liver transplants) over 5 years (average follow-up period, 33.0 +/- 21.7 months). They assessed the risk factors that previously have been associated with the development of CMV disease in adults (age, occurrence of acute rejection episodes, and preoperative donor and recipient CMV serological status) and evaluated the incidence of associated graft loss and mortality. Twenty-two episodes of CMV disease were diagnosed based on evidence of CMV infection and on clinical symptoms; the episodes were treated in 17 patients. A multivariate analysis showed that the development of CMV disease was associated with age of > or = 13 years (P = .02), concomitant liver transplantation (P = .01), and treatment of acute rejection (P = .04). In addition, patients who were CMV-seronegative preoperatively and received a graft from a CMV-seropositive donor (P = .04) or who were CMV-seropositive preoperatively and received a graft from a CMV-seronegative donor (P = .02) were more likely to have CMV disease. Although all patients with CMV disease required hospitalization and were treated with intravenous ganciclovir, CMV disease was not associated with increased allograft loss or mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Circannual variations in baseline blood values of dogs.

Forty-two hematological and biochemical variables routinely measured in dogs as part of a preoperative protocol have been analyzed for circannual changes by analysis of variance (ANOVA) and single cosinor procedures. Data were available from up to 489 adult mongrel dogs of both sexes studied on weekdays over a 5-year span (January 5, 1987 to December 18, 1991). Dogs were housed in individual cages at 24 +/- 1 degrees C with dog chow and tap water available ad libitum and lights on between 06:00 and 18:00 h. A single blood sample/dog was collected by jugular venipuncture between 08:00 and 09:00 h and sent to a commercial laboratory for hematological and biochemical determinations. Data were assigned to date and time of sampling and analyzed for the effect of time of year by ANOVA (across 12 months and 4 seasons), and by the least-squares fit of a precise 1-year cosine. ANOVA and single cosinor described a significant circannual time effect and rhythm for the following: total leukocytes, lymphocytes, hemoglobin, mean corpuscular hemoglobin (MCH), MCH concentration, red cell distribution width, mean platelet volume, creatinine, blood urea nitrogen (BUN), BUN/creatinine ratio, amylase, glucose, chloride, uric acid, direct bilirubin, total protein, albumin, globulin, albumin/globulin ratio, lactate dehydrogenase, alkaline phosphatase, gamma-glutamyltransferase, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)/ALT ratio. A significant effect of season by ANOVA only was found for: Ca, Na, phosphorus, total bilirubin, hematocrit, mean corpuscular volume, and neutrophils. No significant time effect could be found at p < or = 0.05 by either statistical method for: K, Mg, Fe, cholesterol, triglycerides, ASP, red blood cells, monocytes, eosinophils, basophils, or platelets. Acrophases occurred for the most part in either the winter or summer.

Anti-endotoxin monoclonal antibodies inhibit secretion of tumor necrosis factor-alpha by two distinct mechanisms.

OBJECTIVE: To determine whether monoclonal antibodies (mAbs) directed against lipopolysaccharide (LPS, endotoxin) act by promoting LPS neutralization, LPS uptake by macrophages, or both processes, the authors assessed the effects of these agents on LPS-induced cytokine secretion and cellular uptake of LPS. SUMMARY BACKGROUND DATA: MAbs directed against LPS have been shown to attenuate LPS-induced macrophage tumor necrosis factor-alpha (TNF-alpha) secretion, a process that may contribute to protective capacity. The mechanisms by which this process occurs have not been established. METHODS: MAbs directed against LPS were evaluated in vitro for their capacity to (1) inhibit TNF-alpha secretion, and (2) alter fluorescein isothiocyanate-labeled LPS uptake (employing flow cytometry analysis and fluorescence microscopy) by the macrophage-like cell line RAW 264.7. RESULTS: MAb 8G9, an IgG3 directed against the O-antigen polysaccharide region of Escherichia coli 0111:B4 LPS, significantly reduced LPS-induced TNF-alpha secretion and promoted a more than 40-fold increase in LPS uptake by macrophages. The authors established that this was mediated by a Fc receptor-mediated process because 8G9 F(ab')2 fragments that lack the Fc portion of the IgG molecule were capable of inhibiting TNF-alpha secretion, but did not promote increased LPS uptake to the same degree. Cross-reactive, anti-deep core/lipid A mAb 1B6, an IgG2a, also promoted uptake of E. coli 0111:B4 LPS and O-antigen polysaccharide-deficient E. coli J5 LPS, but only inhibited TNF-alpha secretion induced by E. coli J5 LPS to which it binds most efficiently. MAb 3D10, an IgM also directed against the O-antigen polysaccharide region of E. coli 0111:B4 LPS, inhibited TNF-alpha secretion but did not increase cellular uptake of LPS, presumably acting solely due to LPS neutralization. Polymyxin B, an antibiotic that binds stoichiometrically to the lipid A portion of LPS, inhibited TNF-alpha secretion and prevented cellular LPS uptake. CONCLUSIONS: These results suggest that IgG and IgM anti-LPS mAbs exert protective capacity by extracellular neutralization of LPS, while IgG Fc receptor-mediated cellular uptake also may serve to bypass macrophage activation and TNF-alpha secretion by promoting internalization and intracellular neutralization.

Pulsed Doppler frequency and carotid stenosis.

Two hundred and forty-two internal carotid arteries (ICA) were evaluated by independently interpreted arteriography and pulsed Doppler spectrum analysis using ultrasonic arteriography to evaluate the ability of peak systolic frequency (PSF) to predict the degree of internal carotid stenosis. Mean PSF in the 129 (53.3%) high grade ICA stenoses of greater than 50% diameter reduction was 6.55 +/- 0.14 (SEM) khz, while mean PSF in the 113 (46.7%) low grade (less than 50% diameter reduction) stenoses was 3.38 +/- 0.12 (SEM) kHz (P less than 0.0001). Receiver-operator characteristic (ROC) analysis revealed that PSFs of 4.5 kHz (sensitivity 87%, specificity 88%) and 5.0 kHz (sensitivity 83%, specificity 93%) were best for identifying a 50% diameter stenosis. Positive predictive value of 5.0 kHz was 93% (107/115) and negative predictive value was 82.7% (105/127). Linear regression analysis of PSF in kHz versus percentage diameter reduction yielded the equation: % stenosis = 10.7 (PSF) - 4.1 (r = 0.76). A nonlinear equation was also derived: % stenosis = 61.9 - 33.5 (PSF) + 8.7 (PSF)2 - 0.5 (PSF)3 (r = 0.77). Based on this analysis peak systolic frequency criteria measured by pulsed Doppler spectrum analysis appear to be useful for distinguishing high grade from low grade stenoses. Both the linear and nonlinear equations further suggest that PSF can more precisely quantitate the degree of ICA luminal narrowing.

Goldblatt phenomenon in a single kidney: the importance of subselective renal vein renins.

We have reported a case of renovascular hypertension in a patient with a solitary kidney with a significant stenosis of one of three separate renal arteries. Elevated renins were detected only with segmental sampling. We believe cases of renovascular hypertension may be overlooked on angiography and consequently, without segmental renin samples, lateralizing renin elevation may not be discovered.

Correlation of hemodynamically significant internal carotid stenosis with pulsed Doppler frequency analysis.

Systolic and mean pressure gradients across internal carotid stenoses were measured at the time of carotid endarterectomy in the arteries of 90 patients, all of whom underwent angiography. Eighty-two of these patients also had pulsed Doppler ultrasonic arteriography with real-time spectrum analysis. There were 71 (79%) high grade stenoses of greater than 50% diameter reduction by angiography. Significant systolic pressure gradients (greater than or equal to 10 mmHg) were identified in 41 patients (46%), 38 (46%) of whom underwent ultrasonic evaluation. A pulsed Doppler frequency measured within the stenosis equal to or greater than 6.5 kiloHertz had a sensitivity of 94.7% (36/38) in identifying pressure reducing lesions with a specificity of 47.7% (21/44). Positive predictive value was 61% (36/59). Angiographic criteria (50% diameter reduction) exhibited a sensitivity of 97.6% (40/41), a specificity of 36.7% (18/49) and a positive predictive value of 56.3% (40/71). Negative predictive value was 94.7% for angiography and 91.3% for ultrasonic arteriography. A pulsed Doppler frequency equal to or greater than 6.5 kiloHertz appears to accurately identify lesions that are at risk to reduce distal internal carotid pressure under operative conditions with a sensitivity similar to angiography. This criterion has a positive predictive value and specificity that is slightly superior to angiography and a high negative predictive value. Pulsed Doppler spectrum analysis provides physiologic information relative to blood flow velocity that is complimentary to the anatomic data provided by angiography for assessing the potential for hemodynamic significance of internal carotid stenoses.

Renal artery thrombosis: a cause of reversible acute renal failure.

Acute renal failure can be produced by interruption of the arterial blood supply. We describe a case of acute renal failure that developed owing to thrombosis of the renal artery of the only functioning kidney. This thrombosis occurred in an artery that was stenosed probably by an arteriosclerotic plaque. The blood flow was re-established successfully by the passage of the catheter into the thrombosed artery and intra-balloon dilation of the stenosis.

Transcription of adenovirus RNA in permissive and nonpermissive infections.

The mechanism of blocked replication of human adenoviruses in monkey cells was examined. Previous experiments have placed the replicative block at the level of transcription of translation of adenovirus mRNA. Coinfection of the monkey cells with simian virus 40 enhances adenovirus replication in these cells. We compared the adenovirus mRNA transcribed during infection of permissive human cells and enhanced and unenhanced monkey cells. Adenovirus mRNA from enhanced monkey cells appeared to be identical to adenovirus mRNA from human cells. This indicated that simian virus 40 coinfection did not overcome the blocked replication by substituting for a missing adenovirus transcript. Comparison of adenovirus mRNA from enhanced and unenhanced monkey cell infection revealed two types of transcriptional discrepancies. There was a decrease in both the complexity and the relative abundance of several regions of the enhanced adenovirus mRNA. However, neigher of these transcriptional defects was sufficient to totally explain the difference in yield of infectious virus and viral protein seen in these two types of infection.