Fosfomycin/metronidazole compared with doxycycline/metronidazole for the prophylaxis of infection after elective colorectal surgery. A randomised double-blind multicentre trial in 517 patients.

OBJECTIVE--To find out if fosfomycin together with metronidazole was any better than doxycycline with metronidazole for the prophylaxis of infection before elective colorectal operations. DESIGN--Multicentre, double blind, random control trial. SETTING--Nine Swedish hospitals. SUBJECTS-559 patients admitted for elective colorectal operations. INTERVENTIONS--Fosfomycin 8 g and metronidazole 1 g before operation and fosfomycin 8 g eight hours afterwards, or doxycycline 400 mg and metronidazole 1 g before operation, and placebo eight hours afterwards. MAIN OUTCOME MEASURES--Incidence of all types of infection, mortality, and side effects. RESULTS--There were no significant differences between the groups for any of the outcome measures studied, the overall abdominal infection rates (wound, deep, and septicaemia) being 4.6% and 7.4%, and the remote infection rates (pneumonia, urinary tract, and central venous line) 15.1% and 12.8%, respectively. Of the predictors studied, only duration of operation was significantly related to risk of infection. CONCLUSION--The combination of fosfomycin and metronidazole was as safe and effective as that of doxycycline and metronidazole in preventing infections after elective colorectal operations.     

Interleukin 4 enhances osteoblast macrophage colony-stimulating factor,but not interleukin 6, production

To determine if interleukin 4's (IL-4) recently discovered skeletal effects could be explained by its effects on osteoblasts, we have examined IL-4's impact on macrophage colony stimulating factor (M-CSF) and interleukin 6 (IL-6) secretion by the murine osteoblastic cell line MC3T3-E1. Interleukin-4 increased colony-forming activity in MC3T3 supernatants two-threefold with colony cytomorphology, cytohistochemistry, and blockade of the effect by anti-M-CSF antibody, indicating that the IL-4-induced activity was M-CSF. MC3T3 M-CSF supernatant activity increased in a time-dependent manner with positive IL-4 effects seen after a 24-hour exposure. The maximal IL-4 effective dose was 100 U/ml where conditioned media from IL-4-treated cells contained twofold more M-CSF than control cells (400 U/ml versus 200 U/ml M-CSF) as detected by a sandwich M-CSF ELISA. Northern blots showed that IL-4 (200 U/ml) rapidly increased steady-state M-CSF mRNA levels with maximal induction observed by 2 hours followed by a decline to near basal levels by 24 hours. IL-4 also dose dependently increased M-CSF mRNA levels with maximal induction (fourfold) seen at 100 U/ml IL-4. In contrast to its impact on MC3T3 M-CSF production, IL-4 (200 U/ml) did not stimulate MC3T3 IL-6 secretion whereas IL-1 (1 pM) stimulated a 500-fold increase in MC3T3 IL-6 release. When utilized to treat newborn calvarial osteoblast-enriched cultures, IL-4 dose dependently augmented M-CSF production, with the maximal effect seen at 200 U/ml where IL-4-treated, osteoblast-conditioned media contained almost 500 U/ml M-CSF, compared with 200 U/ml M-CSF in controlconditioned media. These observations indicate that the range of IL-4 cellular targets in skeletal tissues include osteoblastic cells, and that this cytokine increases osteoblast expression of M-CSF, a hematopoietic cytokine pivotal for monocyte/macrophage differentiation. Furthermore, IL-4's impact on osteoblast-produced M-CSF levels is selective because IL-6 levels were unaltered by IL-4 treatment.     

Subtyping lymphocytes in peripheral blood by direct immunoalkaline phosphatase labeling and light scatter/absorption flow cytometric analysis.

Evaluation of blood cells to determine immunologic status is becoming an important clinical application of flow cytometric analysis. For a wider use of immunophenotyping technology in clinical laboratories, the authors developed a rapid method to detect monoclonal antibody-labeled cells using forward light scatter/absorption clinical flow cytometers such as the Technicon H*1 and Technicon H*2 differential complete blood count analyzers. Calf-intestinal alkaline phosphatase was conjugated to mouse monoclonal antibodies (anti-CD2, CD3, CD4, CD8, CD19) for direct immunoenzymatic labeling. The combination of 5-bromo-4-chloro-3-indolyl phosphate and nitroblue-tetrazolium salt in diethanolamine buffer at pH 9.6 was selected as buffer/substrate to yield stable, insoluble, and very intense purplish-blue precipitates on the surface of the cells labeled with monoclonal antibody-alkaline phosphatase conjugates. Endogenous alkaline phosphatase in granulocytes was inhibited with levamisole. Early mild fixation of the white cells permitted incubation at 38 +/- 1 degrees C, which accelerated each step of the reaction without disrupting the cells throughout the procedure. The method is competitive with the direct immunofluorescence whole-blood method used on fluorescence flow cytometers in speed, sensitivity, and accuracy, as demonstrated with alkaline phosphatase-conjugated anti-CD2, CD3, CD4, CD8, CD19 monoclonal antibodies.     

Computed tomographic evaluation of the excluded stomach in gastric bypass

Eleven patients who had gastric bypass operations were examined with computed tomography to evaluate the status of the excluded stomach. Three of the patients had dilated excluded stomachs that accounted for the patients' symptomatology. As an upper gastrointestinal series cannot delineate the excluded stomach, computed tomography is the examination of choice for such an evaluation.     

Serum and tissue pharmacokinetics of intravenous metronidazole in surgical patients

Intravenous administration of 1 g metronidazole during 30 min to 12 patients undergoing colorectal surgery yielded mean serum levels of 20.4 (+/- 4.9 SD) mg/l at 1 h, 15.6 (+/- 4.1) at 4 h and 3.9 (+/- 2.0) at 24 h after infusion. The mean elimination half-life of metronidazole was 8 h and the mean apparent volume of distribution 42 l. At 1-4 h after the infusion the median tissue/serum drug concentration ratio was 0.94 for rectus abdominis muscle and 0.76 for colonic mucosa. For adipose tissue the corresponding ratio was significantly lower (0.21, p less than 0.01) and highly unpredictable. Since in gastrointestinal surgery most wound infections develop in the cut surface of the abdominal fat, failure of metronidazole to reach bactericidal concentrations in adipose tissue could be a risk factor in this respect, contributing to the variable reported results of metronidazole prophylaxis.     

Scintigraphic findings in patients with shoulder pain caused by interleukin-2

Interleukin-2 is receiving widespread interest as an immunotherapeutic agent in the treatment of certain cancers. Severe arthralgias recently have been reported as a significant side effect, and the cause of pain is unknown. Because interleukin-2 is an immune modulator, we reviewed the 99mTc-methylene diphosphonate scintigrams in nine patients who had developed shoulder arthralgias while receiving interleukin-2 for metastatic melanoma. In eight of the patients, the scintigrams showed diffuse increased uptake of radionuclide in the shoulders. Four patients had radiographs of their shoulders, all of which were normal. Bone scintigraphy in patients receiving interleukin-2 as immunotherapy for metastatic melanoma shows increased radionuclide activity in the shoulders. This process may relate to the role of interleukin-2 as a mediator in the inflammatory response.     

Significance of endocrine parameters of stress

Thirty two male patients undergoing coronary bypass surgery were given low (group A, 0.01 mg/kg bw) and high dose (group B, 0.035 mg/kg bw) fentanyl anaesthesia. Haemodynamic and hormone responses were investigated from the beginning of anaesthesia until extracorporeal circulation (ECC) (group A: n = 16; group B: n = 16). Significant changes in haemodynamics occurred only in group A including an increase in heart rate (36%) and systolic arterial pressure (21%). Plasma vasopressin (ADH) levels rose significantly in both groups after the beginning or surgical procedure which was markedly less pronounced in patients with high fentanyl (group B). In group A (low dose) a second dose of fentanyl was given after sternotomy, which was followed by a significant decrease in ADH (80% from previous value). No significant variations could be demonstrated in plasma levels of cortisol, ACTH, and human growth hormone (HGH). The data stress the importance of plasma-vasopressin-levels in determining the endocrine stress response following trauma and operation. On the other hand there was a lack of correlation between trauma and pain and frequently reported patterns of the endocrine-metabolic stress response.     

Experiences with a new EEG spectral analyzer in carotid surgery

Spectral analysis with the compressed spectral array display (CSA) and calculation of spectral edge frequency (SEF) was performed in 43 cases undergoing endarterectomy of the carotid bifurcation. New neurologic deficit appeared in 2 patients (= 4.6%). One of them died postoperatively (= 2.3%), the other suffered from permanent paralysis of the hand. Another 9 patients showed loss of high frequency activity (= decrease in SEF) without a new deficit in the postoperative period. A significant EEG event was defined as a decrease in SEF after carotid cross clamping for at least 5 min. Fisher's exact probability test revealed a close correlation between these EEG events and neurologic outcome. The sensitivity of the test, which was calculated on true positive and false negative events, was 100%, the specificity, based on true negative and false positive events, was 76%. The predictability of the test, based on all EEG events, was 18%; respectively 40% when calculated on significant events.     

Salivary cortisol: a practical method for evaluation of adrenal function

Salivary cortisol represents a simple, noninvasive, stress-free measure that can greatly facilitate the longitudinal study of hypothalamic-pituitary-adrenal axis activity in patients with psychiatric disorders. By means of a slight modification of a commercially available radioimmunoassay kit, we studied the stability of salivary cortisol under different conditions, as well as the relationship between plasma and salivary cortisol under basal circadian conditions and following stimulation (CRH) and suppression (dexamethasone). We observed that salivary cortisol was quite stable at room temperature without centrifugation and that salivary and plasma cortisol values were highly correlated. Additionally, we observed a close correspondence in circadian and ultradian fluctuations in salivary and plasma cortisol. The salivary cortisol response to ovine and human CRH was similar to that observed with plasma cortisol, but was greater in magnitude. Finally, employing a plasma criterion as the standard, salivary measures identified 48% of the nonsuppressed Dexamethasone Suppression Tests (DSTs) and 97% of the suppressed DSTs.