The diagnosis of bacterial peritonitis

September

SELECTED SCIMMAKIES

1985

a neuropeptide found in the brain and gut. Analogues have been synthesized in the attempt to obtain a specific antagonist (Eur J Pharmacol 1984:97:179-89). As seen in this study, one of the most effective antagonists at this time appears to be spantide. The possibility of antagonism of bombesin by a substance P antagonist was raised by studies indicating that substance P antagonists would reverse the bombesin-stimulated amylase secretion from dispersed guinea pig pancreatic acini (Biochim Biophys Acta 1984:804:181-91). The studies reported here were carefully executed and demonstrated that the antagonist effect on the central binding of bombesin was specific for spantide, as substance P itself did not affect binding of bombesin. There does not appear to be any similarity between the substance P and bombesin receptors, as bombesin also does not affect substance P binding. The authors then proceeded to investigate whether the ability of the substance P antagonist, spantide. to inhibit central binding of bombesin was paralleled by inhibition of a response that is mediated by the activation of central bombesin receptors. After central injection, bombesin induces hypothermia in cold-exposed rats and grooming at ambient temperature (Science 1977;196:9981001, Brain Res 1980;193:209-20). It has been postulated that these responses are mediated physiologically by endogenous bombesinlike peptides in the central nervous svstem and pharmacologically by the binding of exogenously administered bombesin to central receptors. This study was able to demonstrate that these responses to centrally administered bombesin were inhibited by spantide, and bombesin-induced hypothermia was not inhibited by substance P, which also had no antagonist properties at central bombesin receptors. This is an important study for several reasons. It establishes that a substance P antagonist such as spantide is an antagonist for bombesin receptor binding in the central nervous system as well as in the pancreas, suggesting that this property exists at all bombesin receptors. It demonstrates that a physiologic response to bombesin is inhibited by this antagonist, providing the best data to date that central bombesin receptors mediate this response. This in turn strongly suggests that the pathways exist in the brain to mediate this response endogenously, and indicate that the bombesinlike peptide, which has been demonstrated by immunohistochemical techniques to be present in the rat brain, mediates this physiologic response. It is surprising that an analogue of an apparently structurally unrelated peptide, substance P, would be an effective antagonist of bombesin. In addition to demonstrating that one cannot assume that analogues of specific peptides will only be antagonists to their parent peptide, this study underscores the importance of multiple controls in studies examining the effects of peptides where one is using incompletely characterized antagonists. Finally, the demonstration that these analogues of substance P interact with the bombesin receptor. whereas other analogues and substance P itself do not, may provide some clues as to the physicochemical structure of the bombesin receptor itself.

A. OIJYANG.M.D.

THE DIAGNOSIS PERITONITIS

OF BACTERIAL

Garcia-Tsao G, Corm HO, Lerner E (Veterans Administration Medical Center, West Haven, Connecticut, and Yale University School of Medicine, New Haven, Connecticut) The diagnosis of bacterial peritonitis: comparison of pH, lactate concentration and leukocyte count. Hepatology 1985;5:91-6.

693

During the past 20 yr since Corm first defined bacterial peritonitis (BP) in patients with ascites, this condition has become recognized as an important and life-threatening complication. If untreated, there is a high mortality rate. The clinician who is caring for a patient with ascites is faced with several difficult decisions. How can he decide when a paracentesis is indicated and how does he interpret the initial fluid analysis before the bacteriologic results are available. The question of when to do a paracentesis remains unanswered. The present study addresses the interpretation of paracentesis fluid findings. The number of polymorphonuclear neutrophilic leukocytes (PMNs) has been reported to be the most useful parameter in detecting BP. In Hoefs’ study (Hepatology 1982;2:399407) of 43 patients with BP, all had a PMN count >25Oi m13. There has been dispute, however, as to what the required cutoff point for PMNs should be in order to establish this diagnosis with certainty. Both false-positive and false-negative results have been reported when using this 2591m13 PMN level, and this has led to a search for other determinants of bacterial infection. Gitlin (Hepatology 1982;2:408-11) reported that an ascites pH C7.32 strongly suggested infection. Kao and Reynolds (Hepatology 1983;3:275) reported that they could not confirm the association between low ascitic pH and BP, although their data suggested an increased gradient between arterial pH and the pH of the ascites in infected patients. The present study was based on 70 patients with ascites who had determination of PMN count, as well as pH and lactate levels in ascites and arterial blood. Fourteen patients were considered to have BP, I2 of whom had positive cultures. In 11 of these patients the peritonitis was considered spontaneous. The 51 noninfected specimens had a mean PMN count of 122 but 7 of them had levels >250, thereby raising the question of possible BP. The pH of this non-BP group had a mean value of 7.45. There was almost no difference between arterial and ascites pH. The mean lactate level in the ascites of non-BP patients was 15 mgidl, with a minimal difference between arterial blood and ascites (3 mgidl). The 14 patients with BP all had significantly different results. The ascitic fluid contained a mean of 2686 PMN/m13. The mean pH of the infected ascites was 7.24, with a gradient of 0.22 between ascites and arterial blood. Lactate levels showed a mean of 45 mgi dl in the ascites with a gradient of 13 mgidl between ascites and arterial blood. There was no correlation between the organisms cultured and any of these determinations. The authors conclude that the PMN count remains the single most sensitive test for BP if 500 PMNlml” is accepted as the cutoff point. A pH ~7.35 or a gradient between ascites and peripheral blood of >O.lO pH units are highly suggestive of BP, although not as sensitive a parameter as the PMN count. Lactate levels >25 mgidl in ascites are also highly accurate predictors of BP. Neither glucose levels nor total white blood cell count were of much practical use in detecting BP. Thus, if either the PMN level is >500/m13 or the pH level is ~7.35 in ascitic fluid, BP can be diagnosed with great accuracy (98%). If both these determinants are normal, BP is virtually excluded. Lactate determinations are almost as good as pH but, because they are more time consuming and less available, their routine use is not required.

694

GASTROENTEROLOGY

SELECTED SUMMARIES

Comment.

It appears that the determination of PMN count and pH level in ascitic fluid provides an excellent method for detecting BP before culture reports are available. The use of the pH gradient between arterial blood and ascites may be helpful in cases with an abnormal blood pH. The only false-positives reported were patients with peritoneal metastases who occasionally had an elevated PMN count or low pH. This is probably of little clinical concern because the antibiotic treatment of such patients for a short period of time, pending the results of the cytologic and bacteriologic studies, would not be detrimental. The study did not address the question of how spontaneous BP occurs, nor did it provide guidance as to when a paracentesis is indicated. Although many of these patients have some clinical abnormality (e.g., lowgrade fever, encephalopathy) these findings may continue to fluctuate over a period of weeks. The authors mention that their original series of paracentesis totalled 209. Eighty-seven of these were follow-up examinations and were not included in the present analysis. It would be useful to know, however, why the follow-up taps were done and what they showed. There is a common clinical dilemma when the physician tries to decide how often to retap a sick patient with ascites and how to interpret the follow-up results. In the study by Hoefs, a majority of the patients developed their BP after the first week in the hospital. We would anticipate a significant difference between the initial tap and any subsequent examinations in the delayed group, but there is little information available about such differences. Although it is comforting to know that with the measurement of PMN count and pH on the initial tap we can at least make a diagnosis of BP with great accuracy, we still need help in deciding how to manage the sick patient with persistent ascites.

Vol. 89. No. 3

A, Chen M, Brackett K (Department of Surgery, University of Cincinnati Medical Center, Cincinnati, Ohio) In vitro and in vivo technique for assessing vagus nerve regeneration after parietal cell vagotomy in the rat. J Auton Nerv Syst 1983;9:27-51 [October).

Such parietal cell vagotomy (PCV) abolishes the gastric secretory response to insulin hypoglycemia (e.g., leads to a negative Hollander test) and prevents the recurrence of peptic ulceration-at least for some time. Whether the cut vagal nerve fibers regenerate and reinnervate the parietal cells eventually is not known. What is known is that the Hollander test frequently converts from negative in the early postoperative period to positive at a later time. Perhaps related to this is the increasingly reported recurrence of peptic ulcers long after PCV. In previous studies on rats, the authors noted that PCV abolished acid secretion and the formation of experimental ulcers for <1 wk. Now the authors have studied the sequence of morphologic changes occurring in the intramural nerve fibers of the proximal stomach after PCV. They measured gastric acid secretion under basal conditions and after stimulation by insulin hypoglycemia. Simultaneously, the authors measured the plasma concentration of pancreatic polypeptide (PP) in hopes that the cumbersome collection of gastric juice presently required to test for the completeness of vagotomy may eventually be replaced by the analysis of blood samples. The nervous structures of the gastric wall were studied at weekly intervals after PCV. For examination by light microscopy, the nervous elements were stained with methylene blue and squash preparations were fixed. In normal animals, this method always demonstrated many nerve axons in the muscle coat and some in the mucosa. All nerve axons had disappeared after PCV. Examination of representative samples of the gastric wall by electron microscopy showed the beaded nerve fibers of the epithelium to be nonmyelineated and to contact parietal cells. After PCV, these nerve axons became swollen and contained fibroblasts instead of neurofilaments. Collagen was deposited around the Schwann cells. This degenerative process began to subside by the third week; by the sixth week, the presence of two types of nerve axons, one small, the other large, was striking. By the ninth week, the morphologic appearance of the nerve axons had returned to normal. Fiber regeneration occurred not simply by sprouting of the intact branches of the nerves of Latarjet, as a simultaneous antrectomy did not interfere with the regeneration. Both basal and stimulated gastric acid secretion fell sharply immediately after the operation, but increased with each subsequent week. By the seventh postoperative week, acid secretion was about twice as high as the preoperative level. Disappointingly, plasma concentrations of PP were not affected by the ingestion of food, insulin hypoglycemia, or the injection of secretagogues. This study has demonstrated that PCV leads to a degeneration of intramural nerve axons, which is then followed by their regeneration. This neuropathologic sequence correlates well with the initial drop in gastric acid secretion and the subsequent acid hypersecretion that is observed after PCV in the rat. A similar sequence in humans would explain the conversion from a negative to a positive insulin stimulation and the late ulcer recurrence after therapeutic parietal cell vagotomy.

Preservation of the nerves of Latarjet reduces the incidence of dumping and diarrhea after selective vagotomy.

abnormalities

J. G. SWEETING, M.D.

Reply. We appreciate Dr. Sweeting’s thoughtful comments about our paper. The number of cases of BP is too small for any one hospital to accumulate large enough series of patients to answer many of the questions asked. For example, follow-up findings in the ascitic fluid during antibiotic therapy of BP are currently being examined. Similarly, the findings of paracentesis prior to the development of BP are being examined. These and other investigations are being conducted jointly by the Ascites International Diagnostic Society, a group of physicians who are collaborating in order to achieve large numbers of cases of BP. We believe that paracentesis should be performed at least every z days after therapy has been started until the fluid is sterile and the PMN and pH abnormalities approach or achieve normality. Preliminary findings suggest that the PMN count decreases to half after 2 days of effective therapy. If if doesn’t, one must consider antibiotic therapy to be ineffective or the diagnosis of spontaneous BP to be incorrect, or both. G. GARCIA-TSAO,

M.D.

H. 0. CONN, M.D. E. LERNER

NERVE REGENERATION VAGOTOMY

AFTER

J&e SN, Crocket

Comment.

This study breaks new ground by trying to define in the intramural nerves of the stomach. Very little