Cytomegalovirus esophagitis in patients with AIDS. A clinical, endoscopic, and pathologic correlation.

OBJECTIVE: To examine the clinical presentation, endoscopic features, laboratory diagnosis, and outcome of cytomegalovirus esophagitis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: Retrospective review of endoscopy records and esophageal biopsy material from patients with AIDS during the 24-month period from 1986 to 1988. SETTING: Urban medical center, central receiving county hospital. PARTICIPANTS: Sixteen inpatients or outpatients seen by gastroenterology consultants at a single hospital. INTERVENTIONS: Endoscopy with multiple mucosal biopsies and viral culture of all esophageal mucosal lesions. Proven or suspected cyclomegalovirus disease was verified in patients using immunohistochemical antibody staining of mucosal biopsy specimens. MEASUREMENTS AND MAIN RESULTS: Odynophagia was the most prominent esophageal symptom, seen in 14 of 16 patients with cytomegalovirus esophagitis confirmed by immunohistochemical staining. Ulcerations of the esophagus were identified in all but 1 patient and typically appeared as large, solitary, shallow lesions. Routine hematoxylin and eosin staining of esophageal mucosal and submucosal specimens showed intranuclear inclusions in all patients, whereas cytomegalovirus culture was positive in only 8 of 14 patients. Cytomegalovirus esophagitis was associated with a poor long-term prognosis. CONCLUSION: Cytomegalovirus esophagitis in patients with AIDS is a well-defined entity with characteristic clinical symptoms and endoscopic findings, as well as histopathologic abnormalities.

Detection of HIV in enterochromaffin cells in the rectal mucosa of an AIDS patient.

The human immunodeficiency virus (HIV) was detected by in situ hybridization in the bowel crypt and lamina propria in the rectal mucosa of an acquired immune deficiency syndrome (AIDS) patient. More infected cells were noted in the crypts than the lamina propria. The enterochromaffin cell was one cell type showing the presence of virus. HIV may play an important role in some gastrointestinal disorders in infected individuals.

Human immunodeficiency virus detected in bowel epithelium from patients with gastrointestinal symptoms.

Infectious human immunodeficiency virus (HIV) was recovered from two out of four bowel biopsy specimens from acquired immunodeficiency syndrome (AIDS) patients with chronic diarrhoea of unknown aetiology. In-situ hybridisation of biopsy specimens from rectum and duodenum of other AIDS patients with gastrointestinal complaints showed the presence of HIV-infected cells in both the base of the bowel crypts and the lamina propria. The type(s) of epithelial cell(s) infected could not be determined definitively. However, the association of in-situ labelling of HIV RNA in argentaffin staining cells strongly suggests that enterochromaffin cells derived from neural crest tissue are among the target cells. This evidence that HIV can directly infect the bowel raises the possibility that the virus causes some of the gastrointestinal disorders of AIDS patients.

Hepatic disease in patients with the acquired immune deficiency syndrome (AIDS).

The spectrum of liver disease in patients with acquired immune deficiency syndrome (AIDS) and the clinical impact of diagnostic percutaneous liver biopsy in this population were evaluated by a retrospective review of hepatic histology, clinical features and laboratory data in 85 patients (26 biopsies, 59 autopsies). Only 1 (3.8%) biopsy and 9 (15%) postmortem livers were histologically normal. Macrosteatosis and nonspecific portal inflammation were the most common histologic abnormalities. Intrahepatic AIDS-specific opportunistic infections or malignancies were detected in 42% of both biopsy and autopsy groups, with Mycobacterium avium-intracellulare the most frequent pathogen seen. Kaposi's sarcoma, although not detected on biopsy, was the most common postmortem AIDS-related hepatic finding. Intrahepatic lymphoma, cytomegalovirus hepatitis and hepatic mycoses were less frequently observed. In general, hepatic involvement represented part of a previously diagnosed, widely disseminated disease process, and liver biopsy led to new AIDS-specific diagnoses in only two patients. We conclude that while liver biopsy is a useful diagnostic tool in selected patients with AIDS, the information provided by biopsy rarely influences therapy or leads to improved survival.

Streptokinase alters myocardial creatine kinase depletion after ischaemia and reperfusion in rabbits.

The efficacy of streptokinase as an intracoronary thrombolytic agent is well-recognized. The effect of streptokinase, distinct from its thrombolytic action, on ischaemic myocardium distal to an area of coronary artery occlusion when reperfusion occurs has not been well-defined. In order to do this, myocardial creatine kinase depletion and the histopathology of infarctions produced in rabbits after 1 h of circumflex coronary artery occlusion and mechanical release of the occlusion were assessed. Streptokinase or saline was infused intravenously for 1 h beginning 0.5 h after occlusion. Rabbits were divided into two time intervals: early (less than 10 h) and late (24 h) after release of coronary artery occlusion. When streptokinase was infused in early infarctions, haemorrhage did not correlate with infarction cross-sectional area or myocardial creatine kinase depletion. However, myocardial creatine kinase depletion was 40% less when streptokinase was infused than when saline was infused, suggesting that streptokinase might limit infarct size. In late infarctions, the degree of haemorrhage, infarction cross-sectional area, and myocardial creatine kinase depletion were similar after reperfusion with streptokinase or saline. By 24 h, the beneficial effect of a single dose of streptokinase given early in the course of occlusion-reperfusion myocardial injury was no longer evident in limiting infarct size.

Antibody to the retrovirus associated with the acquired immunodeficiency syndrome (AIDS). Presence in presumably healthy San Franciscans who died unexpectedly.

We performed autopsies and serologic tests in 189 subjects (152 men and 37 women) between 20 and 50 years of age with no history of immunosuppression who died unexpectedly and whose bodies were referred to the San Francisco coroner's office. Forty-eight of the 88 single men for whom addresses were available lived in areas of the city with a high incidence of the acquired immunodeficiency syndrome (AIDS). In addition, 36 of the subjects (30 men) were intravenous drug abusers. Antibody to the retrovirus associated with AIDS was present in 23 (18%) of the 121 subjects whose sera were tested. However, neither pathologic nor laboratory manifestations of AIDS were present in any of the 189 subjects who underwent autopsy. These results suggest that antibody to the retrovirus is common but subclinical manifestations of AIDS are uncommon in San Francisco, a city where the incidence of clinical AIDS is high.

Cytomegalovirus colitis. Report of the clinical, endoscopic, and pathologic findings in two patients with the acquired immune deficiency syndrome.

We report 2 homosexual patients with the acquired immune deficiency syndrome and histopathologic evidence for cytomegalovirus colitis. In each case, the initial endoscopic impression was Kaposi's sarcoma but the appropriate diagnosis was made by histologic demonstration of a cytomegalovirus vasculitis. Clinical manifestations may include diarrhea, abdominal pain, and hematochezia. Fulminant progression to gangrenous bowel was documented in 1 patient and was associated with histologic evidence of severe cytomegalovirus vasculitis. The pertinent clinical, endoscopic, and pathologic findings are reviewed.

Impact of preshunt liver histology on survival following portasystemic shunt surgery for bleeding esophageal varices.

To determine the value of liver histology in predicting one-year survival after protal venous decompression, eight hepatic histologic features were evaluated prospectively in 53 patients. The presence of panlobular fat and of alcoholic hyaline were the only individual features having a significant correlation with outcome. When the predictive power of these histologic features was compared by linear logistic regression analysis to that of 28 clinical and laboratory variables, panlobular fat was the best single predictor, followed in sequence by admission prothrombin time, alcoholic hyaline, admission hematocrit, and Child's C classification. The combination of hematocrit and panlobular fat produced the best two-variable equation, predicting outcome in 79% of patients. No three-variable equation significantly improved upon the two-variable combination of hematocrit and panlobular fat. Therefore certain hepatic histologic features, alone or in combination with other factors, appear to be powerful predictors of one-year mortality. When liver biopsy is obtainable, histologic features should be considered in determining suitability for portasystemic shunt surgery.

Closed-chest electrode-catheter technique for His bundle ablation in dogs.

A modified quadripolar electrode catheter that had two-thirds of the distal surface insulated with high-voltage plastic was inserted in 10 dogs. After a His bundle potential had been recorded, a synchronized direct-current electrical discharge was delivered between the electrodes showing the largest His bundle deflection using a standard direct-current defibrillator, and a metallic plate was positioned over the dog's back. Complete atrioventricular (AV) block was induced in 9 of 10 dogs, which were followed for 3 mo before being killed. During AV block, the QRS complex was broad and not preceded by a His bundle deflection. The mean control cycle length during AV block was 1,441 +/- 223 ms and decreased to 1,151 +/- 181 ms after exercise, a response that was usually abolished by beta-blockade. Overdrive pacing resulted in pacemaker suppression with gradual rate stabilization after 10-20 beats. There was no evidence of myocardial or valvular damage. This technique provides for a stable model of complete AV block and is suitable for experiments in which heart rate control is required. In addition, this technique may be of value for patients with tachycardia requiring His bundle section.

Effects of intravascular clotting on the activation of the complement system: The role of the platelet.

Total hemolytic complement activity and the third component of complement were found to be significantly depressed in vivo in rabbits following the induction of disseminated intravascular coagulation by both thrombin and thromboplastin. Production of severe thrombocytopenia by the administration of platelet antiserum prior to the infusion of thrombin or thromboplastin partially prevented complement activation. The data show that, when clotting is triggered, complement activation takes place and that platelets are required to some extent for this reaction.

Spontaneous delayed splenic rupture--case report of a five-year interval between trauma and diagnosis.

A 27-year-old white man was admitted in shock with a tender distended abdomen 5 years following significant thoraco-abdominal trauma. Immediately following resuscitation he had an emergency exploratory laparotomy because of his critical condition. At operation 3 liters of old and fresh blood were present intraperitoneally and the spleen was ruptured. The spleen was surrounded by and adherent to the omentum and adjacent viscera. Splenectomy was performed and recovery was uneventful. Histologic examination of the spleen confirmed the 5-year interval between injury and rupture. Delayed splenic rupture accounts for 14% of all splenic injuries and has a high mortality. This case represents the longest reported delay between splenic trauma and delayed rupture.

The effect of shock on the inflammatory response. A reevaluation of the role of platelets in the active arthus reaction.

The active Arthus reaction can be inhibited by hypovolemic shock or the infusion of catecholamines. A reevalution of previous work with platelet antiserum indicates that shock rather than thrombocytopenia was responsible for preventing the active Arthus reaction. Immunofluorescent studies of the inhibited Arthus sites reveal that immune precipitates are not present in the extravascular tissues. Since leukocyte aggregates can be seen within venules at the inhibited sites, and they phagocytize BSA-anti-BSA complexes, their failure to migrate out of the vessels is due to the absence of complexes in the extravascular spaces. (Am J Pathol 78:159-170, 1975)

The participation of the platelet in the vascular response to endotoxemia in the rabbit eye.

Platelet depletion by a specific goat antirabbit platelet antiserum profoundly affected the response of the ocular blood vessels to intravenous endotoxin. The altered permeability of the vessels of the iridial portion of the ciliary processes in the thrombocytopenic animals was reduced by 50% at 1(1/2) hours and by 30 to 58% at 4 hours after endotoxin administration. Intravascular fibrin at the 4-hour period could be eliminated by a properly timed platelet depletion. By preventing platelet aggregations and fibrin formation, the permeability alteration could be reduced by 66% and the usual stromal hemorrhages practically eliminated. Underlying these effects of the platelet was evidence of a vascular trauma unrelated to platelet activity and probably dependent to some extent on adrenergic stimulation. Platelet aggregation and/or fibrin formation had to be superimposed on the underlying vascular trauma to produce endothelial denudation.

Corticosteroids and the generalized Shwartzman reaction. Mechanisms of sensitization in the rabbit.

An analysis of the effects of adrenal cortical steroids on the response of the vascular system to bacterial endotoxin has shown that glucocorticoids (cortisone, triamcinolone) are capable of preparing the system for the generalized Shwartzman reaction. On the other hand, the mineralocorticoid desoxycorticosterone acetate does not have this capability. The mechanism of preparation by glucocorticoids has been studied. Administering insulin, with maintenance of normal blood sugar, had no effect on the extent of glomerular capillary thrombosis. Blockade, however, of alpha-adrenergic receptor sites by Dibenzyline caused a significant reduction of the thrombosis. In addition, cortisone-treated animals did not require exogenous stimulation of alpha-adrenergic receptor sites by norepinephrine to localize thrombi in the glomerular capillaries when Hageman factor was activated (by ellagic acid) and fibrinolysis inhibited (by epsilon-aminocaproic acid). It is concluded that glucocorticoids prepare for the generalized Shwartzman reaction by increasing the sensitivity of the microcirculation to stimulation of alpha-adrenergic receptor sites.

The requirement for platelets in the active Arthus reaction.

The active Arthus reaction was completely inhibited in rabbits made thrombocytopenic with platelet antiserum. Platelets or some platelet factor is necessary for the development of immune vasculitis in this model. Since the classic Arthus reaction depends on the union of extravascular antigen with intravascular antibody, it is probable that the missing platelet factor is an agent that alters vascular permeability.

The role of the platelet in the generalized Shwartzman reaction.

Rabbits were injected with an antiplatelet serum to produce selective thrombocytopenia without inducing a significant alteration of their leukocyte counts. Thrombocytopenic levels persisted for 8 hr after the injection of platelet antiserum. During this time, the generalized Shwartzman reaction could not be provoked with the second injection of endotoxin. Since platelet phospholipid is required for the formation of plasma thromboplastin, the results indicate that platelets are essential to the evolution of the generalized Shwartzman reaction and endotoxin triggers the intrinsic rather than the extrinsic clotting system to elicit the lesions.