Infected Clots Research Articles

Diagnosis of the right atrial myxoma after treatment of COVID‐19: A case report

Atrial myxoma is a rare disease but has a broad clinical presentation and complication that involves several systems- heart, lungs, brain, and systemic. An interdisciplinary approach is very important to optimize the outcome in patients with atrial myxomas. A thorough examination by primary care providers is crucial. Then radiologists or cardiologists can help with imaging modalities that can help diagnose and characterize the tumor. Prior to surgical resection by cardiothoracic surgeons, patients need to be evaluated by pulmonologists, cardiologists, and anesthesiologists for preoperative risk stratifications. In patients with neurological complications, pulmonary complications, or infectious endocarditis, input from neurologists, hematologists, infectious disease specialists is essential for patient care. In case antiplatelet/anticoagulation therapy or antibiotic treatment is warranted, pharmacists can provide valuable recommendations. Myxoma is the most common benign cardiac primary tumor, occurring in the right atrium in only 15%-20% of cases. This disease is asymptomatic initially depending upon size of the tumor, and symptoms develop as the tumor spreads. Atrial myxomas are associated with a triad of complications, including obstruction, emboli, and constitutional symptoms (such as fever and weight loss). This regard, embolization of the pulmonary circulation system is a complication of right myxoma. The patient was a 40-year-old male who presented to the emergency department complaining of fever and confusion. He had been previously hospitalized due to COVID-19 and treated with Remdesivir and plasmapheresis. He had tachycardia, tachypnea, thrombocytopenia, and increased liver enzymes. Chest imaging showed nodular lesions with necrotic areas and cavitary lesions in both lungs and the right atrium infected clot was seen in echocardiography. He was treated with intravenous antibiotics and finally underwent heart surgery due to the diagnosis of pulmonary septic embolism. The patient was finally diagnosed with right atrial myxoma according to heart mass histopathology. It is worth noting that the patient's thrombosis had already developed on the right atrial myxoma, which delayed the diagnosis in this patient. This thrombus formation was due to the hypercoagulability state of COVID-19 and following the insertion of a central venous catheter to perform plasmapheresis as a complication of treatment. Special attention should be paid to thromboprophylaxis and the early diagnosis of intravascular and intracardiac thrombosis in COVID-19 patients. Furthermore, the use of imaging modalities is recommended to differentiate thrombus from myxoma.

Human Pythiosis: Emergence of Fungal-Like Organism.

Pythiosis is an emerging infectious disease caused by the aquatic oomycete Pythium insidiosum, a fungal-like organism. It is believed that P. insidiosum's zoospores, its infected form, play major role in pathogenesis. Vascular and ocular infections are the most common clinical manifestation in humans. It is difficult to establish the diagnosis given its relatively rarity and difficulty to distinguish P. insidiosum from other molds. Delay in diagnosis and treatment has been associated with poor outcomes. High index of suspicion is the key, particularly in thalassemia patients with arterial insufficiency and patients with fungal keratitis/endophthalmitis without improvement on antifungal therapy. Tissue culture and zoospore induction remain gold standard for diagnosis; however, DNA-based method should be performed simultaneously. The combination of radical surgery, antifungal agents, and immunotherapy has been recommended. It was previously believed that surgery with negative surgical margins was the essential to survive in vascular pythiosis; however, it was recently found that patients could have residual disease despite documented negative surgical margins as infected clot may be dislodged to proximal arterial sites prior to surgery. Serum β-D-glucan (BG) has been used to monitor disease response after treatment initiation in vascular pythiosis. A significant decrease in BG levels within 2weeks after surgery is indicative of the absence of residual infection. Unfortunately, monitoring tools for ocular pythiosis are not yet available. Itraconazole plus terbinafine have generally been used in P. insidiosum-infected patients; however, antibacterial agents, including azithromycin and linezolid, have also been used with favorable outcomes in ocular disease. Recently, azithromycin or clarithromycin plus doxycyclin were used in two relapsed vascular pythiosis patients with good outcomes.

An in vitro proof-of-principle study of sonobactericide

Infective endocarditis (IE) is associated with high morbidity and mortality rates. The predominant bacteria causing IE is Staphylococcus aureus (S. aureus), which can bind to existing thrombi on heart valves and generate vegetations (biofilms). In this in vitro flow study, we evaluated sonobactericide as a novel strategy to treat IE, using ultrasound and an ultrasound contrast agent with or without other therapeutics. We developed a model of IE biofilm using human whole-blood clots infected with patient-derived S. aureus (infected clots). Histology and live-cell imaging revealed a biofilm layer of fibrin-embedded living Staphylococci around a dense erythrocyte core. Infected clots were treated under flow for 30 minutes and degradation was assessed by time-lapse microscopy imaging. Treatments consisted of either continuous plasma flow alone or with different combinations of therapeutics: oxacillin (antibiotic), recombinant tissue plasminogen activator (rt-PA; thrombolytic), intermittent continuous-wave low-frequency ultrasound (120-kHz, 0.44 MPa peak-to-peak pressure), and an ultrasound contrast agent (Definity). Infected clots exposed to the combination of oxacillin, rt-PA, ultrasound, and Definity achieved 99.3 ± 1.7% loss, which was greater than the other treatment arms. Effluent size measurements suggested low likelihood of emboli formation. These results support the continued investigation of sonobactericide as a therapeutic strategy for IE.

Structure, Mechanics, and Instability of Fibrin Clot Infected with Staphylococcus epidermidis

Health care-associated infection, over half of which can be attributed to indwelling medical devices, is a strong risk factor for thromboembolism. Although most experimental models of medical device infection draw upon isolated bacterial biofilms, in fact there is no infection without host protein contribution. Here we study, to our knowledge, a new model for medical device infection—that of an infected fibrin clot—and show that the common blood-borne pathogen Staphylococcus epidermidis influences this in vitro model of a blood clot mechanically and structurally on both microscopic and macroscopic scales. Bacteria present during clot formation produce a visibly disorganized microstructure that increases clot stiffness and triggers mechanical instability over time. Our results provide insight into the observed correlation between medical device infection and thromboembolism; the increase in model clot heterogeneity shows that S. epidermidis can rupture a fibrin clot. The resultant embolization of the infected clot can contribute to the systemic dissemination of the pathogen.

Sonobactericide: An ultrasound-mediated adjunct treatment for bacterial infective endocarditis—In vitro proof-of-principle

Infective endocarditis (IE) is a bacterial infection of the surfaces within the heart, associated with high morbidity and mortality rates. The predominant bacteria causing IE are Staphylococci, which can bind to existing thrombi on heart valves and generate vegetations (biofilms). In this in vitro study, we test a novel strategy called sonobactericide to treat IE using ultrasound and ultrasound contrast agents, in combination with an antibiotic and a thrombolytic. We simulated IE vegetations using human whole-blood clots infected with Staphylococcus aureus. Histology and live-cell imaging revealed a biofilm layer of fibrin-embedded living Staphylococci. Infected clots were treated under flow for 30 min and degradation was assessed by time-lapse microscopy imaging. Clots were exposed to human plasma flow either alone or with different combinations of therapeutics: oxacillin (172 μg/mL), recombinant tissue plasminogen activator (rt-PA; 3.15 μg/mL), intermittent (50 s on, 30 s off) continuous-wave ultrasound (120 kHz, 0.44 MPa peak-to-peak pressure), and Definity (2 μl/ml). Infected clots exposed to the combination of oxacillin, rt-PA, ultrasound, and Definity achieved 99.3 ± 1.7% clot width loss, which was greater than the other treatment arms. These results demonstrate that sonobactericide may have potential as an adjunct therapy for IE.

Sonobactericide - An Adjunct Therapy for Infective Endocarditis: An In Vitro Proof-of-Concept

Infective endocarditis (IE) is associated with high morbidity and mortality rates. The predominant bacteria causing IE is Staphylococcus aureus (S. aureus), which can bind to existing thrombi on heart valves and generate vegetations (biofilms). In this in vitro study, we evaluated sonobactericide as a novel strategy to treat IE, using ultrasound and an ultrasound contrast agent in combination with an antibiotic and a thrombolytic. We developed a model of IE vegetations using human whole-blood clots infected with S. aureus. Histology and live-cell imaging revealed an outer biofilm layer of fibrin-embedded living Staphylococci around a dense erythrocyte core. Infected clots were treated under flow for 30 minutes and degradation was assessed by time-lapse microscopy imaging. Treatments consisted of either continuous plasma flow alone or with different combinations of therapeutics: oxacillin (antibiotic), recombinant tissue plasminogen activator (rt-PA; thrombolytic), intermittent continuous-wave low-frequency ultrasound (120-kHz, 0.44 MPa peak-to-peak pressure), and an ultrasound contrast agent (Definity®). Infected clots exposed to the combination of oxacillin, rt-PA, ultrasound, and Definity achieved 99.3 ± 1.7% clot width loss, which was greater than the other treatment arms. Size measurements of the effluent suggested low emboli risk. These results demonstrate that sonobactericide could be an effective therapeutic strategy for treating IE.

Endoscopic treatment of an infected retroperitoneal hematoma following endoscopic ultrasound-guided pseudocyst drainage

hematoma following endoscopic ultrasound-guided pseudocyst drainage A 32-year-old man with alcoholic pancreatitis presented with the complaint of abdominal pain and vomiting that necessitated parenteral feeding. Abdominal computed tomography (CT) scan showed a 10-cm pseudocyst in the pancreatic body (● Fig.1) [1]. In view of persisting symptoms and the pseudocyst size, he was referred for endoscopic ultrasound (EUS)-guided cystogastrostomy. Echoendoscopy confirmed the presence of a large pancreatic cyst adherent to the stomach wall. Cystogastrostomy was complicated by spurting of blood from the gastric wall into the pseudocyst cavity. A metal stent was placed across the gastrocystic fistula with initial hemostasis. However, a few minutes later the patient developed hematemesis with a significant drop in hemoglobin. An arteriogram showed active bleeding from a left gastric artery branch (● Fig.2) and transcatheter embolization of this branch was carried out using metal coils. Repeat arteriogram 10 minutes later confirmed successful hemostasis. Prophylactic antibiotics were started. However 5 days later the patient developed high grade fever, and abdominal CT showed a large retroperitoneal hematoma (● Fig.3). We decided to remove the infected clots by using the same technique as for endoscopic necrosectomy. After removal of the metal stent, a gastroscope was passed through the fistula into the retroperitoneal cavity. Blood clots were removed using a Roth Net (● Fig.4) and the cavity was washed with saline. A nasogastric tube was inserted into the cavity and 4-hourly saline lavage was applied through the tube. Another session of endoscopic clot removal was carried out 3 days later, and two double-pigtail catheters (10Fr, 10cm) were inserted into the cavity. CT carried out after the second endoscopy confirmed resolution of the hematoma (● Fig.5), with the patient becoming afebrile soon after that. EUS-guided drainage is the preferred approach for management of pancreatic pseudocyst because of its lower morbidity rate compared with surgical and percutaneous approaches [2]. However, this procedure may be complicated by bleeding [3], and retroperitoneal hematomas arising after bleeding into cyst cavities may become infected. This is the first reported case of management of an infected retroperitoneal hematoma by endoscopic “clot-ectomy.” Fig.3 Abdominal CT shows a large retroperitoneal hematoma. Fig.2 a Metal stent across a gastrocystic fistula, with active bleeding. b Arteriogram showing active bleeding from a left gastric artery branch. Fig.1 Computed tomography (CT) scan showing a 10-cm pancreatic pseudocyst compressing the stomach. Cases and Techniques Library (CTL) E395

Spatiotemporal progression of localized bacterial peritonitis before and after open abdomen lavage monitored by in vivo bioluminescent imaging

Bacterial peritonitis is a life-threatening abdominal infection associated with high morbidity and mortality. The rat is a popular animal model for studying peritonitis and its treatment, but longitudinal monitoring of the progression of peritonitis in live animals has been impossible until now and thus required a large number of animals. Our objective was to develop a noninvasive in vivo imaging technique to monitor the spatiotemporal spread of bacterial peritonitis. Peritonitis was induced in 8 immunocompetent male Wistar rats by placing fibrin clots containing 5x10(8) cells of both Bacteroides fragilis (American Type Tissue Culture [ATCC)] 25,285 and bioluminescent Escherichia coli Xen14. After 1 or 2 days, infected clots were removed and open abdomen lavage was performed. In vivo bioluminescent imaging was used to monitor the spread of peritonitis. Bioluminescent in vivo imaging showed an increase in the area of spread, and the number of E. coli tripled into the rat's abdominal cavity on day 1 after clot insertion; however, on day 2, encapsulation of the clot confined bacterial spread. Bioluminescent E. coli respread over the peritoneal cavity after lavage; within 10 days, however, in vivo imaging showed a decrease of 3-4 orders of magnitude in bacterial load. Bioluminescent in vivo imaging can be effectively used to monitor the spatiotemporal behavior of the peritonitis during 3 different stages of the disease process: initiation, treatment, and follow-up. Imaging allows researchers to repeatedly image the same animal, thereby reducing variability and providing greater confidence in determining treatment efficacies for therapeutic interventions using a small number of animals.

Left atrial giant thrombus infected by Escherichia Coli. Case report

BackgroundLeft atrial thrombi are mostly related to mitral valve disease. The differential diagnosis of clots and myxomas in the left atrium is mostly based on echocardiography. Infection of intracardiac thrombi is extremely rare and mostly reported in ventricular clots or aneurysms following myocardial infarction.Case presentationWe present the case of a 65 year old female with a history of mitral valve disease and chronic atrial fibrillation who suffered repeated embolic strokes and a giant infected clot in the left atrium. Although the patient underwent prompt surgery with removal of the clot and valve replacement the complication of septic emboli to the CNS led her to death. To the best of our knowledge this is the second report of an infected left atrial thrombus.ConclusionThe case is a representative example of a neglected and undertreated patient with catastrophic consequences. Anticoagulant therapy in patients with mitral valve disease and atrial fibrillation should be applied according the currently available guidelines and standards in order to avoid analogous paradigms in the future. Mitral valve substitution should be considered in patients with mitral valve disease presenting thromboembolic complications. Surgery should be considered as the treatment of choice in cases of organized left atrial thrombus and suspected tumor or infected mass.

Protective effect of a novel, potent inhibitor of poly(adenosine 5'-diphosphate-ribose) synthetase in a porcine model of severe bacterial sepsis.

To determine whether activation of the nuclear enzyme poly(adenosine 5'-diphosphate [ADP]-ribose) synthetase (PARS) contributes to mortality rate, myocardial dysfunction, and cardiovascular collapse in a porcine model of sepsis induced by implantation of an infected clot. Prospective, random animal study. Research laboratory at Rush Presbyterian St. Luke's Medical Center. Twenty pigs were chronically instrumented with intracardiac transducers to measure left ventricular pressure, sonomicrometer crystals in the left ventricle to measure short axis diameter, an ultrasonic flow meter to measure cardiac output, and catheters in the pulmonary artery and aorta to measure blood pressures and collect samples. By using a randomized study design, we administered either the novel potent PARS inhibitor PJ34 (10 mg/kg for 1 hr, 2 mg x kg(-1) x hr(-1) for 96 hrs) or vehicle to pigs immediately before intraperitoneal implantation of Escherichia coli 0111.B4 (2.3 +/- 0.1 x 10(10) colony-forming units/kg)-laden fibrin clots to produce peritonitis and bacteremia. In vehicle-treated pigs, 12% survival was recorded at 24 hrs, whereas 83% and 66% survival was recorded in the PJ34-treated animals at 24 and 96 hrs, respectively (p <.05). PJ34 treatment attenuated bacteremia-induced increases in systemic and pulmonary vascular resistances. In controls, peritonitis induced rapid increase in plasma tumor necrosis factor-alpha. PJ34 treatment significantly attenuated this cytokine response. The formation of peroxynitrite and the activation of PARS were confirmed in hearts and lungs of the septic pigs by the immunohistochemical detection of nitrotyrosine and poly(ADP-ribose), respectively. Inhibition of PARS with PJ34 abolished poly(ADP-ribose) formation in septic animals. Treatment with a potent PARS inhibitor improved survival and cardiovascular status and attenuated an important mediator component of the inflammatory response in a lethal porcine model of sepsis.

An improved clinically relevant sepsis model in the conscious rat.

To develop an improved small animal experimental paradigm that more closely mimics human sepsis. Prospective, randomized, controlled animal study. Medical school research laboratory. Male Sprague-Dawley rats (280-320 g). We monitored the hemodynamic, hematologic, and biochemical consequences of abdominal sepsis produced by intraperitoneal implantation of a fibrin clot containing Escherichia coli in conscious, antibiotic-treated, rats. Similar to human sepsis, the implanted, infected clot (LD50 = 5-7 x 10(8) colony forming units/mL, n = 6) elevated cardiac index (>7% vs. sterile clot, p < .05, at 4 hrs), whereas mean arterial pressure and heart rate remained unaffected. The total peripheral resistance index and stroke volume index tended to decrease and increase, respectively. In contrast, an intravenous bolus injection of endotoxin (LD50 of E. coli lipopolysaccharide = 5.6 mg/kg, n = 7), the most commonly used sepsis model, induced profound hypodynamic responses manifested by a 27% decrease (vs. endotoxin vehicle, p < .01) in cardiac index, a 28% increase in the total peripheral resistance index (p < .01), and a 33% decrease in the stroke volume index (P < .01). The infectious peritonitis model also displayed dose-dependent thrombocytopenia (<61%, p < .05), leukopenia (<60%, p < .05), and mortality rate (50% at 5-7 x 10(8) colony forming units/mL, p < .05) with a minimally elevated serum tumor necrosis factor-alpha level (145 vs. 12 +/- 6 pg/mL in controls, p < .05). This rodent model of antibiotic-treated, intra-abdominal infection features key characteristics of clinical sepsis. Although the hyperdynamic response observed in septic patients undergoing resuscitation was not clearly elicited, this paradigm better mimics clinical sepsis compared with the commonly used endotoxin model. Thus, utilization of this paradigm may provide additional opportunities to explore mechanisms of sepsis and to examine novel therapeutics.

Diagnosis of venous access port-related infections.

The accumulation of infected clots under the silicone septum of the reservoir of venous access ports (VAPs) has been reported. We analyzed the relationship between these deposits and the occurrence of VAP-related bloodstream infections (VAP-BSIs) by (1) evaluating the accuracy of paired quantitative blood cultures for diagnosing VAP-BSI before the removal of the device and (2) assessing the accuracy of cultures of the tip and septum (i.e., the internal lumen of the VAP) for diagnosing VAP-BSI after removal of the device. Over a 16-month period, all VAPs removed were prospectively investigated. Before VAP removal, paired quantitative blood cultures were 77% sensitive and 100% specific and had a positive predictive value of 100% and a negative predictive value of 98% for diagnosing VAP-BSI. After VAP removal, tip culture was only 46% sensitive, whereas septum culture was 93.3% sensitive for confirming the diagnosis of VAP-BSI. Thus infected deposits that accumulate under the VAP septum are the source of VAP-BSI.

Migration of rat peritoneal cells after intra-abdominal infection with Bacteroides fragilis and Escherichia coli.

A fibrin clot model for intra-abdominal abscess formation was used to study the migratory properties of peritoneal cells from rats during the early stages of infection. Peritoneal cells and fibrin clot remnant were harvested 6 h after implantation of a sterile, singly infected (Escherichia coli or Bacteroides fragilis) or mixed infected (E. coli and B. fragilis) fibrin clot. Histological study of fibrin clots, removed 6 h after implantation, showed a deeper infiltration by host cells of B. fragilis infected clots compared to the others. This difference in infiltration by peritoneal cells was not due to differences in fibrinolytic activity of the bacterial strains. Differential cell counts of the peritoneal cells from rats implanted with sterile, singly and mixed infected fibrin clots showed distribution over subpopulations to be independent of the bacterial content of the infected clots used. In vitro migration assays showed no significant differences in migration by peritoneal cells from rats implanted with clots containing a different bacterial composition. Since B. fragilis infected fibrin clots were more deeply infiltrated by host defence cells than the other clots, and only mixed infected clots led to persistent abscesses in this model, we conclude that local conditions within the fibrin matrix rather than intrinsic cellular capacities of the host cells are important for the process of abscess formation.

Leukocyte CD18 monoclonal antibody worsens endotoxemia and cardiovascular injury in canines with septic shock

We investigated the effects of a murine monoclonal antibody directed against the canine leukocyte CD11/18 adhesion complex (MAb R15.7) in a canine model of septic shock. Awake 2-yr-old purpose-bred beagles were studied 7 days before and 1, 2, 4, and 10 days after intraperitoneal placement of an Escherichia coli-infected fibrin clot. Starting 12 h before clot placement, animals received 0.5-1 mg/kg iv every 12 h (4 doses total) of either MAb R15.7 (MAb group, n = 8) or, as controls, murine serum protein (n = 8). After infected clot placement, all animals received antibiotic (ceftriaxne, 100 mg.kg-1.day-1 for 4 days). Two of eight control animals and four of eight MAb animals died (P = 0.4). During the first 8 h after clot placement, MAb animals, compared with control animals, had greater (P < 0.06) increases in serum endotoxin levels and higher (P < 0.05) neutrophil counts. Day 1 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) central venous pressure and arterial pH and increased (P < 0.05) arterial lactate. Day 2 after clot placement, MAb animals, compared with control animals, had decreased (P < 0.05) cardiac index and mean arterial pressure. In summary, MAb R15.7, although associated with increased neutrophil counts, worsened serum endotoxemia, acidosis, and cardiovascular function in this canine model of septic shock. These data suggest that in septic shock, antibody directed against this leukocyte membrane protein complex may be harmful, possibly via impairment of normal leukocyte function.

In-vitro activity of peritoneal cells from rats after intra-abdominal infection with Bacteroides fragilis and Escherichia coli.

Peritoneal cells from rats infected intraperitoneally with Escherichia coli and Bacteroides fragilis, alone or in combination were examined in vitro. Cells were harvested 6 h after implantation of fibrin clots infected with E. coli or B. fragilis, separately or containing both species, and assayed for their bactericidal capacities, chemiluminescence and production of cidal metabolites. Peritoneal cell populations from rats with implants of any of the infected clots showed similar distribution of different subpopulations. Bactericidal activity of peritoneal cells did not differ with the bacterial species used. Chemiluminescence values of peritoneal cells from rats with mono-infected B. fragilis or mixed-infected implanted clots, after stimulation with either particles or chemical stimuli, were significantly higher than those of rats with mono-infected E. coli or sterile clots. The same tendency was seen with regard to the production of cidal metabolites such as hydrogen peroxide and superoxide anions although no significant differences were found.

Effect of septic serum on vascular smooth muscle: in vitro studies using rat aortic rings.

Septic shock in humans is characterized by hypotension, low systemic vascular resistance, and high cardiac output. We hypothesized that circulating vasodilatory substances are, in part, responsible for this low systemic vascular resistance. To investigate this possibility, we exposed isolated rat aortic rings to sera from patients with septic shock and to sera from dogs made septic by intraperitoneal implantation of infected clots. Isolated rings from rat thoracic aortas were mounted on hooks in chambers filled with modified Krebs' buffer and bubbled with 95% oxygen/5% CO2. After documentation of functional endothelium, the rings were precontracted with norepinephrine. Serum was then added and ring tension measured continuously over the next 20 mins. Sera from normal humans increased ring tension by 6% (60 +/- 39 [SEM] mg tension/mg ring). Sera from nine patients with septic shock decreased tension by 30% (350 +/- 42 mg tension/mg ring; p less than .001). In response to sera from control dogs, tension increased by 16% (122 +/- 37 mg tension/mg ring). In contrast, septic dog sera caused tension to decrease by 36% (278 +/- 38 mg tension/mg ring;p less than .001). Vasodilation was unaffected when the septic patient and dog sera were dialyzed to remove molecules less than 10,000 molecular weight. Chemical deendothelialization with sodium deoxycholate also did not affect the vasodilatory response to septic patient or dog sera. Septic sera can relax rat aortic smooth muscle. Dialyzing to exclude the effects of small molecules and removing the endothelium did not eliminate this vasodilatory response. These data suggest the presence in septic serum of circulating substances capable of relaxing vascular smooth muscle that may play an important role in the pathogenesis of the cardiovascular abnormalities in septic shock.

Effects of tissue-type plasminogen activator on Staphylococcus epidermidis--infected plasma clots as a model of infected endocardial vegetations.

The ability of tissue-type plasminogen activator (t-PA) to enhance the effect of antibiotics in the treatment of bacterial endocarditis was studied using plasma clots infected with Staphylococcus epidermidis as a model of infected endocardial vegetations. A concentration-dependent lysis of the infected plasma clots was induced by t-PA, as shown by the decrease in the weight of the clots, a decrease in the amount of incorporated 125I fibrin, as well as the release of staphylococci from the clots into the incubation fluid. The addition of cloxacillin to the incubation medium in various concentrations led to a concentration-dependent decrease of the number of S. epidermidis in the clots. The presence of t-PA did not enhance the antibacterial effect of cloxacillin. It is concluded that the lysis induced by t-PA might enhance the effect of treatment of endocarditis by reducing the size of endocardial vegetations but not by enhancement of the effect of antibiotics on the bacteria embedded in the vegetations.

Effects of nonsteroidal anti-inflammatory drugs on renal function in septic dogs.

The effects of nonsteroidal anti-inflammatory drugs on renal function were studied in 15 chronically instrumented, unanesthetized beagles. In 9 dogs, bacterial peritonitis was induced by implanting in the peritoneal cavity a fibrin clot containing viable Escherichia coli. Six (control) dogs were subjected to laparotomy but were not implanted with an infected clot. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were estimated using standard clearance methods. All measurements were performed after resuscitation with Ringer's lactate to a pulmonary capillary wedge pressure of 6 Torr. When measured 24 hr after laparotomy, there were no significant changes (relative to baseline) in GFR or ERPF in either the septic or control groups. In septic dogs, 60 min after the administration of either indomethacin (2 mg/kg) or ibuprofen (25 mg/kg), GFR decreased an average of 26 +/- 11 ml/min (P = 0.043) and ERPF decreased an average of 100 +/- 27 ml/min (P = 0.02). In controls, administration of indomethacin (2 mg/kg) did not significantly affect either GFR or ERPF. These results suggest that renal function should be carefully monitored in clinical trials of nonsteroidal anti-inflammatory drugs in septic patients.

Laboratory and clinical investigation of recovery of Salmonella typhi from blood.

An experimental study was undertaken of isolation of Salmonella typhi from artificially infected whole blood and blood clot prepared either with small numbers of freshly isolated strains or with the S. typhi Ty2 strain. Results showed that 8 ml of whole blood required a minimum of 50 ml of bile salt broth to dilute the bactericidal effect of the serum. However, the isolation rate for recovery in 210 cases of enteric fever was only 64% when 50 ml of medium was used, as compared to 92% recovery from blood clot from the same group incubated in streptokinase bile salt broth. This probably reflects a very low grade bacteremia in many of the patients. Further investigation showed that, ideally, between 150 and 200 ml of medium is required for satisfactory whole-blood culture. Both the experimental study of artificially infected clots and recovery rates from patients indicate that rapid clot dissolution with streptokinase is preferable to whole-blood culture; this experience has been amply confirmed by almost 5,000 cases over a 20-year period. A 15-ml volume of bile salt broth with 100 U of streptokinase is adequate for the clot from 8 ml of blood, and savings on media and incubator space have considerable cost benefits in developing countries.

Aseptic lateral sinus thrombosis.

Occlusion of a lateral sinus by an infected clot is encountered with diminishing frequency as compared with its common occurrence before the days of chemotherapy. Of great rarity is aspetic thrombosis of this venous channel secondary to cranial trauma. When infection is present, the clinical picture is one of sepsis. If the clot is sterile, the patient can be asymptomatic. In 90 per cent of specimens we examined, the lumen of the right lateral sinus was larger than the left. With such inequality, occlusion of the left sinus will not cause the same degree of intracranial hypertension as results from a right sided thrombus. When thrombosis of the right lateral sinus is present and a small left sinus exists, the mastoid, parietal, frontal and occipital emissary veins on the left are too small to carry the additional venous return. Papilledema, retinal hemorrhages and optic atrophy are important diagnostic findings. A