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Biomedical subjects

D J Sexton

Publications and source records attributed to D J Sexton.

At least 55 records · Page 3Linked to original sources

Predictors of prognosis and risk of acute renal failure in bacterial endocarditis.

BACKGROUND: The epidemiology, criteria for diagnosis and treatment of bacterial endocarditis has changed substantially in the past 2 decades, yet little attention has been given to the changing etiologies of renal insufficiency and the predictors of renal failure or the relationship between renal failure and mortality in patients with bacterial endocarditis. OBJECTIVE: To study the risk factors for the development of acute renal failure and death among patients with definite bacterial endocarditis. SETTING: Tertiary referral university medical center. METHODS: Retrospective chart review of 204 consecutive episodes of definite bacterial endocarditis as defined by the Duke criteria. Logistic regression was used to identify clinical and biochemical predictors of death and the development of acute renal failure. RESULTS: Two hundred and four episodes of endocarditis identified in 185 patients were evaluated. The overall mortality for the group was 20%. The presence of prosthetic valve endocarditis and thrombocytopenia was associated with increased risk of death in hospital. One third of the patients developed acute renal failure (defined as a serum Cr of 2 mg/dl or above). The presence of acute renal failure increased the odds (OR) of dying by 5 (p = 0.0001). Clinical and biochemical variables at presentation that were significantly associated by univariate analysis with the risk of developing acute renal failure were: increased age, a history of hypertension, thrombocytopenia, the presence of Staphylococcus aureus, and prosthetic valve infection. Age (OR 2.9, p = 0.002) and the degree of thrombocytopenia (OR 0.2, p = 0.0001) were independently associated with an increased risk of developing acute renal failure. Patients who developed acute renal failure as a result of septic syndrome or following cardiac surgery had a higher mortality when compared to other causes of acute renal failure. CONCLUSION: Acute renal failure associated with bacterial endocarditis remains a frequent clinical problem that is often associated with a fatal outcome. Patients with increased age, and the degree of thrombocytopenia were independent risk factors for developing acute renal failure.

Acute Kidney Injury↗

Infection control: past, present, and future issues.

Primary care providers serve as role models for the prevention of nosocomial infections through membership on hospital infection-control committees and daily patient care. This article will review five fundamental infection control measures: surveillance, isolation, hand washing, disinfection, and sterilization.

Cross Infection↗

Dissociation of bacteriophage T4 DNA polymerase and its processivity clamp after completion of Okazaki fragment synthesis.

The mechanism of bacteriophage T4 DNA polymerase (gp43) and clamp (gp45) protein dissociation from the holoenzyme DNA complex was investigated under conditions simulating the environment encountered upon completion of an Okazaki fragment. Lagging strand DNA synthesis was approximated using a synthetic construct comprised of a doubly biotinylated, streptavidin-bound 62-mer DNA template, paired with complementary primers to generate an internal 12-base gap where the 5'-end primer contained either a 5'-OH (DNA primer) or a 5'-triphosphate (RNA primer) group. Rapid kinetic measurements revealed that upon encountering the blocking primer, the holoenzyme either dissociates from DNA (approximately 40%) or strand-displaces the blocking strand (approximately 60%). The two blocking oligonucleotides (DNA or RNA) induce a 30-50-fold increase in the rate of holoenzyme dissociation, with both polymerase and clamp proteins dissociating simultaneously. Inhibition of ATP hydrolysis by ATP-gamma-S did not have a measurable effect upon holoenzyme dissociation from DNA. The presence of gp32, the single-strand binding protein, caused a small (3-fold) increase in the rate constant for dissociation.

Bacteriophage T4↗

Catheter-related bacteremia and outcome of attempted catheter salvage in patients undergoing hemodialysis.

BACKGROUND: Dual-lumen cuffed catheters are used for vascular access in patients undergoing hemodialysis. The incidence and appropriate management of catheter-related bacteremia are unknown. OBJECTIVE: To determine the incidence and outcome of catheter-related bacteremia and to assess the efficacy of catheter salvage. DESIGN: Prospective, observational study. SETTING: University hospital inpatient service and four affiliated outpatient dialysis units. PATIENTS: 102 patients with end-stage renal disease who underwent hemodialysis with dual-lumen cuffed catheters between 1 April 1995 and 1 January 1996. MEASUREMENTS: Number of days that the catheter remained in situ, treatment (catheter removal or attempted salvage with antibiotic therapy), and outcome of bacteremia. Microbiological cultures were done to identify catheter-related bacteremia. RESULTS: 102 patients had a total of 16,081 catheter-days. Forty-one patients (40%) developed 62 episodes of bacteremia (3.9 episodes per 1000 catheter-days [95% CI, 3.0 to 4.9 episodes per 1000 catheter-days]). Twenty-four catheters (39%) were removed immediately, and 38 (61%) were left in place during treatment. Only 12 (32%) of the 38 catheters were salvaged successfully. Salvage was less likely to succeed in patients with gram-positive bacteremia than in patients with gram-negative bacteremia, but this difference was not statistically significant (P = 0.14). Nine of the 41 patients (22%) who developed bacteremia had the following complications: osteomyelitis (6 patients), septic arthritis (1 patient), infective endocarditis (4 patients), and death (2 patients). All complications followed an episode of gram-positive bacteremia, and none was associated with attempted catheter salvage. CONCLUSIONS: Bacteremia frequently occurs in patients undergoing hemodialysis with dual-lumen catheters. Antibiotic therapy without catheter removal is unlikely to eradicate catheter-related bacteremia in these patients, but attempted salvage may not increase the risk for complications.

Adult↗

Bacterial endocarditis in hemodialysis patients.

Infective endocarditis (IE) is one of the most serious complications of bacteremia. Hemodialysis patients with prosthetic vascular access devices such as dual-lumen cuffed venous catheters and polytetrafluoroethylene (PTFE) grafts are at increased risk for bacteremia compared with patients with primary arteriovenous fistulae (PAVF). We present 20 cases of IE in hemodialysis patients seen at our institution over a 7-year period. Eight patients had PTFE grafts, 11 had dual-lumen cuffed catheters, and one had a PAVF. All patients underwent transthoracic echocardiography (TTE) and 16 patients also received transesophageal echocardiography (TEE). The Duke Criteria were used to characterize patients as definite or possible IE. Organisms were Staphylococcus aureus (55%), Staphylococcus epidermidis (25%), and Enterococcus sp (10%). The mitral valve (50%) was the most commonly affected valve, followed by aortic (30%) and right-sided IE (25%). Valve replacement was performed in five patients, of whom three survived hospitalization. The overall mortality rate for the series was 30%. All the dual-lumen cuffed catheters were removed, while only two of the eight PTFE grafts were removed. Four of the six patients who died had PTFE grafts, of which one was judged to be infected and removed. Echocardiography was essential to the diagnosis of IE. Vegetations were found in 50% by TTE and 81% by TEE. Six patients with no vegetations on TTE were found to have vegetations on TEE.

Arteriovenous Shunt, Surgical↗

Role of echocardiography in evaluation of patients with Staphylococcus aureus bacteremia: experience in 103 patients.

OBJECTIVES: The purpose of this prospective study was to examine the role of echocardiography in patients with Staphylococcus aureus bacteremia (SAB). BACKGROUND: The reported incidence of infective endocarditis (IE) among patients with SAB varies widely. Distinguishing patients with uncomplicated bacteremia from those with IE is therapeutically and prognostically important, but often difficult. METHODS: One hundred-three consecutive patients undergoing both transthoracic (TTE) echocardiography and transesophageal (TEE) echocardiography were prospectively evaluated. All patients presented with fever and > or = 1 positive blood culture and were followed up for 12 weeks. RESULTS: Although predisposing heart disease was present in 42 patients (41%), clinical evidence of infective endocarditis (IE) was rare (7%). TTE revealed anatomic abnormalities in 33 patients, but vegetations in only 7 (7%), and was considered indeterminate in 19 (18%). TEE identified vegetations in 22 patients (aortic valve in 5, mitral valve in 9, tricuspid valve in 4, catheter in 2 and pacemaker in 2, abscesses in 2, valve perforation in 1 and new severe regurgitation in 1; 26 total [25%]). Using Duke criteria for the diagnosis of IE, definite IE was present in 26 patients (25%). Clinical findings and predisposing heart disease did not distinguish between patients with and without IE. The sensitivity of TTE for detecting IE was 32%, and the specificity was 100%. The addition of TEE increased the sensitivity to 100%, but resulted in one false positive result (specificity 99%). TEE detected evidence of IE in 19% of patients with a negative TTE and 21% of patients with an indeterminate TTE. At follow-up, cure of staphylococcal infection occurred in a similar percentage of patients with and without IE (77% and 75%, respectively). However, death due to sepsis was significantly more likely among patients with IE (4 of 26 [15%]) than among those without IE (2 of 77 [3%]) (p = 0.03). CONCLUSIONS: Our results suggest that IE is common among patients admitted to the hospital with SAB and is associated with an increased risk of death due to sepsis. TEE is essential to establish the diagnosis and to detect associated complications. Therefore, the test should be considered part of the early evaluation of patients with SAB.

Aged↗

Assembly and disassembly of DNA polymerase holoenzyme.

The complex task of genomic replication requires a large collection of proteins properly assembled within the close confines of the replication fork. The mechanism and dynamics of holoenzyme assembly and disassembly have been investigated using steady state and pre-steady state methods as opposed to structural studies, primarily due to the intrinsic transient nature of these protein complexes during DNA replication. The key step in bacteriophage T4 holoenzyme assembly involves ATP hydrolysis, whereas disassembly is mediated by subunit dissociation of the clamp protein in an ATP-independent manner.

Bacteriophage T4↗

An evaluation of the Duke criteria in 25 pathologically confirmed cases of prosthetic valve endocarditis.

Six studies have compared the sensitivity of the Duke criteria with that of the Beth Israel criteria for the diagnosis of infective endocarditis without attempting to distinguish between native valve and prosthetic valve cases. After reviewing clinical data from 372 cases of suspected prosthetic valve endocarditis, we selected 25 cases in which pathological confirmation of prosthetic valve endocarditis was obtained. By using the Duke criteria and then the Beth Israel criteria, we reassigned a diagnostic classification to these 25 cases on the basis of clinical parameters alone. Using the Duke criteria, we correctly classified 19 cases (76%) as definite endocarditis and rejected none, while the Beth Israel criteria correctly classified six cases as probable endocarditis (24%) and rejected five cases (20%). Similar to previous investigators who examined the diagnostic sensitivity of the Duke criteria and Beth Israel criteria, we found that the Duke criteria appear more sensitive than the Beth Israel criteria in pathologically confirmed cases of prosthetic valve endocarditis.

Drug Resistance, Microbial↗

The great imitator: Rocky Mountain spotted fever occurring after hospitalization for unrelated illnesses.

We describe two patients who had Rocky Mountain spotted fever after they were admitted to the hospital for emergency and elective surgical procedures. We initially thought one patient had a hospital-acquired infection; the correct diagnosis was deduced from epidemiologic clues elicited by consultants. These two cases were also unusual in that one patient had a recurrent rash after an abbreviated course of low-dose doxycycline therapy and the other patient had transient and self-limiting postinfectious polyneuropathy. These cases illustrate that community-acquired infection with Rickettsia rickettsii can occur simultaneously with other disease processes and sometimes mimic a nosocomial infection.

Amputation, Traumatic↗

Seroepidemiology of Rickettsia typhi, spotted fever group rickettsiae, and Coxiella burnetti infection in pregnant women from urban Tanzania.

Immunofluorescent antibody (IFA) testing was performed on sera drawn from 150 pregnant women in the port city of Dar es Salaam, Tanzania. Prevalence of antibodies to Rickettsia typhi was 28%, higher than in any of the 12 other African countries in which serosurveys using IFA testing have been performed. Seroprevalence of antibodies to spotted fever group rickettsiae antigens was 25.3%, comparable with that found in other sub-Saharan countries endemic for Amblyomma ticks. Only 4.7% of women were seropositive for Coxiella burnetii.

Adolescent↗

Immunoperoxidase and immunofluorescent staining of Rickettsia rickettsii in skin biopsies. A comparative study.

OBJECTIVE: To compare immunofluorescent and immunoperoxidase staining of Rickettsia rickettsii in skin biopsies of patients suspected of having Rocky Mountain spotted fever (RMSF). DESIGN: Immunofluorescent staining results for R rickettsii from skin biopsies of patients suspected of having RMSF were obtained by computer and chart review. Immunoperoxidase staining for R rickettsii was performed on formalin-fixed, paraffin-embedded skin biopsies from the same patient population. PATIENTS: Twenty-six patients who were clinically suspected of having RMSF were included in this study. Skin biopsies of these patients were examined for evidence of RMSF by immunofluorescence and routine histology. MAIN OUTCOME MEASURES: The sensitivity and specificity of both immunofluorescent and immunoperoxidase staining techniques were calculated. The chi 2 method was used to assess significance. RESULTS: Both tests were highly significant for the detection of R rickettsii (P < .01). The sensitivity and specificity of the immunofluorescent and immunoperoxidase staining techniques for the identification of RMSF were identical. No significant difference between these tests was identified (P > .05). CONCLUSION: The sensitivity and specificity of immunofluorescent and immunoperoxidase staining of R rickettsii in routinely processed, paraffin-embedded skin biopsies of patients suspected of having RMSF are identical. Although not as rapid as the immunofluorescent technique, immunoperoxidase staining of R rickettsii has advantages over the immunofluorescent technique; these include easier antigen localization and concomitant viewing of the corresponding histopathology.

Biopsy↗

Protein-protein and protein-DNA interactions at the bacteriophage T4 DNA replication fork. Characterization of a fluorescently labeled DNA polymerase sliding clamp.

The T4 DNA polymerase holoenzyme is composed of the polymerase enzyme complexed to the sliding clamp (the 45 protein), which is loaded onto DNA by an ATP-dependent clamp loader (the 44/62 complex). This paper describes a new method to directly investigate the mechanism of holoenzyme assembly using a fluorescently labeled cysteine mutant of the 45 protein. This protein possessed unaltered function yet produced substantial changes in probe fluorescence intensity upon interacting with other components of the holoenzyme. These fluorescence changes provide insight into the role of ATP hydrolysis in holoenzyme assembly. Using either ATP or the non-hydrolyzable ATP analog, adenosine 5'-O-(3-thiophosphate), events in holoenzyme assembly were assigned as either dependent or independent of ATP hydrolysis. A holoenzyme assembly mechanism is proposed in which the 44/62 complex mediates the association of the 45 protein with DNA in an ATP-dependent manner not requiring ATP hydrolysis. Upon ATP hydrolysis, the 44/62 complex triggers a conformational change in the 45 protein that may be attributed to the clamp loading onto DNA.

Adenosine Triphosphate↗

Negative predictive value of the Duke criteria for infective endocarditis.

With use of new Duke criteria, 405 episodes of suspected endocarditis were previously classified as "definite," "possible," or "rejected" endocarditis. To determine the negative predictive value of the Duke clinical criteria for the classification of suspected endocarditis, chart review and follow-up were performed for the 52 episodes in which the diagnosis of endocarditis was rejected. Three of 52 episodes were reclassified to possible endocarditis; 49 episodes in 48 patients met the criteria for rejected endocarditis. Of these 49 episodes, 31 (63%) had a firm alternate diagnosis other than endocarditis, 17 (35%) had resolution of the clinical syndrome leading to the suspicion of endocarditis with < or = 4 days of antibiotics, and 1 patient had no evidence of endocarditis at surgery. Echocardiograms recorded in 3 patients with rejected endocarditis had evidence of oscillating valvular masses, and blood cultures were positive in 13 episodes; none of these patients had evidence of endocarditis at follow-up. Follow-up or outcome information was available in all 49 episodes. Excluding the 5 in-hospital deaths, mean duration (+/- SD) of follow-up was 39.9 +/- 28.8 months (range 0.5 to 108.0); in living patients, mean time to final follow-up was 56.2 +/- 25.2 months (range 25.0 to 108.0). One patient had possible infective endocarditis at autopsy. No patient in our series whose diagnosis of endocarditis had been rejected had proven endocarditis. Therefore, the negative predictive value of the Duke clinical criteria for endocarditis is at least 92%.

Adult↗

Rocky Mountain spotted fever presenting with acute monarticular arthritis.

This report describes a 30-year-old man who presented with an acute multisystem illness which was diagnosed as Rocky Mountain spotted fever (RMSF). Near the time of admission the patient was noted to have a newly developed aseptic monarticular arthritis of the right knee. The arthritis resolved in association with resolution of his systemic illness. To our knowledge, there have been no prior reports of acute arthritis in association with RMSF.

Acute Disease↗