Hemodialysis exacerbates enzymuria in patients with acute renal failure: brief report.
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Biomedical subjects
Publications and source records attributed to M A Cooper.
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In nephrotic syndrome, iron is presented to the tubule fluid in a nonreactive form in association with transferrin as a result of the glomerular protein leak. At an alkaline pH, iron remains bound to transferrin throughout the nephron and is excreted as such in the urine. As urine pH decreases below 6, iron is dissociated from transferrin. In the dissociated form, iron exists in the urine in a soluble, ultrafiltrable, and labile state. It is suggested that iron is maintained in this state by chelation to a relatively small organic compound, such as citrate. This non-transferrin-bound iron is capable of catalyzing bleomycin degradation of DNA, suggesting that this labile form of iron is able to catalyze free radical formation and cause tubule cell injury. Urine from proteinuric states represents one of the few, if not only, biologic fluids containing large amounts of reactive iron species. This may explain the mechanism by which proteinuric states cause tubulointerstitial disease and renal failure.
BACKGROUND: The indications are still being developed for the various procedures available to treat thrombotic and nonthrombotic subclavian vein obstruction. This article explores our experience with the surgical options, primarily with chronic venous occlusion, but also with acute thrombosis. METHODS: Twelve patients presented with acute or chronic venous thrombosis or nonthrombotic venous obstruction. Treatment included thrombolysis, vein patch angioplasty, thrombectomy, first rib resection, venolysis, and/or subclavian vein bypass by either jugular vein transposition or prosthetic axillojugular bypass. RESULTS: Six patients experienced relief of all symptoms; the other six have had relief from pain but continue to have occasional swelling. CONCLUSIONS: On the basis of our anecdotal experiences and those of others, the following protocol has been developed. After acute thrombosis, lytic therapy is recommended. If successful, first rib resection and venolysis should be considered; if unsuccessful and the patient has significant symptoms, immediate thrombectomy is indicated. If patency is established, rib resection and venolysis should follow. Persistent stenosis is treated by angioplasty, either with a vein patch or percutaneously. Complete occlusion is managed by jugular vein transposition or axillojugular bypass. Temporary arteriovenous fistulas accompany all open venous repairs.
High-voltage electrical injuries may be devastating, with extensive burns, cardiac arrest, amputations, and long, complicated hospitalizations. Low-voltage injuries, after other pathologic and high-voltage sources are ruled out, tend to be rather benign acutely although they may have significant long-term morbidity, including chronic pain syndromes. Lightning injuries affect 800 to 1000 persons per year. In lightning injury, cardiac arrest is the main cause of death, burns tend to be superficial, ad injuries often are what one would expect of short-circuiting or overloading the body's electrical systems (tinnitus, blindness, confusion, amnesia, cardiac arrhythmias, and vascular instability). Although high-voltage injuries may require the services of trauma surgeons, in general, therapy for low-voltage and lightning injury is supportive and involves cardiac resuscitation for the more seriously injured and supportive care for the less severely injured. Long-term problems from sleep disturbances, anxiety attacks, pain syndromes, peripheral nerve damage, fear of storms (for lightning patients), and diffuse neurologic and neuropsychologic damage may occur in both electrical and lightning patients. Other sequelae--such as seizures or severe brain damage from hypoxia during cardiac arrest and spinal artery syndrome from vascular spasm--are indirect results of electrical and lightning injury.
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OBJECTIVE: To define sources of job satisfaction and stress among emergency physicians and assess self-projected career longevity. DESIGN: A survey containing questions regarding emergency medicine (EM) practice satisfaction was mailed to 1,317 diplomates of the American Board of Emergency Medicine (ABEM). Specific sources of practice satisfaction and dissatisfaction, self-reported burnout or impairment, and plans for remaining in the specialty were assessed. Data were compared between two groups of physicians, namely, those residency-trained in EM and those attaining certification through the practice or special category tracts. RESULTS: Of the physicians returning the survey, 25.2% stated that they felt burned out or impaired and 23.1% planned to leave the practice of EM within five years. Perceptions of burnout/impairment and plans to stop practice were associated with less overall practice satisfaction but were not significantly different between the two groups of physicians. Burnout/impairment was linked with psychiatric, drug, or alcohol problems and the feeling that EM had contributed to that problem. CONCLUSION: This study confirms the relatively high levels of projected attrition in EM and supports the perception that stress and burnout are associated with the specialty. Differences in job satisfaction and stress between those ABEM diplomates who were residency-trained in EM and those who became eligible for the board examination through practice or special-category eligibility appear minor.
PURPOSE: To evaluate the role of maintenance daily oral etoposide (VP-16) chemotherapy for germ cell patients who had a response to salvage therapy. PATIENTS AND METHODS: Thirty-seven patients were entered onto this trial, and 34 were fully assessable. This was as heavily pretreated patient population, with a median of two prior salvage regimens. The salvage treatment that immediately preceded oral VP-16 consisted of autologous bone marrow transplantation in 14 patients (41%), surgery in 10 (29%), and standard-dose salvage chemotherapy in 10 (29%). Daily oral VP-16 was administered at a dose of 50 mg/m2 for 21 consecutive days every 4 weeks for three cycles. RESULTS: The major toxicity with daily oral VP-16 was leukopenia. Three patients had grade III and two grade IV leukopenia. Two of these patients had granulocytopenic fever. Other grade III toxicities included thrombocytopenia (n = 1) and mucositis (n = 2). Twenty-three patients started daily oral VP-16 while in complete remission (CR) following salvage therapy. Seventeen (74%) remain continuously disease-free, with a median follow-up time of 36 months (range, 26 to 49) from initiation of daily oral VP-16. Eleven patients started daily oral VP-16 while in partial remission (PR) following salvage therapy. Three of these 11 patients converted to CR, but all three subsequently relapsed. CONCLUSION: Maintenance oral VP-16 was well tolerated in this heavily treated patient population. Results in this poor-risk population were encouraging.
During the first month after bone marrow transplantation, approximately 15% of patients develop acute renal failure (ARF). This usually occurs in the setting of hepatic veno-occlusive disease (VOD). Prior clinical data have suggested that this form of ARF has a hemodynamic basis, analogous to the hepatorenal syndrome (HRS). If so, then proximal tubular injury would not be expected. To directly test this hypothesis, enzymuria (N-acetyl-beta-D-glucosaminidase [NAG]) was quantitated in the following groups of patients within the first 35 days after BMT: (1) VOD+ARF (serum creatinine level > 1.5 mg/dL; N = 10); (2) VOD with relatively normal renal function (serum creatinine level < 1.5 mg/dL; N = 11); and (3) patients without hepatic or renal complications (BMT controls; N = 12). For comparison, NAG was also quantitated in the following groups of non-BMT patients: (1) toxic/ischemic acute tubular necrosis (ATN) (N = 10); (2) jaundice without azotemia (N = 5); and (3) HRS (N = 6). Urine samples from eight healthy subjects established normal NAG concentrations (2.5 +/- 0.5 microU/mg urinary creatinine; mean +/- SE). All non-BMT patients with ATN had markedly elevated NAG levels (61 +/- 12; P < 0.001), validating the test as a marker of tubular damage. NAG concentrations were significantly elevated in all of the control BMT patients (24 +/- 3; P < 0.01), and the presence of VOD was associated with further striking increments (approximately 50 times normal). However, the degree of enzymuria was virtually identical for VOD patients with (125 +/- 27) and without (122 +/- 17) ARF. Jaundice in a non-BMT setting was associated with only mild NAG elevations (11 +/- 2). However, striking enzymuria was noted in all HRS patients (61 +/- 20), equaling the levels seen with ATN. The following conclusions were derived: (1) subclinical tubular injury, as defined by enzymuria, appears to be ubiquitous after BMT; (2) VOD dramatically increases the extent of enzymuria; (3) the degree of enzymuria in VOD patients is not correlated with renal dysfunction, implying that the associated ARF has a large hemodynamic component; and (4) HRS and ATN manifest comparable degrees of enzymuria, suggesting that substantial tubular damage exists in both of these forms of ARF.
The etiology of testicular cancer is unknown. Familial testicular cancer is a rare entity that adds further information to research regarding the genetic influence on germ cell tumors. We report on 5 brothers, including 2 identical triplets and 1 fraternal brother, with testicular cancer and discuss the epidemiological factors. It appears that environmental and genetic factors must be considered.
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The in-vitro activity of PD 131628, the active metabolite of the prodrug PD 131112, was compared with that of ciprofloxacin and members of other groups of antimicrobial agents against 701 recent clinical isolates and strains with known mechanisms of resistance. The MIC90s of PD 131628 against the Enterobacteriaceae were between 0.008 and 0.5 mg/L; PD 131628 was one- to four-fold more active than ciprofloxacin against these strains and was four-fold more active than ciprofloxacin against Pseudomonas aeruginosa. Against the Gram-positive species tested, PD 131628 was two- to four-fold more active than ciprofloxacin, inhibiting all strains of Staphylococcus aureus and Streptococcus pneumoniae with 0.5 mg/L or less. PD 131628 was very active against Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis, with MIC90s ranging from 0.004 to 0.008 mg/L. Organisms with decreased susceptibility to other quinolones had decreased susceptibility to PD 131628, but there was no cross-resistance between this class of antimicrobial and other classes. The protein binding of PD 131628 was at most 25% across a broad range of concentrations. The addition of 70% human serum had little effect on the MICs, but caused a two- to eight-fold increase in MBCs.
The in-vitro activity of tosufloxacin (A-61827) was compared with that of temafloxacin, ciprofloxacin and selected members of other groups of antimicrobial agents, against 684 recent distinct clinical isolates and strains with known mechanisms of resistance. Against members of the Enterobacteriaceae, ciprofloxacin was slightly more active than tosufloxacin, which was more active than temafloxacin. The MIC90 of tosufloxacin for all species of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp. was less than or equal to 1 mg/L. Tosufloxacin was slightly more active than temafloxacin, and four to eight fold more active than ciprofloxacin, against the Gram-positive species tested. The MIC90 of tosufloxacin for Staphylococcus aureus was 0.12 mg/L, and for Streptococcus pneumoniae was 0.5 mg/L. All strains of Neisseria spp., Haemophilus influenzae and Moraxella catarrhalis were inhibited by tosufloxacin at a concentration of less than or equal to 0.12 mg/L. Tosufloxacin was the most active quinolone against the anaerobic organisms tested. Cross resistance between quinolones was seen, but not between quinolones and other groups of antimicrobials. The protein binding of tosufloxacin across a range of concentrations averaged 60%. Human serum at a concentration of 70% decreased the bactericidal activity of tosufloxacin by about four-fold.
A single 400-mg oral dose of sparfloxacin was given to each of six healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 52 h. The mean peak concentration in plasma of 1.6 micrograms/ml was attained at a mean time of 2.7 h postdose. The mean peak concentration in inflammatory fluid of 1.3 micrograms/ml was attained at a mean time of 5 h postdose. The mean elimination half-life in plasma was 17.6 h, and that in inflammatory fluid was 19.7 h. The overall penetration into inflammatory fluid was 117%. Urinary recovery within the first 52 h postdose was 8.8% of the administered dose. Our results indicate that a once-daily dosage of sparfloxacin should be adequate to treat systemic infections caused by most common bacterial pathogens.
The in-vitro activity of SR 44337 was compared with that of other broad-spectrum parenteral cephalosporins, plus imipenem and co-amoxiclav. SR 44337 showed good activity against the Enterobacteriaceae, with MIC90s of less than 0.5 mg/L against all species tested, with the exception of Citrobacter spp. (MIC90 2 mg/L) and Serratia spp. (MIC90 4 mg/L). Of the agents tested, only ceftriaxone showed consistently greater activity against this family of organisms. SR 44337 had higher activity than ceftriaxone against Acinetobacter spp. and Pseudomonas aeruginosa, and was the most active agent tested against Neisseria meningitidis (MIC90 0.004 mg/L). All strains of N. gonorrhoeae, Haemophilus influenzae and the streptococci (excluding the enterococci) were susceptible to less than or equal to 0.25 mg/L of SR 44337, which was also the most active cephalosporin tested against Staphylococcus aureus. SR 44337 was stable to hydrolysis by the TEM-1, SHV-1 and P99 beta-lactamases, and was more stable than ceftriaxone to the K-1 beta-lactamase.
The kill kinetics of sparfloxacin and ciprofloxacin have been investigated under anaerobic conditions against Bacteroides fragilis and Escherichia coli. The results for E. coli were compared with those obtained under aerobic conditions. It was found that the quinolones were bactericidal under anaerobic conditions. This bactericidal activity is inhibited by the presence of chloramphenicol, a known protein synthesis inhibitor. Filamentation was seen with B. fragilis after 2 h exposure to either agent.