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Biomedical subjects

W E Sanders

Publications and source records attributed to W E Sanders.

At least 73 records · Page 4Linked to original sources

Intoxications from the seas: ciguatera, scombroid, and paralytic shellfish poisoning.

Sporadic cases and outbreaks of intoxications borne by fish and shellfish have increased in frequency during recent years. Ciguatera, scombroid, and paralytic shellfish poisoning account for nearly 16 per cent of all reported foodborne outbreaks of disease in the United States. Fishborne ciguatera and paralytic shellfish poisoning are characterized by gastrointestinal and neuromuscular manifestations attributable to toxins of dinoflagellates. These toxins impair sodium transport in cell membranes. Treatment is primarily supportive. Scombroid fish intoxication resembles histamine poisoning and may be treated effectively with antihistamines or cimetidine. Prevention of these intoxications at present depends upon avoidance of potential vectors.

Animals↗

Type I beta-lactamases of gram-negative bacteria: interactions with beta-lactam antibiotics.

The interaction of type I beta-lactamases with diverse beta-lactam compounds representing cephalosporins, cephamycins, penicillins, penams, penems, carbapenems, monobactams, and clavams was examined by using various Enterobacteriaceae and Pseudomonas aeruginosa as sources of the enzymes. The ability of a given drug to reversibly induce beta-lactamase was unrelated to its ability to select mutants stably derepressed for beta-lactamase production. Imipenem was one of the most-potent enzyme inducers, yet it did not select derepressed mutants. Many of the newer cephalosporins were poor enzyme inducers but readily selected derepressed mutants. Resistance to hydrolysis did not predict a drug's inhibitory activity against derepressed mutants. The activity of the penems, penams, and carbapenems was least affected by derepression of beta-lactamase, whereas the activity of anionic cephalosporins and aztreonam was most affected.

Anti-Bacterial Agents↗

Evidence for multiple forms of type I chromosomal beta-lactamase in Pseudomonas aeruginosa.

The multiple stages of derepression of the type I chromosomal beta-lactamase in Pseudomonas aeruginosa were examined. Mutants partially and fully derepressed for beta-lactamase were selected from a wild-type clinical isolate. An analysis of the beta-lactamase produced by these mutants and the induced wild type revealed significant differences in the products of derepression at each stage. Beta-lactamase produced by the fully derepressed mutant showed a lower affinity (Km, 0.113 mM) for cephalothin than that produced by the partially derepressed mutant (Km, 0.049 mM). However, due to a very large Vmax, the former possessed a much greater hydrolytic efficiency. Differences in substrate profile were also noted. Only beta-lactamase from the fully derepressed mutant hydrolyzed cefamandole, cefoperazone, and cefonicid. The partially derepressed mutant possessed a single beta-lactamase band with a pI of 8.4. The fully derepressed mutant possessed this band and an additional major band with a pI of 7.5. Induction of the wild type with cefoxitin produced both bands. The changes in physiologic parameters of the enzymes produced in the different stages of derepression suggest a complex system for beta-lactamase expression in P. aeruginosa. This may involve at least two distinct structural regions, each of which is under control of the same repressor.

Chromosomes, Bacterial↗

Characterization of beta-lactamases in situ on polyacrylamide gels.

An inhibitor-based characterization system which allowed the identification of beta-lactamases after isoelectric focusing on polyacrylamide gels was developed. This system, using potassium clavulanate and oxacillin, distinguished type I chromosomally mediated enzymes from other beta-lactamases of gram-negative bacteria.

Clavulanic Acids↗

The occult dorsal carpal ganglion.

Chronic wrist pain has many causes, the diagnosis of which is often difficult. Clinical and anatomical research in this area has replaced the diagnosis of "wrist sprain" with a differential diagnosis including carpal chondromalacia, dynamic carpal instability, positive and negative ulnar variance, triangular fibrocartilage complex injuries, and early carpal avascular necrosis. The ubiquitous dorsal ganglion can also cause chronic wrist discomfort and the diagnosis of "occult dorsal carpal ganglion" should be included in the differential diagnosis. Nine patients with chronic wrist pain were diagnosed clinically as having an occult dorsal carpal ganglion despite the absence of a palpable mass. Each was treated by limited dorsal capsulectomy with excision of a small portion of the dorsal scapho-lunate ligament, and small intracapsular ganglia and/or cystic mucinous degeneration of the capsule were found in all nine patients. Of the eight patients available for follow-up examination, the preoperative pain was relieved in seven of the eight and no recurrences were noted at follow-up averaging six months.

Adolescent↗

Microbial resistance to newer generation beta-lactam antibiotics: clinical and laboratory implications.

Certain nonfastidious, gram-negative bacilli possess the ability to rapidly develop resistance to many of the newer "enzyme stable" beta-lactam antibiotics. This finding poses many clinical problems including emergence of resistance during therapy with the drugs. Therapeutic alternatives for patients are severely limited when this problem occurs because multiple drug resistance may arise simultaneously. To date, two mechanisms have been found to be responsible for this resistance. The first, which produces multiple beta-lactam resistance, is the induction of chromosomal beta-lactamases that mediate resistance to nonsubstrate drugs by the creation of a nonhydrolytic barrier that blocks access to target proteins within the cell. The second mechanism, which produces beta-lactam/aminoglycoside resistance, involves a change in outer membrane permeability. Outbreaks of nosocomial infections with these multiple drug-resistant organisms and spread of the strains throughout the hospital are already being seen. Control of these problems can only be achieved through the judicious and restricted use of these new antibiotics.

Aminoglycosides↗

Role of beta-lactamases and outer membrane proteins in multiple beta-lactam resistance of Enterobacter cloacae.

The chromosomal beta-lactamase and outer membrane proteins of Enterobacter cloacae were examined to determine their relative contributions to multiple antibiotic resistance in this organism. Mutants altered in beta-lactamase expression, whether derived in the laboratory or recovered from patients treated with one of the new beta-lactam antibiotics, were found to have no detectable alterations in outer membrane proteins. Derepression of beta-lactamase in these mutants was associated with high-level resistance to multiple beta-lactam antibiotics, while loss of inducible beta-lactamase (i.e., production of basal enzyme levels only) was associated with acquisition of susceptibility to many beta-lactam antibiotics, including cephalothin. In contrast, alteration in outer membrane proteins was associated with only moderate-level resistance to beta-lactam antibiotics. However, this included resistance to such drugs as amdinocillin and Sch 34343, which were unaffected by derepression of beta-lactamase. Resistance to chloramphenicol and tetracycline also accompanied changes in outer membrane proteins. Although the outer membrane proteins of various strains of E. cloacae were similar, there did appear to be some major strain-to-strain variations. Thus, it appears that alterations in both beta-lactamase and outer membrane proteins can affect the susceptibility of E. cloacae to many antibiotics. However, alterations in beta-lactamase alone are sufficient to produce high-level multiple beta-lactam resistance in this organism.

Anti-Bacterial Agents↗

Selection of multiple antibiotic resistance by quinolones, beta-lactams, and aminoglycosides with special reference to cross-resistance between unrelated drug classes.

The ability of three quinolones, two beta-lactams, and one aminoglycoside to select resistant mutants was examined in tests with 30 isolates of commonly encountered nosocomial pathogens. Ciprofloxacin and norfloxacin, two new quinolone derivatives, were no more likely to select resistant mutants than amikacin, whereas nalidixic acid, an older quinolone derivative, was the most likely of the six drugs examined to select resistant mutants. Mutational frequencies of 10(-7) to 10(-8) were observed in most instances. In general, the mutants were 8 to 16 times less susceptible to the drug used for selection. Although most quinolone-selected mutants were cross-resistant only to other drugs within this class, certain mutants of Klebsiella pneumoniae selected by nalidixic acid, ciprofloxacin, or norfloxacin were also less susceptible to beta-lactam antibiotics. This unusual pattern of multiple drug resistance was associated with changes in outer membrane proteins of the organism. Multiple drug resistance was also observed in beta-lactam-selected mutants of Enterobacter cloacae and Pseudomonas aeruginosa (beta-lactams), amikacin-selected mutants of Providencia stuartii and P. aeruginosa (aminoglycosides), and beta-lactam- or amikacin-selected mutants of Serratia marcescens (beta-lactams plus aminoglycosides). These results underscore the need to examine carefully the frequency with which resistance to any new antibiotic develops, as well as the patterns of multiple drug resistance which may occur simultaneously.

Amikacin↗

Traumatic plastic deformation of the radius and ulna. A closed method of correction of deformity.

More than 50 cases of plastic deformation of the forearm in children have been reported in the literature, but no method of reduction other than osteoclasis has been described. Fourteen patients with plastic deformation of one or both bones of the forearm were observed over a period of five years. Of these 14, nine were cared for acutely, and a closed reduction was performed by placing the apex of the plastically deformed bone over a fulcrum and applying significant pressure for several minutes. The average correction was 85% of the angulation present prior to reduction. The clinical findings in these patients treated by closed reduction were compared with those observed in untreated cases seen by the authors and those in the literature. Early reduction of the plastic deformation decreased the clinical deformity, allowed treatment of adjacent fractures, and led to earlier return of full pronation and supination of the forearm.

Adolescent↗

Vitamin B6-dependent Streptococcus mimicking fungi in a patient with endocarditis.

A patient was referred to our hospital with a tentative diagnosis of fungal endocarditis based upon clinical symptoms, suggestive travel history, and microscopic visualization in blood cultures of gram-negative bulbous filaments that appeared to be fungal elements. Subcultures of the blood culture bottles were unsuccessful on all media with the exception of blood agar plates, which had been cross-streaked with Staphylococcus aureus. These plates grew vitamin B6-dependent streptococci. This nutritionally variant organism was determined by biochemical tests to be Streptococcus mitis (mitior). It had a penicillin MIC and MBC of 0.015 micrograms/mL and 0.03 micrograms/mL, respectively and streptomycin MIC and MBC of 0.78 micrograms/mL and 1.56 micrograms/mL, respectively. The patient was treated with these two agents and recovered. We stress the importance of suspecting vitamin B6-dependent streptococci, even when gram stains may suggest presence of other microorganisms.

Diagnosis, Differential↗

Infection due to organisms of the Mycobacterium fortuitum complex after augmentation mammaplasty: clinical and epidemiologic features.

Periprosthetic infections due to Mycobacterium fortuitum and Mycobacterium chelonei occurred in 17 women over a 3.5-year period after implantation of prostheses for breast augmentation. The median incubation period for 16 of the women was 28 days (range, one week to over two years) after surgery; etiologic diagnosis was usually delayed for weeks to months. Odorless and serosanguineous or purulent material was found when the implants were removed, and acid-fast bacilli were often present when smears were examined. Wound infections were chronic and refractory to therapy with various antimicrobial agents. Persistent or recurrent mycobacterial infections complicated attempts to implant new prostheses. Whereas M. fortuitum isolates were susceptible to amikacin, multiple strains of M. fortuitum were distinguished by conventional antituberculous and broth microdilution susceptibility tests. Several clusters of infections were temporally and geographically related; however, sporadic cases were also reported, and no evidence of a contaminated common product or other single source of infection was found.

Adult↗

Clinical experience with azlocillin.

Mezlocillin and azlocillin are new semi-synthetic ureidopenicillins. Both possess a broad spectrum of activity in vitro. Potency of activity against Gram-positive and fastidious Gram-negative organisms and against obligate anaerobes is comparable. Mezlocillin is more active against Enterobacteriaceae while azlocillin is more potent against Pseudomonas species. Although direct comparative studies in serious Gram-negative bacillary infections have not been performed, it would appear prudent to administer mezlocillin in disease due to Enterobacteriaceae, and to prescribe azlocillin preferentially when the aetiological agent is presumed or known to be Pseudomonas. The use of azlocillin to treat serious infections with Ps. aeruginosa is described here. A variety of clinical and laboratory observations may permit implication of Pseudomonas in the aetiology of specific infections.

Adult↗

Effects of clindamycin on derepression of beta-lactamases in gram-negative bacteria.

Depression of beta-lactamases in certain non-fastidious Gram-negative bacilli has been responsible for (i) the rapid development of resistance to a variety of beta-lactam antibiotics and (ii) antagonism between beta-lactam antibiotics. Therefore, the effects of a variety of inhibitors of macro-molecular synthesis on derepression of beta-lactamase were investigated with four strains each of enterobacter and Pseudomonas aeruginosa. When tested at concentrations that were not inhibitory to growth, clindamycin was the most effective inhibitor of derepression of beta-lactamases in some of the strains examined. In one enterobacter isolate, clindamycin completely prevented derepression of beta-lactamases. This effect was highly specific as clindamycin did not influence constitutive beta-lactamase or depression of other inducible enzymes in this same strain. These results suggest that clindamycin may selectively inhibit synthesis of beta-lactamase under repressor control in some bacteria without affecting synthesis of other proteins or replication. Such selective inhibition may provide a new approach for the enhancement of the antibacterial activity of certain beta-lactam antibiotics.

Cefamandole↗