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Biomedical subjects

K Shannon

Publications and source records attributed to K Shannon.

15 recordsLinked to original sources

Prevalence of resistance to beta-lactam antibiotics in Escherichia coli isolated from blood from 1969-1991.

MICs of beta-lactam antibiotics were determined for blood culture isolates of Escherichia coli from patients in St. Thomas' Hospital, London between 1969 and 1991. There was correlation between MICs of carbenicillin and those of amoxycillin (Kendall's coefficient of rank correlation, tau = 0.67), mezlocillin (tau = 0.73), cephaloridine (tau = 0.64) and amoxycillin/clavulanic acid (tau = 0.72), but less correlation between MICs of carbenicillin and cefuroxime (tau = 0.31). During the two decades, the geometric mean MICs increased for carbenicillin (6.6-fold increase in mean MIC), mezlocillin (3.4-fold increase in mean MIC), cephaloridine (two-fold increase in mean MIC) and, to a smaller extent, amoxycillin/clavulanic acid (1.2-fold increase in mean MIC), but not for cefuroxime. These changes were the result of increases in the proportion of isolates that were resistant to carbenicillin and not of changes in the phenotype of carbenicillin-resistant isolates.

Amoxicillin

Mutations of the ras proto-oncogenes in childhood monosomy 7.

ras gene mutations are the most frequent molecular changes found in the preleukemic syndromes of adults and may play a role in initiating these diseases and in their progression to acute leukemia. However, little is known about the incidence or importance of these genetic mutations in childhood myeloproliferative states (MPS). The bone marrow (BM) monosomy 7 syndrome accounts for a large percentage of childhood MPS. Although the duration of the MPS is quite variable, children with monosomy 7 eventually develop acute myeloid leukemia (AML). We investigated 20 children (13 with MPS, 7 with AML) with BM monosomy 7 or 7q- for the presence of ras gene mutations using the polymerase chain reaction and hybridization with mutation-specific oligonucleotides. Mutations of N-ras and K-ras were detected in three children. Two patients carrying a ras mutation were in the myeloproliferative phase, and one had acute leukemia. All three patients with ras mutations either died of their disease or relapsed after BM transplantation as compared with 8 of 17 without ras mutations. However, this difference is not statistically significant (P = .14, not significant). We conclude that ras mutations are observed in childhood monosomy 7, though less frequently than in adult MDS, and may play a limited role in the progression of this disease to acute leukemia. More patients are needed to address the prognostic role of ras mutations in this rare disease.

Bone Marrow

Experience with 998 cutaneous melanomas of the head and neck over 30 years.

Between 1960 and 1990, a total of 998 patients were treated at the Sydney Melanoma Unit for cutaneous melanoma of the head and neck. There were 595 male and 403 female patients, with a median age of 53 years. The most common primary lesion site was the face (47%), followed by the neck (29%), scalp (14%), and ear (10%). Histologic types were as follows: superficial spreading 30%, nodular melanoma 28%, lentigo maligna melanoma 16%, and other 26%. All patients underwent surgical treatment. Primary closure of wounds was achieved in 52% of patients, and excision margins were 2 cm or less in 45%. A total of 152 patients had therapeutic neck dissections, and 234 had elective neck dissections. The overall local recurrence rate was 13%, and this was significantly influenced by increasing tumor thickness and Clark level. The recurrence rate in the neck after neck dissection was 24%, and the rate of parotid recurrences was 14%. Melanoma-specific survival was 77% at 5 years and 66% at 10 years for the entire group. By univariate analysis, survival varied significantly with age, tumor thickness, ulceration, anatomic sub-site, histologically positive nodes, and the presence of distant metastases. A diagnosis of lentigo maligna melanoma and elective lymph node dissection both appeared to improve survival. With multivariate analysis, all of these factors remained significant prognostic factors except elective node dissection, which lost its beneficial influence.

Female

Hyperproduction of TEM-1 beta-lactamase in clinical isolates of Escherichia coli serotype O15.

During an outbreak of infection with ampicillin-resistant, TEM-1 beta-lactamase-producing Escherichia coli serotype O15, some strains were noted to differ from the majority in that they showed reduced susceptibility to amoxycillin/clavulanic acid (Augmentin), ureidopenicillins and first generation cephalosporins and produced increased amounts of beta-lactamase. The plasmid from one such isolate was compared with that from an isolate that produced normal amounts of beta-lactamase. Restriction analysis with EcoRI revealed extra fragments in the plasmid from the beta-lactamase hyperproducer and use of DNA-DNA hybridisation with a biotinylated TEM-1 probe showed genetic rearrangement in the beta-lactamase hyperproducer so that the TEM gene appeared to be present in larger amounts and was located on a smaller fragment than for the plasmid from the strain that produced normal amounts of beta-lactamase.

DNA, Bacterial

Alcohol protects the diaphragm during dietary restriction.

We recently reported that alcoholic rat diaphragm develops greater contractile force than diaphragm of pair-fed control animals. The present experiment examines whether alcohol or dietary restriction is the more likely cause of this surprising finding. We conditioned 10 rats using a liquid diet containing ethanol as 36% of calories. Ten pair-fed control animals received an equal amount of isocaloric, ethanol-free liquid diet. Ten ad libitum control animals had unrestricted access to lab chow and water. Rats were killed after 30 weeks. Left costal diaphragm strips were studied in vitro at optimal length using direct stimulation at supramaximal voltage. Isometric force was measured and divided by muscle cross-section to compute stress. Maximal tetanic stresses developed by muscle from pair-fed controls were systematically less than alcoholic and ad libitum control values (p less than 0.0001); this did not depend on temperature (25 degrees vs. 37 degrees; p greater than 0.50). Pair-feeding increased twitch half-relaxation times (p less than 0.03) and shifted the tetanic stress-stimulation frequency relationship leftward by 10 Hz (p less than 0.01). Diaphragm of pair-fed rats continued to generate lower stresses during the fatigue caused by repeated contractions (p less than 0.01). We conclude that dietary restriction associated with pair-feeding compromises diaphragm performance in rats. Chronic alcohol consumption prevents or reverses these changes, since diaphragm function of alcoholic and ad libitum control animals was not different.

Alcoholism

Relapsing post-hepatitis aplastic anemia. Immunosuppressive therapy.

A 20-month-old Hispanic male developed severe aplastic anemia after an episode of non-A, non-B hepatitis. Prompt and complete recovery of all hematopoietic cell lines occurred after treatment with antithymocyte globulin (ATG) and high-dose corticosteroids. Severe aplasia recurred two months later coincident with a mild upper respiratory infection. A second course of immunosuppressive therapy was followed by complete, sustained improvement. The authors' experience provides clinical evidence indicating that immunologic mechanisms are important in the treatment of severe post-hepatitis aplastic anemia. Children in whom aplastic anemia recurs after immunosuppressive treatment may respond to a second course of therapy.

Adrenal Cortex Hormones

Echocardiographic features of total anomalous pulmonary venous drainage into the coronary sinus.

Echocardiograms were obtained from five infants with total anomalous pulmonary venous drainage to the coronary sinus or the portal system or the superior vena cava and from one child with a secundum atrial septal defect and a large coronary sinus due to persistence of the left superior vena cava. The results demonstrate that an enlarged coronary sinus is positioned consistently posterior to the left atrium in approximately the same horizontal plane as the aortic valve. Echocardiographically the coronary sinus can be located as an echo complex behind the left atrium by using the aortic root as a reference point. The echo complex can be differentiated from the other spurious echoes in the left atrium by its characteristic phasic motions. The additional demonstration of the enlarged common pulmonary venous chamber behind the right atrium confirms the diagnosis of anomalous pulmonary venous drainage to the coronary sinus. For other types of anomalous pulmonary venous return, anatomic diagnosis with single crystal M mode echocardiography is not always possible because of the positional variability of the common pulmonary venous chamber in relation to the left atrium.

Coronary Vessel Anomalies

The activity of cephalosporins on beta-lactamase-producing Neisseria gonorrhoeae.

The antibacterial activity of cephaloridine, cephalothin, cephalexin, cephradine, cefazolin, cefamandole, cefuroxime and cefoxitin was determined for six beta-lactamase-producing gonococci isolated in Great Britain and the USA. Cefuroxime was most active against small and large inocula, then cefoxitin, while cephaloridine was least active. Cefamandole was more active than cefazolin and cephalothin, but only on small inocula, and these three antibiotics, with the slightly inferior cephalexin and cephradine, all had moderate activity against large inocula. The inoculum effect (or lack of it) with cephaloridine, cefamandole, cefoxitin, and possibly cefazolin and cephalothin, may be explicable in terms of the level of their susceptibility to enzymic degradation, but this appears not to be true of the inoculum effect with cefuroxime, cephalexin and cephradine. The enzymes from the various strains had closely similar isoelectric points, apparently the same as that for TEM I from E. coli.

Amidohydrolases

Antibacterial activity of netilmicin, a new aminoglycoside antibiotic, compared with that of gentamicin.

The antibacterial activity of netilmicin (Sch 20569), a new semisynthetic aminoglycoside, was compared with that of gentamicin against a variety of gram-negative bacteria, staphylococci, and streptococci. Both antibiotics had similar activity against most organisms, but netilmicin had appreciably greater activity against gram-negative organisms that were resistant to gentamicin because these species synthesized aminoglycoside 3-N-acetyltransferase I or aminoglycoside 2''-O-nucleotidyltransferase. Netilmicin was also more active than gentamicin against gentamicin-resistant strains of Staphylococcus aureus that produced two enzymes-aminoglycoside-2''-O-phosphotransferase and aminoglycoside-6'-N-acetyltransferase.

Anti-Bacterial Agents