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Biomedical subjects

K MacDonald

Publications and source records attributed to K MacDonald.

53 records · Page 3Linked to original sources

Effect of insulin and insulin-like growth factors I and II on phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate breakdown in liver from humans with and without type II diabetes.

We have characterized a plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phospholipase C (PLC) and a cytosolic phosphatidylinositol (PI)-specific PLC in human liver. Epinephrine, 1 x 10(-5) M, and vasopressin, 1 x 10(-8) M, stimulated PIP2-PLC which was enhanced by guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S). PI-PLC stimulation was not observed by these agents. Insulin and insulin-like growth factors (IGF-I and IGF-II) in the presence and absence of GTP gamma S did not stimulate PIP2-PLC or PI-PLC in plasma membranes and cytosol preparations nor phosphoinositide breakdown in isolated human hepatocytes. Furthermore, serendipitly we found that PIP2-PLC activity was increased in liver membranes from obese patients with type II diabetes when compared to obese and lean controls. We conclude that in human liver, insulin and IGFs are not members of the family of hormones generating inositol trisphosphate (IP3) as a second messenger. Furthermore, the increased PIP2-PLC in diabetic liver may result in: (a) increased intracellular concentrations of IP3 and thus increased Ca2+, which has been postulated to induce insulin resistance; and (b) increased diacylglycerol and thus increased protein kinase C which phosphorylates the insulin receptor at serine residues inactivating the insulin receptor kinase. While the mechanism of increased PIP2-PLC activity in diabetes is unknown, it may initiate a cascade of events that result in insulin resistance.

Calcium↗

Ciprofloxacin for eradication of methicillin-resistant Staphylococcus aureus colonization.

Ciprofloxacin (750 mg orally twice a day) was used to treat 22 episodes of methicillin-resistant Staphylococcus aureus (MRSA) colonization among 20 patients. Most patients had serious, progressive underlying medical diseases and had multiple sites of colonization. Eleven had previously received parenteral vancomycin therapy. Duration of ciprofloxacin therapy was from seven to 28 days. Therapy was discontinued in eight patients because of minor adverse reactions (two patients) or serious events attributed to underlying diseases (six patients). These serious events included seizures in two patients with known seizure disorders. Of the remaining 14 courses of therapy, 11 (79 percent) were associated with eradication of MRSA colonization. For the 18 patients who received at least two weeks of therapy, results of cultures from 47 of the 56 colonized sites became negative. Recolonization with MRSA occurred in four patients within one month. Increased resistance to ciprofloxacin was observed in seven of the 22 treatment episodes; this was associated with treatment failure in three patients and successful therapy in one patient; therapy was discontinued for other reasons in three patients. For comparison, medical records of 31 patients whose clinical specimens revealed MRSA but who did not receive ciprofloxacin were reviewed. MRSA colonization (as opposed to infection) was not eradicated in any patient who received only a single drug or no specific therapy directed against MRSA; four of seven patients given combination therapy had colonization eradicated. Although there is the potential for increased resistance, ciprofloxacin is an important new option that can be used as a single agent for eradication of MRSA colonization. Additional study is needed to define the optimum use of ciprofloxacin as a single agent and in combination therapy for MRSA colonization and infection.

Adult↗

Bowel flora changes in humans receiving cefixime (CL 284,635) or cefaclor.

Twelve healthy young male subjects received either cefixime, a new oral cephalosporin (CL 284,635), or cefaclor (six subjects on each drug) orally for 2 weeks. In the case of cefixime, single daily doses of 400 mg were taken; with cefaclor, the dosage was 250 mg three times daily. Modest changes in the fecal flora were noted in both drug groups, but the changes were of different types. In the case of cefixime, there was more of an impact on the indigenous flora, and in the case of cefaclor, there was more ingrowth of new flora. With cefixime, Enterobacteriaceae were usually decreased (the decrease in Escherichia coli count was statistically significant), as were counts of clostridia and sometimes Bifidobacterium spp.; the Bacteroides fragilis group was eliminated in one subject. Coincident with these decreases, four subjects had increases in counts of group D streptococci of 3 logs or more. There was new appearance of Clostridium difficile in four subjects and of Staphylococcus aureus in one; four new strains of Enterobacteriaceae appeared. With cefaclor, there was no decrease of E. coli counts; two subjects had elimination of Bifidobacterium spp. There was little change in counts of group D streptococci. On the other hand, there were 13 new strains of Enterobacteriaceae, two of S. aureus, and three of C. difficile.

Bacteria↗

Bridging the gap: parent-child play interaction and peer interactive competence.

A multimeasure, multicontext study of the relationship between father-child and mother-child play and children's competence with preschool peers was conducted. 13 boys and 14 girls, ages 3-4 years, and their parents participated. Children were videotaped while playing with each parent separately for 20 min in their homes. Children's social competence with their peers was independently evaluated by 3 measures: (1) rankings of preschool teachers of popularity with peers, (2) Q-sort ratings of children's competence by their teachers, and (3) assessments of social interaction with 3 different preschool peers on separate occasions. Differential patterns of maternal and paternal behavior were associated with the social competence of boys and girls. Paternal physical play, engagement, and maternal verbal behavior were positively related to children's peer relations, especially for boys. Paternal directiveness was negatively related to popularity for boys and girls, while maternal directiveness was positively linked with popularity for girls. Opportunities for learning to regulate affect are hypothesized to contribute to these relationships. The study illustrates the linkages between family and peer social systems.

Affect↗

A randomized, double-blind comparison of sulbactam/ampicillin and clindamycin for the treatment of aerobic and aerobic-anaerobic infections.

In a randomized, prospective, double-blind trial, sulbactam/ampicillin was compared with clindamycin in terms of efficacy and safety for the treatment of bacterial infections. Both sulbactam/ampicillin and clindamycin were given with gentamicin when this course was indicated by clinical or laboratory findings. In five patients the site of infection was pleuropulmonary; in 14, bone; in 11, skin and soft tissue; and in one, intraabdominal. The commonest anaerobes isolated were anaerobic cocci and Bacteroides species; the commonest aerobic and facultative bacteria were Enterobacteriaceae, Pseudomonas aeruginosa, and various gram-positive cocci. All of six assessable patients given sulbactam/ampicillin alone had satisfactory clinical responses, as did seven of nine patients given sulbactam/ampicillin plus gentamicin, all of six patients given clindamycin alone, and six of nine patients given clindamycin plus gentamicin. Pathogens were totally or partially eradicated in four of five, eight of nine, four of five, and three of nine assessable patients given these same regimens. Adverse reactions and laboratory abnormalities were relatively uncommon. Overall, sulbactam/ampicillin was as effective as clindamycin in the treatment of aerobic or mixed aerobic-anaerobic infections; however, the concomitant use of gentamicin was frequently required with both regimens.

Aged↗

Integration of haemophilic boys into normal schools.

Advances in the medical treatment of haemophilia have made it possible for the majority of haemophilic children to attend ordinary rather than special schools. A survey carried out in the Glasgow and Edinburgh regions among families with haemophilic children and the schools which these children attend has drawn attention to certain implications of this new policy.

Absenteeism↗

Cytologic, ultrastructural and immunologic features of intracytoplasmic hyaline bodies in fine needle aspirates of hepatocellular carcinoma.

Intracytoplasmic hyaline bodies in malignant cells from an aspirate of a liver mass are suggestive of hepatocellular carcinoma. Such inclusions were studied by light and electron microscopy and by immunocytochemistry in fine needle aspirates from five cases of hepatocellular carcinoma. Seen by light microscopy, the inclusions were round or ovoid and were surrounded by a prominent halo. By both light and electron microscopic immunocytochemistry, the hyaline bodies showed negative staining for alpha-fetoprotein, alpha-1-antitrypsin and cytokeratin. Ultrastructurally, they were not membrane bound and were composed of filamentous, finely granular material, resembling the early stages of Mallory bodies.

Aged↗