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Biomedical subjects

H G Stiver

Publications and source records attributed to H G Stiver.

At least 37 records · Page 2Linked to original sources

Prophylactic amantadine dose and plasma concentration-effect relationships in healthy adults.

Amantadine dose, plasma concentration, prophylactic and adverse effect relationships for prevention of influenza A virus infection in healthy young adult subjects were investigated in a double-blind, placebo-controlled study. Seventy-four subjects with hemagglutination inhibition antibody titers less than or equal to 16 against an attenuated influenza A virus AF9/Montreal/3/72 (H3N2) were randomly allocated to groups taking 0 (placebo), 25, 100, or 150 mg amantadine syrup prophylactically twice a day for 31 doses. Eighteen other subjects were randomly allocated to control groups for investigation of drug toxicity (150 mg) or concurrent other virus infection (placebo). Steady-state trough plasma concentrations were 110 +/- 39, 302 +/- 80, and 572 +/- 207 ng/ml (X +/- SD) for the three amantadine doses and increased out of proportion to dose. Prophylaxis groups were challenged intranasally with virus after the fifth dose at steady state; control subjects received saline solution. No subject became ill. Input virus was recovered 48 or 72 hr after challenge from nose or throat swabs of nine of 21 subjects taking placebo, one of 18 subjects taking 100 mg amantadine, three of 18 subjects taking 25 mg amantadine, and six of 17 subjects taking 150 mg amantadine. There were no differences in seroconversion rates or adverse symptoms. Our data do not support a change in the recommended amantadine prophylactic dose for influenza A virus infection in healthy young adults. We defined trough steady-state plasma concentrations associated with the recommended amantadine dose of 100 mg twice a day that should be mimicked in devising dose schedules for populations with differing amantadine kinetics.

Adolescent↗

Complement activation and stimulation of chemotaxis by Chlamydia trachomatis.

The stimulus for the migration of polymorphonuclear leukocytes (PMNs) in acute chlamydial infection was studied in vitro by examining the chemotaxigenic effect of L2 and DE Chlamydia trachomatis elementary bodies (EB) upon the plasma of three healthy donors. In each individual experiment, chemotactic response was assessed with PMNs and plasma from the same respective donor, and no specific antibodies against C. trachomatis were detected in the plasma of any donor. Chemotaxis was observed in an agarose plate assay and was quantitated as the chemotactic differential, or CD (directed migration of PMNs minus random movement of PMNs). For each donor, the mean CD was significantly greater (P less than 0.005) when plasma preincubated for 2 h with L2 EB was used as the chemoattractant than when (i) plasma alone, (ii) plasma preheated to 56 degrees C for 30 min before incubation with L2 EB, or (iii) L2 EB in phosphate-buffered saline (PBS) was used as the potential chemoattractant. Similarly, in the one donor in whom DE EB were studied, the mean CD was also significantly greater (P less than 0.005) for plasma preincubated with DE EB as compared with (i) plasma alone or (ii) DE EB in PBS. Complement activation by C. trachomatis EB was assessed by radioimmunoassay for C5a des-arginine in all chemoattractant preparations used in the chemotaxis assay. Mean C5a des-arginine levels were high in plasma samples preincubated with L2 EB (171.00 +/- 10.64, 107.00 +/- 4.76, and 89.70 +/- 1.74 ng per ml) or DE EB (37.40 +/- 15.76 ng per ml) but were undetectable (less than 4.0 ng per ml) in (i) plasma alone, (ii) preheated plasma incubated with L2 EB, and (iii) PBS containing L2 EB. Thus, L2 EB and DE EB of C. trachomatis exert a chemotaxigenic effect upon normal antibody-negative plasma, and this effect is at least in part a result of complement activation and generation of the potent chemotaxin C5a.

Chemotaxis, Leukocyte↗

Comparative cervical microflora shifts after cefoxitin or cefazolin prophylaxis against infection following cesarean section.

The aerobic and anaerobic cervical microflora was determined before operation and on day 4 after operation in groups of women undergoing a clinical trial of prophylaxis with three doses of cefoxitin, cefazolin, or placebo for infectious complications of nonelective cesarean section. Floral shifts occurred post partum, with return of Escherichia coli and Bacteroides fragilis and a decrease in Candida colonization. No significant differences in flora existed preoperatively among patients receiving cefoxitin, cefazolin, or placebo, but by day 4, both antibiotic groups had greater enterococcal colonization. This difference was more marked with cefoxitin than with cefazolin. No difference in E. coli or B. fragilis colonization was noted by day 4 in placebo and antibiotic groups. Resistance developing in isolates in the antibiotic groups was mainly a result of enterococcal colonization. Results of this study indicate that a three-dose cephalosporin prophylactic regimen resulted in a significant selection of resistant enterococcal colonization but there was no increase in nosocomial infection in the antibiotic groups compared to the placebo group. There did not appear to be significant differences in either species selection or antibiotic resistance of aerobic or anerobic microflora between the cefoxitin and cefazolin groups.

Bacteria, Aerobic↗

Multicenter comparison of cefoxitin versus cefazolin for prevention of infectious morbidity after nonelective cesarean section.

A randomized double-blind placebo-controlled comparison of prophylactic cefoxitin, an antibiotic with good activity against anaerobic bacteria, with cefazolin, an agent effective predominantly against aerobes, was undertaken in 354 women who underwent nonelective cesarean section (124 receiving cefoxitin, 119 cefazolin, and 111 placebo). Among the placebo group, 24.3% developed genital tract-related infection, in comparison to 5.6% of the cefoxitin patients and 6.7% of the cefazolin patients (P less than 0.001). Standard febrile morbidity, fever index, and duration of postoperative hospital stay were also significantly less in the antibiotic prophylactic groups. For patients with febrile morbidity, the mean fever index was less in the cefoxitin group (24.8 degree-hours) than that in the cefazolin group (42.7 degree-hours), and this difference approached statistical significance (P less than 0.1, greater than 0.05). Postoperative hospital stay longer than 1 week for infectious morbidity occurred in 26% of cefoxitin patients, a significantly lower incidence compared to the 66% rate for patients who received cefazolin, and the 57% incidence for patients in the placebo group (P less than 0.05).

Adult↗

Intrathecal penetration of N-formimidoyl thienamycin in normal rabbits: potentiation by coadministration of renal dipeptidase enzyme inhibitor.

The intrathecal penetration of N-formimidoyl thienamycin (MK0787) with or without coadministration of the renal dipeptidase enzyme inhibitor (MK791) in normal rabbits was studied immediately before and after the third dose of 40 mg/kg infused intravenously at daily 6-h intervals. Mean +/- standard error peak concentrations in cerebrospinal fluid were 0.23 +/- 0.02 and 0.53 +/- 0.12 micrograms/ml without and with coadministration of MK791, respectively (P less than 0.05, Student's t test). Penetration into cerebrospinal fluid (based on the ratio of cerebrospinal fluid to plasma area under the concentration-time curves) were 4.4 and 6.0%, respectively. N-Formimidoyl thienamycin penetrated uninflamed meninges, and peak concentrations were significantly augmented by coadministration of MK791.

Animals↗

Cerebrospinal fluid shunt infections. A review of 35 infections in 32 patients.

The authors have reviewed the clinical manifestations and therapy of hydrocephalus shunt infections in 32 patients with a total of 35 shunt infections. These 35 infections accounted for 43 hospital admissions. First infections usually developed within 2 months following surgery. At the time of diagnosis, 89% of patients were febrile. Fever and cough as a symptom complex characterized the initial clinical presentation in six of 19 episodes of infection complicating ventriculoatrial (VA) shunts, as compared with none of 21 episodes in which infection complicated ventriculoperitoneal (VP) shunts. Seven of 21 infectious episodes occurring in patients with VP shunts in situ were associated with significant abdominal pain and tenderness. These patients usually had no other clinical features to suggest shunt infection. Both of these symptom complexes often led to delays in diagnosis and treatment. Causative organisms included Staphylococcus epidermidis in 21, Staphylococcus aureus in seven, Gram-negative aerobic bacilli in seven, diphtheroids in five, Streptococcus species in four, and anaerobes in three. Five infections were polymicrobial in nature. Positive blood cultures were seen in 13 of 17 infectious episodes complicating VA shunts, as compared with only three of 13 other infections. When the shunt was completely removed, with or without replacement, all 13 patients were cured. When intravenous antibiotics were administered in conjunction with incomplete shunt removal, only eight of 15 courses resulted in cure. Intraventricular antibiotics were administered in four patients and all were cured. Therapy of shunt infections with parenteral antibiotics and incomplete shunt removal is associated with an unacceptably high failure rate.

Adolescent↗

Detection of a complement-derived chemotactic factor for tumor cells in human inflammatory and neoplastic effusions.

A chemotactic factor for neoplastic cells can be generated in vitro by incubating human C5 or C5a with leukocytic or pancreatic lysosomal enzymes and is also detectable in experimental inflammatory exudates. The authors therefore sought evidence for the existence of this factor in human effusions. Using the Boyden chamber assay, they detected chemotactic activity for MB-MDA-231 human breast carcinoma cells and Walker ascites tumor cells in human inflammatory and neoplastic exudates, including ascites, pleural effusions, synovial fluids and cerebrospinal fluids. Chemotactic activity was not found in transudates, normal cerebrospinal fluid, or normal serum. Human ovarian adenocarcinoma cells from one of the effusions migrated toward autologous ascites and towards the C5-derived chemotactic factor that had been prepared in vitro. In gel filtration the chemotactic factor behaved generally as a molecule having a molecular weight of approximately 6000 daltons. The activity was blocked after incubation with antiserums directed against C5 but not by antiserums directed against C3 or C4. In vitro, chemotactic activity for tumor cells could be generated by incubating extracts of exudate cells with autologous plasma or with purified C5. The authors conclude that a chemotactic factor for tumor cells can be formed in human effusions and that this factor has properties similar to those of a previously described C5-derived chemotactic factor.

Antibodies↗

Self-administration of intravenous antibiotics: an efficient, cost-effective home care program.

The effects of a home care program with 102 courses (2336 patient-days) of intravenous antibiotic therapy were evaluated. Home care nurses changed the intravenous cannula site every 3 days. The initial hospital stay averaged 11.8 days and the duration of home therapy averaged 22.9 days. The diseases treated included osteomyelitis, septic arthritis, endocarditis, cystic fibrosis and pneumonia, staphylococcal bacteremia, blastomycosis, actinomycosis and other soft tissue infections. All classes of commonly used antibiotics, including penicillins, cephalosporins, aminoglycosides and amphotericin B, were administered, alone or in combination. There were no side effects that necessitated discontinuation of home treatment or readmission to hospital. The average cost per patient-day was $58, compared with an estimated $193 for in-hospital therapy; in addition, 2336 hospital bed-days were made available. Most patients were able to resume many or all of their daily activities while receiving intravenous antibiotic therapy.

Adolescent↗

Plasmid pattern analysis of Staphylococcal epidermidis isolates from patients with prosthetic valve endocarditis.

The electrophoretic pattern formed by individual bacterial plasmid DNA molecules of differing molecular size was evaluated as an epidemiological marker among isolates of Staphylococcus epidermidis from patients with prosthetic valve endocarditis (PVE). Purified covalently closed circular plasmid DNA was obtained from selected isolates, and 79% of the plasmids were found to be less than 10 megadaltons in size; only these small plasmids were sought in subsequent screening gels. Crude cell lysates obtained by a rapid lysis technique and screened by agarose gel electrophoresis revealed the presence of one or more small plasmids in 54 of 58 (93%) PVE isolates; 79% contained two or more. Among 45 plasmid-containing isolates from cases of sporadic PVE at three institutions there were no identical plasmid patterns, although several isolates differed by a single plasmid. In contrast, among nine isolates from a cluster of cases of PVE in Canada, two groups of three isolates each had identical plasmid patterns. Additional clinical data suggested that these isolates were epidemiologically related. Phage typing distinguished one of the groups with plasmid pattern identity, but not the other, from the three isolates with dissimilar patterns. Plasmid pattern analysis shows promise as an epidemiological marker for clinically important isolates of S. epidermidis.

DNA, Circular↗

Toxic shock syndrome in the postoperative patient.

Toxic shock syndrome occurred in two patients within seven days of operation in women in whom Staphylococcus aureus was isolated from the wound incisions. Both patients had negative vaginal cultures. One patient was menstruating at the time of onset of the disease and the other was seven days' postpartum. Although toxic shock syndrome mainly occurs in menstruating women who use tampons and have positive vaginal cultures for Staphylococcus aureus, wound infection may also be a source for toxin production and adsorption.

Adult↗

Meningitis in the central Arctic: a 4-year experience.

There were 37 cases of meningitis during a 4-year period among the native and white populations served by the Churchill Health Centre in northern Manitoba, an annual incidence of 128 per 100 000 in the overall population and of 202 per 100 000 among the Inuit. Bacterial meningitis predominated; Neisseria meningitidis and Haemophilus influenzae each accounted for one third of the cases. There were five deaths, and 14 of the survivors had severe sequelae. Therefore, although the doctors and nurses involved in the study had improved access to telecommunication and air transportation services in caring for patients in isolated northern settlements, and despite their efforts to be vigilant for possible cases of meningitis and to begin vigorous treatment early, the incidence, morbidity and mortality of this disease remained relatively high, particularly among the Inuit.

Arctic Regions↗

Infectious complications of endoscopic retrograde cholangiopancreatography. A prospective assessment.

A prospective assessment of the bacterial complications of endoscopic retrograde cholangiopancreatography (ERCP) was made in 97 unselected patients undergoing 101 endoscopies. Blood cultures were taken before and five and ten minutes after completion of the procedure. In an attempt to identify a potential source of infection, aspirates were taken from the pancreaticobiliary duct (PBD) after injection of contrast material. Blood cultures from all procedures were negative. In 14 patients PBD aspirates yielded Pseudomonas aeruginosa, pyocin type 22 and serotype O6, suggesting a common source for this organism. Isolation of this strain ceased after more rigorous cleansing and disinfection of the endoscope. The occurrence of bacteremia following ERCP is low, but there is a risk of transmission of potential nosocomial pathogens with this procedure.

Bile Ducts↗

Pseudomonas sternotomy wound infection and sternal osteomyelitis. Complications after open heart surgery.

Pseudomonas aeruginosa sternotomy wound infections occurred in five patients who underwent open heart surgery. The initial isolate in each case was from a mediastinal chest tube routinely cultured on removal. Soft-tissue infection developed in two patients, and sternal osteomyelitis developed in three patients. Pseudomonas-typing studies showed a correlation between five isolates from chest-tube suction pumps used postoperatively and the wound isolates. Analysis of antibiograms of Pseudomonas wound isolates from the cardiac surgery ward from 1975 to 1977 showed eight of 15 with the same antibiogram as the sternotomy pathogens, compared with two of 13 isolates from other wards.

Cardiac Surgical Procedures↗

Impaired serum antibody response to inactivated influenza A and B vaccine in cancer patients.

The serum antibody response to vaccination with bivalent inactivated influenza vaccine containing A/Port Chalmers/1/73 (H3N2) and B/Hong Kong/5/72 antigens was assessed in 44 patients with cancer and in 27 healthy control subjects. A fourfold or greater increase in antibody titre after vaccination occurred in 16 of the 44 cancer patients and 25 of the 27 controls for the A antigen, and in 14 of the 44 cancer patients and 20 of the 27 controls for the B antigen. Patients with lymphoma, who tended to have hypogammaglobulinemia, responded less well than did patients with solid tumours. Among the latter the failure to show a fourfold or greater increase in antibody titre correlated with a poorer 18-month survival.

Adult↗

Combination antibiotic therapy in an outbreak of prosthetic endocarditis caused by Staphylococcus epidermidis.

The efficacy of combination antibiotics in vivo and in vitro was studied during an outbreak of prosthetic endocarditis caused by Staphylococcus epidermidis in 10 patients. The epidemic curve suggested that patients were infected at the time of their operation, with an interval from that time until diagnosis of 11 days to 20 months. The overall mortality was 50%. Four of six patients treated with gentamicin in combination with a penicillin analogue, a cephalosporin or clindamycin survived without reoperation. One of four patients survived when treated with regimens that did not include gentamicin. In vitro studies showed a median minimum inhibitory concentration for methicillin of 8.0 microgram/mL, compared with 0.1 microgram/mL for cephalothin, clindamycin and gentamicin, and a synergistic bactericidal effect between gentamicin and methicillin, cephalothin or clindamycin. These data suggest that gentamicin is a valuable component of combination antibiotic therapy in prosthetic endocarditis caused by S. epidermidis.

Adult↗

Intravenous antibiotic therapy at home.

During a 12-month period, 23 patients aged 12 to 78 years were treated for 8 to 40 days (mean, 23 days) at home with intravenous (i.v.) antibiotics. Diseases treated included bone and joint infection (14 patients), blastomycosis (two), actinomycosis (two), staphylococcal bacteremia (two), endocarditis (two), and candidal pyelonephritis (one). After initial in-hospital training, patients self-administered their drugs through a heparin-lock i.v. cannula, which was changed regularly by a visiting home care nurse. Antibiotics administered included cloxacillin, penicillin G, cephalosporins, gentamicin, carbenicillin, and amphotericin B. Patient and family acceptance of the program was good, the program was therapeutically effective, and, apart from a decreased prevalence of phlebitis with the heparin lock at home, side effects were no different from those of in-hospital-treated patients. The cost of home therapy was $ 40 per patient-day compared with an estimated $ 137 had the patients remained in hospital. Most patients were able to resume normal activities while receiving home i.v. therapy.

Actinomycosis↗