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Biomedical subjects

C M Nolan

Publications and source records attributed to C M Nolan.

At least 91 records · Page 5Linked to original sources
PubMed1979

Antibody response to infection in multiple myeloma. Implications for vaccination.

We report the humoral immune response of a patient with multiple myeloma to rapidly successive episodes of meningococcal and pneumococcal meningitis. Specific antibody responses included a high bactericidal titer (1:640) against the infecting meningococcus and a sharp increase (from 198 to 8,097 ng/ml antibody nitrogen) in antibody to the type-specific capsular polysaccharide of the infecting pneumococcus. These data, showing the production of protective antibodies against the two pathogens, suggest that some patients with multiple myeloma might also respond to appropriately administered bacterial vaccines. This fact should be ascertained because vaccination could potentially reduce the high rate of bacterial infections associated with this disease.

Antibodies, Bacterial↗
PubMed1979

Treatment of bacterial meningitis with intravenous amoxicillin.

Eleven children with bacterial meningitis were treated intravenously with amoxicillin sodium to evaluate the efficacy of the parenteral form of amoxicillin for this serious infection and to measure the penetration of the drug into cerebrospinal fluid (CSF). The infecting organisms were Haemophilus influenzae in nine cases and Streptococcus pneumoniae in two. Nine patients had optimal responses to amoxicillin sodium, 200 mg/kg per day for 14 days. Bacteria were also eradicated from CSF of the other two, but one experienced fever and culture-negative CSF pleocytosis after cessation of amoxicillin, and the other developed H. influenzae empyema 2 weeks after termination of therapy. By comparison, 7 of 10 children with meningitis responded optimally to ampicillin (nonrandomized design) during the period of study. The mean peak CSF concentration of amoxicillin was 3.14 mug/ml (ca. 7% of the concomitant mean peak serum level) early during therapy. However, meningeal penetration of the drug declined to a mean peak of 0.63 mug/ml on the final day of therapy. Mild transient neutropenia, noted in five patients, was the most common side effect of amoxicillin sodium therapy; five patients treated with ampicillin also experienced reversible neutropenia. Thus, intravenous amoxicillin sodium provided therapy for bacterial meningitis comparable to that of ampicillin in this limited case-control study.

Amoxicillin↗
PubMed1979

Rosaramicin versus penicillin G in experimental Pneumococcal meningitis.

Rosaramicin, a new macrolide antibiotic, was compared with penicillin G in the treatment of pneumococcal meningitis in rabbits. Animals were infected intracisternally with 10(4) colony-forming units of Streptococcus pneumoniae type III (rosaramicin minimal inhibitory/bactericidal concentrations, 0.25/0.5 mug/ml; penicillin G minimal inhibitory/bactericidal concentrations, 0.03/0.06 mug/ml). Treatment was instituted 96 h later. Infusion of rosaramicin at 25 mg/kg per h intravenously for 8 h produced a peak cerebrospinal fluid (CSF) drug concentration of 1.54 mug/ml (range, 0.87-3.6 mug/ml). During this infusion the numbers of pneumococci in CSF decreased from 6.2 +/- 0.5 to 3.36 +/- 1.12 log(10) colony-forming units per ml. Penicillin G, infused at 30 mg/kg per h for 8 h, reached a similar concentration in CSF but caused a greater reduction (P < 0.01) in CSF bacteria, from 6.4 +/- 0.36 to 1.3 +/- 0.67 log(10) colony-forming units per ml. Penicillin G, at 100 mg/kg per day intramuscularly for 5 days, cured 7 of 10 rabbits with pneumococcal meningitis. A higher dose, 300 mg/kg per day for 5 days, was no more efficacious: 11 of 14 rabbits were cured. Rosaramicin at 100 mg/kg per day intramuscularly for 5 days cured only 5 of 15 rabbits with meningitis, but a higher dosage regimen of that drug (250 mg/kg per day intramuscularly) produced acute, fulminant enterocecitis and death within 48 h in seven of eight rabbits. No cytotoxin was detected in the feces of one rabbit with acute enterocecitis. Thus the efficacy of rosaramicin in experimental pneumococcal meningitis, measured by bacterial clearance from CSF and by treatment outcome, was less than that of penicillin G. In addition, high-dose parenteral rosaramicin caused acute, fulminant enterocecitis in a high proportion of treated rabbits.

Animals↗
PubMed1979

Interactions between human granulocytes and Blastomyces dermatitidis.

We studied interactions in vitro between human granulocytes and the yeast-like form of Blastomyces dermatitidis, because granulocytes are prominent in the host response to systemic blastomycosis. In Boyden chamber assays, broth culture filtrates of B. dermatitidis contained levels of granulocyte chemotactic activity that were significantly higher than those present in similar culture filtrates of Histoplasma capsulatum and Cryptococcus neoformans, two fungi that characteristically do not elicit granulocytes in infected tissues. Microscopic study, including electron microscopy, demonstrated that granulocytes phagocytosed B. dermatitidis promptly and efficiently. Moreover, granulocytes emitted light (chemiluminescence) at a brisk rate during phagocytosis of B. dermatitidis, indicating activation of intracellular metabolic pathways. However, fungicidal assay showed that granulocytes (1:1 cell-yeast ratio, 10% serum) killed only 29% of the B. dermatitidis inoculum during 3 h of incubation. Taken together, these findings suggest that there is disparity between phagocytosis and intracellular killing of B. dermatitidis by human granulocytes, perhaps because of resistance of this fungus to granulocyte microbicidal mechanisms.

Blastomyces↗
PubMed1978

Treatment of typhoid carriers with amoxicillin. Correlates of successful therapy.

Fifteen chronic enteric carriers of Salmonella typhi were treated with amoxicillin trihydrate, 2 g by mouth, three times per day. Nine of ten patients who were able to take the full amoxicillin regimen were cured; among five patients treated with a lower daily amoxicillin dosage because of gastrointestinal (GI) side effects, only two were cured (P less than .05). The mean serum amoxicillin concentration at termination of therapy was higher (P less than .01) in five patients who were cured (10.4 +/- 1.6 microgram/ml) than in the four who failed (3.0 +/- 0.7 microgram/ml), although the latter values were all above the minimal inhibitory concentrations for infecting organisms. This study suggests that amoxicillin treatment of chronic typhoid carriers could be enhanced by treating with doses sufficient to provide suprainhibitory serum concentrations of the antibiotic. However, GI intolerance to amoxicillin could limit this therapeutic approach.

Administration, Oral↗
PubMed1978

Experimental pneumococcal meningitis. IV. The effect of methyl prednisolone on meningeal inflammation.

This study was undertaken to determine whether adrenal corticosteroids suppress meningeal inflammation in experimental pneumococcal meningitis in rabbits and, if so, whether the mechanism of suppression involves inhibition of chemotactic activity in CSF or modification of granulocyte responses to inflammation mediators. It was found that methyl prednisolone, administered intramuscularly in doses of 15 or 30 mg/kg 24 hr and 48 hr after induction of meningitis, significantly reduced (p less than 0.01) the mass of granulocytes present in the meninges 72 hr after infection, the time of maximum meningeal inflammation. The larger dose of steroid produced approximately twice the suppressive effect of the smaller dose (p less than 0.05). The regime of methyl prednisolone that produced maximal suppression of meningeal inflammation (30 mg/kg/day) did not alter CSF chemotactic activity or chemotactic responsiveness and phagocytic activities of granulocytes from rabbits with meningitis. However, steroid therapy inhibited an increase in granulocyte adherence that was observed in untreated animals with meningitis (p less than 0.05). Thus methyl prednisolone in doses of 15 and 30 mg/kg given daily to rabbits with pneumococcal meningitis produced a suppressive effect on meningeal inflammation that was dose-dependent and was possibly mediated by inhibition of granulocyte adherence.

Animals↗
PubMed1977

Polymyxin B and rifampin: new regimen for multiresistant Serratia marcescens infections.

Polymyxin B and rifampin were given to 12 patients with multi-drug-resistant nosocomial Serratia marcescens infections. Eight cures were achieved; drug hepatotoxicity occurred once; one fatal suprainfection was encountered; and two patients died during therapy of causes related to severe underlying illnesses. Polymyxin B and rifampin were uniformly synergistic in vitro against the infecting strains and against 40 additional clinical isolates of S. marcescens.

Adult↗
PubMed1977

Nephropathy associated with methicillin therapy. Prevalence and determinants in patients with staphylococcal bacteremia.

The nephropathy associated with methicillin sodium therapy is considered to be rare, but its prevalence is unknown. We reviewed the antibiotic therapy of 81 cases of Staphylococcus aureus bacteremia to establish the frequency and determinants of methicillin nephropathy in that disease. Fifty-two patients received methicillin; nine (17%) experienced the characteristic clinical signs previously associated with drug-induced acute interstitial nephritis. This nephropathy uniformly subsided after methicillin was withdrawn, and did not always include deterioration of renal function. Factors that correlated with methicillin nephropathy were endocarditis and prolonged treatment, but not intravenous drug abuse. There was only one adverse reaction among 29 patients treated with a cephalosporin. It was similar to the nephropathic reactions to methicillin. Thus, reversible renal abnormalities are prevalent during methicillin therapy, particularly among patients with staphylococcal infections such as endocarditis. When prolonged therapy with methicillin is required, the urinary sediment and renal excretory function should be monitored.

Adult↗
PubMed1976

Staphylococcus aureus bacteremia. Current clinical patterns.

One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics.

Adolescent↗
PubMed1975

Experimental pneumococcal meningitis: III. Chemotactic activity in cerebrospinal fluid.

Chemotactic activity was assayed in CSF of rabbits with pneumococcal meningitis to further characterize the inflammatory response in this infection. CSF chemotactic activity was detected in increasing levels for 72 hr after infection. Activity was stable at 56 degrees and was inactivated by agents which denature proteins. Gel filtration demonstrated two chemotactically active fractions in infected CSF with mol wts of approximately 3000 and 11,000. Bacterial products appear to account for a portion of the observed CSF chemotactic activity, but the role of host factors remains to be clarified.

Animals↗
PubMedDate not supplied

Penetration of cefotaxime and moxalactam into cerebrospinal fluid of rabbits with experimentally induced Escherichia coli meningitis.

Penetration of the new beta-lactam antibiotics cefotaxime and moxalactam into cerebrospinal fluid (CSF) was studied in rabbits with experimentally produced Escherichia coli meningitis. Cefotaxime reached peak concentrations (mean +/- SEM) of 31.9 +/- 5.4 micrograms/ml in serum and 2.8 +/- 0.3 micrograms/ml in CSF after an infusion of 50 mg/kg per hr for 8 hr. Moxalactam, after an infusion of 12.5 mg/kg per hr iv, produced peaks of 31.0 +/- 13.1 micrograms/ml in serum and 9.7 +/- 1.2 micrograms/ml in CSF. Both drugs reduced the initial concentration of E. coli in the CSF by greater than 1,000-fold. An infusion of 100 mg/kg per hr of cephalothin produced a peak concentration of 76.5 +/- 15.2 micrograms/ml in serum but resulted in a concentration of only 0.17 +/- 0.05 micrograms/ml in CSF and had no bactericidal activity in CSF. Paper chromatography of CSF from cefotaxime-treated rabbits showed that 85.3% (+/- 3.1%) of the antibiotic activity was ascribed to desacetylcefotaxime, a metabolite that is less potent than the parent drug. Neither cefotaxime nor moxalactam was taken up in vitro by rabbit choroid plexus tissue, but cephalothin was taken up at a rate of 9.6 +/- 1.1 microgram/g per hr. Perhaps cefotaxime and moxalactam reached higher concentrations in CSF than did cephalothin because they are not removed from the CSF by the exit pump of the choroid plexus. The fact that levels of cefotaxime in CSF are lower than those of moxalactam could be attributed to the presence of desacetylcefotaxime, a metabolite that is less active than cefotaxime.

Animals↗
PubMedDate not supplied

Clinical experience with cefotaxime in obstetric and gynecologic infections.

Infections in the upper genital tract continue to be one of the leading causes of serious morbidity for obstetric and gynecologic patients. The polymicrobial, mixed aerobic and anaerobic isolates recovered from women with such infections demand broad-spectrum antimicrobial activity. In the past, combination therapy has been given in order to attain this coverage. In a multicenter open study, cefotaxime was used for treatment of endomyometritis after cesarean section, pelvic cellulitis after hysterectomy, and acute pelvic inflammatory disease. The drug effected a clinical cure in 93% of 104 women. In a randomized comparative study conducted at one center, cefotaxime cured 97% of 36 cases of post-cesarean section endomyometritis; clindamyclin plus gentamicin cured 94% of 18 cases of the same infection. There was no evidence of significant alteration in hematopoietic, hepatic, or renal function with either regimen. Cefotaxime appears to be a safe, extremely effective antimicrobial drug that is ideally suited for single-agent treatment of serious soft-tissue pelvic infections in obstetric or gynecologic patients.

Adolescent↗
PubMedDate not supplied

Epidemiologic aspects of M. pneumoniae disease complications: a review.

As early as the 1940s, erythema multiforme exudativum (Stevens-Johnson syndrome) and hemolytic anemia were associated with outbreaks of atypical pneumonia, a disease later found to be caused by Mycoplasma pneumoniae. Epidemiologic evidence has also associated neurological complications, especially aseptic meningitis and meningoencephalitis, with M. pneumoniae infections. Urticarial and morbilliform skin rashes often appear late in the course of M. pneumoniae pneumonia. A multitude of other complications have been ascribed to M. pneumoniae infections, often reported as case reports diagnosed by serologic antibody titers only. More systematic investigations are needed to assess the frequency of complications to M. pneumoniae infections. Isolation of the agent, not only serologic titer rises, should be required before a syndrome is attributed to M. pneumoniae infection.

Adult↗