Biomedical subjects

J D Klinger

Publications and source records attributed to J D Klinger.

At least 37 records · Page 2Linked to original sources

PubMed1985

Comparison of cefpiramide (HR-810) and four anti-pseudomonal beta-lactam agents against pseudomonas isolates from children with cystic fibrosis.

Cefpiramide (HR-810), ceftazidime, piperacillin, ticarcillin, and aztreonam were tested against tobramycin-sensitive and -resistant strains of Pseudomonas aeruginosa and tobramycin/amikacin-resistant isolates of Ps. cepacia recovered from the sputum of patients with cystic fibrosis. Against Ps. aeruginosa, none of the drugs inhibited 90% of the test strains at levels of less than 128 mg/l. Median minimal, inhibitory concentrations (MIC50) for all of the beta-lactam agents were lower for tobramycin-sensitive versus tobramycin-resistant isolates of Ps. aeruginosa. Ceftazidime was the most effective agent against Ps. cepacia. Aminoglycoside-resistance appears to be associated with significant beta-lactam resistance in Ps. aeruginosa isolated from the sputum of patients with cystic fibrosis.

Anti-Bacterial Agents↗

PubMed1985

In-vitro activity of ciprofloxacin and other antibacterial agents against Pseudomonas aeruginosa and Pseudomonas cepacia from cystic fibrosis patients.

The in-vitro activities of ciprofloxacin, a new oxyquinoline derivative, norfloxacin and six anti-pseudomal beta-lactam antibiotics were tested against pulmonary isolates of smooth and mucoid colony forms of Pseudomonas aeruginosa, and Ps. cepacia from children with cystic fibrosis. Ciprofloxacin was the most effective of the agents tested against either species. Minimal inhibitory concentrations of ciprofloxacin were 0.5, and 16 mg/l, for 90% of the Ps. aeruginosa and Ps. cepacia strains tested, respectively. No effect of inoculum size or discordance between inhibitory or bactericidal concentrations was observed. Ciprofloxacin is a potentially useful agent for the treatment of acute pseudomonal pulmonary exacerbations in children with cystic fibrosis.

Anti-Bacterial Agents↗

PubMed1985

Prevalence of myopia in school children in Vanuatu.

The onset of myopia typically occurs in childhood and increases during puberty. We studied the vision and refractive errors of 977 school children (ages 6 to 17 years) in 1983. Myopia in the group was extremely low; 97% had vision of 6/6, and 1.3% had myopia greater than 0.25D. Regression analysis revealed a change in mean refraction of -0.016D/year for males and -0.024D/year for females. There were no significant differences between males and females. These children engaged in about 8 hours of school work per day, and we conclude that genetic factors predominate over environmental factors in the determination of myopic refractive errors for this group.

Adolescent↗

PubMed1985

Pharmacokinetics and cerebrospinal fluid penetration of ceftazidime in children with meningitis.

The single dose pharmacokinetics and cerebrospinal fluid (CSF) penetration of ceftazidime were determined in 10 children with bacterial meningitis. Serum ceftazidime pharmacokinetics showed a distinct age dependence in which the clearance in children less than 1 month of age was markedly reduced. Ceftazidime concentrations in CSF, which ranged from 1.4-8.5 micrograms/ml, exceeded the minimum bactericidal concentrations for infecting pathogens throughout the 8-hour sampling period. These concentrations were found to be independent of CSF cell count, protein concentration or the day of therapy on which the study was performed. The ratio of CSF to serum ceftazidime concentration increased with time, suggesting that ceftazidime was cleared more slowly from CSF than from peripheral blood. Our data support the initiation of a study comparing the efficacy of ceftazidime to conventional therapy in children with bacterial meningitis.

Age Factors↗

PubMed1985

Pseudomonas cepacia colonization among patients with cystic fibrosis. A new opportunist.

Pseudomonas cepacia colonization among patients with cystic fibrosis (CF) at our center has increased from 7% (of 419 patients) to 15% (of 450 patients) over the past 5 yr (July 1978 through June 1983). The proportion of patients dying with P. cepacia colonization has increased over this 5-yr period (Year 1, 9% (1/11) of the deaths were associated with P. cepacia; Year 5, 55% (16/29) were associated with P. cepacia). These observations have led to a heightened concern regarding the presence of P. cepacia in the CF population. Characteristics of the patient population that might relate to P. cepacia colonization were reviewed. Increasing numbers of patients in good clinical condition became colonized with P. cepacia. Females in good clinical condition who acquire P. cepacia appear to be at special risk of developing severe and unexpected pulmonary complications that often end in death. In contrast, males, regardless of clinical condition, appear less likely to experience an immediate decline in clinical status. Hospitalization is potentially implicated in contributing to the increase in P. cepacia colonization because many patients' initial positive cultures were concurrent with or followed a hospital stay. Sixteen patients with CF and P. cepacia had siblings with CF, 6 of whom subsequently acquired P. cepacia. This frequency is more than double that in our overall CF population.

Adult↗

PubMed1985

Biochemical and pathologic evidence for proteolytic destruction of lung connective tissue in cystic fibrosis.

The risk for proteolysis of lung connective tissue was evaluated in patients with cystic fibrosis (CF) with chronic, severe lung infections by measuring uninhibited elastase activity in sputum samples and urinary excretion of desmosines (cross-linking amino acids in elastin). Of the 16 patients included in the study, 11 were infected with Pseudomonas aeruginosa, 2 with Pseudomonas cepacia, and 2 with both P. aeruginosa and P. cepacia. Uninhibited elastase activity (0.34 to 20.2 micrograms elastin degraded/mg protein/30 min) was detected in the sputum samples from each of 13 patients tested. Serine elastase activity was detected in the sputum of each of 12 patients, and metalloelastase (P. aeruginosa elastase and possibly macrophage elastase) activity was detected in the sputum of 11 of 12 patients tested. Male patients with CF excreted significantly more elastin cross-links (desmosines) in their urine than did control male subjects (3.6 +/- 1.7 micrograms/kg/24 h versus 1.5 +/- 0.6 micrograms/kg/24 h; p less than 0.01), and there was a significant correlation (p less than 0.05) between urine desmosine excretion and the severity of lung disease in the patients with CF as indicated by chest roentgenogram score. In 3 autopsied patients, abnormal elastin fibers were seen by light microscopy in all lung compartments. Fragmented and exfoliated elastin, evidence of active elastolysis, was noted in bronchial ulcers and abscesses. The results of this study suggest that proteolytic destruction of lung connective tissue is an ongoing process in the chronically infected CF lung and that this proteolysis contributes to the pathologic changes observed in airways and alveolar parenchyma.

Adolescent↗

PubMed1985

Use of an automatic refraction device in a Third World country.

The vision welfare services in many Third World countries are compromised by the shortage of trained ophthalmic vision care workers. We investigated the feasibility of fulfilling part of the needs in this area by training local personnel in the use of automatic refraction devices. A nurse from the Vila Base Hospital in Vanuatu was given minimal training in the use of such an instrument (Nikon NR 2000), and given guidelines for the preparation of ophthalmic prescriptions. Sixty-nine subjects in the Village of Mélé in Vanuatu were seen by both the nurse and an optometrist, and the prescriptions issued by both workers were compared. The use of automatic refractors under those conditions holds promise for filling the needs in Third World countries, and suggestions are given for adapting these instruments for the particular conditions encountered during this study.

Adolescent↗

PubMed1984

Proteinases release mucin from airways goblet cells.

The mucin-release effect of proteinases on airways epithelium was assessed in vitro. Using explants of rabbit tracheal mucosa-submucosa we determined that elastase and alkaline proteinase from Pseudomonas aeruginosa, pancreatic trypsin and elastase and the microbial proteinases subtilisin, thermolysin and pronase, all stimulate mucin release from goblet cells. On the other hand Streptomyces caespitosus proteinase pancreatic chymotrypsin and collagenase fail to trigger mucin release. Bovine trachea and human nasal polyp epithelium also release mucins in response to proteinases. Mucin release activity is dependent on proteolytic activity of enzymes which have a fairly broad, but generally similar, substrate specificity. The cellular mechanism of action is not known. We propose that mucin secretion in response to proteinases represents a useful defence mechanism but also forms the basis for hypersecretory states and airways obstruction in chronic endobronchial inflammatory states.

Animals↗

PubMed1984

Cultures of thoracotomy specimens confirm usefulness of sputum cultures in cystic fibrosis.

Bacteriologic cultures of sputum and specimens obtained at thoracotomy from 17 patients with cystic fibrosis were compared. All organisms found in the surgical specimens were found in the sputum. Only two surgical specimens failed to yield any organisms. The most frequently isolated organisms were Pseudomonas aeruginosa (41%) and Pseudomonas cepacia (35%). Serotypes of P. aeruginosa and antibiogram results on both P. aeruginosa and P. cepacia further supported the concordance of the isolates from the two sources. In addition, anaerobic cultures were obtained in specimens from 10 patients with CF and revealed two patients with anaerobic colonization of the lower respiratory tract. These findings also correlated well with the sputum cultures. The correlation of sputum and lung specimen culture results supports the value of sputum culture in the management of lung disease in CF.

Adolescent↗

PubMed1984

A double-blinded comparative study of sultamicillin and potassium penicillin V in the treatment of childhood streptococcal pharyngitis.

Fifty-two children with positive pharyngeal cultures for group A streptococci were randomized to receive phenoxymethyl penicillin or sultamicillin, an ester of ampicillin and sulbactam. By serological and bacteriological criteria, sultamicillin was effective in 100% of the 20 evaluable cases of infection and carriage while penicillin was effective in six out of eight (75%) and three out of eight (93%) respectively. Of the eight children with infections treated with sultamicillin, three (37.5%) became recolonized with the organism compared to none of the children in the penicillin group. These differences were not statistically significant.

Adolescent↗

PubMed1984

In vitro activities of aztreonam, piperacillin, and ticarcillin combined with amikacin against amikacin-resistant Pseudomonas aeruginosa and P. cepacia isolates from children with cystic fibrosis.

Amikacin, combined with aztreonam, piperacillin, or ticarcillin, synergistically inhibited amikacin-resistant sputum isolates of Pseudomonas aeruginosa and P. cepacia from children with cystic fibrosis. Ticarcillin-amikacin was the least active combination. Aminoglycoside resistance should not preclude the use of beta-lactam-aminoglycoside combinations in the treatment of pulmonary infections in cystic fibrosis.

Amikacin↗

PubMed1984

Ceftazidime as initial therapy for suspected bacterial infections in hospitalized pediatric patients.

Ceftazidime, a new beta-lactam antibiotic, was used to treat 60 children with suspected bacterial infections occurring outside the central nervous system. The patients ranged in age from 0.1 to 21 years and received 30 mg of ceftazidime per kg up to a total single dose of 1 g administered every 8 h. Fifty-three pathogens were isolated from 43 children before the initiation of therapy. All children responded clinically, although one child failed bacteriologically and five children were considered colonized at the end of ceftazidime therapy. Adverse reactions associated with ceftazidime administration were primarily alterations in laboratory parameters and were clinically insignificant. Ceftazidime administered on an 8-h dosing regimen is effective monotherapy for the treatment of childhood infections.

Adolescent↗

PubMed1984

Pulmonary cellular response to chronic irritation and chronic Pseudomonas aeruginosa pneumonia in cats.

A model of chronic pulmonary infection was used for studying cellular events in a sequential manner. In this model, agarose beads containing Pseudomonas aeruginosa were instilled endotracheally into cats. Nine cats were inoculated with agarose beads containing P. aeruginosa, and four others were inoculated with sterile beads. With a fiberoptic bronchoscope, bronchial washings were obtained biweekly for up to 30 weeks. The quantitative pulmonary inflammatory cell response and alveolar macrophage morphology of the animals exposed to P. aeruginosa were compared with those for the animals exposed to a chronic irritant (agarose beads). Bronchial washings of all animals before inoculation showed that 70 to 90% of the cells were macrophages. After inoculation with P. aeruginosa, a persistent inflammatory response was observed (60 to 70% granulocytes). In the sterile-bead-inoculated group, the response was less prominent (30 to 40% granulocytes). As early as 2 weeks after inoculation, alveolar macrophages from infected animals were larger and had cytoplasmic features that differed from those of controls. Electron microscope examination showed prominent surface alterations in alveolar macrophages from the infected cats. These alterations persisted from 2 to 12 weeks after infection. In animals inoculated with sterile beads, alveolar macrophages exhibited less extensive surface changes that had resolved by week 8. Histologically, chronic bronchiolitis and pneumonia were more severe in the infected animals than in controls. This model of chronic inflammation and macrophage stimulation, which is similar to the chronic pneumonia of cystic fibrosis, may be a useful approach to answer questions on the role of macrophage activation in chronic lung disease.

Animals↗

PubMed1984

Proteinases of Pseudomonas aeruginosa evoke mucin release by tracheal epithelium.

We have determined the potential of exoproducts from pathogenic bacteria to stimulate the release of high molecular weight mucins from goblet cells of airway epithelium in a rabbit tracheal explant system. Culture supernatants from proteolytic strains of Pseudomonas aeruginosa and Serratia marcescens, but not supernatants from a number of non-proteolytic strains, released mucins from goblet cells. Highly purified elastase and alkaline proteinase from P. aeruginosa stimulated goblet cell mucin release in a dose-dependent fashion. Lipopolysaccharide, exotoxin A, and alginate of P. aeruginosa did not possess mucin release properties. Proteolytic activity was required for mucin release by P. aeruginosa elastase, but such release in goblet cells was not mediated by cyclic AMP. Morphologic studies suggested rapid release of mucins from goblet cells was response to elastase by a process resembling apocrine secretion. Several nonbacterial proteinases mimicked the effect of Pseudomonas proteases. These studies provide support for the hypothesis that bacterial and other play a role in the pathogenesis of mucus hypersecretion in acute and chronic lung infections.

Adenylyl Cyclases↗

PubMed1984

An in-hospital evaluation of the sonic mist ultrasonic room humidifier.

It is generally recognized that nebulizers can be a source of nosocomial infection. 'Cold mist' room humidifiers are a particular problem because they are difficult to sterilize. We evaluated a new device, the Sonic Mist ultrasonic room humidifier, to determine how quickly it became contaminated during continuous use by a population of cystic fibrosis patients. In addition, the study was designed to test the effectiveness of placing a bacterial filter on the air inlet of the humidifier. We found that the entire humidifier could withstand repeated gas sterilization. Data obtained from 18 humidifiers involving cystic fibrosis patients indicate that the earliest humidifier contamination occurred after 5 days of continuous use. Although all patients had large numbers of gram-negative bacilli as predominant sputum flora, only 7 episodes of contamination were found during 34 humidifier-use periods. Three units equipped with filters became contaminated (5-7 days) and four unfiltered units became contaminated (6-11 days), indicating that the use of an inlet filter made no apparent difference. The organisms recovered from contaminated units were not found as sputum flora and would not generally be considered of clinical significance in cystic fibrosis sputum cultures. Probable sources of the organisms were room dust and hand contamination. A further test of the inlet filter was performed by exposing filtered and unfiltered units to mist from an intentionally contaminated humidifier. Again, the contamination rate was low and the filter apparently made no difference. These results indicate that the Sonic Mist humidifier may be appropriate for hospital use if adequate sterilization and contamination-monitoring practices are followed.

Cross Infection↗

PubMed1983

Once-daily vs. continuous aminoglycoside dosing: efficacy and toxicity in animal and clinical studies of gentamicin, netilmicin, and tobramycin.

The dosing frequency of aminoglycoside antibiotics may alter efficacy and toxicity independent of total daily dose. Once-daily tobramycin dosing was compared with continuous infusion in three models of efficacy. Acute pneumonia due to Pseudomonas aeruginosa in guinea pigs responded better to once-daily dosing, and chronic pneumonia in rats and endocarditis in rabbits responded equally to both regimens. Dogs given gentamicin, tobramycin, or netilmicin once daily, with maximum serum concentrations of greater than 100 mg/liter, had less nephrotoxicity than dogs given continuous infusions. Tobramycin was given once daily or continuously to 52 patients with cystic fibrosis who in 10 days had no change in creatinine clearance or hearing despite maximum serum tobramycin concentrations of 40 mg/liter. Intermittent dosing of aminoglycosides, causing infrequent large maximum serum concentrations, may be less toxic and equally efficacious as frequent dosing.

Adult↗

PubMed1983

Efficacy and safety of ceftriaxone in serious pediatric infections.

Thirty-four patients aged 1 month to 19 years were treated with ceftriaxone for suspected bacterial infections. Bacterial pathogens were isolated from 25 children. The overall bacterial cure rate was 88%, with an overall clinical response rate of 96%. No side effects requiring cessation of therapy were observed. Ceftriaxone proved to be safe and effective in the treatment of serious infections in children.

Adolescent↗

PubMed1983

Suppression of in vitro lymphocyte DNA synthesis by killed Pseudomonas aeruginosa.

Whole antibiotic-killed classic Pseudomonas aeruginosa organisms elicited human lymphocyte [3H]thymidine (TdR) uptake in vitro after 5 days in culture. However, high concentrations of the same preparation did not elicit [3H]TdR incorporation. The investigation of this lymphocyte unresponsiveness revealed that a high dose of P. aeruginosa, when added to lymphocyte cultures together with optimal concentrations of lymphocyte activators (e.g., plant lectins or whole killed Staphylococcus aureus Cowan 1), caused a potent, nonspecifically expressed inhibition of lymphocyte [3H]TdR uptake in response to these mitogens. High doses of P. aeruginosa were not cytotoxic to lymphocytes, and the inhibition caused was reversed when lymphocytes were washed free of bacteria. The inhibition of [3H]TdR uptake by high-dose P. aeruginosa did not require the generation of adherent suppressor cells or prostaglandin-mediated, steroid-sensitive or radiation-sensitive suppressor mechanisms. At optimal lymphocyte stimulatory concentrations of P. aeruginosa, the addition of indomethacin or the depletion of adherent cells caused an increase in lymphocyte [3H]TdR incorporation. This is consistent with an adherent-cell population regulating [3H]TdR uptake in response to P. aeruginosa via a prostaglandin-dependent pathway. This population was not involved in the inhibition of lymphocyte [3H]TdR uptake by high concentrations of P. aeruginosa.

Cell Survival↗