Biomedical subjects

B Ramsey

Publications and source records attributed to B Ramsey.

At least 37 records · Page 2Linked to original sources

PubMed1994

Nebulizer delivery of tobramycin to the lower respiratory tract.

We characterized a tobramycin aerosol generated by five nebulizers: Micron One, Pulmosonic, Pulmo-Aide, DeVilbiss Model 65, and UltraNeb 100 by particle size and drug concentration. The Micron One nebulizer did not produce a recoverable aerosol, while the Pulmosonic had a minimal output; therefore three machines were examined for their ability to deliver tobramycin to the lower respiratory tract of patients with cystic fibrosis (CF). The DeVilbiss 65 had the greatest output: with air as the carrier gas it produced an aerosol with > 60% of the particles having a mean mass aerodynamic diameter (MMAD) of > 5.5 microns. Using helox shifted the MMAD so that > 65% of the particles were < 5.5 microns. Increasing the power in the DeVilbiss 65 increased the output of particles > 9.2 microns, without a change in the particles < 3.3 microns. With air as the carrier gas the Pulmo-Aide and the UltraNeb 100 produced an aerosol with > 60% particles, < 3.3 microns MMAD. Using helox the UltraNeb 100 increased the amount of aerosol with a < 3.3 microns MMAD to 98%. Tobramycin delivery to the lower respiratory tract with the Pulmo-Aide and UltraNeb 100 was compared using air or helox by measuring sputum drug concentration. Pulmo-Aide failed to produce detectable tobramycin in sputum in 2 out of 9 patients with CF. With the UltraNeb 100, all patients had measurable sputum tobramycin immediately after administration (range, 16.2-3385 micrograms/g), but no statistically significant difference was found when using either compressed air, helox, or ambient air.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Disposition of drugs in cystic fibrosis. VI. In vivo activity of cytochrome P450 isoforms involved in the metabolism of (R)-warfarin (including P450 3A4) is not enhanced in cystic fibrosis.

OBJECTIVE: To determine whether the activity of cytochrome P450 isoforms involved in the metabolism of (R)-warfarin is enhanced in cystic fibrosis. DESIGN: Six adult subjects with cystic fibrosis and six healthy control subjects, matched by age and sex, were administered (R)-warfarin as a single intravenous bolus dose (0.375 mg/kg), and urine and plasma samples were collected for 192 hours. The concentration of (R)-warfarin in plasma and the concentration of (R)-warfarin and its metabolites in urine were determined by HPLC and GC/MS, respectively. Plasma protein binding of (R)-warfarin was measured by ultrafiltration. RESULTS: The unbound plasma clearance of (R)-warfarin was not significantly (p > 0.05) different between the cystic fibrosis and the control groups (cystic fibrosis, 997 +/- 483 ml/hr/kg; control, 788 +/- 219 ml/hr/kg). The unbound metabolic clearances of (R)-warfarin to its oxidative metabolites--6-hydroxywarfarin, 7-hydroxywarfarin, 8-hydroxywarfarin, and 10-hydroxywarfarin (mediated by P450 3A4)--were also similar (p > 0.05) in the two groups (6-hydroxywarfarin: cystic fibrosis: 124.2 +/- 72.8 ml/hr/kg, control: 99.4 +/- 37.3 ml/hr/kg; 7-hydroxywarfarin: cystic fibrosis: 43.8 +/- 32.2 ml/hr/kg, control: 34.5 +/- 10.6 ml/hr/kg; 8-hydroxywarfarin: cystic fibrosis: 80.4 +/- 85.4 ml/hr/kg, control: 69.5 +/- 39.5 ml/hr/kg; 10-hydroxywarfarin: cystic fibrosis: 4.38 +/- 2.72 ml/hr/kg, control: 16.28 +/- 13.71 ml/hr/kg). CONCLUSION: The in vivo activity of cytochrome P450 isoforms involved in the metabolism of (R)-warfarin, including P450 3A4, is not enhanced in cystic fibrosis.

Adult↗

PubMed1993

Disposition of drugs in cystic fibrosis. IV. Mechanisms for enhanced renal clearance of ticarcillin.

To investigate the hypothesis that renal secretion of penicillins is enhanced in cystic fibrosis the maximal tubular secretion rate (Tmax) of ticarcillin and the serum concentration of ticarcillin at half-maximal secretion rate (TC50) were determined in patients with cystic fibrosis (n = 6) and control subjects (n = 6). Each subject received three consecutive constant-rate intravenous infusions of ticarcillin (4, 13, and 70 mg/kg/hr; 2 1/2 hours each) simultaneously with a constant-rate (30 mg/kg/hr) infusion of insulin. Urine samples were collected at 1/2-hour intervals and serum samples at the midpoint of the urine collections. Ticarcillin and inulin concentrations in serum and urine were determined by high-performance liquid chromatographic and a spectrophotometric method, respectively. Ticarcillin serum protein binding was determined by ultrafiltration. Steady-state ticarcillin serum concentrations were achieved at all three infusion rates. The TC50 was significantly lower (p < 0.05) in patients with cystic fibrosis (33.7 +/- 12.2 micrograms/ml) compared with that in control subjects (77.6 +/- 38.4 micrograms/ml). In contrast, the Tmax was similar (cystic fibrosis, 0.25 +/- 0.12 mg/min/kg; control, 0.22 +/- 0.14 mg/min/kg; p > 0.05). These data indicate that renal clearance of penicillins is enhanced in cystic fibrosis because of greater affinity of the renal secretory system for these drugs.

Adolescent↗

PubMed1993

Nontuberculous mycobacterial disease in adult cystic fibrosis patients.

This study was conducted to determine the prevalence of mycobacterial disease in an adult cystic fibrosis (CF) population and to determine if there were any patients at higher risk for this disease within the group. Sixty-four patients (28 women, 36 men), ranging in age from 17 to 50 years were screened. One-step purified protein derivative skin testing with controls was performed and sputum was taken for examination. Eight of 64 had positive sputum culture for nontuberculous Mycobacterium. The CF patients with positive mycobacterial sputum cultures tended to be older and to have lower clinical scores than those who did not have Mycobacterium organisms in sputum. Guidelines to determine whether mycobacterial disease or colonization is present should be pursued for the CF population.

Adolescent↗

PubMed1992

Impact of sinusitis in cystic fibrosis.

The cause of cystic fibrosis has been determined to be faulty ionic transport of chloride across the apical membrane of epithelial cells lining exocrine glands. The subnormal ionic transport leads to dehydration of extra cellular fluids and the development of thickened inspissated mucous secretions. The vast majority of patients with cystic fibrosis develop sinus disease with panopacification of the sinuses present in 90% to 100% of patients older than 8 months of age. Indications for surgical management of sinusitis in children with cystic fibrosis include (1) chronic nasal obstruction with mouth breathing, (2) chronic purulent draining nasal secretions unresponsive to medical treatment, and (3) persistent headaches thought to be related to sinusitis. Operative therapy is based on computerized tomographic scan findings and can be performed endoscopically. Postoperative management is critical for ensuring successful surgical results. Antibiotics, topical steroids, and cleansing of the surgical fields must be performed on a regular basis to ensure adequate healing. The impact of sinusitis on the cystic fibrosis population is significant. Approximately 20% of patients will eventually require surgical treatment of their sinuses. Chronic sinusitis may cause deformities of the external nasal skeleton, a loss of the sense of smell, and headaches.

Cystic Fibrosis↗

PubMed1992

Evolution of airway microbiology in the infant with cystic fibrosis: role of nonpseudomonal and pseudomonal pathogens.

Bacterial colonization of the airways of the infant with cystic fibrosis is usually established early in life, and, once established, is difficult to eradicate and is associated with progressive lung disease. Thus, understanding of early airway microbiology is critical to the development of appropriate early interventions such as prophylactic antibiotics, immunotherapy, and, potentially, gene therapy. The barriers to the study of infant airway microbiology are discussed, and the properties of infant lung anatomy, physiology, and immunity, which predispose the young patient to serious infection, are reviewed. We examine the natural history of lung infection in young patients, reviewing the roles of each of the main bacterial pathogens. Recent research on risk factors for early Pseudomonas aeruginosa colonization, including the potential role of respiratory viral infections, is discussed. We conclude with a discussion of the role of prophylactic antibiotic therapy.

Anti-Bacterial Agents↗

PubMed1991

Disposition of drugs in cystic fibrosis. I. Sulfamethoxazole and trimethoprim.

The disposition of sulfamethoxazole and trimethoprim, after constant rate intravenous administration (10 mg/kg/hr sulfamethoxazole and 2 mg/kg/hr trimethoprim for 1 hour), was investigated in adult patients with cystic fibrosis (n = 7) and in age-matched healthy subjects (control subjects, n = 8). The total plasma clearance of sulfamethoxazole was found to be increased in cystic fibrosis (0.0262 +/- 0.0064 L/hr/kg) when compared with that found in control subjects (0.0188 +/- 0.0043 L/hr/kg). This increase in clearance was found to be primarily attributable to an increase in the metabolic clearance of sulfamethoxazole to N4-acetylsulfamethoxazole (0.00903 +/- 0.00247 versus 0.00355 +/- 0.00049 L/hr/kg) with the renal clearance of sulfamethoxazole remaining unchanged. These conclusions were not altered when the pharmacokinetic parameters were computed for the unbound drug or when they were normalized with respect to body surface area. These data indicate that, in cystic fibrosis, the enzymes mediating the metabolism of sulfamethoxazole to N4-acetylsulfamethoxazole, N-acetyltransferase(s), may be induced, activated, or both, or that the uptake of sulfamethoxazole by cells that metabolize sulfamethoxazole to N4-acetylsulfamethoxazole is enhanced. The total plasma clearance of trimethoprim was also found to be increased in cystic fibrosis (0.1808 +/- 0.0440 L/hr/kg) when compared with that found in control subjects (0.1139 +/- 0.0193 L/hr/kg). In contrast to sulfamethoxazole, this increase in clearance was found to be primarily attributable to an increase in the renal clearance of trimethoprim (0.1240 +/- 0.0299 versus 0.0720 +/- 0.0166 L/hr/kg). These data indicate that the tubular secretion of trimethoprim may be enhanced in cystic fibrosis.

Adult↗

PubMed1991

The accuracy of creatinine clearance with and without urine collection as a measure of glomerular filtration rate.

Conventional creatinine clearances involving urine collections over 2, 4 and 24 hours and creatinine clearance predicted from plasma creatinine concentrations without urine collection were compared to glomerular filtration rate (GFR) estimated by 99mTc DTPA clearance in 171 patients with a wide range of GFR. All creatinine clearance methods involving urine collection had standard errors of the estimate of GFR greater than predictions from formulae. Predictions of creatinine clearance by formulae had coefficients of variation of the estimate of approximately 23% when compared to isotopically determined GFR. Creatinine clearances determined by these equations in patients with stable renal function are an easier and at least as accurate a guide to GFR as methods involving urine collection.

Body Weight↗

PubMed1991

Probenecid pharmacokinetics in cystic fibrosis.

Probenecid pharmacokinetics were studied in 5 cystic fibrosis (CF) subjects and 5 control subjects at oral dosages of 5, 15, and 30 mg/kg. Serum and urine samples were collected for 8 h after administration and assayed by reverse phase high performance liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. All parameters were compared by 2-tailed analysis of variance with two major groupings: patient and dose. Both CF subjects and controls demonstrated dose-dependent kinetics, i.e., decreased elimination constant and decreased total body clearance with increasing dosage. The volume of distribution and time to peak were the only parameters that were not significantly dose dependent. At all dosages studied, we found no significant difference in total body clearance by CF subjects. Urinary recovery in an 8-hour period was not significantly different between CF subjects and controls nor was the percentage of dose recovered in the urine at each dosage level. Time to peak concentration varied widely between 0.5 and 4 h in both CF subjects and controls. We conclude, that CF patients have normal probenecid clearance, and that the standard dose for a CF patient is sufficient to attain a serum area under the curve equivalent to that of controls.

Administration, Oral↗

PubMed1990

Pharmacokinetics of ticarcillin in patients with cystic fibrosis: a controlled prospective study.

We compared the pharmacokinetics of ticarcillin at a dose of 120 mg/kg in 11 patients with cystic fibrosis to 11 control subjects matched for age and sex. The mean elimination half-life of ticarcillin in serum was 70.8 minutes in the control subjects and 53.1 minutes in the patients with cystic fibrosis. The total body clearance of ticarcillin was significantly higher in cystic fibrosis patients (65.6 +/- 22.0 versus 46.2 +/- 10.9 ml/min/m2 in control subjects; p = 0.017). The nonrenal clearance of ticarcillin was also significantly higher in patients with cystic fibrosis (24.8 +/- 11.1 versus 13.3 +/- 6.0 ml/min/m2 for the control group; p = 0.006). There was no significant difference in volume of distribution between the two groups. We concluded that the shorter elimination half-life and the higher total body clearance of ticarcillin in patients with cystic fibrosis are a result of an increase in both renal and nonrenal elimination.

Adolescent↗

PubMed1989

Endobronchial infection in cystic fibrosis.

In symptomatic patients with cystic fibrosis, the recovery of bacteria in an inflammatory exudate from the lower respiratory tract is strong evidence of endobronchitis. It is not known when this chronic infection begins, the etiologic agents during infancy or the mechanism of evolution from Haemophilus influenzae and Staphylococcus aureus to Pseudomonas aeruginosa. Antibiotic administration to "suppress" the infection in relatively well patients is an unproven benefit. During an exacerbation of bronchitis, administration of appropriate antibiotics decreases sputum bacterial density and is accompanied by decreased amounts of indicators of inflammation in sputum: pulmonary function improves, particularly that reflecting medium to small airway status. In the future aggressive diagnostic procedures will be followed by therapeutic and prophylactic antibiotic administration conducted in a manner to minimize emergence of antibiotic-resistant bacteria. Adjunctive therapy, to minimize those aspects of the host response which inflict lung damage, will become standard.

Anti-Bacterial Agents↗

PubMed1988

Autonomic regulation of potassium release from human labial salivary glands in vitro.

Labial salivary-gland slices from normal human subjects were incubated in vitro according to various protocols. The autonomic regulation of these was significantly different from that of most major salivary glands. K release was stimulated by incubation with a cholinergic agonist but not with alpha- or beta-adrenergic agonists. The cholinergically-induced K release was dependent on agonist concentration and was inhibited by the addition of atropine, and by the removal of Ca in the presence of EGTA.

Adult↗

PubMed1988

Sputum changes associated with therapy for endobronchial exacerbation in cystic fibrosis.

We sought to define objective indicators of the resolution of Pseudomonas aeruginosa endobronchial infection in patients with cystic fibrosis. We prospectively studied 75 patients admitted for treatment of a pulmonary exacerbation and quantitated sputum bacterial density, DNA content, and the concentration of albumin and total protein in sputum, and compared these values with clinical evaluation. Eleven of the 75 patients had systemic signs, fever, and leukocytosis, which we arbitrarily defined as due to endobronchial infection. At the end of hospitalization, these 11 patients were afebrile, had peripheral leukocyte counts in the normal range, and were judged improved. Sputum P. aeruginosa density, DNA content, and total protein content on admission were similar in the two illness groups. Hospitalization and parenteral antibiotic administration for an average of 14.6 days were associated with improved pulmonary function in all 75 subjects (P values for forced vital capacity, forced expiratory volume at 1 second, and peak expiratory flow rate were all less than 0.001). With improvement, there was a decrease in sputum P. aeruginosa density (mean of both groups decreased from 10(7.80) CFU/g on admission to 10(5.96) CFU/g; P less than 0.001), and a decreased DNA concentration (overall mean 4.73 +/- 4.75 on admission to 2.76 +/- 2.49 mg/g; P less than 0.002). The decrease in sputum total protein concentration for both groups was not significant (overall mean 60.5 +/- 48.4 to 43.9 +/- 38.2 mg/g; P = 0.06). Sputum albumin concentrations did not change in either group. We conclude that in cystic fibrosis subjects with a pulmonary exacerbation, bacterial density, sputum DNA and protein content decrease with hospitalization and parenteral antibiotic therapy. At the end of treatment, these indices of sputum infection and inflammation correlate with improved pulmonary function and clinical improvement. These changes are independent of the presence or absence of fever on admission.

Adolescent↗

PubMed1985

Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis sputum.

We studied sputum tobramycin concentrations after intravenous administration in 10 cystic fibrosis patients. Tobramycin concentrations were determined by a bioassay and a radioenzymatic assay (REA). The bacterial density of Pseudomonas aeruginosa in sputum was examined serially during therapy. Bioactivity of tobramycin in the sputum was low and increased little during treatment. In contrast, tobramycin content (as assayed by REA) showed a progressive accumulation of the drug to high concentrations: a mean of 82 micrograms/g sputum after 3 wk of therapy in 4 patients. Pseudomonas aeruginosa was eradicated from the sputum in 3 of 4 patients receiving antibiotic therapy for 3 wk. Eradication correlated with tobramycin sputum concentrations measured by REA, which were 20-fold greater than the apparent tobramycin inhibitory concentration. A bactericidal effect of aminoglycosides in the presence of sputum in vitro could only be reliably produced with concentrations 25-fold the MIC. We conclude that tobramycin penetrates cystic fibrosis (CF) sputum and accumulates over time. Although CF sputum antagonized the bioactivity of aminoglycosides, 3 wk of intravenous therapy combined with an antipseudomonal beta-lactam antibiotic may be effective in eradication of P. aeruginosa from sputum of certain CF patients.

Adolescent↗

PubMed1985

Electron microprobe analysis of human labial gland secretory granules in cystic fibrosis.

X-ray microanalysis of freeze-dried labial gland cryosections revealed that Na concentration was doubled and the Ca/S concentration ratio was decreased in secretory granules of labial glands from patients with cystic fibrosis (CF) when compared with glands from normal subjects. Other results suggested that the decrease in the Ca/S concentration ratio resulted from an increase in S concentration. These findings imply that mucous granules in labial saliva showed a CF-related increase in Na and S content, and such changes would be expected to affect the rheology of the mucus after exocytosis. In contrast with a previous study in human parotid glands, no evidence was found for CF-related changes in cytoplasmic or nuclear Na, K, and Ca concentrations. Significant elemental differences were found between secretory granules and nuclei and cytoplasm of control cells.

Adolescent↗

PubMed1984

Disposition of tobramycin in patients with cystic fibrosis: a prospective controlled study.

The pharmacokinetics of tobramycin in adolescents or young adults with cystic fibrosis and in age-matched controls were prospectively compared. Patients with CF had a higher tobramycin total body clearance (121.2 +/- 14.2 ml/min/1.73 m2) than did controls (102.2 +/- 18.9 ml/min/1.73 m2, P less than 0.05). This was not associated with a higher glomerular filtration rate (iothalamate total body clearance 147.5 +/- 29.2 ml/min/1.73 m2 in patients vs 142.9 +/- 33.3 ml/min/1.73 m2 in controls) or a lower binding of gentamicin to serum proteins (14.3% +/- 2.6% in patients vs 17.4% +/- 3.8% in controls). Tobramycin renal clearance was not significantly different in the two groups (89.5 +/- 17.9 ml/min/1.73 m2 in patients vs 81.0 +/- 15.8 ml/min/1.73 m2 in controls). In the control group, tobramycin total body and renal clearances were highly correlated with iothalamate total body clearance (r = +0.95 and +0.88, P less than 0.01). In patients with cystic fibrosis, the correlation was not significant (r = +0.56, P greater than 0.05 for total body clearance, and r = 0.32, P greater than 0.1 for renal clearance). There was no significant difference in volume of distribution normalized to body surface area or in half-life of elimination. The higher tobramycin total body clearance without an increase in renal clearance, and the lower correlation with glomerular filtration rate indicate that an extrarenal clearance pathway might play a significant role in the elimination of tobramycin from the serum of patients with cystic fibrosis.

Adolescent↗

PubMed1983

Bioactivity of gentamicin in purulent sputum from patients with cystic fibrosis or bronchiectasis: comparison with activity in serum.

Two mechanisms of potential biologic antagonism of gentamicin in purulent sputum from patients with cystic fibrosis or bronchiectasis were studied: reduction of activity by ions and antibiotic binding. Antagonism by ions was assessed by examination of the activity of gentamicin against Pseudomonas aeruginosa in dialysates of serum or sputum in ion-depleted broth. The ionic content of the dialysates increased and reflected differences in the ion content of serum and sputum. Gentamicin had significantly less activity against P aeruginosa in sputum or serum dialysates than in ion-depleted broth alone. When gentamicin was mixed with serum or sputum before dialysis, the level of antipseudomonas activity of the sputum dialysates was significantly lower than that of the serum dialysate; this finding was correlated with greater binding by sputum. Thus, both binding and antagonism by ions evidently reduce the level of bioactivity of gentamicin in serum and in sputum. Purulent sputum, whether from children with cystic fibrosis or adults which bronchiectasis, is more inhibitory than serum; the greater degree of binding, rather than differences in the composition or quantity of cations, explains this difference.

Adult↗

PubMed1983

Unilateral congenital ptosis and amblyopia.

Amblyopia was detected in 15 of 55 children with unilateral congenital ptosis. Anisometropia was the main cause of the amblyopia in 10 cases, and strabismus alone was the cause in 2 cases. In three cases amblyopia developed after ptosis surgery.

Adolescent↗