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Biomedical subjects

C E Johnson

Publications and source records attributed to C E Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1991

Disposition of high-dose methotrexate in an obese cancer patient.

The disposition of many drugs in obesity is altered, although little is known of the effect of obesity on the pharmacokinetics of anti-cancer drugs. In this report the authors describe the pharmacokinetics of high-dose methotrexate in an obese woman (184% ideal body weight) with osteosarcoma. For this patient, both the volume of distribution at steady-state (0.398 l/kg) and systemic clearance (0.0956 l/h/kg) of methotrexate were increased compared with values observed in adult patients with osteosarcoma. The terminal elimination half-life (9.29 hours) of methotrexate was similar to other reported values in adult patients, thus indicating that increases in methotrexate volume of distribution and clearance may offset each other in obesity. Based on the experience gained from this patient, the authors suggest that renal function and methotrexate serum concentrations should be monitored in obese patients receiving high-dose methotrexate with leucovorin rescue.

Adult↗
PubMed1991

Suramin. A potent inhibitor of melanoma heparanase and invasion.

Suramin, a polysulfonated naphthylurea, has anti-reverse transcriptase and anti-proliferative activities and inhibits the binding of various growth factors to their cell surface receptors. This drug is used in the treatment of acquired immunodeficiency syndrome and several types of cancers. Increased levels of circulating glycosaminoglycans have been observed in suramin-treated cancer patients, suggesting that it may inhibit glycosaminoglycan catabolism. Melanoma-derived heparanase, a heparan sulfate-specific endo-beta-D-glucuronidase that plays an important role in metastatic melanoma cell invasion through basement membranes, is inhibited by suramin in a dose-dependent manner: 100% inhibition was observed at a concentration of approximately 100 microM. Structurally related polysulfonated compounds, such as trypan blue and Evans blue, had lower heparanase inhibitory activities: the concentrations required for 50% heparanase inhibition (ID50) were 310-320 microM and six times higher than for suramin (ID50 = 46 microM). Oversulfated heparin tetrasaccharide, whose average molecular size is similar to suramin, had also much lower heparanase inhibitory activity than suramin. The inhibition constants (Ki) for suramin and oversulfated heparin tetrasaccharide were 48 and 290 microM, respectively. Suramin had a remarkable inhibitory activity against B16 melanoma cell invasion through reconstituted basement membranes (ID50 less than 10 microM). The inhibitory effects of suramin on melanoma heparanase and cell invasion appeared to be completely independent of its antiproliferative activity, because significant effects on melanoma cell growth were not observed at the concentrations of suramin used in this study. The results suggest that the antimetastatic effects of suramin may be due to its antiinvasive rather than antiproliferative activities.

Animals↗
PubMed1991

Host factors and early therapeutic response in acute otitis media.

To evaluate the relationship between eradication of bacterial infection and clinical improvement in children with otitis media, we reviewed the clinical outcome of bacterial otitis media in patients enrolled in double-blind trials of antibacterial therapy from 1979 to 1988. Cultures of middle ear exudates showed the distribution of bacterial pathogens to be similar to that observed in other geographic areas. Two hundred ninety-three patients had otitis media caused by bacterial pathogens and underwent repeat tympanocentesis after 3 to 6 days of therapy. Bacteriologic success was demonstrated in 253 patients (86%); 40 patients (14%) had bacteriologic failure. Children who had bacteriologic failure were younger than those with bacteriologic success (median age 10.6 vs 18.5 months; p = 0.001); 38% of patients who had bacteriologic failure were black, compared with 18% of patients with bacteriologic success (p = 0.007). Gender, history of frequent otitis media, and presence of bilateral otitis media were not risk factors for bacteriologic failure. Clinical success was demonstrated in 261 patients (89%); 32 patients (11%) had clinical failure. Agreement between clinical and bacteriologic response was 86% (95% confidence interval: 81.6% to 89.6%). Ninety-three percent (236/253) of subjects whose infection was eliminated had clinical resolution, whereas 37% (15/40) of those with bacteriologic failure had persisting symptoms or signs of clinical failure. We conclude that failure to eliminate bacteria from the middle ear is often associated with persistent signs and symptoms. Bacteriologic failure affects children less than 18 months of age almost exclusively. Bacteriologic and clinical failure are frequently discordant; mechanisms unrelated to the bacterial infection may explain some of the persisting clinical signs.

Acute Disease↗
PubMed1991

Cefixime compared with amoxicillin for treatment of acute otitis media.

Cefixime was compared with amoxicillin for treatment of acute otitis media in a randomized trial. Results of tympanocentesis on day 3 to 5 of therapy were used as the major outcome. Total daily doses were 8 mg/kg of cefixime and 40 mg/kg of amoxicillin. One hundred twenty-six patients were randomly assigned to receive treatment; 64 cultures grew pathogens. Pathogens were eradicated from the middle ear after 3 to 5 days of therapy in 27 (79.4%) of 34 children given amoxicillin and 26 (86.7%) of 30 children given cefixime (p = 0.47). When Streptococcus pneumoniae cases were analyzed, bacteriologic cure occurred in 14 (93.3%) of 15 children given amoxicillin and 12 (75%) of 16 given cefixime (p = 0.333). When cases of Haemophilus influenzae infection were analyzed, significantly more cures occurred with cefixime (10/10, 100%) than amoxicillin (8/13, 62%) (p = 0.046). Pathogens associated with failure of amoxicillin therapy were H. influenzae (five cases, two beta-lactamase-positive), S. pneumoniae (one case), and Moraxella catarrhalis (one case, beta-lactamase-positive). The four failures with cefixime therapy were all in patients infected with S. pneumoniae. Rates of rash, diarrhea, and vomiting were the same in both groups and did not necessitate stopping therapy. We conclude the following: (1) Cefixime and amoxicillin were equivalent in overall clinical and bacteriologic efficacy for otitis media. (2) Cefixime was more efficacious than amoxicillin in treating H. influenzae otitis media and should be preferred when H. influenzae is the suspected etiologic agent. (3) Side effects of both drugs were mild and equivalent.

Acute Disease↗
PubMed1991

Selenium status of preterm infants fed human milk, preterm formula, or selenium-supplemented preterm formula.

The selenium status of 46 orally fed vitamin E-sufficient preterm infants (birth weight less than 1700 gm) was studied longitudinally for 3 weeks to determine the efficacy of selenium supplementation. Infants were fed either human milk (n = 21; 24 ng selenium/ml), preterm formula (n = 13; 7.8 ng selenium/ml), or preterm formula supplemented with sodium selenite (n = 12; 34.8 ng selenium/ml). Plasma and erythrocyte selenium and glutathione peroxidase activity and urinary and dietary selenium content were evaluated on study day 1 (day enteral feeds reached 100 kcal/kg/day) and weekly for 3 weeks. Throughout the study, selenium intakes of infants fed preterm formula plus sodium selenite were greater than those of infants fed human milk, which were greater than those of infants fed preterm formula (p less than 0.001). After 3 weeks no differences were observed among groups for plasma or erythrocyte selenium or glutathione peroxidase. Plasma selenium and glutathione peroxidase values within all groups were low compared with those reported for term infants fed human milk. Whereas urinary selenium levels of infants fed preterm formula plus sodium selenite were greater than those of infants fed preterm formula at weeks 1 and 2 (p less than 0.01), infants fed human milk and preterm formula had lower levels at week 3 than on study day 1 (p less than 0.05). We conclude that blood selenium measurements typically used to monitor selenium status do not reflect dietary selenium intakes of orally fed preterm infants.

Enteral Nutrition↗
PubMed1991

Absent or rare human immunodeficiency virus infection of bone marrow stem/progenitor cells in vivo.

An important question in human immunodeficiency virus (HIV) pathogenesis is whether HIV-infected bone marrow CD34+ stem/progenitor cells serve as a significant reservoir of virus in HIV-infected individuals. Our data indicate that infection of bone marrow stem/progenitor cells with HIV occurs rarely, if ever, in vivo. In the present study, CD34+ cells were immunomagnetically purified from the bone marrow of HIV-seropositive individuals, and purified cells or colony-forming cells of the granulocyte/macrophage lineage were analyzed for HIV proviral DNA by the polymerase chain reaction. No HIV DNA was detected in colony-forming cells of the granulocyte/macrophage lineage from HIV-positive patients. Furthermore, no virus was found in CD34(+)-enriched cells from six of seven samples from asymptomatic HIV-infected individuals and four of four samples from patients with AIDS-related complex or AIDS. Thus, infected stem cells are not a major source of persistent HIV and do not account for hematopoietic suppression. These findings have positive implications for the concept of marrow reconstitution with autologous stem cells, genetically engineered for HIV resistance, following marrow-ablative antiviral therapy.

DNA, Viral↗
PubMed1991

Pharmacokinetics and pharmacodynamics of nifedipine in children with bronchopulmonary dysplasia and pulmonary hypertension.

The pharmacokinetics and associated pharmacodynamics of nifedipine were studied in nine children aged 5 to 68 mo with bronchopulmonary dysplasia and pulmonary artery hypertension after a single oral dose of 1.44 mumol/kg (0.5 mg/kg). In the cardiac catheterization laboratory, hemodynamic measurements were made in duplicate just before the nifedipine dose and at 5 min and 0.5 and 1.0 h after the dose. The plasma nifedipine concentration was measured by HPLC at each of the above times and at 2.5, 4.0, 6.0, and 8.0 h after the dose. The mean (+/- SD) maximum plasma concentration and the time to maximum plasma concentration were 243.4 +/- 194.5 nmol/L and 1.0 +/- 0.8 h, respectively. The mean area under the plasma concentration-time curve was 761 +/- 509 nmol.h/L. The mean elimination rate constant and t1/2 were 0.456 +/- 0.194 h-1 and 1.8 +/- 0.8 h, respectively. Nifedipine caused a significant (p less than or equal to 0.05) reduction in the mean pulmonary artery pressure by 5 min and in the mean pulmonary vascular resistance index and mean aortic pressure by 30 min, and these reductions remained significant through the 1-h measurement interval. The magnitude of acute hemodynamic response correlated closely with the plasma nifedipine concentrations. No significant change occurred in the mean arterial oxygen saturation or cardiac index during the study period. The percentage changes from baseline in the mean pulmonary artery pressure and mean pulmonary vascular resistance index were approximately double the percentage change in the mean aortic pressure, suggesting that nifedipine had some degree of selective impact on the pulmonary vascular bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Cell-cycle associated transcriptional regulation of ribonucleotide reductase in L1210 leukemia cells and drug-resistant variants.

Previous studies from this laboratory have shown that the steady-state levels of the mRNA for the non-heme iron (NHI) subunit of ribonucleotide reductase were markedly elevated in hydroxyurea-resistant L1210 cell lines with minimal changes in the mRNA levels for the effector-binding (EB) subunit. In the present study, wild-type L1210 cells and their drug-resistant variants [hydroxyurea-resistant (HU-7); deoxyadenosine-resistant (Y-8); and deoxyadenosine/pyrazoloimidazole-resistant (ED2)] were synchronized by EGTA treatment in the G0/G1-phase of the cell cycle. Upon the addition of CaCl2, the cells reentered the cell cycle. The steady-state levels and the transcriptional rates of the mRNAs for the EB subunit and glyceraldehyde-3-phosphate dehydrogenase were measured and found to be similar in the drug-resistant variants compared to the wild-type cells. While the steady-state level of the mRNA for the NHI subunit was increased 35-fold in the HU-7 cell line, the transcription rate was increased only 7-fold. The increase in the transcription rate did not account for the large increase in the steady-state level. These data indicate that the increased steady-state level of the mRNA for the NHI subunit in the HU-7 L1210 cell line was not due to cell-cycle differences and that post-transcriptional processing and/or stability may play a role as well.

Animals↗
PubMed1991

Perceptual features for normal listeners' phoneme recognition in a reverberant lecture hall.

Johnson et al (1988) found that normal-hearing listeners' consonant recognition scores on a nonsense syllable test were significantly better when they were seated within versus beyond the critical distance of a typical lecture hall. The present study used a Sequential Information Analysis (SINFA) to document a priori perceptual features for Johnson et al's subjects' confusion errors to the initial and medial consonant portions of the stimuli. The features and the percent of information transmitted for them differed as a function of consonant position in the stimulus and whether the subjects were seated within or beyond the critical distance of the room. Generally, more information was transmitted within rather than beyond the critical distance for both initial and medial consonants. However, less information was transmitted for features for the medial than for the initial consonant position. Beyond the critical distance, high-frequency features (e.g., sibilant) were transmitted somewhat better than those based more on low-frequency energy (e.g., voicing). Place of articulation features were not transmitted as well for the initial as for the medial position and they suffered in both positions as distance increased. The effects of reverberation on the subjects' perception are discussed and compared to results of other studies.

Acoustics↗
PubMed1991

Pharmacotherapy of otitis media.

The clinical manifestations of acute otitis media and otitis media with effusion are the result of abnormal eustachian tube function most often caused by inflammation from infection or allergy. The majority of cases involve bacterial infection of the middle ear caused by Streptococcus pneumoniae, Haemophilus influenzae, or Branhamella catarrhalis. Nearly half of all children will have had at least one episode of acute otitis media by 1 year of age, and over 70% by 3 years of age. The signs and symptoms include pain with rubbing or tugging at the ear, fever, irritability, lethargy, and hearing loss. The primary therapy for acute otitis media and otitis media with effusion is antibiotics with the goal of preventing possible complications and providing symptomatic relief. Amoxicillin remains the initial drug of choice in communities where beta-lactamase-producing strains of the common middle ear pathogens are infrequently isolated. If resistant organisms are prevalent, cefaclor, amoxicillin-clavulanate, or cotrimoxazole should be selected. Adjuvant agents such as decongestants have not been shown to provide additional therapeutic benefit. Children who develop chronic otitis media may require prophylactic antibiotic therapy and insertion of typanostomy tubes.

Acute Disease↗
PubMed1991

Stability of an extemporaneously compounded terbutaline sulfate oral liquid.

The stability of terbutaline sulfate in an extemporaneous oral liquid formulation refrigerated for 55 days was studied. A suspension was prepared by grinding commercially available 5-mg terbutaline sulfate tablets, adding Purified Water, USP, to form a paste, and then adding Simple Syrup, NF. A control solution was prepared from analytical grade terbutaline sulfate powder in Simple Syrup, NF. The final concentration of terbutaline sulfate in both preparations was 1 mg/mL. Three samples of each formulation were stored in 4-ounce amber glass prescription bottles in the dark at 4 degrees C. Immediately after preparation and at 10, 19, 35, and 55 days, samples were visually inspected, tested for pH, and assayed in duplicate by high-performance liquid chromatography. On days 0 and 35, 100-microL samples of each suspension and solution were placed on agar plates for microbiological testing. On day 55, the mean percentages of the initial terbutaline sulfate concentrations remaining were 103.8% in the suspension and 91.7% in the solution. Color, odor, and pH of the samples did not change appreciably, and colony counts of bacteria were within acceptable limits. An extemporaneously prepared liquid preparation of terbutaline sulfate in Simple Syrup, NF, is stable under the conditions studied for up to 55 days; however, since microbiological testing was not performed on day 55, it is recommended that the preparation be stored for no longer than 30 days.

Drug Compounding↗
PubMed1990

Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair.

Adherence of monocytes to endothelial cells or extracellular matrices is likely to play a critical role in triggering monocyte activation in extravascular sites of infection, chronic inflammatory disorders, tissue damage and neoplastic growth. We have constructed a cDNA library from monocytes adhered for 30 min on plastic and have screened it by differential hybridization for mRNA rapidly induced by adherence. Two of the cDNA isolated have been identified as IL-1 beta and superoxide dismutase. Sequence data from three other adherence specific clones demonstrates the presence of ATTTA mRNA instability sequences in their 3' untranslated regions signifying inflammation-associated genes. The deduced amino acid sequences indicate the presence of open reading frames with sequence homologies to a family of host defense cytokines, one of them being identified as IL-8. Of the 14 clones initially identified, 4 have been analyzed for induction of mRNA expression. Although 3 of the 4 clones were equally induced by PMA and LPS under nonadherent conditions, all 4 cDNA showed distinct patterns of induction with adherence to extracellular matrix components or endothelial cells. The deduced amino acid sequence homologies indicate that we have isolated cDNA that code for three unique gene products. These cDNA belong to a gene family of early host defense cytokines involved in inflammation and cell growth, but which are differentially regulated by adherence to different surfaces.

Amino Acid Sequence↗
PubMed1990

Is magnetic resonance imaging useful in guiding the operative approach to large pituitary tumors?

Forty-two patients with large pituitary tumors were studied with magnetic resonance imaging scans. Based on the operative findings, the tumors were divided into two groups. Tumors in Group 1 (n = 35) were soft or partially necrotic and were easily removed by suction and curettage. Tumors in Group 2 (n = 7) were firm and required sharp dissection or use of the laser for removal. Tumors were divided into two groups based on the long TR signal: a) isointense in comparison with white matter, or b) hyperintense in comparison with white matter. All 7 firm tumors (Group 2) had an isointense signal on long TR sequences. Thirty-two of 35 soft tumors showed a hyperintense signal on long TR sequences, and 3 an isointense signal. Based on these results, we recommend a transsphenoidal approach for the initial operation in patients with large pituitary tumors. If the tumor is largely isointense on the magnetic resonance imaging scan, we discuss with the patient preoperatively the possibility (70% in this series) that the tumor may be too firm to remove in a single transsphenoidal procedure. In these circumstances, a second, transcranial, procedure may be required to decompress the suprasellar structures adequately.

Adenoma↗
PubMed1990

Benign lumbar arachnoiditis: MR imaging with gadopentetate dimeglumine.

MR imaging was performed in 13 patients with benign lumbar arachnoiditis both before and after IV injection of gadopentetate dimeglumine. The arachnoiditis was proved by previous myelography in 12 patients and by noncontrast MR imaging in one patient. The disease was presumably the result of previous myelography and/or surgery. It was characterized as mild in two patients, moderate in two patients, and severe in nine patients. Imaging was performed on a 1.5-T unit, and both short and long TR images were obtained before and after contrast administration. Noncontrast MR images demonstrated changes consistent with arachnoiditis in all patients. After contrast, three patients had no enhancement, three patients had minimal enhancement, three patients had mild enhancement, and four patients had moderate enhancement. In no case did contrast enhancement alter the diagnosis or reveal additional findings that could not be seen on the noncontrast images. Gadopentetate dimeglumine enhancement plays little role in the diagnosis of lumbar arachnoiditis. If used for another reason, however, short TR scans may show enhancement of adherent roots in some cases. In addition, administration of gadopentetate dimeglumine will not cause sufficient enhancement to hinder the detection of arachnoiditis on long TR images and may aid in recognition of adherent roots on short TR images.

Adult↗
PubMed1990

Fusobacterium osteomyelitis associated with intraosseous gas.

The diagnosis of acute anaerobic osteomyelitis was made in a 57-year-old hypertensive diabetic woman complaining of groin pain and fever. Roentgenograms and computed tomography demonstrated intraosseous gas in the right femoral head and surrounding soft tissue. Cultures obtained from open biopsy were positive for the anaerobic gram-negative bacillus Fusobacterium necrophorum, a normal inhabitant of the mouth, bowel, and urogenital tract. The patient responded to an antibiotic regimen of metronidazole combined with initial debridement and drainage, followed by resection of the femoral head (Girdle-stone arthroplasty). The hospital course was complicated by fungal and pseudomonal superinfection. The patient was afebrile and ambulatory at discharge two months after admission. A case of Fusobacterium necrophorum osteomyelitis causing intraosseous gas seems not to have been previously reported in the literature.

Female↗
PubMed1990

Urinary N-acetyl-beta-glucosaminidase and the selection of children for radiologic evaluation after urinary tract infection.

Urinary levels of N-acetyl-beta-glucosaminidase (NAG) were measured in 147 consecutively enrolled children younger than 13 years of age with urinary tract infection to determine whether elevated levels were a predictor of urologic abnormalities. The children were classified as having cystitis if results of 0 or 1 of the following tests were positive and as having pyelonephritis if results of greater than or equal to 2 tests were positive: (1) temperature greater than 38 degrees C, (2) serum C-reactive protein greater than 1 mg/dL, (3) erythrocyte sedimentation rate greater than 25 mm/h, and (4) 1-deamino-8-D-arginine vasopressin-renal concentrating protein less than 810 mOsm/kg. Urinary NAG to creatinine ratios did not distinguish cases of cystitis from those of pyelonephritis. Urinary NAG was useful in identifying children with cystitis who had vesicoureteral reflux of grades II through V. Of 6 children with cystitis and vesicoureteral reflux, 5 had levels of NAG more than 1 SD above the mean, whereas of 75 children without vesicoureteral reflux, only 15 had such an elevation (P = .003). Of those children with a normal NAG level, 60 (98.4%) had normal radiologic evaluation results, and only 1 child (1.6%) had vesicoureteral reflux. Levels of NAG did not identify children with pyelonephritis who had vesicoureteral reflux. It is concluded that (1) urinary NAG is of no value in localizing the site of urinary tract infection, and (2) an NAG level within 1 SD of the mean in a child with cystitis indicates a low risk of urologic abnormalities, and radiologic evaluation may be omitted unless infection recurs.

Acetylglucosaminidase↗
PubMed1989

Human monocyte inflammatory mediator gene expression is selectively regulated by adherence substrates.

During the process of extravasation, monocytes transiently adhere to capillary endothelium and subsequently with a variety of extracellular matrix components. These early interactions are likely to serve as modifiers of transcriptional activity and serve to prime monocytes for rapid synthesis of mediators. We have previously reported that adherence to plastic rapidly induced or down-regulated steady-state mRNA levels of a number of monocyte inflammatory mediator genes. We now report that adherence to surfaces pretreated with fibronectin resulted in TNF-alpha and CSF-1 mRNA levels approximating adherence to plastic, whereas adherence to fibronectin, fibronectin/anti-fibronectin complexes, or collagen resulted in markedly decreased levels of CSF-1 induction and lysozyme down-regulation. In contrast, monocyte adherence to collagen induced the highest sustained levels of TNF-alpha expression. PMA, but not the chemotactic factor FMLP, stimulated non-adherent monocytes to express c-fos and TNF-alpha and down-regulate lysozyme mRNA. Although all donors responded to adherence, several failed to produce CSF-1 mRNA after PMA stimulation in the non-adherent state. These data demonstrate that monocyte mediator expression may be more dependent on the selectivity of signals induced by adherence to different substrates than the initial chemotactic response.

Antigens, Surface↗