Biomedical subjects

J McCarty

Publications and source records attributed to J McCarty.

At least 19 recordsLinked to original sources

PubMed1998

Development of tearing in preterm and term neonates.

BACKGROUND: Although term and preterm infants have the capacity to secrete tears, the relative contribution of basal and reflex secretion of tears has not been previously assessed together in a prospective study. This information potentially has practical clinical importance. OBJECTIVES: To measure basal and reflex tear secretion in preterm (30-37 weeks after conception) and term (38-42 weeks) newborns and to determine the developmental pattern of tear production. METHODS: Tear secretion was evaluated by applying Schirmer tear test strips to the inferior fornix for 5 minutes before (reflex plus basal secretion) and after (basal secretion) applying a topical anesthetic agent. RESULTS: Seventy infants (36 preterm and 34 term) were tested. Mean (+/- SD) basal tear secretion was 6.2 (+/- 4.5) mm in preterm and 9.2 (+/- 4.3) mm in term infants and increased progressively with increasing weight (P<.001) for all newborns. Mean (+/- SD) reflex tear secretion was 7.4 (+/- 4.8) mm in preterm and 13.2 (+/- 6.5) mm in term infants and also increased with increasing weight (P<.001) for all newborns. CONCLUSIONS: Preterm infants have reduced reflex and basal tear secretion. This may mask the diagnosis of a nasolacrimal duct obstruction, concentrate topically applied medications, and allow corneas to quickly become dry during ophthalmological examination and treatment. By term, tear production in newborns is similar to that in adults.

Diagnostic Techniques, Ophthalmological↗

PubMed1998

Randomized, double-blind study of ciprofloxacin and cefuroxime axetil for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

In a prospective, multicenter, double-blind study, the interval to clinical relapse in patients with acute bacterial exacerbations of chronic bronchitis from whom a pretherapy pathogen was isolated was compared following treatment with ciprofloxacin or cefuroxime axetil. Clinical and microbiological responses at the end of therapy were secondary efficacy variables. Outpatients randomly received either ciprofloxacin or cefuroxime axetil (500 mg twice a day for 14 days). Three hundred seven patients with acute exacerbations of chronic bronchitis were enrolled, of whom 208 had an exacerbation due to a bacterial pathogen. Clinical resolution at the end of ciprofloxacin and cefuroxime axetil therapy for patients for whom efficacy could be evaluated was 93% and 90%, respectively. Bacteriologic eradication rates were statistically higher for ciprofloxacin recipients (96% [89 of 93]) than for cefuroxime axetil recipients (82% [80 of 97]) (P < .01). The median infection-free interval was 146 days for ciprofloxacin recipients vs. 178 days for cefuroxime axetil recipients (P = .37). In conclusion, ciprofloxacin was associated with an infection-free interval and clinical response that were similar to those associated with cefuroxime axetil, but the bacteriologic eradication rate associated with ciprofloxacin was statistically significantly higher than that associated with cefuroxime axetil.

Acute Disease↗

PubMed1997

Rapid and sensitive detection of Chlamydia trachomatis using a ligatable binary RNA probe and Q beta replicase.

A simple assay format was developed for the direct detection of C. trachomatis rRNA utilizing ligation of recombinant MDV-1 probe RNA fragments hybridized to 23S rRNA after capture and release from a solid support. Assay background (equivalent to 10(4) targets) was suppressed by blocking sequences in the 5' MDV reporter probe fragment complementary to the 3' fragment by prehybridization of a DNA oligonucleotide. A pair of reporter fragments bearing a deletion within the region, obtained by a hydrid-selection-amplification protocol, yielded a low level of assay background which was reduced to < 2% with a blocker directed against the remaining pairing sequence. This probe set showed a sensitivity of 10(3) molecules of 23S rRNA (> 95% responding) and could detect a single elementary body (EB) of Chlamydia trachomatis or 1-10 EB added to a clinical matrix of pooled negative human cervical swab samples. The time of first appearance of amplification products by real-time fluorescence detection showed a linear response to log increases in the target level over a 10(5)-fold range, permitting the determination of target level within an order of magnitude. The assay showed approximately 10(9)-fold discrimination over Chlamydia pneumonae (TWAR) rRNA. High levels of cultured C. albicans, E. coli, S. aureus, or N. gonorrhoeae had no detectable effect on assay background or the ability to detect a single elementary body.

Bacteriological Techniques↗

PubMed1997

Oropharyngeal candidiasis in patients with AIDS: randomized comparison of fluconazole versus nystatin oral suspensions.

A total of 167 human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis were randomly assigned to receive 14 days of therapy with liquid suspension fluconazole (100 mg once daily) or liquid nystatin (500,000 U four times daily). At day 14, 87% of the fluconazole-treated patients were clinically cured, as opposed to 52% in the nystatin-treated group (P < .001). Fluconazole eradicated Candida organisms from the oral flora in 60%, vs. a 6% eradication rate with nystatin (P < .001). The fluconazole group had fewer relapses noted on day 28 (18%, vs. 44% in the nystatin group; P < .001). This relapse difference no longer existed by day 42. Fluconazole oral suspension as a systemic therapy was more effective than liquid nystatin as a topical therapy in the treatment of oral candidiasis in HIV-infected patients and provided a longer disease-free interval before relapse.

AIDS-Related Opportunistic Infections↗

PubMed1997

Chlamydia pneumoniae in acute otitis media.

BACKGROUND: Aerobic bacterial pathogens are recovered from 65 to 85% of patients with acute otitis media (AOM). Although Chlamydia pneumoniae is a common pathogen of pediatric pneumonia, it has rarely been cultured from children with chronic otitis media and its role in AOM is unknown. METHODS: We cultured for C. pneumoniae in tympanocentesis aspirates and nasopharyngeal swabs from 101 consecutive, otherwise healthy children with AOM or refractory AOM. A control group of 50 similarly aged, healthy children was evaluated for nasopharyngeal carriage of C. pneumoniae. Specimens were also evaluated by PCR for C. pneumoniae. RESULTS: C. pneumoniae was recovered by tympanocentesis in 8 (8%) of 101 children with AOM. Among the 8 children with C. pneumoniae-positive-AOM, 5 had C. pneumoniae detected by PCR in middle ear fluid, none had C. pneumoniae recovered by nasopharyngeal culture or PCR and 5 were younger than 16 months. C. pneumoniae was the sole pathogen isolated in 2 patients. Copathogens included beta-lactamase-positive positive Haemophilus influenzae (2), beta-lactamase positive Moraxella catarrhalis (1), penicillin-resistant Streptococcus pneumoniae (2) and penicillin-susceptible S. pneumoniae (1). C. pneumoniae was recovered from nasopharyngeal culture in 2 additional patients with C. pneumoniae-negative AOM and in none of 50 healthy control children, although 2 controls were positive by PCR from the nasopharynx. CONCLUSIONS: This is the first study to report the isolation of C. pneumoniae in middle ear fluid of children with AOM.

Acute Disease↗

PubMed1997

Study of use of cefdinir versus cephalexin for treatment of skin infections in pediatric patients. The Cefdinir Pediatric Skin Infection Study Group.

Three hundred ninety-four patients, aged 6 months to 12 years, entered a multicenter, randomized, controlled, investigator-blind study comparing cefdinir, 7 mg/kg of body weight twice a day, with cephalexin, 10 mg/kg four times a day, each given for 10 days. The most common infections treated were impetigo and secondary infection of preexisting dermatitis. The most common pathogens isolated were Staphylococcus aureus and Streptococcus pyogenes. Two hundred thirty-one patients were microbiologically evaluable. Microbiologic eradication rates were 164 of 165 pathogens (99.4%) in the cefdinir group and 152 of 156 pathogens (97.4%) in the cephalexin group (P = 0.14). Clinical cure rates were 116 of 118 patients (98.3%) in the cefdinir group and 106 of 113 patients (93.8%) in the cephalexin group (P = 0.056). Sixteen percent of cefdinir patients and 11% of cephalexin patients experienced adverse events (P = 0.11), the most common being diarrhea, which affected 8% of the cefdinir group and 4% of the cephalexin group. Cefdinir appears to be an effective and well-tolerated agent for the treatment of uncomplicated skin and skin structure infections in pediatric patients.

Cefdinir↗

PubMed1996

A multicenter, open label trial of azithromycin for the treatment of children with acute otitis media.

OBJECTIVE: In this multicenter, open label trial the investigators evaluated the efficacy and safety of azithromycin suspension administered once daily for 5 days for the treatment of clinically and bacteriologically established acute otitis media. METHODS: Two hundred eligible children with acute otitis media from 10 US centers were treated with 10 mg/kg of azithromycin oral suspension on Day 1, followed by 5 mg/kg once daily for the next 4 days. Tympanocentesis and subsequent culture of middle ear effusion were performed at baseline. Clinical efficacy was evaluated on Days 6, 11 and 30. RESULTS: Analysis of clinical efficacy in evaluable patients 11 days after the initiation of therapy showed that the rate of satisfactory responses (cured or improved) ranged from 79.6 to 82.4% in patients infected with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis. Satisfactory clinical response at Day 30 was reported in 70% of evaluable patients, and eradication of S. pneumoniae, H. influenzae and M. catarrhalis was presumed in 64 to 73%. Relapses occurred in 14% of the evaluable patients. Among the treated patients 8.5% reported mild or moderate side effects. CONCLUSION: Azithromycin is an effective, safe and well-tolerated treatment for children with acute otitis media.

Acute Disease↗

PubMed1995

Conserved ATPase and luciferase refolding activities between bacteria and yeast Hsp70 chaperones and modulators.

We have reconstituted an ATP-dependent protein folding machinery using purified yeast cytosolic proteins. The S. cerevisiae Hsp70 Ssa1p and the DnaJ homolog Ydj1p refolded denatured firefly luciferase. In E. coli, efficient refolding of luciferase requires the Hsp70 DnaK and two modulators, DnaJ and GrpE, that synergistically stimulate its ATPase activity. Exchanging DnaJ homologs between the S. cerevisiae and E. coli systems revealed that their ability to stimulate Hsp70 ATPase activity was conserved. In contrast, GrpE further stimulated only DnaK's ATPase activity. Efficient refolding of luciferase by Ssa1p and DnaJ, but not by DnaK and Ydj1p, suggests that a compatible Hsp70/DnaJ homolog pair can act as a protein folding machinery.

Adenosine Triphosphatases↗

PubMed1995

Thrombopoietin, the Mp1 ligand, is essential for full megakaryocyte development.

The development of megakaryocytes (MKs) from their marrow precursors is one of the least understood aspects of hematopoiesis. Current models suggest that early-acting MK colony-stimulating factors, such as interleukin (IL) 3 or c-kit ligand, are required for expansion of hematopoietic progenitors into cells capable of responding to late-acting MK potentiators, including IL-6 and IL-11. Recently, the Mp1 ligand, or thrombopoietin (Tpo), has been shown to display both MK colony-stimulating factor and potentiator activities, at potencies far greater than that of other cytokines. In light of these findings, we tested the hypothesis that Tpo is absolutely necessary for MK development. In this report we demonstrate that neutralizing the biological activity of Tpo eliminates MK formation in response to c-kit ligand, IL-6, and IL-11, alone and in combination, but that these reagents only partially reduce MK formation in the presence of combinations of cytokines including IL-3. However, despite the capacity of IL-3 to support the proliferation and initial stages of MK differentiation, elimination of Tpo prevents the full maturation of IL-3-induced MK. These data indicate that two populations of MK progenitors can be identified: one that is responsive to IL-3 but can fully develop only in the presence of Tpo and a second that is dependent on Tpo for both proliferation and differentiation. Thus, our results strongly suggest that Tpo is the primary regulator of MK development and platelet production.

Animals↗

PubMed1995

Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infection in women. The minimum effective dose. The Urinary Tract Infection Study Group [corrected].

BACKGROUND: Three studies were undertaken to determine the minimum effective dosing regimen of ciprofloxacin for the treatment of acute, symptomatic, uncomplicated lower urinary tract infection. METHODS: All studies were multicenter, prospective, randomized, double-blind trials. A total of 970 evaluable patients with a diagnosis of urinary tract infection received oral ciprofloxacin (200 mg to 500 mg daily in one or two divided doses for 1, 3, 5, or 7 days) or norfloxacin (400 mg twice daily [BID] for 7 days). The primary measure of efficacy was bacteriologic eradication at the end of therapy. RESULTS: In study 1, bacteriologic eradication was reported in 95 (89%) and 101 (98%) of patients in the groups who received ciprofloxacin, 500-mg single dose and 250 mg BID for 7 days, respectively. Clinical success occurred in 101 patients (94%) who received a 500-mg single dose and in 103 patients (100%) who were administered 250 mg BID for 7 days. In study 2, eradication rates in the groups who received ciprofloxacin, 100 mg BID for 3 days, 250 mg BID for 3 days, and 250 mg BID for 7 days, were 98 (93%), 95 (90%), and 98 (93%), respectively. Clinical success was reported in 102 (97%), 105 (100%), and 104 (98%) of the patients, respectively. In study 3, the eradication rates in the groups who received ciprofloxacin in dosages of 500 mg once daily for 3 days and 500 mg once daily for 5 days and norfloxacin in a dosage of 400 mg BID for 7 days were 137 (92%), 134 (90%), and 133 (94%) of the women, respectively. Clinical success was the same (97%) in all three groups. Overall, short-course (either 3- or 5-day) therapy with ciprofloxacin was statistically equivalent to conventional (7-day) therapy with either ciprofloxacin or norfloxacin. Single-dose ciprofloxacin therapy was statistically less effective than conventional treatment. CONCLUSIONS: Ciprofloxacin at a dosage of 100 mg BID for 3 days was the minimum effective dose for the treatment of uncomplicated urinary tract infection in women.

Acute Disease↗

PubMed1995

Pyridoxine as therapy in theophylline-induced seizures.

Theophylline-induced seizures have significant morbidity and mortality and are difficult to treat. Theophylline therapy for asthma has been observed to depress plasma pyridoxal 5'-phosphate (PLP) levels which may decrease gamma-aminobutyric acid (GABA) synthesis and thereby contribute to seizures. We hypothesized that treatment with pyridoxine might prove beneficial in theophylline-induced seizures. One hundred thirty-nine mice were injected with 250 mg theophylline/kg ip and 89 mice were injected with 250-750 mg pyridoxine/kg ip as treatment. Decreased rates of seizure (42 vs 70%, p < 0.002) and death (29 vs 56%, p < 0.002) were observed. Six New Zealand White rabbits were given 115 mg theophylline/kg iv over 50 min followed by treatment with an iv bolus of 115 mg pyridoxine/kg, with subsequent continuous drip infusion of 230 mg/kg over 50 min. Serum theophylline levels and plasma PLP levels showed significant negative correlation prior to pyridoxine infusion with a mean peak theophylline level of 182 micrograms/ml and a mean low PLP level of 64 nM/L. Electroencephalogram (EEG) tracings were obtained before infusions, during theophylline infusion and during pyridoxine infusion. All 6 rabbits developed abnormal EEGs during theophylline infusion and all 6 rabbit EEG patterns returned to baseline during treatment with pyridoxine. These findings suggest that pyridoxine may partially reverse theophylline-induced central nervous system toxicity.

Aminophylline↗

PubMed1994

Comparative study of the safety and efficacy of clarithromycin and amoxicillin-clavulanate in the treatment of acute otitis media in children.

The safety and efficacy of clarithromycin was compared with those of amoxicillin-potassium calvulanate for the treatment of acute otitis media in children. In a multicenter, randomized, investigator-blinded trial, 180 patients (6 months to 12 years of age) with acute otitis media were allocated to receive either clarithromycin, 15 mg/kg in two divided doses (n = 90), or amoxicillin-clavulanate, 40 mg/kg in three divided doses (n = 90), for 10 days. Middle ear samples were obtained by tympanocentesis from 175 of 180 patients. Pathogens were isolated from 137 samples (76%). Eighty-six patients in each treatment group were considered for efficacy analysis. Clinical cure or improvement was achieved within 4 days after treatment in 80 (93%) of 86 patients receiving clarithromycin and in 82 (95%) of 86 patients receiving amoxicillin-clavulanate. Recurrence of infection was observed between 5 and 35 days after treatment in 9 (11%) of 80 patients in the clarithromycin group and in 8 (10%) of 82 patients in the amoxicillin-clavulanate group. Middle ear effusion was found with similar frequency at the end of therapy and at follow-up visits in both treatment groups. Mild gastrointestinal signs and symptoms, the most common side effects, were noted in 20% and 52% of patients in the clarithromycin group and the amoxicillin-clavulanate group, respectively (p < 0.001). We conclude that clarithromycin is a safe and effective antimicrobial agent for the treatment of acute otitis media in children.

Acute Disease↗

PubMed1993

Evaluation of families wherein a single male manifests a phenotype of X-linked lymphoproliferative disease (XLP).

The Epstein-Barr virus (EBV)-induced diseases of males with X-linked lymphoproliferative disease (XLP) include fatal infectious mononucleosis (IM), non-Hodgkin lymphoma (ML), agammaglobulinemia, and aplastic anemia. These phenotypes also occur as sporadic cases in families, and EBV seronegative males in these families must be considered at risk for XLP until they seroconvert normally to EBV. Given that 50% of males inheriting the defective XLP gene die following primary EBV infection, it is vital that they be identified pre-EBV infection. Here we report results using molecular genetic techniques to provide information as to the relative risks of EBV negative males and potential carrier females in ten families wherein a single male had died of IM.

Adolescent↗

PubMed1993

Immunogold localization of the DnaK heat shock protein in Escherichia coli cells.

Previously reported cell fractionation experiments have yielded conflicting information on the cellular localization of the DnaK heat shock protein of Escherichia coli. Here we used immunogold labelling of ultra-thin sections to determine the localization of DnaK in unstressed cells at 30 degrees C as well as in heat-shocked cells. In cells grown at 30 degrees C, gold particles were found predominantly in the cytoplasm, indicating that the majority of the DnaK molecules are cytoplasmic; however, a fraction of the gold particles was located in proximity to the membranes, raising the possibility that a subpopulation of DnaK proteins is membrane-associated. Heat shock of the cells did not induce detectable relocalization of DnaK.

Antibodies, Bacterial↗

PubMed1993

Vascular cell adhesion molecule-1 is expressed in human coronary atherosclerotic plaques. Implications for the mode of progression of advanced coronary atherosclerosis.

Endothelial attachment is the initial step in leukocyte recruitment into developing atherosclerotic lesions. To determine whether vascular cell adhesion molecule-1 (VCAM-1) expression may play a role in inflammatory cell recruitment into human atherosclerotic lesions, immunohistochemistry was performed with a polyclonal rabbit antisera, raised against recombinant human VCAM-1, on 24 atherosclerotic coronary plaques and 11 control coronary segments with nonatherosclerotic diffuse intimal thickening from 10 patients. Immunophenotyping was performed on adjacent sections to identify smooth muscle cells, macrophages, and endothelial cells. To confirm VCAM-1-expressing cell types, double immunostaining with VCAM-1 antisera and each of the cell-specific markers and in situ hybridization were performed. All atherosclerotic plaques contained some VCAM-1, compared to 45% of control segments. VCAM-1 was found infrequently on endothelial cells at the arterial lumen din both plaques (21%) and in control segments (27%), but was prevalent in areas of neovascularization and inflammatory infiltrate in the base of plaques. Double immunostaining and in situ hybridization confirmed that most VCAM-1 was expressed by subsets of plaque smooth muscle cells and macrophages. The results document the presence of VCAM-1 in human atherosclerosis, demonstrate VCAM-1 expression by human smooth muscle cells in vivo, and suggest that intimal neovasculature may be an important site of inflammatory cell recruitment into advanced coronary lesions.

Animals↗

PubMed1992

A controlled trial of a single dose of azithromycin for the treatment of chlamydial urethritis and cervicitis. The Azithromycin for Chlamydial Infections Study Group.

BACKGROUND: Currently, there is no single-dose therapy that is effective in the treatment of urethral or endocervical infections with Chlamydia trachomatis. Azithromycin is a new azalide antibiotic that has substantial activity against C. trachomatis, is concentrated intracellularly, and has a long half-life in serum and tissue. METHODS: We conducted a trial in which 299 female patients and 158 male patients with uncomplicated genital infection and a positive C. trachomatis antigen test were randomly assigned to receive either azithromycin (1 g once orally) or doxycycline (100 mg orally twice daily for seven days). Only patients subsequently determined to have a culture positive for C. trachomatis at base line were included in the evaluation of efficacy. RESULTS: Among the patients who could be evaluated, 5 of the 141 patients (4 percent) treated with azithromycin did not respond to treatment, as compared with 3 of the 125 patients (2 percent) treated with doxycycline (difference between groups, 2 percent; 95 percent confidence interval, 0 to 6 percent). Of the patients evaluated 21 to 35 days after treatment, none of 112 treated with azithromycin and 1 of 102 treated with doxycycline had a positive culture. The rates of bacteriologic cure were similar for the 98 female patients (97 percent) and the 43 male patients (95 percent) treated with azithromycin. Seventeen percent of the patients who received azithromycin and 20 percent of those treated with doxycycline had mild-to-moderate drug-related side effects, mainly gastrointestinal symptoms. CONCLUSIONS: A single 1-g dose of azithromycin is as effective for the treatment of uncomplicated genital chlamydial infections as a standard seven-day course of doxycycline.

Adolescent↗

PubMed1992

Loracarbef versus penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in an adult population.

Loracarbef, a member of the carbacephem class of beta-lactam antibiotics, is a potent anti-bacterial agent. In a double-blind, randomized clinical trial to assess the efficacy and safety of loracarbef in the treatment of streptococcal pharyngitis and tonsillitis, 107 adult patients were treated with loracarbef (200 mg capsules twice a day or 15 mg/kg/day suspension) and 111 patients were treated with penicillin VK (250 mg capsules four times a day or 20 mg/kg/day suspension) for 10 days. In the loracarbef treatment group, 96.6% of the evaluable patients had a favorable clinical response 3-5 days after therapy, a result that compared favorably with the 93.9% response rate achieved in the penicillin group. The clinical failure/relapse rates were 3.4% for loracarbef-treated patients and 6.1% for patients receiving penicillin. Bacteriologic response data approximated the clinical results, with a successful response in 89.9% of the loracarbef-treated patients and 91.5% of the penicillin recipients. Two (1.9%) loracarbef-treated patients with rash and one (0.9%) penicillin-treated patient with diarrhea discontinued the study early because of these adverse events. The incidence of adverse events was comparable in the two treatment groups except for increased cough, which was reported by 3.7% of the loracarbef-treated patients and none of the penicillin recipients. These data support the conclusion that loracarbef is comparable to penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in adults.

Adult↗

PubMed1992

Loracarbef (LY163892) versus cefaclor in the treatment of bacterial skin and skin-structure infections in an adult population.

Loracarbef (LY163892), a member of the class of beta-lactam antibiotics known as carbacephems, is characterized by a high level of chemical stability and a broad spectrum of antibacterial activity that persists in the presence of beta-lactamase. The efficacy and safety of loracarbef, 200 mg (twice daily), and cefaclor, 250 mg (three times daily) (one patient received 178 mg of cefaclor suspension, three times daily), were compared in a randomized, double-blind, multicenter trial conducted in adults with skin and skin-structure infections due predominantly to Staphylococcus aureus. Examination within 72 hours after the completion of therapy indicated a favorable clinical response in 84 (93.3%) of the 90 loracarbef-treated patients evaluable for efficacy and in 79 (95.2%) of the 83 evaluable patients treated with cefaclor. Pathogens were eradicated in 83 (92.2%) of the patients in the loracarbef group and 74 (89.2%) of those in the cefaclor group. Only four adverse events--headache/migraine, diarrhea, abdominal pain, and nausea--occurred in greater than 2% of the total study population. The overall incidence of adverse events in the 201 loracarbef-treated and 192 cefaclor-treated patients evaluated for safety was 19.9% and 24.5%, respectively. Adverse events that required hospitalization or discontinuation of treatment occurred in four patients in the cefaclor group but in none of those treated with loracarbef. There were no statistically significant differences in the clinical or bacteriologic response or the incidence of side effects between the two treatment groups. These findings indicate that loracarbef given twice daily is comparable in safety and efficacy to cefaclor given three times daily in the treatment of adults with skin and skin-structure infections.

Adolescent↗