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Biomedical subjects

K Freeman

Publications and source records attributed to K Freeman.

At least 19 recordsLinked to original sources
PubMed1998

Class restriction of cephalosporin use to control total cephalosporin resistance in nosocomial Klebsiella.

CONTEXT: Resistance to most or all cephalosporin antibiotics in Klebsiella species has developed in many European and North American hospitals during the past 2 decades. OBJECTIVE: To determine if restriction of use of the cephalosporin class of antibiotics would reduce the incidence of patient infection or colonization by cephalosporin-resistant Klebsiella. DESIGN: A before-after comparative 2-year trial. SETTING: A 500-bed, university-affiliated community hospital in Queens, NY. PATIENTS: All adult medical and surgical hospital inpatients. INTERVENTION: A new antibiotic guideline excluded the use of cephalosporins except for pediatric infection, single-dose surgical prophylaxis, acute bacterial meningitis, spontaneous bacterial peritonitis, and outpatient gonococcal infection. All other cephalosporin use required prior approval by the infectious disease section. MAIN OUTCOME MEASURE: Incidence of patient infection or colonization by ceftazidime-resistant Klebsiella during 1995 (control period) compared with 1996 (intervention period). RESULTS: An 80.1% reduction in hospital-wide cephalosporin use occurred in 1996 compared with 1995. This was accompanied by a 44.0% reduction in the incidence of ceftazidime-resistant Klebsiella infection and colonization throughout the medical center (P<.01), a 70.9% reduction within all intensive care units (P<.001), and an 87.5% reduction within the surgical intensive care unit (P<.001). A concomitant 68.7% increase in the incidence of imipenem-resistant Pseudomonas aeruginosa occurred throughout the medical center (P<.01). All such isolates except one were susceptible to other antibiotics. CONCLUSION: Extensive cephalosporin class restriction significantly reduced nosocomial, plasmid-mediated, cephalosporin-resistant Klebsiella infection and colonization. This occurred at the price of increased imipenem resistance in P aeruginosa, which remained susceptible to other agents. Thus, an overall reduction in multiply-resistant pathogens was achieved within 1 year.

Adult↗
PubMed1998

Efficacy of DHE photodynamic therapy for respiratory papillomatosis: immediate and long-term results.

OBJECTIVES/HYPOTHESIS: Recurrent respiratory papillomatosis is a potentially life-threatening disease that affects both children and adults and can result in complete respiratory obstruction. Conventional therapies cannot prevent multiple recurrences. The authors have been evaluating photodynamic therapy (PDT) to treat this disease since 1988. This study compared the efficacy of PDT with dihematoporphyrinether (DHE) with traditional therapy. STUDY DESIGN: This was a randomized prospective trial of DHE-PDT. Patients were randomly assigned to receive one of two doses of DHE--3.25 mg/kg or 4.25 mg/kg body weight. They were compared with a concurrent control group. Disease extent was evaluated by direct laryngoscopy before treatment and over a 1-year period following treatment. Results were also compared with two historical cohorts of patients treated with lower doses of DHE. METHODS: Eighty-one patients, ages 4 to 74 years, with moderate to severe recurrent disease were enrolled. Forty-eight received PDT and 33 in the control group were treated with conventional therapy. Both PDT groups received 50 J laser light to activate the drug. Patients received an intravenous infusion of DHE as outpatients 48 to 72 hours before treatment. During direct laryngoscopy, light (630 nm) was delivered by an argon-pumped dye laser. Tissue biopsies were analyzed for presence of human papillomavirus (HPV). RESULTS: There was notable improvement with either drug dose over the first year. Those receiving 4.25 mg/kg DHE experienced a significantly larger decrease in papilloma growth rate. Three-year follow-up of a subset of patients confirmed that improvement was maintained. There was no impact of DHE-PDT on persistence of HPV DNA. CONCLUSION: This therapy holds promise for the treatment of laryngeal papillomas.

Adolescent↗
PubMed1997

The effects of ion implantation on rate of tooth movement: an in vitro model.

Recently, the ion-implantation process has been applied to orthodontic wires. By altering the surface composition of a wire, the ion-implantation process supposedly decreases the frictional forces produced during tooth movement. The purpose of this study was to compare the amount of tooth movement produced by different orthodontic wire compositions, under identical conditions, by using an in vitro model. The wires tested were stainless steel, nickel-titanium (control and ion implanted), and beta-titanium (control and ion implanted). The amount of tooth movement was measured and compared. Results demonstrate that, stainless steel produced the least frictional force during in vitro tooth movement, followed by ion-implanted nickel-titanium, ion-implanted beta-titanium, untreated nickel-titanium, and finally, untreated beta-titanium. A Wilcoxon rank sum test showed statistically significant differences in the amount of movement seen with the ion-implanted wires when compared with their untreated counterparts.

Analysis of Variance↗
PubMed1997

Mesh diagram analysis: developing a norm for Puerto Rican Americans.

Cephalometric radiography is an important diagnostic aid in orthodontics. Mesh analysis is a proportionate cephalometric method of graphically assessing disharmonies of the craniofacial complex. Original norms for this analysis were created from a white, European American sample. Norms for black Americans of African descent were developed in another study. The purposes of this investigation were: (1) to develop a standard mesh diagram from a Puerto Rican American population; (2) to compare the diagram with previously established data from the white sample; (3) to develop linear and angular means for the Legan, Burstone, Ricketts, DiPaolo, and Steiner analyses for a Puerto Rican American population; and (4) to assess the use of a panel for selecting esthetically pleasing faces. The subjects in the study had no previous orthodontic treatment, had Class I occlusion with 6 mm or less of crowding per dental arch, and had two parents and two sets of grandparents who were were born in Puerto Rico. Sixty-nine patients met the study criteria, and 50 of those patients (20 males and 30 females) were selected as having esthetically pleasing faces by the panel. Male and female norm diagrams were created and these were compared with those developed previously. Linear and angular measurements were also compared. Significant differences between the ethnic groups were found in the dentoalveolar region. Similarities were noticed in the upper face height and anterior cranial base length. The panel selection results showed no agreement within the sexes, occupations, or ethnic groups.

Adolescent↗
PubMed1997

The ten test.

The authors describe a new test for clinical sensibility, initiated in response to the need of the senior author for a rapid, reliable method to evaluate sensibility. Using this test, the patient develops a ratio between normal light moving touch and diminished moving touch. Subsequent determinations can detect serial changes. The ratios obtained can be compared with a standard scale of sensibility with a high degree of validity and reliability. The interexaminer and intraexaminer results obtained are reliable and repeatable. Statistical evaluations substantiating the validity of the test are presented. Simplicity and depend-ability recommend this test for use in a busy clinical setting.

Humans↗
PubMed1997

Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis.

A prospective, open, multicentre study was performed to investigate the efficacy and safety of long-term treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six-area, six-sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four-point scales. Response was further evaluated on a five-point scale. Adverse events, blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five-point scale. One hundred subjects were enrolled and 65 completed 48 weeks of treatment. Withdrawals occurred due to remission (three), inadequate response (seven), protocol violations (11) and adverse events (14, of which seven were probably treatment related). Cyclosporin produced rapid and highly significant improvements in all indices of disease activity. Sixty-five subjects considered that they had shown a considerable improvement or complete clearance of disease. Most patients relapsed after cessation of treatment, but neither signs nor symptoms had returned to baseline severity 8 weeks later. Blood pressure and serum creatinine levels increased slightly, and in one subject renal impairment was a major factor contributing to withdrawal of the drug. Overall, 85 subjects rated the tolerability of cyclosporin as good or very good. The results indicate that cyclosporin has a place in the long-term treatment of severe atopic dermatitis provided that appropriate patients are selected and careful monitoring is performed.

Adolescent↗
PubMed1997

Effect of supplemental gases on end-tidal CO2 and oxygen saturation in patients undergoing fentanyl and midazolam outpatient sedation.

Forty-six American Society of Anesthesiologists Class I and II adults were randomly assigned to one to two study groups. Each subject received 0.7 microgram/kg of fentanyl and a titrated dose of midazolam. One group received 100% supplemental oxygen (O2) while another group received 50% nitrous oxide (N2O) and 50% O2. End-tidal carbon dioxide (EtCO2) and O2 saturation (SpO2) were measured at 5-min intervals throughout the procedure. We conclude that there was no significant difference in EtCO2 or O2 saturation between the two groups.

Adult↗
PubMed1996

Missense mutations at the FKBP12-rapamycin-binding site of TOR1.

The TOR genes were first identified in Saccharomyces cerevisiae by the isolation of mutants which exhibit dominant resistance to the immunosuppressive and antifungal drug rapamycin (Rm). The originally characterized Rm-resistant (RmR) TOR1-1 and TOR2-1 alleles contain an Arg in place of a conserved Ser residue, which lies adjacent to the phosphatidylinositol (PI) kinase-related domain of TOR (Ser1972 in TOR1; Ser1975 in TOR2). Additional spontaneous RmR mutants containing Lys, Ile or Asn substitutions were subsequently isolated. As this Ser is a potential site for protein kinase C phosphorylation, we were interested in determining whether the observed RmR is due to steric hindrance of the FKBP12-Rm-TOR interaction or whether phosphorylation at this site is required to mediate the interaction. Using site-directed mutagenesis, we replaced the Ser1972 residue of TOR1 with either a conservative residue, Ala, an alternative potential phosphorylation site, Thr, or Asp to mimic phosphorylation. The TOR1 (S1972A) mutant protein retained Rm sensitivity (RmS), whereas both the Thr and Asp substitutions conferred RmR. RmS correlated with the ability to interact with FKBP12-Rm in a two-hybrid assay: both wild-type TOR1 and the S1972A mutant retained the ability to interact with FKBP12-Rm, whereas the S1972T, S1972D and S1972R mutants failed to interact. All mutant TOR1 proteins were able to complement the growth defect of tor1 null alleles, suggesting that the Ser1972 residue may not be required for TOR1 function in cycling cells. Since a TOR1(S1972A) mutant protein confers a RmS phenotype, interacts with FKBP12-Rm in a two-hybrid assay, and functions in vivo, we conclude that phosphorylation at Ser1972 is not necessary for the interaction between TOR1 and FKBP12-Rm.

Base Sequence↗
PubMed1996

Multimerization of Hsp42p, a novel heat shock protein of Saccharomyces cerevisiae, is dependent on a conserved carboxyl-terminal sequence.

Rap1p is a transcriptional regulator of Saccharomyces cerevisiae, which plays roles in both transcriptional activation and silencing. To identify proteins involved in Rap1p-dependent regulation of transcription, we used the two-hybrid system to screen for Rap1p-interacting proteins. Two of the clones isolated from this screen encode a truncated protein with homology to small heat shock proteins (HSPs). Here we present an analysis of this novel S. cerevisiae HSP, which we name Hsp42p. Expression of HSP42 is regulated by a range of stress conditions similar to S. cerevisiae HSP26, with which Hsp42p shares most homology. However, HSP42 expression is more sensitive to increased salt concentration and to starvation and, in contrast to HSP26 is expressed in unstressed cells. Hsp42p interacts with itself in the two-hybrid assay. This interaction is dependent on a hydrophobic region which is conserved among small HSPs. Using bacterially expressed Hsp42p fusion proteins. we demonstrate that this is a direct interaction. Fractionation of yeast protein extracts by size demonstrates that all of the Hsp42p in these extracts is present in complexes with a molecular mass of greater than 200 kDa, suggesting that Hsp42p exists in high molecular mass complexes.

Amino Acid Sequence↗
PubMed1996

Oral fluconazole compared with bladder irrigation with amphotericin B for treatment of fungal urinary tract infections in elderly patients.

Fungal urinary tract infections are increasingly prevalent in the elderly in acute and chronic care settings. This randomized trial compares the efficacy and safety of oral fluconazole with the efficacy and safety of bladder irrigation with amphotericin B for treatment of funguria (> or = 10,000 cfu/mL of urine) in 109 hospitalized elderly patients. A second treatment course was given for persistent funguria. Indwelling bladder catheters were present in 69% of the patients. While Candida albicans was the predominant isolate from catheterized patients, C. albicans, Candida tropicalis, and Torulopsis glabrata were recovered from noncatheterized patients. Two days after completion of treatment, funguria was eradicated in 96% of the patients treated with amphotericin B and 73% of those treated with fluconazole (P < .05). At 1 month after study enrollment, the mortality rate associated with all causes was greater among patients who were treated with amphotericin B bladder irrigation than among those who received oral fluconazole therapy (41% vs. 22%, respectively; P < .05); this finding suggests that local therapy may be associated with poorer survival. The proportion of patients without funguria at 1 month after study enrollment was similar in the two treatment groups (84%, amphotericin B group; 80%, fluconazole group). A few minor and mild adverse events occurred.

Administration, Oral↗
PubMed1996

Teleconsulting: a practical account of pitfalls, problems and promise. Experience from the TEAM project group.

In Wales the Tele Education and Medicine (TEAM) project has given clinicians, in both the primary- and secondary-care sectors, practical experience in teleconsulting. From this project we have been able to identify the potential pitfalls and problems in developing and using this new technology. These problems include: using teleconsulting simply because it is fashionable; the failure to base it on the needs of the patients and the primary-care physicians; the failure to validate accuracy, acceptability and cost; the failure to adapt to new technical improvements; and the failure to scale up from a pilot project to a wider teleconsulting service. In our experience technical support is essential and is best facilitated by multisite cooperation, rather than small free-standing projects.

Dermatology↗
PubMed1996

Patterns of ganglioside expression in B cell neoplasms.

Twenty seven B cell neoplasms were examined by high performance thin layer chromatography (HPTLC) and immune thin layer chromatography (ITLC) to determine ganglioside expression. Patterns of expression in the cells were compared with conventional morphology, genotype, and glycoprotein immunophenotype. Patterns of ganglioside expression were found for each of the tumor types analyzed (5 acute lymphoblastic lymphomas (ALL), 5 Burkitt's Lymphomas (BL), 4 chronic lymphocytic leukemias (CLL), and 3 diffuse poorly differentiated lymphomas (DPDL), 7 diffuse histiocytic lymphomas (DHL), and 3 multiple myelomas (MM). GM3 was the predominant ganglioside found in all B cell neoplasms except multiple myeloma where GM2 was equivalent to GM3. GM1 was detected by ITLC in all B cell tumors, but significant amounts were found by HPTLC only in ALL, CLL, and DHL. Small amounts of GD3 and GD2 were found in several B cell neoplasms. Significant amounts of other gangliosides were not found. The expression of GM2 on the MM cell lines, a cell type derived from outside of the nervous system, is unusual. This high level of expression was also seen in metabolic labeling studies. GM2 was readily detectable in the SKMM1 human multiple myeloma cell line by flow cytometry and served as a target for human complement-mediated cytotoxicity. Although the functions of gangliosides are largely known, the patterns of gangliosides found for this system of human B cell malignancies may serve to provide targets for specific immunotherapy and clues to their functions.

Burkitt Lymphoma↗
PubMed1996

School attendance, health-risk behaviors, and self-esteem in adolescents applying for working papers.

Since health-risk behaviors are often encountered in clusters among adolescents, it was hypothesized that adolescents with poor school attendance would be associated with more health-risk behaviors (e.g., substance use, violence) than those who attend school regularly. This study assessed the relationship between poor school attendance and health-risk behaviors, and described health-risk behaviors and self-esteem among adolescents seeking employment. In this cross-sectional study, school attendance (poor vs. regular attendance) was related to health-risk behaviors by asking 122 subjects seen at a New York City Working Papers Clinic to complete both a 72-item questionnaire about their health-risk behaviors and the 58-item Coopersmith Self-Esteem School Form Inventory. Chi-square and Fisher's Exact Tests were performed. The poor and regular attenders of school differed significantly in only 5 out of 44 items pertaining to health-risk behaviors. Self-esteem measures for the two groups did not differ from one another or from national norms. In this sample, depression "in general" (global) and "at home," but not "at school," were associated significantly with suicidal thoughts/attempts and serious past life events (e.g. family conflict, sexual abuse). There were no significant associations between depression or self-esteem and illicit substance or alcohol use. We found few associations between poor school attendance and health-risk behaviors in this sample of employment-seeking adolescents. The poor and regular attenders of school were similar in most aspects of their health-risk behaviors and self-esteem.

Adolescent↗
PubMed1995

Genetic polymorphism of the alpha 2-adrenergic receptor is associated with increased platelet aggregation, baroreceptor sensitivity, and salt excretion in normotensive humans.

It is likely that a number of independent heritable traits, each encoded by a singular gene, contribute to pathologic elevations in blood pressure in humans. Genetic polymorphisms of individual genes may result in intermediate phenotypes which, by themselves, do not raise blood pressure, but, coupled with environmental or epistatic forces, contribute to the prevalence of human hypertension. The gene for the alpha 2-adrenergic receptor encoded by chromosome 10 (C10 A2AR) is polymorphic, and Southern blotting with a cDNA probe following restriction enzyme digest of this gene results in fragments of either 6.3 kb or 6.7 kb in size. We reported an association between homozygosity for the 6.3 kb allele and hypertension in blacks. Blacks with hypertension also have an increased risk for thrombotic stroke, increased baroreceptor sensitivity, and decreased sodium excretion. We noted that the C10 A2AR, which modulates norepinephrine release in blood-pressure-regulating regions of the brain, is also expressed on platelets and in the kidney. We postulated that functional changes associated with the C10 A2AR gene polymorphism could be responsible for increased baroreceptor sensitivity, epinephrine-mediated platelet aggregation, and decreased sodium excretion in some individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1995

Molecular and genetic analysis of the toxic effect of RAP1 overexpression in yeast.

Rap1p is a context-dependent regulatory protein in yeast that functions as a transcriptional activator of many essential genes, including those encoding ribosomal proteins and glycolytic enzymes. Rap1p also participates in transcriptional silencing at HM mating-type loci and telomeres. Overexpression of RAP1 strongly inhibits cell growth, perhaps by interfering with essential transcriptional activation functions within the cell. Here we report a molecular and genetic analysis of the toxic effect of RAP1 overexpression. We show that toxicity does not require the previously defined Rap1p activation and silencing domains, but instead is dependent upon the DNA-binding domain and an adjacent region of unknown function. Point mutations were identified in the DNA-binding domain that relieve the toxic effect of overexpression. Two of these mutations can complement a RAP1 deletion yet cause growth defects and altered DNA-binding properties in vitro. However, a small deletion of the adjacent (downstream) region that abolishes overexpression toxicity has, by itself, no apparent effect on growth or DNA binding. SKO1/ACR1, which encodes a CREB-like repressor protein in yeast, was isolated as a high copy suppressor of the toxicity caused by RAP1 overexpression. Models related to the regulation of Rap1p activity are discussed.

Alleles↗
PubMed1995

Pressure ulcer pain: assessment and quantification.

A cross-sectional study design was used to document perception of pressure ulcer pain in 132 patients in an acute care setting. Subjects were evaluated by means of the Folstein Mini-Mental State Examination, Beck's Depression Inventory, the Faces Pain Rating Scale, and the Visual Analog Scale for pain intensity. Charts were reviewed for demographic data and related medical treatments. The group comprised 44 subjects (33.3%) who were able to respond to the evaluation instruments and 88 subjects (66.7%) who were unable to respond to the evaluation tools. Forty-one percent of the respondents denied pressure ulcer pain and 59% reported pain of some type. According to the Faces Rating Scale, 32% of this group reported no pain and 68% reported some degree of pain. The respondents included 48% who scored below 24 on the Folstein Mini-Mental State Examination, indicative of cognitive impairment, and 52% who were found to be cognitively intact, with scores of 24 or above. Only 2% (n = 3) were given analgesics for pressure ulcer pain within 4 hours of the interview.

Adult↗
PubMed1994

Evidence that a complex of SIR proteins interacts with the silencer and telomere-binding protein RAP1.

The maintenance of transcriptional silencing at HM mating-type loci and telomeres in yeast requires the SIR2, SIR3, and SIR4 proteins, none of which appear to be DNA-binding proteins. Here we show that SIR3 and SIR4 interact with a carboxy-terminal domain of the silencer, telomere, and UAS-binding protein RAP1. We identified SIR3 and SIR4 in a two-hybrid screen for RAP1-interacting factors and showed that SIR3 interacts both with itself and with SIR4. The interaction between RAP1 and SIR3 can be observed in vitro in the absence of other yeast proteins. Consistent with the notion that native SIR proteins interact with the RAP1 carboxyl terminus, we show that mutation of the endogenous SIR3 and SIR4 genes increases transcriptional activation by LexA/RAP1 hybrids. To test the importance of the RAP1-SIR3 interaction for silencing, we identified mutations in the RAP1 carboxyl terminus that either diminish or abolish this interaction. When introduced into the native RAP1 protein, these mutations cause corresponding defects in silencing at both HMR and telomeres. We propose that RAP1 acts in the initiation of transcriptional silencing by recruiting a complex of SIR proteins to the chromosome via protein-protein interactions. These data are consistent with a model in which SIR3 and SIR4 play a structural role in the maintenance of silent chromatin and indicate that their action is initiated at the silencer itself.

Bacterial Proteins↗