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Biomedical subjects

J Taylor

Publications and source records attributed to J Taylor.

At least 181 records · Page 10Linked to original sources

Liposomal prostaglandin E1 (TLC C-53) in acute respiratory distress syndrome: a controlled, randomized, double-blind, multicenter clinical trial. TLC C-53 ARDS Study Group.

OBJECTIVE: To evaluate the safety and efficacy of an intravenous liposomal dispersion of prostaglandin E1 as TLC C-53 in the treatment of patients with acute respiratory distress syndrome (ARDS). DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled, phase III clinical trial. SETTING: Forty-seven community and university-affiliated hospitals in the United States. PATIENTS: A total of 350 patients with ARDS were enrolled in this clinical trial. INTERVENTION: Patients were prospectively randomized in a 1:1 ratio to receive either liposomal prostaglandin E1 or placebo. The study drug was infused intravenously for 60 mins every 6 hrs for 7 days starting with a dosage of 0.15 microg/kg/hr. The dose was increased every 12 hrs until the maximal dose (3.6 microg/kg/hr) was attained or intolerance to further increases developed. Patients received standard aggressive medical/surgical care during the infusion period. OUTCOME MEASURES: The primary outcome measure was the time it took to wean the patient from the ventilator. Secondary end points included time to improvement of the PaO2/FIO2 ratio (defined as first PaO2/FIO2 > 300 mm Hg), day 28 mortality, ventilator dependence at day 8, changes in PaO2/FIO2, incidence of and time to development/resolution of organ failure other than ARDS. RESULTS: A total of 348 patients could be evaluated for efficacy. The distribution of variables at baseline describing gender, lung injury scores, Acute Physiology and Chronic Health Evaluation II scores, PaO2/FIO2, pulmonary compliance, and time from onset of ARDS or from institution of mechanical ventilation to the first dose of study drug was similar among patients in the liposomal prostaglandin E1 (n = 177) and the placebo (n = 171) treatment arms. There was no significant difference in the number of days to the discontinuation of ventilation in the liposomal prostaglandin E1 group compared with the placebo group (median number of days to off mechanical ventilation, 16.9 in patients receiving liposomal prostaglandin E1 and 19.6 in those administered placebo; p = .94). Similarly, mortality at day 28 was not significantly different in the two groups (day 28 mortality, 57 of 176 (32%) in the liposomal prostaglandin E1 group and 50 of 170 (29%) in patients receiving placebo; p = .55). In contrast, treatment with liposomal prostaglandin E1 was associated with a significantly shorter time to reach a PaO2/FIO2 ratio of >300 mm Hg (median number of days to reaching a PaO2/FIO2 ratio >300 mm Hg: 9.8 days in the liposomal prostaglandin E1 group and 13.7 days in patients receiving the placebo; p = .02). Among the subgroups examined, time to off mechanical ventilation was significantly reduced in patients who received at least 85% of a full dose (i.e., > 45.9 microg/kg) of liposomal prostaglandin E1 (median number of days to discontinuation of ventilation, 10.3 in the liposomal prostaglandin E1 group and 16.3 days in patients receiving placebo; p = .05). The overall incidence of serious adverse events was not significantly different in the liposomal prostaglandin E1 (40%) or placebo-treated (37%) groups. Drug-related adverse events of all kinds were reported in 69% of the patients receiving liposomal prostaglandin E1 compared with 33% of the placebo group, with hypotension and hypoxia (occurring in 52% and 24% of the liposomal prostaglandin E1-treated patients, respectively, and 17% and 5% of the placebo-treated patients, respectively) being noted most frequently. CONCLUSIONS: In the intent-to-treat population of patients with ARDS, treatment with liposomal prostaglandin E1 accelerated improvement in indexes of oxygenation but did not decrease the duration of mechanical ventilation and did not improve day 28 survival.

Adult↗

Using a dual method needs assessment to evaluate the training needs of public health professionals.

A dual method research approach was used to identify the training needs of the public health professionals in Washington. A mail questionnaire was implemented, followed by focus groups with Washington State Department of Health (DOH) and local health department (LHD) professionals. Focus groups were used successfully to enhance and clarify the survey findings by identifying the specific content of the highest rated training needs (interpersonal communication, cross-culture and cross-age communication, participatory teaching/training skills, and electronic communication) and by pinpointing preference for different modes of training delivery for different training needs.

Communication↗

Identification of type-specific domains within glycoprotein G of herpes simplex virus type 2 (HSV-2) recognized by the majority of patients infected with HSV-2, but not by those infected with HSV-1.

A combination of phage peptide display library mapping and pepscanning, with both murine monoclonal antibodies and a panel of well-characterized human sera, have been used in order to define type-specific epitopes of glycoprotein G of herpes simplex virus type 2 (HSV-2) (gG2). Both techniques revealed an immunodominant region of gG2, centred around amino acids 525-587 of the uncleaved gG2 molecule. A soluble peptide, equivalent to amino acids 551-570, when used as antigen in an ELISA format was recognized by three out of five murine MAbs and by 20/26 (77%) Western blot anti-HSV-2-positive human sera, but by only 1/63 Western blot anti-HSV-2-negative sera (specificity, 98%). The sensitivity of detection of human anti-HSV-2 antibodies was increased to 90% using a peptide derived from this region, presented on a nitrocellulose membrane. This highly antigenic and type-specific domain of gG2 is located at the junction between the 'unique' region of gG2 and its C-terminal end, which has approximately 50% identity with gG1. A second antigenic region of gG2, amino acids 351-427, which lies within the 'unique' part of gG2, was also identified by both techniques employed in this study and is recognized by a proportion of anti-HSV-2-positive sera. These findings demonstrate the feasibility of developing a peptide-based type-specific assay for the detection of anti-HSV-2 antibody in human sera based on type-specific epitopes of gG2 and have implications for the understanding of the three-dimensional topography of gG2.

Amino Acid Sequence↗

ABC medium, a new chromogenic agar for selective isolation of Salmonella spp.

We describe a new chromogenic agar medium, ABC medium (alphabeta-chromogenic medium), which includes two substrates, 3, 4-cyclohexenoesculetin-beta-D-galactoside and 5-bromo-4-chloro-3-indolyl-alpha-D-galactopyranoside, to facilitate the selective isolation of Salmonella spp. This medium exploits the fact that Salmonella spp. may be distinguished from other members of the family Enterobacteriaceae by the presence of alpha-galactosidase activity in the absence of beta-galactosidase activity. A total of 1, 022 strains of Salmonella spp. and 300 other gram-negative strains were inoculated onto this medium. Of these, 1,019 (99.7%) strains of Salmonella spp. produced a characteristic green colony, whereas only 1 strain (0.33%) of non-Salmonella produced a green colony. A total of 283 stool samples were cultured onto desoxycholate citrate (DC) agar and ABC medium by direct inoculation and after selective enrichment in selenite broth. Overall, the sensitivity and specificity were superior for ABC medium (100 and 90.5%, respectively) than for DC agar (88 and 26.9%, respectively). We conclude that ABC medium offers a high degree of specificity for the detection of Salmonella spp. in stool samples.

Agar↗

Characterization of the 5' ends for polyadenylated RNAs synthesized during the replication of hepatitis delta virus.

The genome of hepatitis delta virus (HDV) is a 1,679-nucleotide (nt) single-stranded circular RNA that is predicted to fold into an unbranched rodlike structure. During replication, two complementary RNAs are also detected: an exact complement, referred to as the antigenome, and an 800-nt polyadenylated RNA that could act as the mRNA for the delta antigen. We used a 5' rapid amplification of cDNA ends procedure, followed by cloning and sequencing, to determine the 5' ends of the polyadenylated RNAs produced during HDV genome replication following initiation under different experimental conditions. The analyzed RNAs were from the liver of an infected woodchuck and from a liver cell line at 6 days after transfection with either an HDV cDNA or ribonucleoprotein (RNP) complexes assembled in vitro with HDV genomic RNA and purified recombinant small delta protein. In all three situations the 5' ends mapped specifically to nt 1630. In relationship to what is called the top end of the unbranched rodlike structure predicted for the genomic RNA template, this site is located 10 nt from the top, and in the middle of a 3-nt external bulge. Following transfection with RNP, such specific 5' ends could be detected as early as 24 h. We next constructed a series of mutants of this predicted bulge region and of an adjacent 6-bp stem and the top 5-nt loop. Some of these mutations decreased the ability of the genome to undergo antigenomic RNA synthesis and accumulation and/or altered the location of the detected 5' ends. The observed end located at nt 1630, and most of the novel 5' ends, were consistent with transcription initiation events that preferentially used a purine. The present studies do not prove that the detected 5' ends correspond to initiation sites and do not establish the hypothesis that there is a promoter element in the vicinity, but they do show that the location of the observed 5' ends could be controlled by nucleotide sequences at and around nt 1630.

5' Untranslated Regions↗

Unique properties of the large antigen of hepatitis delta virus.

The large form of the hepatitis delta virus (HDV) protein (L) can be isoprenylated near its C terminus, and this modification is considered essential for particle assembly. Using gel electrophoresis, we separated L into two species of similar mobilities. The slower species could be labeled by the incorporation of [(14)C]mevalonolactone and is interpreted to be isoprenylated L (L(i)). In serum particles, infected liver, transfected cells, and assembled particles, 25 to 85% of L was isoprenylated. Isoprenylation was also demonstrated by (14)C incorporation in vitro with a rabbit reticulocyte coupled transcription-translation system. However, the species obtained migrated even slower than that detected by labeling in vivo. Next, in studies of HDV particle assembly in the presence of the surface proteins of human hepatitis B virus, we observed the following. (i) Relative to L, L(i) was preferentially assembled into virus-like particles. (ii) L(i) could coassemble the unmodified L and the small delta protein, S. (iii) In contrast, a form of L with a deletion in the dimerization domain was both isoprenylated and assembled, but it could not support the coassembly of S. Finally, to test the expectation that the isoprenylation of L would increase its hydrophobicity, we applied a phase separation strategy based on micelle formation with the nonionic detergent Triton X-114. We showed the following. (i) The unique C-terminal 19 amino acids present on L relative to S caused a significant increase in the hydrophobicity. (ii) This increase was independent of isoprenylation. (iii) In contrast, other, artificial modifications at either the N or C terminus of S did not increase the hydrophobicity. (iv) The increased hydrophobicity was not sufficient for particle assembly; nevertheless, we speculate that it might facilitate virion assembly.

Amino Acid Sequence↗

Health care providers' perspectives on patient delay for seeking care for symptoms of acute myocardial infarction.

To inform intervention development in a multisite randomized community trial, the Rapid Early Action for Coronary Treatment (REACT) project formative research was undertaken for the purpose of investigating the knowledge, beliefs, perceptions, and usual practice of health care professionals. A total of 24 key informant interviews of cardiologists and emergency physicians and 15 focus groups (91 participants) were conducted in five major geographic regions: Northeast, Northwest, Southeast, Southwest, and Midwest. Transcript analyses revealed that clinicians are somewhat unaware of the empirical evidence related to the problem of patient delay, are concerned about the practice constraints they face, and would benefit from concrete suggestions about how to improve patient education and encourage fast action. Findings provide guidance for selection of educational strategies and messages for health providers as well as patients and the public.

Aged↗

Failure to maintain the benefits of home-based intervention in adolescents with poorly controlled type 1 diabetes.

OBJECTIVE: To determine whether a 6-month home-based intervention program in adolescents with poorly controlled diabetes improves metabolic control and whether benefits are maintained after the intervention. RESEARCH DESIGN AND METHODS: Adolescents with a mean HbA1c of > 9.0% over the preceding 12 months received either routine care in a diabetes clinic and an ambulatory intervention for 6 months (n = 37) or routine care only (n = 32). A diabetes educator provided monthly home visits and weekly phone contact to educate and support the adolescents in setting goals for insulin adjustment, blood glucose monitoring, and target blood glucose range. There was no systematic change in the frequency of insulin injections. After the intervention, there was a 12-month follow-up when the intervention and control groups both received only routine care. Outcome measures were HbA1c and Diabetes Knowledge Assessment (DKN). RESULTS: During the intervention, mean HbA1c fell (baseline: 11.1 +/- 1.3%, 6 months: 9.7 +/- 1.6%; P = 0.0001) and mean knowledge scores increased (P = 0.0001) in the intervention group but not in control subjects. However, this improvement in HbA1c and increase in knowledge was not maintained in the intervention group at 12- and 18-month follow-up assessments. Parents' knowledge scores also improved significantly from baseline levels in the intervention group at 6 and 12 months (P = 0.001, P = 0.005, respectively). CONCLUSIONS: An ambulatory program improves metabolic control and knowledge in adolescents with poorly controlled type 1 diabetes; however, it is effective only while the intervention is maintained.

Adolescent↗

Individual differences in electrodermal responsivity to predictable aversive stimuli and substance dependence.

To determine if the inability to take advantage of the predictability of an aversive stimulus to diminish its psychological impact reflects a deficit in inhibitory control related to the development of substance dependence, we recorded skin conductance responses (SCRs), heart rate (HR), and anticipatory electrodermal nonspecific fluctuations (NSFs) from 175 16-18-year-old boys when a white noise blast was either unpredictable or temporally predictable. Compared with boys who had moderately reduced or augmented SCRs to predictable blasts (moderate and poor modulators, respectively), boys whose SCRs were greatly reduced (good modulators) had fewer symptoms of alcohol and nicotine dependence and more anticipatory NSFs. HR appeared to index an active coping response for good and moderate modulators. The autonomic response pattern evident for good modulators may index an inhibitory control mechanism protecting them from developing substance dependence.

Acoustic Stimulation↗

A comparison of one hundred and fifty consecutive parotidectomies for tumours and inflammatory disease.

The demographic profile and complications are compared and contrasted for 150 consecutive parotidectomies. All patients were under the care of one surgeon (JDL) over a twenty-year period (1977-1997). The case records and contemporaneous database were analysed retrospectively. 111 (74%) procedures were performed for tumours and 39 (26%) for inflammatory disease. The incidence of unexpected permanent facial nerve palsy was 1.8% in the tumour group and zero in the inflammatory group. The overall unexpected palsy rate was 1.3%. Transient paralysis was more common in the inflammatory group than the tumour group (61.5% compared with 33.3%, P<0.02) and was more likely to be panfacial (48.7% compared with 17.1%, P<0.0002). The overall incidence of Frey's syndrome was less than 20% and both salivary fistulae and sialocoeles were infrequent.

Adolescent↗

1',1'-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid: a novel, orally effective cannabinoid with analgesic and anti-inflammatory properties.

1',1'-Dimethylheptyl-Delta-8-tetrahydrocannabinol-11-oic acid (CT-3) is a novel cannabinoid that is under development by Atlantic Pharmaceuticals as an anti-inflammatory and analgesic drug. The objective of the study was to investigate the effects of CT-3 on overt symptom complex (Irwin's test), nociception, gastrointestinal (GI) ulceration, and pharmacological availability after intragastric (i.g.) and intraperitoneal (i.p.) administration. Analgesic studies were assessed in the hot-plate (55 degrees C) and the tail clip tests in mice and in the tail clip test in rats. In addition, pharmacological interaction of CT-3 with the solvent dimethyl sulfoxide (DMSO) was investigated in rats. In mice, CT-3 decreased spontaneous motor activity and induced dose-dependent, analgesic activity in the tail clip and hot-plate tests, with potency similar to morphine sulfate after i.g. and i.p. administration. However CT-3 showed more prolonged duration of analgesic action than morphine. In rats, CT-3 showed marked analgesia in the tail clip test and had similar i.p. and i.g. median effective dose (ED(50) values; 5 mg/kg). CT-3 was devoid of GI ulceration when administered with DMSO either acutely at doses below 100 mg/kg or chronically at a dosage of 30 mg/kg/day for 5 days. In contrast, indomethacin induced GI ulceration and deaths. The concurrent use of DMSO with CT-3 decreased its analgesic action, increased its adverse central nervous system effects, and induced GI ulceration. The evidence indicates that CT-3 exhibits a large dissociation between its anti-inflammatory/analgesic effects and its ulcerogenic actions. CT-3 warrants clinical development as a novel anti-inflammatory and analgesic drug.

Administration, Oral↗

Facial pressure sore complicated by mandibular osteomyelitis.

A case is reported of an 85-year-old woman with mandibular osteomyelitis secondary to a submental pressure sore. The main aetiological factors in the development of the pressure sore were dementia and severe senile kyphosis. Pressure sores are rare in the head and neck region and, though osteomyelitis is a common complication at other anatomical sites, it has not been previously reported in the mandible.

Aged↗

Relationship of internalized racism to abdominal obesity and blood pressure in Afro-Caribbean women.

Racism is associated with increased psychosocial stress and blood pressure in blacks. However, little is known of the relationship of racism to other features of insulin resistance syndrome. This study examined the relationship of internalized racism to abdominal obesity and elevated blood pressure in a population of black Caribbean women aged 20-55 years. One hundred thirty-three randomly selected women from the island of Barbados comprised the study sample. Data collected included anthropometric and blood pressure measurements, and information about internalized racism, anxiety, and depression. The stress measures including anxiety, depression, and internalized racism were significantly correlated with waist circumference (r = .25, r = .21, and r = .25). After adjusting for age, education, anxiety, and depression, internalized racism remained significantly correlated with waist circumference. The odds ratio associated with development of abdominal obesity among those with high internalized racism (OR = 2.4 [95% CI, 1.1,5.3]) was significant (P < .05) after adjusting for age, education, and body mass index. Blood pressure was not independently related to internalized racism. Studies comparing black-white differences in diseases for which abdominal obesity is a risk factor (eg, diabetes and cardiovascular disease) should take into account the potential role of internalized racism in defining the differences between ethnic groups.

Abdomen↗

Inadvertent injection of sodium hypochlorite into the maxillary sinus.

A previously undocumented complication of root canal therapy is reported. A dilute solution of 5-10 mls sodium hypochlorite was inadvertently injected into the maxillary sinus during root canal therapy of a right upper second premolar (5). The patient developed acute, sudden, severe facial pain and swelling necessitating emergency admission to hospital and operative intervention under general anaesthesia. A diagnosis of acute chemical sinusitus was made, further management and discussion follow.

Accidents↗

A comparison of smoothing techniques for CD4 data measured with error in a time-dependent Cox proportional hazards model.

The use of CD4+ T-lymphocyte counts as a covariate presents some unique challenges in survivorship analyses due to the variability of this marker. If one does not account for the measurement error component of this variability in some manner, the estimate of the relative risk parameter in a time-dependent Cox model is biased towards zero, and coverage levels of confidence intervals may be seriously incorrect. We use a two-stage approach to reduce the variability in the observed CD4 counts in order to obtain a more accurate estimate of the relative risk parameter and more valid summary statistics. In the first stage, population based smoothing methods derived from a random-effects model plus a stochastic process or individual based smoothing methods are used to replace the observed longitudinal CD4 counts with less variable imputes at each failure time. In the second stage, we use the imputes in a time-dependent Cox model to estimate the risk parameter and its associated summary statistics. We compare the smoothing methods in simulation studies and find that the use of these smoothing methods results in a substantial reduction in bias for the true risk parameter estimate, better efficiency, and more accurate coverage rates in confidence intervals. We apply our two-stage smoothing methods to the marker CD4 in the ACTG-019 clinical trial part B.

AIDS-Related Complex↗