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Biomedical subjects

J A Stewart

Publications and source records attributed to J A Stewart.

At least 37 records · Page 2Linked to original sources
PubMed2000

Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study.

We conducted this study to determine whether infection with human herpesvirus (HHV) 6A, HHV-6B, or HHV-7 differed between patients with chronic fatigue syndrome and control subjects. We recruited 26 patients and 52 nonfatigued matched control subjects from Atlanta. Serum samples were tested by enzyme immunoassay for seroreactivity to HHV-6, and all were seropositive. Lymphocyte specimens were cocultivated with cord blood lymphocytes and assayed for HHV-6 and HHV-7; neither virus was isolated. Finally, lymphocytes were tested by use of 3 polymerase chain reaction methods for HHV-6A, HHV-6B, and HHV-7 DNA. HHV-6A or HHV-6B DNA was detected in 17 (22.4%) of 76 samples, and there were no significant differences (by matched analyses) between patients (3 [11.5%] of 26) and control subjects (14 [28%] of 50). HHV-7 DNA was detected in 14 subjects, and although control subjects (12 [24%]) were more likely than patients (2 [7.7%]) to be positive, the difference was not statistically significant. We found no evidence that active or latent infection with HHV-6A, HHV-6B, HHV-7, or any combination these 3 HHVs is associated with chronic fatigue syndrome.

Case-Control Studies↗
PubMed2000

Highly potent neurotensin analog that causes hypothermia and antinociception.

The tridecapeptide neurotensin has long been proposed as an endogenous neuroleptic. However, for neurotensin [or neurotensin(8-13) [NT(8-13)], the active fragment] to cause its effects, it must be administered centrally. Here, we report on an analog of NT(8-13), (N-methyl-Arg),Lys,Pro,L-neo-Trp,tert-Leu,Leu (NT69L), which contains a novel amino acid, L-neo5 degrees C (rectal), with a significant effect persisting for over 7 h. NT69L also caused a rapid (within 15 min) and persistent (for over 5 h) antinociceptive effect, as determined by the hot plate test. NT69L was overall the most potent and longest lasting neurotensin analog that has been reported. These studies provide the background for further testing of a stable, potent and long lasting neurotensin analog as a potential neuroleptic.

Analgesics↗
PubMed2000

Brimonidine 0.2% versus dorzolamide 2% each given three times daily to reduce intraocular pressure.

PURPOSE: To evaluate the efficacy and safety of brimonidine compared with dorzolamide given three times daily as monotherapy in patients with primary open-angle glaucoma or ocular hypertension. METHODS: In a double-masked, multicenter, crossover comparison in 40 patients, qualified patients were washed out from their previous medication and randomized to dorzolamide 2% or brimonidine 0.2% for the first 6-week treatment period. Patients then were washed out for 2 weeks and started on the opposite medication for the second 6-week period. RESULTS: Baseline intraocular pressure for all 40 subjects (76 eyes) was 24.1 +/- 2.0 mm Hg. This study found that the 8:00 AM trough intraocular pressure after 6 weeks of therapy for dorzolamide was 20. 7 +/- 3.1 mm Hg and for brimonidine 20.8 +/- 3.2 mm Hg (P =.99). The peak intraocular pressure (2 hours after dosing) for dorzolamide was 18.6 +/- 3.4 mm Hg and for brimonidine 17.8 +/- 2.7 mm Hg (P =.10 ). Dorzolamide caused more stinging upon instillation (P <.01) and brimonidine more itching (P =.01). No statistical differences existed between groups for systemic adverse events. Six patients, all on brimonidine, were discontinued from a treatment period early. Of these, two were discontinued for inadequate pressure control, two with dizziness and fatigue, one with ocular pain, and one for lifestyle reasons (P =.07). CONCLUSIONS: This study found similar efficacy and safety between monotherapy treatment with dorzolamide or brimonidine when each was given three times daily to patients with ocular hypertension or primary open-angle glaucoma.

Adrenergic alpha-Agonists↗
PubMed2000

Differences in ocular surface irritation between timolol hemihydrate and timolol maleate.

PURPOSE: We evaluated the anterior segment surface reaction findings between timolol hemihydrate and timolol maleate. The only known difference between these preparations is the maleate salt. METHODS: After a baseline examination, we randomized 28 healthy subjects (26 completed) to timolol hemihydrate or timolol maleate given in both eyes twice daily, in a double masked fashion, for 1 week. Subjects then were evaluated at the morning trough (hour 0 examination), dosed, and re-evaluated in 1 hour (hour 1 examination). Subjects were left untreated for 1 week and then switched to the opposite medication for the second study period. RESULTS: Corneal staining (graded 0 to 4) for timolol maleate was worse between baseline (0.9) and hour 0 (1.4; P =.009) and baseline and hour 1 (1.4; P =.011). Also, mean punctate corneal staining for timolol maleate was increased from baseline (22.6) to hour 0 (31.7; P =.033) and showed borderline significance to hour 1 (33.4; P =.058), and for timolol hemihydrate there was a borderline significant elevation from baseline (24.2) to hour 1 (29.8; P =.060). When treatment groups were compared, there was a greater change in corneal staining with timolol maleate than timolol hemihydrate from baseline to hour 0 (P =.020) and greater staining with timolol maleate than timolol hemihydrate at hour 0 (P =.032). Nasal conjunctiva showed increased mean staining with timolol maleate from baseline (23.6, P =.035) to hour 0 (29.5, P =.035) and to hour 1 (31.9 P =.038) but not with timolol hemihydrate. There were increased symptoms of ocular dryness from baseline to hour 0 with timolol maleate (P =.012) but not with timolol hemihydrate. CONCLUSIONS: The study suggests that timolol maleate potentially may have more of an irritant effect than timolol hemihydrate on the corneal and nasal conjunctival epithelium.

Adrenergic beta-Antagonists↗
PubMed2000

Therapeutic success of latanoprost 0.005% compared to brimonidine 0.2% in patients with open-angle glaucoma or ocular hypertension.

The purpose of this study was to evaluate the success rate ofmonotherapy with latanoprost 0.005% once daily versus brimonidine 0.2% twice daily in patients with open-angle glaucoma or ocular hypertension. Patients who were prescribed latanoprost or brimonidine as monotherapy were included in this study, and their consecutive charts were retrospectively reviewed. The primary efficacy variable was success of therapy, defined as a reduction in intraocular pressure > or =3 mm Hg without an adverse event leading to discontinuation over a potential of six months of therapy. We included 157 patients in this study. In the latanoprost group, 64 of 92 (70%) were considered successes; 26 of 65 (40%) were successful with brimonidine (P < 0.001). Nine failed brimonidine therapy, and one latanoprost, because of an adverse event, and the rest failed because of inadequate intraocular pressure response. The change from baseline in intraocular pressure was significantly greater with latanoprost (mean +/- S.D., 21.6 +/- 5.1 to 17.1 +/- 3.3 mm Hg) than brimonidine (23.7 +/- 5.6 to 21.9 +/- 5.7 mm Hg) (P = 0.001). Overall, 52 (80%) brimonidine- and 41 (45%) latanoprost-treated patients required additional visit(s) to adjust therapy to further lower intraocular pressure or to assess an adverse event (P < 0.001). In conclusion, latanoprost more likely provides a successful response to therapy than brimonidine when used as monotherapy in primary open-angle glaucoma or ocular hypertensive patients.

Adrenergic alpha-Agonists↗
PubMed2000

An immunoblot assay for detection of immunoglobulin M antibody to human herpesvirus 6.

We identified the human herpesvirus 6 (HHV-6)-dominant immunoglobulin M (IgM)-reactive virion protein as being the same 101-kDa protein (101K) previously identified as the major IgG immunoreactive protein and a specific serologic marker of HHV-6 infection. An immunoblot assay (IB) to detect HHV-6-specific IgM antibodies against the 101K protein in human serum samples was developed. The assay was validated by using acute- and convalescent-phase serum collected from children under 2 years of age in which we previously detected IgG seroconversion to the HHV-6 101K protein. Of 32 serum pairs which previously demonstrated IgG seroconversion to the 101K protein, 29 had IgM reactivity to the same protein in the acute-phase sample and the remaining 3 had reactivity in the convalescent-phase sample. We also detected HHV-6 IgM activity in sera collected from individuals > or =4 years of age who were also IgM seropositive to measles or rubella. Results of cross-adsorption studies using measles virus-, rubella virus-, and HHV-6-infected cells as the adsorbing antigen indicated no cross-reactivity between measles or rubella IgM and HHV-6 IgM in human serum samples. The IgM IB detected HHV-6-specific IgM antibody to the 101K protein in 78% (63 of 81) of tested acute-phase serum collected from young children with an undifferentiated rash illness by using a single serum dilution.

Antibodies, Viral↗
PubMed2000

Antithrombotic and antihypertensive management 3 months after ischemic stroke : a prospective study in an inner city population.

BACKGROUND AND PURPOSE: We sought to examine the frequency, predictors, and effects of nontreatment with antithrombotic and antihypertensive therapies 3 months after ischemic stroke. METHODS: The population-based South London Community Stroke Register prospectively collected data on first-in-a-lifetime strokes between 1995 and 1997. Among patients registered with ischemic stroke, treatment status with antithrombotic and antihypertensive therapies was examined 3 months after the event. RESULTS: In a cohort of 457 patients with ischemic stroke, 393 (86.0%) were considered appropriate for antiplatelet medication, 32 (7.0%) for anticoagulant medication, and 254 (55.9%) for antihypertensive medication. The rates of nontreatment observed 3 months after the event were 24.4% for antiplatelet, 59.4% for anticoagulant, and 29.5% for antihypertensive medication. Independent risk factors for nontreatment with antithrombotic therapies (antiplatelets and anticoagulants) were the subtype of stroke (nonlacunar infarct: OR=1. 60, 95% CI 1.07 to 2.54), stroke severity measured by the Glasgow Coma Scale (GCS) score (GCS </=13: OR 2.08, 95% CI 1.18 to 3.66) and the Barthel Index (BI) score 5 days after the event (BI </=10: OR 1. 85, 95% CI 1.17 to 2.93). For antihypertensive therapies the stroke subtype (OR 2.46, 95% CI 1.33 to 4.54), GCS score (OR 2.97, 95% CI 1. 35 to 6.53), BI score (OR 2.33, 95% CI 1.27 to 4.29), and ethnicity (Caucasian: OR 2.43, 95% CI 1.15 to 5.14) were independently associated with nontreatment. Cox regression modeling showed no significant association between the treatment status and recurrence-free 3-year survival rates after controlling for severity and subtype of stroke. CONCLUSIONS: Secondary prevention for a common disease such as stroke appears to be inadequate in the study area. Healthcare professionals need to consider antithrombotic and antihypertensive therapies for all stroke patients.

Adult↗
PubMed1999

Peptide nucleic acids targeted to the neurotensin receptor and administered i.p. cross the blood-brain barrier and specifically reduce gene expression.

Intraperitoneal injection of an unmodified antisense peptide nucleic acid (PNA) complementary to mRNA of the rat neurotensin (NT) receptor (NTR1) was demonstrated by a gel shift assay to be present in brain, thus indicating that the PNA had in fact crossed the blood-brain barrier. An i.p. injection of this antisense PNA specifically inhibited the hypothermic and antinociceptive activities of NT microinjected into brain. These results were associated with a reduction in binding sites for NT both in brain and the small intestine. Additionally, the sense-NTR1 PNA, targeted to DNA, microinjected directly into the brain specifically reduced mRNA levels by 50% and caused a loss of response to NT. To demonstrate the specificity of changes in behavioral, binding, and mRNA studies, animals treated with NTR1 PNA were tested for behavioral responses to morphine and their mu receptor levels were determined. Both were found to be unaffected in these NTR1 PNA-treated animals. The effects of both the antisense and sense PNAs were completely reversible. This work provides evidence that any antisense strategy targeted to brain proteins can work through i. p. delivery by crossing the normal blood-brain barrier. Equally important was that an antigene strategy, the sense PNA, was shown in vivo to be a potentially effective therapeutic treatment.

Animals↗
PubMed1999

Ethnic differences in incidence of stroke: prospective study with stroke register.

OBJECTIVE: To identify ethnic differences in the incidence of first ever stroke. DESIGN: A prospective community stroke register (1995-6) with multiple notification sources. Pathological classification of stroke in all cases was based on brain imaging or necropsy data. Rates were standardised to European and world populations and adjusted for age, sex, and social class in multivariate analysis. SETTING: A multi-ethnic population of 234 533 in south London, of whom 21% are black. RESULTS: 612 strokes were registered. The crude annual incidence rate was 1.3 strokes per 1000 population per year (95% confidence interval 1.20 to 1.41) and 1.25 per 1000 population per year (1.15 to 1.35) age adjusted to the standard European population. Incidence rates adjusted for age and sex were significantly higher in black compared with white people (P<0.0001), with an incidence rate ratio of 2.21 (1.77 to 2.76). In multivariable analysis increasing age (P<0.0001), male sex (P<0.003), black ethnic group (P<0.0001), and lower social class (P<0.0001) in people aged 35-64 were independently associated with an increased incidence of stroke. CONCLUSIONS: Incidence rates of stroke are higher in the black population; this is not explained by confounders such as social class, age, and sex. Ethnic differences in genetic, physiological, and behavioural risk factors for stroke require further elucidation to aid development of effective strategies for stroke prevention in multi-ethnic communities.

Adolescent↗
PubMed1999

Inhibitory control differences following mild head injury.

Complex inhibitory control, defined as the ability to inhibit a planned or ongoing action, was assessed in a sample of individuals with a history of mild head injury, case-matched with normal control subjects for age and gender. This central act of control was assessed using a modification of the stop-signal paradigm. The group with mild head injury took longer to inhibit their on going action and reported more accidents than the normal control subjects. The group that reported having had a mild head injury did not differ in terms of their go reaction time, number of correct responses, handedness, education level, or reported learning disabilities. Limitations of this design and directions for future research are discussed.

Adolescent↗
PubMed1999

A pilot study of melphalan, tumor necrosis factor-alpha and 41.8 degrees C whole-body hyperthermia.

PURPOSE: To evaluate the feasibilitv of sequencing (based on preclinical modeling) tumor necrosis factor-a (TNF) at two dose levels with melphalan (L-PAM) and 41.8 C whole-body hyperthermia (WBH) for 60 min. PATIENTS AND METHODS: Nine patients with refractory cancer were treated from October 1995 to June 1997. The study encompassed a total of 20 trimodality treatment courses. Three patients were treated at TNF dose level I (50 microg/m2) and six patients were treated at TNF dose level II (100 microg/m2). TNF was delivered as a 24-h intravenous infusion, 48 h prior to the combination of L-PAM and WBH; L-PAM was given over 10 min at target temperature at a dose of 17.5 mg/ m2 based on a previous phase I WBH/L-PAM trial. WBH was administered with an Aquatherm radiant heat device. RESULTS: Myelosuppression was the major toxicity associated with therapy, but there were no instances of bleeding or neutropenic fevers. Grade 3 thrombocytopenia was seen with 15% of treatments. Regarding absolute neutrophil count, 15% of treatments were associated with grade 3 toxicity, and 45% with grade 4 toxicity, and regarding white blood cell count, 50% of treatments were associated with grade 3 toxicity and 10% with grade 4 toxicity. The myelosuppression observed was equivalent to that seen in our earlier phase I study of WBH and L-PAM (without TNF). Only mild toxicities (grade 1 or 2) were associated with TNF; these were seen with <25% of treatments and included nausea, vomiting, diarrhea, fevers, and headache. There were no instances of hypotension. There was no relationship between toxicities observed and the two TNF dose levels. Mild WBH toxicities were seen with less than 15% of treatments; these included nausea, vomiting, and herpes simplex I. Responses included two complete remissions (malignant melanoma, TNF dose level I; breast cancer, TNF dose level II), and two disease stabilizations (both malignant melanoma, TNF dose level I). CONCLUSION: We conclude that the combination of TNF, L-PAM, and WBH is well tolerated at the dose levels studied. The clinical results justify further clinical investigation for this trimodality treatment approach.

Adult↗
PubMed1999

Efficacy and safety of timolol solution once daily vs timolol gel added to latanoprost.

PURPOSE: To compare the efficacy and safety of timolol hemihydrate 0.5% (Betimol, Ciba Vision Ophthalmics, Duluth, Georgia) vs timolol maleate gel-forming solution 0.5% (Timoptic-XE, Merck, Blue Bell, Pennsylvania), both given every morning added to latanoprost 0.005% given every evening. METHODS: A multicenter, randomized, crossover comparison was performed in patients with primary open-angle glaucoma or ocular hypertension. After at least a 4-week run-in period with latanoprost 0.005% (Xalatan, Pharmacia & Upjohn, Kalamazoo, Michigan), both eyes from 30 patients (60 eyes) were randomly assigned to one of the two adjunctive therapies, timolol hemihydrate or timolol maleate gel for 6 weeks. At the end of the first period, the study medicine was discontinued for a 2-week washout period. Patients then received the opposite medication for the second 6-week period. This study had an 80% power to exclude a 1-mm Hg difference between groups. RESULTS: The baseline intraocular pressure after 1 month of latanoprost treatment only for all 30 subjects was 20.8 +/- 2.6 mm Hg. After 6 weeks of timolol hemihydrate, the 24-hour trough intraocular pressure was 17.5 +/- 3.4 mm Hg, and for timolol maleate gel, 17.9 +/- 3.5 mm Hg (P = .74). The peak level 2 hours after dosing for timolol hemihydate was 16.4 +/- 2.6 mm Hg, and for timolol maleate gel, 16.8 +/- 3.8 mm Hg (P = .84). No patient was discontinued from the study because of lack of efficacy. No differences were observed between treatments in visual acuity, anterior segment findings, or adverse events. CONCLUSIONS: Once-daily beta-blocker therapy is an effective ocular hypotensive adjunctive treatment 24 hours after dosing when added to latanoprost, for which timolol hemihydrate 0.5% solution and timolol maleate gel 0.5% appear equally effective and safe.

Adolescent↗
PubMed1999

In vitro binding and CNS effects of novel neurotensin agonists that cross the blood-brain barrier.

Animal studies with neurotensin (NT) directly injected into brain suggest that it has pharmacological properties similar to those of antipsychotic drugs. Here, we present radioligand binding data for some novel hexapeptide analogs of NT(8-13) at the molecularly cloned rat and human neurotensin receptors (NTR-1), along with behavioral and physiological effects of several of these peptides after intraperitoneal (i.p.) administration in rats. One unique analog, NT66L, which had high affinity (0.85 nM) for the molecularly cloned rat neurotensin receptor (NTR-1), caused a drop in body temperature and antinociception at doses as low as 0.1 mg/kg after i.p. injection. At 30 min post-injection, the ED50 for NT66L-induced hypothermia (rectal temperature) and antinociception (hot plate test) was 0.5 and 0.07 mg/kg, respectively. At a dose of 1 mg/kg i.p., NT66L caused 100% of the maximum possible effect for antinociception for up to 2 h after administration. At this dose body temperature lowering was greater than -2.5 degrees C from 20 to 120 min after i.p. administration. These results in animals suggest that NT66L has agonist properties at NTR-1 in vivo after extracranial administration and provide support for its further study in behavioral tests predictive of neuroleptic activity.

Animals↗
PubMed1999

Time accuracy of a barcode system for recording resuscitation events: laboratory trials.

UNLABELLED: Barcode systems for recording clinical data from resuscitation attempts offer the prospect of more complete and time-accurate data collection; in addition, collection of data in digital form and the resulting ease of computer processing promises to facilitate data analysis for quality improvement and research. We conducted trials of such a barcode system, recording events during a videotaped, simulated in-hospital resuscitation, with particular attention to time accuracy. METHODS: Nine subjects watched a videotape of a simulated cardiac resuscitation, recording events first with the barcode system and then with a conventional handwritten form. Recorded times were compared to an accurate record of events (gold standard) from the videotape. RESULTS: Mean absolute errors and standard deviations of errors from the gold standard were significantly smaller with the barcode system (P < 0.01 for both). Numbers of event omissions did not differ significantly. CONCLUSION: The barcode system is more accurate than conventional handwritten recording in capturing event times from a simulated resuscitation. The system shows promise as a means to improve time accuracy of resuscitation records.

Cardiopulmonary Resuscitation↗
PubMed1999

Systemic beta-blockade with once daily Betimol or Timoptic-XE.

The purpose of this study was to evaluate the effect of timolol hemihydrate 0.5% (Betimol [THH], Ciba Vision Ophthalmics) and timolol maleate gel forming solution 0.5% (Timoptic-XE , [TXE], Merck, Inc.), when both are dosed once daily on the exercise performance. Maximum exercise heart rate reflects systemic beta-blockade activity. Fourteen healthy subjects were randomized to receive either placebo (HypoTears , Ciba Vision Ophthalmics), THH, or TXE by a Latin square technique in a three period crossover design. Subjects were dosed one drop every morning beginning three days before exercise testing. The interval between each test was one week. Exercise testing was performed two hours after dosing. Maximum exercise heart rate showed no statistical difference between TXE and THH (174 +/- 13.1 vs. 172 +/- 14.9 beats/min, respectively, P = 0.72). Both active treatments, however, decreased heart rate compared to placebo (185 +/- 7.3 beats/min, P = 0.017). Time to exhaustion showed no difference between groups (P > 0.10). The double product (product of heart rate and systolic blood pressure) did not show a difference between TXE and THH (P = 0.38) but was reduced compared to placebo (P = 0.0053). One subject on TXE was discontinued from the study after the first exercise test because of secondary heart block during the recovery period. It was concluded that TXE and timolol hemihydrate solution show similar systemic beta-blockade activity when both are dosed once a day.

Adrenergic beta-Antagonists↗
PubMed1999

Multicenter comparison of PCR assays for detection of human herpesvirus 8 DNA in semen.

Reported prevalences of human herpesvirus 8 (HHV-8) (Kaposi's sarcoma-associated herpesvirus) in semen have ranged widely. This is possibly due to differences in assay sensitivity, geographic or population-based differences in the true presence of the virus in semen, and PCR contamination. This study assessed interlaboratory sensitivity and reproducibility in the analysis of blinded experimental panels, each consisting of 48 specimens and being composed of semen specimens from different healthy artificial-insemination donors (n = 30) and human immunodeficiency virus (HIV)-infected patients (n = 7) plus positive (n = 4) and negative (n = 7) controls. The experimental panels analyzed in each laboratory were identical except for being independently coded. Of 10 experiments done in five laboratories, 5 experiments from three laboratories had evidence of PCR contamination; all instances of contamination were in the context of nested PCR procedures. In the experiments with no false-positive results, HHV-8 DNA was detected in three (8%) of the 37 semen specimens (two from artificial-insemination donors and one from an HIV-positive patient) but in only 3 (1.6%) of the 184 PCRs in which these specimens were analyzed. This suggests that HHV-8 DNA is present in semen at concentrations that can be too low to allow its consistent detection. This study emphasizes the importance of performing blinded, multi-institution experiments to provide a coherent basis for comparing results and to motivate standardization of methods.

DNA, Viral↗