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Biomedical subjects

J Wolfe

Publications and source records attributed to J Wolfe.

At least 55 records · Page 3Linked to original sources

Relationships among trauma exposure, chronic posttraumatic stress disorder symptoms, and self-reported health in women: replication and extension.

Fifty-two women who served during the Vietnam era were assessed for war-zone exposure, traumatic life events, post-traumatic stress disorder (PTSD), and self-reported health status. Symptoms of PTSD were examined as mediators in the relationship between traumatic exposure and subsequent reports of health problems. Results showed that PTSD symptoms accounted significantly for variance in health problems reported by women with prior traumatic stressor exposure. When the cardinal symptom domains of PTSD (re-experiencing, numbing, avoidance, hyper-arousal) were analyzed separately, the symptom cluster representing hyper-arousal accounted uniquely for the variance associated with health complaints, beyond that contributed by other symptom clusters. Discussion of the results focuses on mechanisms underlying the relationship between specific symptoms of PTSD and self-reported health. Implications for intervention within the medical system are also considered.

Adult↗

Posttraumatic stress disorder and retrospectively reported stressor exposure: a longitudinal prediction model.

There has been recent concern about the degree to which posttraumatic stress disorder (PTSD) symptomatology influences reports of prior exposure to highly stressful life events. In this longitudinal study of 2,942 male and female Gulf War veterans, the authors documented change in stressor reporting across 2 occasions and the association between change and PTSD symptom severity. A regression-based cross-lagged analysis was used to examine the relationship between PTSD symptom severity and later reported stressor exposure. Shifts in reporting over time were modestly associated with PTSD symptom severity. The cross-lagged analysis revealed a marginal association between Time 1 PTSD symptom severity and Time 2 reported stressor exposure for men and suggested that later reports of stressor exposure are primarily accounted for by earlier reports and less so by earlier PTSD symptomatology.

Adult↗

Effects of bone marrow transplantation on the cardiovascular abnormalities in canine mucopolysaccharidosis VII.

The genetic mucopolysaccharidoses (MPS) are a family of lysosomal storage diseases resulting from defective catabolism of glycosaminoglycans (GAGs). Echocardiographic abnormalities in dogs with MPS type VII (Sly syndrome, beta-glucuronidase deficiency) included mitral valve thickening and insufficiency, large aortic dimensions in both the long and short axes, and thickened aortic valves. Grossly, at post mortem examination, there was nodular thickening of the mitral valve, a prominent ductus diverticulum, and a dilated aorta with thickened walls. Histologically, cytoplasmic vacuolation was seen in cells of the mitral valves, coronary arteries, and aorta. By electron microscopy, the cells of the mitral valve were packed with electron-lucent cytoplasmic vacuoles. The mean residual activity of beta-glucuronidase in the aorta and myocardium was <1% of normal, the mean hexosaminidase A activity >2. 5 times normal, and the mean GAG concentrations more than twice normal. In three MPS VII dogs that received heterologous BMT at 6 weeks of age, the echocardiographic abnormalities were improved, and the histopathologic and ultrastructural pathology was reduced. In the aorta and myocardium, the mean beta-glucuronidase activity of the BMT group was 4.5% and 11% of normal, respectively, and the hexosaminidase A activity and GAG concentrations were normalized. Bone Marrow Transplantation (2000) 25, 1289-1297.

Animals↗

Comparison of once- and twice-daily dosing of fluticasone propionate 200 micrograms per day administered by diskus device in patients with asthma treated with or without inhaled corticosteroids.

BACKGROUND: There are limited published data regarding the efficacy of once- versus twice-daily administration of flutica-sone propionate. OBJECTIVE: Our purpose was to evaluate the effectiveness of fluticasone propionate powder 200 microg/d administered as a once- or twice-daily dosage regimen in patients who were currently being treated with bronchodilators only (BD patients) and in patients who required inhaled corticosteroids for maintenance treatment of asthma (ICS patients). METHODS: Five hundred seventy patients were randomly assigned to receive one of the following inhaled treatments through the Diskus device (Glaxo Wellcome, Research Triangle Park, NC) for 12 weeks: fluticasone propionate 100 microg twice daily (FP100BID) or 200 microg once daily (FP200QD) or placebo. RESULTS: BD patients treated with FP100BID, FP200QD, and placebo had mean increases in FEV(1) from baseline to end point of 0. 49 L, 0.37 L, and 0.21 L, respectively (P <.001, FP100BID vs placebo; P =.05, FP200QD vs placebo). ICS patients treated with FP100BID and FP200QD had mean increases in FEV(1) of 0.27 L and 0.11 L, respectively, compared with a decrease in FEV(1) of -0.08 L with placebo (P <.001, FP100BID vs placebo; P =.023, FP200QD vs placebo). BD patients treated with FP100BID and FP200QD had mean increases in morning peak expiratory flow from baseline to end point of 31 L/min and 27 L/min, respectively, compared with a 1 L/min increase in patients treated with placebo. ICS patients treated with FP100BID had a mean increase in morning peak expiratory flow (from baseline to end point) of 18 L/min compared with mean decreases of -3 L/min and -12 L/min in the FP200QD and placebo groups, respectively. More patients were withdrawn from placebo (26% and 48%, in BD and ICS patients, respectively) than from fluticasone propionate (7%-9% [BID-QD] and 18%-32% [BID-QD], in BD and ICS patients, respectively) because of failure to meet predetermined asthma stability criteria. CONCLUSION: The efficacies of FP100BID and FP200QD were comparable with regard to improvement in pulmonary function and asthma stability in BD patients. In ICS patients, asthma control was maintained with FP200QD, whereas FP100BID provided greater improvements in pulmonary function and asthma stability.

Administration, Inhalation↗

Mycobacterium branderi from both a hand infection and a case of pulmonary disease.

Mycobacterium branderi, a potential human pathogen first characterized in 1995, has been isolated from respiratory tract specimens. We report here a case in which M. branderi was the only organism isolated upon culture from a hand infection. This isolate, along with a second isolate from a bronchial specimen, was subjected to conventional identification tests for mycobacterial species. Further analysis by high-performance liquid chromatography (HPLC) of mycolic acids and 16S rRNA gene sequencing was performed, and the antibiotic susceptibility profile was determined for both strains. Biochemical tests and the HPLC pattern were consistent with that of M. branderi and M. celatum, which are very similar. The 16S rRNA gene sequence of both strains corresponded to that of M. branderi and enabled us to confidently differentiate this organism from other closely related species such as M. celatum. This contributes to a further understanding of the status of this species as a potential human pathogen as well as illustrating the need for molecular diagnostics as a complementary method for the identification of rare mycobacterial species.

Chromatography, High Pressure Liquid↗

Evaluation of recA sequences for identification of Mycobacterium species.

16S rRNA sequence data have been used to provide a molecular basis for an accurate system for identification of members of the genus Mycobacterium. Previous studies have shown that Mycobacterium species demonstrate high levels (>94%) of 16S rRNA sequence similarity and that this method cannot differentiate between all species, i.e., M. gastri and M. kansasii. In the present study, we have used the recA gene as an alternative sequencing target in order to complement 16S rRNA sequence-based genetic identification. The recA genes of 30 Mycobacterium species were amplified by PCR, sequenced, and compared with the published recA sequences of M. tuberculosis, M. smegmatis, and M. leprae available from GenBank. By recA sequencing the species showed a lower degree of interspecies similarity than they did by 16S rRNA gene sequence analysis, ranging from 96.2% between M. gastri and M. kansasii to 75.7% between M. aurum and M. leprae. Exceptions to this were members of the M. tuberculosis complex, which were identical. Two strains of each of 27 species were tested, and the intraspecies similarity ranged from 98.7 to 100%. In addition, we identified new Mycobacterium species that contain a protein intron in their recA genes, similar to M. tuberculosis and M. leprae. We propose that recA gene sequencing offers a complementary method to 16S rRNA gene sequencing for the accurate identification of the Mycobacterium species.

Genes, Bacterial↗

Combined salmeterol 50 microg and fluticasone propionate 250 microg in the diskus device for the treatment of asthma.

Three hundred forty-nine patients with asthma previously treated with medium doses of inhaled corticosteroids during a 2-wk, single-blind, run-in period were randomized to treatment with salmeterol 50 microg combined with fluticasone propionate (FP) 250 microg, salmeterol 50 microg, FP 250 microg, or placebo, each given twice daily through a Diskus device for 12 wk. Mean change in FEV(1) at endpoint was significantly (p </= 0.001) greater with the salmeterol/FP combination product (0.48 L) than with placebo (-0.11 L), salmeterol (0.05 L), or FP (0.25 L). The combination product significantly increased the area under the 12-h serial FEV(1) curve relative to baseline over that with placebo, salmeterol, or FP at Day 1, Week 1, and Week 12 (p </= 0.025). Patients in the combination-product group had a significantly greater probability of remaining in the study without being withdrawn because of worsening asthma than did patients in the placebo, salmeterol, or FP groups (p </= 0.002). The combination product significantly increased (p < 0. 001) morning PEF at endpoint (53.5 L/min) as compared with placebo (-14 L/min), salmeterol (-11.6 L/min), or FP (15.2 L/min). The combination product significantly (p </= 0.011) reduced asthma symptom scores and supplemental albuterol use, and significantly increased the percentage of nights with no awakenings as compared with placebo, salmeterol, and FP (p </= 0.016). Combination treatment with salmeterol 50 microg and FP 250 microg given twice daily from the Diskus device provided better asthma control and greater improvement in pulmonary function than did the individual agents, and may simplify the management of asthma in patients who need both classes of drugs for optimal control of their disease.

Adolescent↗

Relative importance of rate and place: experiments using pitch scaling techniques with cochlear implants recipients.

Pitch scaling was used to determine the dependence of perceived pitch on rate and place of stimulation in postlingually deafened adult subjects using cochlear implants. For stimulation rates below about 500 pulses per second (pps), perceived pitch is a strong function of both rate and place. In this range, perceived pitch increases logarithmically with stimulation rate, but decreases with distance from the round window. A 2-mm displacement into the cochlea has an effect similar to that of halving the stimulation rate. Place resolution in this context is comparable with the interelectrode spacing (0.75 mm). At rates approaching 1,000 pps, rate has little effect on perceived pitch. An average of bipolar quality judgments showed that periodic pulsatile stimulation is least pleasant when low frequencies are applied to the region closest to the window.

Adult↗

A strategy for vascular services--testing the 600,000 population model.

BACKGROUND: Vascular services' delivery has been criticised, and re-organisation based on a 600,000 population model suggested. We assessed the feasibility of this model in three geographically disparate English regions. METHODS: Surgical arterial activity by Trust was analyzed using 1994/95 data from Hospital Episode Statistics. A postal survey of acute Trusts was used to assess vascular facilities and personnel. Distances between hospitals and enumeration districts were mapped using a Geographical Information System. MAIN OUTCOME MEASURES: Number (proportion) of Trusts performing over 100 arterial procedures a year. Number (proportion) of Trusts with a vascular on-call rota. Proportion of population likely to live more than 40 km away (equivalent to 1 h blue-light ambulance travel time) from a vascular unit under the proposed model. RESULTS: Twelve of the 32 Trusts (38%) performed over 100 arterial procedures annually; 23 Trusts completed the survey. Of these, five (22%) had a vascular on-call rota. Under the 600,000 model, in East Anglia a further 16.5% of the population would live > 40 km from a vascular unit. In Wessex, a further 0.4% of the population would live > 40 km from a vascular unit. Impact on access in North West Thames was negligible. CONCLUSIONS: A 600,000 population model could be feasible in urbanized regions, but not in geographically remote ones.

Delivery of Health Care↗

Coping with Gulf War combat stress: mediating and moderating effects.

The authors examined relationships between method of coping with combat-related stress and psychological symptoms among Gulf War Army personnel (N = 1,058). Participants were surveyed on return from the Gulf region (Time 1) with the Coping Responses Inventory (R. Moos, 1990) and a measure of combat exposure. Outcomes were symptom measures of posttraumatic stress disorder (PTSD) and depression. At Time 2 (18-24 months) participants completed the same symptom measures and an index of postwar stress. Higher proportions of approach-based coping in the war zone were related to lower levels of psychological symptoms. Combat exposure moderated the effects of coping on Time 1 PTSD. Coping predicted changes in symptoms of depression but not PTSD. Combat exposure affected changes in depression through postwar stress but had a direct negative effect on PTSD.

Adaptation, Psychological↗

Burst pressure of canine carotid arteries.

The burst pressure was measured on 40 freshly excised, unstretched carotid arteries derived from dogs ranging in weight from 20-25 kg. Each carotid artery specimen was tied to the nozzle of a high-pressure nitrogen tank and regulator. The pressure was slowly increased until the artery burst. The burst pressure ranged from 2400 to 6500 mmHg, a value well above typical mammalian systolic pressure.

Animals↗

Changing demographic characteristics of women veterans: results from a national sample.

Women veterans are a small but growing percentage of the U.S. veteran population. There are some indications that, along with this increase, the characteristics and military experiences of younger women veterans differ considerably from those of older colleagues. Many of these characteristics are not well defined, but they could have implications for women's health care needs and health policy initiatives. Using the first sample drawn from the Department of Veterans Affairs' new National Registry of Women Veterans, we designed and administered a telephone survey to a representative sample of women veterans across several major age groups. Groups approximated primary eras of military and wartime service based on the assumption that different eras might be associated with differing military experiences. We found a number of age-related similarities and differences in women veterans' demographic characteristics, military experiences, physical health symptoms, and functional outcomes. Women veterans in general also differed from female civilian counterparts on exposure to sexual trauma. Trends in the population of women veterans are likely to have implications for the variety of health care systems that treat women veterans.

Adult↗

Psychophysiologic assessment of posttraumatic stress disorder in Vietnam nurse veterans who witnessed injury or death.

This study examined whether witnessing death and injury could produce psychophysiologically responsive posttraumatic stress disorder (PTSD). Participants consisted of medication-free female Vietnam nurse veterans with a diagnosis of current PTSD (n = 17) and who never had PTSD (n = 21), related to their military service. Individualized scripts describing personal traumatic military nursing events, a standard military nursing event, and other life events were tape recorded and played back to the participant while heart rate, skin conductance, and facial electromyograms were recorded. Nurses with PTSD showed significantly larger physiologic responses than non-PTSD nurses only during imagery of military-related nursing events. The groups' self-reported emotional responses did not differ during imagery. Psychophysiologic results support the proposition that witnessing death and serious injury to others is sufficiently stressful to cause PTSD.

Analysis of Variance↗

Clustered cadherin genes: a sequence-ready contig for the desmosomal cadherin locus on human chromosome 18.

We describe the assembly of a cosmid and PAC contig of approximately 700 kb on human chromosome 18q12 spanning the DSC and DSG genes coding for the desmocollins and desmogleins. These are members of the cadherin superfamily of calcium-dependent cell adhesion proteins present in the desmosome type of cell junction found especially in epithelial cells. They provide the strong cell-cell adhesion generated by this type of cell junction for which expression of both a desmocollin and a desmoglein is required. In the autoimmune skin diseases pemphigus foliaceous and pemphigus vulgaris (PV), where the autoantigens are, respectively, encoded by the DSG1 and DSG3 genes, severe areas of acantholysis (cell separation), potentially life-threatening in the case of PV, are evident. Dominant mutations in the DSG1 gene causing striate palmoplantar keratoderma result in hyperkeratosis of the skin on the parts of the body where pressure and abrasion are greatest, viz., on the palms and soles. These genes are also candidate tumor suppressor genes in squamous cell carcinomas and other epithelial cancers. We have screened two chromosome 18-specific cosmid libraries by hybridization with previously isolated YAC clones and DSC and DSG cDNAs, and a whole genome PAC library, both by hybridization with the YACs and by screening by PCR using cDNA sequences and YAC end sequence. The contigs were extended by further PCR screens using STSs generated by vectorette walking from the ends of the cosmids and PACs, together with sequence from PAC ends. Despite screening of two libraries, the cosmid contig still had four gaps. The PAC contig filled these gaps and in fact covered the whole locus. The positions of 45 STSs covering the whole of this region are presented. The desmocollin and desmoglein genes, which are about 30-35 kb in size, are quite well separated at approximately 20-30 kb apart and are arranged in two clusters, one DSC cluster and one DSG cluster, which are transcribed outward from the interlocus region. The order of the genes is correlated with the spatial order of gene expression in the developing mouse embryo, and this, and previous transgenic experiments, suggests that long-range genetic elements that coordinate expression of these genes may be present. The complete bacterial clone contig described in this paper is thus a resource not only for future sequencing but also for investigations into the control of expression of these clustered genes.

Bacteriophage P1↗

Protein conjugates of synthetic saccharides elicit higher levels of serum IgG lipopolysaccharide antibodies in mice than do those of the O-specific polysaccharide from Shigella dysenteriae type 1.

Our development of vaccines to prevent shigellosis is based on the hypothesis that a critical (protective) level of serum IgG to the O-specific polysaccharide (O-SP) domain of Shigella lipopolysaccharide (LPS) confers immunity. The O-SP is a hapten and must be conjugated to a protein to induce serum antibodies. The O-SP of Shigella dysenteriae type 1 (approximately 27 tetrasaccharide repeat units), prepared by acid hydrolysis of the LPS, was bound to human serum albumin (HSA) by multiple point attachment (O-SP-HSA): The molar ratio of HSA to O-SP was 1.0. Synthetic saccharides, composed of one or multiples of the O-SP tetrasaccharide, equipped with a spacer at their reducing end, were bound to HSA by a single point attachment: The average molar ratios of the saccharides to HSA ranged from 4 to 24. Serum IgG anti-LPS, elicited in mice by O-SP-HSA or synthetic tetra-, octa-, dodeca-, and hexadecasaccharide fragments, was measured by ELISA. Outbred 6-week-old female mice were injected s.c. three times at biweekly intervals with 2.5 micrograms of saccharide as a conjugate and were bled 7 days after the second and third injections. Excepting the tetramer, conjugates of the octamer, dodecamer and hexadecamer elicited IgG LPS antibodies after the second injection, a statistically significant rise (booster) after the third injection, and higher levels than those vaccinated with O-SP-HSA (P = 0.0001). The highest geometric mean levels of IgG anti-LPS were elicited by the hexadecamer with 9 chains or 9 moles of saccharide/HSA (15.5 ELISA units) followed by the octamer with 20 chains (11.1 ELISA units) and the dodecamer with 10 chains (9.52 ELISA units). Clinical evaluation of these synthetic saccharides bound to a medically useful carrier is planned.

Animals↗

Compliance, elastic modulus, and burst pressure of small-intestine submucosa (SIS), small-diameter vascular grafts.

Small-intestine submucosa (SIS) is cell-free collagen, 100 mu thick, derived from the small intestine. It has been used as a vascular graft and has the highly desirable property of remodeling itself to become host tissue. To date there has been limited reporting on its preimplantation mechanical properties as a vascular graft. In this study, compliance, elastic modulus, and burst pressure have been measured on 5- and 8-mm SIS grafts. The compliance (percent of diameter increase for a pressure rise from 80 to 120 mmHg) was 4.6% av (range 2.9 to 8.6%) for the 5-mm grafts. For the 8-mm graft, the increase in diameter for the same pressure rise was 8.7% av (range 7.2 to 9.5%). The modulus of elasticity (E) increased exponentially with increasing pressure according to E = E(o)e(alphaP), where Eo is the zero-pressure modulus and alpha is the exponent that describes the rate of increase in E with pressure; the units for E, Eo, and P are g/cm2. The mean value for Eo was 4106 (g/cm2 range 1348-5601). The mean value for alpha was 0.0059 (range 0.0028-0.0125). At 100 mmHg, the mean value for E was 8.91 x 10(3) g/cm2 (range 1.02-8.80 x 10(3)). The mean burst pressure for 5.5-mm grafts was 3517 mm Hg (range 2069-4654). In terms of preimplant compliance, the small-diameter SIS graft is about (1/2) as compliant as the dog carotid artery, about four times more compliant than a typical vein graft, and more than an order of magnitude more compliant than synthetic vascular grafts.

Animals↗

Cell pairing and methylation in Tetrahymena thermophila are altered by exogenous homocysteine.

Homocysteine is causally associated with birth defects such as spina bifida, and with premature vascular disease. We have investigated the effects of homocysteine on a cell-cell interaction in a fundamental eukaryotic system, the free-living ciliate Tetrahymena. Exogenously added homocysteine inhibits cell pairing in a dose-dependent manner. These effects are exacerbated by adenosine, which by itself has little demonstrable influence on pairing. S-adenosylhomocysteine (SAH) is a product of the reaction between adenosine and homocysteine, and is an inhibitor of methyl transferases. We therefore predicted that protein methylation would be significantly inhibited by homocysteine. A direct test of that hypothesis involved a demonstration that incorporation of an isotopically labeled methyl group from methionine into proteins was significantly reduced by homocysteine. The undermethylated proteins are of low molecular weight, and might correspond to known methylatable signaling proteins. We show that vanadate, an inhibitor of protein phosphatase, also inhibits cell pairing, and that the effects of vanadate and homocysteine are additive. This is the first demonstration that methylation and possibly phosphorylation play a regulatory role in cell-cell interactions in ciliates.

Animals↗