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Biomedical subjects

J Wolfe

Publications and source records attributed to J Wolfe.

At least 37 records · Page 2Linked to original sources
PubMed2001

Adequacy of pain assessment and pain relief and correlation of patient satisfaction in 68 ED fast-track patients.

INTRODUCTION: The new standards of the joint commission on accreditation of healthcare organizations specify the patient's right to appropriate assessment and management of pain. With this impetus, we looked at our own practice to see how well we assess and manage patients with pain. METHODS: Patients who presented with minor nonemergent pain were interviewed on arrival, and then again before discharge, with use of a structured questionnaire. A total of 68 completed pain surveys were analyzed. RESULTS: With use of a visual analog scale, patients rated their pain on arrival and at discharge; they also rated pain they were willing to accept when it was time for discharge. Sixty percent of the patients went home with more pain than they were willing to accept. Fifty-one percent of the patients were offered something for pain, and only half of them said the pain relief was adequate. The median time from arrival to administration of pain medication was 104 minutes. Surprisingly, the median patient satisfaction rating for overall care was "very good." DISCUSSION: This survey revealed that acute pain conditions are underevaluated and undertreated in one fast-track setting, suggesting that ED staff need more education about the management of acute pain. It also showed that relying on patient satisfaction surveys as surrogate markers for how well we manage pain is erroneous.

Acute Disease↗
PubMed2001

Optimization of hammerhead ribozymes for the cleavage of S100A4 (CAPL) mRNA.

Previously, suppression of the S100A4 mRNA by an endogenously expressed ribozyme in osteosarcoma cells was shown to inhibit their metastasis in rats. As a prelude to performing similar studies with exogenous, synthetic ribozymes, we compared a series of hammerhead ribozymes targeted against different sites in the mRNA. The ribozymes differed only in the 7-base flanking sequences complementary to the substrate and were protected against nucleases by chemical modification. Cleavage efficiency varied widely and was not obviously related to the predicted secondary structure of the target RNA. The most active ribozyme of the series was chosen for further optimization. Lengthening its flanking sequences was counterproductive and reduced cleavage even when using excess ribozyme. Using excess substrate (multiple-turnover kinetics), cleavage was fastest with the (6+8) ribozyme having 6 nucleotides (nt) in stem III and 8 nt in stem I. Although these stems strongly influence ribozyme performance, their optimization is still empirical. Faster cleavage was obtained by adding facilitator oligonucleotides to ribozymes with shorter stems of (6+6) and (5+5) nt. Stimulation was particularly strong in the case of the (5+5) ribozyme, which was poorly active by itself. The enhancement caused by different facilitator oligonucleotides paralleled their expected ability to hybridize to RNA as a function of length and chemical modification.

Antineoplastic Agents↗
PubMed2001

Chemical sensitivity and chronic fatigue in Gulf War veterans: a brief report.

The foci of this brief report are to (1) describe the prevalence of chemical sensitivity (CS) and chronic fatigue (CF) symptomatology and of presumptive multiple CS and CF syndrome diagnoses, and (2) explore the potential overlap between one purported case definition (i.e., chronic multi-symptom illness) and these unexplained symptom syndromes in a well-characterized group of Gulf War veterans. The number of subjects with CS and CF symptomatology and presumptive multiple CS and CF syndrome diagnoses was higher in the Gulf War-deployed group compared with a group deployed to Germany during the Gulf War. However, the percent differences were not significant when comparing the presumptive diagnoses of multiple CS and CF syndrome. The characteristic differences between the groups and the overlap with chronic multi-symptom illness are also discussed.

Adult↗
PubMed2001

Antiviral efficacy and pharmacokinetics of oral adefovir dipivoxil in chronically woodchuck hepatitis virus-infected woodchucks.

The antiviral efficacy of orally administered adefovir dipivoxil was evaluated in an 18-week study (12 weeks of treatment and 6 weeks of recovery) conducted with woodchucks chronically infected with woodchuck hepatitis virus (WHV). Adefovir dipivoxil is a prodrug of adefovir designed to enhance its oral bioavailability. Following administration of 15 mg of adefovir dipivoxil per kg of body weight in four WHV-infected animals, the mean maximum concentration of adefovir in serum was 0.462 microg/ml, with an elimination half-life of 10.2 h, and the oral bioavailability of adefovir was estimated to be 22.9% (+/-11.2%). To study antiviral efficacy, the animals were divided into three groups. There were six animals each in a high-dose group (15 mg/kg/day) and a low-dose group (5 mg/kg/day). A vehicle control group consisted of five animals because WHV DNA was detectable only by PCR at the time of the study in one of the original six animals. Efficacy was evaluated by determining the levels of WHV DNA in serum. The geometric mean WHV DNA level for the high-dose group diminished by >40-fold (>1.6 log(10)) after 2 weeks of treatment and >300-fold (>2.5 log(10)) at 12 weeks. There was a >10-fold reduction in five of six low-dose animals by 2 weeks, but levels were unchanged in one animal. By 12 weeks of treatment there was a >45-fold (>1.6 log(10)) reduction of WHV DNA levels, and serum WHV DNA levels were below the limit of quantification in three of six animals. Viral DNA levels returned to pretreatment levels during the 6-week recovery period. There were no clinically significant changes in body weight, hematology, or serum chemistry values, including bicarbonate or lactate, in any of the treated animals. No histologic evidence of liver injury was apparent in the biopsies. Under the conditions of this study, adefovir dipivoxil was an effective antihepadnaviral agent.

Adenine↗
PubMed2001

Necessity of quality-controlled 16S rRNA gene sequence databases: identifying nontuberculous Mycobacterium species.

The use of the 16S rRNA gene for identification of nontuberculous mycobacteria (NTM) provides a faster and better ability to accurately identify them in addition to contributing significantly in the discovery of new species. Despite their associated problems, many rely on the use of public sequence databases for sequence comparisons. To best evaluate the taxonomic status of NTM species submitted to our reference laboratory, we have created a 16S rRNA sequence database by sequencing 121 American Type Culture Collection strains encompassing 92 species of mycobacteria, and have also included chosen unique mycobacterial sequences from public sequence repositories. In addition, the Ribosomal Differentiation of Medical Microorganisms (RIDOM) service has made freely available on the Internet mycobacterial identification by 16S rRNA analysis. We have evaluated 122 clinical NTM species using our database, comparing >1,400 bp of the 16S gene, and the RIDOM database, comparing approximately 440 bp. The breakdown of analysis was as follows: 61 strains had a sequence with 100% similarity to the type strain of an established species, 19 strains showed a 1- to 5-bp divergence from an established species, 11 strains had sequences corresponding to uncharacterized strain sequences in public databases, and 31 strains represented unique sequences. Our experience with analysis of the 16S rRNA gene of patient strains has shown that clear-cut results are not the rule. As many clinical, research, and environmental laboratories currently employ 16S-based identification of bacteria, including mycobacteria, a freely available quality-controlled database such as that provided by RIDOM is essential to accurately identify species or detect true sequence variations leading to the discovery of new species.

Databases, Nucleic Acid↗
PubMed2001

Identification of Mycobacterium species by multiple-fluorescence PCR-single-strand conformation polymorphism analysis of the 16S rRNA gene.

Identification of mycobacteria to the species level by growth-based methodologies is a process that has been fraught with difficulties due to the long generation times of mycobacteria. There is an increasing incidence of unusual nontuberculous mycobacterial infections, especially in patients with concomitant immunocompromised states, which has led to the discovery of new mycobacterial species and the recognition of the pathogenicity of organisms that were once considered nonpathogens. Therefore, there is a need for rapid and sensitive techniques that can accurately identify all mycobacterial species. Multiple-fluorescence-based PCR and subsequent single-strand conformation polymorphism (SSCP) analysis (MF-PCR-SSCP) of four variable regions of the 16S rRNA gene were used to identify species-specific patterns for 30 of the most common mycobacterial human pathogens and environmental isolates. The species-specific SSCP patterns generated were then entered into a database by using BioNumerics, version 1.5, software with a pattern-recognition capability, among its multiple uses. Patient specimens previously identified by 16S rRNA gene sequencing were subsequently tested by this method and were identified by comparing their patterns with those in the reference database. Fourteen species whose SSCP patterns were included in the database were correctly identified. Five other test organisms were correctly identified as unique species or were identified by their closest relative, as they were not in the database. We propose that MF-PCR-SSCP offers a rapid, specific, and relatively inexpensive identification tool for the differentiation of mycobacterial species.

DNA Primers↗
PubMed2001

Health-related quality of life in Persian Gulf War Veterans.

OBJECTIVE: The objective of this investigation is to describe the health-related quality of life of Persian Gulf War (GW) veterans and to examine the effects of current chronic medical conditions and psychiatric status on physical functioning. METHODS: To measure health-related quality of life, the Medical Outcomes Short Form Survey (SF36) was administered approximately 4 years after the GW to a stratified, random sample of New England-area GW-deployed veterans and a group of military personnel deployed to Germany during the GW. The SF36 scores for the GW-deployed study population (N = 141) were compared with those for the Germany-deployed group (N = 46) and with published U.S. population norms. Multiple linear regression analyses were performed to identify risk factors associated with lower physical health functioning in the GW-deployed study group. RESULTS: Functional health status was significantly lower in the GW-deployed group compared with the Germany-deployed group for each of the SF36 subscales and the two summary scores (Physical Component Summary [PCS] and Mental Component Summary). Compared with the general U.S. population, the GW-deployed group median was between the 25th and 50th percentile for the Physical Functioning subscale and the PCS score. Within the GW-deployed group, lower education, psychological symptomatology, and a higher number of chronic self-reported medical conditions were significant predictors of the PCS score. CONCLUSION: GW-deployed veterans report lower functional health status compared with a group of Germany-deployed veterans and published general U.S. population norms. Within the group of GW-deployed veterans, several current medical and psychological conditions predictive of lower physical functioning levels were identified.

Adult↗
PubMed2001

Fluticasone propionate compared with zafirlukast in controlling persistent asthma: a randomized double-blind, placebo-controlled trial.

OBJECTIVE: The objective of our study was to compare the efficacy and safety of fluticasone propionate (an inhaled corticosteroid) with zafirlukast (a leukotriene modifier) for persistent asthma. STUDY DESIGN: In this randomized placebo-controlled, parallel-group, double-blind, double-dummy trial, patients underwent an 8- to 14-day run-in period followed by 12 weeks of treatment with inhaled fluticasone propionate (88 mg twice daily by metered-dose inhaler), oral zafirlukast (20 mg twice daily), or placebo. POPULATION: We included a total of 338 persistent asthma patients, 12 years of age or older, using short-acting b2-agonists alone. OUTCOMES: measured Efficacy outcomes included changes in pulmonary function, asthma symptoms, rescue albuterol use, nighttime awakenings due to asthma, and quality of life. Safety outcomes included asthma exacerbations, adverse events, and clinically significant laboratory test results. RESULTS: After 12 weeks of treatment, patients taking fluticasone propionate experienced significantly greater improvements in all clinical parameters (symptom scores, percentages of symptom-free and albuterol-free days, albuterol use, and nighttime awakenings) compared with patients taking zafirlukast (P <.05) or placebo (P <.05). Treatment with fluticasone propionate resulted in significantly greater improvements in pulmonary function compared with zafirlukast (P <.05) or placebo (P <.05). Fewer fluticasone propionate patients (4%) had an exacerbation requiring oral corticosteroids compared with those taking zafirlukast (12%) or placebo (10%). CONCLUSIONS: Inhaled fluticasone propionate is more effective than zafirlukast in controlling asthma symptoms, improving pulmonary function, and improving quality of life for patients who are symptomatic with the use of short-acting b2-agonists alone.

Administration, Inhalation↗
PubMed2001

Randomized controlled trial of the tolerability, safety, and efficacy of adapalene gel 0.1% and tretinoin microsphere gel 0.1% for the treatment of acne vulgaris.

A prior meta-analysis of 5 randomized controlled trials indicates that adapalene gel 0.1% is as effective as tretinoin gel 0.025% against acne and has greater tolerability. To determine the tolerability and efficacy of adapalene gel 0.1% versus tretinoin microsphere gel 0.1% in 168 patients with acne vulgaris, we conducted a 12-week, multicenter, randomized, controlled, investigator-masked, parallel-group design study. Efficacy variables included noninflammatory, inflammatory, and total lesion counts; global grade; and global assessment of improvement in acne severity. Skin tolerability variables included erythema, desquamation (scaling), dryness, pruritus, and stinging/burning. Our results showed that the efficacy of adapalene gel 0.1% was comparable to that of tretinoin microsphere gel, and both treatments had similar onset of action. Cutaneous tolerability was noted in both groups, with scores significantly better with adapalene gel 0.1% than with tretinoin microsphere gel 0.1%, and significantly fewer treatment-related adverse events were reported with adapalene gel 0.1%.

Acne Vulgaris↗
PubMed2000

Understanding of prognosis among parents of children who died of cancer: impact on treatment goals and integration of palliative care.

CONTEXT: Parents' understanding of prognosis or decision making about palliative care for children who die of cancer is largely unknown. However, a more accurate understanding of prognosis could alter treatment goals and expectations and lead to more effective care. OBJECTIVES: To evaluate parental understanding of prognosis in children who die of cancer and to assess the association of this factor with treatment goals and the palliative care received by children. DESIGN, SETTING, AND PARTICIPANTS: Survey, conducted between September 1997 and August 1998, of 103 parents of children who received treatment at the Dana-Farber Cancer Institute and Children's Hospital, Boston, Mass, and who died of cancer between 1990 and 1997 (72% of those eligible and those located) and 42 pediatric oncologists. MAIN OUTCOME MEASURE: Timing of parental understanding that the child had no realistic chance for cure compared with the timing of physician understanding of this prognosis, as documented in the medical record. RESULTS: Parents first recognized that the child had no realistic chance for cure a mean (SD) of 106 (150) days before the child's death, while physician recognition occurred earlier at 206 (330) days before death. Among children who died of progressive disease, the group characterized by earlier recognition of this prognosis by both parents and physicians had earlier discussions of hospice care (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06; P =.01), better parental ratings of the quality of home care (OR, 3.31; 95% CI, 1.15-9.54; P =.03), earlier institution of a do-not-resuscitate order (OR, 1.03; 95% CI, 1.00-1.06; P =.02), less use of cancer-directed therapy during the last month of life (OR, 2.80; 95% CI, 1.05-7.50; P =.04), and higher likelihood that the goal of cancer-directed therapy identified by both physician and parent was to lessen suffering (OR, 5.17; 95% CI, 1.86-14.4; P =.002 for physician and OR, 6.56; 95% CI, 1.54-27.86; P =.01 for parents). CONCLUSION: Considerable delay exists in parental recognition that children have no realistic chance for cure, but earlier recognition of this prognosis by both physicians and parents is associated with a stronger emphasis on treatment directed at lessening suffering and greater integration of palliative care. JAMA. 2000;284:2469-2475.

Adult↗
PubMed2000

Cloning, characterization, and mapping of the gene encoding the human G protein gamma 2 subunit.

G proteins play vital roles in cellular responses to external signals. The specificity of G protein-receptor interaction is mediated mostly by the gamma-subunit and the individual members of the gamma-subunit multigene family would hence be expected to each have a particular expression profile. In an experiment designed to isolate genes expressed predominantly in human testis we identified a cDNA fragment corresponding to the gamma2 gene. Although the protein sequence of the gamma2 subunit has previously been published, the cDNA sequence, expression pattern, genomic structure, and localisation of the human GNG2 gene have not been described. We report the complete sequence of the GNG2 cDNA which is 1066 bp long and contains an open reading frame encoding a protein of 71 amino acids. This protein is 100% homologous to the bovine, mouse, and rat G protein gamma2 subunit. The gene structure is very similar to that of other Ggamma-subunit genes in that there are two introns, one located in the 5' UTR and the other within the ORF. We show that this gene is expressed in a range of foetal tissues as well as adult testis, adrenal gland, brain, white blood cells and lung but not in adult liver, muscle, sperm, prostate gland nor in the testes of two different infertile patients. There is evidence that GNG2 is expressed in malignant tissues. Using two independent methods, we have mapped the human GNG2 gene to chromosome 14q21.

Amino Acid Sequence↗
PubMed2000

Symptoms and suffering at the end of life in children with cancer.

BACKGROUND: Cancer is the second leading cause of death in children, after accidents. Little is known, however, about the symptoms and suffering at the end of life in children with cancer. METHODS: In 1997 and 1998, we interviewed the parents of children who had died of cancer between 1990 and 1997 and who were cared for at Children's Hospital, the Dana-Farber Cancer Institute, or both. Additional data were obtained by reviewing medical records. RESULTS: Of 165 eligible parents, we interviewed 103 (62 percent), 98 by telephone and 5 in person. The interviews were conducted a mean (+/-SD) of 3.1+/-1.6 years after the death of the child. Almost 80 percent died of progressive disease, and the rest died of treatment-related complications. Forty-nine percent of the children died in the hospital; nearly half of these deaths occurred in the intensive care unit. According to the parents, 89 percent of the children suffered "a lot" or "a great deal" from at least one symptom in their last month of life, most commonly pain, fatigue, or dyspnea. Of the children who were treated for specific symptoms, treatment was successful in 27 percent of those with pain and 16 percent of those with dyspnea. On the basis of a review of the medical records, parents were significantly more likely than physicians to report that their child had fatigue, poor appetite, constipation, and diarrhea. Suffering from pain was more likely in children whose parents reported that the physician was not actively involved in providing end-of-life care (odds ratio, 2.6; 95 percent confidence interval, 1.0 to 6.7). CONCLUSIONS: Children who die of cancer receive aggressive treatment at the end of life. Many have substantial suffering in the last month of life, and attempts to control their symptoms are often unsuccessful. Greater attention must be paid to palliative care for children who are dying of cancer.

Anorexia↗
PubMed2000

Trauma-related psychophysiological reactivity in women exposed to war-zone stress.

Women are at particular risk for Posttraumatic Stress Disorder (PTSD), but surprisingly little is known about their objective manifestations of the disorder's hallmark symptoms. Although research suggests that people with PTSD exhibit physiological reactivity to the presentation of trauma-related cues, the majority of studies to date have focused on men. We assessed the physiological reactions of three groups of trauma-exposed female Vietnam veterans (those with current PTSD, lifetime PTSD, or no PTSD) to war-related stimuli. Responses of women with current PTSD differed significantly from those without PTSD on skin conductance and systolic blood pressure, and mean levels of reactivity for women with lifetime PTSD fell between the other two groups. Although symptom severity was correlated with physiologic reactivity overall, results suggested differential relationships at the symptom cluster level. Study results replicate earlier findings with men and extend knowledge of autonomic reactivity to an important group of female survivors.

Adult↗
PubMed2000

Fractionating the binding process: neuropsychological evidence distinguishing binding of form from binding of surface features.

We present neuropsychological evidence demonstrating that the binding of form elements into shapes dissociates from the binding of surface detail to shape. Data are reported from a patient with bilateral parietal lesions, GK, who manifests left-side visual extinction along with many illusory conjunctions when asked to discriminate both surface and form information about stimuli. We show that there are effects of grouping on both extinction and illusory conjunctions when the tasks require report of object shape. In contrast, illusory conjunctions involving surface and form information were unaffected by grouping based on shape. In addition, grouping was stronger when forms were presented within the same hemifield than when they appeared in different hemifields, whilst illusory conjunctions of form and colour occurred equally often within and across hemifields. These results support a two-stage account of visual binding: form elements are first bound together locally into shapes, and this is followed by a second stage of binding in which shapes are integrated with surface details. The second but not the first stage of binding is impaired in this patient.

Color Perception↗
PubMed2000

Comparison of powder and aerosol formulations of salmeterol in the treatment of asthma.

BACKGROUND: The efficacy and safety of the aerosol metered-dose inhaler (MDI) formulation of salmeterol for asthma symptoms have been established. Recently, salmeterol has been introduced as a micronized powder formulation administered via a breath-activated multidose powder inhaler (Diskus). OBJECTIVE: A multicenter, randomized, double-blind, double-dummy, parallel-group, placebo-controlled study involving 498 adolescents and adults with mild-to-moderate asthma was conducted to compare the efficacy and safety of salmeterol powder 50 microg twice daily via Diskus, salmeterol aerosol 42 microg twice daily via MDI, and placebo. METHODS: Patients were randomized to one of the three treatment groups for 12 weeks. Efficacy was assessed by serial measurements of forced expiratory volume in one second (FEV1) over 12 hours, daily peak expiratory flow (PEF), self-rated asthma symptom scores, nighttime awakenings, and supplemental albuterol use. Safety of each treatment was evaluated by monitoring vital signs, electrocardiograms, Holter monitoring, and occurrence of adverse events. RESULTS: As compared with placebo, both salmeterol powder and aerosol produced significant improvement in FEV1 and PEF and decreased nighttime awakenings and supplemental albuterol use. There were no significant differences in the efficacy of the two salmeterol formulations. The magnitude of improvement in pulmonary function was undiminished over the 12-week study. Both formulations of salmeterol were well tolerated, with safety profiles not significantly different from placebo. CONCLUSION: Results of this study indicate that salmeterol, administered either as a powder 50 microg twice daily via Diskus or as an aerosol 42 microg twice daily via MDI, produces clinically significant and comparable improvement in pulmonary function and is well tolerated in patients with mild-to-moderate persistent asthma.

Adolescent↗
PubMed2000

In vivo regulation of apoptosis in metaphyseal trabecular bone of young rats by synthetic human parathyroid hormone (1-34) fragment.

Osteoblast differentiation and function can be studied in situ in the metaphysis of growing long bones. Proliferation and apoptosis dominate in the primary spongiosa subjacent to the growth plate, and differentiation and function dominate in the proximal metaphysis. Apoptosis of osteocytes dominates at the termination of the trabeculae in diaphyseal marrow. As parathyroid hormone regulates all phases of osteoblast development, we studied the in vivo regulation by human parathyroid hormone (1-34) (PTH) of apoptosis in bone cells of the distal metaphysis of young male rats. Rats were given PTH at 80 microg/kg per day, once daily, for 1-28 days. Bone cells were defined for flow cytometry as PTH1-receptor-positive (PTH1R(+)) and growth factor-receptor-positive (GFR(+)) cells. Apoptotic cells stained positive for either TdT-mediated dUTP-X nick end labeling (TUNEL) or annexin V (annV(+)) were detected by either flow cytometry or immunohistochemistry. Apoptosis was also assessed at the tissue level by RNAse protection and caspase enzyme activity assays. PTH increased apoptotic osteoblasts in the proliferating zone and apoptotic osteocytes in the terminal trabecular zone, by 40%-60% within 2-6 days of PTH treatment, but values became equivalent to controls after 21-28 days of treatment. This transient increase was confirmed in PTH1R(+), GFR(+) bone cells isolated by flow cytometry. There was no detectable change in the steady-state mRNA levels of selected apoptotic genes. Starting at 3 days, at the tissue level, PTH inhibited activity of caspases, which recognize the DEVD peptide substrate (caspases 2, 3, and/or 7), but not those caspases recognizing LEHD or YVAD peptide sequences. We speculate that the localized and tissue level effects of PTH on apoptosis can be explained on the basis of its anabolic effect on bone. The transient increase in apoptosis in the proliferating zone and terminal trabecular zone may be the result of the increased activation frequency and bone turnover seen with daily PTH treatment. As once-daily PTH increases the number of differentiated osteoblasts, and as these and hematopoietic marrow cells dominate metaphyseal tissue, inhibition of caspase activity may contribute to their prolonged survival, enabling extension of trabecular bone into the diaphyseal marrow to increase bone mass.

Age Factors↗
PubMed2000

An investigation of the impact of posttraumatic stress disorder on physical health.

In a large sample of Gulf War veterans (N = 2301) we examined the relations between PTSD symptoms assessed immediately upon returning from the Gulf War and self-reported health problems assessed 18-24 months later. PTSD symptomatology was predictive of self-reported health problems over time for both men and women veterans, even after the effects of combat exposure were removed from the analysis. Female veterans reported significantly more health problems than male veterans, however, there was no interactive effect of gender and PTSD on health problems. These findings provide further support for the theory that psychological response to stressors impacts health outcome.

Adult↗