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Biomedical subjects

P Fox

Publications and source records attributed to P Fox.

At least 55 records · Page 3Linked to original sources

An investigation into the effects of nicotine gum on short-term memory.

Using a between-subjects 2x2x2 factorial design, 60 smokers and 60 non-smokers (equal number of males and females) performed a short-term memory task requiring delayed free recall of a visually presented supraspan word list. Using a double-blind procedure, half the subjects chewed nicotine gum and the other half chewed placebo gum prior to performing the memory task. Results support previous research findings which show that nicotine significantly improves short-term memory. Sex differences were also investigated, but findings showed no significant differences between male and female subjects. Methodological considerations are discussed and directions for future research are suggested.

Adolescent↗

Defective cytoplasmic granule formation.II. Differences in patterns of radiolabeling of secretory granules in beige versus normal mouse pancreatic acinar cells after [3H]glycine administration in vivo.

We investigated the development of secretory granules in the pancreatic acinar cells of normal (C57BL/6J +/+) and beige (C57BL/6J Lystbg/Lystbg) mice by analyzing the distribution of 3H label in pancreatic acinar cells after a pulse of [3H]glycine administered in vivo. The results provide quantitative confirmation of the hypothesis that the maturation of condensing vacuoles/immature granules to mature granules in pancreatic acinar cells is associated with a significant volume reduction. Beige mice differ from control mice by exhibiting a more rapid distribution of 3H label from the rough endoplasmic reticulum-rich cytoplasm to the secretory granules and a slightly faster rate of maturation of 3H-labeled granules. Beige mouse pancreatic acinar cells also exhibited, as early as 1 h after pulsing with [3H]glycine, a much higher proportion of 3H-labeled secretory granules than did the cells of control mice. These findings identify additional abnormalities in secretory granule formation in pancreatic acinar cells which are related to the beige (Lystbg) mutation and provide support for the hypothesis that beige mice exhibit an abnormal pattern of granule-granule fusion.

Animals↗

Ultrastructural analysis of human skin biopsy specimens from patients receiving recombinant human stem cell factor: subcutaneous injection of rhSCF induces dermal mast cell degranulation and granulocyte recruitment at the injection site.

We performed an ultrastructural analysis of 10 skin biopsy specimens that had been obtained from three women who were undergoing daily subcutaneous dosing with recombinant methionyl-human stem cell factor (rhSCF) as part of a phase I clinical trial. The biopsy specimens were obtained at sites of subcutaneous administration of rhSCF, within approximately 1 to 2 hours of rhSCF injection, and, at the same time, at contralateral control sites that had not been directly injected with rhSCF. We previously reported that subcutaneous dosing with rhSCF in these subjects induced the local development of a wheal and flare response, which was associated with evidence of mast cell degranulation, as well as a systemic increase in numbers of cutaneous mast cells. The present electron microscopic analysis revealed that all biopsies of swollen, erythematous rhSCF-injected sites exhibited anaphylactic degranulation of both mature and immature mast cells, an acute inflammatory response characterized by the migration of neutrophils, basophils (some of which exhibited evidence of piecemeal degranulation), and eosinophils through blood vessel walls into the perivascular and extravascular spaces, and edema and fibrin deposition within the interstitium. By contrast, the control biopsies contained no evidence of mast cell degranulation or acute inflammation. However, both control and rhSCF-injected sites exhibited mast cells that were undergoing granule building and maturation. Thus at the doses tested in these subjects, subcutaneous injection of rhSCF induced anaphylactic-type degranulation of dermal mast cells at the injection site, with an acute inflammatory response that was associated with the recruitment of granulocytes. By contrast, mast cells at sites distant from those directly injected with rhSCF exhibited no evidence of enhanced secretion.

Anaphylaxis↗

Presence of NK1 receptors on a mucosal-like mast cell line, RBL-2H3 cells.

Reverse transcription--polymerase chain reaction of mRNA from rat RBL-2H3 cells yielded a 316 base pair band consistent with that predicted for the neurokinin-1 (NK1) receptor. Saturation and competition binding with 125I-labeled Bolton-Hunter substance P, substance P fragments, and a series of selective tachykinin receptor agonists and antagonists demonstrated that RBL-2H3 cells express high affinity binding sites for substance P on their surfaces with the kinetic and pharmacological properties of NK1 receptors. The pharmacology of these 125I-labeled substance P binding sites was (from most to least potent) [Sar9,Met(O2)11]substance P > substance P 4-11 >> GR82334 << MEN 10,376. However, substance P 1-4, substance P 8-11, substance P 9-11, and [Trp7, beta-Ala8]neurokinin A 4-10 failed to compete for binding. The metabolically stable NK1 receptor agonist, [Sar9,Met(O2)11] substance P, caused a 49% increase in 5-hydroxytryptamine release above basal levels. The results demonstrate the presence of functional NK1 receptors on RBL-2H3 cells, a mucosal-like mast cell line.

Animals↗

Imaging human intra-cerebral connectivity by PET during TMS.

Non-invasive imaging of human inter-regional neural connectivity by positron emission tomography (PET) during transcranial magnetic stimulation (TMS) was performed. The hand area of primary motor cortex (M1) in the left cerebral hemisphere was stimulated with TMS while local and remote effects were recorded with PET. At the stimulated site, TMS increased blood flow (12-20%) in a highly focal manner, without an inhibitory surround. Remote covariances, an index of connectivity with M1, were also focal. Connectivity patterns established in non-human species were generally confirmed. Excitatory connectivity (positive covariance) was observed in ipsilateral primary and secondary somatosensory areas (S1 and S2), in ipsilateral ventral, lateral premotor cortex (M2) and in contralateral supplementary motor area (SMA). Inhibitory connectivity (negative covariance) was observed in contralateral M1.

Brain Mapping↗

A multicenter, uncontrolled clinical investigation of the contraceptive efficacy, cycle control, and safety of a new low dose oral contraceptive containing 20 micrograms ethinyl estradiol and 100 micrograms levonorgestrel over six treatment cycles.

The aim of the trial was to demonstrate the contraceptive efficacy of a new low dose oral contraceptive containing 20 micrograms ethinyl estradiol and 100 micrograms levonorgestrel and to observe cycle control and safety. Data from 805 treated women resulted in 4400 treatment cycles. One pregnancy occurred while on the trial medication as a result of method failure, resulting in a Pearl index of 0.29. Cycle control was good, and cycle length as well as duration and intensity of withdrawal bleeding were not significantly changed during the trial. Intermenstrual bleeding usually occurred as spotting and decreased considerably during the treatment phase. Spotting alone was reported in 12.4% of cycles, breakthrough bleeding alone in 4.5% of cycles, and breakthrough bleeding and spotting together in 1.4% of treatment cycles. The rate of absence of withdrawal bleeding declined throughout the trial to 2.4% in cycle 6. There were no serious adverse events related to treatment, and most adverse events were those commonly observed in clinical trials with oral contraceptives. Headache, breast tension, and nausea were reported by 17.3%, 11.0%, and 7.7% of the women, respectively. There were no clinically relevant changes in laboratory parameters, blood pressure, or weight. In this trial, the new low dose oral contraceptive containing 20 micrograms ethinyl estradiol and 100 micrograms levonorgestrel was shown to be effective, safe, and well tolerated. Cycle control was found to be good and there was a low incidence of adverse events.

Adolescent↗

Facial growth and the need for orthognathic surgery after cleft palate repair: literature review and report of 28 cases.

PURPOSE: Controversy still exists regarding the optimal timing and surgical technique for primary cleft lip and palate (CLP) repair, and treatment protocols vary considerably. This study reviews the literature on timing and technique for primary repair and reports on the outcome for a consecutive group of patients treated by a single surgical protocol at the Sunnyview Cleft Palate Clinic. PATIENTS AND METHODS: Twenty-eight patients treated by a standardized clinical protocol from infancy through adolescence were evaluated with respect to the need for orthognathic surgery to correct jaw size discrepancy. For each patient, data was collected regarding type of cleft deformity, total number of surgical procedures from infancy, surgeon performing the primary repair, and the need or indication for orthognathic surgery. RESULTS: Twenty-five percent of patients treated by this protocol required orthognathic surgery because of anteroposterior jaw size discrepancy. The number of prior operations was not a significant factor. The need for orthognathic surgery was seen in all types of CLP deformity. Different primary surgeons varied considerably in the percentage of their patients who ultimately required orthognathic surgery. CONCLUSION: The results of this study parallel other larger cohort studies with respect to the percentage of patients requiring orthognathic surgery. The number of prior operations does not significantly affect the later need for orthognathic surgery.

Adolescent↗

An examination of differential follow-up rates in cervical cancer screening.

The purpose of this study was to test the hypothesis that follow-up rates for women with abnormal cervical cancer screening results vary by age, ethnicity, and initial screening results in California's Breast and Cervical Cancer Control Program. The sample consisted of women in the screening program who received an abnormal cervical screening result (N = 1.738). Bivariate and logistic regression analyses were utilized to examine variables that account for differences in follow-up rates among these women. Bivariate analysis showed significant differences by age, race/ethnicity, initial screening results, and urban/rural residence. In logistic regression analysis, these variables also retained significance. Severity of diagnosis was a highly significant predictor of follow-up. Women of color, older women, and women with less severe diagnoses should be targeted as groups needing assistance in adhering to follow-up recommendations.

Adult↗

Body image change in pregnancy: a comparison of normal weight and overweight primigravidas.

BACKGROUND: Body image in pregnancy has been linked to maternal and neonatal health. This study examined the relationship between prepregnancy body weight and body image change in primigravid women. METHODS: Through a self-administered, free-response questionnaire, 76 primigravidas of at least 30 weeks' gestation described their feelings about current appearance and body shape and compared these to prepregnancy feelings. Respondents also completed the Body Shape Questionnaire to measure current concern with body shape. RESULTS: Women who were overweight before pregnancy were more likely to have had a positive change in body image when they were at more than 30 weeks' gestation. Women who were normal weight before pregnancy were more likely to have had a negative change. Despite overweight women's positive changes, their body shape concerns were more negative than those of normal weight women. CONCLUSIONS: Our study highlights the relationship between social values, prepregnancy body weight, and body image change during pregnancy. Some women may benefit from discussing their experiences in a patient-centered context.

Adult↗

Substance P as a mediator of colonic secretory reflexes.

The role of substance P in neural reflex pathways activated by stroking was investigated in muscle-stripped segments of distal colon from guinea pigs. Stroking the mucosal surface with a brush at 1 stroke/s evoked an increase in short-circuit current (Isc) indicative of chloride secretion. The response to mucosal stroking was maximally reduced by 69-75% by the antagonist GR-82334. The agonist [Sar9,Met(O2)11] substance P caused a bumetanide-sensitive increase in Isc when added to the mucosal or serosal bath. Ablation of extrinsic afferents with acute or chronic administration of capsaicin did not alter the mucosal stroking response. Reverse transcription-polymerase chain reaction and in situ hybridization revealed the presence of neurokinin1 (NK1) receptor messenger RNA in isolated colonocytes or crypt glands. Ligand binding of 125I-Bolton-Hunter-labeled substance P was inhibited by GR-82334. The 50% inhibitory concentration was 0.84 nM. The results demonstrate a role for substance P released from capsaicin-insensitive submucosal neurons and in mucosal stroking reflexes. The presence of NK1 receptors on isolated colonocytes suggests that appropriate elements are present for axon reflex activation of intestinal epithelial cells.

Animals↗

Caregiver supports: outcomes from the Medicare Alzheimer's disease demonstration.

A randomized 3-year study assessed the effect of expanded community-based services and case management on 5,254 caregivers of dementia clients. A tested policy concern was whether the financing of formal care would result in a reduction of informal assistance. Unmet needs task assistance for the demonstration's treatment group caregivers decreased by 30 percent within 6 months and by about 20 percent over 36 months relative to controls. While treatment group members used slightly more formal care over time, there were no differences between treatment and control groups in primary caregiver hours after 36 months, or in the number of tasks in which primary or secondary caregivers provided assistance.

Activities of Daily Living↗

Measurement choices in multi-site studies of outcomes in dementia.

This paper summarizes the measurement choices made by selected current or recently completed multi-site projects with a common emphasis on measuring outcomes in dementia. Information on number of items and scoring, reason(s) for selecting the measure, and reliability and validity of the measure (either citations providing this information or a report of pertinent unpublished findings) is presented for eight domains: cognition, behavioral symptoms, physical health status, physical functioning and self-care abilities, quality of life, family/staff caregiver outcomes, service use, and cost. We found considerable reliance on the published literature as a guide to measurement choice, motivated largely by measures' superior psychometric properties, their ubiquity in the literature, and/or their brevity or ease of use. There is still evidence of "starting from scratch" in some domains, however. To the extent that these projects reflect the state of the art in dementia-relevant outcomes research, we conclude that comparison of outcomes across studies will continue to be problematic. However, as long as dissemination of methodological as well as substantive findings continues to characterize outcome studies in dementia, there is hope that a more congruent view of how to assess key outcomes in dementia will emerge.

Caregivers↗

An examination of differential follow-up rates in breast cancer screening.

This study was designed to test the hypothesis that follow-up rates for women with abnormal breast screening results would vary by age, ethnicity and initial screening results in California's Breast Cervical Cancer Control Program. The sample was composed of women in this screening program who had received abnormal clinical breast exam (N = 5239) or mammography results (N = 1202). Chi-squared analysis showed significant differences by age and initial screening results but in logistic regression analysis the only demographic variable to retain significance in analysis was age, although size of the clinic was also highly significant. Older women should be targeted as a group needing assistance with compliance with follow-up recommendations.

Adult↗

Goodpasture's epitope in development of experimental autoimmune glomerulonephritis in rats.

The Goodpasture's epitope (GP) has recently been localized to the last 36 AA of the non-collagenous (NCl) domain of the alpha 3 chain of type IV collagen [alpha 3(IV)]. Since alpha 3(IV) induces glomerulonephritis (GN) in rats and rabbits, the purpose of the present study was to determine if the GP epitope itself could induce GN. We immunized rats with synthetic peptides of GP epitope, 36-mer, alone or as protein conjugates. Rats immunized with bovine GBM served as positive controls. Peptide immunized rats developed high titer antibodies to peptides, but only unconjugated 36-mer induced antibody against human and bovine GBM, but not to rat GBM. Acidic residues and the full length 36-mer were important in production of GBM reactive antibodies. Positive controls developed antibody to GBM without reactivity against 36-mer, had IgG and fibrin on the basement membrane, GN and proteinuria. Kidney eluted antibody was reactive with rat, bovine, and human GBM but not 36-mer. GN rat lymphocytes underwent blast transformation to GBM but not peptide, and peptide immunized animals responded only to the respective peptides. None of the animals immunized with GP peptide epitope, despite the development of anti-peptide antibodies or anti-GBM antibodies, developed any in vivo fixation of antibody to the GBM, abnormal proteinuria, or GN. The present study shows that the GP epitope is sufficient to induce an immune response to the epitope, but it is not sufficient to induce GN. This demonstrates that other factors or epitopes are important in the pathogenicity of GBM induced GN in this model. These remain to be delineated.

Animals↗

Practical public health in a primary care setting. Discrete projects confer discrete benefits but a long-term relationship is needed.

Investigates a mechanism for delivering public health advice in a primary care setting--three West Yorkshire general practices--by seconding a public health physician (PHP) to each practice for six months, each practice receiving one day per week. Describes how the topics to be addressed--developing a practice plan for managing information; improving services available for Asian patients; and exploring "value for money" in fundholding--were chosen. Details the procedures and lists the main outcomes. Concludes that placing a public health physician in practices may not be the optimal approach for transferring public health knowledge, but topics important to the practice lend themselves to such an intervention, with potential long-term benefit for public health and primary care.

Family Practice↗

Endovascular covered stent repair of an intercostal artery patch dehiscence from a descending thoracic aortic aneurysm graft.

PURPOSE: To describe the use of endovascular techniques to repair a descending thoracic aortic pseudoaneurysm at a site of patch dehiscence. METHODS AND RESULTS: A 63-year-old hypertensive, diabetic female with a 4-cm aneurysm in the descending thoracic aorta underwent surgical repair with a 35-mm Dacron graft. Dehiscence of the intercostal arterial patch produced a large, 6-cm-diameter pseudoaneurysm that extended into the left thoracic cavity. An endovascular repair was planned using a Dacron stent-graft. Despite induced hypotension and an exteriorized, stiff exchange wire to enhance control of the delivery balloon catheter, the initial attempt failed to close the suture line defect. A customized polytetrafluoroethylene-covered, balloon-expandable stent was successfully deployed using the original stent-graft as a landmark. At 6 months, the contrast-enhanced spiral computed tomographic scan showed patency of the stent-graft and resorption of the pseudoaneurysm. CONCLUSIONS: This communication describes the management of a surgical complication using balloon-expandable covered stents in contrast to either conventional surgery or self-expanding stent-grafts. Transesophageal ultrasound monitoring delineated the suture line leak, identified the position of the stent-grafts, and accurately demonstrated closure of the defect.

Aneurysm, False↗