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Biomedical subjects

J Fulton

Publications and source records attributed to J Fulton.

At least 19 recordsLinked to original sources

Quantitative trait locus mapping in chickens by selective DNA pooling with dinucleotide microsatellite markers by using purified DNA and fresh or frozen red blood cells as applied to marker-assisted selection.

Many large, half-sib sire families are an integral component of chicken genetic improvement programs. These family structures include a sufficient number of individuals for mapping quantitative trait loci (QTL) at high statistical power. However, realizing this statistical power through individual or selective genotyping is yet too costly to be feasible under current genotyping methodologies. Genotyping costs can be greatly reduced through selective DNA pooling, involving densitometric estimates of marker allele frequencies in pooled DNA samples. When using dinucleotide microsatellite markers, however, such estimates are often confounded by overlapping "shadow" bands and can be confounded further by differential amplification of alleles. In the present study a shadow correction procedure provided accurate densitometric estimates of allele frequency for dinucleotide microsatellite markers in pools made from chicken purified DNA samples, fresh blood samples, and frozen-thawed blood samples. In a retrospective study, selective DNA pooling with thawed blood samples successfully identified two QTL previously shown by selective genotyping to affect resistance in chickens to Marek's disease. It is proposed that use of selective DNA pooling can provide relatively low-cost mapping and use in marker-assisted selection of QTL that affect production traits in chickens.

Alleles↗

Subsite-specific incidence rate and stage of disease in colorectal cancer by race, gender, and age group in the United States, 1992-1997.

BACKGROUND: Subsite specific incidence rates of colorectal cancer vary considerably by age, gender, and race. This variation may be related not only to distinctions in exposure to genetic and environment factors but also to current strategies of early detection screening. Patterns of stage of disease in anatomic subsite may reflect the effect of screening. This study used the largest aggregation of cancer incidence data in the U.S. to examine subsite specific incidence rates of colorectal cancer and the relation of stage of disease to anatomic subsites by race, gender, and age group. METHODS: Data on the incidence of invasive colorectal cancer were obtained from 28 population-based central cancer registries. Age-specific and age-adjusted rates and stage distributions were analyzed by subsite, race, and gender. RESULTS: The impact of screening can be observed in the percentage of localized disease, which increased from 31.9% among cancers in the proximal colon to 37.0% in the descending colon to 41.5% in the distal colorectum. Within the same subsite, blacks were less likely than whites to receive a diagnosis of localized disease and more likely to receive a diagnosis of distant disease whereas stage distributions were approximately the same for males and females. Blacks were more likely than whites to receive a diagnosis of proximal colon cancer than distal colorectal cancer. The male-to-female rate ratios progressively increased from the proximal colon to the distal colorectum. The ratios of proximal-to-distal colorectal cancer gradually increased with advancing age. CONCLUSIONS: Differentials in stage of disease by subsites indicate a need for a targeted effort at early detection of cancer in the proximal colon. Risk factors and higher risk populations for colorectal cancers in each subsite need to be studied further to guide actions for improving the efficacy of screening.

Age Factors↗

Experimental use of an illuminated and magnetic tip, flow-directed pulmonary artery catheter for lung resection.

The authors performed a study to design and evaluate a device giving the surgeon added protection against pulmonary artery injury in a closed thoracic compartment. Eleven swine were used for a total of 12 lobectomies. A light-bearing, magnetic-tipped, modified Swan-Ganz catheter was passed through the jugular vein into the left pulmonary artery. By using magnetic guidance through a port site and balloon inflation, cessation of flow in the pulmonary artery was documented by Doppler. Twelve video-assisted lobectomies were performed. Nine of 12 (75%) lobectomies were completed successfully by using the magnetic-tipped, illuminated balloon catheter. In 4 cases, the catheter displaced because of the short left main pulmonary artery in swine. In one case, the balloon was recovered, and successful lobectomy was performed. The use of a magnetic-tipped, flow-directed device may provide an effective means of endovascular control during thoracoscopic pulmonary arterial dissection.

Animals↗

Brain-stimulation reward thresholds raised by an antisense oligonucleotide for the M5 muscarinic receptor infused near dopamine cells.

Oligonucleotides targeting M5 muscarinic receptor mRNA were infused for 6 d into the ventral tegmental area of freely behaving rats trained to bar-press for lateral hypothalamic stimulation. The bar-pressing rate was determined at a range of frequencies each day to evaluate the effects of infusions on reward. M5 antisense oligonucleotide (oligo) infusions increased the frequency required for bar pressing by 48% over baseline levels, with the largest increases occurring after 4-6 d of infusion. Two control oligos had only slight effects (means of 5 and 11% for missense and sense oligos, respectively). After the infusion, the required frequency shifted back to baseline levels gradually over 1-5 d. Antisense oligo infusions decreased M5 receptors on the ipsilateral, but not the contralateral, side of the ventral tegmentum, as compared with a missense oligo. Therefore, M5 muscarinic receptors associated with mesolimbic dopamine neurons seem to be important in brain-stimulation reward.

Animals↗

Glatiramer acetate (Copaxone) treatment in relapsing-remitting MS: quantitative MR assessment.

OBJECTIVE: To evaluate the efficacy of glatiramer acetate (GA, Copaxone; Teva Pharmaceutical Industries, Ltd., Petah Tiqva, Israel) by MRI-based measures in patients with relapsing-remitting (RR) MS. METHODS: Twenty-seven patients with clinically definite RR-MS were treated with either 20 mg of GA by daily subcutaneous self-injection (n = 14) or placebo (n = 13) for approximately 24 months. Axial dual-echo fast-spin-echo T2-weighted images and T1-weighted images before and after gadolinium (Gd) were acquired at 1.5 tesla and transferred into an image processing computer system. The main outcome measures were the number of Gd-enhanced T1 and T2 lesions and their volume as well as brain parenchyma volume. RESULTS: The values of age, disease duration, Expanded Disability Status Scale (EDSS) score, the number of T1- and T2-weighted lesions, and their volume were similar between GA- and placebo-receiving groups at the entry of this study. There was a decrease in the number of T1-enhanced lesions (p = 0.03) and a significant percent annual decrease of their volume in GA recipients compared with those of placebo recipients. There were no significant differences between changes in the two groups in the number of T2 lesions and their volume. The loss of brain tissue was significantly smaller in the GA group compared with that of the placebo group. CONCLUSIONS: These results show that GA treatment may decrease both lesion inflammation and the rate of brain atrophy in RR-MS.

Adult↗

Implementation of an RN/RT-initiated extubation protocol.

Widespread acceptance of the importance of discontinuing ventilator support at the earliest possible opportunity has resulted in a number of efforts to develop a standardized approach to extubation. The implementation of an extubation protocol designed for the medical/surgical intensive care unit of a university-affiliated hospital followed a series of educational sessions that were open to all members of the multidisciplinary team. As part of quality assurance monitoring, data were collected on the first 47 patients who were extubated using these criteria. A clinical outcome was defined as the percentage of patients who required reintubation within 48 hours. The protocol has been well-received by the ICU team and has become an established component of ventilator management.

Clinical Protocols↗

Analysis of FKBP51/FKBP52 chimeras and mutants for Hsp90 binding and association with progesterone receptor complexes.

FKBP51, FKBP52, and Cyp40 bind competitively to Hsp90 through their respective tetratricopeptide repeat (TPR) domains, and any one of the three immunophilins can be isolated in mature steroid receptor complexes. During cell-free assembly reactions, FKBP51 associates preferentially with progesterone and glucocorticoid receptors, but less preference is observed in FKBP51 association with estrogen receptor. A number of mutant FKBP forms were generated to map sequences responsible for FKBP51's preferred association with progesterone receptor. A double-point mutation in the peptidyl prolyl isomerase domain of FKBP51 that reduces enzymatic activity by greater than 90% had no observed effect on FKBP51 interactions with progesterone receptor or Hsp90. Coprecipitation of FKBP51 and FKBP52 truncation mutants with Hsp90 indicated that sequences both upstream and downstream of the TPR domain are necessary for Hsp90 binding. FKBP chimeric constructs were also generated and tested for Hsp90 binding and receptor association. The TPR domain of FKBP51 required appropriate downstream sequences for Hsp90 binding, but FKBP52's TPR domain did not. The C-terminal region of FKBP51 that functionally interacts with the TPR domain to permit Hsp90 binding also conferred preferential association with PR. In conclusion, despite the overall similarity of FKBP51 and FKBP52, these two immunophilins associate differentially with steroid receptors, and the difference relates to both the Hsp90-binding TPR domain and to poorly conserved C-terminal sequences.

Amino Acid Sequence↗

Is surgical management compromised in elderly patients with breast cancer?

OBJECTIVE: The suggestion that breast cancer management is compromised in elderly patients had prompted our review of the results of policies regarding screening and early detection of breast cancer and the adequacy of primary treatment in older women (> or = 65 years of age) compared to younger women (40 to 64 years of age). SUMMARY BACKGROUND DATA: Although breast cancer in elderly patients is considered biologically less aggressive than similar staged cancer in younger counterparts, outcome still is a matter of stage and adequate treatment of primary cancer. For many reasons, physicians appear reluctant to treat elderly patients according to the same standards used for younger patients. There is even government-mandated alterations in early detection programs. Thus, since 1993, Medicare has mandated screening mammography on a biennial basis for women older than 65 year of age compared to the current accepted standard of yearly mammograms for women older than 50 years of age. Using State Health Department and tumor registry data, the authors reviewed screening practice and management of elderly patients with primary breast cancer to determine the effects of age on screening, detection policies (as reflected in stage at diagnosis), treatment strategies, and outcome. METHODS: Data were analyzed from 5962 patients with breast cancer recorded in the state-wide Tumor Registry of the Hospital Association of Rhoda Island between 1987 and 1995. The focus of the data collection was nine institutions with established tumor registries using AJCC classified tumor data. Additional data were provided by the State Health Department on screening mammography practice in 2536 women during the years 1987, 1989, and 1995. RESULTS: The frequency of mammographic screening for all averaged 40% in 1987, 52% in 1987, and 63% in 1995. In the 65-year-old and older patients, the frequency of screening was 34% in 1987, 45% in 1989, and 48% in 1995, whereas in the 40- to 49-year-old age group, the frequency of mammography was 47% in 1987, 61% in 1989, and 74% in 1995 (p < 0.001). There was a lower detection rate of preinvasive cancer in the 65-year-old and older patients, 8.8% versus 13.7% in patients within the 40- to 64-year-old age group (p < 0.001). There was a higher percentage of treatment by limited surgery among elderly patients with highly curable Stage IA and IB cancer with 26.6% having lumpectomy alone versus 9.4% in the younger patients. Five-year survival in that group was significantly worse (63%) than in patients treated by mastectomy (80%) or lumpectomy with axillary dissection and radiation (95%, < 0.001). A similar effect was seen in patients with Stage II cancer. CONCLUSIONS: Breast cancer management appears compromised in elderly patients (older than 65 years of age). Frequency of mammography screening is significantly less in elderly women older than 65 years of age. Early detection of preinvasive (curative cancers) is significantly less than in younger patients. The recent requirement by Medicare of mammography every other year may further reduce the opportunity to detect potentially curable cancers. Approximately 20% of patients had inferior treatment of favorable stage early primary cancer with worsened survival. Detection and treatment strategy changes are needed to remedy these deficiencies.

Adult↗

Intramedullary plasmacytoma in an unusual location in a renal transplant patient.

Transplant patients have increased risk for developing neoplasia. This is due to the use of more potent and long-term immunosuppression. We report a case of a 46-year-old man with a cadaver renal transplant who developed an intramedullary plasmacytoma in an unusual location. The patient had a total right elbow replacement and received 4 weeks of local radiotherapy. The pain completely resolved and the low-dose immunosuppression was continued.

Bone Neoplasms↗

Effects of catecholamines on isolated human colonic smooth muscle.

1. The effects of catecholamines and some adrenoceptor agonists and antagonists on isolated preparations of human colonic smooth muscle obtained from surgical resections were examined. 2. Strips of circular smooth muscle displayed rhythmic myogenic spontaneous contractions which were inhibited by catecholamines with an order of potency of isoprenaline (1.0) > noradrenaline (0.32) > adrenaline (0.2). Phentolamine (0.7 microM) significantly shifted the noradrenaline concentration-response curve (CRC) to the right but had no significant effect on isoprenaline or adrenaline. Propranolol (1 microM) significantly shifted the isoprenaline to the right but had no significant effect on noradrenaline or adrenaline. 3. Salbutamol (30 microM) had no inhibitory effect on the spontaneous activity and ICI 118,551 (1 microM) had no effect on inhibitory responses to isoprenaline. Betaxolol (1 microM) significantly shifted the CRC to isoprenaline to the right. BRL 37344 had no effect on spontaneous activity. 4. Responsiveness of circular strips to catecholamines was not affected by age of the patient and no consistent differences between males and females were shown. 5. Strips of taenia coli exhibited little or no spontaneous phasic activity. Noradrenaline and isoprenaline relaxed KCl-induced tone. The effects of noradrenaline and isoprenaline were antagonized by propranolol but not by phentolamine. BRL 37344 had no effect on KCl-induced tone. 6. In conclusion, catecholamines relaxed spontaneous activity of human colon circular smooth muscle through an action on both alpha- and beta-adrenoceptors. The alpha-adrenoceptors were of the alpha 1-subtype. The beta-adrenoceptor-mediated relaxation appeared to be primarily beta 1. In taenia coli, catecholamines relaxed KCl-induced tone via beta-adrenoceptors only.

Adrenergic alpha-Agonists↗

Acute appendicitis among black South Africans.

Acute appendicitis has become the commonest nontrauma-related abdominal surgical emergency at Cecilia Makiwane Hospital. The records of 122 patients undergoing appendicectomy were reviewed. Attention is drawn to late presentation and the high complication rare encountered. Mortality rate (0.8%) and overall diagnostic accuracy (85%) were acceptable. The need for adequate patient education is stressed as a possible measure to reduce high morbidity associated with late presentation.

Acute Disease↗

The value of tilt table testing with isoproterenol in determining therapy in adults with syncope and presyncope of unexplained origin.

BACKGROUND: Previous studies have shown the effectiveness of tilt table testing in establishing the diagnosis of neurocardiogenic syncope and in dictating therapy in patients with syncope of unknown origin. Most studies have been limited by small numbers of patients and brief follow-up. Tilt table testing was performed with and without isoproterenol hydrochloride in 94 patients, and therapy was determined by the test findings. The patients were followed up for at least 10 months (mean, 17.8 months). METHODS: The 80 degrees tilt table test was performed in 94 consecutive patients who presented with syncope (n = 74) or presyncope (n = 20) and in whom neurologic and cardiac causes were ruled out. Therapy was determined by the tilt test findings. Sixty-seven patients were followed up for 17.8 +/- 5.3 months (mean +/- SD) (range, 10 to 27 months). RESULTS: Forty-nine patients had positive results of tilt studies and received therapy. Of these 49 patients, 36 returned for second tilt studies while they were taking medication, and 30 had negative results. Six patients had medication changes and had negative results of follow-up tilt studies. No symptoms were noted on follow-up in the 24 patients who presented with syncope and who had positive results of tilt tests that responded to therapy. Of these 35 patients presenting with syncope who had negative results of initial tilt studies and who did not receive any therapy, syncope recurred in four patients. Three of 10 patients contacted who presented with presyncope and had negative results of tilt studies reported symptoms. CONCLUSIONS: Tilt table testing is an excellent tool for diagnosing neurocardiogenic syncope in adults and in determining effective therapy in patients presenting with syncope of unknown origin.

Adult↗

Public policy and funding issues. The role of the clinician from a Canadian perspective.

Radiologists and cardiologists may wish to consider an evolution of their roles: Begin to delegate some tasks to others so there is time to concentrate on the areas that are important in terms of the science of diagnosis. Train and empower technicians to do more; they are skilled and are capable of lightening the workload. It is important to offer outreach services to augment the training of other physicians. Many who work in referral and tertiary centers and teaching centers have a limited concept of what it is like to be in a center with limited technology. It is vital to know what is cost-effective and to promote those services. Physicians need media skills and ways to show other clinicians and consumers the importance of their work. It is also important to develop standards for the ordering of diagnostic procedures, to help referring physicians and young physicians to order effectively so that there is less need for policing. Evaluate new technology; informed physicians become partners in the choice and not the victim of the politics. Understand that the values about health care in Canada and the United States are changing. Have a flexible outlook. The world is changing very fast, and medicine needs to change with it. Innovate; try a new approach; take a risk. Continue to do what you already do best. Try to accept a share of social responsibility. If you really think inappropriate consumption of diagnostic services is occurring, try to deal with it. Cardiologists and radiologists have done innovative, creative things, and few people know about them because not everybody reads scientific journals.(ABSTRACT TRUNCATED AT 250 WORDS)

Canada↗