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Biomedical subjects

J Wasson

Publications and source records attributed to J Wasson.

At least 37 records · Page 2Linked to original sources

Pancreatic islet cells express a family of inwardly rectifying K+ channel subunits which interact to form G-protein-activated channels.

Insulin secretion is associated with changes in pancreatic beta-cell K+ permeability. A degenerate polymerase chain reaction strategy based on the conserved features of known inwardly rectifying K+ (KIR) channel genes was used to identify members of this family expressed in human pancreatic islets and insulinoma. Three related human KIR transcript sequences were found: CIR (also known as cardiac KATP-1), GIRK1, and GIRK2 (KATP-2). The pancreatic islet CIR and GIRK2 full-length cDNAs were cloned, and their genes were localized to human chromosomes 11q23-ter and 21, respectively. Northern blot analysis detected CIR mRNA at similar levels in human islets and exocrine pancreas, while the abundance of GIRK2 mRNA in the two tissues was insufficient for detection by this method. Using competitive reverse-transcription polymerase chain reaction, CIR was found to be present at higher levels than GIRK2 mRNA in native purified beta-cells. Xenopus oocytes injected with M2 muscarinic receptor (M2) plus either GIRK2 or CIR cRNA expressed only very small carbachol-induced currents, while co-injection of CIR plus GIRK2 along with M2 resulted in expression of carbachol-activated strong inwardly rectifying currents. Activators of KATP channels failed to elicit currents in the presence or absence of co-expressed sulfonylurea receptor. These results show that two components of islet cell KIR channels, CIR and GIRK2, may interact to form heteromeric G-protein-activated inwardly rectifying K+ channels that do not possess the typical properties of KATP channels.

Amino Acid Sequence↗

Effect of radical prostatectomy for prostate cancer on patient quality of life: results from a Medicare survey.

OBJECTIVES: To assess patient responses to radical prostatectomy and its effects. METHODS: A national sample was taken of 1072 Medicare patients who underwent radical prostatectomy for prostate cancer (1988 through 1990) by mail, telephone, and personal interviews. The effects of the surgery and its complications on these patients' lives were studied through: (1) patient ratings of the extent to which sexual and urinary dysfunctions were "problems" in their lives; (2) two general measures of quality of life, the Mental Health Index and the General Health Index; (3) patient reports of how they felt about the results of treatment and whether they would choose surgery again. RESULTS: On average, dripping urine, particularly to the point where subjects were wearing pads, had a more significant effect on patients than loss of sexual function; incontinence had significant adverse effects on the measures of quality of life and self-reported results of surgery. Overall, postsurgical patients scored comparatively high on the quality of life measures (similar to a cohort of patients with benigh prostatic hyperplasia who had undergone transurethral resection of the prostate), reported feeling positive about the results (81%), and would choose surgical treatment again (89%). Nonetheless, there was variability in patient response to the effects of surgery. CONCLUSIONS: The results demonstrate the ability of many Medicare patients to adapt to adverse outcomes, such as loss of sexual function and incontinence. They also provide evidence of the variability of individual patients' responses to surgical results and reinforce the importance of individualized decision making for patients facing a decision about radical prostatectomy for prostate cancer.

Aged↗

Characterization of the LIM/homeodomain gene islet-1 and single nucleotide screening in NIDDM.

Islet-1 (Isl-1) is a unique transcription factor that binds to the enhancer region of the insulin gene. To evaluate this gene in non-insulin-dependent diabetes mellitus (NIDDM), a full-length human Isl-1 cDNA was isolated and the genomic structure was characterized. The cDNA [2,395 bp plus additional poly(A) residues] contained an open reading frame from an initiator methionine at nucleotide 240 to an opal stop codon at nucleotide 1,286 (GenBank accession number UO7559), encoding a predicted protein of 349 amino acids (39 kDa). From their ends, 23 additional clones were sequenced, revealing 15 incomplete cDNAs and 8 intron-containing partially processed precursors. As determined by Northern blotting and reverse transcriptase-polymerase chain reaction analysis, Isl-1 was most abundantly expressed as a 2.4-kb mRNA in human islets, with a restricted pattern of expression in other adult human tissues. Analysis of genomic clones revealed that Isl-1 is encoded by six exons, varying in size from 168 bp (exon 5) to 1,230 bp (exon 6). Exons 2 and 3 each encode a LIM domain, while the homeodomain is completely contained within exon 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

An assessment of radical prostatectomy. Time trends, geographic variation, and outcomes. The Prostate Patient Outcomes Research Team.

OBJECTIVES: To examine temporal trends and geographic variation in radical prostatectomy rates and short-term outcomes. DESIGN: Population-based study of radical prostatectomy for the years 1984 through 1990. Poisson regression was used to estimate temporal and regional effects. SETTING: The 50 states and the District of Columbia. PARTICIPANTS: A 20% national sample of male Medicare beneficiaries aged 65 years or older. MAIN OUTCOME MEASURES: Rate of radical prostatectomy; 30-day mortality; and major cardiopulmonary complications, vascular complications, or surgical repairs within 30 days of radical prostatectomy. RESULTS: A total of 10,598 radical prostatectomies were identified. The adjusted rate of radical prostatectomy in 1990 was 5.75 times that in 1984. The relative increase was similar in all age groups. Substantial geographic variation existed in rates from 1988 through 1990: all states in the New England and Mid-Atlantic regions had rates equal to or below 60 per 100,000 male Medicare beneficiaries, while all states in the Pacific and Mountain regions had rates equal to or above 130 per 100,000. The mortality and morbidity after radical prostatectomy are not trivial for older men (aged 75 years and older)--almost 2% died and nearly 8% suffered major cardiopulmonary complications within 30 days of the operation. CONCLUSION: The sharp increase and wide geographic variation in radical prostatectomy rates make the evaluation of this surgical procedure a pressing issue. The rising rate of radical prostatectomy among men aged 75 years and older merits special attention.

Aged↗

Patient-reported complications and follow-up treatment after radical prostatectomy. The National Medicare Experience: 1988-1990 (updated June 1993).

To estimate the probabilities of complications and follow-up treatment, a sample of Medicare patients who underwent radical prostatectomy (1988 through 1990) was surveyed by mail, telephone, and personal interview. Respondents reported their current status with respect to continence and sexual function as well as post-surgical treatments they had had to treat residual or recurrent cancer or surgical complications. Over 30 percent reported currently wearing pads or clamps to deal with wetness; over 40 percent said they drip urine when they cough or when their bladders are full; 23 percent reported daily wetting of more than a few drops. About 60 percent of patients reported having no full or partial erections since their surgery, and only 11 percent had any erections sufficient for intercourse during the month prior to the survey. Six percent had surgery after the radical prostatectomy to treat incontinence; 15 percent had treatments or used devices to help with sexual function; 20 percent report having had post-surgical treatment for urethral strictures. In addition 16 percent, 22 percent, and 28 percent reported follow-up treatment for cancer (radiation or androgen deprivation therapy) at two, three, and four years after radical prostatectomy. These estimates of complication and follow-up treatment rates are generally higher, and almost certainly more representative for older men, than estimates previously published. Patients and physicians may want to weight heavily the complications and need for follow-up treatments when considering radical prostatectomy for prostate cancer.

Aged↗

Telephone care as a substitute for routine clinic follow-up.

DESIGN: Randomized trial. SETTING: A primary care clinic. PATIENTS: Four hundred ninety-seven men aged 54 years or older. OBJECTIVE: We examined the hypothesis that substituting clinician-initiated telephone calls (telephone care) for some clinic visits would reduce medical care utilization without adversely affecting patient health. INTERVENTION: Clinicians were asked to double their recommended interval for face-to-face follow-up and schedule three intervening telephone contacts; for control patients, the follow-up interval recommended by their clinician was unchanged. MAIN OUTCOME MEASURES: Use of medical services and health status. RESULTS: During the 2-year follow-up period, 7% of patients withdrew or became unavailable. Telephone-care patients had fewer total clinic visits, scheduled and unscheduled, than usual-care patients (19%, P less than .001). In addition, telephone-care patients had less medication use (14%, P = .006), fewer admissions, and shorter stays in the hospital (28% fewer total hospital days, P = .005), and 41% fewer intensive care unit days (P = .03). Estimated total expenditures for telephone care were 28% less per patient for the 2 years ($1656, P = .004). For the subgroup of patients with fair or poor overall health at the beginning of the study (n = 180), savings were somewhat greater ($1976, P = .01). In this subgroup, improvement in physical function from baseline (P = .02) and a possible reduction in mortality (P = .06) were also observed. CONCLUSION: We conclude that substituting telephone care for selected clinic visits significantly reduces utilization of medical services. For more severely ill patients, the increased contact made possible by telephone care may also improve health status and reduce mortality.

Analysis of Variance↗

The short-term effect of patient health status assessment in a health maintenance organization.

This study was designed to test the short-term effects of health assessment on the process of care and patient satisfaction. The 29 Chart physicians used the Dartmouth COOP Charts to measure their adult patients' health status during a single clinical encounter; the 27 control clinicians used no measure of health status. We compared the change between baseline and post-intervention information for a sample of all study clinicians' patients. Most of the patients were female (67%), well educated (70% had at least a college education) and young (approximately 90% were aged 59 years or younger). We found that the ordering of tests and procedures for women was increased by exposure to the COOP Charts (52% vs. 35%; p < 0.01); the effect in men was not as significant (37% vs. 23%: p = 0.06). Although women reported no change in satisfaction with care, men claimed that the clinician helped in the management of pain (p = 0.02). We conclude that the use of health status measures during a single clinical encounter in an HMO changes clinician test ordering behaviour and may improve the help male patients receive for pain conditions. The long-term impact of these management changes is not known.

Episode of Care↗

Benefits and obstacles of health status assessment in ambulatory settings. The clinician's point of view. The Dartmouth Primary Care COOP Project.

In the past decade physicians have identified the need to expand patient assessment to include global function and quality of life. During the same period, the busy clinic has evolved into the location where this assessment seems most appropriate. Integrating functional health assessment into a busy clinical practice is difficult because the necessary steps require time, thought, recording, and follow-up. Attention to the office ecosystem is very important before any patient care management method is introduced. The clinician must transform the results of health status screening into a specific functional diagnosis. The clinician has to understand the sensitivity, specificity, and predictive value of the measure for a preliminary diagnosis to be made. Often, additional measurements must be taken to establish a specific diagnosis. These steps encompass assessment linkage. Once the specific cause for the dysfunction is recognized, the clinician then has to determine the need for special resources. This is called the resource linkage. By following the steps outlined in this paper, the clinician should be able to overcome many obstacles for functional health status assessment in busy ambulatory settings.

Activities of Daily Living↗

A modified reaction cartridge for direct protein sequencing on polymeric membranes.

A newly designed reaction vessel implements a vertical cross-flow type reactor with the Applied Biosystems multi-mode reaction cartridge design. This cartridge is designed for sequencing samples on polyvinylidine difluoride-type membranes. The benefits of this design include a reduced reaction chamber volume that results in lower rates of chemical consumption and less risk of sample loss or contamination during sequencing. Visualization of the membrane in the reaction chamber during sequencing facilitates optimization of drying, washing, extraction and transfer times. The cycle modifications described in this report are designed to optimize post-coupling extraction, cleavage and post-cleavage extraction steps during "flow across" conditions for polymeric membranes. Also, efficient washing and drying of membranes allows for a fast cycle time of 30 minutes when using Pulsed Liquid chemistry. Examples of Blott cartridge utility for sequencing polyvinylidine difluoride-bound proteins in the low picomole range are shown by analyzing samples prepared by a two-dimensional purification scheme using the 230A HPEC and sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Amino Acid Sequence↗

Opting for a mid-career change: two viewpoints.

While the medical record practice world offers fast-paced days and opportunity for much advancement, the benefits of being an educator include a flexible schedule and time to do research. Here are the opinions of two women who made mid-career changes.

Career Choice↗

A discussion of pediatric modified DRGs.

In an effort to improve the original DRG system to accurately quantify and articulate the more complex children's conditions, the National Association of Children's Hospitals and Related Institutions, Inc. (NACHRI) developed Pediatric Modified DRGs (PM-DRGs). Following is a discussion of why PM-DRGs were developed, how they work, and where their strengths and limitations lie.

Adolescent↗

Consistent N-myc copy number in simultaneous or consecutive neuroblastoma samples from sixty individual patients.

Amplification of the N-myc oncogene is detected in about 30% of untreated neuroblastomas. Amplification is associated with advanced stages of disease and rapid tumor progression. However, it was not known if the N-myc copy number was homogeneous in tumor tissue of an individual patient, or if it changed with time in vivo. Therefore, we have made 66 observations on multiple simultaneous or consecutive tumor samples from 60 patients with neuroblastoma. (a) Simultaneous samples were obtained from different areas of 31 tumor masses from 30 patients: a similar N-myc copy number (1-2, 3-10, or greater than 10) was found in all samples from each patient. (b) Simultaneous samples were obtained from different anatomical sites in ten patients. No difference in N-myc copy number was seen. (c) Finally, 25 patients had two or more tumor samples obtained over time. Thirteen patients had a single copy of N-myc in all samples, and 12 had consistent levels of amplification in all samples. Two of the latter cases had single copy of N-myc in a second-look surgery sample, but no tumor was evident histologically. This study demonstrates that the N-myc copy number in human neuroblastomas is usually consistent within a tumor, not only at different tumor sites, but also at different times in vivo. Overall, these findings suggest that N-myc amplification is an intrinsic biological property of a subset of neuroblastomas, and if amplification is going to occur, it is generally present at the time of diagnosis.

Child↗

Characterization of glucocorticoid receptors in S49 mouse lymphoma cells by affinity labeling with [3H]dexamethasone 21-mesylate.

Glucocorticoid receptors in wild type and mutant S49 mouse lymphoma cells were affinity labeled with [3H]dexamethasone 21-mesylate and analyzed directly by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular weight of receptors in cytosol from wild type cells and nuclear transfer decreased (nt-) mutants was 97,000 (97 kDa). The molecular weight of receptors in cytosol from nuclear transfer increased (nti) mutants was 48 kDa. The 97 kDa receptor in cytosol from wild type cells was digested by chymotrypsin to a 40 kDa steroid-binding receptor fragment but the 48 kDa receptor in cytosol from nti mutants was resistant to digestion by chymotrypsin. In addition to the 48 kDa receptor, cytosol from nti mutants contained 40 and 18 kDa receptor fragments. Cytosol from the nt- mutants also contained 18 kDa receptor fragments. The 40 and 18 kDa receptor fragments were present in multiple subclones of a nti mutant cell line. Formation of these receptor fragments was not prevented by protease inhibitors and was not increased by extended incubation of cytosol samples. Both 48 and 40 kDa forms of the receptor, but not the 18 kDa form, could be activated and bound by DNA-cellulose.

Affinity Labels↗

Assessment of function in routine clinical practice: description of the COOP Chart method and preliminary findings.

The COOP Project, a primary care research network, has begun development of a Chart method to screen function quickly. The COOP Charts, analogous to Snellen Charts, were pretested in two practices on adult patients (N = 117) to test feasibility, clinical utility, and validity. Patients completed questionnaires containing validated health status scales and sociodemographic variables. Practice staff filled out forms indicating COOP Chart scores and clinical data. We held debriefing interviews with staff who administered the Charts. The results indicate the Charts take 1-2 minutes to administer, are easy to use, and produce important clinical data. The patterns of correlations between the Charts and validity indicator variables provide evidence for both convergent and discriminant validity. We conclude that new measures are needed to assess function in a busy office practice and that the COOP Chart system represents one promising strategy.

Activities of Daily Living↗