Rural general practice. Past, present and future.
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Anecdotes as Topic↗
Biomedical subjects
T Murphy
Publications and source records attributed to T Murphy.
TSG101 expression in gynecological tumors: relationship to cyclin D1, cyclin E, p53 and p16 proteins.
Recent studies have shown that in vitro steady-state expression of the tumor susceptibility gene TSG101 is important for maintenance of genomic stability and cell cycle regulation. To determine the contribution of TSG101 expression in neoplastic formation, expression of TSG101 protein levels were evaluated in primary ovarian and endometrial adenocarcinoma tumors. Expression of TSG101 was also examined in various tumor cell lines (PA-1, AN3CA, HeLa, HS578T, HCT116). Full-length TSG101 protein was detected in these tumors and cell lines indicating that intragenic deletions were not characteristic of TSG101. In addition, TSG101 protein levels were compared with aberrations of prominent cell cycle regulatory molecules such as cyclin D1, cyclin E, p16 and p53. Reduced TSG101 protein was observed in 36% (8/22) of ovarian and 17% (1/6) of endometrial adenocarcinoma. Aberrant levels of p53, p16, cyclin D or E were comparable to published studies indicating that the clinicopathological distribution of these cases did not favor advanced stage tumors. Altogether, these findings suggest that a down-regulation of TSG101 is associated with tumorigenesis in a subgroup of gynecological tumors.
Adenocarcinoma↗
Case study to evaluate a standing table for managing constipation.
Standing devices have been advocated as a potentially beneficial treatment for constipation in persons with spinal cord injury (SCI); however, definitive data are lacking. A case of a patient who requested a standing table to treat chronic constipation is presented as an illustration of a method to address this problem on an individual patient level. The patient was a 62-year-old male with T12-L1 ASIA B paraplegia who was injured in 1965. The patient was on chronic narcotics for severe, nonoperable shoulder pain. His bowel program had been inadequate to prevent impactions. A systematic approach was used to measure the effects of a standing table on frequency of bowel movements (BMs) and on length of bowel care episodes. There was a significant (p < 0.05) increase in frequency of BMs and a decrease in bowel care time with the use of the standing table 5 times/week versus baseline. For this patient, the use of the standing table was a clinically useful addition to his bowel care program.
Constipation↗
Fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated indolent lymphoid malignancies.
To evaluate the response rate and potential toxicities, a phase II trial was conducted of fludarabine and cyclophosphamide with filgrastim support in patients with previously untreated low-grade and select intermediate-grade lymphoid malignancies. Symptomatic patients with preserved end organ function received cyclophosphamide 600 mg/m(2) intravenous (iv) day 1 and fludarabine 20 mg/m(2) iv days1 through 5, followed by filgrastim 5 microg/kg subcutaneous starting approximately day 8. Treatment was repeated every 28 days until maximum response or a maximum of 6 cycles. Sixty patients, median age 53.5 years, were enrolled. Thirty-seven patients with non-Hodgkin lymphoma (NHL) were stage IV and 6 were stage III. Eleven of 17 patients with chronic lymphocytic leukemia (CLL) were Rai intermediate risk and 6 were high risk. The overall complete response (CR) rate was 51% and the partial response (PR) rate was 41%. Of patients with CLL, 47% achieved a CR and the remaining 53% achieved a PR. Of patients with follicular lymphoma, 60% achieved CR and 32% achieved a PR. Although the toxicity of this regimen was mainly hematologic, significant nonhematologic toxicities, including infections, were seen. Twenty-four patients subsequently received an autologous or allogeneic stem cell transplant. Engraftment was rapid, and there were no noticeable procedure toxicities in the immediate posttransplant period attributable to the fludarabine and cyclophosphamide regimen. Fludarabine, cyclophosphamide, and filgrastim make up a highly active and well-tolerated regimen in CLL and NHL.
Adult↗
Fusion of 9 beta-satellite and telomere (TTAGGG)n sequences results in a jumping translocation.
A newborn was found to have an isochromosome for the short arm of chromosome 9, i(9p) and a jumping translocation of the whole long arm. In 94.4% metaphases, 9q was fused to the telomere of chromosome 19p and, in 5.6% of metaphases, 9q was fused to the telomere of chromosome 8p. The net result was trisomy for the short arm of chromosome 9. With the pan telomere probe, fluorescent in situ hybridization (FISH) investigations found an interstitial telomere on the der(19) and der(8). The 9 beta and classical satellite probes gave a signal only on the long arm of chromosome 9 involved in the jumping translocation. The 9 alpha satellite probe hybridized to i(9p) and not to the other derivative chromosomes. A combination of chromosome 9 (red) and chromosome 19 (green) paint probes used to rapidly screen metaphases for the jumping translocation found 88 metaphases had a der(19)t(9;19) and 4metaphases had a der(8)t(8;9). For the first time, the junction of a jumping translocation has been shown to involve the telomere sequence (TTAGGG)n and beta-satellite sequences by FISH. In this paper, we also review the simultaneous occurrence of an isochromosome for the short arm and translocation of the whole long arm and constitutional jumping translocations.
Asian↗
Gametes, law and modern preoccupations.
This article surveys a range of recent media stories about human gametes, pinning them to a series of wider preoccupations within late modern life. Three preoccupations are singled out: first, kinship and relational identity; secondly, Nature and globalization; and finally, sexual difference and equality. Each one of these preoccupations has been characterised as iconic; debates about them are said to crystallize who we are, especially our uncertainties, and what we will be in the future. By indexing these preoccupations to the stories about human gametes, the article aims to upset both the increasing attempts to present assisted reproduction technologies as 'familiar' (as Nature's 'helping hand', for example) and the recurring assumptions about this technology's alleged 'novelty' and 'anomaly'. The article concludes that treating reproduction technologies, and their regulation, as 'familiar' risks complacency: equally, assumptions about their 'novelty' narrows the search for effective explanatory tools and regulatory mechanisms. The upshot is that it might be best for us to view reproductive technologies as both less 'familiar' and less 'novel'.
Attitude to Health↗
A model that reproduces syndromes associated with human multiple myeloma in nonirradiated SCID mice.
A human myeloma line was used to create a model of human multiple myeloma in vivo that would reproduce the pathophysiology of the disease, including the cachexia associated with cancer. Unirradiated severe combined immunodeficient (SCID) mice were used as surrogate hosts for in vivo experiments that allowed the effects of autocrine (human) verus paracrine (murine) cytokines on the development of myeloma to be studied. Serum levels of human paraprotein increased over time and with the number of cells transplanted. Transplanted mice developed major syndromes, cachexia and paralysis (due to invasion of bones by myeloma cells), associated with multiple myeloma. Analyses of serum samples obtained from transplanted mice revealed that when the mice were terminal, total serum protein decreased on average by 20%, whereas serum triglycerides decreased on average by 50%. These data indicate the mice were cachectic, which was confirmed by necropsy. The mice had low but measurable levels of both human and murine interleukin (IL)-6, soluble IL-6 receptor, and murine IL-10 in their sera. The presence of these cytokines and the IL-6 receptor in sera are also characteristics of human myeloma in patients. Since human cells do not respond to murine IL-6, it was possible to demonstrate clearly the importance of autocrine IL-6 in establishing myeloma in situ. By reproducing both the hallmarks of a cancer as well as the accompanying paraneoplastic syndromes, this model should be useful in designing more effective therapies for both the primary cancer as well as the accompanying secondary diseases.
Animals↗
The ACE gene and Alzheimer's disease susceptibility.
A recent study suggested that the insertion (I) allele in intron 16 of the angiotensin converting enzyme gene (ACE) is associated with Alzheimer's disease (AD) risk. In our series of 239 necropsy confirmed late onset AD cases and 342 elderly non-demented controls aged >73 years, we found significantly different ACE genotype distributions in the case and control groups (p=0.007). Homozygotes for both the I and D alleles were associated with a higher risk compared to DI heterozygotes. While the APOE epsilon4 allele was strongly associated with AD risk in our series, we found no evidence for an interaction between the APOE and ACE loci. In addition, no interactions were observed between ACE and gender or age at death of the AD cases. A meta-analysis of all published reports (12 case-control series in total) suggested that both the II and ID ACE genotypes are associated with increased AD risk (odds ratio (OR) for II v DD 1.36, 95% confidence interval (CI)=1.13-1.63, OR for DI v DD 1.33, 95% CI=1.14-1.53, p=0.0002).
Aged↗
Mechanical strain inhibits expression of osteoclast differentiation factor by murine stromal cells.
Normal dynamic loading prevents bone resorption; however, the means whereby biophysical factors reduce osteoclast activity are not understood. We show here that mechanical strain (2% at 10 cycles per minute) applied to murine marrow cultures reduced 1, 25(OH)(2)D(3)-stimulated osteoclast formation by 50%. This was preceded by decreased expression of osteoclast differentiation factor (ODF/TRANCE). RT-PCR for ODF/TRANCE revealed that ODF/TRANCE mRNA in strained cultures was 59 +/- 3% of that seen in control cultures. No significant effects on total cell count, thymidine uptake, or alkaline phosphatase activity were induced by strain. To isolate the cell targeted by strain, primary stromal cells were cultured from marrow. Mechanical strain also reduced mRNA for ODF/TRANCE to 60% that of control in these cells. In contrast, mRNA for membrane-bound macrophage colony-stimulating factor was not significantly affected. Soluble ODF ( approximately 2 ng/ml) was able to reverse the effect of strain, returning osteoclast numbers to control. Because osteoclast formation is dependent upon ODF/TRANCE expression, strain-induced reductions in this factor may contribute to the accompanying reduction in osteoclastogenesis.
Alkaline Phosphatase↗
The development of a stroke clinical pathway: an experience in a medium-sized community hospital.
Patients with acute ischemic strokes were studied in a medium-sized community hospital in Mississippi. Studies were done before and after implementation of the stroke clinical care pathway with emphasis on the following clinical indicators: 1) performance of a brain CT scan, 2) the search for the etiology of the stroke, 3) whether the patient was treated emergently for hypertension, 4) the use of measures to prevent deep-vein thrombosis, and 5) prophylactic drug treatment against recurrent stroke after hospital discharge. Following application of the clinical pathway, there was a significant improvement in all the clinical indicators that were felt to require further attention and none had a setback. The length of hospital stay was decreased, and there was no significant increase in the hospital costs in the post-pathway study despite an increase in the number of diagnostic and therapeutic procedures performed. When applied properly, clinical pathways can effectively mobilize hospital resources, maximize quality of care, and at the same time minimize costs.
Aged↗
Ubiquinone (coenzyme Q10) and complex I in mitochondrial oxidative disorder of Parkinson's disease.
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Animals↗
The evolution of hospitalist programs.
In just a few years, hospitalist programs have evolved to a third generation, affording key participants an opportunity to reduce inpatient healthcare costs. Because the method of inpatient payment determines the economic winners and losers in the program, the key participants will benefit from the implementation of a program that includes shared incentives. Even though reduced payments for inpatient services might be offset by reduced variable costs for hospitals and increased office revenues for primary care physicians, a hospitalist program is more likely to achieve sustained success if it is structured so that financial rewards are distributed fairly among the participants.
Contract Services↗
Long term outcome and cost in the management of stage I testicular seminoma.
PURPOSE: To validate the use of surveillance as an alternative to adjuvant RT in clinical stage I seminoma, we analyzed our experience with the two approaches in terms of long term outcome and cost. PATIENTS AND METHODS: Between January 1981 and December 1994, 471 patients with stage I testicular seminoma were treated at our institution. Of these, 245 patients received post-operative RT (25 Gy) to the retroperitoneal lymph nodes, and 226 have been managed with surveillance following orchidectomy. Two patients were included in this series twice; both had RT previously for seminoma, were placed on surveillance for a contralateral seminoma and were analyzed for outcome of both primary tumors. The costs associated with both approaches were estimated in 1994 Canadian dollars (C$). RESULTS: With a median follow-up of 7.7 years in the surveillance patients, and 9.7 years in the adjuvant RT cohort, the 5 year actuarial survival for all patients was 97% and the cause-specific survival (CSS) was 99.8%. Of the 226 patients on surveillance 37 patients have relapsed to date; five of those developed a second relapse. One patient has died of disease. Of the 245 patients treated with adjuvant RT, 14 patients have relapsed and none had a second relapse. The CSS was 100%. Thirteen patients on surveillance (5.7%) and 10 patients treated with post-operative RT (4.1%) have received chemotherapy as part of their management. One hundred and eighty-nine patients on surveillance have received no post-orchidectomy treatment to date. Surveillance was more expensive with an average additional cost per patient per year of Can$2620 over 10 years. CONCLUSIONS: Both adjuvant RT and surveillance give excellent results in stage I seminoma. The documented increased risk of second malignant tumors following RT must be taken into account when considering the additional cost of surveillance. The routine use of post-operative RT in stage I seminoma should be reconsidered and a surveillance program offered to all patients as an alternative management option.
Actuarial Analysis↗
Detection of DNA hybridization using the TISPR-1 surface plasmon resonance biosensor.
Biotinylated oligonucleotide probes were immobilized to the gold sensor surface of the TISPR-1 miniature integrated surface plasmon resonance liquid sensor system for the purpose of detecting specific DNA hybridization. The immobilization of the oligonucleotide capture probes was carried out through streptavidin-biotin binding technology. The sensor detected the immobilization of unlabeled DNA through shifts in index of refraction as the molecules entered and remained selectively bound to the surface in the vicinity of the exponentially decaying surface plasmon resonance wave. The surface immobilization chemistry was proven to be stable for long periods of time, reproducible, and practical for detecting DNA hybridization with the TISPR-1. DNA hybridization was detected as a slow, positive, and small (when compared to protein-protein or antibody-antigen binding experiments) increase in the measured index of refraction under passive hybridization conditions by the TISPR-1 sensor. The DNA hybridization signal was significant (index of refraction change of 0.001) when large fragment PCR-amplified DNA products were hybridized to the oligonucleotide probes (S/N = 6-10). The DNA hybridization techniques were demonstrated using DNA sequences from the HIV genome which encode the Tat and Rev genes.
Base Sequence↗
Entrepreneurial spirit in health services.
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Canada↗
Induced expression of CYP2A5 in inflamed trematode-infested mouse liver.
Trematode infections have long been associated with specific types of cancer. We investigated the ability of the liver fluke Fasciola hepatica to alter host enzymes in a manner that might provide insight into the phenomenon of biologically associated cancers. Our data demonstrate an increased activity of the CYP2A5 isozyme in male mouse liver infected with F.hepatica. Induction of this enzyme was further assessed immunohistochemically. The infection affected CYP2A5 distribution in hepatic tissue. Inflammation and proliferation in liver tissue were observed at the same time that CYP2A5 activity increased. This enzyme is known to participate in the metabolism of several carcinogens which are common contaminants in environments of developing countries where parasitic infections may be prevalent.
Animals↗
Rituximab therapy in hematologic malignancy patients with circulating blood tumor cells: association with increased infusion-related side effects and rapid blood tumor clearance.
PURPOSE: Rituximab was recently approved for use in relapsed, low-grade non-Hodgkin's lymphoma; however, few data exist regarding the safety of this agent in patients with a high number of tumor cells in the blood. METHODS AND RESULTS: After the observation at our institution of a rapid reduction of peripheral-blood tumor cells with associated severe pulmonary infusion-related toxicity in two patients with refractory hematologic malignancies, data on three additional cases were collected from physician-submitted reports of adverse events related to rituximab treatment. Five patients with hematologic malignancies possessing a high number of blood tumor cells were treated with rituximab and developed rapid tumor clearance. The median age was 68 years (range, 26 to 78 years). Patients were diagnosed with B-cell prolymphocytic leukemia (n = 2), chronic lymphocytic leukemia (n = 2), or transformed non-Hodgkin's lymphoma (n = 1). All of these patients had bulky adenopathy or organomegaly. All five patients developed a unique syndrome of severe infusion-related reactions, thrombocytopenia, rapid decrement in circulating tumor cell load, and mild electrolyte evidence of tumor lysis, and all required hospitalization. In addition, one patient developed ascites. These events resolved, and four patients were subsequently treated with rituximab without significant complications. CONCLUSION: Rituximab administration in patients who have a high number of tumor cells in the blood may have an increased likelihood of severe initial infusion-related reactions. These data also suggest that rituximab may have activity in a variety of other lymphoid neoplasms, such as chronic lymphocytic leukemia and B-cell prolymphocytic leukemia.
Adult↗
Outpatient diabetes management of Medicare beneficiaries in four Mississippi fee-for-service primary care clinics.
BACKGROUND: As part of a quality improvement initiative aimed at increasing physician compliance with standards of care for diabetes patients, diabetes practice patterns among Medicare beneficiaries in four primary care clinics were examined in Mississippi. METHODS: Retrospective chart reviews of Medicare beneficiaries with a diagnosis of diabetes were conducted to examine physician compliance with recommended diabetes monitoring services. RESULTS: Fifty-three percent of all beneficiaries did not have a recorded A1c test while 54 percent did not have a recorded foot exam. The percentage without foot exams decreased with quarterly visits. Seventy-two percent and 68 percent of patients had testing for lipids and proteinuria, respectively, although variability in types of testing performed was seen. Seventy-six percent of beneficiaries did not have a referral for a dilated eye exam. CONCLUSIONS: The study has uncovered, within several primary care sites in Mississippi, variable documentation of compliance with many clinically relevant recommendations relating to the care of elderly patients with diabetes. These items can be targeted for improvement as part of a statewide quality improvement initiative for Medicare beneficiaries.
Aged↗