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J W Freeman

Publications and source records attributed to J W Freeman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Novel mutations in the polyadenine tract of the transforming growth factor beta type II receptor gene are found in a subpopulation of human pancreatic adenocarcinomas.

In this study, we determined the incidence of microsatellite instability (MIN) in pancreatic adenocarcinoma and determined whether MIN might target, for mutations, the simple nucleotide repeats of the transforming growth factor beta type II receptor (TGFBR2) gene. Forty-eight surgically resected pancreatic tumor tissue samples and two normal pancreas tissue samples were analyzed in this study. Microsatellite analysis was performed for six loci in 14 of the 48 tumor specimens for which we had matching normal genomic DNA. Only four of the 14 tumors (29%) were MIN-positive as determined by the presence of microsatellite variations in more than one locus. Interestingly, eight of the 14 specimens (57%) showed microsatellite variations or loss of heterozygosity at D18S34, suggesting that this locus may be a critical region of genetic instability in pancreatic tumorigenesis. Of the 48 tumors, only two (4%) showed mutations in the polyA region, one of the MIN-targeted sites of the TGFBR2 gene. DNA sequence analysis of these two specimens showed the presence of a two-base deletion in one tumor specimen and the other tumor specimen showed a base substitution in the polyA tract at codon 128 of the TGFBR2 gene. The fact that these mutations occurred in the polyA tract of some pancreatic tumors suggests that a subpopulation of these tumors may be susceptible to MIN-targeted mutations. The incidence of these mutations are low and similar to that reported for nonhereditary, sporadic colon cancers.

Adenocarcinoma↗
PubMed1998

A randomized trial of solvent/detergent and standard fresh frozen plasma in the treatment of the coagulopathy seen during Orthotopic Liver Transplantation.

BACKGROUND: Viral transmission remains a residual risk in single unit blood component therapy. Virus inactivation of pooled fresh frozen plasma (FFP) by the solvent/detergent (SD) method can be used to reduce this risk but results in some loss of factor activity including factor VIII and (2-antiplasmin. This study was aimed at assessing the clinical effectiveness solvent/detergent treated pooled fresh frozen plasma (SDFFP) in the correction of the coagulopathy seen during Orthotopic Liver Transplantation (OLT) as compared with standard FFP. METHOD: Twenty eight patients with an underlying derangement of coagulation and who were due to undergo OLT were randomized to receive either FFP or SDFFP. They were assessed for side effects, correction of coagulopathy, and seroconversion for viral markers. RESULTS: Patients undergoing OLT showed equal correction of clotting factors and partial thromboplastin time (PTT) when treated with FFP or SDFFP. There was also a similar time course to return to baseline values in each group. There was no significant difference in correction of INR in either group. Usage of other blood components during the operation was identical in the two groups. No seroconversions were seen for HIV, HBC or HCV but only 12 patients were available for long term follow-up. CONCLUSION: SDFFP is an efficacious and safe source of coagulation factors for patients with liver disease undergoing Orthotopic Liver Transplantation. No adverse effects were seen during its administration. Further work is required to ascertain long term possibilities of seroconversion.

Adult↗
PubMed1998

Abnormal spinal fluid in hypertensive encephalopathy.

A 44-year-old white male presented with marked hypertension and encephalopathy. His spinal fluid showed a neutrophilic pleocytosis in the absence of infection. While cases of hypertensive encephalopathy with concomitant minor lymphocytic pleocytosis have been occasionally described, it is distinctly abnormal to have a neutrophilic pleocytosis in this setting.

Adult↗
PubMed1998

Making change.

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Clinical Medicine↗
PubMed1998

Nursing home performance under case-mix reimbursement: responding to heavy-care incentives and market changes.

OBJECTIVE: To examine the effect of case mix-adjusted reimbursement policy and market factors on nursing home performance. DATA SOURCES AND STUDY SETTING: Data from Medicaid certification inspection surveys, Medicaid cost reports, and the Kentucky State Center for Health Statistics for the years 1989 and 1991, to examine changes in nursing home performance stemming from the adoption of case mix-adjusted reimbursement in 1990. STUDY DESIGN: In addition to cross-sectional regressions, a first-difference approach to fixed-effects regression analyses was employed to control for facility differences that were essentially fixed during the survey years and to estimate the effects of time-varying predictors on changes in facility expenditures, efficiency, and profitability. PRINCIPAL FINDINGS: Facilities that increased the proportion of Medicaid residents and eliminated excess capacity experienced higher profitability gains during the beginning phase of case-mix reimbursement. Having a heavy-care resident population was positively related to expenditures prior to reimbursement reform, and it was negatively related to expenditures after the case-mix reimbursement policy was introduced. While facility-level changes in case mix had no reliable influence on costs or profits, nursing homes showing an increased prevalence of poor-quality nursing practices exhibited increases in efficiency and profitability. At the market level, reductions in excess or empty nursing home beds were accompanied by a significant growth in home health services. Moreover, nursing homes located in markets with expanding home health services exhibited higher increases in costs per case-mix unit. CONCLUSIONS: Characteristics of the reimbursement system appear to reward a cost minimization orientation with potentially detrimental effects on quality of care. These effects, exacerbated by a supply-constrained market, may be mitigated by policies that encourage the expansion of home health service availability.

Certification↗
PubMed1998

Speculation.

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Communication↗
PubMed1997

Discrimination of late apoptotic/necrotic cells (type III) by flow cytometry in solid tumors.

A method is described for the discrimination of Type III, late apoptotic, and necrotic cells, to improve the accuracy of proliferation and ploidy determinations of breast tumors. We selected an immunological probe, antitubulin antibody, and a DNA specific stain, propidium iodide (PI), both capable of crossing the permeable membranes of Type III, late apoptotic, and necrotic cells. This study utilized MDA-MB-175-VII breast carcinoma cells deprived of oxygen for up to 11 d to simulate intratumoral hypoxia, and 10 human breast tumors and mouse-human breast tumor xenografts disassociated by mechanical or enzymatic means. After 24 h under hypoxic conditions, the MDA cells displayed characteristics associated with both apoptosis and necrosis. Approximately 50% of day 1 cells showed membrane permeability by trypan blue and absence of DNA laddering; however, by day 3-4 characteristic apoptotic DNA laddering by gel electrophoresis was evident. Substantial DNA content loss, further evidenced by a reduction in PI staining and fluorescent microscopy, was obvious by day 5. By day 10, 98% of cells showed no propidium iodide staining by conventional PI live/dead cell gating, but were positive for antitubulin antibody staining. When the study was extended to the analysis of ten tumors, antitubulin antibody showed a range of 78%-96% staining with a median value of 87.5%, while PI staining showed a range of 8%-74% with a median value of 11.5%. This study demonstrates that a large percentage of cells in tumors and hypoxic cell populations have significantly reduced DNA content, such that conventional live/dead cell gating using PI may include many Type III cells as live cells, thus significantly altering data involving multicolor investigations.

Animals↗
PubMed1997

Alternative/complementary therapies.

The national trends and our regional experience of the utilization of complementary therapies suggest that a significant number of our patients will continue to employ remedies that are outside the mainstream of what has been defined as conventional Western medicine. The data obtained from our survey is very consistent with the national survey published in 1993. Indeed the national interest in alternative/complementary therapies seems to be growing. A recent newspaper article from Minneapolis noted that Allina, one of Minnesota's largest hospital and HMO systems, found, in a 1995 survey, that two-thirds of surveyed households had a least one member who had used some type of alternative or holistic care over the prior two year period. Certainly continued study of the safety and efficacy of alternative/complementary therapies is warranted. This work is being done on many fronts, including the Office of Alternative Medicine at the National Institutes of Health. A most important aspect of such investigations is to improve the understanding of why patients choose these unconventional remedies. For many patients, the answer is simple. They believe these alternative treatments work. For such patients, alternative therapies may constitute a practical way to move from the sterile "high tech" realm of traditional medicine to a more intimate, "high touch" intervention offered by non-physicians. In the end, physicians' most pressing mandate is "to be of use" to patients in their struggles with illness, disability, and impending death. None of us have all the answers, and the studies alluded to in this essay suggest that a significant segment of the population yearns for interventions that have been traditionally outside the practice of most physicians and nurses. The data from our survey corroborates the high utilization rate of alternative/complementary therapies, regionally and is consistent with national data. Our challenge, as caregivers, is to appropriately respond to the notable prevalence of alternative health practices and to the complex societal factors which nurture this usage.

Adolescent↗
PubMed1996

Regulation of P120 mRNA levels during lymphocyte stimulation: evidence that the P120 gene shares properties with early and late genes.

P120 is a growth-regulated nucleolar protein, the expression of which is required for G1- to S-phase transition in lymphocytes. P120 appears to be involved in ribosomal biogenesis presumptively through its putative role as a rRNA methyltransferase. To better understand the role of P120 in cell cycle progression, we examined the regulation of the P120 gene in resting lymphocytes and in mitogen-stimulated lymphocytes as they progress from G1-phase toward S-phase. P120 mRNA was detected after the immediate early gene c-fos and persisted as the cells approached S-phase. A decrease in P120 mRNA coincided with the expression of histone H3 mRNA. The level of P120 mRNA increased as cells proceeded through G1-phase, and this increase was attributed to a more than threefold increase in the P120 transcription rate and an increase in P120 mRNA stability. The P120 gene is transcribed in resting lymphocytes, although the steady-state level of P120 is small or nonexistent. P120 mRNA accumulates in resting cells in the presence of the protein synthesis inhibitor cycloheximide. Furthermore, the steady-state level of P120 mRNA increases in the presence of cycloheximide after PHA-stimulation; this level does not increase in cells not treated with this protein synthesis inhibitor. The presence of cycloheximide increases both the transcription rate of the P120 gene and the stability of P120 mRNA. These studies indicate that P120 expression is cell cycle regulated in a complex manner and that the P120 gene has properties of both early and late genes. This time ordered regulation for P120 expression may represent a necessary step for the cell cycle associated increase in ribosomal biogenesis that is required for G1-to S-phase transition.

Cell Cycle↗
PubMed1996

Effect of pre-reperfusion portal venous blood flush on early liver transplant function.

Portal venous blood for rinsing out the University of Wisconsin solution (UWs) has the advantages of being a physiological fluid, removing acidotic mesenteric venous blood and perhaps resulting in more stable haemodynamic parameters during reperfusion. A group of 209 consecutive adult OLTs carried out between July 1993 and February 1995 were studied prospectively. The UWs was flushed out with 500 ml portal blood in 95 OLTs (group 1) and with 1.0 L 0.5% dextrose at 37 degrees C in 114 OLTs (group 2). The median day 1 and peak day 1-5 AST levels were significantly elevated in the 5% dextrose group: median 755 (118-11090) vs. 546 (121-6150) IU/I (P = 0.007, Wilcoxon); and median 1095 (159-11090) vs. 744 (157-7870) IU/l (p = 0.008, Wilcoxon), respectively. A median of 5 (0-27) units of blood were transfused in group 1 compared to 4 (0-54) units in group 2 (n.s.). There was no difference in peak bilirubin, lowest day 1-5 PT levels, primary nonfunction, median ITU stay, total inpatient stay and 1-month graft survival between the two groups (89% vs. 88%). Pre-reperfusion blood flush may be associated with less hepatocellular damage, without significant additional blood usage.

Adolescent↗
PubMed1996

Comparison of bladder, oesophageal and pulmonary artery temperatures in major abdominal surgery.

In this study we compared urinary bladder and oesophageal temperatures with the core temperature obtained from a pulmonary artery catheter in patients undergoing orthotopic liver transplantation. The bladder temperature was a closer approximation to pulmonary artery temperature in this group of patients than the oesophageal temperature and has much to recommend it in terms of convenience, safety and postoperative patient comfort.

Anesthesia, General↗