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Biomedical subjects

K A Nelson

Publications and source records attributed to K A Nelson.

At least 55 records · Page 3Linked to original sources

Skeletal unloading causes organ-specific changes in immune cell responses.

The effects of skeletal unloading using antiorthostatic tail suspension on the mouse immune system are tissue specific. This phenomenon was demonstrated by analyzing cells from the lymph nodes, spleen, and bone marrow. Phytohemagglutinin-induced T-cell proliferation was depressed in lymph nodes after 11 days of antiorthostatic suspension. In contrast, splenic T-cell proliferation in response to phytohemagglutinin was enhanced. Splenic natural killer cell cytotoxicity was unchanged after suspension, which demonstrated the organ- and cell-specific effects of skeletal unloading. Whereas antiorthostatic suspension induced minimal changes in bone, there was a significant depression in the number of macrophage precursors in the bone marrow. Overall, skeletally unloaded animals had slightly higher blood corticosterone levels than did control animals; however, it did not appear to be responsible for the observed changes. In conclusion, skeletal unloading produces organ- and cell-specific changes in the murine immune system rather than a generalized immunosuppression.

Animals↗

Why referred potential heart donors aren't used.

Heart donor demand far exceeds supply. We evaluated donor referrals to 1 organ procurement agency in an attempt to determine why many potential cardiac donors are not used. Of 430 referrals between September 1989 and August 1991, 169 hearts (39%) were harvested. In potential donors ultimately not yielding a heart, 38.7% were unavailable because the family refused to consent to organ donation, 36% were medically unsuitable, and 16.1% did not meet standard brain death criteria. Of the 94 donors not used for medical reasons, 43.6% had cardiac arrest, 17% had hypotension, 12.8% were drug abusers, 6.4% had sepsis, 5.3% had hepatitis, 5.3% had an acute myocardial infarction, 3.2% had low ejection fraction levels, and 2.1% tested positive for human immunodeficiency virus or syphilis (4.3% were not specified). A significant difference (p = 0.001) in racial distribution surfaced; Blacks and Hispanics constituted 27.2% of the donor group but 46.3% of the non-donor group. These data confirm that strategies must be created to continue educating the public and physicians in order to increase consent rates, optimize donor selection, and improve physician awareness of brain death criteria.

Adult↗

Metoclopramide in anorexia caused by cancer-associated dyspepsia syndrome (CADS).

Anorexia is a common problem in advanced cancer, part of the cancer anorexia-cachexia syndrome. Although the etiology is multifactorial, symptoms suggestive of gastroparesis are often present in patients with cancer anorexia. We have successfully used metoclopramide, a prokinetic agent, to stimulate appetite in advanced cancer and relieve other dyspeptic symptoms associated with anorexia.

Administration, Oral↗

Assessment of upper gastrointestinal motility in the cancer-associated dyspepsia syndrome.

Cancer patients experience many gastrointestinal symptoms which may lead to weight loss. Assessment of gastrointestinal motility may contribute to our understanding of these symptoms and suggest rational therapeutic approaches to the anorexia-cachexia syndrome. We have evaluated a simple, inexpensive, well-tolerated test of upper gastrointestinal motility in patients with advanced cancer. One-centimetre portions of radiopaque nasogastric tubing were ingested with food. Six hours later, a flat-plate abdominal x-ray was obtained to determine the marker placement. Patients were evaluated for gastrointestinal symptoms. Those with more symptoms, particularly early satiety, had a greater incidence of reduced upper gastrointestinal motility.

Adult↗

Nucleoside cyclic 3',5'-phosphates: chair-twist equilibria of the phosphate rings of methyl phosphate and phenylphosphonate derivatives of cTMP.

The cis and trans forms of thymidine methyl cyclic 3',5'-phosphate (9) and of the corresponding phenylphosphonate derivatives (10) were prepared in two steps from the corresponding cyclic amide. 1H NMR spectroscopy showed the phosphorus-containing six-membered rings of cis-9 (MeO and thymin-1-yl cis) to be in the chair conformation, but trans-9 to be approximately 40% in the twist conformation in pyridine-d6 and 33% in acetone-d6. For trans-9, there was resistance of conversion of the chair form into the twist form with the MeO group pseudo-axial with a delta G degrees(C-->T) value of 3.0 kcal/mol. Similarly, for cis-10 (23-39% twist population in CD3CN, acetone-d6, and CDCl3), a delta G degrees(C-->T) value of 0.5-0.6 kcal/mol for placement of the phosphoryl oxygen pseudo-axial was obtained. Both values are taken to be approximations for delta G degrees(C-->T) for cTMP. For trans-10, the twist conformation was populated to the extent of 6-13% with a delta G degrees(C-->T) value of 1.3 kcal/mol.

Hot Temperature↗

Interphase cytogenetics in paraffin sections of routinely processed hydatidiform moles and hydropic abortions.

The differential diagnosis of complete (CM) and partial (PM) hydatidiform moles and hydropic abortions (HA) can be difficult when based on histology alone. Therefore, a more objective approach of chromosome ploidy analysis as detected by in situ hybridization (ISH) was performed on 6 microns paraffin sections of seven cases, originally classified as three CM, two PM, and two HA with a histologic pattern suggestive of triploidy. Probes for repetitive DNA targets in the (peri)centromeric region of chromosomes 1 and X and in the q arm of chromosome Y were used to determine chromosome ploidy and sex chromosome composition. The findings in the three CM were consistent with diploidy: two copies of chromosomes 1 and X and none of chromosome Y. In the two HA with a histologic pattern suggestive of triploidy, three copies of chromosomes 1 and X and none of chromosome Y confirmed triploidy. Two cases originally classified as PM both appeared to have two copies of chromosome 1 with an XX pattern in one case and an XY pattern in the other case, which is consistent with diploidy instead of triploidy. After reviewing, both cases most likely represented CM. We conclude that interphase cytogenetics by ISH on paraffin sections of hydatidiform moles and hydropic abortions enables chromosome ploidy analysis with preservation of histological context.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Missed↗

Acute lumbosacral plexopathy in diabetic women after renal transplantation.

Renal transplantation is an accepted treatment for patients with end stage renal disease from insulin-dependent diabetes mellitus. Acute lumbosacral plexopathy developed following renal transplantation in 4 female patients with insulin-dependent diabetes mellitus between January 1, 1981 and June 30, 1988. In all 4 patients the internal iliac artery was used for revascularization of the renal allograft with ligation of the anterior and posterior divisions. Within 24 hours of surgery they complained of ipsilateral buttock pain, numbness in the leg and weakness below the knee. This complication has not been observed in nondiabetic patients at our institution, nor in diabetic patients when the internal iliac artery was not used. However, lumbosacral plexopathy occurred in 4 of 27 (14.8%) female patients with insulin-dependent diabetes mellitus when the internal iliac artery was used (p less than 0.001). Age, duration of insulin-dependent diabetes mellitus, hypertension, cigarette smoking history and kidney donor were not significant predictors of this complication. This unusual and newly recognized complication appears to result from ischemia of the lumbosacral plexus following ligation of the internal iliac artery in patients with severe small vessel disease.

Acute Disease↗

Ten years of training community urologists and general surgeons to do cadaver kidney retrievals.

We trained 82 community hospital cadaver kidney retrieval teams during a 10-year period ending June 30, 1987. During the last 5 years of that period the concept of multiple organ retrieval was introduced into the training sessions and 429 cadaver kidney grafts were retrieved. Of those kidneys 292 were transplanted at our hospital, and the function of 220 cadaver kidney grafts retrieved by the community hospital teams was compared to that of 72 retrieved by the transplant center retrieval team. Of the cadaver kidney transplants 114 were from multiple organ donors. There was no significant difference in 1-month serum creatinine nadir of surviving grafts (2.1 +/- 1.8 versus 1.9 +/- 1.7 mg. per dl.), 6-month serum creatinine level (1.7 +/- 0.8 versus 1.6 +/- 0.6 mg. per dl.), 12-month serum creatinine level (1.8 +/- 0.9 versus 1.6 +/- 0.6 mg. per dl.) and 5-year actuarial graft survival (44.8 +/- 4.1 versus 52.4 +/- 7.5%), with the community hospital data presented first. The delayed graft function rate was significantly higher in the recipients of cadaver kidney grafts retrieved by community hospital teams (54 versus 35%), which was reduced by the in situ flush technique. There was no significant difference in delayed graft function rate (48 versus 40%) for the 114 cadaver kidney transplants retrieved from multiple organ donors by either community hospital or transplant center teams. With continuing education and quality control, community hospital retrieval teams can provide kidneys satisfactory for transplantation, even when working with multiple organ retrieval teams.

Actuarial Analysis↗

Description of a delivery method for continuously aerosolized albuterol in status asthmaticus.

The use of continuously nebulized beta agonists may be considered in the treatment of status asthmaticus, particularly when conventional therapy is failing. Methods of administration of continuously nebulized beta agonists may be cumbersome. We describe a delivery method which allowed simplification of this process, yielded accurate delivery of a specified dose of albuterol, and was beneficial in a reported case of status asthmaticus.

Adult↗

The use of knee braces during rehabilitation.

This article has profiled the use of knee braces as an augmentation to the overall rehabilitation program following knee injury. It has also outlined other aspects of rehabilitation, the use of continuous passive motion devices, and other forms of exercises and training that, together with bracing, may enhance patient recovery. Continuous passive motion devices have been used for many different orthopedic problems with good success. Understanding the mechanics of how these devices move the knee and the forces that can be applied to the knee is helpful in deciding on their use after ligamentous reconstructions. Rehabilitation of the knee following surgery requires a good understanding of the effects that each exercise has on the knee and the reconstruction. Gradual progression of exercises to the knee following knee ligament reconstruction will not overstress healing tissues. Many different types of knee braces exist, and careful evaluation of them may enhance patient recovery.

Anterior Cruciate Ligament↗

HLA-DQw3-related determinants: analysis of subunit and spatial relationships.

More polymorphism exists among DQ region gene products than is suggested by present serologic definitions of these class II molecules. DQ beta polymorphism among haplotypes carrying the DQw3 specificity is considerable. The TA10 specificity is present on one allele of at least three different DQ beta alleles that carry the DQw3 specificity. We have examined a series of monoclonal antibodies directed against different DQ beta alleles carrying the DQw3 specificity to determine subunit and spatial relationship among the epitopes detected by these antibodies. The antibodies were examined by Western blotting and for their ability to inhibit the binding of fluoresceinated antibodies on either TA10+ or TA10- DQw3 haplotypes. Our results reveal that (1) multiple DQw3-related epitopes exist; (2) several anti-DQw3-related antibodies generated against TA10- DQw3 molecules are unable to inhibit the binding of a TA10-specific antibody on a TA10+ haplotype while strongly inhibiting binding of an antibody detecting the reciprocal DQ beta polymorphism on a TA10- DQw3 haplotype; and (3) there is a strong requirement for three-dimensional conformation in the formation of the majority of the epitopes examined here. Analysis of previously published amino acid sequences for the haplotypes investigated here suggest that charge changes at amino acids 45, and 57, respectively, may have a significant effect in changing the spatial relationship between the DQw3-related epitope(s) and other polymorphic determinants on DQ beta chains.

Amino Acid Sequence↗

Immunotherapy of murine sarcomas with auto-anti-idiotypic monoclonal antibodies which bind to tumor-specific T cells.

Hybridomas producing monoclonal antibodies (mAb) were obtained from BALB/c mice immunized against either of two transplanted, chemically induced syngeneic sarcomas, MCA-1490 or MCA-1511. Two mAb, 4.72 and 5.96, were obtained, one from each immunization. They were found to have apparent anti-idiotypic specificity in that they, when injected s.c., primed naive BALB/c mice for delayed-type hypersensitivity that was specific for the immunizing tumor and required homology at genes linked to the Igh-1 allotype locus. Neither mAb bound tumor antigen. When mice with established transplants of MCA-1490 or MCA-1511 were treated by repeated i.p. injections of the appropriate anti-idiotypic mAb (4.72 and 5.96, respectively), a significant reduction in tumor growth was observed in those mice that had received the appropriate mAb. The idiotope defined by mAb 4.72 was expressed by T cells in mice responding to MCA-1490. mAb 4.72 bound to T cell suppressor factors that were specific for MCA-1490 and were derived from T cell hybridomas or sera of mice bearing MCA-1490. mAb 4.72 also bound to cells from lymph nodes draining the area of a growing MCA-1490 tumor. It was used, in combination with cell sorting, to establish a T cell line, which mediated delayed-type hypersensitivity to MCA-1490 and inhibited the outgrowth of MCA-1490 in BALB/c mice. Thus, mAb specific for idiotopes on T cells responding to syngeneic tumor antigen had both direct immunotherapeutic activity and could be used to establish cultures of tumor-reactive T cells.

Animals↗

Induction of immunity to a human tumor marker by in vivo administration of anti-idiotypic antibodies in mice.

Anti-idiotypic antibodies are described that were raised against murine monoclonal antibody 8.2, an antibody specific for a human melanoma-associated cell surface marker called p97. The 8.2 idiotopes recognized by this anti-idiotypic antiserum are binding site-associated and are shared by other monoclonal anti-p97 antibodies with the same specificity as antibody 8.2. Mice immunized with the anti-idiotype demonstrate delayed-type hypersensitivity reactions when challenged with melanoma (p97-positive) tumor cells.

Animals↗

Broviac catheter-related bacteremia in oncology patients.

In 27 pediatric oncology patients (median age, 2 years) undergoing chemotherapy for malignant tumours, Silastic Broviac catheters were placed to provide vascular access. The catheters were in place for a total of 174 patient-months. There were 14 episodes of Broviac catheter-related bacteremia or fungemia that occurred in six patients: one patient had six bacteremic episodes, one patient had four episodes, and four patients each had one bacteremic episode. Cultures of blood drawn from Broviac catheter were positive in all instances, and in 12 of 14 samples drawn from the peripheral vein. The most common initial symptoms were fever and chills. The species causing the infections were Enterobacter cloacae (three cases), Staphylococcus epidermidis (three cases), Staphylococcus aureus (three cases), Klebsiella pneumoniae (two cases), Escherichia coli (two cases), Pseudomonas dentrificans, Pseudomonas aeruginosa, and Candida tropicalis. Antimicrobials administered through the catheter cured the infection in ten of the 11 cases in which they were used.

Adolescent↗

Detection of antibodies to embryonic antigens in sera of multiparous or colon tumor-bearing rats by a new indirect immunofluorescence assay.

An indirect immunofluorescence assay using antigen coupled to agarose beads detected high titers of antibody to embryonic antigens in sera from multiparous rats and rats bearing colon carcinomas. Sera from pregnant rats had antibody titers greater than 10(3) and some rats still had titers greater than 10(2) 30 weeks after the end of pregnancy. Rats which developed colon carcinomas after treatment with 1,2-dimethylhydrazine were bled monthly between the end of treatment and detection of carcinoma. Antibody to embryonic antigens appeared in their sera at least 2 months before roentgenologic diagnosis of tumor.

Animals↗