Bob Tiffany annual Nursing Lecture. Expert nursing: a necessary extravagance.
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Adult↗
Biomedical subjects
J Clark
Publications and source records attributed to J Clark.
The value of histopathological examination of conceptual products.
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Abortion, Incomplete↗
Role of tryptase in immediate cutaneous responses in allergic sheep.
In this study, we used a specific tryptase inhibitor, APC-366 [N-(1-hydroxy-2-napthoyl)-L-arginyl-L- prolinamide hydrochloride] to investigate the effect of intradermally administered tryptase and tryptase released by antigen challenge on the immediate cutaneous reaction (ICR) in allergic sheep. The surface areas of cutaneous wheals produced by intradermal injections (0.05 ml) of 1 and 10 ng tryptase alone, tryptase combined with 3 U heparin (tryptase-heparin), or Ascaris suum antigen (10(-5) dilution) with or without pretreatment with APC-366 (1 mg/ml) were measured at 20 and 60 min after challenge. Intradermal injections of 1 and 10 ng tryptase alone (n = 7) produced an ICR of < or = 20% of that obtained after injection of histamine (5% wt/vol). Intradermal injection of tryptase-heparin (n = 7), however, resulted in 50 (1 ng) and 82% (10 ng) of the ICR to histamine (both, P < 0.05 vs. tryptase alone). APC-366 inhibited (P < 0.05) the ICR to 1 and 10 ng tryptase-heparin by > or = 70% at all times (n = 8) but had no effect on the histamine-induced ICR (n = 3). A combination of the histamine H1 antagonist chlorpheniramine (2 mg/kg iv) and the H2 antagonist metiamide (3 mg/kg iv) given 40 min before challenge (n = 8) inhibited the response to 1 and 10 ng tryptase-heparin by 42 and 62% at 20 min and by 96 and 86% at 60 min, respectively (all, P < 0.05). APC-366 also blocked the ICR to A. suum antigen by 68% (P < 0.05) in nine sheep. These results indicate that intradermal injection of tryptase-heparin can induce an ICR. This ICR can be inhibited by APC-366 or a combination of the histamine H1 and H2 antagonists, suggesting that the tryptase response is mediated by histamine. APC-366 also blocks the mast cell-mediated ICR to intradermally injected A. suum antigen. Collectively, these results suggest that tryptase may modulate mast cell histamine release.
Animals↗
Mapping the X chromosome breakpoint in two papillary renal cell carcinoma cell lines with a t(X;1)(p11.2;q21.2) and the first report of a female case.
A t(X;1)(p11.2;q21.2) has been reported in cases of papillary renal cell tumors arising in males. In this study two cell lines derived from this tumor type have been used to indicate the breakpoint region on the X chromosome. Both cell lines have the translocation in addition to other rearrangements and one is derived from the first female case to be reported with the t(X;1)(p11.2;q21.2). Fluorescence in situ hybridization (FISH) has been used to position YACs belonging to contigs in the Xp11.2 region relative to the breakpoint. When considered together with detailed mapping information from the Xp11.2 region the position of the breakpoint in both cell lines was suggested as follows: Xpter-->Xp11.23-OATL1-GATA1-WAS-TFE3-SY P-t(X;1)-DXS255-CLCN5-DXS146-OATL2- Xp11.22-->Xcen. The breakpoint was determined to lie in an uncloned region between SYP and a YAC called FTDM/1 which extends 1 Mb distal to DXS255. These results are contrary to the conclusion from previous FISH studies that the breakpoint was near the OATL2 locus, but are consistent with, and considerably refine, the position that had been established by molecular analysis.
Carcinoma, Papillary↗
Transplantation of cartilagenous tissue generated in vitro into articular joint defects.
The purpose of this pilot study was to determine whether isolated rabbit chondrocytes will form cartilagenous tissue in culture and whether this tissue can be used as a cartilage transplant in order to resurface damaged joints. Chondrocytes were isolated from rabbit articular cartilage, plated as a monolayer on Millicell-CMR filters and maintained in cell culture. The cells formed cartilagenous tissue that could be removed from the filter support by two weeks in culture. The chondrocytes synthesize type II collagen indicating that they maintained their phenotype under these conditions. For the transplant studies, two types of articular surface defects, either full thickness into subchondral bone or intra-chondral, were created in rabbits. The cartilagenous tissue was placed in the defect either without fixation or with the topical application of an adhesive agent (Cell-Tak or Nexaband Avian). The joints were examined within two weeks following the surgery. No transplants remained in the defects in those animals in which tissue fixation had been attempted with Cell-Tak. Those grafts fixed into the cartilage defect with Nexaband Avian remained in place but consisted of a condensed layer of acellular tissue. However, cartilagenous tissue was present and intact in five of the six animals in which the transplant had been placed, in the absence of adhesive, into a full thickness defect. In conclusion, cartilagenous tissue generated in vitro can survive transplantation but an appropriate method to fix grafts into intra-chondral defects is required.
Animals↗
Speech perception and production in children wearing a cochlear implant in one ear and a hearing aid in the opposite ear.
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Adolescent↗
Immunotherapy of an experimental adenocarcinoma of the prostate.
We have developed and tested a fractionated, purified and deproteinized emulsion of a mycobacterial cell wall (MCW) and report on a controlled study of this compound in the treatment of the experimental R3327-H adenocarcinoma of the prostate. The intraperitoneal route of administration was found ineffective at the weekly dose of 500 micrograms. The intratumoral administration of 1000 micrograms of MCW exhibited significant antitumor activity. Tumors larger than 2.2 cm.3 in volume showed evidence of temporary regression, but no cures were recorded in these animals. Complete tumor regression was found in 50% of the rats with tumor volumes less than 2.2 cm.3 at the onset of treatment. The animals in this group not responding initially were treated with a second 3-week course of MCW which resulted in complete tumor regression in one-half of the animals, for a total cure rate, in the smaller tumor cohort, of 75%. Mycobacterial cell wall is an effective biological response modifier in the Dunning R3327-H adenocarcinoma of the prostate in Copenhagen rats. Additional studies to elucidate the effect of the compound in relation to dose and tumor volume are underway.
Adenocarcinoma↗
Scintigraphic evaluation of pancreatic transplants using technetium-99m-sestamibi.
UNLABELLED: The purpose of this study was to evaluate the feasibility of using 99mTc-sestamibi in the assessment of pancreatic transplant. METHODS: Ten transplant recipients with a history of insulin-dependent diabetes mellitus were studied. Fourteen 99mTc-sestamibi studies were performed. Each patient was injected intravenously with 10 mCi of 99mTc-sestamibi. Two-second frames were obtained for 1 min, followed by serial dynamic and static images every 5 min for 30 min. Technetium-99m sestamibi studies, read by two nuclear medicine physicians, were correlated with clinicopathologic findings and compared to the ten 201Tl studies obtained in seven of these patients. RESULTS: On 99mTc-sestamibi images, normally functioning grafts showed adequate perfusion on the angiogram and good uptake followed by clearance on static images. Time-activity curves showed an initial upslope followed by a downslope after the initial uptake peak. The quality of 99mTc-sestamibi images was superior to those of 201Tl in five, similar in four and marginally inferior in one paired study. Technetium-99m-sestamibi was used for both flow and static images, whereas a 99mTc radiotracer angiogram was needed to accompany the 201Tl study. CONCLUSION: Our preliminary experience indicates that 99mTc-sestamibi helps evaluate pancreatic transplants and provides high count statistics, which result in better image quality and diagnostic detail. Extensive quantitative studies are being performed to further evaluate this agent's role in the clinical management of pancreatic transplant patients.
Adult↗
Developing an immunisation protocol for the primary health care team.
Health visitors based at the Ely Bridge fundholding practice in Cardiff were concerned about the low uptake in child immunisations. The health visitor team describe how they developed a joint immunisation protocol in collaboration with primary health care team colleagues to enable improved uptake in line with the Health of the Nation and GP contract targets.
Child, Preschool↗
Histologic localization of surgically transplanted syngeneic seminiferous tubule segments into testis with Fast Blue as tracer.
Spermatogenesis is a complex differentiative process influenced by the testicular extratubular and intratubular tissue environments. One method of determining the relative importance of intratubular versus extratubular factors in cases of deficient spermatogenesis has been syngeneic seminiferous tubule transplantation. Generally in such a scheme, tubule segments from a testis deficient in spermatogenesis are transplanted into an intact recipient testis, and the progression of spermatogenesis in transplanted tubules is examined histologically. However, this experimental approach has been complicated by the tedious histologic serial sectioning required to locate these transplanted tubules and the need to distinguish them from recipient testis solely by structural differences. A method is described for the surgical transplantation of seminiferous tubule segments into rat testes that uses prelabeling donor tubules in vitro with the fluorescent tracer Fast Blue to facilitate their localization. The technique was evaluated by transplanting cut segments of Fast Blue-labeled seminiferous tubules from 15-day-old rat testis into normal adult rat testis (recipient), then localizing and histologically examining the progression of spermatogenesis in the transplanted tubules for up to 28 days. Transplanted tubules were easily identified in sections of recipient testis by fluorescent microscopy; intense Fast Blue staining with low background was seen up to 28 days after transplantation. Histologically, transplanted tubules had limited germ cell differentiation in recipient testis for the Fischer rat strain. At 10 days after transplantation, tubules had characteristics qualitatively similar to tubules from 25-day-old rat testis, with increased tubular diameter and abundant germ cells at the pachytene spermatocyte stage.(ABSTRACT TRUNCATED AT 250 WORDS)
Amidines↗
Conservative management of pediatric pancreatic pseudocyst using octreotide acetate.
Pancreatic pseudocysts in children are rare. A total of 213 cases have been reported in the literature, the majority secondary to trauma (65%). Treatment options range from conservative, non-operative management to operative drainage. Octreotide acetate, a long-acting analog of somatostatin, is a synthetic peptide with a variety of endocrine and gastrointestinal functions. Octreotide has been successfully used following pancreatic surgery to reduce exocrine function and most recently in the management of adult pancreatic pseudocysts. We report the efficacy of octreotide, as an adjunct to treatment, in two children with pancreatic pseudocyst. Each child was treated conservatively with bowel rest, hyperalimentation, and octreotide acetate (2.5 micrograms/kg SQ QD). Complete resolution of the pseudocysts occurred within 5 weeks. We conclude that octreotide acetate is a safe and potentially effective adjunct in the treatment of pediatric pancreatic pseudocyst, and should be added to the management of pseudocyst before drainage procedures.
Child↗
Characterization of a vitamin D3-resistant human chronic myelogenous leukemia cell line.
A variant of the chronic myelogenous leukemia cell line, RWLeu-4, that is resistant to the antiproliferative effects of vitamin D3 was established. Although RWLeu-4 proliferation is inhibited by 1 nmol/L vitamin D3, the resistant cells (JMRD3) continue to proliferate in the presence of 100 nmol/L vitamin D3. Both cells express similar patterns of differentiation-specific antigens after treatment with vitamin D3, and both express the retinoblastoma gene product (p110Rb). Vitamin D3 treatment of the sensitive RWLeu-4 cells decreased the level of the p110Rb protein, as well as its phosphorylation. In contrast, vitamin D3 treatment of JMRD3 had no effect on p110Rb expression or phosphorylation. Both RWLeu-4 and JMRD3 express similar vitamin D3 receptors and vitamin D3-inducible enzyme activities. Differences were detected in the DNA binding characteristics of the vitamin D3 receptors as determined by electrophoretic mobility shift studies. However, sequence analysis of the DNA-binding domain and immunoblot analysis showed no differences in the receptors. We conclude that some process subsequent to vitamin D3 receptor activation is altered in JMRD3 that partially separates vitamin D3-induced inhibition of proliferation from the induction of differentiation.
Base Sequence↗
Concurrent cis-platinum and radiation with or without surgery for advanced head and neck cancer.
PURPOSE: This study was undertaken to assess the efficacy of concurrent cis-platinum and radiation in patients with advanced head and neck cancer and to determine if patients responding to the preoperative regimens may be cured without radical surgery. METHODS AND MATERIALS: One hundred and one patients with potentially operable Stage III and IV squamous cell carcinoma of the head and neck received 45 Gy at 1.8 Gy fractions and continuous infusion cis-platinum 20 mg/m2 over 24 h on days 1 through 4 and 22 through 25 of the radiation schedule. Three to 4 weeks later, radical surgery of the primary site and neck dissections for patients presenting with cervical adenopathy was undertaken or if a complete response had been achieved, continued with radiation to 72 Gy with another course of concurrent continuous infusion cis-platinum. RESULT: Complete and partial responses were achieved in 92% of the primary sites and 95% of the nodes. Over 80% of the patients were rendered tumor free at surgery after only the initial course of chemotherapy and radiation. There were no grade 3 or 4 toxicities from chemotherapy and radiation. Ninety-five percent of the patients who initiated treatment completed it. With a median follow-up of 41 months for all patients, 49% of the patients have survived disease free up to 9 years, independent of whether or not their primary tumors were resected or were treated definitively by further chemotherapy sensitized radiation. The disease-specific survival is 78% after 3 years with no local failures thereafter. CONCLUSION: These findings suggest that continuous infusion cis-platinum administered concurrently with radiotherapy can improve survival in advanced head and neck cancer. Patients responding to the preoperative regimen may be cured without radical surgery, which can be reserved for salvage.
Actuarial Analysis↗
Combined-modality therapy of esophageal cancer with radiotherapy, etanidazole, and cisplatin-fluorouracil, with or without surgery: neurotoxicity, other toxicities and outcome.
PURPOSE: To investigate whether etanidazole and cisplatin can be given safely together and to evaluate the relationship between incidence of peripheral neuropathy and cumulative exposure to etanidazole and cisplatin, as well as other toxicities and treatment outcome. METHODS AND MATERIALS: Thirty-two previously untreated patients with locally advanced esophageal cancer were entered on a Phase I study of etanidazole combined with radiation therapy and chemotherapy. Cisplatin/5-FU (two cycles, weeks 1 and 4) and etanidazole (weeks 2, 3 and 5) were given concurrently with radiation therapy. Eligible patients then underwent surgical resection. All patients were scheduled to receive two additional cycles of cisplatin/5-FU chemotherapy after completion of radiation therapy (definitive arm) or surgery (preoperative arm). RESULTS: Of 19 fully evaluable patients, nine (47%) developed peripheral neuropathy. Six of six patients, 65 years or older, experienced peripheral neuropathy, compared with three of 13 patients less than 65 years old (p = .003). For patients younger than 65 years, two of the two patients with single dose area under the curve (AUC) > 4.0 mMhr experienced peripheral neuropathy, compared with one of 11 patients with single-dose AUC < 4.0 mMhr (p = .03). Grade 4 toxicity included neutropenia (23%) and thrombocytopenia (26%). No other Grade 4 toxicity was observed. The pathologic complete response rate in patients who underwent surgical resection was 29%. CONCLUSION: This regime of chemotherapy, radiotherapy, and etanidazole had acceptable toxicity. However, combining etanidazole and cisplatin appears to increase the risk of developing peripheral neuropathy for at least some categories of patients. Further studies of these interactions are needed.
Adenocarcinoma↗
Positive pretransplant crossmatches predict early graft loss in liver allograft recipients.
We evaluated the influence of donor-recipient HLA compatibility and recipient pretransplant antidonor sensitization on liver allograft recipient survival. The overall graft survival results for 67 cyclosporine-prednisone treated liver allograft recipients at 3, 6, and 12 months posttransplant were 86%, 83%, and 83%, respectively. No significant differences were observed when comparing the one-year survivals of 81% vs. 85% for men and women or 80% vs. 85% for adult and pediatric patients. Similarly, no differences were observed when comparing one-year graft survivals for well vs. poorly matched recipients of 77% vs. 83% for recipients with < or = 2 HLA A, B vs. > 2 HLA A, B mismatches (MMs) and 82% vs. 82% for recipients with 0-1 HLA-DR MMs vs. 2 HLA-DR MMs, respectively. Pretransplant transfusion history and race also did not influence survival. Standard NIH (long-incubation) and anti-human globulin (AHG) crossmatches were performed. The 12% of recipients (8/67) displaying a positive NIH crossmatch experienced significantly poorer 3-, 6-, and 12-month survivals of 62% vs. 89%, 62% vs. 86%, and 62% vs. 86% (all P < 0.05), respectively, than the 59 NIH-crossmatch negative recipients. Similarly, the 16% (11/67) of recipients displaying a positive AHG crossmatch had significantly poorer 3-, 6-, and 12-month survivals of 63% vs. 91%, 54% vs. 89%, and 54% vs. 89% (all P < 0.05) respectively, than the 56 AHG crossmatch-negative recipients. NIH and AHG crossmatch-positive sera were treated with dithioerythritol (DTE) to establish whether reactivity was due to IgM or IgG immunoglobulin. One-year graft survivals of 65% vs. 30% (P < 0.05) were observed when the crossmatch-positive sera reactivities were due to IgM vs. IgG immunoglobulin. While graft survivals were improved when positive crossmatch serum reactivity was due to IgM, these survivals were still significantly poorer than when the crossmatches were completely negative (86% vs. 60%, P < 0.05 for NIH-negative vs. NIH-positive, but DTE-negative, and 88% vs. 77%, P < 0.05 for AHG-negative vs. AHG-positive, but DTE-negative). Therefore, an NIH- or AHG-positive crossmatch, due either to IgM or IgG reactivity, results in poor early (3- and 6-months) liver allograft survival. Crossmatch-positive recipients experienced significantly (P < 0.05) more rejections and more steroid-resistant rejections (P < 0.05) than crossmatch-negative recipients.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Cytoplasmic sequences of the growth hormone receptor necessary for signal transduction.
To study structure-function relationships of the growth hormone (GH) receptor (GHR), two functional systems have been developed. CHO cells were transiently cotransfected with the cDNA encoding the full-length rat GHR and with a construct consisting of the 5' flanking region of one of two GH-dependent genes encoding ovine beta-lactoglobulin or serine protease inhibitor 2.1 (Spi 2.1, formerly Spi.1; the corresponding rat gene has recently been redesignated Spin2a) coupled to the bacterial reporter gene encoding chloramphenicol acetyltransferase (CAT). Transfected cells were grown in the absence and presence of human GH and dexamethasone for the Spi 2.1 gene construct. GH was able to activate each promoter (with approximately 4-fold induction of CAT activity) in a dose-dependent manner. For both tests, the maximal effect was observed at 20 nM human GH. These tests have been used to identify functional domains of the GHR. Two truncated (T) GHRs, lacking most or part of the cytoplasmic domain [called T276 (ending at residue 276) and T436 (ending at residue 436)], were unable to stimulate CAT activity. The GHR contains a proline-rich region, called "Box I," conserved in the cytokine/GH/prolactin receptor family. Alanine substitutions for the four prolines of GHR Box I were introduced. Single proline-to-alanine mutations did not affect the functional activity of the GHR. However, modification of the four prolines together or deletion of the Box I (15 amino acids between positions 279 and 293) resulted in the complete absence of GH stimulation. Thus, the proline-rich region, shown to be important for other members of this receptor superfamily, is also critical for GH signal transduction.
Amino Acid Sequence↗
Regulation and specificity of MNDA expression in monocytes, macrophages, and leukemia/B lymphoma cell lines.
The expression of the human myeloid cell nuclear differentiation antigen (MNDA) was observed specifically in cells of the granulocyte-macrophage lineage in our earlier reports. The specificity of MNDA expression for cells in the granulocyte-macrophage lineage was reexamined in cell lines established from patients with Philadelphia chromosome-positive chronic myeloid leukemia. Cell lines that expressed MNDA exhibited myeloid cell features and granulocyte or monocyte differentiation could be induced in vitro, while cell lines exhibiting properties of very early stage cells or multipotential cells did not express MNDA. Cells originating from cases of Burkitt's lymphoma were negative. By contrast, three lymphoblastoid cell lines (immortalized in vitro with Epstein-Barr virus) were weakly positive and MNDA was up-regulated by interferon-alpha (IFN-alpha) treatment. As we reported previously, MNDA mRNA level in adherent monocytes is elevated by IFN-alpha; in this study, we further assessed MNDA expression in in vitro monocyte-derived macrophages. Three additional agents (endotoxin, phytohemagglutinin, and phorbol ester) and other conditions that affect function, cytokine production, differentiation, and/or growth of monocytes were examined for their ability to alter MNDA expression. The results varied with the agent, cell type, and stage of differentiation. Changes in MNDA expression occurred slowly (hours to days), suggesting that MNDA could mediate changes realized over a long period. The results also reveal a discordance in certain MNDA positive cells between steady-state levels or changes in levels of protein and mRNA indicating that the regulation of MNDA expression occurs at more than one point. Changes in MNDA expression are consistent with a role in opposing macrophage differentiation and activation of monocytes/macrophages.
Antigens, Differentiation, Myelomonocytic↗