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Biomedical subjects

J Norton

Publications and source records attributed to J Norton.

At least 73 records · Page 4Linked to original sources
PubMed1994

Does naloxone cause a positive urine opiate screen?

STUDY OBJECTIVE: To determine whether the excreted metabolites of naloxone hydrochloride cause positive urine toxicologic screens for opiates. DESIGN: Prospective, randomized, double-blinded human protocol. SETTING: Urban Level I military emergency department. PARTICIPANTS: Fourteen adult volunteers who took no routine medications, were not pregnant, had no known sensitivity to naloxone, and who were negative for a pretest urine and serum toxicologic screen. INTERVENTIONS: We administered either 2 or 4 mg IV naloxone to 14 subjects. Urine drug screening was obtained before administration and at 60 minutes, 6 hours, and 48 hours after administration. RESULTS: All urine drug screens using the enzyme-multiplied immunoassay technique were negative for opiates at both dosage levels. The sample size of 14 yielded a power of more than .99 to detect the difference between positive and negative samples. CONCLUSION: Although the metabolites of naloxone hydrochloride are similar in structure to oxymorphone and are excreted in human urine for several days, naloxone was not associated with a positive enzymatic urine screen for opiates.

Adult↗
PubMed1994

A prospective study of cellular and immunologic changes in skin of allogeneic bone marrow recipients. Relationship to clinical and histologic features of acute graft-versus-host disease.

The inflammation-associated molecules intercellular adhesion molecule (ICAM)-1, endothelial lymphocyte adhesion molecule (ELAM)-1, vascular cell adhesion molecule (VCAM)-1, human leukocyte antigen (HLA)-DR, interleukin (IL)-2R (CD25), CD34, alpha-1-antichymotrypsin (alpha 1-ACT), and L1 antigen were studied in skin from marrow recipients to determine the timing and distribution of their expression in relation to the clinical and histologic evolution of graft-versus-host disease (GvHD). Four phases were recognized: 1. pretransplant with no immunohistologic change; 2. posttransplant with no evidence of GvHD when dermal alpha 1-ACT + macrophages were increased; 3. posttransplant with clinical, but not histologic, evidence of GvHD with increased keratinocyte HLA-DR and ICAM-1 expression and increased numbers of VCAM-1+ dermal cells; and 4. posttransplant with clinical and histologic evidence of GvHD characterized by an infiltrate of CD25+ T cells, L1+, alpha 1-ACT+ and VCAM-1+ macrophages, L1 antigen expression on keratinocytes accompanied by further increases in HLA-DR and ICAM-1, and increased endothelial ELAM-1 staining with a reciprocal decrease in CD34. A sequential accumulation of cellular and molecular changes, therefore, occurs in the evolution of acute GvHD, and immunostaining for HLA-DR, ICAM-1, and VCAM-1 may be helpful in diagnosing early disease.

Adolescent↗
PubMed1993

Regional distribution of amyloid beta-protein precursor, growth-associated phosphoprotein-43 and microtubule-associated protein 2 messenger RNAs in the nigrostriatal system of normal and Weaver mutant mice and effects of ventral mesencephalic grafts.

Using in situ hybridization histochemistry with [32P]oligonucleotide probes, we studied the cellular localization of RNA transcripts for amyloid beta-protein precursor (beta APP), growth-associated phosphoprotein-43 (GAP-43) and microtubule-associated protein 2 (MAP2) in the mesostriatal system of normal (+/+) and weaver (wv/wv) mutant mice, which lose mesencephalic dopamine neurons. In addition, expression of the same messages was studied in ventral mesencephalic cell suspensions transplanted to the weaver striatum. Transcripts encoding GAP-43, MAP2 and isoforms beta APP695, beta APP714 and beta APP751 were present in normal substantia nigra and progressively reduced in weaver substantia nigra; such a reduction was correlated with dopamine neuron loss. The survival of dopamine neurons in unilateral intrastriatal grafts was documented by methamphetamine-induced rotational asymmetry tests and by tyrosine hydroxylase immunocytochemistry. High hybridization signals were obtained for GAP-43, MAP2, beta APP695, beta APP714 and beta APP751 RNA transcripts in the grafted tissue; the beta APP770 species--normally seen in striatum and not substantia nigra--was not expressed in the grafts, but it was present in the recipient striatum. Following immunocytochemical labelling with antibodies, GAP-43 and MAP2 immunoreactivities were seen in cell processes in the grafts and surrounding tissue, whereas beta APP immunoreactivity was mainly found in grafted cell bodies. These results suggest that the transplanted mesencephalic cells mature very similarly to those in the normal substantia nigra, expressing different mRNAs that are normally present in the ventral midbrain and which are reduced in the weaver mutant as a consequence of dopamine neuron loss.

Amyloid beta-Protein Precursor↗
PubMed1993

Reciprocal expression of CD34 and cell adhesion molecule ELAM-1 on vascular endothelium in acute cutaneous graft-versus-host disease.

The expression of CD34 and endothelial leucocyte adhesion molecule-1 (ELAM-1) on endothelial cells was studied in skin biopsies from normal human donors and recipients of allogeneic bone marrow. Both molecules were demonstrable on a variable number of cells in normals with no significant change after marrow transplantation in patients with no clinical evidence of skin disease. In patients with graft-versus-host disease (GvHD), however, there was a striking decrease in CD34-positive cells with a corresponding increase in ELAM-1 positivity. These changes were similar to those occurring in cultured endothelial cells after the addition of certain cytokines. They were seen only in the presence of a lymphocytic infiltrate and were not observed in the early stages of GvHD before lymphocytic infiltration was discernible. The reciprocal expression of these molecules may thus be important in the adhesion of lymphocytes to endothelium and their entry into the skin in GvHD and may be modulated by local cytokine release.

Acute Disease↗
PubMed1993

Alzheimer's disease is rare in Cree.

A community survey and subsequent clinical assessment of 192 Cree aged 65 years and over registered in two Reserves in Northern Manitoba identified only one case of probable Alzheimer's disease among eight cases of dementia, giving a prevalence of 0.5% for Alzheimer's disease and 4.2% for all dementias. This contrasted with an age-adjusted prevalence of 3.5% for Alzheimer's disease and 4.2% for all dementias in an age-stratified sample of 241 English-speaking residents of Winnipeg. Although it was not so for all dementias, the difference between the groups for prevalence of Alzheimer's disease was highly significant (p < .001). The age-specific patterns of all dementias in the two groups were significantly different, however (p = .0254).

Aged↗
PubMed1993

The pathology of bone marrow transplantation.

The pathological complications of bone marrow transplantation are complex and may affect any organ in the body. The causes are often multifactorial and include the effects of chemotherapy, the conditioning regimen, drugs used in the post-transplant period such as immunosuppressants and antibiotics, graft-versus-host disease (GvHD) and the effects of the primary disease itself. Infections are common and result from the immunosuppressive effects of cytotoxic drugs and irradiation, GvHD and marrow failure. Haemorrhage is not infrequent. Graft-versus-host disease remains a significant problem and can be difficult to diagnose. Some of its histological features simulate the effects of chemoradiation and the diagnostic lesions may not be present early in the disease, when treatment is most effective. Evidence has accumulated that inflammatory cytokines have a key role in the pathogenesis of GvHD. It can be prevented by eliminating T-cells from the donor marrow but this procedure adversely affects marrow engraftment, increases the changes of rejection and results in a higher incidence of leukaemic relapse. Immunohistochemical staining for various cytokine-inducible molecules has led to some improvement in early diagnosis.

Bone Marrow↗
PubMed1993

Cytokine gene expression in skin and lymphoid organs in graft versus host disease.

AIM: To determine if human graft versus host disease (GvHD) is associated with any detectable change in cytokine gene expression in the skin and lymphoid organs. METHODS: Reverse transcriptase and the polymerase chain reaction were used to amplify mRNA for interleukins-1 (IL-1), -2 (IL-2), -4 (IL-4) and -6 (IL-6), IL-2 receptor (IL-2R), tumour necrosis factors alpha (TNF-alpha) and beta (TNF-beta), gamma interferon (IFN gamma) and granulocyte macrophage colony stimulating factor (GM-CSF) in frozen punch biopsy specimens of skin and necropsy samples of skin, lymph node, and spleen. RESULTS: No cytokine mRNA was detected in the punch biopsy specimens except weak signals for IL-6 and IL-1 and GM-CSF in two normal donors and IL2-R in one patient with GvHD. In samples of skin taken at necropsy, however, significant quantities of mRNA for TNF-alpha, TNF-beta, and IL-4 were detected in patients who had or had had GvHD in contrast to those without the disease whose skin lacked mRNA for these products but contained detectable quantities of IL-1, IL2-R, IL-6 and GM-CSF. There seemed to be a reciprocal relation between TNF-alpha and IL-4. In necropsy samples of lymph node and spleen a pattern of cytokine production similar to that in the skin was observed with a preponderance of TNF-alpha, TNF-beta and IL-4 in patients with GvHD and GM-CSF and IL-6 in those without the disease. CONCLUSIONS: The local synthesis of these molecules would explain many of the morphological and immunohistological features of GvHD. The failure to detect TNF-alpha, TNF-beta, and IL-4 in skin biopsy specimens exhibiting GvHD is probably due to their small size but further investigations are required.

Adolescent↗
PubMed1993

Hypospermatogenesis is the cause of infertility in the male weaver mutant mouse.

The pathologic phenotype of the testis in both prepuberal and postpuberal male weaver mutant mice was studied by light microscopy. Morphometric analysis of seminiferous tubules was carried out. Epididymal fluid was examined for the presence of spermatozoa. The seminiferous tubules of 21-day-old prepuberal weaver mutant mice lacked patent lumina and had more degenerated cells than control mice. Fifty-six day-old weaver mutants had many germinal epithelial cells located within the adluminal compartment that were in advanced stages of degeneration. Round spermatids were enlarged and multinucleated. Round spermatids and spermatocytes had sloughed into the lumen. Compared to control mice, elongated spermatids were seen less frequently. In older weaver mice, the degenerative process involved germ cells in both the adluminal and basal compartments. In 143- and 226- day-old weaver mutants, the Sertoli cells were atrophic. Diameters of seminiferous tubules in weaver mice were significantly reduced when compared to control mice. Sperm were either absent or very low in number in the epididymal fluid of postpuberal weaver mice. We conclude that spermatogenesis is abnormal in male weaver mutant mice. The testicular phenotype is characterized by a degenerative process that affects both germ cells and supporting cells.

Aging↗
PubMed1992

Expression of adhesion molecules in human intestinal graft-versus-host disease.

The distribution of three cellular adhesion molecules, ICAM-1, ELAM-1 and VCAM-1, was studied in normal rectal mucosa and in graft-versus-host disease (GvHD) using immunohistological and morphometric techniques. In normal controls, ICAM-1 was demonstrable on endothelial cells and leucocytes within the lamina propria, ELAM-1 on endothelial cells only and VCAM-1 on lamina propria leucocytes, many of which exhibited long dendritic processes surrounding the glands. In GvHD, the enterocytes became positive for ICAM-1 and this was often associated with the presence of intra-epithelial LFA-1+ lymphocytes and macrophages, the latter containing debris of apoptotic cells. The staining was, however, restricted to the luminal membrane of the epithelial cells, raising doubts about the role of ICAM-1 as a ligand for LFA-1 on mucosal leucocytes in rectal GvHD. ELAM-1 expression was increased in GvHD both in terms of the length of positive endothelium and staining intensity. VACM-1 was increased on endothelial cells but not leucocytes in the lamina propria in contrast to our previous findings in cutaneous GvHD where VCAM-1+ dendritic cells were increased and endothelial cells remained negative. Normal patterns of adhesion molecule staining were seen in two biopsies exhibiting no morphological evidence of GvHD, from patients who had strong clinical evidence of the disease, indicating that immunostaining for these molecules is unlikely to be of help in improving the sensitivity of histological diagnosis. However, the possibility that adhesion molecule staining may be useful in improving diagnostic specificity by helping to distinguish GvHD from identical histological changes produced by irradiation and cytotoxic drugs is worthy of further investigation.

Adolescent↗
PubMed1992

Epidermal damage in skin of allogeneic marrow recipients: relative importance of chemotherapy, conditioning and graft v. host disease.

The relative importance of previous chemotherapy, conditioning and graft v. host disease in producing the epidermal damage associated with allogeneic bone marrow transplantation was investigated by enumerating individually necrotic cells. A small number was seen in many pre-transplant biopsies and was related to the time interval between biopsy and the last dose of chemotherapy. Their presence did not predispose patients to develop graft v. host disease in the post-transplant period. In post-transplant patients without rashes the degree of epidermal damage at 14 days was similar to that seen in the pre-transplant period indicating that the effects of the conditioning regime were insignificant. In patients with rashes clinically classical of graft v. host disease, necrotic cells were increased above the pre-transplant levels even in the absence of a lymphocytic infiltrate. Lymphocytic infiltration was seen more frequently in biopsies taken later after transplantation and after the onset of the rash and was associated with the maximal amount of epidermal damage. Comparison of the degree of epidermal damage in pre- and post-transplantation specimens lacking a lymphocytic infiltrate resulted in the correct identification of the majority of patients with clinical evidence of graft v. host disease. This approach may, thus, be useful in diagnosing early graft v. host disease especially if combined with keratinocyte HLA-DR staining.

Adolescent↗
PubMed1992

Immunohistological study of distribution of gamma/delta lymphocytes after allogeneic bone marrow transplantation.

The distribution of T lymphocytes expressing the gamma/delta form of the T cell receptor was studied in the liver, intestine, and major lymphoid organs, after bone marrow transplantation (BMT), including cases of graft versus host disease (GvHD). The number of gamma/delta as a proportion of the total number of CD3 positive cells did not differ from that found in normal tissues; the higher percentage normally found in the intestinal epithelium and splenic red pulp was maintained. This, and the results of a previous study undertaken on the skin, provide no evidence that gamma/delta T cells have a particularly important role in T cell regeneration after marrow transplantation or in the pathogenesis of the epithelial lesions associated with GvHD.

Adult↗
PubMed1992

A prospective randomized trial comparing the infectious and noninfectious complications of an externalized catheter versus a subcutaneously implanted device in cancer patients.

PURPOSE: To compare the frequency of infectious episodes or other problems occurring with an externalized catheter (Hickman) versus a subcutaneously implanted device (Port-a-Cath, Pharmacia, Piscataway, NJ) in cancer patients, we performed a prospective, randomized study in 100 cancer patients (age range, 5 to 74 years). PATIENTS AND METHODS: Patients who were chemotherapy candidates and required an indwelling catheter were monitored prospectively and evaluated during the 180 days after the insertion of the catheter and again at time of study closure. The frequency of catheter use, reason for access, and any problems that might have been related to catheter use were noted. All data were collected prospectively and included the patient's age, sex, underlying malignancy, temperature, and leukocyte and absolute granulocyte counts at the time of catheter insertion and when complications occurred. The time to and reason for removal of the catheter, as well as any intercurrent infectious or mechanical problems, were also determined. RESULTS: Most of the infections that occurred were caused by gram-positive organisms, especially staphylococci or streptococci. A total of 22 complications (11 in each group) resulted in removal of the central line. Only one infection in the Hickman catheter group and four in the Port-a-Cath group led to removal of the central line. All other infectious episodes were successfully treated without removal of the catheters. The mean device life was 230 days for the Hickman catheter and 318 days for the Port-a-Cath (not significant). CONCLUSION: There were no differences between the two study groups regarding incidence of documented infections or mechanical or thrombotic complications.

Adolescent↗
PubMed1992

Adhesion molecule expression in human hepatic graft-versus-host disease.

An immunohistological study of the distribution of three cellular adhesion molecules, ICAM-1, VCAM-1 and ELAM-1, was undertaken on normal liver and liver biopsies taken from allogeneic bone marrow transplant (BMT) recipients. In normal controls, ICAM-1 was seen on vascular endothelium and sinusoidal lining cells, and VCAM-1 on Kuppfer cells and dendritic macrophages in portal tracts. ELAM-1 staining was virtually absent. Biopsies from BMT recipients with histological evidence of hepatic graft-versus-host disease (GVHD) showed ICAM-1 expression on damaged bile duct epithelium in only one of five cases, in contrast to four of five showing epithelial HLA-DR expression. Increased numbers of VCAM-1 positive portal tract macrophages were seen in GVHD and also in non-GVHD pathology. No increase in vascular endothelial expression of VCAM-1 or ELAM-1 was seen. These findings contrast with previous studies on other target sites for GVHD, namely skin and gastrointestinal tract, where the expression of all three molecules is increased on various cells. Although the lack of adhesion molecule expression in the liver in GVHD in this study may be related to the timing of biopsies or immunosuppressive therapy, it is likely to represent to some extent variation in cell and molecular changes occurring in the different tissues affected by GVHD.

Adolescent↗
PubMed1992

Varying heparin requirements in hemodialysis patients receiving erythropoietin.

A two-phase study was undertaken to investigate the incidence, extent, and management of increased heparin needs occurring during erythropoietin (EPO) therapy in the hemodialysis patient. Individual heparin doses and activated clotting time (ACT) test values were the parameters used to indicate changes in heparin requirements. It appears that increased heparin requirements are frequently associated with EPO therapy, and awareness of this finding, coupled with close ACT monitoring, may possibly prevent complications associated with undetected increases in heparin requirement.

Adult↗
PubMed1991

Proliferation in human bladder carcinoma measured by Ki-67 antibody labelling: its potential clinical importance.

Ki-67 is a monoclonal antibody which recognises a human nuclear antigen expressed in proliferating cells. The antibody was used to assess proliferation in primary human bladder tumours from 64 patients. Ki-67 index (the number of Ki-67 positive tumour cells divided by the total number of tumour cells %) was derived from 59 tumours. A wide range of Ki-67 indices were recorded, range 3.0-65.8%, mean 20.2%. The Ki-67 index correlated with known prognostic factors: T stage (P = 0.002) and histological grade (P less than 0.001), early stage disease and more differentiated tumours having lower Ki-67 indices. Patients with invasive disease (21 patients) had significantly higher Ki-67 indices than those with non-invasive disease (P = 0.01). Patients with metastatic disease at presentation (four cases) all had a Ki-67 index of greater than or equal to 29%. Ki-67 antibody staining is a simple technique for assessing the proliferation fraction than can be performed on a small amount of tissue taken at routine biopsy without prior injection of thymidine analogues.

Aged↗
PubMed1991

ICAM-1 expression on epidermal keratinocytes in cutaneous graft-versus-host disease.

An immunohistological study of epidermal keratinocytes for the intercellular adhesion molecule, ICAM-1 (CD54), was undertaken on skin biopsies from allogeneic bone marrow transplant recipients. In control biopsies from normal donors and patients prior to transplantation, staining was weak and confined to relatively few cells. After transplantation there was a significant increase in both the number of positive cells and their staining intensity in biopsies showing histological evidence of GVHD but not in those exhibiting normal appearances or epidermal abnormalities that could be attributed to cytotoxic drugs or irradiation. There was a strong positive correlation between ICAM-1 and HLA-DR expression by keratinocytes. All cases exhibiting increased ICAM-1 also exhibited an increase in HLA-DR antigens. The converse was not true, however, as 6 biopsies exhibited HLA-DR positivity without detectable increases in ICAM-1. Both ICAM-1 and HLA-DR antigen synthesis may be stimulated by local cytokine release following interactions between donor and recipient cells in the early posttransplant period. Our present findings suggest that immunostaining for ICAM-1 has little value in the early diagnosis of cutaneous GVHD but further, more detailed prospective studies would be of value.

Cell Adhesion Molecules↗