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Biomedical subjects

S J Harper

Publications and source records attributed to S J Harper.

65 records · Page 4Linked to original sources
PubMed1991

Posthypoxic myoclonus (the Lance-Adams syndrome) in the intensive care unit.

The neurological assessment of patients admitted to the intensive care unit after successful resuscitation from cardiopulmonary arrest may be difficult. We describe the cases of two patients who developed myoclonus within 24 hours of hypoxic respiratory and cardiac arrest. Initially, the clonic movements were thought to be generalised convulsions and were treated as such, until it became evident that the patients were aware and distressed. Posthypoxic myoclonus is a rare complication of successful cardiopulmonary resusitation. Recognition depends on the awareness that the syndrome exists, and is important so that correct therapy can be instituted. There may be important prognostic implications. Both our patients had normal intellectual recovery with moderate residual neurological disability from their movement disorder.

Clonazepam↗
PubMed1991

Propofol and alfentanil infusions for sedation in intensive therapy.

Forty-four patients, with admission APACHE II scores between 5 and 24, undergoing mechanical ventilation in the intensive therapy unit, received a sedative regimen consisting of continuous infusions of propofol and alfentanil. Patients were randomly allocated to one of three groups to receive either alfentanil 0.25 microgram kg-1 min-1 (10 patients), 0.50 microgram kg-1 min-1 (15 patients) or 0.75 microgram kg-1 min-1 (18 patients) for analgesia. An infusion of propofol 20-200 mg h-1 ran concurrently to maintain a satisfactory level of sedation. Patients received the infusions for between 4 and 260 h and 38 patients spent more than 90% of this time at satisfactory sedation levels. After stopping the infusions all patients had short times to wakening (mean 3-18 min) and to establish spontaneous respiration (mean 8-28 min), suggesting no significant cumulation. Some depression of blood pressure was seen on starting the infusions, which was in general easily treated with fluids or small increases in inotropic agents. One patient, however, was withdrawn from the trial because of haemodynamic instability. This combination of drugs can be recommended for sedation of general intensive-therapy patients, provided the cost is not felt to be prohibitive.

Adolescent↗
PubMed1990

Neoplastic transformation of a human colonic epithelial cell line: in vitro evidence for the adenoma to carcinoma sequence.

The purpose of this study was to establish an in vitro model for tumor progression in colorectal carcinogenesis, by transforming the premalignant human colonic PC/AA adenoma cell line to the malignant phenotype. A rare clonogenic variant AA/C1 [colony-forming efficiency (CFE) on plastic of 1.05%] was isolated from the diploid PC/AA adenoma cell line (C. Paraskeva, S. Finerty, and S. Powell, Int. J. Cancer, 41: 908-912, 1988). AA/C1 was aneuploid and when treated with 1 mM sodium butyrate for 14 days gave rise to the AA/C1/SB cell line which had an increased CFE on plastic (6.13%) although the cells remained anchorage dependent and nontumorigenic. After exposure of these AA/C1/SB cells to the carcinogen N-methyl-N'-nitro-N'-nitrosoguanidine an anchorage-independent cell line was isolated (AA/C1/SB10). On continuous in vitro passage, the CFE in agarose of AA/C1/SB10 has increased to 17.3% and the cells have become tumorigenic producing adenocarcinomas in athymic nude mice. AA/C1, AA/C1/SB, and AA/C1/SB10 cell lines have common chromosomal abnormalities including a pericentric inversion of chromosome 1 with deletion of part of the short arm and monosomy for chromosome 18. This in vitro progression provides the first reported experimental evidence for the adenoma to carcinoma sequence in the human colon, and the cytogenetic evidence suggests that it is relevant to in vivo carcinogenesis.

Adenoma↗
PubMed1988

Homologous blood use and conservation techniques for cardiac surgery in the United Kingdom.

The transfusion laboratories of 32 cardiothoracic surgical centres for adults were surveyed to determine the donor blood requirement for open heart surgery in the United Kingdom. Details of the transfusion practice and the use of blood conservation techniques were sought from a representative senior cardiac anaesthetist at each centre. Suitable data were received from 24 transfusion laboratories (75%) and 29 anaesthetists (90%). The mean (SD) blood use was 5.07 (1.53) units per operation. Seven centres routinely transfused fresh frozen plasma to all patients postoperatively. Experience with autologous deposit (three centres), "cell separators" (four centres), and the reinfusion of shed mediastinal blood (four centres) was limited. Prebypass phlebotomy for postbypass reinfusion (14 centres) and the infusion of residual oxygenator blood (27 centres) were the conservation techniques most commonly applied. In only nine centres was a postoperative normovolaemic anaemia to a haemoglobin concentration of less than 100 g/l accepted. Applying blood conservation techniques more widely would help to maintain blood supplies and reduce morbidity and mortality related to transfusion.

Anemia↗
PubMed1987

In vivo expression of mRNA for the Ca++-binding protein SPARC (osteonectin) revealed by in situ hybridization.

In situ hybridization is used to survey the tissue-specific and developmental expression of the cloned mouse gene Sparc, coding for a protein homologous to the bovine Ca++-binding protein, osteonectin. High levels of SPARC RNA are found in osteoblasts and odontoblasts. In addition, high grain counts are associated with a variety of other cell types in the embryo and newborn mouse, including parietal endoderm, deciduum, whisker follicles (connective tissue sheath), peripheral nerve trunk, skin (dermis), and stomach (submucosa). Spatially restricted but high levels of SPARC mRNA are also seen in the adult adrenal glands, testis, and ovary. This pattern of differential gene expression demands a reassessment of the function originally proposed for osteonectin, and predicts a much wider role for the protein in a variety of biological processes.

Adrenal Glands↗
PubMed1979

Measurement of medication compliance in a clinical setting. Comparison of three methods in patients prescribed digoxin.

Medication compliance is an important medical process, and useful methods are needed to measure compliance in clinical practice. Interview, pill count, and serum digoxin concentration (SDC) were compared in 173 patients prescribed digoxin to determine (1) feasibility, ease, timeliness; (2) reasons for noncompliance; and (3) validity of interview and pill count compared with SDC. All patients were interviewed; among 33 (19%) not taking their medication correctly, nine (5%) did not know how. Pill counts were possible for 68 patients (39%). One patient had a correct pill count. Steady-state SDCs were obtained for 143 patients (83%), but were not available during patients' visits. The SDCs for 25 patients were less than 0.50 ng/mL. Interviews correlated with SDCs, pill counts did not. Pill counts and SDCs required telephoning patients before appointments. In clinical practice, interview may be the most useful methof of measuring medication compliance.

Aged↗
PubMedDate not supplied

Visceral glomerular epithelial cell DNA synthesis in experimental and human membranous disease.

BACKGROUND: Membranous nephropathy (MN) is a 'non-proliferative' glomerulonephritis. However, visceral glomerular epithelial cell (vGEC) proliferating cell nuclear antigen staining and increased glomerular histone mRNA in passive Heymann nephritis (PHN), suggest that vGECs may enter the cell cycle and undergo DNA synthesis. We used in situ hybridisation for histone mRNA, an S-phase specific marker, to investigate this possibility and identify the cellular origin of histone mRNA in PHN and MN. METHODS: PHN was induced in 16 Sprague-Dawley rats. There were 8 saline/serum controls. 12 animals were sacrificed on days 5 and 10. Renal biopsies from 10 proteinuric cases with MN and matched controls were studied. RESULTS: Day-5 Heymann animals demonstrated more S-phase cells/glomerulus than controls (0.53 +/- 0.09 vs. 0.195 +/- 0.045; p < 0.01). Glomerular S-phase cells were also increased in patients compared to controls (0.24 +/- 0.07 vs. 0.04 +/- 0.018; p < 0.03). In both experimental and human MN, the peripheral location and morphology of glomerular histone mRNA-positive cells was typical of vGECs. CONCLUSION: The results in PHN indicate that vGECs recently injured with antibody and complement enter into the cell cycle and undergo DNA synthesis. The S-phase vGECs in MN may indicate the persistence of immune injury. Whether or not this process leads to cell replication is open to question.

Adult↗
PubMedDate not supplied

Response to mucosal antigen challenge in IgA nephropathy.

While IgA nephropathy (IgAN) is characterized by the deposition of glomerular IgA, the source of the deposited IgA is not known, with both the mucosal and systemic IgA systems being implicated. In order to investigate mucosal and systemic antibody production to mucosal antigen challenge in IgAN, 9 patients and 11 controls were immunized intranasally with tetanus toxoid (TT). There was no significant difference in the serum or saliva IgG, IgA, IgA1, or IgA2 antibody production to TT. However, in IgAN there was an increase of in vitro IgA anti-TT production in Epstein-Barr virus transformed cultures of peripheral blood lymphocytes taken after mucosal immunization. This increase in traffic of immunocompetent cells between the systemic and mucosal systems could play a role in the link between the mucosa and glomerulus in IgAN. Systemic immunization with TT following mucosal priming did not result in any difference in the antibody response between patients and controls. There was no evidence from this study that mucosal immunization results in an enhanced antibody response in IgAN or that mucosal priming alters the subsequent systemic antibody response.

Administration, Intranasal↗
PubMedDate not supplied

In vitro immunoglobulin isotype suppression in immunoglobulin A nephropathy.

IgA nephropathy (IgAN) is characterized by mesangial IgA deposition, and up-regulation of the IgA system is frequently described. This study investigated in vitro immunoglobulin isotype production by peripheral blood mononuclear cells from patients with IgAN and controls, without mitogenic stimulation and under the influence of cell cycle inhibitors and cyclosporin A (CyA). In controls, only IgM production was suppressed by cell cycle inhibitors, and no isotype was affected by CyA. This suppressible IgM production may represent antigen-independent 'natural antibody'. In IgAN, IgM, IgA and IgG were all suppressed by cell cycle inhibitors, and CyA suppressed IgA production. This state of altered immune activation in IgAN demonstrates T-cell-independent IgA production, suggesting that it is IgA 'natural antibody'. In conclusion, we suggest that mesangial IgA deposition may not be antigen dependent but due to some non-immune characteristic of the IgA molecule.

Adult↗
PubMedDate not supplied

Increased IgA and decreased IgG production by Epstein-Barr virus transformed B cells in culture in IgA nephropathy.

Despite many studies describing IgA upregulation both in vivo and in vitro in IgA nephropathy (IgAN), the underlying mechanism of increased IgA production is not known. In this study, Epstein-Barr virus was used to transform B cells in vitro in a T-cell-independent manner in order to investigate immunoglobulin production by B cells in IgAN. B cells from patients with IgAN produced more IgA and less IgG in culture than controls. While both IgA subclasses contributed to the increase in IgA production, only IgA1 synthesis was significantly higher than controls. These results of increased IgA production in patients with IgAN, with a concomitant decrease in IgG production, demonstrate hyperactivity of B cells restricted to the IgA isotype in IgAN.

Adolescent↗