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Biomedical subjects

N Smith

Publications and source records attributed to N Smith.

At least 127 records · Page 7Linked to original sources

Intravenous anti-D immunoglobulin in the management of immune thrombocytopenic purpura.

Approximately 70% to 80% of Rh-positive adults and children with acute or chronic immune thrombocytopenic purpura or HIV-related thrombocytopenia respond to infusions of anti-D immunoglobulin. The speed of onset of response is slower than that seen with intravenous immunoglobulin. Anti-D immunoglobulin is well tolerated, with occasional adverse reactions similar to those seen in treatment with polyclonal intravenous immunoglobulin, but anemia requiring blood transfusion can occur. Response is generally better in younger patients and those who have responded to other forms of treatment. Inhibition of Fc receptor-mediated platelet destruction by anti-D immunoglobulin-opsonized erythrocytes is the most likely mechanism of action, although the relative ineffectiveness of a monoclonal anti-D immunoglobulin preparation in treatment of immune thrombocytopenic purpura suggests that other mechanisms may exist. Hepatitis C has been transmitted by intravenous anti-D immunoglobulin preparations when used in the prevention of Rh immunization, prior to the introduction of screening donor plasma for hepatitis C virus antibodies. However, an intravenous solvent-detergent-treated preparation is now available.

Adult↗

Indeterminate cell histiocytosis--a clinicopathological entity with features of both X- and non-X histiocytosis.

An otherwise healthy 50-year-old woman presented with a 6-month history of having developed more than 100 generalized, non-confluent, reddish-brown, partially yellow-coloured papules. A non-epidemotropic, monomorphous infiltrate of vacuolated mononuclear, and occasionally multinuclear, histiocytes, positive for factor XIIIa and macrophage markers HAM56 and KiM1p, was consistent with the clinical impression of generalized eruptive histiocytomas. However, the additional reactivity for S100 protein, in the absence of features of histiocytosis X, suggested a diagnosis of indeterminate cell histiocytosis (ICH). Further immunohistochemical studies, performed on snap-frozen material, characterized the lesions as being diffusely positive with LN3 (HLA-DR), Leu4 (CD3) and Leu3 (CD4), the infiltrate in the upper dermis as reactive for OKT6 (CD1) and IOT6c (CD1c), and the infiltrate in the lower dermis as reactive for a variety of macrophage markers. Ultrastructural studies showed various non-specific features of histocytic disorders, but no Birbeck granules. Our findings confirm those of previous reports suggesting that ICH is a distinct histiocytic entity, characterized by immunophenotypic features of both X- and non-X histiocytoses. Generalized eruptive histiocytoma seems to be an early indeterminate stage of various non-X histiocytic syndromes including ICH, multicentric reticulohistiocytosis, xanthogranuloma and xanthoma disseminatum. The distribution pattern of the various X/non-X histiocytic markers suggests dermal arrest of antigen-presenting cells during their physiological trafficking from the skin to the lymph nodes.

Female↗

Use of Read codes in development of a standard data set.

General practice has a wealth of data that could be used for purposes such as assessing health needs, planning, and audit. If this potential is to be realised appropriate data must be easily accessible and of high quality. This article describes the experience of an information project team in developing and coding a standard data set, with the aim of meeting the needs of commissioners, public health, and general practitioners. The Read coding classification seemed the logical choice for the standard data set because Read codes are the basis of a standard classification of general practice data. However, the coding structure has several weaknesses that were difficult to resolve, and the standard data set had to be changed to match available codes. This paper may prove helpful to similar project teams attempting to develop and use a standard data set.

Classification↗

Randomized trial of intravenous immunoglobulin prophylaxis for patients with chronic lymphocytic leukaemia and secondary hypogammaglobulinaemia.

Forty-two patients with chronic lymphocytic leukaemia (CLL), serum IgG levels < 5.5 milligrams and a history of two or more recent infections, were randomized to receive infusions of 18 g human intravenous immunoglobulin (IVIg) or human albumin placebo every three weeks. During the 12 month study 122 infections were documented but only four were associated with neutropenia. Ten patients (24%) with IgG levels < 3.0 milligrams experienced 65% of the infections. In response to IVIg there were immediate and accumulative increases in serum IgG levels and an associated decrease in total and serious infections. If three further infections occurred, placebo patients were commenced on 18 g IVIg, and IVIg patients were increased to 24 g IVIg. Approximately 50% of these cases subsequently remained infection free. The study shows the usefulness of prophylactic Sandoglobulin in CLL patients with hypogammaglobulinaemia, and suggests that this may be justified in those with recurrent infections and serum IgG levels < 3 milligrams.

Agammaglobulinemia↗

Effect of dietary salt load on transepithelial Na+ exchange in freshwater rainbow trout (Oncorhynchus mykiss)

Dietary Na+ loads (0.5&shy;70 mmol kg-1 fish) were almost completely absorbed within 7 h, and branchial Na+ excretion commenced within 1 h. Na+ loads of less than 1 mmol kg-1 were lost through the gills through a significant decrease in Na+ influx with unaltered Na+ efflux rate (compared with Na+ fluxes in unfed fish). At higher salt loads (>18 mmol kg-1), Na+ loss increased as a result of significantly higher Na+ efflux rates, with no further decrease in Na+ influx rate. Tissue Na+ concentrations were unchanged, apart from a significant increase in blood plasma Na+ concentration in fish loaded above 18 mmol kg-1. The results show that branchial Na+ fluxes may be rapidly adjusted in response to prevailing conditions, and possible control mechanisms are discussed.

Journal Article↗

Scuba diving: how high the risk?

The host factors that represent the most risk for scuba-diving safety are poor fitness, overweight, chronic diseases, structural abnormalities of the heart and lungs, and multiple risk factors for CAD. Any of these factors, plus inexperience, a history of irresponsible behavior, or participation in technical diving should alert medical underwriting that a scuba diver has excess risk for fatal accidents.

Cause of Death↗

The incidence of prostate cancer progression with undetectable serum prostate specific antigen in a series of 394 radical prostatectomies.

PURPOSE: Serum prostate specific antigen (PSA) has been reported to be a sensitive indicator of recurrent carcinoma after radical prostatectomy but it is not absolute. Disease progression with undetectable PSA levels has been described but the incidence of this phenomenon is unknown. MATERIALS AND METHODS: We retrospectively analyzed the records of 394 consecutive men who underwent radical prostatectomy between 1980 and 1991 to characterize the incidence of recurrent carcinoma despite undetectable serum PSA levels. RESULTS: Of the 394 men 133 had documented evidence of disease recurrence, 3 (2.3%) despite undetectable serum PSA levels (2 had local and systemic evidence of disease progression). Histological dedifferentiation characterized these recurrences. CONCLUSIONS: Although a post-prostatectomy detectable serum PSA level precedes clinical evidence of disease progression by years, rare patients (2.3% in our series) in whom recurrent disease is characterized by marked histological dedifferentiation will remain negative for PSA.

Aged↗

Occupational tooth abrasion in a dental technician: loss of tooth surface resulting from exposure to porcelain powder--a case report.

A dental technician suffered abrasion of his anterior teeth because of his technique of handling porcelain powder during the construction of restorations. To keep the brush moist, he habitually licked it as he applied porcelain powder to restorations. The porcelain powder, which is extremely abrasive, acted as a grinding powder between his maxillary and mandibular anterior teeth. Adjunctive orthodontics and a combination of adhesive, minimal-intervention restorations were used to create an esthetic and functional solution.

Adult↗

Dementia assessment: to do or not to do?

In this article, the authors summarise the diagnostic investigations that may be used to assess the health status of people with dementia. They express their concern with opposition to the use of the investigations on the grounds of expense and the incapacity of the tests to definitively diagnose Alzheimer's disease. The argument of the paper is that thorough investigation of people with dementia is warranted. Without such assessment, reversible or arrestable conditions that produce symptoms of dementia are not detected or treated. When dementia is diagnosed early, people with the condition and their carers are better prepared to plan and cope and expenses associated with mismanagement of people with some forms of dementia are minimised. The authors conclude that withholding diagnostic investigation of dementia deprives a group of people of the health care to which they are entitled.

Aged↗

Virus-like particles in Eimeria nieschulzi are associated with multiple RNA segments.

RNA preparations from sporulated oocysts of Eimeria nieschulzi were found to contain 2 double-stranded RNA segments of 5.0 kb and 5.7 kb that were not present in other species of Eimeria. Treatment of crude lysates with RNase A revealed that in addition to these two segments, 3 other segments of 0.57 kb, 0.72 kb and 11.5 kb were protected from digestion, suggesting that they were enclosed within particles. Virus-like particles with a diameter of approximately 39 nm were purified by caesium chloride buoyant density centrifugation. Four of the five RNA segments copurified with these particles. In keeping with the nomenclature generally adopted for protozoan viruses, we have named this new isolate ENV 1. The largest RNA segment does not cosediment with ENV 1 particles and may be derived from another RNA-protein complex that is unstable under the conditions used. The particle size and genome structure of ENV 1 both differ from that of the Eimeria stiedae virus (ESV), which is the only other virus to have been isolated from Eimeria to date. Short cDNA clones derived from ENV 1 show significant homology to a region of the Leishmania virus (LRV 1) genome that encodes an RNA-dependent RNA polymerase. The polymerase sequences from ENV 1 and LRV 1 are more closely related to each other than to any other protein sequences in the GenEMBL Database. This raises intriguing questions about the origins of the two viruses, since Eimeria and Leishmania normally infect different hosts and also show different cell tropisms within these hosts.

Amino Acid Sequence↗

Fibronectin gene expression differs in normal and abnormal human wound healing.

The overproduction of fibronectin and type I collagen in keloids and hypertrophic scars implicates altered regulation of extracellular matrix components as an important aspect of these wound healing pathologies. However, little is known about the similarities and differences in extracellular matrix gene expression during normal and abnormal wound healing. This study compared the content of fibronectin messenger RNA and rates of fibronectin protein biosynthesis in fibroblasts derived from normal skin, normal scar, keloid, and hypertrophic scar. Fibronectin expression was enhanced in cells from both normal and abnormal wounds relative to cells from quiescent normal skin. Matched pairs of normal and keloid fibroblasts from the same individuals were also compared, and three of the four pairs showed higher fibronectin expression by the keloid cells at the levels of messenger RNA and protein synthesis. This was consistent with previous studies showing elevated steady state content of fibronectin in keloid cells relative to normal cells from the same individual. Fibronectin messenger RNA and protein content in the tissues from which these cells were derived was examined by in situ hybridization and immunohistochemistry. These studies revealed that in vivo, the steady state content of fibronectin messenger RNA and protein was highest in abnormal wounds, less in most normal scars, and lowest in normal skin. Thus, fibroblasts from keloids and hypertrophic scars overexpressed fibronectin in vivo relative to normal skin and normal scar and retain this characteristic in vitro relative to normal skin. Although normal scars contained little fibronectin protein and messenger RNA, cultured fibroblasts derived from these scars had contents of fibronectin messenger RNA and rates of biosynthesis in vitro similar to those of keloid fibroblasts. This indicates that the fibronectin regulatory pathway in scar fibroblasts is influenced by the tissue environment. These results are discussed with respect to the relationship of fibronectin expression in keloids, hypertrophic scars, and normal wounds in human beings.

Journal Article↗

Desmoplastic malignant melanoma. An immunocytochemical study of 25 cases.

Using a panel of seven cell markers, we studied the value of immunocytochemical labelling in the histological diagnosis of desmoplastic malignant melanoma. Sections from routine formalin-fixed tissue of 45 surgical specimens were obtained from 25 cases of malignant melanoma that showed well-marked desmoplastic or neurotropic features. Routinely stained sections (Haematoxylin- and -eosin and melanin stains) were compared with the following panel of seven antibodies: S-100, neuron-specific enolase (NSE), vimentin, factor XIIIa (FXIIIa), desmin and the newer, supposedly more specific antimelanoma antibodies HMB45 and NKIC3. S-100 and NSE were the most sensitive antibodies for desmoplastic malignant melanoma with strong labelling of spindle cells in most cases. In contrast, results for NKIC3 were more variable; results were negative in nearly half the tumours, but strong labelling was seen in six cases (27%). Positive labelling for HMB45 was noted in five tumours (22%); it was mostly confined to small groups of cells in the superficial part of the lesions. Tumour spindle cells were negative for FXIIIa in all cases; there was no increase in the number of positive dermal dendritic cells compared to conventional and spindle cell melanoma. All tumours were desmin-negative, but most were vimentin-positive. Our findings indicate that immunocytochemistry is of less value in the diagnosis of desmoplastic malignant melanoma that it is with other types of malignant melanoma. However, positive or negative labelling for S-100 protein and NSE is useful for suggesting or excluding a diagnosis of desmoplastic malignant melanoma; neither marker is specific and, in particular, positive labelling is also found in most neurofibromas and benign cellular naevi.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Anti-idiotypic activity against anti-myeloperoxidase antibodies in pooled human immunoglobulin.

We investigated the ability of six different pooled human immunoglobulin (PHIG) preparations to inhibit the binding of anti-myeloperoxidase (MPO) antibodies to MPO. All six PHIG preparations inhibited the binding of anti-MPO antibodies from six sera to MPO in a concentration-dependent manner in the concentration range 0.016-10 mg/ml. There was considerable variation in the ability of each PHIG preparation to inhibit the binding of anti-MPO antibody in a given serum. Further differences were seen in the ability of a given PHIG to inhibit anti-MPO binding in different sera. F(ab')2 fragments from two PHIG preparations also inhibited in a concentration-dependent manner anti-MPO binding to MPO in all six sera in the concentration range 0.002-2.65 mg/ml, with a maximum inhibition of 42%. Little inhibition was seen with F(ab')2 of normal human IgG from individual donors (1.8-12.2% at the maximum concentration of 2 mg/ml). F(ab')2 fragments from three anti-MPO containing sera and two affinity-purified anti-MPO antibodies were eluted by affinity chromatography from Sepharose-bound PHIG F(ab')2 and showed anti-MPO antibody activity. We have shown that PHIG and F(ab')2 fragments of PHIG inhibit anti-MPO binding to MPO, and further that F(ab')2 fragments of PHIG bind to F(ab')2 fragments of anti-MPO antibodies. These observations indicate binding between the variable regions of PHIG and the antigen binding site of anti-MPO antibodies, and are consistent with an anti-idiotypic reaction. The variability seen in the inhibitory effect of the different PHIG preparations in anti-MPO-positive sera implies differences in their anti-idiotype content, while the variability of the inhibitory effect of a particular PHIG preparation between different sera suggests heterogeneity in the idiotypic repertoire of anti-MPO antibodies. Such variations in the inhibitory effect of different PHIG preparations on antibody binding may be an important determinant of their therapeutic effect.

Animals↗

Tumour necrosis factor-alpha and other cytokines in Guillain-Barré syndrome.

The efficacy of plasma exchange implicates myelinotoxic humoral factors in the pathogenesis of Guillain-Barré syndrome. Candidate factors include autoantibodies to peripheral nerve myelin, which are not unique to Guillain-Barré syndrome; and cytokines such as tumour necrosis factor-alpha (TNF-alpha) which are T cell/macrophage products. Plasma cytokine concentrations were determined in 26 patients with Guillain-Barré syndrome undergoing plasma exchange, 25 with other acute neurological diseases, and 40 healthy controls. Raised TNF-alpha concentrations (> 25 pg/ml) were found in seven of 26 patients with Guillain-Barré syndrome v none of 23 disease controls (p = 0.001). The peak grade of clinical deficit correlated with TNF-alpha concentrations (r = 0.6, p < 0.01). There was no significant difference between interleukin-1 beta or interferon-gamma concentrations in patients and disease controls. The data suggest that TNF-alpha may be a critical factor in the pathogenesis of Guillain-Barré syndrome.

Cytokines↗