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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 343 records · Page 19Linked to original sources

Amnihook versus amnicot for amniotomy in labour.

In a study of 100 women in established labour we investigated two devices currently used for amniotomy, the Amnihook, a long rigid instrument and the Amnicot, a finger stall with a plastic hook on the end. No overall difference was found in operator ease of use or maternal discomfort. There were significantly fewer babies with long scratches p = 0.02, Odds ratio 0.19 (95% CI 0.05 to 0.68) and the mean scratch length was almost halved in the Amnicot group (p < 0.05, 95% CI for difference between means 0.653 to 6.71). Our findings support the theoretical advantage of a reduction in fetal scalp trauma using a flexible device for amniotomy.

Amnion↗

Expression of O6-alkylguanine-DNA-alkyltransferase in situ in ovarian and Hodgkin's tumours.

The cellular expression of O6-alkylguanine-DNA-alkyltransferase (ATase) may be an important factor in determining tumour sensitivity to certain alkylating agents. In a comparative study, we have examined the inter- and intracellular distribution of ATase in tumour biopsies of a series of patients with Hodgkin's disease and ovarian cancer using a rabbit antihuman ATase antiserum. The antibody recognises the ATase protein on western blots of cell-free extracts of a number of ovarian tumours with ATase activities varying from 20 to 420 fmol/mg protein as determined by in vitro assay and there was a linear correlation between ATase activity and the intensity of the band on western blots (r = 0.993). Immunohistochemical staining was seen in all of the ovarian tumours examined and was confined to the nucleus. This is in contrast to the Hodgkin's tissue, where staining was much reduced and present in both nuclei and cytoplasm. The results suggest that in ovarian tumours the general resistance to nitrosourea chemotherapy may be related to the high cellular expression of ATase protein: this is in contrast to the more chemosensitive Hodgkin's disease. This raises the possibility that it might be feasible to predict sensitivity or resistance to these alkylating agents by immunohistochemical staining of tumour or tissue specimens.

Adult↗

The Christie Hospital breast conservation trial: an update at 8 years from inception.

In 1990, we published the results of a clinical trial involving 708 patients with breast carcinoma of 4 cm or less in diameter, who, following lumpectomy, were randomized to have radiotherapy to the tumour bed only (limited field, LF group) or to the whole breast and regional nodes (wide field, WF group). No adjuvant systemic therapy was prescribed. At the time the median follow-up was 37 months. We present the updated results after an extended median follow-up of 65 months. The overall survival is 72.7% and 71.2% for the LF and WF groups respectively. The actuarial breast recurrence rate (first event) is 15% (LF) versus 11% (WF) for infiltrating ductal carcinoma, whereas, for infiltrating lobular carcinoma, the recurrence rate was 34% (LF) versus 8% (WF). A high actual recurrence rate of 21% (LF) and 14% (WF) was also found for extensive ductal carcinoma in situ. It was extremely rare for medullary, mucoid or tubular carcinomas to recur. Salvage surgery was possible in 86% (LF) and 90% (WF) respectively. The recurrence rate in the breast following lumpectomy and wide field irradiation is comparable with others reported in the literature. This trial also shows the lumpectomy with limited field irradiation is feasible, albeit with a higher breast recurrence rate; the latter could be reduced by improved selection and refinement of the technique.

Aged↗

Multiple primary tumours in a population-based series of patients with histopathologically peer-reviewed sarcomas.

Multiple primary tumours occurring in a three-year population-based series of patients with histopathologically peer-reviewed sarcomas from North West England were ascertained in order to look at the patterns of neoplasms seen. A total of 30 out of the 310 patients entered in the study had additional primary tumours. Very few patients were aged under 60 years at diagnosis of both their malignancies. The youngest was a known case of neurofibromatosis and, although seven patients were diagnosed with a sarcoma and carcinoma of the breast--a combination of cancers characteristic of the Li-Fraumeni cancer family syndrome--no other patients could directly be identified as suffering from any other cancer predisposition syndrome.

Adult↗

Pneumococcal capsular polysaccharide-meningococcal outer membrane protein complex conjugate vaccines: immunogenicity and efficacy in experimental pneumococcal otitis media.

Vaccines composed of pneumococcal capsular polysaccharides (PS) conjugated to outer membrane protein complex (OMPC) from Neisseria meningitides group B bacteria were tested in the chinchilla otitis media model. Monovalent (types 6B and 23F), bivalent (6B+23F), and tetravalent (6B+14+19F+23F) PS-OMPC conjugate vaccines elicited significant total serum antibody responses against all four PS. Type 6B vaccine elicited IgG, IgM, and IgA antibodies after a single dose and an anamnestic IgG response after a second vaccine dose on day 28. Type 6B and 19F vaccines prevented or greatly attenuated pneumococcal otitis media after direct middle ear challenge with the immunizing serotype, type 14 vaccine was not protective by this challenge route, and type 23F pneumococci were not sufficiently virulent in chinchillas to test vaccine effectiveness. The promising results with two serotypes suggest the PS-OMPC conjugates may be useful in human infants.

Animals↗

Identification of cellular proteins that bind to the human immunodeficiency virus type 1 nef gene product in vitro: a role for myristylation.

The human immunodeficiency virus (HIV) type 1 nef gene product was expressed as an N-terminal fusion protein with glutathione-S-transferase (GST) in the baculovirus system. The resulting nefGST fusion protein was found to be authentically myristylated at the N terminus and could be purified to homogeneity by one-step affinity chromatography on immobilized glutathione. The high affinity of nefGST for glutathione was exploited to develop an assay to identify cellular proteins capable of interacting with nef. Several such proteins were identified in extracts from the Jurkat human T cell line. The interaction between nef-binding proteins and immobilized nefGST could be specifically competed by the addition of soluble nef. Cell fractionation showed that nef-binding proteins were present in both cytosolic and membrane-associated fractions. A non-myristylated derivative failed to bind to the membrane-associated proteins but was able to bind to the cytosolic group, albeit with reduced affinity. In addition, a single protein present in both soluble and membrane-associated fractions exhibited myristylation-independent binding to nef. By analogy with other myristylated proteins such as MARCKS (myristylated alanine-rich C kinase substrate) and the Rous sarcoma virus transforming protein, src, the membrane-associated proteins that bind only to myristylated nef may represent a specific membrane target for nef. The cytosolic proteins that interact with nef may constitute soluble components of an as yet unidentified signal transduction pathway which is the target of nef action in the HIV-1-infected cell.

Acylation↗

Chondroid syringoma with hyaline cell change.

Four cases of chondroid syringoma containing large numbers of hyaline or plasmacytoid cells are described. Three cases occurred in the hand and one in the foot. Hyaline cells are commonly seen in mixed tumours and myoepitheliomas of salivary glands and rarely in chondroid syringomas. The hyaline-cell change in three of the cases initially caused diagnostic difficulties and the possibility of sarcoma was raised in two cases. In addition to the characteristic hyaline cells, the presence of tubulo-glandulo-ductal structures, benign squamous epithelium and myxochondroid stroma aided diagnosis. Immunohistochemically, the hyaline cells exhibited positivity for vimentin, cytokeratin, S-100 protein, carcino-embryonic antigen, focal glial fibrillary acidic protein (3 cases), neuron-specific enolase (3 cases) and focal alpha-smooth muscle actin (2 cases). Occasional cells were Ber EP4 positive (2 cases). In some cells, a striking peripheral ring-like positivity for cytokeratin and S-100 protein was noted. Ultrastructurally, desmosomes, varying numbers of tonofibrils and non-bundling intermediate filaments were seen. Scanty fine filaments with vague focal densities were detected in some cells. Our studies suggest that the hyaline cells represent modified epithelial as well as myoepithelial cells. One of our cases also exhibited collagenous spherulosis.

Actins↗

Lymphomas of mucosa-associated lymphoid tissue arising in the urinary bladder.

The clinical, histological and immunohistochemical findings in five primary lymphomas of the urinary bladder are reported. One patient had both lymphoma and transitional cell carcinoma of the bladder. All of the lymphomas showed histological features of mucosa-associated lymphoid tissue (MALT) lymphomas with centrocyte-like cells in all cases. One patient with pre-existing cystitis glandularis showed lymphoepithelial lesions. Biopsies from four patients contained reactive germinal centres and, in two of these, there was follicular colonization by tumour cells. In three patients, repeat biopsies, over several years, showing the changes of MALT lymphoma, were diagnosed as cystitis. We suggest that a large proportion of primary lymphomas of the bladder are lymphomas of MALT and that the characteristic morphological and immunohistochemical features of these tumours should be sought in biopsies containing large numbers of lymphoid cells.

Adult↗

Divergent differentiation in small round-cell tumours of the soft tissues with neural features--an analysis of 10 cases.

A series of 10 small round-cell tumours, having in common evidence of neural differentiation, were investigated by immunohistochemistry and electronmicroscopy. In seven, evidence of divergent muscle and/or epithelial differentiation was found. This phenomenon thus appears more common than previously appreciated and suggests that there may be a continuous and overlapping phenotypic spectrum from Ewing's tumour of soft tissue to intra-abdominal desmoplastic small cell tumour.

Adolescent↗

Immunocytochemical localization of inflammatory cytokines and vascular adhesion receptors in radicular cysts.

Odontogenic cysts are one of the commonest bone destroying lesions of the maxillofacial skeleton, with the inflammatory radicular cyst being the commonest jaw cyst. Explants of radicular cysts produce an interleukin-1-like activity which could explain the osteolysis seen with these tumours though the cellular source of this osteolytic activity is unknown. In the present study, cytokines with known inflammatory and osteolytic activity: interleukin-1 (IL-1), tumour necrosis factor (TNF), interleukin-6 (IL-6), and the chemotactic cytokine interleukin-8 (IL-8) have been localized immunocytochemically in radicular cysts. The cellular adhesion receptors ICAM-1 and ELAM-1 have also been immunolocalized. All specimens showed positive staining for IL-1 (alpha and beta) and IL-6, with these cytokines being located in epithelial and vascular endothelial cells. Only two specimens demonstrated TNF and IL-8 staining, which was located in macrophages. All specimens demonstrated ELAM-1 staining in endothelium and ICAM-1 staining in epithelium, endothelium and mononuclear cells. These findings show that radicular cysts contain two bone-modulating cytokines, IL-1 and IL-6, and that these appear to be synthesized mainly by the epithelial cells. Cysts also contain a proportion of activated blood vessels whose endothelial cells express the cellular adhesion receptors ICAM-1 and ELAM-1.

Alveolar Bone Loss↗

Extended triple intrathecal chemotherapy trial for prevention of CNS relapse in good-risk and poor-risk patients with B-progenitor acute lymphoblastic leukemia: a Pediatric Oncology Group study.

PURPOSE: The Pediatric Oncology Group (POG) acute leukemia in childhood (ALinC) 13 study tested two treatment regimens that used different CNS chemoprophylaxis for children older than 12 months with non-T, non-B acute lymphoblastic leukemia (ALL) and with no demonstrable CNS disease at diagnosis. PATIENTS AND METHODS: With the first regimen, standard (S), six injections of triple intrathecal chemotherapy (TIC), consisting of methotrexate (MTX), hydrocortisone (HC), and cytarabine (ara-C), were administered during intensification treatment and at every-8-week intervals throughout the maintenance phase for 17 additional doses. The second regimen, standard and MTX pulses (SAM), also specified six TICs during intensification, but substituted every-8-week pulses of intermediate-dose parenteral methotrexate (IDM; 1 g/m2) for the 17 maintenance TIC injections, with a low-dose intrathecal (IT) MTX boost administered with the first four maintenance IDM pulses. Otherwise, systemic therapy on regimen SAM was identical to regimen S. There were 1,152 patients randomized to the S and SAM regimens after stratification by risk group (age/leukocyte count) and immunophenotype. RESULTS: The 5-year probabilities (+/- SE) of an isolated CNS relapse were regimen S: good risk (n = 381), 2.8% +/- 1.3%; poor risk (n = 196), 7.7% +/- 3.2%; good + poor risk (n = 577), 4.7% +/- 1.5%; regimen SAM: good risk (n = 388), 9.6% +/- 2.2%; poor risk (n = 187), 12.7% +/- 4.2%; good + poor risk (n = 575), 10.9% +/- 2.2%. In poor-risk patients, approximately one third of the isolated CNS relapses occurred before preventive CNS therapy was begun at week 9. Hence, regimen S has provided better CNS preventive therapy for both good- and poor-risk patients (P < .001 overall). The difference is statistically significant for good-risk patients (P < .001), but not for poor-risk patients (P = .20). Neither treatment has shown a significant advantage in terms of general outcome. CONCLUSION: TIC injections extended throughout the intensification and maintenance periods are superior to IDM pulses for prevention of CNS leukemia. Our results with TIC seem comparable with those achieved with other contemporary methods of CNS preventative therapy. Thus, extended TIC affords a reasonable alternative to CNS irradiation plus upfront IT MTX for patients with B-progenitor ALL.

Antineoplastic Combined Chemotherapy Protocols↗

Symptoms of sensory neuropathy in adults with NIDDM in the U.S. population.

OBJECTIVE: To ascertain the prevalence and determinants of sensory neuropathy symptoms through structured interview of a representative sample of people with diabetes in the U.S. population. RESEARCH DESIGN AND METHODS: The 1989 National Health Interview Survey consisted of a representative sample of 84,572 persons in the U.S. > or = 18 yr of age. A household respondent identified all people in the household believed to have diabetes (n = 2829). Subjects who could not be personally interviewed (n = 129) and individuals who stated they did not have diabetes (n = 295) were excluded. A detailed questionnaire was administered to 99.3% of the remaining 2405 subjects. Questions on symptoms of sensory neuropathy included whether during the past 3 mo the subjects had experienced numbness or loss of feeling, pain or tingling, or decreased ability to feel hot or cold. The neuropathy questions were also administered to a representative sample of 20,037 subjects who were not known to have diabetes. RESULTS: Prevalence of symptoms of sensory neuropathy was 30.2% among people with IDDM. This prevalence was 36.0% for men with NIDDM and 39.8% for women with NIDDM, compared with 9.8 and 11.8% for nondiabetic men and women, respectively. In logistic regression, factors independently related to symptoms of sensory neuropathy in people with NIDDM included duration of diabetes, hypertension, hyperglycemia, and glycosuria. Long duration of NIDDM (> or = 20 yr) was associated with a twofold increased risk of symptoms of sensory neuropathy compared with those with 0-4 yr of diabetes. Hypertension was associated with a 60% higher likelihood of symptoms. Diabetic individuals whose blood glucose was high all or most of the time or whose urine tests showed glucose all of the time were > 2 times as likely to have symptoms of sensory neuropathy than those who did not report hyperglycemia or glycosuria. Age, sex, ethnicity, cigarette smoking, and height were not determinants of sensory neuropathy. CONCLUSIONS: Symptoms of sensory neuropathy affect 30-40% of diabetic patients in the U.S. Men and women are affected equally. Prevalence of these symptoms increases with longer duration of diabetes; hypertension and hyperglycemia predispose to symptoms of sensory neuropathy.

Adolescent↗

Lessening the burden of diabetes. Intervention strategies.

OBJECTIVE: To evaluate the impact of primary and secondary interventions on the development of complications from diabetes, we modeled the effects of primary and secondary interventions for diabetes on a single well-studied complication, diabetic retinopathy. RESEARCH DESIGN AND METHODS: A model was developed to predict cumulative incidence of retinopathy in IDDM and NIDDM. Risk functions are based on duration of diabetes. The effects of intervention strategies were simulated by altering the retinopathy risk. The effects of the simulations were assessed using cumulative incidence. RESULTS: Simulations of delaying the onset of IDDM from 2 to 8 yr and decreasing the retinopathy rates by 20-80% were performed for each type of retinopathy. Simulating primary prevention shifted the cumulative incidence curves to the right, and simulating secondary intervention shifted the curves downward. Primary prevention was less effective than secondary prevention. This difference was more apparent for IDDM than for NIDDM, where disease duration and exposure to retinopathy risk were shorter. All interventions shifted the development of retinopathy to later in life. CONCLUSIONS: The greatest effect on cumulative incidence of all forms of retinopathy occurs when primary and secondary interventions are combined.

Adult↗

Structural characteristics of Australasian psychiatric practice.

A questionnaire examining structural and basic process characteristics of psychiatric practice was prepared by the RANZCP Quality Assurance Committee and circulated to all Fellows of the College in 1991. There were 830 replies (48%). A one in two sample of the replies was analysed and forms the basis of the descriptive report presented in this paper.

Australia↗