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Biomedical subjects

J Nicholls

Publications and source records attributed to J Nicholls.

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

Primary chemotherapy for stage II nonseminomatous germ cell tumors of the testis.

Between 1979 and 1989, 122 patients with clinical stage II testicular nonseminoma were treated with primary platinum-based combination chemotherapy following orchiectomy. Of the patients 58 had Royal Marsden Hospital stage IIA (nodes less than 2 cm. in diameter) and the other 64 had stage IIB (nodes 2 to 5 cm. diameter) disease. With a median followup after chemotherapy of 5.5 years, 118 patients (97%) were disease-free. Two patients died of progressive germ cell tumors, 1 of bleomycin toxicity and 1 of coincidental disease. The 5-year actuarial survival probability was 95% (95% confidence intervals 91 to 99%) and the 5-year failure-free survival probability was 92% (95% confidence intervals 88 to 97%). Tumor substage was not predictive of relapse but did indicate the probability of lymphadenectomy for a post-chemotherapy residual mass since this was performed in 17% of the patients with stage IIA disease and 39% with stage IIB disease (p < 0.05). Resected specimens contained mature teratoma (29), necrosis alone (5) or embryonal carcinoma (1). We conclude that for these clinical stages primary chemotherapy was as effective as primary lymph node dissection and a major operation was avoided in 68% of the cases.

Actuarial Analysis↗
PubMed1994

Peripheral blood involvement in non-Hodgkin's lymphoma detected by clonal gene rearrangement as a biological prognostic marker.

Peripheral blood from 67 patients with non-Hodgkin's lymphoma was examined at initial diagnosis for the presence of circulating lymphoma cells by DNA hybridisation using immunoglobulin and T-cell receptor gene probes. Clonal gene rearrangement was found in 31% (21/67) of patients and correlated with clinical stage, histological grade and bone marrow involvement. Clinical stage and the presence of lymphoma cells in peripheral blood were prognostic factors for progression-free survival in all patients on univariate analysis, but the detection of lymphoma cells was not independent of stage. It was also not a significant predictor for survival. In patients with intermediate- and high-grade lymphoma, the detection of lymphoma cells in peripheral blood was a significant prognostic factor for progression-free survival (PFS) and survival only on univariate analysis. The 3-year PFS was 17% in patients with circulating lymphoma cells compared with 75% if these were absent (P < 0.05). The presence of lymphoma cells in peripheral blood is associated with extensive disease and may be a biological marker of poor disease control. Sensitive techniques of detection should form part of large prospective studies in non-Hodgkin's lymphoma.

Adult↗
PubMed1994

Maternal expressed emotion in conduct and emotional disorders of childhood.

Maternal expressed emotion (EE) scales were rated for children aged 6-11 with conduct disorders, emotional disorders and a group of non-referred children matched for sex and age (N = 30 in each of the three groups). Maternal warmth distinguished significantly between the three groups (CD < ED < Controls), while criticism distinguished the group of conduct disordered children. Maternal criticism was positively associated with child behaviour ratings even within the non-referred group. These observational ratings of warmth and criticism were found to be much more strongly associated with child behaviour than maternal ratings of their family environment.

Adult↗
PubMed1994

Detection of wild type and exon 5-deleted splice variant oestrogen receptor (ER) mRNA in ER-positive and -negative breast cancer cell lines by reverse transcription/polymerase chain reaction.

Using reverse transcription (RT)/PCR we have shown that four breast cancer cell lines expressed oestrogen receptor (ER) mRNA, irrespective of whether they were assessed as ER-positive (MCF-7 and BT-474) or ER-negative (MDA-MB-231 and BT-20) by enzyme immunoassay (EIA). In addition to the wild type (WT) form, they were all found to express the exon 5-deleted variant (V) form of ER mRNA by RT/PCR; this is thought to code for a truncated constitutively active protein. By Northern blot analysis only the ER-positive cell lines (MCF-7 and BT-474) were found to express detectable levels of ER mRNA. Oestradiol-induced growth was found only in the ER-positive (by EIA) cell lines. These results confirm that the differences between ER-positive and ER-negative cell lines are quantitative rather than qualitative. As low levels of ER mRNA could be detected by RT/PCR, this may reflect the greater sensitivity of this approach. The presence of exon 5-deleted V form ER mRNA in addition to the WT form in all four breast cancer cell lines may allow these lines to be used to assess differential regulation of transcription and the impact of this on their oestrogen dependence.

Base Sequence↗
PubMed1994

GnRH neurons and other cell populations migrating from the olfactory neuroepithelium.

Cell migration from the olfactory neuroepithelium to the brain has been widely studied during vertebrate development. Immunocytochemical analysis has revealed that many of the migrating cells contain GnRH (Gonadotropin-Releasing Hormone). The GnRH positive cells migrate from the medial olfactory placode, steam along the nasal septum, cross the basal forebrain and reach the hypothalamic and septal areas from where they control the release of hypophyseal gonadotropic peptides. A peculiar feature of these cells is that they start expressing GnRH during migration. We have analysed the presence of immunoreactivity for peptides typically expressed in olfactory neurones, along the migratory pathway followed by GnRH neurones. We have used polyclonal antibodies raised against carnosine and olfactory marker protein (OMP), and performed double immunolabelling on mouse embryos and on early neonatal Brazilian opossum (Monodelphis domestica) tissues. Beside the GnRH neurones we observed other migrating cells along the pathway traced by olfactory terminal and vomeronasal nerves. Most of these cells co-express carnosine and OMP. The carnosine/OMP migrating cells are detectable in later developmental stages than GnRH neurones. GnRH neurones do not express either OMP or carnosine. By keeping in culture explants of the brain together with the olfactory region from newborn opossums, we have shown that it is possible to obtain the migration of the different populations in vitro. Moreover the GnRH cells are co-distributed, but different from those expressing olfactory markers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Control of aromatase in breast cancer cells and its importance for tumor growth.

Three approaches have been taken to elucidate further the biological importance of intratumoural aromatase activity. (i) MCF7 and T47D hormone-dependent breast cancer cell lines both showed detectable aromatase activity in vitro. The up-regulation of this by TGF alpha indicates the possible existence of an autocrine growth stimulatory loop involving aromatase. (ii) Both tamoxifen and cytotoxic chemotherapy caused the suppression of aromatase activity in breast carcinomas in vivo. Aromatase activity prior to treatment did not predict for clinical response to tamoxifen. (iii) Transfection of aromatase into MCF7 cells led to their growth being stimulated by low doses of androgens and this was inhibited by the aromatase inhibitor CGS 16949A.

Aromatase↗
PubMed1993

In-situ carcinoma adjacent to recurrent nasopharyngeal carcinoma. Evidence of a new growth?

Eighty biopsies from 74 patients with recurrent nasopharyngeal carcinoma diagnosed in the years 1988 to 1990 inculsive were reviewed. The overlying epithelium was assessed for the presence of in-situ malignant change using a Gomori reticulin stain in addition to the routine haematoxylin and eosin stain. In-situ change was seen in the overlying epithelium or adjacent epithelium in 11 of these biopsies from 10 patients (13.5%). These changes were extensive and where normal epithelium was seen there was an abrupt transition from the normal to abnormal epithelium. As patients treated for NPC sustain such a high risk of developing another new growth, close and careful follow up of these patients will allow a good opportunity for research into the carcinogenesis of this tumor.

Carcinoma in Situ↗
PubMed1993

Assessment of psychosocial experiences in childhood: methodological issues and some illustrative findings.

The development of a new standardised investigator-based interview, PACE (Psychosocial Assessment of Childhood Experiences), for the assessment of acute life events and long-term psychosocial experiences is described. An application of PACE to a sample of 84 children referred to psychiatric clinics and 22 general population controls, is presented. Reliability was assessed using a separate clinic sample of 15 child-parent pairs. The findings showed that PACE has satisfactory reliability and discriminant validity.

Adaptation, Psychological↗
PubMed1993

Characterization and ontogeny of P1-purinoceptors on rat vas deferens.

1. The P1-purinoceptors which mediate the inhibition by adenosine of nerve-mediated contraction of the rat vas deferens have been investigated by use of the agonists N6-cyclopentyladenosine (CPA) and 5'-N-ethylcarboxamidoadenosine (NECA) and the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The ontogeny of the responses to adenosine and to the two co-transmitters which induce the contractions in this tissue, adenosine 5'-triphosphate (ATP) and noradrenaline (NA), have also been studied. 2. The order of potency for the adenosine agonists in inhibiting the nerve-mediated contractions was CPA = NECA > adenosine. Micromolar concentrations of DPCPX were required to antagonize the inhibition by adenosine and NECA of nerve-mediated responses, whereas the inhibitory effect of CPA was antagonized by nanomolar concentrations of the antagonist. 3. NECA and adenosine inhibited contractions induced by ATP (10 microM) or by NA (10 microM), NECA being at least ten fold more potent than adenosine, whereas CPA was inactive. Micromolar concentrations of DPCPX were required to antagonize the effect of adenosine on the contractions induced by ATP (10 microM). 4. Nerve-stimulated contractions could be observed in neonatal tissues from day 15 and increased with age, and could be inhibited by adenosine from this time, the potency of adenosine decreasing with age. Responses to ATP also appeared at day 15 and increased with age up to day 25, while responses to NA were present from day 10 (the earliest day tested) and decreased with age. 5. These results show that the rat vas deferens contains both prejunctional Al-receptors and postjunctional A2-receptors, and that adenosine acts on the latter populations to inhibit nerve-mediated contractions.The high potency of adenosine in the neonate and the parallel development of responses to ATP and to nerve-mediated contractions support suggestions that purinergic responses may be particularly important in neonatal tissues.

Adenosine↗
PubMed1993

A district confidential enquiry into deaths due to asthma.

BACKGROUND: The aim was to establish a continuing district based confidential enquiry into deaths from asthma. METHODS: A confidential enquiry was conducted in an English health district. Subjects comprised 24 residents of the Norwich health district aged between 16 and 65 years who had died between 1988 and 1991 with asthma as the principal cause of death. RESULTS: Twenty one of the patients (88%) died away from hospital. Overall the routine asthma management was appropriate in all respects in only four patients. In five cases the drug treatment was considered inappropriate, in 10 cases (42%) there was no written evidence that the patient had received advice and education, and only six cases had a written management plan. In 17 patients (71%) the fatal attack of asthma developed rapidly (in under three hours). The medical care during the final attack was found to have been inappropriate in six cases. Seventeen cases (71%) had psychological or social factors that were considered to have been of potential importance. CONCLUSIONS: This study has shown the feasibility of organising a confidential enquiry into asthma deaths within a health district. The distinguishing features of such an enquiry are that it is continuing, that the quality of care given to those patients who died is compared against a recognised standard, and that there is a structured system for feeding back the conclusions of the enquiry to the local medical community.

Asthma↗
PubMed1993

Comparative clinical, microbiologic, and economic audit of the use of oral ciprofloxacin and parenteral antimicrobials.

OBJECTIVE: To examine the use of oral ciprofloxacin and parenteral antimicrobials in the treatment of acute infection (respiratory tract, urinary tract, blood) in hospitalized patients, with particular reference to severity of infection, outcome, and associated economic implications of each treatment. DESIGN: A prospective, multicenter comparative audit was conducted in the UK over an 18-month period. The audit was undertaken by clinical pharmacists who reviewed the antimicrobial treatment of patients with infective episodes, who were receiving or could have received oral therapy. PARTICIPANTS: Clinical pharmacists who collated the data all are employed in teaching hospitals. MAIN OUTCOME MEASURES: Patients were identified for analysis by their type of infection, severity of illness, antimicrobial prescribed, route of administration, and response to therapy. Additionally, data on costs of the antimicrobials prescribed and the supplementary costs of drug administration were calculated. RESULTS: Four hundred eighty-five patients were enrolled for analysis; 208 of the patients had respiratory tract infection, 112 had urinary tract infection, 138 had septicemia, and 27 had mixed infections. Sepsis scores were applied to 152 patients receiving oral ciprofloxacin and 333 patients receiving parenteral antimicrobials and yielded mean scores of 5.9 (SD 3.1, range 1-13) and 8.7 (SD 4.2, range 1-22), respectively. Of 485 patients, 188 were paired according to sepsis score results and route of administration. Resolution occurred in 133 patients (79 receiving oral and 54 receiving parenteral therapy), further therapy was required in 49 (11 oral and 38 parenteral), and treatment was withdrawn in 6 (4 oral and 2 parenteral). Microbiologic assessment yielded positive results in 227 patients (47 percent). Drug acquisition costs (based on 1 UK pound = 1.80 US $) per course of treatment were $47.23 (SD $38.32, range 5.40-218.70) for the oral group and $173.70 (SD 209.77, range 2.11-1021.40) for the parenteral group. Overall costs for treatment courses were $74.00 (SD $52.81, range 8.10-309.17) and $305.59 (SD $304.70, range 14.69-1345.00) for the two groups, respectively (p < 0.001). CONCLUSIONS: This study suggest that, in patients with moderate infective episodes, oral ciprofloxacin may reduce overall treatment costs compared with the use of parenteral antimicrobial agents.

Adolescent↗
PubMed1993

Wound performance.

The purpose of this study was to collect information about wound management practices which would establish baseline wound healing data. This data would be used to make measurable comparisons with new wound management techniques. This study focuses on data collected from the surgical area of Auckland Hospital. All patients whose wounds were surgically acquired were included in the study. Data collection was started immediately post-operatively and continued at each dressing change until the patient was discharged. The data collection tool was developed from "nursing expectations" of wound healing performance. This previously undefined set of expectations is an aggregate of the result of nursing knowledge, nursing experience and individual patients' conditions. The tool was refined against actual wound recovery and became a standard to test the accuracy of expectations. The wounds involved in this study were categorised and allocated expected healing rates. This was linked with discharge planning. It was against the stated range of expectations that wounds were measured for performance, as--"better than (expected)," "average," or "less than." Patients were divided into three broad age groups that reflected a particular health status and pre-existing influences. The groups chosen were: "20 years and under," "20 to 70 years" and "70 years plus." These groups were used as indicators to determine risk for wound management. Wound healing was measured as to whether it met nursing expectations. Factors such as wound appearance, complications, solutions and induction antibiotic cover were also measured. Findings show the hospital has a minimal level of complications of surgically acquired wounds.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Extent of nasopharyngeal carcinoma involvement inside the nasopharynx. Lack of prognostic value on local control.

A study on the use of fiberscopic examination and multiple biopsy specimens taken from the nasopharynx in the assessment of the extent of nasopharyngeal carcinoma (NPC) involvement inside the nasopharynx found that the involvement often was more extensive than the detected with conventional methods. In the current study, 247 patients with NPC were studied with the use of fiberscopic examination, and multiple biopsy specimens were taken from the superior wall, posterior wall, and lateral wall of the nasopharynx on both sides. It was confirmed that the tumor often involved the nasopharynx extensively. Also, the extent of primary tumor involvement inside the nasopharynx was correlated with the American Joint Committee (AJC) T stage and the degree of paranasopharyngeal extension of the tumor (P = 0.0100 and 0.0009, respectively), as well as with the size of the largest node and the lowest neck level involved by the node in the ipsilateral neck (P = 0.0005 and 0.005, respectively). However, the extent of primary tumor involvement inside the nasopharynx, expressed as either the number of the six standard sites or the number of the AJC subsites that were involved, had no predictive value on the control of the primary tumor (P = 0.3773 and 0.7794, respectively) at a median follow-up time of 27 months. Except when salvage brachytherapy is contemplated for persistent or recurrent NPC, the extent of primary tumor involvement inside the nasopharynx should not be routinely studied.

Actuarial Analysis↗
PubMed1992

Acute hemorrhagic myocarditis in systemic lupus erythematosus.

We report a 46-year-old patient with longstanding systemic lupus erythematosus (SLE) who developed rapidly progressive heart failure and died. At postmortem, there was a unique picture of hemorrhage and mild inflammation present in the myocardium causing the heart failure. As far as we are aware, this picture has not been described before in SLE and is similar to that seen in the cardiac allograft hyperacute rejection.

Coronary Vessels↗
PubMed1992

Does extragonadal presentation impart a worse prognosis to abdominal germ-cell tumours?

The prognostic significance of extragonadal rather than gonadal presentation of germ-cell tumour in 51 patients presenting between 1979 and 1988 with abdominal tumours was compared with that of 51 control patients with testicular primary tumours matched for bulk fo disease, serum tumour marker concentration, age and year of treatment. Very large volume tumour was found at initial staging in 24 extra-gonadal cases (47%) and high tumour markers in 29 (57%). Actuarial survival at 2 and 5 years was 82% and 70% for cases and 78% and 63%, respectively, for controls. These outcomes were not significantly different and the relative hazard of death for cases compared with controls was 0.7 (95% confidence intervals 0.3-1.5). Thus the presentation of germ-cell tumours with a retroperitoneal mass does not itself adversely influence prognosis compared with testicular presentation with equivalent disease extent. However it is rare for extragonadal presentation to be associated with small volume disease.

Abdominal Neoplasms↗