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Biomedical subjects

C Knight

Publications and source records attributed to C Knight.

At least 55 records · Page 3Linked to original sources
PubMed1999

Can perineural invasion on prostate needle biopsy predict prostate specific antigen recurrence after radical prostatectomy?

PURPOSE: We evaluated the role of perineural invasion identified on prostate needle biopsy as a predictor of prostate specific antigen (PSA) recurrence after radical prostatectomy. MATERIALS AND METHODS: Between 1993 and 1998 radical prostatectomy was performed in 319 consecutive patients. Prostate needle biopsies were reviewed in all cases. We compared perineural invasion with other preoperative parameters, including digital rectal examination, PSA and biopsy Gleason score, for the ability to predict PSA recurrence with recurrence defined as any serum PSA level greater than 0.2 ng./ml. RESULTS: Perineural invasion was identified on 77 of 319 preoperative prostate biopsies (24%). There was PSA recurrence in 46 patients (14.4%) at a mean followup of 25.4 months (range 0.2 to 62.1). Perineural invasion statistically correlated with PSA recurrence. Kaplan-Meier analysis revealed disease-free survival rates of 24 versus 64% when perineural invasion was and was not present in the prostate biopsy (p = 0.0003, log rank 12.92). Multivariate analysis demonstrated that perineural invasion (p = 0.012) and PSA (p = 0.005) were independent preoperative predictive factors of PSA recurrence. When perineural invasion was compared with postoperative parameters, including disease stage, surgical margins and seminal vesicle invasion, it was not an independent predictor because it closely correlated with tumor stage. CONCLUSIONS: Perineural invasion on preoperative prostate needle biopsy is a strong independent predictor of PSA recurrence in patients in whom prostate cancer was treated with radical prostatectomy.

Adult↗
PubMed1998

The role of transcranial Doppler in nonarteritic ischemic optic neuropathy.

PURPOSE: To investigate through the use of cerebral Doppler technology whether emboli are a more common cause of nonarteritic anterior ischemic optic neuropathy (NAION) than previously recognized. METHODS: Eleven patients with a recent (<121 days) history of nonarteritic anterior ischemic optic neuropathy and 10 age-matched controls (event > 121 days) were examined using a Nicolet Pioneer 2020 transcranial Doppler (TCD) unit with a 2-MHz bilateral continuous monitoring capability. The right and left middle cerebral arteries were evaluated simultaneously for 30 minutes at a depth of 50 to 55 mm, and the number of emboli, blood flow velocities, and pulsatility indices were recorded. Data were stored by computer, and hard-copy color recordings were made. RESULTS: None of 11 patients with a recent history of NAION demonstrated microemboli by TCD examination. One patient in the control group who had a remote history of NAION had a microembolic event rate of 12 per hour (six over 30 minutes). This patient had a history of prosthetic cardiac valve replacement and was taking anticoagulation medication at the time of the examination. CONCLUSIONS: Our study did not reveal an increased incidence of embolic events in patients with NAION when they were examined in a transcranial Doppler study of the middle cerebral arteries. This study does not support embolism as a frequent cause of NAION.

Arteritis↗
PubMed1998

Long-term (5 year) effects of transient (silent) ischaemia on left ventricular systolic function in stable angina. Clinical and radionuclide study.

AIMS: (a) to assess short (1 year) and long-term (5 year) changes in left ventricular ejection fraction in patients with stable coronary disease with or without ECG evidence of transient ischaemia during daily life on routine therapy, and (b) to assess whether patients with recurrent transient ischaemic episodes have a particular propensity to gradual deterioration in left ventricular ejection fraction in the absence of infarction. METHODS AND RESULTS: One hundred and forty eight patients (127 males; mean age 59 years), part of a natural history cohort of 172 patients who had undergone exercise testing, 48 h ambulatory ST monitoring, and resting radionuclide ventriculography at baseline, and who had not suffered any intervening cardiac event, underwent repeat radionuclide ventriculography at 1 year follow-up on identical or very similar medications. Furthermore, 56 patients (50 males; mean age 65 years) of this cohort, who had ischaemia both on exercise testing and ambulatory monitoring at baseline (n=33), or no ischaemia on either test at baseline (n=23), and who had suffered no intervening event, underwent repeat exercise testing, ambulatory monitoring and radionuclide ventriculography at a mean of 61.8 months follow-up. In 38 of these 56 cases, long-term testing mirrored baseline testing in terms of presence or absence of ischaemia (both tests +, n=25; both tests -, n=13). At one year there was no change in left ventricular ejection fraction, either for the whole group (n=148; left ventricular ejection fraction 47=11.6% - 47.13+11.07%, P=ns) or for subgroups with (n=62; left ventricular ejection fraction 48+12.1%-48.5+10.5%, P=ns) and without (n=86; left ventricular ejection fraction 46.2+10.4%-46.2+11.3%, P=ns) evidence of transient ischaemia at baseline. At 61 months, there was a small fall in mean left ventricular ejection fraction for the total study group (n=56; left ventricular ejection fraction 45.8+9.3%-42.1+8.8%, P<0.05); however, this fall was not significant for those patients with both baseline and 5 year evidence of transient ischaemia (n=25; left ventricular ejection fraction 44.9+8.7%-41.3+7.5%, P=0.056). CONCLUSION: In medically treated stable coronary patients who do not suffer any intervening cardiac event, recurrent transient (silent) ischaemic episodes do not, in themselves, lead to gradual deterioration in left ventricular systolic function over a 1-5 year period.

Adult↗
PubMed1998

Anti-RNA polymerases and other autoantibody specificities in systemic sclerosis.

Sera from 735 patients with systemic sclerosis were classified according to antinuclear antibody (ANA) pattern as follows: centromere (25%), homogeneous (26%), fine speckled (21%), fine speckled with nucleolar (14%), coarse speckled (7%), nucleolar only (3%) and cytoplasmic only (3%). Immunoprecipitations using 35S-labelled HeLa cell antigen extract were performed using sera from 374 of these patients to detect the systemic sclerosis-specific antibodies to RNA polymerases I and III. The sera were selected to represent each ANA group, but focused on those giving fine speckled nucleoplasmic staining (with or without nucleolar staining) where all 86 sera positive for these antibodies were concentrated. Immunoprecipitates from a further 93 sera from patients with ANA-positive autoimmune diseases other than systemic sclerosis did not precipitate RNA polymerases. In addition, all sera were tested for antibodies to the extractable nuclear antigens topoisomerase I, nRNP, Ro, La and PM-Scl. Sera positive for antibodies to these antigens gave clear correlations with ANA patterns but, of the examples tested, none contained antibodies precipitating RNA polymerase I or III. Thus, sera containing antibodies to RNA polymerases I and III were exclusive of both anticentromere and anti-topoisomerase I, and formed a major serological subgroup (11.7%). Clinically, 77% were patients with diffuse cutaneous disease reflected by higher skin scores and a significantly higher incidence of renal involvement (33%) than patients with antibodies to topoisomerase I (3%).

Adult↗
PubMed1998

Inclusion body disease in two captive Australian pythons (Morelia spilota variegata and Morelia spilota spilota).

Two captive Australian pythons, one carpet and one diamond python, presented with signs of central nervous system dysfunction. The carpet python was agitated. Its head was tilting and it was incoordinated and had convulsions. It was treated with antibiotics and anthelmintics but was eventually euthanased after failing to respond to therapy. The diamond python had flaccid paralysis of the caudal half. It was not treated and became disoriented and died. Hepatocytes from both pythons contained irregular 2 to 10 micron eosinophilic intracytoplasmic inclusion bodies. The brain of the diamond python was not available for examination. Occasional neurones in the carpet python brain contained similar inclusion bodies and other changes suggestive of viral infection. The clinical signs and histopathological findings in both pythons were consistent with boid inclusion body disease.

Animals↗
PubMed1998

Cloning, characterization, and tissue expression pattern of mouse tuftelin cDNA.

Tuftelin is a protein that has been suggested to function during enamel crystal nucleation. Published sequences for bovine tuftelin cDNA and genomic clones proposed different reading frames that radically affected the derived amino acid sequence of the tuftelin carboxyl-terminus. We have isolated and characterized a full-length mouse cDNA clone and a partial porcine cDNA clone that include the region of the proposed frame-shift. The mouse tuftelin clone is 2572 nucleotides in length, exclusive of the poly(A+) tail. Translation from the 5'-most ATG yields a protein of 390 amino acids with an isotope-averaged molecular mass of 44.6 kDa and an isoelectric point of 5.9. Comparison of the bovine, mouse, and porcine cDNAs supports the revised bovine tuftelin amino acid sequence and suggests that the bovine tuftelin translation initiation codon be re-assigned to a more 5' ATG. Re-assigning the translation initiation codon lengthens the tuftelin protein by 52 amino acids, 51 of which are identical between bovine and mouse. At the carboxyl-terminus, the revised bovine and the mouse sequences match at 39 of the final 42 amino acid positions, compared with 2 identities with the originally published bovine reading frame. Northern blot analysis reveals that tuftelin is not ameloblast-specific but is expressed in multiple tissues, including kidney, lung, liver, and testis. Two tuftelin RNA messages, of 2.6 and 3.2 kb, were detected. DNA sequence characterization of an RT-PCR amplification product confirmed expression of tuftelin in kidney, and identified an alternatively spliced mouse tuftelin mRNA lacking exon 2.

Amino Acid Sequence↗
PubMed1998

A hirudin-sensitive, growth-related proteinase from human fibroblasts.

We have identified a hirudin-sensitive proteinase from human fibroblasts. Inhibition of this enzyme results in partial inhibition of cell growth in culture. The enzyme has a molecular weight of about 38000, and can be isolated by affinity chromatography with a hirudin-agarose matrix. The enzyme is apparently not closely related to thrombin, but does show a high level of amino acid sequence homology with fragments of a protein isolated from the synovial fluid of rheumatoid arthritis patients, which acts as a mitogen for human T lymphocytes.

Amino Acid Sequence↗
PubMed1998

The effect of enhanced milk yield of dairy cows by frequent milking or suckling on intake and digestibility of the diet.

Groups of 9 or 10 cows were assigned to one of three treatments 1) machine-milking three times daily, 2) machine-milking six times daily, and 3) suckling three times daily in addition to machine-milking three times daily. Treatments were conducted during the first 6 wk postpartum. During wk 5, digestibility of the diet was estimated by the indigestible neutral detergent fiber method. During wk 6, milk yield and dry matter intake (DMI) were recorded daily, and plasma concentrations of glucose, nonesterified fatty acids, urea, protein, growth hormone, insulin, insulin-like growth factor I, oxytocin, and prolactin were determined. Milk yields were 38.5, 46.8, and 52.7 kg/d, and DMI were 18.1, 21.2, and 17.2, for cows on treatments 1, 2, and 3, respectively. Plasma glucose concentrations decreased, and plasma nonesterified fatty acid concentrations increased, for cows on treatments 2 and 3 compared with cows on treatment 1. Digestibility of dry matter was 57.5, 60.5, and 60.6%; of organic matter was 62.6, 64.6, and 66.8%; and of crude protein was 59.3, 62.7, and 64.6% for cows on treatments 1, 2, and 3, respectively. Concentrations of all assayed hormones, except insulin, increased moderately for cows on treatment 2 compared with cows on treatment 1 and increased dramatically for cows on treatment 3. Insulin concentrations followed the opposite trend. The DMI were positively related to milk yields and negatively related to oxytocin concentrations. Digestibility was negatively related to plasma glucose concentrations in a nonlinear pattern. The possible involvement of hormones in improvement of digestibility is discussed.

Animals↗
PubMed1998

The future of clinical nurse specialists in psychiatric-mental health nursing.

The role of the clinical nurse specialist in psychiatric-mental health nursing is undergoing transformation secondary to massive changes occurring within the health care delivery system, as well as the larger society. In order to address these changes and their influence upon the evolution of the advanced practice role of clinical nurse specialists in psychiatric-mental health nursing, an Ad Hoc Committee consisting of twelve members of The Society of Certified Clinical Specialists in Psychiatric Nursing of the New Jersey State Nurses' Association met in 1996 and 1997 in order to explore and define the future of clinical nurse specialists in psychiatric-mental health nursing. This report is a summary of salient findings by the Committee which define numerous influences upon the role of psychiatric nurses in advanced practice, including factors affecting health care changes and influences of health care changes upon clinical nurse specialists in psychiatric-mental health nursing, along with recommendations for the future by members of the Ad Hoc Committee of the New Jersey Society of Certified Clinical Specialists in Psychiatric Nursing. The report is divided into three sections and is presented in three consecutive issues. Part Three is the final segment of this three part series. It contains the committee's final recommendations for the future.

Forecasting↗
PubMed1997

A novel series of 2,5-substituted tryptamine derivatives as vascular 5HT1B/1D receptor antagonists.

The design, synthesis, and activity of a novel series of 2,5-substituted tryptamine derivatives at vascular 5HT1B-like receptors is described. Several important auxiliary binding sites of the 5HT1B-like receptor have been proposed following various modifications to the 2-substituent and especially to the methylene- or ethylene-linked 5-side chain. Careful design of new molecules based on a proposed pharmacophoric model of the 5HT1B-like receptor has resulted in the discovery of ethyl 3-[2-(dimethylamino)ethyl]-5-[2-(2, 5-dioxo-1-imidazolidinyl)ethyl]-1H-indole-2-carboxylate (40), a highly potent, silent, competitive, and selective antagonist which shows affinity at the vascular 5HT1B-like receptors only. Changes to the size of the 2-ester substituent have a significant effect on affinity at the 5HT1B-like receptor and other receptors. Prudent placement of the carbonyl substituent in the heterocycle of the 5-side chain is crucial for good affinity and selectivity over the 5HT2A and other receptors. Several key structural and electronic features were identified which are crucial for producing antagonism within a tryptamine-based series. An electron deficient indole ring system appears essential in order to achieve antagonism, and this is achieved by the inclusion of electron-withdrawing groups at the 2-position of the indole ring. The molecule displacement within the receptor resulting from the inclusion of the bulky 2-substituents also enhances antagonism as this results in the removal of the pi electron density of the indole ring from the region of the receptor normally occupied by the indole ring of 5HT. There also appears to be a structural requirement on the side chain incorporating the protonatable nitrogen, and this is achieved by the inclusion of the bulky 2-ester group which neighbors the 3-ethylamine side chain.

Animals↗
PubMed1997

Nonsurgical septal reduction for hypertrophic obstructive cardiomyopathy: outcome in the first series of patients.

BACKGROUND: Some patients with hypertrophic obstructive cardiomyopathy may gain symptomatic relief from a reduction in the extent of obstruction to left ventricular outflow. We present the outcome of the first series of patients treated with an alternative method of gradient reduction using catheter techniques. METHODS AND RESULTS: Eighteen patients were treated with selective intracoronary alcohol injection to induce localized septal infarction. Patients underwent echocardiographic measurement of left ventricular dimensions and Doppler echocardiographic evaluation of left ventricular outflow tract gradients before the procedure, on the first postoperative day, and at a median follow-up of 3 months after the procedure. In addition, patients underwent exercise testing and symptom evaluation before and 3 months after nonsurgical septal reduction. There was a significant reduction in left ventricular outflow tract obstruction after the procedure (preprocedure, 67 mm Hg [95% CI, 48 to 87 mm Hg]; postprocedure, 25 mm Hg [95% CI, 16 to 34 mm Hg]; P=.0006), which persisted at 3-month follow-up (22 mm Hg [95% CI, 12 to 32 mm Hg]; P=.001). This was associated with a significant improvement in symptoms. There was a small but not significant increase in exercise capacity (n=10; preprocedure, 418 seconds [95% CI, 273 to 563 seconds]; postprocedure, 452 seconds [95% CI, 283 to 621 seconds). Left ventricular dimensions were not significantly altered by nonsurgical septal reduction. CONCLUSIONS: Nonsurgical septal reduction significantly reduces left ventricular outflow tract obstruction and improves symptoms in some patients with hypertrophic obstructive cardiomyopathy. The technique may provide an alternative to surgical myomectomy in selected patients.

Adolescent↗
PubMed1997

Emergency, cardiac arrest! Can we teach the skills?

The European Resuscitation Council (ERC) has produced basic life support (BLS) and advanced life support (ALS) guidelines (1992) in an attempt to standardize the training and delivery of cardiopulmonary resuscitation (CPR). In response to this, the Avon and Gloucestershire College of Health, Glenside Centre (now University of the West of England), conducted a small survey, testing students' knowledge and skills in delivering CPR. Students were able to improve knowledge levels, but did not uniformly improve practical skills. Following this, the college formed a resuscitation team whose members coordinate CPR training in the curriculum, using uniform teaching packs which follow the ERC Guidelines (ERC 1992a), and resuscitation equipment purchased by the college as the result of the research findings. In addition to maintaining uniform content, sessions are compulsory and students' CPR skills are tested, with a 70% competency level set as a pass. Student results and attendance are stored on a college database, along with tutor information regarding updating of CPR skills. To achieve these developments, the college has had to consider time allocation within the curriculum, training of tutors, funding of resources and funding of a compulsory training programme, which supports a ratio of one tutor to six students. Evaluations of the changes are favourable, as students' CPR skills and knowledge show obvious improvement and the students' general confidence and enthusiasm are enhanced.

Cardiopulmonary Resuscitation↗
PubMed1997

The effectiveness of DRL in the management and treatment of severe behaviour disorders following brain injury.

Effective management of behaviour disorders following brain injury is essential if individuals are to achieve their rehabilitation potential. Best practice dictates that the intrusiveness of any operant approach used be minimal, remain in operation for the shortest time possible, and emphasize skill building. Ideally, treatment gains should maintain following its withdrawal. Reinforcement methods fulfil these criteria in that they are less intrusive, concerned with the establishment of pro-social behaviours, and encourage positive staff-patient interaction. While their efficacy has been well documented with other clinical populations, less is known regarding treatment of behaviour disorders in survivors of brain injury. Some existing studies are characterized by methodological weakness that limit understanding of any contribution made to observed improvement, and little is known regarding maintenance of treatment effects. In this paper the effectiveness of a variant of differential reinforcement, DRL, will be examined. Three cases will be presented which demonstrate increased behavioural control in response to the use of DRL. A strength of this paper is that the use of appropriate single-case design methodology, and follow-up data up to 18 months after treatment, permits more robust conclusions regarding the efficacy of DRL to be made. These are discussed, together with practical points regarding programme design.

Activities of Daily Living↗
PubMed1997

Tolerance of volunteers to cyclosporine A-dilauroylphosphatidylcholine liposome aerosol.

Cyclosporine A (CsA) in liposomes of dilauroylphosphatidylcholine (DLPC), containing 118 micrograms of CsA/L of aerosol with a particle size of 1.6 to 1.7 micron diameter, was inhaled by 10 nonsmoking, normal volunteers each for 45 min. Aerosol was administered through an Aerotech II nebulizer (CIS-US, Inc., Bedford, MA) mouthpiece. Eight of the 10 volunteers had tracheal irritation and intermittent coughing following exposure. FEV1 and FVC values were mildly reduced, but returned to normal in 1 h. Blood chemical and hematologic values were unchanged at any time point after as opposed to before inhalation. Nine of the 10 volunteers later inhaled DLPC only, administered through the nebulizer mouthpiece. There was no change in FEV1 or FVC values, and there was no coughing or tracheal irritation. Subsequently, five of the volunteers who had previously had respiratory reactions inhaled CsA-DLPC liposome aerosol for 45-min, but through a mouth-only face mask. There was no tracheal irritation, coughing, or changes in spirometric measures. Blood concentrations of CsA at 15 min after the 45-min inhalation with a face mask averaged 83 +/- 42 ng/ml (mean +/- SD). At 24 h after treatment, CsA was undetectable in blood of the initial 10 volunteers. These studies indicate that CsA-DLPC liposome aerosol can be safely explored as a treatment for patients with moderately severe asthma.

Administration, Inhalation↗
PubMed1997

Processing of the gap junction protein connexin50 in the ocular lens is accomplished by calpain.

Gap junction channel forming connexins share a common membrane topology which has four transmembrane spanning segments with the amino- and carboxy termini both located on the cytoplasmic side. Both, mutation and truncation of the carboxyl tail of some connexins have been shown previously to have profound effects on channel function. Truncation of the carboxyl tail of connexin50 (Cx50) and connexin46 (Cx46) occurs naturally during the maturation of fiber cells in the mammalian lens. This system therefore offers the unique opportunity to study not only the cleavage process but also the functional role played by the cleaved domain, in a physiologically relevant context. As a first step, we now report on the cleavage of the 70 kDa ovine isoform of Cx50. The calcium-activated neutral protease calpain (EC 3.4.22.17) was identified as the enzyme which removed a 32 kDa carboxyl portion from the Cx50 molecule in mature lens fiber cells. The amino-terminal 38 kDa portion remained embedded in the plasma membrane and was isolated and visualized as channel structures. The amino-terminal sequence of the cleaved 32 kDa portion matched an interior portion of the published amino acid sequence of the ovine Cx50 isoform. Thus, two closely spaced calpain cleavage sites were identified in the Cx50 molecule which were located carboxy-terminal from the predicted exit of the fourth transmembrane spanning segment by 62 or 72 amino acid residues, respectively. These data provide the basic information required for the future construction of Cx50 mutants to explore the functional consequences of this cleavage.

Amino Acid Sequence↗
PubMed1997

Use of a modified version of the Overt Aggression Scale in the measurement and assessment of aggressive behaviours following brain injury.

Aggressive behaviour creates a significant challenge in neurorehabilitation. Despite the success in using behaviour modification principles in the treatment of post-acute behavioural problems, psychopharmacological approaches to the management of aggression are more frequently reported. However, inconsistencies apparent in the literature hinder inter-study comparisons of treatment methods. These include severity of brain injury, neuropsychological status and rigour of experimental methodology used. Data about aggression is also inconsistently reported, especially with regard to classification and severity. Descriptions of how aggressive behaviour responded to pre-treatment is also generally absent. In this paper an observational rating scale is described in an attempt to address these inconsistencies. The Overt Aggression Scale has been modified by increasing the range of interventions to reflect current practice in neurorehabilitation, and by changing the language to make it suitable for UK users. A range of antecedents has also been added to make the scale useful in behavioural analysis. Preliminary results indicate inter-rater reliability is good, and it is a valid indicator of type and severity of aggression. Antecedents and interventions used in the management of aggressive behaviours in neurorehabilitation are also illustrated. Clinical use of the scale is also discussed.

Aggression↗