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Biomedical subjects

M King

Publications and source records attributed to M King.

At least 91 records · Page 5Linked to original sources
PubMed1999

Effects of dextran on tracheal mucociliary velocity in dogs in vivo.

We have previously shown that dextran (molecular weight 4kDa) is a potential mucolytic agent, reducing the viscoelasticity and spinnability of cystic fibrosis (CF) sputum and improving its mucociliary clearability during in vitro testing. We wished to see whether low molecular weight (LMW) dextran had similar effects on mucus rheology when administered by aerosol to living dogs, and whether the administration of dextran increased the rate of mucociliary clearance. Healthy mongrel dogs were anesthetized with pentobarbital and intubated. After a 30-min Ringer aerosol delivery during spontaneous breathing, tracheal mucociliary velocity (TMV by charcoal marker particle transport) was measured under bronchoscopic control, and mucus for viscoelasticity analysis (magnetic rheometer) was collected by the endotracheal tube method. Then LMW dextran in Ringer vehicle was delivered by aerosol via the endotracheal tube, followed by the same procedures. We performed eight experiments in eight dogs, involving 30 min administrations of dextran aerosol; all dogs received inhalations of 20 mg/ml, 65 mg/ml, and 200 mg/ml dextran. Compared with Ringer control, TMV increased to 145% of control (P=0.0417) at 65 mg/ml dextran. Mucus viscoelasticity (G*) significantly decreased to 19% of control (P=0.0426) at 65 mg/ml. This in vivo study supports our previous in vitro testing, that LMW dextran decreases the mucus viscoelasticity and increases the rate of mucociliary clearance. We estimate the dosage received by aerosol at 65 mg/ml to be within the effective concentration range studied in vitro, i.e. 10-15 mg/ml final concentration. The results are consistent with the proposed mechanism that the saccharide moieties in LMW dextran compete for hydrogen bonding sites with other mucous glycoproteins. These new hydrogen bonds are structurally and rheologically ineffective, thus reducing the overall cross-link density, and making the mucus more easily cleared by ciliary and cough mechanisms.

Administration, Inhalation↗
PubMed1999

Progress with the HeartSaver Ventricular Assist Device.

BACKGROUND: Ventricular assist devices (VADs) have been shown to be effective for short- or long-term circulatory support. Devices are either being adapted or newly designed for longer term or permanent support, with the goal to provide patients with improved quality of life. Since 1990, a program has been in place to develop a totally implantable, permanent VAD. METHODS: A multidisciplinary team is developing this VAD with specific goals in mind: (1) that it have an intrathoracic position, (2) that it be a totally implantable device without any percutaneous connections, and (3) that it be possible to communicate with the device from remote locations. These goals would allow for complete patient mobility and flexibility for follow-up. RESULTS: The electrohydraulically actuated VAD combines the blood pump, volume displacement chamber, energy converter, and internal electronic module into a single compact unit. The device called the HeartSaver VAD is powered by a transcutaneous energy transfer system and can be remotely monitored and controlled. Prototypes of different versions of the device have been tested in vitro and in vivo with satisfactory performance. CONCLUSIONS: The prototypes of the HeartSaver VAD have functioned well under test conditions and fulfilled the outlined goals. Further development and testing of the design are being conducted before clinical availability.

Animals↗
PubMed1999

The effect of spiritual beliefs on outcome from illness.

We aimed to assess the role of spiritual belief in clinical outcome of patients nine months after hospital admission. Two hundred and fifty patients admitted to a London teaching hospital were recruited and followed up for nine months. Outcome measures were clinical status as recorded in the outpatient records and patients' self reported health status and beliefs. A hundred and ninety-seven (79%) patients professed some form of spiritual belief, whether or not they engaged in a religious activity. Strength of belief was lower in patients who were in a more serious clinical state on admission (F = 3.099, d.f. = 2 and 192, p = 0.05). Case note information was available nine months later for 234 patients (94%) and contained useful information for judging clinical outcome in 189 (76%). Patients with stronger spiritual beliefs were 2.3 times more likely (CI = 1.1-5.1, p 0.033) to remain the same or deteriorate clinically nine months later. Other predictors of poor outcome were male gender and sleep disturbance at time of admission to hospital. We conclude that a stronger spiritual belief is an independent predictor of poor outcome at nine months in patients admitted to two acute services of a London hospital. It is more predictive of outcome than physical state assessed by clinicians, or self-reported psychological state, at admission.

Adult↗
PubMed1999

On the antioxidant activity of melatonin.

Melatonin has been widely reported to be an effective antioxidant. Studies of its ability to inhibit the autoxidation of lipids in homogeneous solution and in model heterogeneous systems show that melatonin is not a peroxyl radical trapping antioxidant. In contrast, melatonin can inhibit metal ion-catalyzed oxidation processes.

Antioxidants↗
PubMed1999

Liver-specific and seasonal expression of transgenic Atlantic salmon harboring the winter flounder antifreeze protein gene.

We have analyzed the inheritance and expression of a line of transgenic salmon harboring the antifreeze protein gene from the winter flounder. The genomic clone 2A-7 coding for a major liver-type antifreeze protein gene (wflAFP-6) was integrated into the salmon genome. From a transgenic founder (#1469), an F3 generation was produced. In this study, southern blot analysis showed that only one copy of the antifreeze protein transgene was integrated into a unique site in F3 transgenic fish. The integration site was cloned and characterized. Northern analysis indicated that the antifreeze protein mRNA was only expressed in the liver and showed seasonal variation. All of the F3 offspring contained similar levels of the antifreeze protein precursor protein in the sera and the sera of these offspring showed a characteristic hexagonal ice crystal pattern indicating the presence of antifreeze activity. In addition, the antifreeze protein precursor protein level was found to vary with the season, being highest in the month of November and lowest in May. This study had demonstrated a tissue-specific and stable expression of the antifreeze protein transgene in the F3 generation of the transgenic salmon 1469 line.

Animals↗
PubMed1999

Symptoms 2 weeks, 3 months and 12 months after treatment of early breast cancer: the patients' perspectives.

The physical symptoms and side-effects reported by patients treated for early breast cancer with surgery (S), (breast conservation or mastectomy), radiotherapy (R) and chemotherapy (C) are reported. As part of a large quality-of-life study, eligible patients were invited to complete a questionnaire at three and 12 months after treatment for early breast cancer. Symptoms 2 weeks after surgery were retrospectively collected at the 3-month questionnaire. Comparing the commonly used different therapy combinations (S, S+R, S+C and S+R+C) we found the only loco-regional symptom to show a significant difference between these groups was chest tightness (P<0.001). Both anxiety about attending for and discomfort during C were significantly higher than during R (P<0.00005 and 0.00001 respectively). We found that the addition of R and, or, C to S resulted in surprisingly little variation in physical side-effects.

Journal Article↗
PubMed1999

Prosodic preservation in Landau-Kleffner syndrome: a case report.

Landau-Kleffner syndrome (LKS) is a rare acquired condition of auditory verbal agnosia and convulsive disorder in children. It has been proposed that there is a functional relationship between electrical disturbance and the speech defect. Prosody or the melody of language, as described by Monrad-Krohn (1947), is one aspect of non-verbal communication which is distributed bilaterally in the brain. Prosodic parameters of expression and perception in one 7.5-year-old child were tested to see if they were preserved as a means of communication. The child was observed during video-electroencephalogram (EEG) monitoring over a 48-hour period. All utterances were recorded and subject to analysis for the salience and variation of acoustic correlates of prosody. Prosodic comprehension was measured using specific perceptual tasks previously presented to normal children between the ages of 5.5 and 8.5. Despite being unable to meaningfully use or perceive phonemes, the child was able to use variations in fundamental frequency, duration and intensity of utterances, to convey both emotional and propositional intent. Similarly, the child was able to discriminate prosodic contours of a male adult voice to an age equivalent to 5.5 to 6.5 years. This argues in favour of the notion for educating such children not only through the visual channel but also through the auditory channel.

Agnosia↗
PubMed1999

Effect of aerosolized uridine-5'-triphosphate on airway clearance with cough in patients with primary ciliary dyskinesia.

Primary ciliary dyskinesia (PCD) is a genetic disease characterized by abnormal ciliary structure and function and impaired mucociliary clearance. Because patients with PCD use cough clearance as an airway defense mechanism, we tested the hypothesis that aerosolized uridine-5'-triphosphate (UTP) would improve clearance during cough by its actions to stimulate Cl- secretion and mucin release by goblet cells. We measured clearance during cough in 12 patients with PCD (ages 14 to 71 yr, FEV1 43% to 89% predicted) in a double blind, randomized, crossover study after aerosolization of a single dose of UTP (5 mg/ml, 3.5 ml) or vehicle (0.12% saline, 3.5 ml). Clearance during cough (whole lung) was quantified during and after a series of controlled coughs by measuring the clearance of [99mTc]Fe2O3 particles via gamma camera scanning over 120 min. Safety parameters were recorded during and after drug delivery. Aerosolized UTP improved whole-lung clearance during cough as compared with vehicle (from 0 to 60 min: 0.40 +/- 0.07%/min [UTP] versus 0.26 +/- 0. 04%/min [vehicle] [mean +/- SEM], p = 0.01), and from 0 to 120 min: 0.38 +/- 0.05%/min [UTP] versus 0.25 +/- 0.04%/ min [vehicle], p = 0. 02). Aerosolized UTP is safe, with no serious adverse effects. Whole-lung clearance during cough in patients with defective ciliary function is enhanced after inhalation of UTP.

Administration, Inhalation↗
PubMed1999

The struck-off mystery.

Observations on ward rounds suggested that psychiatric patients might be at special risk of removal from their general practitioner's list. Little has been published on why patients are struck off and our first attempt at investigation was by direct appeals for patients. This drew a small and unsatisfactory sample. We then asked two family health services authorities to distribute questionnaires to struck-off patients. One agreed, but later withdrew cooperation. There is a danger that struck-off patients will become an underclass excluded from primary care. We propose anonymous collection of information by health authorities, so that policy can be reviewed if necessary.

Community Psychiatry↗
PubMed1999

Ethnicity and outcome of psychosis.

BACKGROUND: An excess of psychotic illness in Black people has been found in cross-sectional studies. Little is known about the outcome of psychosis in different ethnic groups in the UK. AIMS: To compare the incidence, nature and long-term outcome of psychosis in different ethnic groups. METHOD: A five-year, prospective study of an epidemiological cohort of people with a first contact for psychosis. RESULTS: Age-standardised incidence rates for schizophrenia and non-affective psychosis were higher for Black and Asian people than Whites. Stability of diagnosis and course of illness were similar in all ethnic groups. During the fifth year, Black people were more likely than others to be detained, brought to hospital by the police and given emergency injections. CONCLUSIONS: The nature and outcome of psychotic illness is similar in all ethnic groups but Black people experience more adverse contacts with services later in the course of illness.

Adolescent↗
PubMed1999

British psychiatry and homosexuality.

BACKGROUND: Opposition to homosexuality in Europe reached a crescendo in the 19th century. What had earlier been regarded as a vice evolved as a perversion or psychological illness. Official reviews of homosexuality as both an illness and (for men) a crime led to discrimination, inhumane treatments and shame, guilt and fear for gay men and lesbians. Only recently has homosexuality been removed from all international diagnostic glossaries. AIMS: To review how British psychiatry has regarded homosexuality over the past century. METHOD: Review of key publications on homosexuality in British psychiatry. RESULTS: The literature on homosexuality reflects evolving theories on sexuality over the past century. The assumptions in psychoanalysis and the behavioural sciences that sexuality could be altered led to unscientific theory and practice. CONCLUSIONS: Mental health professionals in Britain should be aware of the mistakes of the past. Only in that way can we prevent future excesses and heal the gulf between gay and lesbian patients and their psychiatrists.

Attitude of Health Personnel↗
PubMed1999

Acute effects of inhalable particles on the frog palate mucociliary epithelium.

This work was designed to evaluate the toxicity of inhalable particles [less than/equal to] 10 microm in aerodynamic diameter (PM(10)) collected from the urban air in São Paulo, Brazil, to the mucociliary apparatus using the frog palate preparation. Seven groups of frog palates were immersed in different concentrations of PM(10) diluted in Ringer's solution during 120 min: 0 (control, n = 31); 50 (n = 10); 100 (n = 9); 500 (n = 28); 1,000 (n = 10); 5,000 (n = 11); and 10,000 microg/m(3) (n = 10). Mucociliary transport and transepithelial potential difference were determined at 0, 30, 60, and 120 min exposure. Additional groups (control and 500 microg/m(3)) were studied by means of morphometric analyses (quantification of the amount of intraepithelial and surface mucins), measurement of cilia beat frequency, and quantification of total glutathione. Mucociliary transport and transepithelial potential difference were significantly decreased at higher concentrations of PM(10) (p = 0.03 and p = 0.02, respectively). Exposure to PM(10) also elicited a significant decrease of total glutathione (p = 0. 003) and depletion of neutral intraepithelial mucins (p = 0.0461). These results show that PM(10) can promote significant alterations in ciliated epithelium in vitro.

Aerosols↗
PubMed1999

The teaching and learning principles of metropolitan Aborigines with diabetes.

This study was undertaken at a leading Aboriginal health agency in Adelaide called Nunkuwarrin Yunti (King & Wilson 1998). One of the aims not previously reported involved identifying the way that metropolitan Aborigines prefer to learn about their diabetes management. An ethnographic approach was used to interview ten Aboriginal health professionals and four clients (n = 14) about this topic. The results indicated the worldview held by metropolitan Aborigines about diabetes health care, the Aboriginal learner, beliefs about teaching and learning, the characteristics of an effective teacher and a suggested teaching plan.

Adult↗
PubMed1999

Successful treatment of severe muscle necrosis with intravenous immunoglobulin.

Intravenous immunoglobulin (IVIG) is an effective treatment for a range of conditions believed to have an autoimmune basis, including inflammatory muscle disease. We describe a patient with muscle disease characterized by severe necrosis without clinical or biopsy evidence of inflammation or vasculitis, who responded to treatment with IVIG.

Biopsy↗
PubMed1999

Dermal and transdermal delivery of protein pharmaceuticals: lipid-based delivery systems for interferon alpha.

The dermal and transdermal delivery of protein pharmaceuticals faces enormous challenges, and at the same time has very significant potential for the non-invasive treatment of both localized and systemic diseases. In this article we review the various approaches used to enhance and control the delivery of protein therapeutic agents through the dermal barrier. We show results of the delivery of interferon (IFN) alpha, an antiviral agent used in the treatment of condylomata acuminata (genital warts), using lipid-based delivery systems (LBDS). In the general category of LBDS, we investigated the use of liposomes and fatty acylation as ways to increase IFNalpha delivery into human skin.

Acetylation↗
PubMed1999

Mucus-controlling agents: past and present.

Airway mucus is the secretory product of the mucous cells. The mucus is a variable mixture of water, mucous glycoproteins, low molecular weight ions, proteins, and lipids, the physical properties of which are important for airway defense. The factors that contribute to the physical properties of mucus are complex, and there are several pharmacologic strategies that potentially can serve to improve the clearability of airway mucus. In vitro results suggest potential benefit from the additive effects of selected combinations of mucoactive medications. Further studies are required to confirm these findings, to perform direct assessments of mucus clearability, and to extend the observations to patients with various types of pulmonary diseases for which mucoactive treatments are required.

Drug Combinations↗