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Biomedical subjects

C Clarke

Publications and source records attributed to C Clarke.

At least 19 recordsLinked to original sources

Comparative efficacy and safety of amorolfine nail lacquer 5% in onychomycosis, once-weekly versus twice-weekly.

Amorolfine is a new topical antifungal of the phenylpropyl morpholine class which is highly active both in vitro and in vivo against yeasts, dermatophytes and moulds responsible for superficial fungal infections. Human pharmacological studies have established that amorolfine has a persistent antifungal effect in the nail bed and in the skin without being systemically absorbed. This has been confirmed by clinical work showing that amorolfine is effective in treating dermatomycoses and onychomycoses when administered as cream or nail lacquer. It is ineffective when given orally for systemic mycoses or bacterial infections in animals. In earlier studies a 5% concentration of amorolfine nail lacquer was found to produce a better cure rate in onychomycosis than a lower concentration of 2%. From data available on the penetration of amorolfine and on the persistence of mycologically relevant tissue concentrations, it appeared likely that once- or twice-weekly application of nail lacquer should suffice to produce a satisfactory therapeutic effect in onychomycosis. The aim of this investigation was to assess the efficacy and tolerability of 5% amorolfine nail lacquer given once versus twice weekly to patients with onychomycosis of finger nails and toe nails.

Administration, Topical

An appraisal of low-temperature embedding by progressive lowering of temperature into Lowicryl HM20 for immunocytochemical studies.

The progressive lowering of temperature (PLT) method of embedding for electron microscope immunolabelling has been examined with the objective of formulating a standardized protocol which can be applied to a wide variety of samples. The methods described cover fixation, processing of samples by the PLT method, embedding in Lowicryl HM20 and subsequent immunolabelling. Each of the steps in the fixation and embedding protocol has been assessed for its potential to retain both morphology and antigenicity. Comparison of samples embedded in Lowicryl K4M and HM20 at -25 degrees C indicate an increased membrane contrast in HM20 sections, and a further improvement in morphology when samples were embedded in HM20 at -50 degrees C rather than at -25 degrees C. The results of applying the methods described are demonstrated in a range of samples of both mammalian and botanical origin, which includes solid tissues, cells in suspension, and cells grown in vitro as a monolayer culture and embedded in situ. Samples processed by this method have been immunolabelled using a wide range of antibodies recognizing nuclear, cytoplasmic, cell membrane and extracellular matrix antigens.

Acrylic Resins

DNA-mediated transfer of a human gene that confers resistance to mitomycin C.

Attempts to complement the defect in the mitomycin C (MMC)-sensitive Chinese hamster ovary (CHO) mutant MMC3 led to the isolation of hybrids with high resistance to the cytotoxic action of the drug. Hybrid cells selected with MMC after fusion of MMC3 cells to human diploid fibroblasts were approximately five times more resistant to MMC than wild-type CHO cells but retained the original MMC3 sensitivity to another DNA cross-linking agent, diepoxybutane. To confirm that the MMC resistance was genetically determined and was of human origin, DNA from the resistant hybrids was introduced into MMC3 cells, and transfectants were selected in MMC. These cells had the same level of MMC resistance as the hybrids. Thus we have identified a human gene that can confer MMC resistance to CHO cells. Identification of the gene should help understand the mechanisms of MMC resistance in mammalian cells.

Animals

Hyperventilation reduces transcutaneous oxygen tension and skin blood flow.

Transcutaneous oxygen tension (PtcO2) is often used to monitor neonates and infants in special care units and the operating room. The transcutaneous index (TCI = PtcO2/arterial oxygen tension [PaO2]) is known to depend both on age and on cardiac index but is assumed to be independent of other physiologic variables. In this study we have shown that TCI also depends upon arterial carbon dioxide tension (PaCO2). Five young pigs were anesthetized and paralyzed and their lungs mechanically ventilated while they were monitored with PtcO2 electrodes and serial arterial blood gas analyses. For a 45 degrees C PtcO2 sensor, the mean TCI during normocapnia was 0.78, whereas during hyperventilation (PaCO2 = 20 mmHg) the mean TCI was reduced 65%, to 0.27. The corresponding TCI values for a 43 degrees C sensor were 0.33 and 0.065, representing an 80% decrease in TCI during hyperventilation. Hypoventilation had little effect upon TCI as long as hypoxemia was avoided. Twelve awake adult volunteers with radial artery cannulas were monitored with PtcO2 sensors at several body sites and two sensor temperatures. For a 44 degrees C sensor on the chest, the mean TCI decreased from 0.77 at normocapnia to 0.60 at a PaCO2 of 17 mmHg, a 22% change. For the same sensor on the foot, TCI decreased from 0.63 to 0.32, a 49% change. For a 42 degrees C sensor under the same conditions, the corresponding TCI decreases were 51 and 64%. Six of the volunteers were also monitored with laser-Doppler skin blood flow probes located on the chest, hand, and foot.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Persistence of supply dependency of oxygen uptake at high levels of delivery in adult respiratory distress syndrome.

OBJECTIVE: To identify any plateau in oxygen consumption (VO2) when oxygen delivery (DO2) is increased in patients with the adult respiratory distress syndrome (ARDS). DESIGN: Clinical prospective study; multiple regression analysis was done to assess the relationship between VO2 and DO2 for pooled data and for each individual patient. SETTING: University hospital ICU. PATIENTS: Twenty consecutive patients aged 18 to 78 yrs (mean 43.5) in whom ARDS was present during their ICU stay. INTERVENTIONS: Multiple measurements were obtained in individual patients (mean number of measurements 40, range 20 to 83) and mathematical models were fitted to both pooled and individual patient data. DO2 ranged from 212 to 1550 mL/min.m2 with a maximum of 758 to 1550 mL/min.m2 (mean 1136). Because of the large variations between patients, it was not justifiable to describe a relationship for the pooled data and each case was analyzed individually. MEASUREMENTS AND MAIN RESULTS: We found the optimal regression model to be linear in 13 patients, cubic in four, and either cubic or linear in one. Two patients demonstrated no significant relationship. The relationship for the group was determined from each patient's data and was best described by linear regression. CONCLUSIONS: In no patient was there evidence of a plateau, despite high levels of DO2 being achieved in all patients.

Adolescent

Hemodynamic and mitochondrial parameters during hypoxia and reoxygenation in working rat hearts.

Hypoxia and reoxygenation in working rat hearts were investigated in this study. Cardiac hemodynamic parameters which decline immediately under hypoxic conditions, recover during reoxygenation. Biochemical and ultrastructural alterations exhibit a more complicated pattern. There is a primary phase in hypoxic perfusion up to 15 min with a steep increase of ADP contents and ATPase activities, and a severe fall of ATP/ADP ratios in mitochondria, as well as in tissue. High CAT (carboxyatractyloside) sensitivity of the ATPase is observed at 5 min of hypoxia. Furthermore, the number of ATPase particles visible at the inner mitochondrial membrane decreases. During the ensuing second phase of hypoxic perfusion (from 30 min on) the damage of mitochondrial ultrastructure becomes more evident. The amount of ATPase particles visible at the inner mitochondrial membrane further decreases. ATPase activities fluctuate, however, they remain connected with the membrane during hypoxia. ATP/ADP ratios attain values of almost 1. During reoxygenation (after 30 min of hypoxia) the levels of mitochondrial adenine nucleotides, oxidative phosphorylation rate and respiratory control index increase within 20 min and then slightly decline again. The ATP/ADP ratio is diminished in the course of reoxygenation. ATPase activity also decreases within 20 min of reoxygenation and the ADP/O ratio reaches control values. The ATPase activity gains its highest sensitivity towards CAT at 10 min of reoxygenation attaining a value similar to that of 5 min of hypoxic perfusion. It is suggested that hypoxia and reoxygenation under our conditions result in reversible derangement of ATPase and mitochondrial membrane structure.

Adenine Nucleotides

Informal carers of the dementing elderly: a study of relationships.

This study investigated the problems involved in caring for a dementing person in the community from the perspective of their resident informal carer. It also examined the informal carer's relationships with both the dementing person and the statutory and voluntary services. Symbolic interaction theory was applied to this study since it considers the social meanings that things have as a result of an interactional process. To investigate this process, a qualitative research methodology was employed, comprising a diary, interview and post-contact notes. The sample was gathered from multiple referral sources: health, social and voluntary services. The diagnosis of a dementia was confirmed by the individual's own GP. Many of the results from this study support previous work in the field and four recommendations arise from analysis of the data. These are that formal carers could have a greater awareness of the needs of different groups of informal carers, the needs of informal carers in the very early stages of caring for a dementing person, the informal carer's need for counselling and the different reactions to offers of respite and long-term care which are seen as depending upon the relationship between the informal carer and the dementing person.

Adaptation, Psychological

Mortality in elderly patients admitted for respite care.

OBJECTIVE: To determine whether admitting elderly patients to hospital to give temporary relief to their carers is associated with increased mortality. DESIGN: Prospective multicentre study comparing the mortality of patients admitted on a one off or rotational basis with that experienced while they were awaiting admission. SETTING: A wide range of urban and rural district general, geriatric or long stay, and general practitioner hospitals. PATIENTS: 474 Patients aged 70 or over who had 601 admissions. MAIN OUTCOME MEASURE: Death. RESULTS: 16 (3.4%) Of the 474 patients (2.7% of all 601 admissions) died while in hospital during an average stay of 15.7 days whereas 23 (4.9%) patients died while awaiting admission (average waiting time was 34.2 days). The 16 deaths in hospital and the 23 deaths during the longer waiting period correspond to death rates of 19.9 and 12.5 per 10,000 person days respectively. The difference between these of 7.4 is not statistically significant (95% confidence interval -3.6 to 18.3). The estimated relative risk of dying in hospital is 1.59 but the 95% confidence interval is wide (0.84 to 3.01). CONCLUSION: Although the death rates are slightly higher in those admitted to hospital for relief care than in those awaiting admission, the difference was not significant, and the death rate in both groups was reassuringly small.

Aged

Arrangement of repetitive sequences in the genome of herpesvirus Sylvilagus.

Herpesvirus sylvilagus is a lymphotropic (type gamma) herpesvirus of cottontail rabbits (Sylvilagus floridanus). Analysis of virion DNA of herpesvirus sylvilagus has revealed that the genome consists of one stretch of about 120 kilobase pairs of internal, unique DNA flanked by a variable number of 553-base-pair tandem repeats. The G + C content of the repetitive DNA is extremely high (83%), as determined by sequencing. The organization of the herpesvirus sylvilagus genome is, therefore, similar to that of the primate lymphotropic viruses herpesvirus saimiri and herpesvirus ateles.

Base Sequence

The association of Angelman's syndrome with deletions within 15q11-13.

The inheritance of Angelman's syndrome, a disorder characterised by mental retardation, epilepsy, ataxia, and a happy disposition, is debated because affected sibs occur less frequently than expected with autosomal recessive inheritance. After discovering two unrelated patients with a small deletion of the proximal long arm of chromosome 15, 10 further patients with Angelman's syndrome were reassessed. Five had apparently normal karyotypes, four had a deletion within 15q11-13, and one had a pericentric inversion, inv(15)(p11q13) involving the same chromosomal region. In the latter case, the healthy mother had the same pericentric inversion, indicating that the patient also had a submicroscopic mutation on his other chromosome 15. These data map the Angelman locus to 15q11-13 and suggest that de novo visible deletions (associated with a low recurrence risk) and autosomal recessively inherited cases combine to give an overall sib recurrence risk of less than 25%.

Ataxia