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Biomedical subjects

C Lanigan

Publications and source records attributed to C Lanigan.

At least 19 recordsLinked to original sources
PubMed1998

Extent of laminin-5 assembly and secretion effect junctional epidermolysis bullosa phenotype.

Junctional epidermolysis bullosa (JEB) is an autosomal recessive skin blistering disease with both lethal and nonlethal forms, with most patients shown to have defects in laminin-5. We analyzed the location of mutations, gene expression levels, and protein chain assembly of the laminin-5 heterotrimer in six JEB patients to determine how the type of genetic lesion influences the pathophysiology of JEB. Mutations within laminin-5 genes were diversely located, with the most severe forms of JEB correlating best with premature termination codons, rather than mapping to any particular protein domain. In all six JEB patients, the laminin-5 assembly intermediates we observed were as predicted by our previous work indicating that the alpha3beta3gamma2 heterotrimer assembles intracellularly via a beta3gamma2 heterodimer intermediate. Since assembly precedes secretion, mutations that disrupt protein-protein interactions needed for assembly are predicted to limit the secretion of laminin-5, and likely to interfere with function. However, our data indicate that typically the most severe mutations diminish mRNA stability, and serve as functional null alleles that block chain assembly by resulting in either a deficiency (in the nonlethal mitis variety) or a complete absence (in lethal Herlitz-JEB) of one of the chains needed for laminin-5 heterotrimer assembly.

Adult↗
PubMed1997

Topical anaesthesia for cataract surgery.

First, do no harm. We believe that the analgesia provided by topical anaesthetic is adequate for small-incision cataract surgery and does not compromise the safety of the surgery. In addition, the lack of amaurosis is ideal for day-case surgery, which itself is increasingly popular. If preventable, why not prevented? The greatest attraction of topical anaesthesia is its complete absence of the complications described for injectional local anaesthetic techniques. We therefore recommend that our colleagues consider topical anaesthetic for patients undergoing small-incision cataract surgery under local anaesthesia. Our policy for the past 3 years has been to use only topical or general anaesthetics for cataract surgery.

Administration, Topical↗
PubMed1993

The effects of beta 2-agonists and caffeine on respiratory and limb muscle performance.

The possibility that respiratory muscle function may be improved by drug therapy is of clinical importance, but remains controversial. A series of studies concerning the effects of maximally tolerated dosages of terbutaline, tulobuterol (a new beta 2-agonist) and caffeine on respiratory muscle strength and limb muscle strength and endurance were undertaken in normal subjects. Drugs were administered orally, 2 h before study. Caffeine produced a small but statistically significant increase in the stimulated contraction force at 20 Hz, and a small beneficial effect on recovery from a fatiguing protocol; maximum voluntary contraction force of the quadriceps was increased by 3.8%. Terbutaline and tulobuterol had no beneficial effects on either respiratory or limb muscle function. We conclude that conventional dosages of these bronchodilator drugs do not greatly affect skeletal muscle performance.

Adrenergic beta-Agonists↗
PubMed1990

Effect of chronic airflow limitation on resting oxygen consumption.

The work of breathing in patients with severe chronic airflow limitation is increased even at rest but little is known about the magnitude of this increase. Resting oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory quotient (RQ) were measured in 13 patients with severe chronic airflow limitation (mean FEV1 0.78 1, vital capacity 2.1 1) and compared with those of 13 age, weight, and height matched control subjects. Whereas mean RQ was the same in the two groups (0.82), mean VO2 and VCO2 were higher in the patients (+ 18 ml min-1 and + 15 ml min-1 respectively). When VO2 was standardised for body surface area it was 10.9% higher in the patients (p less than 0.05). If the increased resting VO2 in these patients were solely due to increased activity of the respiratory muscles, it would represent a fourfold increase in the oxygen cost of breathing.

Body Surface Area↗
PubMed1990

Effect of acute hypercapnia on limb muscle contractility in humans.

The effect of acute hypercapnia on skeletal muscle contractility and relaxation rate was investigated. The contractile force of fresh and fatigued quadriceps femoris (QF) and adductor pollicis (AP) was studied in normal humans by use of electrical stimulation. Maximum relaxation rate from stimulated contractions was measured for both muscles. Acute hypercapnia led to a rapid substantial reduction of contraction force. The respiratory acidosis after 9% CO2 was breathed for 20 min [mean venous blood pH 7.26 and end-tidal PCO2 (PETCO2) 65.1 Torr] reduced 20- and 100-Hz stimulated contractions of QF to 72.8 +/- 4.4 and 80.0 +/- 5.1% of control values, respectively. After 8 and 9% CO2 were breathed for 12 min, AP forces at 20- and 50-Hz stimulation were also reduced. Twitch tension of AP was reduced by a mean of 25.5% when subjects breathed 9% CO2 for 12 min [mean arterialized venous blood pH (pHav) 7.25 and PETCO2 66 Torr]. Over the range of 5% (pHav 7.38 and PETCO2 47 Torr) to 9% CO2, there was a linear relationship between twitch tension loss and pHav, arterialized venous blood PCO2, and PETCO2. Acute respiratory acidosis (mean PETCO2 61 Torr) increased the severity of low-frequency fatigue after intermittent voluntary contractions of AP. At 20 min of recovery, twitch tension was 63.2 +/- 13.4 and 46.8 +/- 16.4% of control value after exercise breathing air and 8% CO2, respectively. Acute hypercapnia (mean PETCO2 65.1 and 60.5 Torr) did not alter the maximum relaxation rate from tetanic contractions of fresh QF and from twitch tensions of AP.

Acidosis, Respiratory↗
PubMed1989

Carnitine and weakness in haemodialysis patients.

Weakness in haemodialysis patients has been attributed to several factors including carnitine deficiency. Malnutrition, neuropathy, uraemic myopathy and parathyroid hormone excess may all be important. Six haemodialysis patients were shown to have reduced muscle power compared with a normal population, and to be malnourished by dietary assessment, and features of their weakness were investigated. Total carnitine was normal in plasma but elevated in muscle, with an excess of esterified carnitine in both plasma and muscle and diminished free plasma carnitine. Muscle biopsy showed no features of carnitine deficiency and electromyography showed a non-specific neuropathy with additional myopathic changes in some. Dietary supplementation with L-carnitine (2 g/day) for 6 weeks in a placebo-controlled trial showed a redistribution of carnitine fractions but no subjective or objective improvement in muscle function. There was no improvement in the plasma lipid profile. The weakness of haemodialysis patients is multifactorial. We have not demonstrated total carnitine depletion in either muscle or plasma, and oral supplementation of L-carnitine has no demonstrable effect in this group.

Administration, Oral↗
PubMed1988

Performance of transcutaneous PO2 and PCO2 dual electrodes in adults.

Three commercially-available combined PO2-PCO2 electrodes were assessed in vitro, and in adults breathing air, hypoxic and hypercapnic mixtures, for speed of response, correlation with end-tidal gas tensions and drift. Differences in the 90% response time of the individual electrodes were more marked in vitro than in vivo. Changes in end-tidal gas tensions were reflected by proportionate changes in transcutaneous oxygen and carbon dioxide (PtcO2 and PtcCO2) but, in the individual subject, PtcO2 and PtcCO2 were generally poor indicators of the end-tidal values. During steady-state recordings, the PtcO2 signal drifted upwards by more than 12 mm Hg during 140 min in vivo recording in all three electrodes, without changes in either PtcCO2 or end-tidal values. The dual electrodes tested provide non-invasive estimates of qualitative, but not quantitative, change in blood-gas tensions and are likely to have only a limited role to play in adult anaesthetic practice.

Adult↗
PubMed1987

The relative accuracy of three transcutaneous dual electrodes at 45 degrees C in adults.

Measurements made by transcutaneous electrodes can be compared with arterial blood gases in several different ways. The relationship between them is commonly expressed by a linear regression equation, and a correlation coefficient, r, calculated. However calculation of the bias and the precision of transcutaneous electrode readings is more helpful in clinical practice. The differences between the two methods are explained by comparing the relationship of three transcutaneous dual electrodes to endtidal gases in adults.

Adult↗
PubMed1987

Drift in vivo of transcutaneous dual electrodes.

TcPO2 and tcPCO2 monitoring is widely used but the in vitro drift of the new combined sensors is unknown. We tested the in vivo stability of 3 such electrodes in six adults, compared to nasal endtidal values from a mass spectrometer. Each electrode was remembraned within 5 days and had a 2 point dry gas calibration at 45 degrees C before fixing to the subjects' right arms. TcPO2, tcPCO2 and endtidal values were averaged over four minutes after 30 minutes equilibration, and then at seven subsequent 20 minute intervals. We observed that (1) Endtidal values remained stable (2) tcPCO2 differed from baseline by less than 3 torr (3) tcPO2 rose significantly in all three electrodes by an average of 16 to 21% and, (4) in vivo drift greatly exceeded separately determined in vitro changes. We discuss the possible explanations for the observed results, and conclude that skin permeability changes may play an important role. In the light of the large in vivo tcPO2 drift, transcutaneous dual electrodes are not reliable trend indicators of blood gases in adults.

Adult↗
PubMed1987

Monitoring oxygenation.

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Blood Gas Monitoring, Transcutaneous↗