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Biomedical subjects

J Lawson

Publications and source records attributed to J Lawson.

At least 37 records · Page 2Linked to original sources

The nitric oxide system and cortisol-induced hypertension in humans.

1. The aim of the present study was to assess the role of the nitric oxide (NO) system in cortisol-induced hypertension in humans. 2. Plasma and urinary nitrate/nitrite concentrations and plasma concentrations of arginine and symmetric (SDMA) and asymmetric (ADMA) dimethyl arginine were measured in six subjects on a restricted nitrate diet who were treated with 80 mg/day cortisol and in subjects on an unrestricted nitrate diet who were treated with cortisol (80 mg/day, n = 6, or 200 mg/day, n = 10) for 5 days. 3. Cortisol significantly increased systolic and mean arterial pressure. Significant reductions in plasma nitrate/nitrite concentrations were observed in subjects on a restricted nitrate diet on days 3, 4 and 5 of cortisol treatment (to 11 +/- 1, 10 +/- 1, 11 +/- 1 pmol/L, respectively) compared with pretreatment (16 +/- 1 pmol/L; P < 0.01). There were no significant changes in plasma arginine, ADMA or SDMA concentrations. 4. Cortisol treatment significantly increased blood pressure and reduced plasma nitrate/nitrite concentrations. Reductions in plasma nitrate concentrations are not explained by changes in substrate availability or in endogenous nitric oxide synthase inhibitors. These data support a role for the NO system in cortisol-induced hypertension in humans.

Arginine↗

Birth centre practices in Australia.

The aim of this study was to review birth centre practices in Australia. Questionnaires were completed from 22 of 24 centres. Great variations were observed between the centres in clinical practices like number of routine antenatal visits, pattern of medical review, and transfer rates. Definition of low-risk as expressed by booking and transfer criteria also showed great variations, and generally these criteria became more liberal with experience. From 1991 to 1995 there was an average increase of approximately 1,000 bookings per year in the 22 centres taken together. The average transfer rate over the whole period was 22% antepartum and 18% intrapartum. The transfer rates increased slightly over the 5-year period, by 4.8% during pregnancy and 2.5% intrapartum. A majority was optimistic about the future, and estimated that the potential market for birth centres was around 16% compared with the present figure of less than 5%. A general view was that women were not well informed about the birth-centre option.

Australia↗

Optic disc anomalies and frontonasal dysplasia.

AIMS: To document the optic disc abnormalities in patients with frontonasal dysplasia in association with basal encephalocele. METHODS: Names and hospital numbers of patients with midline clefts were obtained from the ophthalmology and genetics database. Six patients were identified who had the following common findings: midline facial cleft with midline cleft lip and palate; hypertelorism; absent corpus callosum; basal (sphenoethmoidal) encephalocele; and pituitary deficiency (five out of six cases). Ophthalmic examination was performed with fundal photography where possible. RESULTS: Two patients had unilateral and one a bilateral peripapillary staphyloma. Two patients had bilateral optic disc hypoplasia and one appeared to have a peripapillary staphyloma in one eye and a morning glory disc in the other. CONCLUSION: Optic disc abnormalities were found in all patients with this constellation of clinical findings. This association appears to represent a distinct subgroup within the spectrum of frontonasal dysplasia. The presence of midline facial anomalies and any dysplastic disc should alert the physician as to the presence of an encephalocele.

Abnormalities, Multiple↗

Enhanced lipid peroxidation in patients positive for antiphospholipid antibodies.

The mechanism leading to the formation of antiphospholipid antibodies (aPL) is still unknown. Because an in vitro study suggested that aPL may derive from pro-oxidant conditions, we sought a relationship between aPL and isoprostanes, indices of lipid peroxidation in vivo. Thirty patients with systemic lupus erythematosus have been studied. Seventeen (56.6%) were positive for aPL because they had lupus anticoagulant and/or high titer of anticardiolipin antibodies (aCL). Plasma levels of tumor necrosis factor (TNF ) and urinary excretion of two isoprostanes, 8-epi-PGF2alpha and IPF2alpha -I, free radical catalyzed oxidation products of arachidonic acid, were measured. Patients with systemic lupus erythematosus had higher urinary excretion of 8-epi-PGF2alpha and IPF2alpha -I than controls; urinary excretion of the two isoprostanes was highly correlated (Rho = 0.74, P < .0001). Urinary 8-epi-PGF2alpha was highly correlated with both aCL titer (Rho = 0. 70, P < .0001) and TNF (Rho = 0.84, P < .0001), a measure of disease severity. Excretion of this isoprostane was also higher in those patients who exhibited aPL (P < .0001). Comparable correlations were observed with the isoprostane IPF2alpha -I. No difference of 8-epi-PGF2alpha was observed between patients with and without previous history of thrombosis. This study, showing the existence of a close association between aPL and increased in vivo lipid peroxidation, supports the hypothesis that these antibodies may result from pro-oxidative conditions and suggests that inflammation may play an important role.

Adolescent↗

A study comparing VVI and DDI pacing in elderly patients with carotid sinus syndrome.

OBJECTIVE: To determine whether single chamber ventricular demand (VVI) pacing is adequate for elderly patients with carotid sinus syndrome. DESIGN: Prospective double blind randomised cross over study. SETTING: Tertiary referral centre. PATIENTS: 30 consecutive patients aged over 60 years with carotid sinus syndrome referred for cardiac pacing. INTERVENTION: Patients underwent dual chamber pacemaker implantation and were then randomised to two three-month periods of VVI and DDI pacing. MAIN OUTCOME MEASURES: Responses to cardiovascular tests (vasodepression during carotid sinus massage, pacemaker effect, postural blood pressure measurements, and response to head up tilt), and symptoms. RESULTS: 11 patients developed profound hypotension during upright carotid sinus massage while pacing VVI compared with only two while pacing DDI. The upright pacemaker effect was greater in VVI (VVI, -31 (SD 19) mm Hg v DDI, -4 (12) mm Hg; P < 0.001). Postural blood pressure measurements and responses to head up tilt did not vary. Eleven patients were unable to tolerate VVI pacing and had to be withdrawn early from this limb of the study (group A). Fourteen of the remainder completed diary cards and did not express a preference (group B). No patient preferred VVI. Group A patients were older (group A, 78 (6) years v group B, 70 (9) years; P < 0.05), were more likely to be female (group A, 73% v group B, 14%; P < 0.01), and were more likely to have orthostatic hypotension while pacing DDI (group A, 46% v group B, 0%; P < 0.01). Group A and B patients could not be differentiated by other prepacing clinical or haemodynamic variables. CONCLUSIONS: Elderly patients with carotid sinus syndrome are likely to develop symptomatic hypotension following VVI pacing. The optimum pacing mode for individual patients cannot be predicted by simple cardiovascular tests before pacing.

Aged↗

Thermal Effects In Vivo from Holmium: YAG Lasing in the Intracoronary Setting.

While the thermal effect of laser energy does ablate atheromatous plaque, thermal injury to adjacent tissue produces high rates of arterial thrombosis and spasm. Holmium:YAG lasers use a pulsed laser source to maximize photoblative effects while minimizing thermal effects. These lasers have been utilized clinically to ablate thousands of complex coronary lesions with low rates of spasm and thrombosis, suggesting that little or no thermal injury occurs with these devices. However, we have been able to detect thermal injury in patients angioscopically in coronary arteries after holmium:YAG lasing. Here we report the use of directional coronary atherectomy (DCA) to ÒbiopsyÓ arteries in patients following holmium:YAG laser treatment, allowing direct histologic examination of lased tissue. Thirty such lased DCA samples were matched for patient age, gender, target vessel, and lesion characteristics with thirty control DCA samples obtained from patients undergoing DCA without prior lasing. Blinded pathologic examination correctly identified 27/30 control samples but only 18/30 lased samples. Subsequent unblinded analysis, sometimes with recutting and restaining of tissue blocks, resulted in the detection of thermal effects in 27/30 lased samples. The thermal effects seen included edge disruption, charring, coagulation necrosis, and most commonly, vacuolization. We conclude that holmium:YAG lasing does produce detectable thermal effects in tissue in most patients. These effects can be quite subtle or can be extensive, but do not predict poor patient outcome.

Journal Article↗

Fludrocortisone in the treatment of hypotensive disorders in the elderly.

OBJECTIVE: To evaluate tolerance of fludrocortisone in older patients with hypotensive disorders. DESIGN: Prospective case series. SETTING: Syncope clinic. PATIENTS: 64 Consecutive patients over 65 years (mean age 80 years) with one or more hypotensive disorders (orthostatic hypotension, vasodepressor carotid sinus syncope, and/or vasodepressor neurocardiogenic syncope. INTERVENTIONS: Fludrocortisone in daily doses of 100 micrograms [corrected] (72%), 50 micrograms [corrected] (27%), and 200 micrograms [corrected] (one patient). MAIN OUTCOME MEASURES: Adverse events, treatment withdrawal. RESULTS: During follow up 13 patients died of unrelated causes. Of the remainder 33% discontinued fludrocortisone at a mean of five months. Reasons for discontinuing treatment were hypertension, five; cardiac failure, four; depression, three; oedema, three; and unspecified, two. In those who continued treatment supine systolic and diastolic blood pressure did not differ significantly from baseline (follow up two to 21 months). Hypokalaemia developed in 24% at a mean of eight months; in no case was treatment withdrawn because of hypokalaemia. CONCLUSION: Fludrocortisone, even in low doses, is poorly tolerated in the long term in older patients with hypotensive disorders.

Aged↗

Results from a Mantoux screening programme of staff in the care of the elderly and mental health fields at Wakari Hospital, Dunedin.

AIM: To assess the level of occupational exposure to tuberculosis among the staff at Wakari Hospital, Dunedin. METHODS: 368 staff (including around 90% of the nurses) were given a 5 TU Mantoux test, and the results were analysed. RESULTS: 39.5% of people had a positive reaction. The data was examined in terms of age, length of service and area of work. Ethnic background was not considered. Comparisons with a preemployment group and a subsample of those under the age of 35 years revealed an effect from occupational exposure alone. The proportion of positive reactions was similar across both short and long stay areas of the care of the elderly and mental health services. Despite the occurrence of several diagnosed active cases of tuberculosis within the last four years, the rate of positive reactions was similar across all clinical areas. CONCLUSIONS: This unexpectedly high rate of positive reactions challenges the Tuberculosis Guidelines (1992) categorisation of healthcare personnel outside a tuberculosis ward as at medium rather than high risk of infection, and reinforces the need to develop consistent protocols for staff and patient screening. It also raises the question of the actual risk status of other continuing care facilities throughout New Zealand.

Adolescent↗

Clinical effects and utility of intracoronary diltiazem.

Coronary artery spasm is a known complication of coronary interventions, for which intracoronary nitroglycerin (ICN) is the treatment of choice. Some forms of intense spasm are resistant to ICN. Calcium channel antagonists are also known to be effective for coronary artery spasm, including nitroglycerin-resistant spasm. Here we describe a protocol for the clinical use of intracoronary diltiazem (ICD). By this protocol, ICD can be safely given without disturbing the clinical status of patients. ICD (2.5 mg) given slowly over 1 minute produced no vasodilitation of normal vessel segments but did produce significant dilatation of stenotic segments above and beyond the effects of nitrates. Mean minimum lumen diameter increased 18%, from 0.89 +/- 0.06 mm to 1.06 +/- 0.07 mm (mean +/- SEM, P < 0.001). ICD produced clinically insignificant changes in systolic blood pressure, diastolic blood pressure, heart rate, and PR, QRS, and QT intervals. This protocol has been employed to safely use ICD to relieve both nitroglycerin-resistant epicardial artery spasm and nitroglycerin-resistant distal microvascular spasm (the no-reflow phenomenon).

Adult↗

Phenamide, a fungicidal metabolite from Streptomyces albospinus A19301. Taxonomy, fermentation, isolation, physico-chemical and biological properties.

A new derivative of phenylalanine, phenamide, was discovered from the fermentation broth of an actinomycete identified as a member of the Streptomyces albospinus cluster. Phenamide was purified using successive C18 reverse phase and cation exchange chromatography. Its structure was determined by spectroscopic and chemical methods. Its molecular formula, C14H20N2O3, was determined by HRFAB-MS. Phenamide showed activity against Septoria nodorum, the causal agent of wheat glume blotch.

Antifungal Agents↗

Efficacy of preconditioning with intracoronary diltiazem in preventing laser-induced spasm.

Laser energy produces a multitude of effects, resulting both in therapeutic tissue ablation and complications such as laser-induced spasm (LIS). LIS can occur during lasing itself or during subsequent adjunctive angioplasty. Intracoronary diltiazem (ICD) can partially reverse LIS after it occurs. To determine whether pre-treatment with ICD might prevent LIS during laser interventions, 3 groups of 50 lesions each were studied. Group 1 served as controls receiving no ICD during the procedure. Group 2 received 2.5 mg ICD before lasing. Group 3 received ICD before lasing and then a second infusion of 2.5 mg ICD after lasing but before adjunctive therapy. There were no differences in clinical characteristics of the 3 groups. Over 75% of lesions in each group were complex (B2 or C) lesions, and average lesion length was 15 mm in all 3 groups. Procedural success was > or = 94% in all groups. There was no significant difference among groups in pre-procedure artery stenosis, post-procedure stenosis, laser power used or number of laser pulses delivered. Pretreatment with ICD produced vasodilation of the minimum lumen diameter from 0.86 +/- 0.1 to 1.0 +/- 0.1 mm (p < 0.01) and was well tolerated. Control patients exhibited a 12% incidence of LIS. Group 2 had an 80% reduction of LIS during lasing (p < 0.01) but had increased LIS during adjunctive therapy with the same 12% incidence of LIS overall. Group 3 had only a 2% incidence of LIS (p < 0.01). We concluded that pretreatment with ICD significantly reduces LIS. Multiple infusions of ICD are necessary to sustain this protective effect.

Adult↗

Immunological characterization of urinary 8-epi-prostaglandin F2 alpha excretion in man.

F2-isoprostanes are prostaglandin (PG) F2-like compounds that are formed in vivo directly by free radical-catalyzed lipid peroxidation. One of the compounds that can be produced in abundance by such mechanism is 8-epi-PGF2 alpha, a potent vasoconstrictor. We have developed an enzyme immunoassay and a radioimmunoassay for measuring urinary concentrations of 8-epi-PGF2 alpha by raising antibodies against this compound. The antisera presented high titers (> 1/300,000) and provided highly sensitive assays (IC50, 8 and 24 pg/ml, for EIA and RIA, respectively); cross-reactivity with other PG was negligible. The interassay reproducibility of EIA was assessed by measuring the same urine stored frozen in aliquots after solid phase extraction and thin-layer chromatography (17%, n = 13). Measurements of urinary 8-epi-PGF2 alpha by immunoassays were validated using different antisera and by comparison with gas chromatography/mass spectrometry. Healthy volunteers excreted 25 +/- 12 ng of 8-epi-PGF2 alpha/mmol creatinine (n = 19), with no circadian variation over three consecutive 8-hr collection periods (n = 10); preliminary results showed that excretion increased as a function of age. Urinary excretion of 8-epi-PGF2 alpha was unchanged by treatment with two nonsteroidal antiinflammatory drugs, Ibuprofen at 1.2 g/day for 4 days (n = 4) or aspirin as a single administration of 1 g (n = 6). In contrast, the urinary excretion of 11-dehydro-thromboxane B2, a platelet cyclooxygenase-derived metabolite was reduced by more than 80% after aspirin administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The natural history and clinical consequences of aspiration in acute stroke.

Sixty consecutive patients admitted to a teaching hospital with acute stroke were studied prospectively for 3 months to define the natural history and consequences of lung aspiration. Using videofluoroscopy, aspiration was identified in 25 patients (42%) within 72 h of stroke onset, and had resolved in all but three patients (8%) after 3 months. It was closely related to the presence of dysphagia, which itself resolved within 2 weeks in all but the persistent aspirators. Lower respiratory tract infection (LRTI) was more common in aspirating patients (68%) than non-aspirators (6%). The use of intravenous fluids without oral intake did not appear to prevent LRTI in aspirating patients who were also dysphagic. Pneumonia occurred after 2 weeks in the three patients subsequently found to aspirate persistently. Aspiration is a transient phenomenon in most cases of acute stroke; it is associated with a high incidence of LRTI, but mortality in this series was not significantly associated either with respiratory tract infection or aspiration itself.

Aged↗