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Biomedical subjects

S Shaw

Publications and source records attributed to S Shaw.

At least 199 records · Page 11Linked to original sources

Reduced plasma cyclic GMP but normal renal responses to atrial natriuretic factor in pre-hypertension.

The amount of, and response of the kidneys to, endogenous natriuretic factor(s) could be important in the pathogenesis of essential hypertension. Searching for possible disturbance(s) related to atrial natriuretic factor (ANF) and its second messenger, cyclic guanosine monophosphate (c-GMP), we assessed plasma immunoreactive (ir) ANF and c-GMP, effective renal plasma flow (ERPF), glomerular filtration rate (GFR), urinary c-GMP, absolute and fractional (FE) excretions of sodium (Na) and chloride (Cl) before and during infusions of low ANF doses or vehicle (V) in 7 normotensive sons of essential hypertensive parents (SEH) compared with 7 sons of normotensive parents (SN). Each subject was infused at 2-week intervals in a single-blind randomized sequence with 4 different solutions: V only or ANF 0.004, 0.008 and 0.016 microgram/kg/min, infused over 90 min. Plasma irANF was lower in SEH than in SN (p < 0.001) during vehicle infusion. Basal plasma c-GMP levels were, on all 4 different study days lower (p < 0.05 to < 0.01) in SEH in SN. Response of plasma c-GMP to infused ANF was also slightly decreased in SEH (p < 0.05 to < 0.01). BP, ERPF and GFR did not differ between SEH and SN and were unchanged during the 4 infusions. Urinary c-GMP excretion, FENa and FECl increased dose-dependently during ANF (p < 0.05 to < 0.0001) but not V infusions. These findings indicate that at the stage of pre-hypertension a disturbance in the ANF-c-GMP regulatory pathway may occur, which is expressed primarily at the circulatory rather than the renal excretory level.

Atrial Natriuretic Factor↗

Fragrance contact dermatitis: a worldwide multicenter investigation (Part I).

OBJECTIVE: The aim of this study was to determine the prevalence of responses to selected fragrance materials in patients with suspect fragrance allergy and to evaluate risk factors and associations with such responses. The validity of using specific fragrance ingredients versus a mixture of fragrances was evaluated in terms of predicting allergy to different fragrance ingredients. METHODS: One hundred sixty-seven subjects were evaluated in seven centers worldwide with a fragrance mix, the eight ingredients in the fragrance mixture, six other well-known fragrance allergens, balsam of Peru, and 15 lesser studied fragrance materials. RESULTS: The age of the patients was 44.9 +/- 17.5 years (mean +/- SD). More than 85% were women. A relatively high proportion gave a past history of atopic disease. Facial eruptions (40%) and hand involvement (26.7%) were the most common topographic sites. All but 4 of the 35 fragrance materials produced a positive response in > 1%. A reaction to fragrance mix occurred in 47.3%. Seven of the 34 ingredients tested produced an allergic response in more than 10% of those tested. Men were more likely than women to exhibit a positive response to five fragrance ingredients. White persons were more likely to react to perfume mix (52.8% versus 25.3%) and certain ingredients in the mix than Asian persons. Allergy to benzyl salicylate was more common in Japan than in Europe or the United States. CONCLUSION: The age at which patients with perfume allergy present for evaluation is similar to that of other contactants. Atopic individuals may be overrepresented in this group of patients. Face involvement is likely. White persons are more likely to react to fragrance mix, whereas in Asian patients benzyl salicylate was a more frequent allergen. Fragrance mix corrected with 85.6% of positive responses to fragrance ingredients. The addition of ylang ylang oil, narcissus oil, and sandalwood oil to fragrance mix would be expected to pick up 94.2% with positive responses to fragrance materials; adding balsam of Peru increases this to 96%.

Adult↗

Inhibition of rat glomerular mesangial cell sodium/hydrogen exchange by hydrogen peroxide.

1. pHi regulation in glomerular mesangial cells (GMC) includes both Na+/H+ and Cl-/HCO3-exchange. As a fall in pHi may protect against H2O2-mediated GMC damage during ischaemia-reperfusion, the involvement of these mechanisms in the GMC pH1 response to H2O2 was assessed using confluent GMC grown in RPMI medium with 20% fetal calf serum (10-15 passages). 2. Cells were loaded with BCECF-AM and pH1 evaluated using standard fluorometric-ratio techniques. In HEPES buffer, GMC exposure to H2O2 dose-dependently (25 mumol/L-1 mmol/L) decreased pHi over 10 min from 7.3 +/- 0.1 to 6.7 +/- 0.1 (at 100 mumol/L) partly due to rapid non-competitive inhibition of amiloride-sensitive Na+/H+ exchange. 3. BCECF fluorescence in free solution was unchanged by H2O2 and averaged 100 +/- 9 nmol/2.6 x 10(6) cells/pH unit. Similarly, zero-Na+/high-K+ buffer, used to minimize passive H+ entry, did not prevent the fall in pHi while GMC H+-formation/extrusion, assessed by the rate of extracellular acidification in low-capacity buffer (0.05 mmol/L), was rapidly inhibited. 4. In contrast, following only a brief 3 min exposure to 1 mmol/L H2O2, HCO3-/CO2 buffer potentiated the inhibition of Na+/H+ exchange from 50 to 80% of control and reduced the acidification from pHi 6.6 +/- 0.1 to 7.15 +/- 0.05. This effect was reversed (to pHi 6.8 +/- 0.07) by pretreatment with 200 mumol/L DIDS, an inhibitor of Cl-/HCO3- exchange. 5. Thus, the decrease in GMC pHi in response to H2O2 in HEPES, partly mediated by inhibition of Na+/H+ exchange and a possible redistribution of intracellular H+, is antagonized in HCO3-/CO2 through a DIDS-sensitive Cl-/HCO3- exchange mechanism. This may act to negate potentially protective effects of low pHi and potentiate oxidative damage to membrane lipids, enzymes and intracellular organelles on reperfusion.

Animals↗

Role of intracellular signalling pathways in hydrogen peroxide-induced injury to rat glomerular mesangial cells.

1. Brief exposure of cultured rat glomerular mesangial cells (GMC) to H2O2 in nominally bicarbonate-free solution induced a rapid dose dependent, dantrolene-inhibitable increase in intracellular free Ca2+ from 65 +/- 6 to 203 +/- 14 nmol/L and a prolonged release of [14C]-arachidonic acid [14C]-AA which preceded the onset of cell membrane damage assessed by trypan-blue uptake. 2. Ca2+ responses were potentiated in HCO3-/CO2 containing buffers and reached values of 1145 +/- 100 nmol/L at 1 mmol/L H2O2. In HCO3-/CO2 solutions, but not HEPES buffer, H2O2-induced Ca2+ increases were markedly attenuated by verapamil (100 mumol/L) or removal of extracellular calcium. 3. Enhanced release of [14C]-AA was partially attenuated by inhibitors of key intracellular signalling mechanisms including the phospholipase-A2 (PLA2) inhibitor mepacrine (100 mumol/L), the NADPH oxidase inhibitor diphenyliodonium (10 mumol/L), the mitochondrial calcium-cycling inhibitor ruthenium red (10 mumol/L) and the iron chelator dipyridyl (100 mumol/L). Release was unaffected by protein kinase C inhibition with H7 (100 mumol/L), inositol triphosphate antagonism with neomycin (1 mmol/L) or overnight treatment with the G-protein antagonist pertussis toxin (5 micrograms/mL). 4. Several structurally diverse lipoxygenase inhibitors, including esculetin, baicalein and phenidone, over the dose range 1-100 mumol/L, also prevented [14C]-AA release and markedly protected against cell membrane damage. No drug directly scavenged H2O2 assessed by UV absorption. 5. These results indicate that H2O2 activates in GMC a complex series of interrelated pathological mechanisms which in turn contribute to a prolongation of oxidative damage beyond the time of the initial exposure. These include an increase in intracellular calcium which, depending upon conditions, appears to be mediated by release from intracellular stores as well as Ca2+ entry from the extracellular space. In turn there is a sustained release of arachidonic acid, which may partly depend on prolonged activation of PLA2 but not phospholipase C. 6. Release of [14C]-AA could be attenuated by inhibitors of NADPH oxidase, mitochondrial calcium-cycling, iron chelators and a structurally diverse range of lipoxygenase inhibitors in association with protection from H2O2-mediated cell membrane damage.

Animals↗

Chloromethylisothiazolone/methylisothiazolone (CMI/MI) use test with a shampoo on patch-test-positive subjects. Results of a multicentre double-blind crossover trial.

A randomized, multicentre, double-blind, 2-period crossover study with 2 shampoos was performed on subjects patch-test-positive to 100 ppm CMI/MI. One shampoo was preserved with 15 ppm a.i. CMI/MI, the other with 0.3% imidazolidinyl urea (IU). 27 subjects from 5 European dermatology clinics participated. 1 subject discontinued use after severe adverse reactions to the CMI/MI-preserved shampoo and did not evaluate the other shampoo. Another 2 subjects developed moderate symptoms with the CMI/MI-preserved shampoo and discontinued its use, but tolerated the IU-preserved shampoo for the full 2-week period. 2 subjects discontinued use after 1 or 2 washes after severe adverse reactions to the IU-preserved shampoo. 1 of these subjects tolerated the CMI/MI-preserved shampoo for 2 weeks without any untoward effects. However, the majority of subjects had negative findings on the scalp, face, neck, and hands for both shampoos. The physicians' global evaluation data indicated that shampoo with CMI/MI caused fewer skin problems than shampoo with IU (38% versus 27%, n.s.), with over 1/3 of the subjects (35%) having no skin problems with either preservative. The current study showed that most subjects previously sensitized to CMI/MI can successfully use shampoo preserved with CMI/MI. Since some subjects previously sensitized to CMI/MI, or possibly to IU, may develop clinical reactions, it would still be prudent for the clinician to advise alternative products to patients with sensitivity to a shampoo or cosmetic ingredient. Full ingredient labelling will ensure that this is possible. As the overall rate of adverse effects in sensitized individuals was low, studies of this nature should also be conducted for other allergens.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross-Over Studies↗

Speech perception in children using the advanced Speak speech-processing strategy.

The Speak speech-processing strategy, developed by the University of Melbourne and commercialized by Cochlear Pty Limited for use in the new Spectra 22 speech processor, has been shown to provide improved speech perception for adults in both quiet and noisy situations. The present study evaluated the ability of children experienced in the use of the Multipeak (Mpeak) speech-processing strategy (implemented in the Nucleus Minisystem-22 cochlear implant) to adapt to and benefit from the advanced Speak speech-processing strategy (implemented in the Nucleus Spectra 22 speech processor). Twelve children were assessed using Mpeak and Speak over a period of 8 months. All of the children had over 1 year's previous experience with Mpeak, and all were able to score significantly on open-set word and sentence tests using the cochlear implant alone. Children were assessed with both live-voice and recorded speech materials, including Consonant-Nucleus-Consonant monosyllabic words and Speech Intelligibility Test sentences. Assessments were made in both quiet and in noise. Assessments were made at 3-week intervals to investigate the ability of the children to adapt to the new speech-processing strategy. For most of the children, a significant advantage was evident when using the Speak strategy as compared with Mpeak. For 4 of the children, there was no decrement in speech perception scores immediately following fitting with Speak. Eight of the children showed a small (10% to 20%) decrement in speech perception scores for between 3 and 6 weeks following the changeover to Speak. After 24 weeks' experience with Speak, 11 of the children had shown a steady increase in speech perception scores, with final Speak scores higher than for Mpeak. Only 1 child showed a significant decrement in speech perception with Speak, which did not recover to original Mpeak levels.

Adolescent↗

Kidney transplantation decreases the tissue level of advanced glycosylation end-products.

We have studied the effect of chronic renal failure (CRF) and kidney transplantation on advanced glycosylation end-products (AGE) measured as collagen-linked fluorescence (CLF) in the skin and peritoneum of non-diabetic patients. Of 34 patients with CRF, 18 were studied before the commencement of peritoneal dialysis (CRF group), and 16 were studied 5-31 weeks after kidney transplantation (transplant group). The control group consisted of 24 patients with normal renal function. Skin CLF in the CRF group (20.9 +/- 2.02 U/mg) was higher than in the control (8.52 +/- 1.08 U/mg, P = 0.0001) and transplant groups (10.7 +/- 2.43 U/mg, P = 0.003). Peritoneal CLF in the CRF group (30.5 +/- 5.64 U/mg) was higher than in the control group (16.1 +/- 2.25 U/mg, P = 0.031) but was not different from the transplant group (19.4 +/- 3.66 U/mg, P = 0.11). Peritoneal CLF of control and transplant groups were not different (P = 0.45). The results of this study suggest that restoration of renal function affects tissue AGE levels.

Adult↗

Semen contact urticaria.

An allergic reaction to human seminal fluid was first reported by Halpern et al. 1967. Since then there have been more than 30 cases recorded in the literature but it remains a rare cause of dyspareunia.

Adult↗

Effect of cigarette smoking and nicotine on plasma endothelin-1 levels.

Although cigarette smoking is an established risk factor for atherosclerosis, the true mediator of vessel diseases associated with smoking is not known. Because endothelin-1 (ET-1) exhibits potent vasoconstrictor activity, it may act as a mediator in this condition. We determined venous ET-1 and nicotine levels in 12 smokers (age 21-24 years, 2-52 pack-years) before and 10 min, 4 h, and 8 h after the beginning of smoking. To distinguish an isolated effect of nicotine, 11 nonsmokers (age 24-50 years) were investigated while they were wearing a transdermal nicotine delivery system (TNDS). ET-1 was measured by RIA and nicotine by HPLC. Baseline ET-1 plasma levels before the exposure to either smoking or nicotine administration were comparable in smokers (1.07 +/- 0.3 pg/ml) and in nonsmokers (1.04 +/- 0.3 pg/ml). Smokers had borderline significantly higher ET-1 plasma levels within 10 min after the onset of smoking (1.3 +/- 0.3 pg/ml vs. 1.08 +/- 0.3 pg/ml; p = 0.055) but not after 4 and 8 h. Nonsmokers exposed to TNDS did not exhibit any significant plasma ET-1 changes. We conclude that the increase in plasma ET-1 after cigarette smoking is of borderline significance and is a transitory phenomenon restricted to the first 10 min after the onset of smoking. Although nicotine itself seems to be an unlikely mediator, other smoke components, such as CO or tar, may be responsible for the increase in plasma ET-1 in smokers. The absence of an ET-1 increase after transcutaneous nicotine application underscores the safety of TNDS in smoking withdrawal therapy.

Adult↗