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Biomedical subjects

R White

Publications and source records attributed to R White.

At least 109 records · Page 6Linked to original sources
PubMed1999

Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older.

BACKGROUND: Older patients with advanced breast cancer are less likely to receive chemotherapy than younger patients. Vinorelbine is an attractive alternative in this setting because of its clinical activity and low frequency of side effects. This multicenter, phase II trial was designed to assess the safety and efficacy of intravenous vinorelbine as first-line therapy in women > or = 60 years old. PATIENTS AND METHODS: Fifty-six women (median age, 72 years; range 60-84 years), with measurable advanced breast cancer and no prior chemotherapy for metastatic disease, were enrolled and included in the analysis. Vinorelbine 30 mg/m2 was administered weekly for 13 weeks and then every two weeks until development of progressive disease; doses were reduced or delayed to manage toxicity. RESULTS: The objective response rate was 38% (95% confidence interval (95% CI): 24%-51%); median duration of response, nine months; median time to disease progression in all patients, six months. The major dose-limiting toxicity was hematologic, which led to a median dose intensity of 20.6 mg/m2/week. Grade 3-4 nonhematologic toxicity consisted of asthenia (7%); nausea and generalized pain (5%); vomiting, chest pain, abdominal pain, and elevated AST (4%); fever, diarrhea, constipation, and injection site reaction (2%). Neurotoxicity and alopecia were grade 1-2 and relatively infrequent. CONCLUSIONS: Vinorelbine offers a promising alternative for the management of advanced breast cancer in elderly patients who are concerned about the subjective side effects of cytotoxic chemotherapy. The dose-limiting toxicity is neutropenia, which is readily managed with dose adjustment. Nonhematologic toxicity, including gastrointestinal side effects, is minimal. Randomized studies are warranted to compare the activity of vinorelbine with that of other regimens in elderly patients.

Aged↗
PubMed1999

Phenotypic characterization of histiocytes infiltrating a leiomyofibrosarcoma.

We described previously a unique cutaneous tumour in a young pig, which was characterized by several criteria as a histiocytic leiomyofibrosarcoma. The lipid-laden macrophages (histiocytes) which permeated the tumour were CD2+/CD18+/CD49d+ but MAC387 (L1 antigen) and CD15 negative. The present study compared the phenotypes of histiocytes in tumour metastases in the liver with resident liver macrophages, revealing differential expression of certain macrophage activation markers. After repeated subcutaneous passage of the tumour in athymic (nu/nu) mice, flow cytometry demonstrated a rapid loss of porcine MHC Class II, but a more prolonged expression of porcine MHC Class I, consistent with our immunohistological observations. Mouse macrophages (CD2+/F4.80+) infiltrated the later-passage tumours, suggesting that the histiocytes were not of neoplastic origin.

Animals↗
PubMed1999

Familial risk estimation in systemic sclerosis.

BACKGROUND: Familial systemic sclerosis has been rarely reported. Assumptions have therefore been made implying no familial disease aggregation. This study critically challenges the assumption using a methodical population-based epidemiological approach to quantify the prevalence and characteristics of familial systemic sclerosis. METHODS: In this retrospective cohort study the systemic sclerosis prevalence in first degree family members was compared between 715 systemic sclerosis patients (710 families) and 371 randomly ascertained age and gender group-matched general practice controls (371 families). These data, obtained by telephone questionnaire (living patients) or medical records review (deceased patients and untraceable patients of unknown living status), were validated, where necessary, and expressed in terms of relative risk, absolute risk and population point prevalence. RESULTS: Systemic sclerosis affecting first degree members was validated in ten of 710 families. Reporting of systemic disease in another four more distant family members, and the co-occurrence of systemic and localised disease in three families was also documented. Observed and expected disease subtype concordance was 80% (44-97%) and 68% respectively and the female predominance among familial cases was similar to that for non-familial disease. The risk of disease in a subsequent first degree relative was compared to the risk in an initial first degree family member. Its estimated magnitude was wide (11-158). However, use of population prevalence data to determine the expected number of systemic sclerosis patients in the negative cohorts' families suggests the higher estimate is more realistic. Despite the high magnitude, the absolute disease risk in first degree family members remained low--approximating 1%. The population prevalence of familial systemic sclerosis approximated 1.4/million. CONCLUSIONS: This study substantially increases the otherwise small list of documented instances of familial systemic sclerosis. More importantly, it quantifies the risk for the first time, ranking it as the disease's most powerful determinant identified to date.

Cohort Studies↗
PubMed1999

Changes in cardiac ANG II postmyocardial infarction in rats: effects of nephrectomy and ACE inhibitors.

We evaluated in rats the time course of changes in cardiac versus plasma ANG I and II postmyocardial infarction (MI) and the effects of nephrectomy and angiotensin-converting enzyme (ACE) inhibitors on the early changes post-MI. Acute coronary artery ligation was induced in conscious rats using the two-stage model, and plasma and cardiac tissue were obtained shortly (6 h, 1 and 3 days) and chronically (1, 4, and 8-9 wk) after MI. In an additional group of rats, bilateral nephrectomy was performed 18 h before the coronary artery ligation, and samples were obtained at 6 h post-MI. Furthermore, in two additional groups of rats, treatment with enalapril and quinapril was started 3 days before the ligation, and samples were obtained at 1 or 3 days post-MI. In these groups of rats, plasma and left ventricular (LV) (infarct and infarct free) ANG I and II were measured by RIA after separation on HPLC. In control rats, plasma ANG I and II showed a clear increase at 6 h post-MI but subsequently only minor increases were observed. In contrast, LV ANG II showed major increases at 6 h and 1 day post-MI, which had returned to normal by 3 days in the infarct-free LV and after 1(-2) wk in the infarct LV. LV ANG I showed a more gradual increase and remained elevated in the infarct up to 8-9 wk. Nephrectomy preceding the MI lowered ANG I and II in plasma but enhanced their increases in the heart at 6 h post-MI. Both ACE inhibitors decreased plasma ANG II associated with large increases in plasma ANG I. They also inhibited the increases in LV ANG II in both the infarct and infarct-free LV at 1 and 3 days post-MI with however no significant increase in LV ANG I. In conclusion, induction of a MI in conscious rats leads to rapid and marked, but only short-lived, increases in cardiac tissue ANG II in both the infarct and infarct-free parts of the LV. Pretreatment with ACE inhibitors, but not nephrectomy, blocks this increase. Local production appears to play a major role in the increases in cardiac ANG II post-MI.

Angiotensin I↗
PubMed1999

Biomechanical assessment of gait in below-knee walking casts.

The introduction of modern synthetic casting bandages for splinting of fractures and soft tissue injuries has allowed the development of new casting techniques. Casts can be constructed with a greater degree of function so that controlled motion and stabilisation can be provided within the same cast. This study has shown that a very efficient gait can be achieved with modern synthetic bandages, if they are correctly applied. The authors have compared the gait of volunteer subjects fitted respectively with below-knee walking casts constructed from a rigid glass fibre bandage and a flexible glass fibre bandage which is reinforced. These casts were wrapped so that minimal amounts of bandage were used whilst appropriate strength and stiffness was provided. The temporal and spatial factors of cast gait were not statistically different from normal gait. The cast gait was found to be slightly more asymmetrical (dominant versus non-dominant leg) when a cast was worn and there was also a greater Physiological Cost Index (PCI). The flexible bandage has some advantages compared with the rigid bandage as normal footwear can be worn, the casts are more comfortable and they could be removed with shears, obviating the need for a power saw.

Adult↗
PubMed1998

The inducible prostaglandin biosynthetic enzyme, cyclooxygenase 2, is not mutated in patients with attenuated adenomatous polyposis coli.

Germ-line mutations in the APC gene cause adenomatous polyposis coli (APC), a syndrome in which patients develop hundreds to thousands of precancerous adenomatous colorectal polyps. We described previously an attenuated form of APC (AAPC) resulting from very 5' mutations in APC in which affected patients exhibit fewer colorectal polyps and a later age of onset of colorectal cancer. However, because striking variations in colorectal polyp numbers occur among patients carrying identical AAPC mutations, alleles of another gene may modify the expression of the APC disease phenotype. We tested the hypothesis that loss of function of human cyclooxygenase 2 (COX-2), known to modify the APC phenotype in the Apc delta716 mouse, results in a decreased tumor burden in AAPC patients that develop very few colorectal polyps. Genomic DNA sequence analysis of human COX-2 revealed a silent mutation in exon 3 that was evenly distributed between two classes of patients with AAPC, those with small or large numbers of colorectal polyps. We also found no difference in levels of COX-2 mRNA in transformed blood lymphocytes among AAPC patients of either class or patients with classical APC, and no alterations that correlated with a lesser or greater number of colorectal polyps were detectable within approximately the first 1 kb of the promoter sequence. Therefore, mutation of the human COX-2 gene does not appear to be responsible for a low tumor burden among AAPC subjects.

Adenomatous Polyposis Coli↗
PubMed1998

Toxicity evaluation of petroleum blending streams: inhalation subchronic toxicity/neurotoxicity study of a light alkylate naphtha distillate in rats.

A 13-wk inhalation study was conducted with Sprague-Dawley CD rats (12/sex/group) were exposed by inhalation for 13 weeks to a light alkylate naphtha distillate (LAND-2, C4-C10; average molecular weight 89.2) at actual average concentrations of 0 (room air), 668, 2220, or 6646 ppm, 6 h/d, 5 d/wk; 12 additional rats/sex in the control and high dose groups were held after final exposure for a 4-wk recovery period. The highest exposure concentration was 75% of the lower explosive limit. Standard parameters of subchronic toxicity were measured throughout the study; at necropsy, organs were weighed and tissues processed for microscopic evaluation. Neurotoxicity evaluations consisted of motor activity (MA) and a functional operational battery (FOB) measured pretest, during 5, 9, and 14 wk of the study, and after the 4-wk recovery period. Whole-body perfusion and microscopic examination of selected organs and nervous tissue from the control and high dose rats were conducted at the end of exposure. No test-related mortality or effects on physical signs, body weight, or food consumption were observed. Statistically significant increases in absolute and relative kidney weights in high-exposure males correlated with microscopically observed hyaline droplet formation and renal nephropathy, effects in male rats that are not toxicologically significant for humans. Increased liver weights in both sexes at the highest dose had no microscopic correlate and appeared reversible after the 4-wk recovery period. Exposure to LAND-2 at any dose did not produce neurotoxicity measured by MA, FOB, or neuropathology. The no-observed-effects level (NOEL) for LAND-2 was 2220 ppm for subchronic toxicity and > or =26646 ppm for neurotoxicity.

Administration, Inhalation↗
PubMed1998

Effects of K+ channel openers on relaxations to nitric oxide and endothelium-derived hyperpolarizing factor in rat mesenteric artery.

Relaxation of methoxamine-precontracted, endothelium-intact, rat mesenteric artery in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 100 microM) and indomethacin (10 microM) is attributed to endothelium-derived hyperpolarizing factor (EDHF). The potency of carbachol in the presence (but not the absence) of L-NAME was reduced by levcromakalim and pinacidil, activators of ATP-sensitive K+ channels (KATP). EDHF-mediated relaxation to Ca2+ ionophore A23187 was unaffected by these compounds but was inhibited by verapamil at the level of the smooth muscle. Levcromakalim and pinacidil had the same effects at both reduced and standard levels of tone. Glibenclamide (10 microM), a KATP blocker, alone did not affect carbachol relaxations but abolished both relaxation to levcromakalim and pinacidil and their inhibitory action on EDHF released by carbachol. Levcromakalim inhibited the endothelium-dependent hyperpolarization of mesenteric arteries to carbachol but not to A23187. Thus, levcromakalim or pinacidil inhibit EDHF, but not nitric oxide, release by carbachol through an action on the endothelium.

Animals↗
PubMed1998

Sequence-based design of a peptide probe for the APC tumor suppressor protein.

BACKGROUND: Proteins form specific associations, but predictive rules for protein pairing are generally unknown. Here, we describe amino-acid sequence patterns capable of mediating specific pairing of a widespread protein motif: the parallel, dimeric, alpha-helical coiled coil. The pairing rules were tested by designing a 54-residue peptide (anti-APCp1) that is predicted to dimerize preferentially with a coiled-coil sequence from the adenomatous polyposis coli (APC) tumor suppressor protein. RESULTS: As judged by circular dichroism, ultracentrifugation and native gel electrophoresis, anti-APCp1 formed a specific, helical, dimeric complex with the target APC coiled coil. On western blots of APC fragments expressed in Escherichia coli, the designed peptide detected a pattern of bands identical to the pattern detected by an antibody directed against the APC coiled coil. Peptide-mediated precipitation experiments showed that anti-APCp1 bound and sequestered wild-type and mutant APC proteins in extracts of human colon cancer cell lines. In addition, binding of the designed peptide preserved native APC-beta-catenin complexes. CONCLUSIONS: These biochemical experiments demonstrate that the anti-APC peptide preferentially forms a heterodimeric coiled coil with mutant and full-length APC proteins. The specificity of the designed peptide is sufficient to support several applications that commonly use antibodies. The observed specificity of anti-APCp1 validates the pairing rules used as the basis for the probe design, and it suggests that residues in the core positions of coiled coils help impart pairing selectivity.

Adenomatous Polyposis Coli Protein↗
PubMed1998

A role for natural killer cells in the immunopathogenesis of multiple sclerosis.

Seventeen relapsing-remitting (R/R) multiple sclerosis (MS) patients and age/sex matched controls were studied every 6 weeks for 2 years. Disease activity, determined both clinically and by serial MRI, was correlated with natural killer (NK) cell functional activity (FA) and phenotype. Mean NK cell FA is significantly lower in MS patients, compared to controls (P < 0.001), while variability around the means is significantly greater (P < 0.01). The spectrum of mean NK cell FA, observed in the patient cohort, along with cyclical nature of the FA and phenotype over time, observed in both patients and controls, may begin to explain the discrepant results reported in previous studies. In R/R MS, there is a significant correlation between reductions (valleys) in NK cell FA and the development of active lesions on MRI, new (P < 0.001) or enlarging (P = 0.05). More importantly, a significant number of active lesions, new (P = 0.01) and enlarging (P = 0.02), are preceded by a reduction in NK cell FA. The correlation between the onset of clinical attacks and valleys of NK cell FA is also significant (P = 0.002). When taken together, the results suggest that reductions (valleys) in NK cell FA represent periods of susceptibility for the development of active lesions on MRI and clinical attacks. A significant positive correlation is also identified between mean NK cell FA for each R/R MS patient and total number of active MRI lesions developed by that patient over the 2 years (P = 0.001). The results would suggest that R/R MS patients with a higher mean NK cell FA are at greater risk for the development of active lesions. These results support the proposal that NK cells may play a role in the immunopathogenesis of R/R MS.

Adult↗
PubMed1998

Evaluation of the immobilized artificial membrane phosphatidylcholine. Drug discovery column for high-performance liquid chromatographic screening of drug-membrane interactions.

Chromatographic retention factors (k') of a series of eight beta-adrenoceptor antagonist compounds (beta-adrenolytic drugs) were determined employing an immobilized artificial membrane column (IAM.PC.DD). The influence of mobile phase pH, ionic strength, and organic modifier composition was studied in order to examine column performance. After the IAM.PC.DD columns were exposed to approximately 7000 column volumes of a 0.01 M PBS mobile phase, five out of six columns tested showed significant peak broadening and decreased k' values indicative of premature column failure. The data suggested that the immobilized phospholipids stationary phase was removed by the 0.01 M PBS mobile phase. The beta-adrenolytic drug's log k'IAM values obtained with an IAM.PC.DD column were compared to an esterIAM.PC.MG column for predicting drug membrane interactions. For the linear regression analysis between log k'IAM and the logarithm of the n-octanol-water partition coefficients (rIAM.PC.DD = 0.8710 vs. rIAM.PC.MG = 0.9538), the C18 HPLC retention factors (rIAM.PC.DD = 0.8408 vs. rIAM.PC.MG = 0.9380), the liposome partition coefficients (rIAM.PC.DD = 0.8887 vs. rIAM.PC.MG = 0.9187), and various pharmacokinetic parameters, significantly better correlations were obtained with the esterIAM.PC.MG column than the IAM.PC.DD column.

Acebutolol↗
PubMed1998

Renal growth characteristics in children born with multicystic dysplastic kidneys.

OBJECTIVES: To report on the growth characteristics of the affected and contralateral kidneys in children born with multicystic dysplastic kidneys (MCDKs). METHODS: Thirty-three patients were enrolled from 1970 to 1995: 23 were initially managed nonoperatively (mean follow-up 3.39 years), and 10 underwent nephrectomy. Patients underwent radionuclide renal imaging and contrast voiding cystography. Serial ultrasonography was used to obtain measurements of the affected and contralateral kidneys. Blood pressure measurements and serum creatinine levels were available in some patients. RESULTS: Among the 23 nonoperative patients, the affected MCDK involuted in 4 patients during a mean follow-up of 4.5 years at a rate of 1.02 cm/yr (24% annually); 7 kidneys decreased in size at a mean rate of 0.38 cm/yr (5.8% annually); 6 grew at a mean rate of 1.16 cm/yr (9.9% annually); 1 kidney did not change in size; and 5 children were lost to follow-up. The mean size of the contralateral kidneys at birth was 5.3 cm, 2 standard deviations larger than normal. Over time, this relative hypertrophy was maintained at a growth rate of 0.89 cm/yr (18.5% annually). Two patients who had undergone nephrectomy also had serial postoperative ultrasonic renal measurements, and contralateral growth was 0.61 cm/yr (12.16% annually). All but 1 patient had normal blood pressure measurements and serum creatinine levels. CONCLUSIONS: Most MCDKs involute or decrease in size over time, although this may take many years. Contralateral hypertrophy is seen at birth and is maintained during childhood growth, regardless of whether the affected kidney is removed. There is no associated hypertension or malignancy when the dysplastic kidney is left in place.

Follow-Up Studies↗
PubMed1998

Alleles of APC modulate the frequency and classes of mutations that lead to colon polyps.

Most inherited mutant alleles of the adenomatosis polyposis coli gene (APC) cause the appearance of large numbers of colon polyps, the familial polyposis syndrome. (These mutant alleles are designated APCp alleles.) A subset of APC mutations, the attenuated or APC(AP) alleles, predispose to only a few colon polyps. This leads to the hypothesis that if mutation of the inherited normal allele is rate limiting in polyp development, the increased number of polyps associated with the APCp allele indicates that the frequency of mutations that can lead to polyp formation is higher among APCp carriers than among APC(AP) carriers. We have previously suggested that the APC protein might modulate the frequency of mutations, such as loss of heterozygosity (LOH), necessary for colon polyp formation. We thus reasoned that tumours from patients who carry an APC(AP) allele might show a reduced frequency of LOH compared with tumours from patients who carry an APCp allele. Loss of AAPC mutant alleles is designated as LOH(AP). Screening of tumours from APC(AP) carriers revealed a reduction of LOH compared with that of an unselected group of polyposis patients. In fact, no loss of the inherited APC(N) allele was observed, although sequencing showed that the inherited APC(N) allele had frequently undergone point mutations and small deletions in the tumours. A low frequency loss of the inherited APC(AP) allele was seen. These findings support the suggestion that the APC(AP) allele has residual gene activity and that this activity modulates the spectrum and frequency of mutations that lead to adenoma formation.

Adenomatous Polyposis Coli↗
PubMed1998

Modulation of relaxation to levcromakalim by S-nitroso-N-acetylpenicillamine (SNAP) and 8-bromo cyclic GMP in the rat isolated mesenteric artery.

1. Levcromakalim caused concentration-dependent relaxations of methoxamine-induced tone in both endothelium-denuded and intact vessels. Its potency was reduced by the nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP; 0.1 microM or 1 microM) in both denuded and intact vessels. The maximal relaxation (Rmax) was reduced only in denuded vessels. 2. SNAP was more potent in endothelium-denuded than intact vessels but there were no differences in Rmax. Glibenclamide (10 microM) did not affect relaxation to SNAP in endothelium-denuded or intact vessels. 3. The soluble guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) increased the potency and Rmax of levcromakalim in endothelium-intact vessels. ODQ had no effect in denuded vessels. 4. ODQ (10 microM) reduced the vasorelaxant potency of SNAP in both intact and endothelium-denuded vessels by 190-fold and 620-fold, respectively. 5. 8-bromo cyclic GMP (10 or 30 microM) reduced both the potency and Rmax of levcromakalim in de-endothelialized vessels, but had no effect in intact vessels although it reduced both the potency and Rmax of levcromakalim in intact vessels incubated with ODQ (10 microM). 6. In the presence of ODQ (10 microM), SNAP (0.1 microM or 1 microM) reduced the potency of levcromakalim in intact vessels, without altering Rmax, but had no effect in denuded vessels. SNAP (50 microM) reduced both the potency and Rmax of levcromakalim in intact and endothelium-denuded vessels. 7. Therefore, although SNAP causes relaxation principally through generation of cyclic GMP, it can modulate the actions of levcromakalim through mechanisms both dependent on, and independent of, cyclic GMP; the former predominate in endothelium-denuded vessels and the latter in intact vessels.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

The actions of some cannabinoid receptor ligands in the rat isolated mesenteric artery.

1. The actions of a number of cannabinoid receptor ligands were investigated using the myograph-mounted rat isolated mesenteric artery. Anandamide, CP 55,940, HU-210, palmitoylethanolamide and WIN 55,212-2 all caused concentration-dependent relaxations of methoxamine-precontracted vessels which were not affected by removal of the endothelium. 2. Precontracting vessels with 60 mM KCl instead of methoxamine greatly reduced the vasorelaxant effects of anandamide and palmitoylethanolamide. High K+ solution caused a modest decrease in the relaxant potency of CP 55,940 and HU-210, and had no effect on relaxations induced by WIN 55,212-2. 3. Relaxations of methoxamine-induced tone by anandamide, CP 55,940 and HU-210, but not palmitoylethanolamide and WIN 55,212-2, were attenuated by the cannabinoid receptor antagonist, SR 141716A. Relaxation of vessels contracted with 60 mM KCl by CP 55,940 was also sensitive to SR 141716A. 4. Anandamide and CP 55,940 caused small but concentration-dependent contractions in resting vessels in the absence of extracellular calcium. These were not sensitive to SR 141716A. Palmitoylethanolamide and WIN 55,212-2 produced smaller contractions only at higher concentrations. 5. Anandamide and CP 55,940, but not palmitoylethanolamide and WIN 55,212-2, caused concentration-dependent inhibition of the phasic contractions induced by methoxamine in calcium-free conditions, but only anandamide caused inhibition of contractions to caffeine under such conditions. These inhibitory effects were not antagonised by SR 141716A. 6. The present study provides the first detailed investigation of the actions of cannabinoid agonists on vascular smooth muscle. Our results show that these compounds exert both receptor-dependent and -independent effects on agonist-induced calcium mobilization in the rat isolated mesenteric artery.

Amides↗
PubMed1998

The actions of the cannabinoid receptor antagonist, SR 141716A, in the rat isolated mesenteric artery.

1. The actions of the cannabinoid receptor antagonist, SR 141716A, were examined in rat isolated mesenteric arteries. At concentrations greater than 3 microM, it caused concentration-dependent, but endothelium-independent, relaxations of both methoxamine- and 60 mM KCl-precontracted vessels. 2. SR 141716A (at 10 microM, but not at 1 microM) inhibited contractions to Ca2+ in methoxamine-stimulated mesenteric arteries previously depleted of intracellular Ca2+ stores. Neither concentration affected the phasic contractions induced by methoxamine in the absence of extracellular Ca2+ 3. SR 141716A (10 microM) caused a 130 fold rightward shift in the concentration-response curve to levcromakalim, a K+ channel activator, but had no effect at I microM. 4. SR 141716A (10 microM) attenuated relaxations to NS 1619 (which activates large conductance. Ca2+-activated K+ channels; BK(Ca)). The inhibitory effect of SR 141716A on NS 1619 was not significantly different f'rom, and was not additive with, that caused by a selective BKc,, inhibitor, iberiotoxin (100 nM). SR 141716A (1 microM) did not effect NS 1619 relaxation. 5. SR 141716A (10 microM) had no effect on relaxations to the nitric oxide donor S-nitroso-N-acetylpenicillamine, or relaxations to carbachol in the presence of 25 mM KCl. 6. The results show that, at concentrations of 10 microM and above. SR 141716A causes endothelium-independent vasorelaxation by inhibition of Ca2+ entry. It also inhibits relaxations mediated by K+ channel activation. This suggests that such concentrations of SR 141716A are not appropriate for investigation of cannabinoid receptor-dependent processes.

Animals↗
PubMed1998

Acute effects of ambient inhalable particles in asthmatic and nonasthmatic children.

Although increases in inhalable particle (PM10) concentrations have been associated with acute reductions in the level of lung function and increased symptom reporting in children, including children with asthma, it is not clear whether these effects occur largely in asthmatic children, or even whether asthmatic children are more likely to experience these effects than children without asthma. To address these points, the following subgroups of children were selected from a survey population of all 2,200 elementary school children (6 to 13 yr of age) in a pulp mill community on the west coast of Vancouver Island: (1) all children with physician-diagnosed asthma (n = 75 participated), (2) all children with an exercise-induced fall in FEV1 without diagnosed asthma (n = 57), (3) all children with airway obstruction (FEV1/FVC < 0.76) without either of the above (n = 18), and (4) control children without any of the above (n = 56). The children were followed for as long as 18 mo with twice daily measurements of peak expiratory flow (PEF) and daily symptom diary recording. Maximum daily PM10 concentration was 159 microm/m3 (median, 22.1), but only 8 d (1.2%) had concentrations above 100 microg/m3. In an analysis that accounted for time-varying covariates, and serially correlated and missing data, for the entire sample of children, increases in PM10 were associated with reductions in PEF and increased reporting of cough, phlegm production, and sore throat. For the subgroup of children with diagnosed asthma, PEF in the time period with the highest PM10 concentrations fell by an estimated 0.55 L/min (95% CI, 0.06 to 1.05) for a 10 microg/m3 PM10 increase above the mean daily PM10 concentration of 27.3 microg/m3 and the odds of reported cough increased by 8% (95% CI, 0 to 16%); no consistent effects were observed in the other groups of children. It is concluded that children experience reductions in PEF and increased symptoms after increases in relatively low ambient PM10 concentrations, and that children with diagnosed asthma are more susceptible to these effects than are other children.

Adolescent↗