Biomedical subjects

D W Thomas

Publications and source records attributed to D W Thomas.

At least 37 records · Page 2Linked to original sources

PubMed2001

Karyotypes found in the population declared at increased risk of Down syndrome following maternal serum screening.

Of the 65 328 pregnancies of South Australian mothers screened by the South Australian Maternal Serum Antenatal Screening (SAMSAS) Programme between 1 January 1991 and 31 December 1997, 3431 (5.25%) were declared at increased risk of fetal Down syndrome. Fetal or neonatal karyotype was determined in 2737/3431 (79.8%) of these pregnancies, including 16 with early fetal loss. Interrogation of the database of the South Australian Neonatal Screening Service showed 643 live-born infants whose phenotype was not subsequently questioned among the 694 pregnancies whose karyotype was not determined. Of the remaining 51/3431 pregnancies, 19 ended in early fetal loss without karyotyping and no newborn screening or other records could be found for 32 cases. The 129 instances of abnormal karyotype found were Down syndrome (84), trisomy 18 (four), trisomy 13 (three), triploidy (two), female sex chromosome aneuploidy (six) and male sex chromosome aneuploidy (five), inherited balanced rearrangements (19), mosaic or de novo balanced abnormalities (four) and unbalanced karyotypes (two). In the pregnancies declared at increased risk of fetal Down syndrome, only the karyotype for Down syndrome occurred with a frequency greater than that expected for the general, pregnant population.

Down Syndrome↗

PubMed2001

Producing proteins in transgenic plants and animals.

The requirement for large quantities of therapeutic proteins has fueled interest in the production of recombinant proteins in plants and animals. The first commercial products to be made in this way have experienced much success, and it is predicted that in the future a plethora of protein products will be made using these 'natural' bioreactors.

Animals↗

PubMed2001

Characterization and analysis of biphalin: an opioid peptide with a palindromic sequence.

Among the many opioid peptides developed to date as nonaddictive analgesics, biphalin has exhibited extraordinary high potency and many other desirable characteristics. Biphalin is an octapeptide consisting of two monomers of a modified enkephalin, attached via a hydrazine bridge, and with the amino acids assembled in a palindromic sequence. Its structure is (Tyr-D-Ala-Gly-Phe-NH-)-2. However, this unique peptide, like any other synthetic peptide, needs strict quality control because of certain drawbacks associated with peptide synthesis. This paper discusses our approaches to characterizing and analyzing biphalin. Many techniques were used, including elemental analysis, amino acid analysis, amino acid sequence analysis (AASA), mass spectrometry (MS), 1H-NMR, 1H-correlated spectroscopy (COSY)-NMR, high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Electrospray ionization (ESI) mass spectrometry, which included both ESI-MS and ESI-MS/MS, was performed to confirm the full sequence because AASA results alone verified only the monomer sequence, and not the full sequence. Although the 1H-NMR results led to a preliminary assignment of many protons, the 1H COSY-NMR results allowed for unequivocal assignment of almost all protons. Peptide purity was determined using two techniques, reversed-phase HPLC and CE. The counter-ion of the peptide, trifluoroacetic acid, was determined by CE, using an indirect detection method developed previously in our laboratory. This paper illustrates successful application of nonconventional techniques to characterize and analyze a structurally modified peptide, biphalin, when standard techniques for peptide analysis are inadequate.

Chromatography, High Pressure Liquid↗

PubMed2001

Cyclosporin A-induced gingival overgrowth is unrelated to allograft function in renal transplant recipients.

BACKGROUND: Severe gingival hyperplasia (GH) is one of the most frequent side-effects associated with the prescription of Cyclosporine-A (CsA). AIM: This study statistically modeled the medical and dental risk factors for the development of GH following CsA administration to determine whether renal function post-transplantation was related to the incidence or extent of GH in 236 consecutive renal transplant patients. METHOD: All patients were at least 6 months post-transplant and medicated with both traditional oral CsA (n=220 individuals) and the new microemulsion form CsA-Me (n=229 individuals). Patients had either received CsA alone (n=45 individuals) or cyclosporine and nifedipine (n=191 individuals). Gingival overgrowth was assessed and computerized data, available for all patients included; pre- and post-transplant medical history and post-transplant renal function, i.e., serum creatinine levels, documented rejection episodes and glomerular filtration rates (GFR). These data together with CsA serum levels and last-recorded dose of CsA, CsA-Me, nifedipine, azathioprine and prednisolone, were analysed by multivariate regression analysis using SPSS. RESULTS: The extent and severity of hyperplasia was significantly correlated with the dosage and serum level of CsA at 3, 6 and 12 months post-transplantation; last recorded dosage, however (p<0.0001), was the most accurate predictor of hyperplasia. Gingivitis (p<0.0001) and plaque (p<0.002), were associated with hyperplasia. Duration of renal replacement therapy, age at transplantation, post-transplant interval serum creatinine levels and documented rejection episodes were unrelated with the extent and severity of GH. Of all the renal variables only the correlation of GFR with last recorded doses of CsA and CsA-Me, approached significance; this was then considered for inclusion in the model. CONCLUSION: In a multiple regression analysis including GFR, however, only last CsA (and CsA-Me) doses and gingivitis score were selected for inclusion in the final model. These data demonstrate that inter-patient variation in the extent and severity of GH and renal function post-transplantation are unrelated and are mediated independently.

Adolescent↗

PubMed2001

Intra-operative blood salvage in abdominal trauma: a review of 5 years' experience.

We performed a retrospective audit of 1235 patients presenting between 1992 and 1997, following the introduction of intra-operative blood salvage at our hospital. Twenty-two cases of severe abdominal trauma requiring emergency laparotomy and intra-operative blood salvage were identified. The impact of intra-operative blood salvage in aiding resuscitation and reducing demand on allogeneic blood supplies is discussed.

Abdominal Injuries↗

PubMed2001

Skin and oral fibroblasts exhibit phenotypic differences in extracellular matrix reorganization and matrix metalloproteinase activity.

BACKGROUND: Oral mucosal wounds are characterized by rapid re-epithelialization and remodelling. In vitro, oral mucosal fibroblasts exhibit a fetal phenotype with increased extracellular matrix reorganizational ability, migration and experimental wound repopulation when compared with skin fibroblasts. OBJECTIVES: To investigate whether phenotypic differences in the expression and production of matrix metalloproteinase (MMP) -2 and tissue inhibitors of metalloproteinases (TIMPs) could play an important part in mediating these in vitro differences. METHODS: Skin and oral mucosal fibroblast MMP-2, TIMP-1 and TIMP-2 mRNA expression and protein production were studied in three-dimensional collagen lattices using quantitative competitive reverse transcriptase-polymerase chain reaction (QCRT-PCR), enzyme-linked immunosorbent assay (ELISA), zymography and reverse zymography. RESULTS: Oral mucosal fibroblasts exhibited increased levels of the 62-kDa active form of MMP-2 and lattice contraction when compared with skin fibroblasts. Oral mucosal and skin fibroblast MMP-2 gene expression and synthesis of the 72-kDa pro-MMP-2 was similar as assessed by QCRT-PCR, zymography and ELISA. Differential MMP-2 activation was, however, related to phenotypic differences in TIMP activity between the skin and oral mucosal fibroblasts, as assessed by reverse zymography. CONCLUSIONS: These studies propose a mechanism by which fibroblast phenotype may contribute directly to the observed preferential remodelling of oral wounds.

Adolescent↗

PubMed2001

Pregabalin in patients with postoperative dental pain.

Pregabalin is an analogue of the inhibitory neurotransmitter gamma-aminobutyric acid. In preclinical models, it has shown activity as an analgesic agent. A randomized, double-blind, placebo-controlled, parallel-group trial was undertaken to compare pregabalin to placebo and 400 mg of ibuprofen using a dental pain model. Study medication was administered postoperatively to patients who had undergone elective surgery to remove one or two third molars, at least one of which was mandibular and fully or partially impacted in bone. The study was conducted in the UK at a single centre and evaluated pregabalin at doses of 50 and 300 mg. Primary efficacy parameters included pain relief (PR), pain intensity difference (PID), pain relief intensity difference (PRID), time to onset of analgesia, and duration of analgesia. The patient's global impression of the study medication was used as a secondary efficacy parameter. Efficacy data were evaluated for the intent-to-treat (ITT) population, defined as all randomized patients who took study medication. Results showed that there were statistically significant differences in PR, PID, and PRID between the 300-mg pregabalin group and placebo. In addition, the 300-mg pregabalin group had a significantly longer duration of analgesia than the ibuprofen group and had the highest score on the patient global impression of study medication. Adverse events were reported more frequently in the pregabalin 300-mg group. Pregabalin appears to have significant analgesic properties in the third molar extraction model. Further research is needed to confirm these findings.

Adolescent↗

PubMed2001

Nerve morbidity following wisdom tooth removal under local and general anaesthesia.

Two hundred and one patients had unilateral removal of the lower third molars under local anaesthesia and a further 234 patients had either bilateral or unilateral removal under general anaesthesia. A total of 634 lower third molars were extracted by four experienced surgeons (two consultants and two senior grade staff). All patients were reviewed independently 1-week postoperatively and any sensory disturbance and its location was recorded. Patients with sensory disturbance were subsequently reviewed at 1 month and again at 6 months if recovery was not complete. This study demonstrated little difference in the adverse event rate per tooth extracted between procedures under local and general anaesthesia. However, within the general anaesthetic group, the few unilateral procedures showed evidence of higher risk, but the number was too small for valid satisfactory analysis. The risk of nerve morbidity was also greater where the duration of the procedure was longer than 15 minutes in unilateral cases.

Adult↗

PubMed2001

Reduced total plasma homocyst(e)ine in children and adolescents with type 1 diabetes.

OBJECTIVES: The objective was to investigate total plasma homocyst(e)ine (tHcy), methylenetetrahydrofolate reductase (MTHFR) genotype, and the contribution of diet to homocysteine values in children and adolescents with type 1 diabetes and a control group. STUDY DESIGN: A total of 78 children with type 1 diabetes and 59 members of an age- and sex-matched control group were recruited. Fasting samples were collected for tHcy, MTHFR genotype, serum vitamin B(12), serum folate, red cell folate, and plasma creatinine. Food frequency questionnaires targeted intake of folate, vitamin B(6), and vitamin B(12). RESULTS: Fasting tHcy was reduced in patients compared with the control group (4.7 vs 5.9 micromol/L, P <.001). Serum folate (P =.002), red cell folate(P <.001), and serum vitamin B(12) (P =.005) were higher, and plasma creatinine was lower. A significant difference in tHcy values between patients and the control group persisted after correction was done for these factors (r = 0.1, P =.02). No difference was seen in the frequency of MTHFR polymorphisms. tHcy was not elevated in those patients with the 677TT or 677T/1298C genotypes, although red cell folate was significantly higher in members of the case (P =.01) and control groups (P =.05) with a 677 TT genotype. Dietary intake of folate correlated with serum folate (r = 0.4,P =.005). CONCLUSION: tHcy values are lower in children and adolescents with type 1 diabetes. Higher serum levels of folic acid and vitamin B(12), reflecting differences in dietary intake between children with diabetes and members of a control group, partially account for this difference.

Adolescent↗

PubMed2001

Physiological ecology of Mediterranean Blue Tits (Parus caeruleus). I. A test for inter-population differences in resting metabolic rate and thermal conductance as a response to hot climates.

Blue Tits (Parus caeruleus) are widely distributed throughout Europe, reaching the southern limit of their range on islands in the Mediterranean and in northern Africa. On Corsica, one population located at Pirio in the Fango Valley breeds roughly one month later than populations in adjacent valleys or on the continent, thus exposing nestlings to high ambient temperatures (T(a)). We tested the hypothesis that nestlings and possibly adult Blue Tits at Pirio would exhibit a reduction in resting metabolic rate (MR) and an increase in thermal conductance as a physiological response to high T(a). We compared the thermoregulatory response and evaporative water loss for nestlings from Pirio in Corsica and one continental site (Vic-le-Fesq) and for adults from two Corsican (Pirio and Muro) and one continental site (La Rouvière). At 12-14 days of age, nestlings from Pirio showed two distinct thermoregulatory patterns. Nestlings under 8.0 g behaved as heterotherms, whereby MR was correlated only with body temperature. At body masses above 8.0 g nestlings progressively acquired the ability to regulate T(b) and at masses >9.0 g they behaved as homeotherms. When considering homeothermic nestlings and adults, population of origin did not affect either thermal conductance or resting MR. For homeothermic nestlings, mass-specific resting MR (mW x g-(1)) was 15.5 +/- 2.6 and 17.5 +/- 2.5 for nestlings from Vic-le-Fesq and Pirio, respectively. For adults, mass-specific resting MR (mW x g-(1)) was 17.5 +/- 2.0, 17.8 +/- 1.6, and 17.9 +/- 1.0 for birds from Pirio, Muro, and La Rouvière, respectively. Although there was a weak but positive effect of T(a) on evaporative water loss for homeothermic nestlings, no such trend was evident for adults over the range of T(a) tested in this study. We thus find no evidence to indicate that either nestlings or adults exhibit the exponential increase in evaporative water loss associated with the non-convective regulation of T(b) within the range of T(a) tested (roughly <or=35 degrees C). We conclude that there is no evidence for a specific physiological adaptation in the Pirio population. Measures of nestbox temperatures indicate that nestlings rarely experience temperatures in excess of 33 degrees C. We conclude that, although some years may be hot enough to impose a thermal stress, temperatures at Pirio are not high enough to consistently impose a selective pressure for physiological adaptations to heat.

Journal Article↗

PubMed2001

Liver transplantation in cystic fibrosis.

Liver disease is the second most common cause of death in patients with cystic fibrosis (CF). Improvement in surgical techniques, medical management, and imaging modalities has broadened the range of options for treatment of these patients. Medical management with ursodeoxycholic acid and nutritional support may help decelerate the progression of liver disease. A timely evaluation of CF patients with liver involvement for transplantation is important. Such evaluation should not be delayed until signs of hepatic decompensation occur. Combined lung-liver transplant can be considered for patients with advanced pulmonary disease. Pretransplant management of portal hypertension with a portosystemic shunt procedure is an option for patients with well-preserved synthetic liver function. Improvement in lung function after liver transplantation and no significant risk of pulmonary infection with immunosuppressive therapy have been reported. Review of individual center experiences have shown satisfactory survival and improved quality of life for CF patients undergoing liver transplant.

Cystic Fibrosis↗

PubMed2001

Receptors for prostaglandin E(2) that regulate cellular immune responses in the mouse.

Production of prostaglandin E(2) (PGE(2)) is enhanced during inflammation, and this lipid mediator can dramatically modulate immune responses. There are four receptors for PGE(2) (EP1-EP4) with unique patterns of expression and different coupling to intracellular signaling pathways. To identify the EP receptors that regulate cellular immune responses, we used mouse lines in which the genes encoding each of the four EP receptors were disrupted by gene targeting. Using the mixed lymphocyte response (MLR) as a model cellular immune response, we confirmed that PGE(2) has potent antiproliferative effects on wild-type responder cells. The absence of either the EP1 or EP3 receptors did not alter the inhibitory response to PGE(2) in the MLR. In contrast, when responder cells lacked the EP2 receptor, PGE(2) had little effect on proliferation. Modest resistance to PGE(2) was also observed in EP4-/- responder cells. Reconstitution experiments suggest that EP2 receptors primarily inhibit the MLR through direct actions on T cells. Furthermore, PGE(2) modulates macrophage function by activating the EP4 receptor and thereby inhibiting cytokine release. Thus, PGE(2) regulates cellular immune responses through distinct EP receptors on different immune cell populations: EP2 receptors directly inhibit T cell proliferation while EP2 and EP4 receptors regulate antigen presenting cells functions.

Animals↗

PubMed2000

A role for fractalkine and its receptor (CX3CR1) in cardiac allograft rejection.

The hallmark of acute allograft rejection is infiltration of the inflamed graft by circulating leukocytes. We studied the role of fractalkine (FKN) and its receptor, CX(3)CR1, in allograft rejection. FKN expression was negligible in nonrejecting cardiac isografts but was significantly enhanced in rejecting allografts. At early time points, FKN expression was particularly prominent on vascular tissues and endothelium. As rejection progressed, FKN expression was further increased, with prominent anti-FKN staining seen around vessels and on cardiac myocytes. To determine the capacity of FKN on endothelial cells to promote leukocyte adhesion, we performed adhesion assays with PBMC and monolayers of TNF-alpha-activated murine endothelial cells under low-shear conditions. Treatment with either anti-FKN or anti-CX(3)CR1-blocking Ab significantly inhibited PBMC binding, indicating that a large proportion of leukocyte binding to murine endothelium occurs via the FKN and CX(3)CR1 adhesion receptors. To determine the functional significance of FKN in rejection, we treated cardiac allograft recipients with daily injections of anti-CX(3)CR1 Ab. Treatment with the anti-CX(3)CR1 Ab significantly prolonged allograft survival from 7 +/- 1 to 49 +/- 30 days (p < 0.0008). These studies identify a critical role for FKN in the pathogenesis of acute rejection and suggest that FKN may be a useful therapeutic target in rejection.

Animals↗

PubMed2000

Antibiotic prescribing for dental conditions: general medical practitioners and dentists compared.

OBJECTIVE: To compare the level of prescribing and types of antibiotics prescribed for dental problems by general medical practitioners and dentists. DESIGN: Secondary analysis of standard consultation data and prescription records from four different settings. SETTING: 30 participating general practices in the General Practice Morbidity Database for Wales in 1996. SUBJECTS: 1,185 attendances for tooth-related problems, at 30 participating practices in the General Practice Morbidity Database for Wales in 1996. Standard consultation records from a GDP emergency dental rota, and two weekend emergency dental clinics: one in a health centre, the other in a dental hospital. RESULTS: More than two thirds (68%) of attendances at general medical practices for tooth-related problems resulted in a prescription for antibiotics. In contrast less than a third (28%) of patients seen by a GDP rota, about half (52%) of patients at a weekend emergency clinic in a health centre, and just more than a third (38%) of patients attending the dental hospital clinic received antibiotics. General medical practitioners were also more likely to prescribe broad-spectrum antibiotics than dentists. CONCLUSION: For acute dental problems general medical practitioners are more likely to prescribe antibiotics than dentists. There also appear to be inter-professional differences in the tendency to prescribe broad spectrum antibiotics. Initiatives to rationalise prescribing for dental conditions may need to target doctors as well as dentists.

Anti-Bacterial Agents↗

PubMed2000

Out-of-hours dental services: a survey of current provision in the United Kingdom.

OBJECTIVE: To describe the variety of arrangements for providing out-of-hours dental care in the UK. DESIGN: A telephone interview survey of health authorities and health boards. SETTING: United Kingdom. SUBJECTS: 104 health authority contacts, usually consultants in dental public health, dental advisers or others in a position to describe the local dental service arrangements. RESULTS: At weekends, 25 authorities have no formal dental care arrangements for unregistered patients, 55 have separate arrangements for registered and unregistered patients, and 44 have 'universal access' arrangements--for anyone in an area, regardless of their registration status. On weekday nights over two-thirds (82/124) of UK health authorities have no formal arrangements for unregistered patients. Where there are separate 'safety-net' services intended for unregistered patients only they are usually (in 48 of 55 authorities) emergency treatment sessions. A fifth of authorities reported planned changes to their local out-of-hours arrangements, including the introduction of telephone triage, and moves to make care available at more times, to more people or from centralised premises. CONCLUSIONS: There is extremely wide geographical variation in the organisation of out-of-hours dental services provided in the United Kingdom. In many parts of the UK there are no formal out-of-hours care arrangements for unregistered patients, even at weekends. This unequal provision will mean inequitable access for many unregistered patients. With increasing demands from a growing unregistered population, and various government initiatives to make primary care services more integrated and accessible, the highly fragmented pattern of provision in many areas may no longer be acceptable.

Catchment Area, Health↗

PubMed2000

Risk factors in the development of cyclosporine-induced gingival overgrowth.

BACKGROUND: Severe gingival hyperplasia (GH) is one of the most frequent side-effects associated with the prescription of cyclosporine-A (CsA). Using the largest group of renal allograft recipients assembled for this purpose, in this study, we statistically modeled the genetic (HLA), medical, and dental risk factors for the development of GH subsequent to administration of CsA. METHODS: Two hundred thirty-six renal transplant patients underwent full dental examination to quantify the extent and distribution of hyperplasia and dental disease (gingivitis, plaque, and calculus). Computerized data from all patients included pre-transplant medical history and dosage of nifedipine and azathioprine, as well as dose and serum levels of CsA and CsA microemulsion. Donor and host HLA haplotype were studied to investigate potential association of haplotype and donor-host mismatching with the development of GH. We evaluated the data by multivariate regression analysis, using Statistical Package for Social Sciences (SPSS). RESULTS: There was no association with age, sex, duration of renal replacement therapy, or interval since transplantation or pre-transplant disease (P>0.05). There also was no association of disease with host HLA haplotype, but degree of HLA-A mismatching was protective for GH development (P<0.002). GH was associated with the dose and serum levels of CsA (P<0.001) and the last dose of CsA microemulsion (P=0.009) but not nifedipine (P=0.10). Gingival inflammation and plaque were also strongly associated with GH (P<0.0003). In multivariate analysis, however, the last recorded dose of CsA (P<0.0001), presence of local gingival inflammation (P<0.0001), and gingivitis (P<0.003) were the independent predictors of the extent and severity of GH. CONCLUSIONS: Inter-patient variation in the extent and severity of GH is related to CsA dose and serum levels. Differences in host HLA phenotype do not explain individual susceptibility to GH, but donor-host HLA-A mismatching may be important. Inter-site variation in the extent and severity of the disease is related to local gingival inflammation.

Adolescent↗

PubMed2000

Hyperoxia for management of acid-base status during deep hypothermia with circulatory arrest.

BACKGROUND: Which blood gas strategy to use during deep hypothermic circulatory arrest has not been resolved because of conflicting data regarding the advantage of pH-stat versus alpha-stat. Oxygen pressure field theory suggests that hyperoxia just before deep hypothermic circulatory arrest takes advantage of increased oxygen solubility and reduced oxygen consumption to load tissues with excess oxygen. The objective of this study was to determine whether prevention of tissue hypoxia with this strategy could attenuate ischemic and reperfusion injury. METHODS: Infants who had deep hypothermic circulatory arrest (n = 37) were compared retrospectively. Treatments were alpha-stat and normoxia (group I), alpha-stat and hyperoxia (group II), pH-stat and normoxia (group III), and pH-stat and hyperoxia (group IV). RESULTS: Both hyperoxia groups had less acidosis after deep hypothermic circulatory arrest than normoxia groups. Group IV had less acid generation during circulatory arrest and less base excess after arrest than groups I, II, or III (p < 0.05). Group IV produced only 25% as much acid during deep hypothermic circulatory arrest as the next closest group (group II). CONCLUSIONS: Hyperoxia before deep hypothermic circulatory arrest with alpha-stat or pH-stat strategy demonstrated advantages over normoxia. Furthermore, pH-stat strategy using hyperoxia provided superior venous blood gas values over any of the other groups after circulatory arrest.

Acid-Base Imbalance↗

PubMed2000

Vasoconstrictor responses in thromboxane receptor knockout mice: tubuloglomerular feedback and ureteral obstruction.

The role of thromboxane (TP) in the vasoconstriction induced by tubuloglomerular feedback or 18-h ureteral obstruction was studied in wild type mice (TP +/+), and in heterozygous (TP +/-) and homozygous TP receptor knockout mice (TPR -/-). TGF function was assessed from the response of stop flow pressure (PSF) to a maximum increase in loop of Henle flow rate (0-30 nL min-1). PSF fell by 6.4 +/- 0.4 mmHg in wild-type mice, by 6.1 +/- 0.6 mmHg in TP +/-, and by 7.9 +/- 0.7 mmHg in TP -/- mice. In the presence of the TP receptor agonist U46,619 (10-5 M) the PSF reduction increased to 10. 4 +/- 0.8 mmHg in TP +/+, and to 10.6 +/- 2.8 mmHg in TP +/-, but was unchanged at 7.7 +/- 0.7 mmHg in TP -/-. Mean arterial blood pressures were comparable between groups (103 +/- 3 mmHg in TP +/+, 113 +/- 4.6 in TP +/- and 113 +/- 2.4 mmHg in TP -/- mice). Intratubular pressure following unilateral ureteral obstruction was significantly higher in TP -/- than in TP +/+ mice both in the early phase (0-3 h) and late phase (18 h) of obstruction. These results indicate that chronic TP receptor deficiency does not significantly alter maximum TGF responses in mice, and that it is accompanied by exaggerated vasodilatation during short-term unilateral ureteral obstruction and attenuated vasoconstriction during longer lasting obstruction. We conclude that thromboxane is primarily a regulator of renal vascular tone under pathophysiological conditions.

Animals↗