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Biomedical subjects

R Green

Publications and source records attributed to R Green.

At least 37 records · Page 2Linked to original sources
PubMed2002

Preventing cardiovascular disease in hypertension: effects of lowering blood pressure and cholesterol.

BACKGROUND: In guidelines for the primary prevention of cardiovascular disease, systolic blood pressure (SBP) or diastolic blood pressure (DBP) is treated with medication at lower levels of risk than those at which statin treatment is recommended for cholesterol lowering. AIM: To compare the potential benefits of antihypertensive medication and statin therapy in hypertensive patients, and examine whether this policy is rational. DESIGN: Retrospective cross-sectional survey. METHODS: We studied 146 men and 150 women aged 56 (54-58) (mean (95% CI)) years and 60 (58-62) years, respectively, who had commenced drug therapy for hypertension within 10 years in five general practices in Greater Manchester. Coronary heart disease (CHD) and stroke risk were calculated, and the potential benefit of blood pressure lowering treatment and statin therapy estimated using the results of published meta-analyses of clinical trials. RESULTS: Blood pressure before treatment was initiated was 176 (173-179)/102 (100-104) mmHg in men and 176 (172-179)/98 (96-100) mmHg in women. Serum cholesterol was 5.7 (5.5-5.9) mmol/l and high density lipoprotein (HDL) cholesterol 1.3 (1.2-1.4) mmol/l in men. The corresponding values in women were 6.3 (6.1-6.5) mmol/l and 1.5 (1.4-1.6) mmol/l. Of the men, 44% (36-52%) smoked and 23% (17-31%) had diabetes mellitus, whereas 27% (20-35%) of the women smoked and 26% (19-34%) had diabetes. These risk factors gave the combined group of men and women a CHD risk of 19.7% (12.0-28.0%) (median (IQR)) and a stroke risk of 8.8% (3.8-13.9%) over the next 10 years. All patients were prescribed antihypertensive medication and 15% subsequently received statin treatment. The 10-year CHD risk would be expected to decrease to 16.5% (10.1-23.5%) on anti-hypertensive therapy. Had statin treatment been given instead, it would have been reduced to 13.2% (8.05-18.7%). For stroke, the 10-year risk on antihypertensive therapy was calculated as 5.5% (2.4-8.6%) and on statin 6.2% (2.7-9.9%). This meant that combined CHD and stroke risk would be reduced from 29.4% (17.5-41.5%) to 22.4% (17.5-41.5%) on antihypertensive therapy and to 20.1% (11.9-28.2%) on statins. The difference between statin and antihypertensive therapy was statistically significant (p<0.0001). DISCUSSION: Because the object of drug treatment in mild-moderate hypertension is to reduce cardiovascular disease risk and not simply to decrease blood pressure, current recommendations and practice should be revised so that more patients can benefit from evidence-based therapy favouring a more holistic approach, including cholesterol-lowering therapy.

Anticholesteremic Agents↗
PubMed2001

Effect of acute saline volume expansion in the anaesthetised DeltaF508 cystic fibrosis mouse.

It has been suggested that CFTR Cl(-) channels in the renal inner medullary collecting duct may be involved in mediating increased renal salt excretion during extracellular fluid volume expansion. To investigate this hypothesis, in-vivo clearance experiments were performed comparing wild-type (WT) and DeltaF508-CFTR transgenic mice (cftr (tm2Cam)). Control animals were given a 0.1-ml bolus of 0.9% saline, followed by I.V. infusion at 0.3 ml x h(-1). Volume expansion was applied by infusing a 1-ml bolus of 0.9% saline followed by infusion at 0.6 ml x h(-1). No significant differences in renal NaCl handling between WT mice ( C(Na)=1.2 +/- 0.3 microl x min(-1), C(Cl)=4.0 +/- 0.5 microl x min(-1)) and DeltaF508-CFTR mice ( C(Na)=1.7 +/- 0.5 microl x min(-1), C(Cl)=4.1 +/- 0.8 microl x min(-1)) were observed under control conditions. Volume expansion resulted in large significant increases in NaCl clearance in both WT mice ( C(Na)=7.0 +/- 0.9 microl x min(-1), C(Cl)=12.0 +/- 0.6 microl x min(-1)) and DeltaF508-CFTR mice ( C(Na)=7.2 +/- 1.6 microl x min(-1), C(Cl)=11.0 +/- 2.2 microl x min(-1)). However, there was no significant difference between WT and DeltaF508-CFTR mice. In conclusion, renal NaCl excretion is not significantly different under basal conditions and during saline volume expansion in DeltaF508-CFTR mice. The data suggest that CFTR is not a physiologically important mediator of volume natriuresis.

Anesthesia↗
PubMed2001

A note on hair whorl position and cattle temperament in the auction ring.

The objective of this study was to further describe the relationships between facial hair whorls and temperament in cattle. Cattle (n=1636) from six commercial cattle auctions in Colorado and Texas were observed. Whorl location was classified according to lateral position (left, right, or middle) and height (high: above the top of the eye, middle: at eye level, low: below the bottom of the eye). A 4-point temperament score was used to rate each animal while it was in the auction ring. Cattle with a score of 1 remained calm and stood still or walked around, and those with a score of 4 were highly agitated and hit the ring fence, walls, partitions, or people with its head. The cattle observed were 75% Bos taurus beef breeds, 21% Holstein dairy cattle, 3% Bos indicus beef breeds, and 1% non-Holstein dairy breeds. Ten percent of cattle surveyed had no facial hair whorl, while 86% had a single spiral hair whorl, of which 47% had middle-middle whorl placement. Animals with a high whorl position or no hair whorl had higher temperament scores (P=0.01). Cattle with low whorls were more likely to have greater lateral displacement of whorls off of the centerline than cattle with high or middle whorls (P<0.01). Abnormally shaped whorls were more common on cattle with low whorls (P<0.01) and on cattle with lateral whorls located off of the centerline (P<0.01). Cattle with hair whorls on the centerline had more variable temperament scores (P=0.04). Beef cattle had more abnormal whorls than Holsteins (P<0.01). Temperament scores showed that Holsteins were calmer than beef cattle (P<0.01). Facial hair whorls in cattle may be a useful management tool in assessing which animals may become disturbed in novel environments.

Journal Article↗
PubMed2001

Analysis of mutations at residues A2451 and G2447 of 23S rRNA in the peptidyltransferase active site of the 50S ribosomal subunit.

On the basis of the recent atomic-resolution x-ray structure of the 50S ribosomal subunit, residues A2451 and G2447 of 23S rRNA were proposed to participate directly in ribosome-catalyzed peptide bond formation. We have examined the peptidyltransferase and protein synthesis activities of ribosomes carrying mutations at these nucleotides. In Escherichia coli, pure mutant ribosome populations carrying either the G2447A or G2447C mutations maintained cell viability. In vitro, the G2447A ribosomes supported protein synthesis at a rate comparable to that of wild-type ribosomes. In single-turnover peptidyltransferase assays, G2447A ribosomes were shown to have essentially unimpaired peptidyltransferase activity at saturating substrate concentrations. All three base changes at the universally conserved A2451 conferred a dominant lethal phenotype when expressed in E. coli. Nonetheless, significant amounts of 2451 mutant ribosomes accumulated in polysomes, and all three 2451 mutations stimulated frameshifting and readthrough of stop codons in vivo. Furthermore, ribosomes carrying the A2451U transversion synthesized full-length beta-lactamase chains in vitro. Pure mutant ribosome populations with changes at A2451 were generated by reconstituting Bacillus stearothermophilus 50S subunits from in vitro transcribed 23S rRNA. In single-turnover peptidyltransferase assays, the rate of peptide bond formation was diminished 3- to 14-fold by these mutations. Peptidyltransferase activity and in vitro beta-lactamase synthesis by ribosomes with mutations at A2451 or G2447 were highly resistant to chloramphenicol. The significant levels of peptidyltransferase activity of ribosomes with mutations at A2451 and G2447 need to be reconciled with the roles proposed for these residues in catalysis.

Binding Sites↗
PubMed2001

Renal proximal tubule function is preserved in Cftr(tm2cam) deltaF508 cystic fibrosis mice.

1. Changes in proximal tubule function have been reported in cystic fibrosis patients. The aim of this study was to investigate proximal tubule function in the Cftr(tm2cam)deltaF508 cystic fibrosis (CF) mouse model. A range of techniques were used including renal clearance studies, in situ microperfusion, RT-PCR and whole-cell patch clamping. 2. Renal Na(+) clearance was similar in wild-type (1.4 +/- 0.3 microl min(-1), number of animals, N = 12) and CF mice (1.6 +/- 0.4 microl min(-1), N = 7) under control conditions. Acute extracellular volume expansion resulted in significant natriuresis in wild-type (7.0 +/- 0.8 microl min(-1), N = 8) and CF mice (9.3 +/- 1.4 microl min(-1), N = 9); no difference between genotypes was observed. 3. In situ microperfusion revealed that fluid absorptive rate (Jv) was similar under control conditions between wild-type (2.2 +/- 0.4 nl mm(-1) min(-1), n = 10) and CF mice (1.9 +/- 0.3 nl mm(-1) min(-1), n = 11). Addition of a forskolin-dibutyryl cAMP (db-cAMP) cocktail to the perfusate caused no significant change in Jv in either wild-type (2.6 +/- 0.7 nl mm(-1) min(-1), n = 10) or Cftr(tm2cam)deltaF508 mice (2.0 +/- 0.5 nl mm(-1) min(-1), n = 10). 4. CFTR expression was confirmed in samples of outer cortex using RT-PCR. However, no evidence for functional CFTR was obtained when outer cortical cells were stimulated with protein kinase A or forskolin-db-cAMP using whole-cell patch clamping. 5. In conclusion, no functional deficit in proximal tubule function was found in Cftr(tm2cam)deltaF508 mice. This may be a consequence of a lack of whole-cell cAMP-dependent Cl(-) conductance in mouse proximal tubule cells.

Animals↗
PubMed2001

Genetic remodeling of protein glycosylation in vivo induces autoimmune disease.

Autoimmune diseases are among the most prevalent of afflictions, yet the genetic factors responsible are largely undefined. Protein glycosylation in the Golgi apparatus produces structural variation at the cell surface and contributes to immune self-recognition. Altered protein glycosylation and antibodies that recognize endogenous glycans have been associated with various autoimmune syndromes, with the possibility that such abnormalities may reflect genetic defects in glycan formation. We show that mutation of a single gene, encoding alpha-mannosidase II, which regulates the hybrid to complex branching pattern of extracellular asparagine (N)-linked oligosaccharide chains (N-glycans), results in a systemic autoimmune disease similar to human systemic lupus erythematosus. alpha-Mannosidase II-deficient autoimmune disease is due to an incomplete overlap of two conjoined pathways in complex-type N-glycan production. Lymphocyte development, abundance, and activation parameters are normal; however, serum immunoglobulins are increased and kidney function progressively falters as a disorder consistent with lupus nephritis develops. Autoantibody reactivity and circulating immune complexes are induced, and anti-nuclear antibodies exhibit reactivity toward histone, Sm antigen, and DNA. These findings reveal a genetic cause of autoimmune disease provoked by a defect in the pathway of protein N-glycosylation.

Animals↗
PubMed2001

(Serious) sadomasochism: a protected right of privacy?

Several adult male members of a sadomasochistic sex club were arrested for violating a U.K. statute passed in 1861--The Offences Against the Person Act. The sex acts spanned a 10-year period and were videotaped. They involved manipulation of the genitalia with hot wax, sand paper, fish hooks, and needles. The sexual interactions were consensual. This analysis tracks the case from trial, to the Court of Appeal, to the House of Lords, and on to the European Court of Human Rights. It examines whether or not these sexual behaviors should be protected under a right to privacy. It contrasts state concerns of bodily harm, albeit consented to, in sex with those incurred in sport.

Boxing↗
PubMed2001

Hand preference, sexual preference, and transsexualism.

Atypical handedness patterns, i.e., persons being less exclusively right-handed, have been found previously in large samples of male and female homosexuals and in small samples of male and female transsexuals compared to controls. The posited role of prenatal androgen influencing both cerebral hemispheric dominance and psychosexual development warrants further study with large samples of transsexuals. 443 male-to-female transsexuals and 93 female-to-male transsexuals were studied for their use of the right or left hand in six common one-handed tasks. Both male and female transsexuals were more often nonright-handed than male and female controls were. Results suggest an altered pattern of cerebral hemispheric organisation in male and female transsexuals.

Brain↗
PubMed2001

Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1.

The C-terminal BRCT region of BRCA1 is essential for its DNA repair, transcriptional regulation and tumor suppressor functions. Here we determine the crystal structure of the BRCT domain of human BRCA1 at 2.5 A resolution. The domain contains two BRCT repeats that adopt similar structures and are packed together in a head-to-tail arrangement. Cancer-causing missense mutations occur at the interface between the two repeats and destabilize the structure. The manner by which the two BRCT repeats interact in BRCA1 may represent a general mode of interaction between homologous domains within proteins that interact to regulate the cellular response to DNA damage. The structure provides a basis to predict the structural consequences of uncharacterized BRCA1 mutations.

Amino Acid Sequence↗
PubMed2001

High prevalence of low serum vitamin B12 in a multi-ethnic Israeli population.

This study ascertained serum vitamin B12 levels among patients with Gaucher disease and among healthy Israelis. Serum B12 and metabolites' levels were studied in consecutive adult patients with Gaucher disease not treated with enzyme plus Ashkenazi Jewish neighbour-controls, together with healthy blood-donor volunteers of various ethnicities. Each group showed a high incidence of low serum B12 concentrations, with a 22.3% incidence among Ashkenazi Jews and 40% among patients with Gaucher disease. These findings raise questions on the individual and community levels of serum B12. We recommend evaluation of B12 levels among geographically contingent peoples.

Adult↗
PubMed2001

An update of the Zenith endovascular graft for abdominal aortic aneurysms: initial implantation and mid-term follow-up data.

PURPOSE: To evaluate the initial and mid-term results of the Zenith endovascular grafting system for infrarenal abdominal aortic aneurysms. METHODS: Prospective databases at seven centers were used to assess a cohort of patients that underwent treatment for aortic, aortoiliac, or iliac aneurysms since 1995. Data were analyzed to yield descriptive characteristics that pertained to the patients, the aortic morphologic features, the graft configuration, and the complications. Follow-up imaging data were used to determine size changes of the aneurysm sac, endoleak rates, and further complications. Finally survival data were expressed with a Kaplan-Meier analysis. RESULTS: A total of 528 patients were treated with the Zenith endograft. Most of the patients (66%) were considered to be at a high physiologic risk for open repair. Successful graft implantation was accomplished in all but four patients. An overall endoleak rate of 15% was noted, of which 4% was treated urgently because they were thought to represent attachment site faults. The mean follow-up period was 18 months. A total of eight endograft migrations were detected after 2 years of follow-up with an early version of the system. There were three late conversions; two ruptures occurred during the follow-up period. CONCLUSION: This early and mid-term data support the use of the Zenith endovascular graft for the treatment of aortic and aortoiliac aneurysms in properly selected patients. The risks of significant complications or aneurysm rupture are low.

Angioplasty↗
PubMed2001

Eumovate (clobetasone butyrate) 0.05% cream with its moisturizing emollient base has better healing properties than hydrocortisone 1% cream: a study in nickel-induced contact dermatitis.

BACKGROUND: The emollient base of a topical corticosteroid, through its moisturizing properties, can be a useful treatment adjunct. OBJECTIVE: To compare the healing properties of Eumovate trade mark (clobetasone butyrate) 0.05% cream with its emollient base, hydrocortisone 1% cream and with no treatment. METHODS: A single-centre, double-blind, intra-individual, comparative study that involved 18 volunteers with nickel-induced contact dermatitis. Following a positive patch test to nickel, sub-therapeutic amounts (10 micro l = 3 mg cm(-2)) of each of the treatments were applied twice daily for seven days to each of the four test sites. RESULTS: In terms of the primary endpoint, a physician's global assessment after 7 days of treatment, clobetasone butyrate (CB) 0.05% cream showed a significantly better response than hydrocortisone (HC) 1% cream (78% vs 39%, difference -0.4, 95% CI -0.7 to -0.1; p = 0.046) or no treatment (78% vs 28%, difference -0.5, 95% CI -0.9 to -0.1; p = 0.016). CB 0.05% cream also showed a better response than its emollient base (78% vs 56%), though statistical significance was not achieved. In terms of moisturizing effects, there was no difference in transepidermal water loss (TEWL) between CB 0.05% cream and its emollient base. CB 0.05% cream treated sites did, however, have significantly lower values (i.e. were more moisturized) than untreated sites (difference -8.5, 95% CI -12.0 to -4.86; p < 0.001) or HC 1% treated sites (difference -7.1, 95% CI -11.0 to -3.4; p < 0.001). In terms of skin blanching activity, as expected the steroid-based creams achieved lower colorimetric values than the emollient base cream. CONCLUSIONS: These results from experimentally induced skin inflammation indicate that CB 0.05% (as Eumovate 0.05% cream) has both more effective anti-inflammatory activity and better moisturizing properties than hydrocortisone 1% cream and that these effects are in part due to its efficient emollient base.

Administration, Cutaneous↗
PubMed2001

How long after drug ingestion is activated charcoal still effective?

OBJECTIVE: The recent American Academy of Clinical Toxicology/European Association of Poisons Centres and Clinical Toxicologists position statement on activated charcoal stated "there are insufficient data to support or exclude its use after 1 hour of ingestion.'' The purpose of this study was to determine the effectiveness of activated charcoal administered 1, 2, and 3 hours after drug ingestion. METHODS: This was a human volunteer, randomized crossover study. Ten volunteers ingested 4 g of acetaminophen on four occasions at least 1 week apart. One ingestion served as a control and the other three as experimental ingestions with charcoal being administered at 1, 2, and 3 hours after acetaminophen dosing. Eight blood specimens were obtained over the initial 8 hours for serum acetaminophen concentrations that were used for calculation of routine pharmacokinetic parameters. Repeated measures of ANOVA and Tukey's HSD test were used for statistical analysis. RESULTS: Pharmacokinetic parameters for acetaminophen in our volunteers were consistent with literature values. The mean area under the curve (AUC+/-SD) for the control and the 1-, 2-, and 3-hour groups were 221 +/- 54, 154 +/- 71, 206 +/- 67 and 204 +/- 58 mg/L/h, respectively. The 1-hour group was the only one differing from control (p < 0.01). The decrease of bioavailability at 1 hour was 30.3%, which is similar to previous studies. CONCLUSION: Our data do not support the administration of activated charcoal as a gastrointestinal decontamination strategy beyond 1 hour after drug overdose.

Acetaminophen↗
PubMed2001

Second-hand smoke at work: the exposure, perceptions and attitudes of bar and restaurant workers to environmental tobacco smoke.

OBJECTIVES: To investigate the knowledge of, and perceptions, attitudes and exposure to second-hand smoke (SHS) of staff in the New Zealand hospitality industry. METHOD: Face-to-face interviews with bar staff, waiters, and bar and eating-place managers and owners in Wellington during the 1999-2000 summer. An analysis was made of the 1999 New Zealand Electoral Roll to find the number of those most exposed to SHS. RESULTS: 435 interviews with full data recovery were completed at 364 locations; 59% of interviewees were exposed to SHS, including 77% of those at licensed premises. More than half of those exposed to workplace smoke reported irritation from SHS to their throat or lungs. Less than a third were aware of the risk of strokes from SHS. Three-quarters of interviewees wanted some sort of smoking restriction in bars. CONCLUSIONS: The majority of interviewees were at risk of premature death and disease because of exposure to workplace smoke, and had an incomplete knowledge of the dangers to which they were exposed. More than 5,000 similar workers in New Zealand appear to share this risk. IMPLICATIONS: This industry needs legislation to make it smoke free.

Adolescent↗
PubMed2001

Cellular localization of divalent metal transporter DMT-1 in rat kidney.

We have demonstrated that the kidney plays an important role in iron balance and that metabolically significant reabsorption of this ion occurs in the loop of Henle and the collecting ducts [Wareing M, Ferguson CJ, Green R, Riccardi D, and Smith CP. J Physiol (Lond) 524: 581-586, 2000]. To test the possibility that the divalent metal transporter DMT1 (Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, and Hediger MA. Nature 388: 482-488, 1997) could represent the apical route for iron entry in the kidney, we raised and affinity-purified an anti-DMT-1 polyclonal antibody and determined DMT-1 distribution in rat kidney by Western analysis, immunofluorescence, and confocal microscopy. The strongest DMT1-specific (i.e., peptide-protectable) immunoreactivity was found in the collecting ducts, in both principal and intercalated cells. Thick ascending limbs of Henle's loop and, more intensely, distal convoluted tubules exhibited apical immunostaining. Considerable intracellular DMT-1 immunoreactivity was seen throughout the nephron, particularly in S3 segments. The described distribution of DMT-1 protein is in agreement with our previous identification of nephron sites of iron reabsorption, suggesting that DMT-1 provides the molecular mechanism for apical iron entry in the distal nephron but not in the proximal tubule. Basolateral iron exit may be facilitated by a different system.

Animals↗