Biomedical subjects

Roy Sherwood

Publications and source records attributed to Roy Sherwood.

7 recordsLinked to original sources

PubMed2006

Prevalence and mechanism of nonsteroidal anti-inflammatory drug-induced clinical relapse in patients with inflammatory bowel disease.

BACKGROUND & AIMS: It has been variably suggested that nonselective NSAIDs and cyclooxygenase (COX)-2 selective inhibitors aggravate or ameliorate clinical disease activity in patients with inflammatory bowel disease. We assessed the effect of these drugs in patients with inflammatory bowel disease (n = 209) and the possible mechanisms. METHODS: First, patients with quiescent Crohn's disease and ulcerative colitis received the non-NSAID analgesic acetaminophen (n = 26) and the conventional NSAIDs naproxen (n = 32), diclofenac (n = 29), and indomethacin (n = 22) for 4 weeks. The Harvey-Bradshaw index was used to define relapse. Second, to assess the mechanism of relapse, intestinal inflammation was quantitated (fecal calprotectin) before and during treatment (20 patients/group) with acetaminophen, naproxen (topical effect, COX-1 and -2 inhibitor), nabumetone (COX-1 and -2 inhibitor), nimesulide (selective COX-2 inhibitor), and low-dose aspirin (selective COX-1 inhibition). RESULTS: Nonselective NSAIDs were associated with a 17%-28% relapse rate within 9 days of ingestion. No patient had an early relapse on acetaminophen, nimesulide, or aspirin, whereas those on naproxen and nabumetone (20%) experienced relapse. These clinical relapses were associated with escalating intestinal inflammatory activity. CONCLUSIONS: NSAID ingestion is associated with frequent and early clinical relapse of quiescent inflammatory bowel disease, and the mechanism appears to be due to dual inhibition of the COX enzymes. Selective COX-2 inhibition with nimesulide and COX-1 inhibition with low-dose aspirin appear to be well-tolerated in the short-term.

Acetaminophen↗

PubMed2006

Rapid elimination of protein S-100B from serum after minor head trauma.

Protein S-100B is released into the circulation after traumatic brain injury, and its serum concentration relates to measures of injury severity and outcome. These properties have led to interest in its development as a marker for clinical use, particularly in the prediction of adverse outcome for those with apparently trivial injuries. Before it can be used in populations of patients with head injuries, however, more needs to be understood about its release and elimination. This study was designed to estimate the elimination half-life of S-100B from the circulation after minor head trauma. We studied 14 patients with minor head injuries and measured serum S-100B serially after initial assessment in the Emergency Department of an inner city teaching hospital. We used curve-fit analysis to estimate the elimination constant that best fitted our data, and from this estimated the elimination half-life of protein S-100B. We estimated the mean half-life in this setting to be 97 min (95% confidence interval [CI] of 75-136 min). S-100B is cleared rapidly, relative to the time elapsed between injury and initial assessment in the Emergency Department. Variation in the time elapsed between injury and sampling is likely to influence the accuracy of head injury outcome prediction based on S-100B concentrations in serum, and should be considered when designing future studies.

Adult↗

PubMed2003

Maternal electrolyte and liver function changes during pregnancy at high altitude.

BACKGROUND: High-altitude (HA) hypoxia leads to profound cardiovascular, respiratory and electrolyte changes, and pregnancy at HA has been associated with increased incidence of preeclampsia and intrauterine growth restriction. OBJECTIVE: To examine the effect of high altitude on maternal serum electrolytes and liver enzymes. DESIGN: Cross-sectional study of 77 pregnant women at 6-40 weeks of gestation resident at HA (4370 m above sea level) and 80 at sea level (SL) and 13 and 15 nonpregnant women at each altitude, respectively. Serum electrolytes (sodium, potassium, calcium and phosphate), creatinine, bilirubin and liver enzymes (alkaline phosphatase (ALP), aspartate transaminase (AST) and gamma-glutamyl transferase (gamma-GT)) were measured. RESULTS: Pregnancy at HA, compared to SL, was associated with higher serum osmolality (0.4%), sodium (0.7%), creatinine (14%) and phosphate (5%) concentrations and lower potassium (10%) concentration. Calcium and albumin-corrected calcium concentrations were higher at HA compared to SL in nonpregnant women (8%), with no difference in pregnant women. AST, gamma-GT and ALP concentrations were not significantly different between HA and SL, neither in pregnant nor in nonpregnant women. AST and gamma-GT were lower in pregnant compared to nonpregnant women (30%) at HA, whereas the difference was not significant at SL. Total bilirubin concentrations were higher at HA compared to SL by about 25% both in pregnant and in nonpregnant women, the difference reaching statistical significance only in the pregnant group. CONCLUSIONS: Pregnancy at HA is associated with increased osmolality, sodium, creatinine, calcium, phosphate and total bilirubin concentrations. Liver enzyme activities are similar to SL.

Adult↗

PubMed2003

Subclinical intestinal inflammation: an inherited abnormality in Crohn's disease relatives?

BACKGROUND & AIMS: One approach to unraveling the genetics of complex inherited disease, such as Crohn's disease, is to search for subclinical disease markers among unaffected family members. We assessed the possible presence, prevalence, and inheritance pattern of subclinical intestinal inflammation in apparently healthy relatives of patients with Crohn's disease. METHODS: A total of 49 patients with Crohn's disease, 16 spouses, and 151 (58%) of 260 available first-degree relatives underwent a test for intestinal inflammation (fecal calprotectin concentration). The mode of inheritance was assessed from 36 index patients (by variance component analysis) when more than 50% of relatives were studied. RESULTS: Fecal calprotectin concentrations in patients with Crohn's disease (47 mg/L; confidence interval [CI], 27-95 mg/L) and relatives (11 mg/L; CI, 9-14 mg/L) differed significantly (P < 0.0001) from controls (4 mg/L; CI, 3-5 mg/L), whereas that of the spouses did not (4 mg/L; CI, 3-6 mg/L; P > 0.5). Fecal calprotectin concentration was increased in 49% of all relatives studied. The increased fecal calprotectin concentration among the relatives of the 36 index patients had an inheritance pattern that was most consistent with an additive inheritance pattern. CONCLUSIONS: There is a high prevalence of subclinical intestinal inflammation in first-degree relatives of patients with Crohn's disease that conforms best to an additive inheritance pattern. The genetic basis for this abnormality may represent a risk factor for Crohn's disease.

Adult↗

PubMed2003

Heterocellular hereditary persistence of fetal haemoglobin affects the haematological parameters of beta-thalassaemia trait.

To assess and define the effects of heterocellular hereditary persistence of fetal haemoglobin (HPFH) on the haematological phenotype of heterozygous beta-thalassaemia, we have studied a large kindred that included a total of 204 subjects with 60 beta-thalassaemia carriers, of whom 35 were also heterozygous, and five homozygous, for heterocellular HPFH. The study was possible because of the homogeneity of the beta-thalassaemia mutation and the ability to genotype the heterocellular HPFH allele. Heterocellular HPFH had a significant effect on the mean corpuscular haemoglobin (MCH), mean corpuscular volume (MCV) and haemoglobin (Hb) A2 values in the beta-thalassaemia carriers and accounted for 29%, 30% and 24% of their respective variances. beta-thalassaemia subjects with heterocellular HPFH had higher MCV and MCH values, concomitant with lower levels of Hb A2, and a reduced ineffective erythropoiesis. We conclude that co-inheritance of heterocellular HPFH leads to a primary increase in gamma-chain synthesis in beta-thalassaemia trait and can be another confounding factor in the use of red cell indices and Hb A2 levels in population screening for beta-thalassaemia.

Adolescent↗

PubMed2003

Subclinical intestinal inflammation and sacroiliac changes in relatives of patients with ankylosing spondylitis.

BACKGROUND & AIMS: It has been suggested that subclinical intestinal inflammation plays a pathogenic role in the spondylarthropathy of ankylosing spondylitis (AS). We assessed the possible presence and inheritance pattern of subclinical intestinal inflammation in first-degree relatives of patients with AS. The relationship between this inflammation and the subjects' HLA-B27 genotype as well as computerized tomographic sacroiliac abnormalities was also assessed. METHODS: A total of 124 of 213 (58%) available first-degree relatives of 47 patients with AS in Iceland underwent investigation for intestinal inflammation (fecal calprotectin concentration), HLA-B27 genotyping, and computerized tomography of the sacroiliac joints. RESULTS: A total of 41% of the first-degree relatives had subclinical intestinal inflammation, whereas 15 of 17 spouses were normal. Variance components analyses suggest that the inheritance pattern of this inflammation is affected by a major additive gene. Some sacroiliac changes, suggestive of early AS, differed significantly between subjects with and without subclinical intestinal inflammation (mean diameter of subchondral cysts [2.9 vs. 1.2 mm; P = 0.026] and blurring of joint margins [9 of 44 (20%) vs. 1 of 41 (2%); P = 0.02]). Intestinal inflammation and sacroiliac changes did not relate to the subjects' HLA-B27 status. CONCLUSIONS: Many first-degree relatives of patients with AS appear to have an inherited abnormality that leads to subclinical intestinal inflammation. The association between the presence of this inflammation and the sacroiliac changes suggests that it may play a pathogenic role in the spondylarthropathy of AS.

Adult↗

PubMed2002

Plasma homocysteine and cognitive impairment in an older British African-Caribbean population.

OBJECTIVES: To investigate the association between homocysteine concentrations and cognitive impairment in an older African-Caribbean population. To investigate other measures of risk for vascular disease and nutritional status as potential confounding factors. DESIGN: A secondary analysis from a cross-sectional community study. SETTING: The sample was drawn from registration lists for seven primary care services in south London, United Kingdom. PARTICIPANTS: Two hundred forty-eight individuals aged 55 to 75 who were born in a Caribbean nation and for whom homocysteine concentrations had been ascertained. MEASUREMENTS: Plasma homocysteine and serum folate were assayed from frozen samples. Cognitive impairment as a composite measure was derived from 11 psychometric tests. Other measures of risk for vascular disease were considered as potential confounding factors: diagnosed hypertension/diabetes mellitus; physical exercise; and concentrations of cholesterol, triglycerides, and fibrinogen. RESULTS: Cognitive impairment was classified in 68 (27%) participants. Raised homocysteine (highest quartile: >13.85 micromol/L) was significantly associated with cognitive impairment (odds ratio (OR)=2.50, 95% confidence interval (CI)=1.33-4.69). This association persisted after adjustment for age, occupation, other measures of vascular risk, folate, body mass index, and waist:hip ratio (OR=3.00, 95% CI=1.35-6.69). As with other risk factors for vascular disease in this sample, the association was significant only in those with less education (P-value for interaction=.049). CONCLUSION: Raised homocysteine was associated with cognitive impairment in this sample, but this was modified by previous educational attainment. This association was independent of other measures of vascular risk and was not explained by folate concentrations.

Black or African American↗