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Biomedical subjects

A Rowland

Publications and source records attributed to A Rowland.

At least 19 recordsLinked to original sources
PubMed2005

Pantoprazole in severe acid-peptic disease: the effectiveness and safety of 5 years' continuous treatment.

OBJECTIVE: This is our final report on the clinical effectiveness and safety of long-term pantoprazole in patients with severe peptic ulcer or reflux disease during continuous treatment for up to 5 years. METHODS: Patients (n= 150) with peptic ulcer or reflux erosive oesophagitis running an aggressive course or with complications, and refractory to H2-receptor antagonists, were entered into this 5-year programme. Assessment was by serial endoscopy, clinical examination, serum gastrin estimation, gastric mucosal histology and mucosal endocrine cell quantification. RESULTS: Healing results were presented earlier. The estimated rates of remission on maintenance treatment with pantoprazole (n = 115) were 82% at 1 year, 75% at 2 years, 72% at 3 years, 70% at 4 years and 68% at 5 years. Helicobacter pylori infection appeared not to influence the outcome in reflux patients, with roughly two-thirds continuing in remission irrespective of infection. Only four patients had adverse events considered to be definitely related to pantoprazole. Median gastrin levels rose by 1.5-2-fold and were higher in those with H. pylori infection; 13 patients had levels >500 ng/L on at least one occasion, but these high levels were not sustained. Histological changes were more marked in patients infected with H. pylori: chronic gastritis decreased in the antrum and increased in the corpus, which also showed atrophic changes. The total number of endocrine cells in the antrum showed little variation over 60 months but fell by around one-third in the corpus. CONCLUSION: Long-term treatment with pantoprazole is effective and safe.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Ranitidine bismuth citrate with clarithromycin alone or with metronidazole for the eradication of Helicobacter pylori.

BACKGROUND: Both triple therapy with ranitidine bismuth citrate (RBC) plus two antibiotics for 7 days and dual therapy of RBC with clarithromycin for 14 days have been extensively studied; both regimens effectively eradicate Helicobacter pylori. However, few studies have assessed the efficacy of dual therapy given for 7 days. AIM: To compare the efficacy and safety of RBC 400 mg with clarithromycin 500 mg, alone or with metronidazole 400 mg, given twice daily for 7 days for the eradication of H. pylori. METHODS: This single centre, randomized, double-blind study involved 118 patients with dyspepsia or a history of peptic ulcer disease. H. pylori infection was detected initially by CLO test, and confirmed in 109 patients by urea breath test and/or microbiology culture. H. pylori eradication was assessed 4 and 12 weeks after the end of treatment by urea breath test. H. pylori antibiotic susceptibility was assessed pre-study in all patients, and post-treatment in patients with a positive post-treatment urea breath test. Adverse events were recorded throughout the study. RESULTS: H. pylori was eradicated in 93% of patients who received RBC with clarithromycin and metronidazole and in 84% of patients who received RBC with clarithromycin (intention-to-treat rates). Per protocol eradication rates were 98% and 90% for triple therapy and dual therapy, respectively. The eradication of metronidazole-resistant H. pylori was achieved in 100% and 88% of patients following dual therapy and triple therapy, respectively, and acquired resistance to clarithromycin occurred in only one patient following treatment failure. Both treatments were well-tolerated; only one patient (2%) was withdrawn from each treatment group due to adverse events. CONCLUSIONS: RBC with clarithromycin and metronidazole is a highly effective and well-tolerated triple therapy regimen for the eradication of H. pylori. RBC with clarithromycin dual therapy has a similar efficacy, and offers an alternative to triple therapy when there are concerns about treatment with metronidazole or the use of multiple antibiotics. Both regimens are effective against antibiotic-resistant strains of H. pylori.

Adult↗
PubMed2001

Pantoprazole therapy in the long-term management of severe acid peptic disease: clinical efficacy, safety, serum gastrin, gastric histology, and endocrine cell studies.

OBJECTIVE: Pantoprazole is the third proton pump inhibitor to become available. When this study was started, there were few data on its long-term use. Our aim was to investigate this aspect and, because powerful inhibitors of acid secretion can cause hypergastrinemia and, in experimental animals, enterochromaffin-like cell hyperplasia, we also monitored serum gastrin and endocrine cell histology. METHODS: One hundred fifty patients refractory to H2-receptor antagonists, running an aggressive course or with complications, were entered into a 5-yr treatment program. We performed serial endoscopy, checked for adverse events, and laboratory values. We also monitored serum gastrin, gastric endocrine cell histology, and antral and corpus gastritis. RESULTS: This report presents results from up to 3 yr of treatment. Cumulative healing on 40-80 mg of pantoprazole was 82% at 4 wk and 92% by 12 wk. Most patients became asymptomatic within 4 wk. Remission on maintenance treatment with 40 mg (n = 111) was 85% at 12 months and 78% at 24 months. Treatment was safe; only four patients had adverse events definitely related to pantoprazole. Elevations in gastrin were modest and there were no significant changes in gastric endocrine cells. The number of enterochromaffin-like cells tended to decrease. CONCLUSION: Pantoprazole is effective, safe, and does not seem to be associated with large increases in serum gastrin or alterations in gastric endocrine cells.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Reliability of reporting on lifestyle and agricultural factors by a sample of participants in the agricultural health study from iowa.

PURPOSE: Information on agricultural practices has been obtained by questionnaire in several epidemiologic investigations. This project evaluated the reliability of self-reported information on pesticide use and various demographic and lifestyle factors among a group of farmers from Iowa.METHODS: 2,921 Iowa farmers participating in the Agricultural Health Study completed enrollment questionnaires approximately one year apart. Responses on the two questionnaires were compared for percent agreement and by Kappa statistics to evaluate reliability.RESULTS: Percent agreement for ever/never use of specific pesticides and application practices was quite high and generally ranged from 70% to over 90% and did not vary by age or educational level. Kappas were typically in the 0.50 to 0.60 range. Agreement was lower (typically 50% to 60%) for duration or frequency of use of specific pesticides. Agreement on lifestyle and non-agricultural factors was comparable to that reported in other studies.CONCLUSIONS: Level of agreement regarding pesticide use in this population is similar to that found for diet, physical activity, and medical conditions, which have been successfully evaluated in many epidemiologic studies. Information on agricultural practices from self-completed questionnaires has sufficient reliability for use in epidemiologic investigations.

Journal Article↗
PubMed2000

Allogeneic blood and bone-marrow stem-cell transplantation in haematological malignant diseases: a randomised trial.

BACKGROUND: Autologous transplantation with peripheral blood stem cells (PBSC) results in faster haematopoietic-cell repopulation than with bone marrow. We prospectively compared bone marrow and PBSC for allogeneic transplantation. METHODS: Adult HLA-identical sibling donors provided bone marrow and lenograstim-mobilised PBSC. 39 patients with malignant haematological disorders were infused with either bone marrow (n=19) or PBSC (n=20) after standard conditioning regimens in a double-blind, randomised fashion. The identity of the infused products for all patients remained masked until 1 year after the last patient had received transplantation. FINDINGS: The PBSC group had significantly faster neutrophil recovery to 0.5x10(9)/L (median 17.5 vs 23 days, p=0.002), and platelet recovery to 20x10(9)/L (median 11 vs 18 days, p<0.0001) and to 50x10(9)/L (median 20.5 vs 27 days, p=0.02) than the bone-marrow group. PBSC patients were discharged from hospital earlier than were bone-marrow patients (median 26 vs 31 days, p=0.01). At 4 weeks after transplantation, absolute lymphocytes (0.48 vs 0.63, p=0.08) and CD25 cells (0.04 vs 0.08, p=0.007) were higher in the PBSC group, and the proportion of patients with absolute lymphopenia (74% vs 33%, p=0.03) and CD4 lymphopenia (59% vs 24%, p=0.05) was significantly higher in the bone-marrow group. There was no significant difference in the occurrence of acute or chronic graft-versus-host disease and overall survival. The probability of relapse was significantly higher in the bone-marrow group than in the PBSC group (p=0.01); all five relapses occurred among bone-marrow recipients. INTERPRETATION: Our small study indicates that PBSCs are better than bone marrow for allogeneic transplantation from HLA-identical siblings in terms of faster haematopoietic and immune recovery, and have the potential to reduce disease recurrence.

Adult↗
PubMed2000

A model for predicting the frequency of high pesticide exposure events in the Agricultural Health Study.

The frequency of self-reported high pesticide exposure events (HPEE) has been recorded in the NCI/EPA/NIEHS Agricultural Health Study (AHS). Fourteen percent (14%) of the enrolled applicators responding reported "an incident or experience while using any pesticide which caused an unusually high exposure." These data show, as expected, that the probability of a report of an HPEE increases with the cumulative number of days of pesticide application reported by the applicator. We have developed a three-parameter model that predicts the risk odds ratio (OR) of an HPEE as a function of the number of days that pesticides are applied. These events are costly in terms of resulting health-care visits, lost time from work, and potential risk for cancer and other chronic diseases. We propose that failure to carefully follow all the pesticide manufacturer's label requirements, inexperience, and random events (i.e., breaking hose) are the three factors responsible for the events observed. Special precautions for new or infrequent users of pesticides are indicated.

Agriculture↗
PubMed2000

Comparison of marrow and blood cell yields from the same donors in a double-blind, randomized study of allogeneic marrow vs blood stem cell transplantation.

Forty healthy adult donors underwent marrow (BM) as well as peripheral blood (PBSC) stem cell collections for their HLA-identical adult siblings with hematologic malignancies. BM was harvested on day 1 (target 3 x 108 nucleated cells/kg, 10 microg/kg lenograstim (glycosylated G-CSF) administered on days 2-6, and a single leukapheresis performed on day 6. The blood volume processed was the higher of 200% donor blood volume or 10 liters. The total nucleated cell (TNC) yields from PBSC were 1.1- to 4.3-fold higher than BM (median 7.0 vs 3.1 x 10(8)/kg, P < 0.0001). Although BM contained a higher proportion of CD34+cells (1.3% vs 0.7%, P < 0. 0001) and a comparable proportion of CD3+ cells (median 29% vs 26%, P = 0.4), the absolute numbers of CD34+ and CD3+ cells and their subsets were several times higher in PBSC. There was a poor correlation between BM and PBSC CD34 and TNC numbers, but a significant correlation between BM and PBSC CD3 numbers. Only five of 40 BM harvests contained >/=2 x 10(6) CD34+ cells/kg compared with 35 of 40 PBSC harvests (P < 0.0001). We conclude that the numbers of progenitor and immunocompetent cells in PBSC are several times higher than in BM. It is possible to collect adequate numbers of progenitor cells from blood after lenograstim stimulation more frequently than from marrow, and donors yielding low quantities of progenitor cells from BM usually deliver better quantities from PBSC. Bone Marrow Transplantation (2000) 25, 501-505.

Adjuvants, Immunologic↗
PubMed2000

A low CD34+ cell dose results in higher mortality and poorer survival after blood or marrow stem cell transplantation from HLA-identical siblings: should 2 x 10(6) CD34+ cells/kg be considered the minimum threshold?

We studied the effect of the CD34+ cell dose on transplant-related mortality (TRM) and survival in 39 patients randomized to receive lenograstim-mobilized PBSCT (n = 20) or BMT (n = 19) from HLA-identical siblings. Both marrow and blood were harvested, and one infused in a double-blind fashion. The median nucleated (7.0 vs 3.2 x 10(8)/kg; P < 0.0001), CD34+ (3.7 vs 1.5 x 10(6)/kg; P = 0.002), CFU-GM (42 vs 19 x 10(4)/kg; P = 0.002), and CD3+ (1.9 vs 0.3 x 10(8)/kg; P < 0.0001) cell doses with PBSCT were higher. Thirteen patients (6 BMT and 7 PBSCT) experienced TRM at 15-733 days (median 57); 10 of 20 receiving <2 x 10(6) CD34+ cells/kg compared with three of 19 receiving > or =2. Eight of 20 patients receiving <2 x 10(6) CD34+ cells/kg are alive compared with 14 of 19 receiving > or =2. In Cox analysis, CD34+ cell dose > or =2 x 10(6)/kg was associated with lower TRM (RR 0.2, P = 0.01), and higher overall (RR 3.7, P = 0.01) and event-free (RR 3.2, P = 0.02) survival. Other cell populations and the source of stem cells did not affect TRM or survival. We conclude that 2 x 10(6) CD34+ cells/kg may be the ideal minimum cell dose for allogeneic transplantation although lower doses do not preclude successful therapy. Since the likelihood of obtaining this threshold CD34+ cell number is significantly greater from blood than marrow, PBSCT may be preferable to marrow for allografts from HLA-identical siblings.

Adolescent↗
PubMed1999

Preparing for inactivity: how insectivorous bats deposit a fat store for hibernation.

During late autumn insectivorous bats must deposit a fat store to cover their energy demands throughout the period of hibernation, yet the density of aerial insects by this time has already declined from its peak in midsummer. Krzanowski (1961) suggested that bats are able to deposit a fat store by manipulating their energy expenditure; specifically by selecting cold roosting locations rather than warm roosts, and depressing their body temperatures during the day roosting period. It was hypothesized that these behavioural changes result in very low daily energy demands, and despite reduced food intake the animals are still able to gain body fat. We made several tests of this hypothesis. First, we explored the thermo-selection behaviour of long-eared bats (Plecotus auritus) in the summer and in the pre-hibernal period. We found that in summer bats preferred temperatures of about 32-35 degrees (about thermoneutral), but in the pre-hibernal period they preferred much colder temperatures of about 10 degrees. Second, using open-flow respirometry we found that in the cold pre-hibernal bats entered torpor for an average of 14 h each day. Compared with bats held at 30 degrees (that did not go torpid), the bats at 7 degrees expended less energy. The extent of saving was sufficient to positively affect their mass balance, despite the fact that bats at lower temperature also had reduced digestive efficiencies. Our findings support the hypothesis that during the pre-hibernal period insectivorous bats manipulate their mass balance primarily by alterations in their energy expenditure, specifically utilizing energy-sparing mechanisms such as torpor.

Adipose Tissue↗
PubMed1995

Target-peptide-induced changes in the structure and dynamics of calmodulin as probed by frequency domain fluorimetry of bound Tb(III).

Tb(III) luminescence is used to probe the conformational change induced in the calcium regulatory protein calmodulin upon binding to a target peptide. The luminescence lifetime for Tb(III) measured by frequency domain fluorimetry increases from 1278 microseconds for the calmodulin complex to 1496 microsecond for the complex of calmodulin and M13, a peptide derived from the calmodulin target protein myosin light chain kinase. The intensity of the Tb(III) emission increases over the solution value by a factor of 726 and 891 when bound to calmodulin and to the complex of calmodulin and M13 respectively. The sensitivity of the Tb(III) decay rate to deuterated solvent was also measured and is consistent with a single water molecule bound to the metal in both the calmodulin and calmodulin-M13 complex. The most dramatic change induced by M13 is the threefold reduction in the width of the Tb(III) lifetime distribution, which is interpreted to be a target-peptide-induced annealing of the previously flexible metal-binding site.

Amino Acid Sequence↗
PubMed1993

Expression of vascular endothelial growth factor does not promote transformation but confers a growth advantage in vivo to Chinese hamster ovary cells.

Vascular endothelial growth factor (VEGF) is a mitogen with a specificity for endothelial cells in vitro and an angiogenic inducer in vivo. We tested the hypothesis that VEGF may confer on expressing cells a growth advantage in vivo. Dihydrofolatereductase--Chinese hamster ovary cells were transfected with expression vectors which direct the constitutive synthesis of VEGF. Neither the expression nor the exogenous administration of VEGF stimulated anchorage-dependent or anchorage-independent growth of Chinese hamster ovary cells in vitro. However, VEGF-expressing clones, unlike control cells, demonstrated an ability to proliferate in nude mice. Histologic examination revealed that the proliferative lesions were compact, well vascularized, and nonedematous. Ultrastructural analysis revealed that capillaries within the lesions were of the continuous type. These findings indicate that the expression of VEGF may confer on cells the ability to grow in vivo in the absence of transformation by purely paracrine mechanisms. Since VEGF is a widely distributed protein, this property may have relevance for a variety of physiological and pathological proliferative processes.

Animals↗
PubMed1993

Breath-holding: helping parents cope.

Breath-holding is relatively rare but can occur in infants as young as six months. Ann Rowland describes some typical episodes and suggests strategies to help parents cope.

Adaptation, Psychological↗
PubMed1991

Aluminium sulphate in water in north Cornwall and outcome of pregnancy.

OBJECTIVE: To determine whether the excess aluminum sulphate accidentally added to the local water supply in north Cornwall in July 1988 had an adverse effect on the outcome of pregnancies. DESIGN: Outcomes of all singleton pregnancies in the affected area at the time of the incident (n = 92) were compared with those in two control groups: pregnancies in this area completed before the incident (n = 68) and pregnancies in a neighbouring area (n = 193). SUBJECTS: Mothers in the three groups, among whom there were 13 miscarriages, five terminations of pregnancy, and 336 live births. MAIN OUTCOME MEASURES: Fetal and perinatal loss, birth weight, gestation, obstetric complications, neonatal condition, and congenital defects. RESULTS: Among 88 pregnancies in women exposed to excess aluminum sulphate there was no excess of perinatal deaths (n = 0), low birthweight (n = 3), preterm delivery (n = 4), or severe congenital malformations (n = 0). There was, however, an increased rate of talipes in exposed fetuses (four cases, one control; p = 0.01). CONCLUSIONS: Because of small numbers it is not possible to say that high doses of aluminum sulphate are safe in pregnancy, but there is no evidence from this study of major problems apparent at birth.

Abnormalities, Drug-Induced↗
PubMed1990

Water contamination in North Cornwall: a retrospective cohort study into the acute and short-term effects of the aluminum sulphate incident in July 1988.

IN JULY 1988 the drinking water supply of part of Cornwall was contaminated with 20 tons of aluminum sulphate solution. Emergency measures ensured that aluminum sulphate levels in most parts of the water distribution system were rapidly reduced, but residents were supplied with water containing raised concentrations of aluminum and other metals for at least a few days. A retrospective cohort study compared 480 individuals in the exposed area with 532 individuals resident in an area served by a different water supply. The exposed group were more likely to complain of all 18 symptoms in the questionnaire enquiry. They had a significantly higher relative risk of experiencing painful joints. These symptoms were reported by less than a quarter of the respondents exposed to contaminated water. This may represent a previously unrecognised acute effect of water contamination with aluminum sulphate, but the study does not exclude the possibility that the threshold for symptom reporting was lowered by anxiety and by the publicity associated with the incident. The overall response rate of the study was low (45%) and reflects the difficulties in both carrying out and interpreting environmental epidemiological studies of acute incidents.

Accidents, Occupational↗
PubMed1989

Expression and secretion of gro/MGSA by stimulated human endothelial cells.

Melanoma growth stimulatory activity factor (MGSA) is a polypeptide which was initially isolated from Hs294 human melanoma cells. Its sequence is identical to the deduced amino acid sequence of the human gro cDNA, isolated from a human tumor cell line. MGSA stimulates the proliferation of malignant melanoma cells, but its function for normal cells has not been defined. Here we report that human umbilical vein endothelial cells are capable of synthesizing and secreting MGSA. The expression and secretion of MGSA are strongly induced by factors often involved in inflammation such as IL-1, TNF, LPS and thrombin. The induction of MGSA mRNA is dose and time dependent and is independent of new protein synthesis. This stimulation could be mimicked by TPA, suggesting that the action could be mediated through activation of protein kinase C. Furthermore, addition of MGSA to the endothelial cell cultures induces gro/MGSA gene expression, implying that an autocrine mechanism exists. Our data suggest that the protein encoded by gro/MGSA mRNA may play a role in inflammation and exert its effects on endothelial cells in an autocrine fashion.

Cells, Cultured↗