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Biomedical subjects

T Lind

Publications and source records attributed to T Lind.

At least 37 records · Page 2Linked to original sources
PubMed1999

Quality of life in patients with heartburn but without esophagitis: effects of treatment with omeprazole.

OBJECTIVE: Because improvement in quality of life (QoL) is an important therapeutic goal in patients with heartburn but without esophagitis, the aim of the present study was to compare the impact of omeprazole 20 mg or 10 mg daily with that of placebo on QoL in patients with heartburn as the predominant symptom. METHODS: QoL was measured at baseline and after 4 wk using two validated questionnaires, the Psychological General Well-Being (PGWB) index and the Gastrointestinal Symptom Rating Scale. RESULTS: The two questionnaires were completed by 163 patients in the omeprazole 20 mg group, 163 in the omeprazole 10 mg group, and 82 in the placebo group. The reflux dimension of the Gastrointestinal Symptom Rating Scale showed a significant improvement in terms of reflux symptoms on omeprazole 20 mg versus omeprazole 10 mg and placebo, and on omeprazole 10 mg compared with placebo. The total score of the PGWB index improved significantly more on both doses of omeprazole than on placebo. The mean scores rose from 96.8 to 103.9 on omeprazole 20 mg, from 98.4 to 106.0 on omeprazole 10 mg, and from 98.0 to 100.6 on placebo. All dimensions of the PGWB index improved on treatment with omeprazole, but the improvements were most pronounced in the dimensions depicting anxiety, depressed mood, and self-control. CONCLUSIONS: It is concluded that treatment with omeprazole 20 mg and omeprazole 10 mg restores QoL to a level comparable with that observed in a healthy population.

Adolescent↗
PubMed1999

Antimicrobial susceptibility testing of Helicobacter pylori in a large multicenter trial: the MACH 2 study.

Culture and susceptibility testing of Helicobacter pylori strains was performed in a large multinational, multicenter randomized clinical trial. Culture was carried out on gastric biopsy samples obtained from 516 patients at entry and had a sensitivity of 99% when the [(13)C]urea breath test was used as a reference. Susceptibility testing was performed for clarithromycin and metronidazole on 485 strains by an agar dilution method and the epsilometer test (Etest) and for amoxicillin by an agar dilution method only. Resistance to clarithromycin (>1 microgram/ml) was found in 3% of the H. pylori strains, with a perfect correlation between Etest and agar dilution methods. Resistance to metronidazole (>8 microliter/ml) was found in 27% of the strains by agar dilution, but there were important discrepancies between it and the Etest method. No resistance to amoxicillin was found. The logarithms of the MICs of the three antibiotics against susceptible strains had a distribution close to normal. The impact of resistance was tested in the four arms of the trial. There were not enough clarithromycin-resistant strains to evaluate the impact of resistance on the cure rate of clarithromycin-based regimens. For metronidazole-resistant strains, the impact noted in the clarithromycin-metronidazole arm was partially overcome when omeprazole was added (76% eradication for resistant strains versus 95% for susceptible strains). Secondary resistance to clarithromycin occurred in strains from 12 of 105 patients (11.4%) after the failure of a clarithromycin-based regimen to effect eradication. The detection of point mutations in clarithromycin-resistant strains was performed by a combination of PCR and restriction fragment length polymorphism. Mutations (A2142G and 2143G) were found in all strains tested except one. This study stresses the importance of performing susceptibility tests in clinical trials in order to explain the results of different treatments.

Anti-Bacterial Agents↗
PubMed1998

The putative tumor suppressors EXT1 and EXT2 are glycosyltransferases required for the biosynthesis of heparan sulfate.

Hereditary multiple exostoses, characterized by multiple cartilaginous tumors, is ascribed to mutations at three distinct loci, denoted EXT1-3. Here, we report the purification of a protein from bovine serum that harbored the D-glucuronyl (GlcA) and N-acetyl-D-glucosaminyl (GlcNAc) transferase activities required for biosynthesis of the glycosaminoglycan, heparan sulfate (HS). This protein was identified as EXT2. Expression of EXT2 yielded a protein with both glycosyltransferase activities. Moreover, EXT1, previously found to rescue defective HS biosynthesis (McCormick, C., Leduc, Y., Martindale, D., Mattison, K., Esford, L. E., Dyer, A. P., and Tufaro, F. (1998) Nat. Genet. 19, 158-161), was shown to elevate the low GlcA and GlcNAc transferase levels of mutant cells. Thus at least two members of the EXT family of tumor suppressors encode glycosyltransferases involved in the chain elongation step of HS biosynthesis.

Amino Acid Sequence↗
PubMed1998

Characterization of the glycosyltransferase enzyme from the Escherichia coli K5 capsule gene cluster and identification and characterization of the glucuronyl active site.

Bacterial capsular polysaccharides play an important role in virulence and survival. The Escherichia coli K5 capsule consists of a repeat structure of -4)GlcA-beta(1,4)-GlcNAc alpha(1-, identical to N-acetylheparosan. A 60-kDa protein, KfiC, has been identified as a bifunctional glycosyltransferase, responsible for the alternating alpha and beta addition of each UDP-sugar to the nonreducing end of the polysaccharide chain. Using hydrophobic cluster analysis, a conserved secondary structure motif characteristic of beta-glycosyltransferases was identified along with two highly conserved aspartic acid residues at positions 301 and 352 within the KfiC protein. Site-directed mutagenesis was used to identify catalytically active amino acids within domain A of the KfiC protein. The conserved aspartic acid residues at 301 and 352 were shown to be critical for the beta addition of UDP-GlcA (uridine diphosphoglucuronic acid) to defined nonreducing end oligosaccharide acceptors, suggesting that these conserved aspartic acid residues are catalytically important for beta-glycosyltransferase activity. A deleted derivative of the kfiC gene was generated, which encoded for a truncated KfiC (kfiC') protein. This protein lacked 139 amino acids at the C terminus. This enzyme had no UDP-GlcA transferase activity but still retained UDP-GlcNAc transferase activity, indicating that two separate active sites are present within the KfiC protein.

Amino Acid Sequence↗
PubMed1998

Risk factors for rebleeding and fatal outcome in elderly patients with acute peptic ulcer bleeding.

OBJECTIVE: Mortality after peptic ulcer bleeding (PUB) is high in elderly patients despite therapeutic advances. Little is known about what actually determines rebleeding and mortality. The objective of this study was to investigate which factors may have an independent influence upon rebleeding and mortality in patients with PUB. DESIGN: Prospective cohort study. PARTICIPANTS: Patients, above 60 years of age, hospitalized due to an endoscopically verified acute PUB were included in the study (n = 508). INTERVENTIONS: The occurrence of rebleeding within 3 days and mortality within 30 days was registered for all patients. A predefined set of variables with a potential to influence rebleeding and mortality was analysed in a multiple logistic regression model. MAIN OUTCOME MEASURES: Odds ratios (with confidence intervals) for all predefined variables with respect to influence upon rebleeding and mortality, respectively. RESULTS: The risk of rebleeding was significantly increased with greater age and if the patient was suffering from shock, while omeprazole infusion, acetylsalicylic acid (ASA)/non-steroidal anti-inflammatory drug (NSAID) intake before admission and gastric ulcer localization were associated with a lower risk. Mortality was significantly increased with greater age, heart disease and blood pressure < 100 mmHg at admission. Previous ulcer history and the presence of a Forrest class IIa ulcer significantly reduced this risk. CONCLUSIONS: Elderly patients in shock admitted due to their first peptic ulcer bleeding run the greatest risk of an unfavourable outcome.

Acute Disease↗
PubMed1997

Failure strength of a new meniscus arrow repair technique: biomechanical comparison with horizontal suture.

A new method for arthroscopic all-inside repair of vertical meniscus lesions by use of a biodegradable fixation device ("meniscus arrow") has been developed, including a set of cannulas for easy insertion via standard arthroscopic portals. The technique is described. A study to test the fixation properties was performed in the laboratory. Twenty-four fresh frozen bovine medial menisci were defreezed and divided into three groups. In all menisci an artificial vertical lesion was created with a scalpel 3mm from the peripheral rim. Repair in group I was done with a single horizontal Maxon-O suture using an Acufex double-barrel cannula (Acufex Meniscal Stitcher; Acufex Microsurgical, Norwood, MA). A knot was tied on the capsular side. Repair in group II was made with one 13 mm Biofix Meniscus arrow (Bioscience Ltd, Tampere, Finland). In group III repair was performed like in group II but the menisci were incubated in isotonic saline at 21 degrees C for 24 hours before testing. Menisci in group I and II were tested within 3 hours after defreezing. Prior to testing total separation of central and peripheral part of meniscus was performed. Thus only the repair site was tested. Pull-out tests to failure were made in a computer-based Nene M5 testing machine with a cross-head speed of 5 mm/min. Median failure load in group I: 49 N (range 43 to 77 N), in group II: 53 N (range 42 to 65 N) and in group III: 54 N (range 35 to 74 N). No statistically significant differences in failure load was found between the groups. Thus initial failure strength for arrow-repaired bovine menisci is comparable to that of a horizontal suture.

Animals↗
PubMed1997

Continuous intravenous infusion of omeprazole in elderly patients with peptic ulcer bleeding. Results of a placebo-controlled multicenter study.

BACKGROUND: Does profound acid inhibition by continuous infusion of omeprazole for 72 h reduce further bleeding in elderly patients with peptic ulcer bleeding (PUB)? METHODS: Three hundred and thirty-three patients > or = 60 years old with PUB were randomized to omeprazole (80 mg + mg/h) or placebo as continuous infusion for 72 h. From day 4 to 21 all patients received 20 mg omeprazole orally once daily. RESULTS: When evaluated on day 3, the primary variable 'overall outcome' (based on an ordinal ranking scale; see Study variables) (P = 0.017) and the secondary variables, surgery (P = 0.003), degree (P = 0.004) and duration of bleeding (P = 0.003) all favored the omeprazole group. Blood transfusions, need for endoscopic treatment, and mortality were not statistically different. On follow-up, by day 21, the mortality in the group initially receiving intravenous omeprazole was 6.9%, while the intravenous placebo group showed an extremely low mortality, 0.6%. CONCLUSION: Three days' infusion of omeprazole improved overall outcome and reduced need for intervention in PUB patients.

Aged↗
PubMed1997

Heartburn without oesophagitis: efficacy of omeprazole therapy and features determining therapeutic response.

BACKGROUND: Data are limited on the value of effective antisecretory therapy in the relief of heartburn in patients without oesophagitis. METHODS: Patients with heartburn, without endoscopic signs of oesophagitis, were randomized to double-blind treatment with omeprazole, 20 or 10 mg once daily, or placebo, for 4 weeks (n = 509). Pre-treatment oesophageal acid exposure was assessed using 24-h intra-oesophageal pH monitoring. Heartburn was assessed at 2 and 4 weeks. RESULTS: At 4 weeks the proportion of patients with complete absence of heartburn was 46% (95% confidence interval, 39-53%) with 20 mg omeprazole, 31% (25-38%) with 10 mg omeprazole, and 13% (7-20%) with placebo. Satisfaction with therapy was reported by 66%, 57%, and 31% of the patients, respectively. CONCLUSION: Omeprazole, 20 and 10 mg once daily, provides rapid relief of heartburn in patients without endoscopic oesophagitis.

Anti-Ulcer Agents↗
PubMed1996

[Treatment of acute lateral ankle ligament ruptures. A prospective 9-13-year follow-up study of three different therapies in 79 patients].

In a prospective study of 79 patients with arthrographically verified acute ruptured lateral ankle ligaments we have evaluated the long-term results of three different treatments: operation and walking-cast, walking-cast alone and elastic bandage. The average follow-up period was 11 (9-13) years, and 32 parameters concerning interview, clinical and radiographic examinations were statistically analysed. The three kinds of treatment were found to be equal, since only one parameter showed significant difference at a 5% level using Fisher's exact and the Mann-Whitney test, and no difference by using the Kruskal-Wallis test for homogeneity. Residual disabilities and late complications, such as instability, pain on activity, and the number of secondary ligament reconstructions and talocrural arthroses were low. It was concluded that nonoperative treatment provided adequate results even after a decade.

Bandages↗
PubMed1996

Serial hematologic changes and pregnancy outcome.

OBJECTIVE: To reevaluate the concept that poor maternal hematologic changes relate to increased placental protein hormones, increased birth weight, and placenta to birth weight ratio. METHODS: Sixty-nine normal women were studied prospectively. On several occasions, pre-pregnancy, during pregnancy, and post-delivery, plasma volume was measured together with maternal hematologic indices and placental protein hormone levels. Birth weight and placental weight were measured at delivery. RESULTS: The decrements in hemoglobin concentration and hematocrit were apparent by 7 weeks' gestation. By 12 weeks, these progressive changes resulted mostly from the increase in plasma volume, and both hemoglobin concentration and hematocrit continued to decrease until near term. Increments in red cell and hemoglobin mass were maximal at 12-28 weeks of pregnancy. Concentrations of the placental hormones hCG and human placental lactogen at 12 weeks showed a lack of correlation with hemoglobin concentration or any other hematologic index. The correlations of birth weight with hemoglobin concentration and hematocrit at 36 weeks were not significant when we controlled for the effect of plasma volume. Neither hemoglobin mass at 36 weeks nor the change in hemoglobin concentration, hematocrit, and mean cell volume from the pre-pregnancy value to that at 36 weeks were significantly related to birth weight, placental weight, or the placenta to birth weight ratio. CONCLUSION: Low hemoglobin in late pregnancy reflects plasma volume changes, rather than poor maternal nutrition or adaptation, and is not linked to discordant placenta to birth weight ratio.

Confidence Intervals↗
PubMed1996

Eradication of Helicobacter pylori using one-week triple therapies combining omeprazole with two antimicrobials: the MACH I Study.

BACKGROUND: Eradication of Helicobacter pylori provides potential cure in the majority of patients with peptic ulcer disease, and eradication rates of more than 90% have been reported, using omeprazole in combination with two antimicrobials. The choice of antimicrobials, dose regimen and duration of treatment have varied between studies, however, and an optimal treatment still has to be established. MATERIALS AND METHODS: We conducted an international, randomized, double-blind, placebo-controlled study involving more than 100 patients in each of six treatment groups in 43 hospital gastrointestinal units in Canada, Germany, Ireland, Sweden, and the United Kingdom. Patients (n = 787) with proved duodenal ulcer disease were randomized to treatment twice daily for 1 week with omeprazole, 20 mg (O), plus either placebo (P) or combinations of two of the following antimicrobials: amoxicillin, 1 gm (A), clarithromycin, 250 or 500 mg (C250, C500), or metronidazole, 400 mg (M). Eradication of H. pylori was evaluated by 13C-UBT, performed before and 4 weeks after treatment cessation. RESULTS: The eradication rates for the all-patients-treated analysis were 96%, OAC500; 95%, OMC250; 90%, OMC500; 84%, OAC250; 79%, OAM; and 1%, OP. OAC500 and OMC250 achieved eradication rates with lower 95% confidence interval limits exceeding 90%. All regimens were well-tolerated, 96% of patients complied with their dose regimen, and 2.3% of the patients discontinued treatment owing to adverse events. CONCLUSIONS: Omeprazole triple therapies given twice daily for 1 week produce high eradication rates, are well-tolerated, and are associated with high patient compliance. The two most effective therapies were those combining omeprazole, 20 mg, with either amoxicillin, 1 gm, plus clarithromycin, 500 mg, or metronidazole, 400 mg, plus clarithromycin, 250 mg, all given twice daily.

Amoxicillin↗
PubMed1995

Accessible hyaluronan receptors identical to ICAM-1 in mouse mast-cell tumours.

Immunohistochemical studies of the hyaluronan (HA)-receptor (R), originally found on liver endothelial cells (LEC) and related to the intercellular adhesion molecule 1 (ICAM-1), showed that polyclonal antibodies against HARLEC (HA receptor on LEC) also stain structures in mouse mastocytomas, mainly vessels. To test if intravenously administered HA might target the tumour receptors in vivo, mice carrying an inoculated mastocytoma in one hind leg muscle were injected in the tail vein with 125I-tyrosine (T)-labelled HA and killed 75 min after injection when organs and tissues were checked for radioactivity. When doses exceeding the binding capacity of the liver were injected, a significant increase in radioactivity (up to five-fold) within the tumour tissue was found. The weight adjusted difference between control and tumour tissue was greater for smaller tumours, probably due to necrosis in the larger. HA-staining of tumours from animals receiving 125I-T-HA, showed HA in areas that also stained weakly for ICAM-1 using monoclonal antibodies. ICAM-1 staining was dramatically increased after hyaluronidase treatment of the sections, indicating that the HA is bound to these receptors and thereby blocks antibody recognition.

Animals↗
PubMed1995

Long-term outcome after ruptured lateral ankle ligaments. A prospective study of three different treatments in 79 patients with 11-year follow-up.

In a prospective study of 79 patients with arthrographically verified acute ruptured lateral ankle ligaments we have evaluated the long-term results of 3 different treatments: operation and walking-cast for 5 weeks, walking-cast alone, and elastic bandage. The follow-up period was 11 (9-13) years. Residual disabilities and late complications, such as instability, pain on activity, and the number of ligament reconstructions and talocrural arthroses were equally low in all 3 groups. We conclude that nonoperative treatment seems adequate.

Activities of Daily Living↗
PubMed1994

Absorption of non-haem iron from food during normal pregnancy.

OBJECTIVE: To determine whether the increased iron demands of pregnancy could be met by increased absorption from dietary sources. DESIGN AND SETTING: Longitudinal prospective study in the research unit of a maternity hospital. SUBJECTS: 12 normal pregnant women. INTERVENTIONS: At 12, 24, and 36 weeks' gestation (within one week) and 16-24 weeks after delivery women ate a breakfast of meat, bread, and orange juice (3.2 mg iron), extrinsically labelled with the stable isotope iron-54 (2.8 mg); the stable isotope iron-57 (200 micrograms) was given intravenously. MAIN OUTCOME MEASURES: Serum samples were taken for 10 hours after administration of the isotopes; ratios of the isotopes were measured by inductively coupled plasma mass spectrometry, and the absorption of oral iron was calculated. RESULTS: The geometric mean (95% confidence interval) absorption of iron at 12, 24, and 36 weeks' gestation was 7% (5% to 11%), 36% (28% to 47%), and 66% (57% to 76%) respectively. At 16-24 weeks after delivery the absorption was 11% (6% to 21%). The mean increase in absorption at 36 weeks (compared with that at 12 weeks) was 9.1 times (6.0 to 13.7). One pregnant woman developed iron deficiency anaemia but was otherwise indistinguishable from the others. CONCLUSIONS: An increase in the absorption of iron from food is a physiological consequence of normal pregnancy, not the result of developing anaemia during pregnancy, and such an increase is large enough to meet the increased requirements of pregnancy provided that the dietary intake is adequate.

Female↗
PubMed1994

Comparison of stable isotopes and radioisotopes in the measurement of iron absorption in healthy women.

1. Stable isotope methods are being used to investigate the absorption of dietary iron. In order to be certain that this new methodology is accurate, we have compared results obtained using stable isotopes and inductively coupled plasma mass spectrometry with those determined using a radioisotope and whole body counting. 2. The stable isotope 54Fe (2.8 mg) was given to 10 healthy non-pregnant women. Six women received the isotope in aqueous form, and four took it with a meat meal. The 54Fe served as a carrier for 10 ng of the radioisotope 59Fe. An ampoule (200 micrograms) of the isotope 57Fe or 58Fe was then given intravenously, and in serum samples taken over the next 10 h the ratios of the stable iron isotopes were measured by inductively coupled plasma mass spectrometry and the oral iron absorption was calculated. This was then compared with the results obtained by using a whole body counter to measure (on day 0 and day 14) the gamma-activity emitted by the radioisotope. 3. The mean iron absorption measured by both methods ranged from 8% to 45%. Measurement of the post-absorptive serum enrichment of the stable isotopes provided estimates of absorption from both aqueous and food iron which were similar to that yielded by whole body counting, the mean difference being -1.5% (95% confidence interval -5.2 to 2.1%). Absorption estimated by stable isotopes exhibited the same inverse relationship with the serum ferritin level (body iron stores) to that known to exist with whole body counting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Biosynthesis of heparin/heparan sulfate. Identification of a 70-kDa protein catalyzing both the D-glucuronosyl- and the N-acetyl-D-glucosaminyltransferase reactions.

The D-glucuronosyl- (GlcA) and N-acetyl-D-glucosaminyl- (GlcNAc) transferase reactions involved in heparin/heparan sulfate biosynthesis were assayed, measuring transfer of radiolabeled GlcA or GlcNAc monosaccharide units from the corresponding UDP-sugars to the appropriate oligosaccharide acceptors. The assays were applied to enzyme purification from bovine serum. The two activities remained inseparable through a series of different chromatographic steps, resulting in approximately -2000-fold purification. Further purification was achieved by chromatofocusing, which showed an isoelectric point of pH approximately -7.0, similar for both activities. SDS-polyacrylamide gel electrophoresis (PAGE) of subfractions from the chromatofocusing procedure revealed an approximately 70-kDa protein in amounts reflecting enzyme activity. SDS-PAGE followed by extraction of gel segments and renaturation of proteins showed that the GlcA- and GlcNAc-transferase activities were both recovered from the same single segment, corresponding to the 70-kDa component. It is proposed that the two glycosyltransferase reactions are catalyzed by the same Golgi enzyme (see also Lidholt, K., Weinke, J. L., Kiser, C. S., Lugemwa, F. N., Bame, K. J., Cheifetz, S., Massagué, J., Lindahl, U., and Esko, J. D. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 2267-2271).

Animals↗