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Biomedical subjects

S Mulder

Publications and source records attributed to S Mulder.

14 recordsLinked to original sources

Methodological issues in comparing injury incidence across countries.

The primary objective was to describe the methodological challenges and devise solutions to compare injury incidence across countries. The research design was a mixed methods study, consisting of a consultation with an expert group and comparison of injury surveillance systems and data from ten European countries. A subset of fractures, selected radiologically verifiable fractures and a method of checking the national representativeness of sample emergency department data were devised and are proposed for further development. These methodological considerations and developments will be further refined and tested and should prove useful tools for those who need to compare injury incidence data across countries.

Data Collection↗

Multicentre quality control study for detection of Mycobacterium tuberculosis in clinical samples by nucleic amplification methods.

The aim of this study was to evaluate the laboratory performance of nucleic acid amplification tests (NATs) for detection of the Mycobacterium tuberculosis complex. A proficiency panel consisting of eight sputum specimens and four specimens diluted in phosphate-buffered saline (PBS) was sent to 82 laboratories in 23 countries by the Quality Control for Molecular Diagnostics (QCMD) TB programme. The performance of different NATs was analysed in combination with a questionnaire on the applied methods. Seventy-eight participants (95.2%) contributed a total of 85 evaluable data sets. The percentage of correct results on the eight sputum samples was 86.3% (586/679). Of the sputum specimens considered as 'smear-negatives' (650 CFU/250 micro L), only 61.2% (104/170) were reported positive. The percentage of correct results for the three scored PBS samples was 75.7% (193/255). The total number of false-positive results was 11 (4.3%); these were reported for seven (8.2%) of the 85 data sets. In 32 (37.6%) data sets an 'in-house' NAT method was used, and in 53 (62.4%) sets a commercial assay was tested. The percentage of data sets achieving correct results on all sputum samples was 35.3% and 37.8%, respectively. For the PBS samples this was 45.8% and 41.5%. Overall, the results of this study demonstrated that the performance of NATs for the detection of M. tuberculosis has improved since previous studies. The percentage of false-positives has decreased considerably. However, a large number of procedures still lack sufficient sensitivity for application to smear-negative samples.

Humans↗

Setting priorities in injury prevention: the application of an incidence based cost model.

OBJECTIVES: To make detailed calculations on the direct medical costs of injuries in the Netherlands to support priority setting in prevention. METHODS: A computerised, incidence based model for cost calculations was developed and incidence figures derived from the Dutch Injury Surveillance System (LIS) which provides national estimates of the annual number of patients treated at an emergency department. A comprehensive set of cost elements (that is, health care segments) was obtained from health care registrations and a LIS patient survey. Patients were assigned to specific groups based on LIS characteristics (for example, age, injury type). Average costs per patient group were calculated for each cost element and total costs estimated by adding costs for all patient groups. RESULTS: The direct costs of injury average 2000 guilders per injury patient attending an emergency department. Home and leisure injuries account for over half of the costs, although cost per patient is highest for motor vehicle injuries. Injuries to the lower extremities account for almost half of the total costs and are incurred mainly in the home or recreation. Motor vehicle crashes are the major cause of head injuries. CONCLUSIONS: The model permits continuous and detailed monitoring of injury costs. Estimates can be compiled for any LIS patient group or injury subcategory. The results can be used to rank injuries for prioritisation of prevention by injury categories (for example, traffic, home, or leisure), or by specific scenarios (for example, fall at home).

Costs and Cost Analysis↗

Microwell hybridization assay for detection of PCR products from Mycobacterium tuberculosis complex and the recombinant Mycobacterium smegmatis strain 1008 used as an internal control.

A microwell hybridization assay was developed for the detection of the PCR products from both Mycobacterium tuberculosis complex bacteria and the recombinant Mycobacterium smegmatis strain 1008 that is used as an internal control to monitor inhibition in the PCR based on the M. tuberculosis complex-specific insertion sequence IS6110. The test is based on specific detection with digoxigenin-labeled oligonucleotide probes of biotinylated PCR products which are captured in a microtiter plate coated with streptavidin. The captured PCR products are hybridized separately with two probes, one specific for the PCR product from IS6110 from M. tuberculosis complex and the other specific for the PCR fragment from the modified IS6110 fragment from the recombinant M. smegmatis 1008. The microwell hybridization assay discriminates perfectly between the two types of amplicon. The amount of PCR product that can be detected by this assay is 10 times less than that which can be detected by agarose gel electrophoresis. The test can be performed in 2 h. It is much faster and less laborious than Southern blot hybridization. Furthermore, the interpretation of results is objective. The assay was used with 172 clinical samples in a routine microbiology laboratory, and the results were in complete agreement with those of agarose gel electrophoresis and Southern blot hybridization.

DNA, Bacterial↗

Lysophosphatidic acid-induced Ca2+ mobilization in human A431 cells: structure-activity analysis.

Lysophosphatidic acid (LPA; 1-acyl-sn-glycero-3-phosphate) is a platelet-derived lipid mediator that activates its own G-protein-coupled receptor to trigger phospholipase C-mediated Ca2+ mobilization and other effector pathways in numerous cell types. In this study we have examined the structural features of LPA that are important for activation of the Ca(2+)-mobilizing receptor in human A431 carcinoma cells, which show an EC50 for oleoyl-LPA as low as 0.2 nM. When the acyl chain at the sn-1 position is altered, the rank order of potency is oleoyl-LPA > arachidonoyl-LPA > linolenoyl-LPA > linoleoyl-LPA > stearoyl-LPA = palmitoyl-LPA > myristoyl-LPA. The shorter-chain species, lauroyl- and decanoyl-LPA, show little or no activity. Ether-linked LPA (1-O-hexadecyl-sn-glycero-3-phosphate) is somewhat less potent than the corresponding ester-linked LPA; its stereoisomer is about equally active. Deletion of the glycerol backbone causes a 1000-fold decrease in potency. Replacement of the phosphate group in palmitoyl-LPA by a hydrogen- or methyl-phosphonate moiety results in complete loss of activity. A phosphonate analogue with a methylene group replacing the oxygen at sn-3 has strongly decreased activity. All three phosphonate analogues induce cell lysis at doses > 15 microM. Similarly, the methyl and ethyl esters of palmitoyl-LPA are virtually inactive and become cytotoxic at micromolar doses. None of the LPA analogues tested has antagonist activity. Sphingosine 1-phosphate, a putative messenger with some structural similarities to LPA, elicits a transient rise in intracellular [Ca2+] only at micromolar doses; however, cross-desensitization experiments indicate that sphingosine 1-phosphate does not act through the LPA receptor. The results indicate that, although many features of the LPA structure are important for optimal activity, the phosphate group is most critical, suggesting that this moiety is directly involved in receptor activation.

Animals↗

Routine application of the polymerase chain reaction for detection of Mycobacterium tuberculosis in clinical samples.

AIM: To investigate the use of the polymerase chain reaction (PCR) in the routine laboratory for the detection of Mycobacterium tuberculosis in clinical samples. METHODS: Samples were divided and processed separately for the detection of M tuberculosis by microscopy, culture and PCR. After DNA extraction, PCR was performed with primers specific for the insertion element IS6110 and the product was analysed by agarose gel electrophoresis, Southern blotting or dot blotting and hybridisation with a digoxigenin labelled internal probe. Each sample was tested for inhibitors of Taq polymerase with the aid of an internal control. Multiple negative and positive controls were used to monitor each step of the procedure. RESULTS: The data from two laboratories, using the same operating procedures, were combined. Of 1957 specimens, 79 (4%) were culture and PCR positive, while 1839 (93.9%) were negative in both tests. Thirty specimens (1.5%) were PCR positive only and nine (0.5%) were culture positive but PCR negative. CONCLUSION: Using culture and clinical history as the gold standard, sensitivity and specificity for PCR were 92.1% and 99.8%, respectively. With elaborate precautions, PCR is a suitable and reliable method for the detection of M tuberculosis in clinical samples in a routine microbiology laboratory.

Bacteriological Techniques↗

Incidence of medically treated burns in The Netherlands.

During the period January 1988 to December 1989, medically treated burn injuries in The Netherlands were recorded prospectively by three registration systems. These systems cover patients treated in burn units, in general and university hospitals, and by general practitioners. Incidence rates and 95 per cent confidence intervals were calculated, and basic epidemiological data about severity and localization of the burns and about accident circumstances were collected. The overall incidence rate of medically treated burns over all levels of medical care is estimated to be about 280 per 100,000 persons per year. This overall incidence figure appeared to be about three times as high for 0-4-year-old children: 775 per 100,000 per year. At all levels of medical care, scalds are the most frequent type of burn, resulting in an overall incidence rate among 0-4-year-old children of 430 per 100,000 per year. Incidence rates are lowest among the elderly (55 years and over), but this age group suffers a higher mortality from burns. Furthermore, it appeared that males are more prone to serious burns than females, whereas female are more often treated for less severe burns. Most of the accident circumstances for serious burns were related to professions, whereas most of the circumstances for less severe burns were related to household activities.

Adolescent↗

Transdermal scopolamine reduces nausea and vomiting after outpatient laparoscopy.

The authors evaluated the effect of transdermal scopolamine on the incidence of postoperative nausea, retching, and vomiting after outpatient laparoscopy in a double-blind, placebo-controlled study. A Band-Aid-like patch containing either scopolamine or placebo was placed behind the ear the night before surgery. Anesthesia was induced with fentanyl (0.5-2 micrograms/kg iv), thiopental (3-5 mg/kg iv), and succinylcholine (1-1.5 mg/kg iv) and maintained with isoflurane (0.2-2%) and nitrous oxide (60%) in oxygen. Scopolamine-treated patients had less nausea, retching, and vomiting compared with placebo-treated patients (P = 0.0029). Severe nausea and/or vomiting was present in 62% of the placebo group but only 37% of those getting the scopolamine patch. Repeated episodes of retching and vomiting were also less frequent in the scopolamine group compared with the placebo group (23% vs. 41%; P = 0.0213) as was the need for additional antiemetic therapy (13% vs. 32%; P = 0.0013). Patients in the scopolamine group were also discharged from the hospital sooner (4 +/- 1.3 vs. 4.5 +/- 1.5 h; P = 0.0487). Side effects were more frequent among those patients treated with the scopolamine patch (91% vs. 45%; P less than 0.05) but were not troublesome. The authors conclude that transdermal scopolamine is a safe and effective antiemetic for outpatients undergoing laparoscopy.

Administration, Cutaneous↗

Hollenhorst plaques: retinal manifestations and the role of carotid endarterectomy.

The ocular examinations and hospital records of 64 patients with Hollenhorst plaques were retrospectively reviewed to document any associated visual defects and to determine if carotid endarterectomy prevented the occurrence of new plaques or symptoms. One hundred nine Hollenhorst plaques were seen in 75 eyes; 18 had multiple plaques simultaneously. Visual field defects were noted in 14 eyes, four of which corresponded to the location of Hollenhorst plaques. Twenty-eight carotid endarterectomies were performed ipsilateral to a Hollenhorst plaque: 24 patients had no symptoms; four patients developed new ipsilateral asymptomatic Hollenhorst plaques at 1 to 50 months after operation. Two late strokes occurred, one of which was ipsilateral to a new Hollenhorst plaque, during a mean follow-up of 50 months (range 8 to 102 months). Thirty-seven eyes with asymptomatic Hollenhorst plaques did not undergo ipsilateral operation. Two eyes developed new Hollenhorst plaques during a mean follow-up of 23 months (range 1 to 132 months). Eight eyes in patients with no symptoms had multiple Hollenhorst plaques, one of which was associated with a subsequent stroke. Of the 29 eyes with a single Hollenhorst plaque, one subsequently experienced an ipsilateral stroke, and another had a transient ischemic attack (1 and 3 years later, respectively). Visual field defects infrequently corresponded to locations of Hollenhorst plaques. The cerebral hemisphere ipsilateral to asymptomatic plaques had a slightly increased risk of subsequent transient ischemic attack or stroke compared to the contralateral side without Hollenhorst plaques. The number of simultaneous Hollenhorst plaques in the retinal circulation did not predict clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Toxicity of cyclohexanone oxime. I. Hematotoxicity following subacute exposure in rats.

Cyclohexanone oxime (CHO) was given po to male and female Fischer 344 rats at dose levels of 10, 25, 75, 150, and 300 mg/kg, five times a week for a period of 2 weeks. Control animals received distilled water. All animals given intermediate dose levels (10, 25, 75, and 150 mg/kg) and one half of the animals which were dosed at the high dose (300 mg/kg) as well as one half of the controls were terminated 14 days after administration of the first dose. The remaining rats received no treatment for an additional 14 days and were sacrificed on Day 28 of the study (recovery phase). Dose-related decreases in erythrocyte number, hemoglobin, and hematocrit, with an accompanying increase in reticulocytes and circulating nucleated erythrocytes, were observed in both sexes at Day 14. Methemoglobin levels, determined only at the high dose, were elevated in both sexes at this time. Splenomegaly and hepatomegaly were observed in both sexes at 14 and 28 days. Histopathological examination of the spleen and bone marrow revealed dose-related erythroid hyperplasia at 14 days which subsided by Day 28. The above effects were more pronounced in males. Erythrocyte numbers were only slightly depressed and reticulocytes mildly elevated in males at Day 28. Hematological values were not statistically different from controls in females at this time. These results suggest that CHO induces oxidative damage to the erythrocyte, resulting in a hemolytic anemia accompanied by increased erythropoiesis. The toxic effects appear reversible upon cessation of exposure.

Anemia, Hemolytic↗

Toxicity of cyclohexanone oxime. II. Acute dermal and subchronic oral studies.

Dermal exposure of rabbits to cyclohexanone oxime (CHO) for 24 hr at 0, 0.8, 2, and 5 g/kg caused dose-related reticulocytosis on the day after dosing as well as a decrease in hemoglobin in the 5-g/kg females 7 days postdosing. Gavage of rats 5 days a week for 13 weeks at levels of 0, 0.25, 2.5, and 25 mg/kg resulted in a dose-related decrease in erythrocyte number, hemoglobin, and hematocrit, with an accompanying increase in circulating reticulocytes and nucleated erythrocytes, in both sexes. Also seen were corneal opacities and an increased incidence of Howell-Jolly bodies. Results suggested an increased erythropoiesis in the spleen and bone marrow. The data from satellite groups terminated at 30 and 60 days revealed no effect at the lower test level, but results from the end of the study showed a clear cumulative dose response down to the 0.25-mg/kg level. Males were affected earlier and at lower doses than females. These results, along with those of a subacute study with a recovery period, suggest that CHO induces an oxidative attack on erythrocytes which appears reversible upon cessation of exposure.

Administration, Oral↗