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Biomedical subjects

P Lind

Publications and source records attributed to P Lind.

At least 109 records · Page 6Linked to original sources

The incidence of hyperthyroidism in Austria from 1987 to 1995 before and after an increase in salt iodization in 1990.

Between 1963 and 1990, Austria had iodized salt prophylaxis of endemic goitre with 10 mg KI (7.5 mg I) per kg. This was obviously insufficient, as urinary iodine excretion ranged from 42 to 78 microg I per g of creatinine and goitre in adults remained in the endemic range of 15%-30%. Therefore salt iodization was doubled in 1990. The aim of this study was to assess the annual incidence of different types of hyperthyroidism (HT) before and after this increase in salt iodization. The incidence of HT was recorded in 14 nuclear medicine centres from 1987 to 1995. In five additional centres data were available from 1992 onwards. Data prior to 1992 were documented retrospectively, while those after 1992 were recorded prospectively. The 14 centres drew patients from an area with a population of approximately 4.23 million while all 19 institutes were estimated to cover an area with a population of 5.4 million (the total population of Austria is 7.86 million). A total of 414232 persons were examined for the first time in the participating centres. HT and the type of HT were defined by clinical examination, serum TSH, thyroid hormone levels in blood, ultrasonography, scintigraphy and serum autoantibody titres. HT was classified into immunogenic HT (Graves' or Basedow's disease, GD) and HT with intrinsic thyroid autonomy (uni-, multinodular or disseminated Plummers' disease, PD). HT was also divided into overt (o) or subclinical (sc) disease. The following data were calculated: annual incidence per 100000 and the relative risk (RR) for HT with 95% confidence intervals (CI). In addition, linear trends were calculated for each type of HT by means of logistic regressions. In the 19 centres a total of 47834 patients with HT were registered from 1987 to 1995. PD accounted for 75% of all cases of HT and GD for 19%, while other types of HT were present in 6%. From 1987 to 1989 (time period T0), the annual incidence of oPD was 30.5 (95% CI 29.6-31.5) per 100000. The RR compared to the baseline period T0 was highest in 1992 (1.37; 1.3-1.45) and decreased to 1.17 (1.1-1.24) in 1995. The annual incidence of scPD in T0 was 27.4 (26.5-28.3) per 100000. The RR was highest in 1991 (1.64; 1.56-1.73) and was 1.60 (1. 51-1.69) in 1995. In oPD and scPD a higher RR was observed in persons older than 50 years of age, particularly in men. The incidence of oGD in T0 was 10.4 (9.8-10.9) per 100000; the maximum RR increased to 2.19 (2.01-2.38) in 1993 and decreased to 1.95 (1.78-2.13) in 1995. The incidence of scGD was 1.9 (1.6-2.1) in T0. The maximum RR was observed in 1994 (2.47; 2.04-3.0) and it was still 2.26 (1.85-2.77) in 1995. The increased incidence of oGD and scGD was evenly distributed in all ages and both sexes. The time course of different types of HT following the increase in salt iodization could be divided into two phases: an increase in the incidences of HT with peaks after 1-4 years and a subsequent decrease, the only exception being scGD. The effect was more pronounced in GD than in PD. PD showed an age and gender dependency over time, while GD did not.

Adult↗

Trichinella spiralis, T. britovi, and T. nativa: infectivity, larval distribution in muscle, and antibody response after experimental infection of pigs.

The infectivity of Trichinella spiralis, T. nativa, and T. britovi was experimentally compared in pigs. Blood sampling was performed weekly, and muscle juices were obtained at slaughter 10 weeks after inoculation. Muscle larvae were found in all of four pigs inoculated with T. spiralis [mean 190 larvae per gram (lpg)] and in three of four pigs inoculated with T. britovi (mean 7 lpg). No larvae were found in pigs inoculated with T. nativa. For T. spiralis and T. britovi, the neck muscle (m. splenius) appears to be a predilection site in addition to the tongue, the diaphragm, and the jaw. High antibody responses were found in all experimental groups, independent of the antigen used, and even in pigs in which no muscle larvae were recovered. The strong and consistent antibody response found with meat juice indicates the usefulness of this material where a blood sample is not obtainable, e.g. meat samples from wild animals. Immunoblotting (Western blots) on slaughter sera revealed no species specificity when comparing homologous versus heterologous staining.

Animals↗

A study of virulence parameters for Toxoplasma gondii infections in mice.

With the aim of establishing assessments of the virulence of Toxoplasma gondii isolates for mice, we investigated weight loss, serum levels of haptoglobin, and serum levels of tumor necrosis factor-alpha (TNF-alpha) as alternative parameters to mouse mortality. Groups of BALB/c mice were inoculated i.p. with increasing parasite doses (5 x 10(1), 10(4), and 10(6)) of isolate 119 and with a low dose (5 x 10(1)) of isolates GT1 and NED. The inoculation dose was inversely correlated with the interval to the onset of weight loss (starting at days 9, 7, and 5, respectively) and the onset of increase in serum haptoglobin (starting at about days 8, 6, and 4, respectively). The GT1 strain (inducing 100% mortality at day 9) also gave the fastest response in terms of weight loss (onset by day 8) and increase in serum haptoglobin (onset by day 6), which occurred 1-2 days before these parameters were affected in the other low-dose groups. The low-dose NED and 119 inoculations were distinguished by continued weight loss, which lasted until day 20 in the former group (max. average weight loss 2.9 g as compared with 0.4 g).

Animals↗

Monoclonal antibodies to Toxoplasma gondii strain 119 identify recently isolated Danish strains as one group.

Four mAb raised against the Danish Toxoplasma gondii strain 119, were selected by screening hybridoma supernatants by indirect immunofluorescence against tachyzoites of the RH strain in order to obtain strain-restricted markers. Strain restriction extended beyond discrimination of the 119 and RH strains, as demonstrated on a further six T. gondii reference strains [BK and GT1 (group A), NTE and 561 (group B), and NED and C56 (group C)]. The bradyzoite-specific mAb, 4.3, reacted to the GT1, NTE and 561 strains, but not to the BK, NED or C56 strains. The tachyzoite-specific mAb, 4.25, reacted to all strains tested except the RH strain, while mAb 5.1 reacted to tachyzoites of strains NTE and 561, but not to those of the BK, GT1, NED or C56 strains. Monoclonal antibody 5.15 reacted with the same strain restriction as monoclonal antibody 5.1, but to bradyzoites as well as tachyzoites. A T. gondii strain collection representative for a small geographic area (Denmark) was established within a short time span from a variety of animal species. Using the mAb as typing reagents to this Danish strain collection, all 36 animal and two human strains were identified as having the same reaction pattern as strains 119, NTE and 561.

Animals↗

Epidemiology of thyroid diseases in iodine sufficiency.

Epidemiology of thyroid diseases in iodine-sufficient areas (ISA) deals with sporadic goiter, thyroid autoimmune diseases, and thyroid cancer. A comparison between the different studies performed is difficult because methods have changed over time and selection criteria and definitions such as prevalence or incidence were not used consistently by some authors. Sporadic goiter: in ISA, autoimmune processes play a major role in the development of sporadic goiter. In adults, sporadic diffuse goiter is most frequent in young women (16%), perhaps due to additional relative iodine deficiency especially in pregnancy, and declines with age (<10%). Sporadic nodular goiter increases from 5% in young women to 9% in older women. Autoimmune thyroid disease (AITD): thyroid autoantibodies (TAb) and histopathological lymphocytic infiltration of the thyroid is much more common in ISA (4.6% in women; 1.1% in men) than in iodine-deficient areas (IDA). The prevalence and incidence of hypothyroidism and hyperthyroidism varies, depending on whether overt and subclinical forms are included and whether newly or previously diagnosed dysfunction is considered. In an overview of the literature, the prevalence is 2 in 1000 for overt and 6 in 1000 for subclinical hyperthyroidism in ISA. The values for hypothyroidism are 5 in 1000 and 15 in 1000, respectively. Change from IDA to ISA: in former IDA, the percentage of hyperthyroidism increases up to 4 years after salt iodination. Whereas this effect is transient for Plummer's disease, a change from IDA to ISA seems to lead to a permanent increase in overt and subclinical Graves' disease. Thyroid cancer: most studies demonstrate that the histopathological types of thyroid cancer are different in IDA and ISA. There is a tendency toward an increase in differentiated and decrease of anaplastic cancer. The ratio of papillary to follicular thyroid cancer ranges from 6.5:1 to 3.4:1 in areas with high iodine intake, decreases 3.7:1 to 1.6:1 in areas with moderate iodine intake, and ranges from 1.7:1 to 0.19:1 in IDA.

Adult↗

Experimental porcine neosporosis.

Six gilts were inoculated intramuscularly with 2.5x10(6) tachyzoites of Neospora caninum on three different days of gestation to study the pathogenic effect of Neospora infection in pigs, including possible transplacental transmission. The gilts were euthanized 59, 30, and 9/10 days postinoculation (p.i.), corresponding to days 107, 102/106 and 110/111 of pregnancy. With the exception of one animal (euthanized day 9 p.i.) all gilts seroconverted as measured by the indirect, fluorescent antibody test (IFAT). Neosporosis with multifocal intralobular necrotizing hepatitis was seen in the two gilts inoculated 9/10 days before euthanasia. The uterus of one gilt inoculated 59 days before euthanasia revealed granulomatous and focal necrotizing endometritis with a corresponding multifocal necrosis of the trophoblasts of two fetuses. Transplacental neosporosis was indicated in the two fetuses by strongly elevated Neospora IFAT titres in pleural fluid and by the presence of multifocal necrotizing encephalitis and hepatitis together with non-suppurative myocarditis, pneumonitis, nephritis and hepatitis. Furthermore, N. caninum was re-isolated in cell culture from one of these fetuses. A third fetus from the same gilt revealed only disseminated, pinpoint necroses in the liver. Immunohistochemically, N. caninum tachyzoites were detected in association with histopathological changes in the liver and the endometrium of the gilts, and in the brain, liver, and allantochorion of the three fetuses.

Animals↗

Use of muscle fluid as a source of antibodies for serologic detection of Salmonella infection in slaughter pig herds.

Fluid drained from a muscle tissue sample was used as an alternative to serum for the detection of specific anti-Salmonella antibodies in an indirect LPS enzyme-linked immunosorbent assay (ELISA). In the first study, serum and muscle fluid from 3 pigs experimentally infected with Salmonella typhimurium showed parallel dilution-response relationships when ELISA optical density (OD) values were plotted against sample dilution. ELISA results obtained with serum diluted 1:400 corresponded to those from muscle fluid diluted 1:30. In a second study, using the predetermined dilutions of individually paired serum and muscle fluid samples from 103 pigs, a high degree of concordance between the serum ELISA and the muscle fluid ELISA was observed. Limits of agreement between the 2 methods were calculated as -8.9 to 12.3 OD%, which was considered acceptable. The muscle fluid ELISA had specificities of 0.91-1.0 and sensitivities of 0.80-0.89 at various cutoff values as compared with the serum ELISA. Muscle fluid is a useful postmortem alternative to serum when used with an ELISA to detect anti-Salmonella antibodies.

Abattoirs↗

Thallium-201 uptake with negative iodine-131 scintigraphy and serum thyroglobulin in metastatic oxyphilic papillary thyroid carcinoma.

We report a case of a 48-yr-old woman who underwent surgery because of papillary oxyphilic thyroid carcinoma pT3. After total thyroidectomy, we administered 2960 MBq (131)I for ablation of the residual tissue. initial follow-up visits showed no clinical, radiological or scintigraphic evidence of residual or metastatic thyroid tissue. Serum thyroglobulin levels (Tg) and (131)I whole-body scintigraphy were negative. Three years after thyroidectomy, the patient experienced seizures, and as a consequence a brain tumor was removed. It was an undetected metastasis of the primary thyroid carcinoma. Histological examinations showed that neither the primary tumor nor the metastasis produced any Tg. With this fact in mind and the knowledge of negative (131)I whole-body scans we had to concentrate on radiological (CT and MRI scans) and nonspecific scintigraphic methods such as 201TI whole-body scintigraphy in our management of the patient. Further follow-up demonstrated multiple metastasis by 201TI whole-body scan (mediastinum, bones and soft tissue), and most of them have been removed by surgery. This case report demonstrates that, in addition to (131)I whole-body scans and measurement of serum Tg, the use of nonspecific tracers like 201TI is important to detect (131)I and/or Tg negative metastases.

Carcinoma, Papillary↗

[Toxicity and radiation dosage of 2-(18F)-2-desoxy-D-glucose in positron emission tomography].

2-[18F]-FDG, a non-physiological glucose analogue, is the most important positron-emission- tomography (PET) radiopharmaceutical. As an example we refer to the production of 2-[18F]-FDG at the research center in Karlsruhe. 2-[18F]-FDG is synthesized in a "no carrier added" process. It is delivered at a maximal filling volume of 10 ml from a 14.5 ml batch with a batch-to-batch yield fluctuation from 5075 to 50,750 MBq and a specific activity from 1 to 10 GBq/mumol. The residual remaining synthesis reagents like solvents or catalysts have no toxicological relevance. The applicated dose per patient is in a range from 185 to 370 MBq and 1000 times lower than the correlating concentrations of stable FDG which can be regarded harmless in animals. 2-[18F]-FDG does not interfere with normal glucose metabolism. It is taken up by cells and phosphorylated to 2-[18F]-FDG-6-phosphate. The following dephosphorylation step is slow and the labeled compound is retained over several hours within the cells. Non-metabolized 2-[18F]-FDG is excreted rapidly in the urine to an extent of about 16% after 60 min, and 50% after 135 min, respectively. Fluorine-18F decays by emission of 511 KeV gamma photons. The whole body effective dose is reported to be 21 to 27 microSv/MBq. In case of an intravenous injection of 370 MBq this leads to a total dose of 7.8 to 10 mSv. The critical organ is the bladder wall (radiation dose 120 to 170 microSv/MBq or 80 to 100 mrem/mCi). The risk of a radiation induced late malignoma at 10 mSv can be estimated to be 1:2000. The genetical risk as a consequence of FDG-PET diagnostics would be 1:100,000 to 2:100,000 for dominant, and 5 times higher for recessive mutations.

Blood Glucose↗

Thyroglobulin and low-dose iodine-131 and technetium-99m-tetrofosmin whole-body scintigraphy in differentiated thyroid carcinoma.

UNLABELLED: Determination of thyroglobulin (Tg) levels, determined under endogenous thyroid-stimulating hormone stimulation after withdrawal of L-thyroxin treatment (off-T4), has been proven to be the most sensitive method for evaluation of patients with recurrent malignancy or distant metastases. This study uses a comparative approach between low-dose 131I scan and the previously reported highly sensitive 99mTc-tetrofosmin whole-body scintigraphy, using Tg-off-T4 as a basis for comparison. METHODS: Fifty-eight consecutive patients of our follow-up program with primary thyroid carcinoma ablated with thyroidectomy and radioiodine therapy were examined after L-thyroxin withdrawal over 3-4 wk with 131I (185 MBq) and 99mTc-tetrofosmin whole-body scintigraphy and Tg determination (off-T4) within 5 days. Patients with Tg levels above 0.5 ng/ml were defined as Group A (n = 29). Group B (n = 29) comprised patients who had Tg levels (off-T4) below 0.5 ng/ml. RESULTS: Iodine-131 revealed only 19 of 44 tumor sites (43.18%). Additionally, three remnants could be demonstrated. Sensitivity showed decreasing values for local recurrences (4 of 7, 57.1%), bone lesions (7 of 13, 53.85%) and mediastinal (2 of 4, 50%), lung parenchymal (3 of 7, 42.85%) and lymph node (2 of 9, 22.2%) metastases. Whole-body scintigraphy with 99mTc-tetrofosmin revealed a total of 39 of 44 malignant lesions (88.6%). Sensitivity was superior for lung parenchymal metastases (9 of 9, 100%), mediastinum (4 of 4, 100%) and lymph nodes (9 of 10, 90%) and inferior for bone metastases (11 of 13, 84.6%). Local recurrences could be detected in 6 of 7 patients (85.7%), and thyroid remnants were detected in 2 cases (2 of 11, 18.2%). One liver metastasis could not be detected because of the physiologic tracer distribution of 99mTc-tetrofosmin. Thyroglobulin-off-T4 detected malignant recurrence or metastases in 18 of 19 patients (94.7%) when a cutoff of 3 ng/ml was used and in 16 of 19 patients (84.2%) when a cutoff of 10 ng/ml was used. Specificity was calculated as 71.8% when a cutoff of 0.5 ng/ml was used, 89.7% when a cutoff of 3 ng/ml was used and 100% when a cutoff of 10 ng/ml was used. CONCLUSION: Scintigraphy with 99mTc-tetrofosmin showed clear advantages concerning sensitivity in most metastatic lesions when compared with low-dose 131I scan. Despite a slight lower specificity, 99mTc-tetrofosmin whole-body scintigraphy has, therefore, been proven to be a useful tool in the assessment of metastatic lesions in differentiated thyroid carcinoma.

Adenocarcinoma, Follicular↗

Characterization of the CCR2 chemokine receptor: functional CCR2 receptor expression in B cells.

We have derived anti-human CCR2-specific mAbs by immunization with synthetic peptides corresponding to CCR2 sequences presumably involved in the interaction with its ligand(s). The characterization of these mAbs includes the ability to recognize the CCR2 receptor specifically, as well as the function based on their ability to promote Ca2+ influx or to block MCP-1-induced Ca2+ influx and chemotaxis. One mAb (MCP-1 R02) that is directed to the NH2 terminal domain of the CCR2 receptor has MCP-1 agonist activity, and two that recognize the third extracellular domain (MCP-1R04 and MCP-1 R05) have MCP-1 antagonist activity. We analyzed the presence of CCR2 in several PBL and tonsil-derived leukocyte populations and found expression of this receptor in monocytes, activated T cells, and, surprisingly, in B cells. CCR2 receptor expression in B cells was further corroborated in Southern blot using CCR2-specific probes. Moreover, both MCP-1 and the agonist mAb trigger specific B cell migration via a PTX-sensitive mechanism, indicating the presence of a functional CCR2 receptor in these cells.

Antibodies, Monoclonal↗

The time course of the specific antibody response by various ELISAs in pigs experimentally infected with Toxoplasma gondii.

With the aim of developing routine serological tests for monitoring the Toxoplasma infection status of Danish swine herds, four ELISAs based on tachyzoite antigen were set up: (1) an indirect ELISA for IgG-antibody; (2) a blocking ELISA for antibody to the membrane antigen, P30; (3) an indirect ELISA for IgM; (4) a reverse, antibody-catching IgM-ELISA. Groups of pigs (number between 6 and 10) were inoculated with tachyzoites of the RH-strain, tissue cysts of two complete strains, or oocysts in two doses (10(3) and 10(4). All inoculations were tolerated well. Irrespective of strain and stage used for inoculation, specific IgG and anti-P30 blocking activity appeared after 1-2 weeks, with OD-values stabilizing after 3-6 weeks and persisting throughout the study period (3-4 months). Specific IgM appeared quickly, but was short-lived (approximately 2 weeks). A cut-off OD-value of 0.36 for positive seroreaction in the indirect IgG-ELISA was determined on the basis of 69 sera from four herds, investigated in the dye-test (serum dilution 1:10) and ELISA. The chosen cut-off gave optimal combined sensitivity and specificity of 0.94 and 0.92, respectively, using the dye-test as a standard. Corresponding figures for the blocking ELISA were 37% inhibition as cut-off, with sensitivity and specificity of 0.94 and 0.94, respectively. Sera from a total of 87 pigs, experimentally infected with bacteria of the genera Salmonella, Yersinia or Actinobacillus and with the parasites Isospora suis, Trichinella spiralis or Ascaris suum, in no case produced cross-reactions in the IgG-ELISA. However, 3/9 pigs inoculated with 50 000 sporocysts of Sarcocystis miescheriana gave maximal OD-readings of 0.40-0.45 during the 13-15 weeks observation period. None of the sera from heterologously infected animals produced inhibitions in the anti-P30 blocking ELISA exceeding 36%.

Animals↗

Evaluation of thyroid nodules with technetium-99m tetrofosmin dual-phase scintigraphy.

Technetium-99m tetrofosmin, a lipophilic cationic complex molecule, was introduced for myocardial imaging. In some biodistribution studies it has also been reported to accumulate in the thyroid gland. Our objectives were to determine which thyroid nodules retain tetrofosmin and whether preoperative evaluation of malignancy is possible. Tetrofosmin scintigraphy was performed in 57 patients with a cold thyroid nodule on previously performed pertechnetate scintigraphy. All patients had undergone ultrasonography and sonographically guided fine-needle aspiration biopsy. The tetrofosmin scintigrams were obtained 5 min (early image) and 1 h (late image) after intravenous injection of 370 MBq. Only nodules that showed clear tracer retention after 1 h in comparison with retention at 5 min were classified as TETRO positive. Nodules without late retention were classified as TETRO negative. All patients underwent surgery and the histological results were compared with the results of tetrofosmin scintigraphy. Ten out of 11 patients with thyroid carcinoma (two pT1, three pT2, five pT4) were TETRO negative. One patient with papillary carcinoma (pT2) was TETRO positive. The mean nodular to thyroid tissue (N/T) ratio for the late scan was 1.0+/-0.20. There were 21 patients with thyroid adenomas (seven follicular, seven microfollicular and seven oxyphilic); 15 of these patients were TETRO positive and six TETRO negative. The mean N/T ratio for the late images was 1.34+/-0.41. All patients with degenerative goitre (24 cases) and the one patient with Hashimoto's disease were TETRO negative after 1 h and the N/T ratio was 0.92+/-0.12 on the late scan. Our results indicate that 99mTc-tetrofosmin scanning is of little value preoperatively in distinguishing thyroid carcinoma from other thyroid nodules. Tetrofosmin tends to demonstrate thyroid adenomas but does not have a routine role in the assessment of thyroid nodules.

Adenocarcinoma, Follicular↗

Toxoplasma gondii infection in the mountain hare (Lepus timidus) and domestic rabbit (Oryctolagus cuniculus). II. Early immune reactions.

As already reported, the mountain hare is much more susceptible than the domestic rabbit to oral inoculation with Toxoplasma gondii, as judged by pathological changes and dissemination of parasites within the body. In the present paper, further interspecies variations are reported. Concentrations of the acute phase reactant haptoglobin were raised in hares but not in rabbits one week post-infection (pi), probably reflecting the severe tissue damage present. No difference in the early humoral immune response of hares and rabbits was found, both species producing IgM and IgG antibodies to T. gondii one week pi. Lymphocyte stimulation tests performed before and one week after inoculation showed a high proliferative response to the parasite in blood cell cultures from rabbits but not hares. The fatal outcome of T. gondii infection in the hares is probably due, at least in part, to the lack of cellular response.

Animals↗

Long-term humoral antibody responses by various serologic tests in pigs orally inoculated with oocysts of four strains of Toxoplasma gondii.

Antibody titers to Toxoplasma gondii were determined in 16 pigs orally inoculated with 1000 or 10,000 oocysts of one of the four strains (GT-1, ME-49, TS-2, TC-2) of T. gondii. Pigs were euthanized on postinoculation days 103-875 and their tissues were bioassayed for T. gondii. Antibody titers were measured in the modified agglutination test (MAT) using formalin-preserved (test A) or acetone-preserved (test B) tachyzoites, latex agglutination test (LAT), indirect hemagglutination test (IHA), enzyme-linked immunobsorbant assay (ELISA), and the Sabin-Feldman dye test (DT). Toxoplasma gondii was isolated from all but two (one with GT-1 strain and one with TC-2 strain) of the inoculated pigs. Results of the serologic tests varied by test used, by strain of T. gondii and from pig to pig within groups. One pig inoculated with the TC-2 strain was considered not to be infected because it remained seronegative in all tests and T. gondii was not isolated from its tissues by bioassay. The IHA and LAT did not produce consistently positive results with infected pigs and two pigs remained seronegative (< 1:64) in both tests. At the time of necropsy, IHA titers had declined to < 1:64 in five pigs and LAT titers had declined to < 1:64 in four pigs. The MAT (test A) and ELISA detected antibodies in all infected pigs but ELISA did not detect antibody at the time of necropsy in one pig. Antibody titers peaked earliest in the DT. Antibody titers in the MAT (test B) peaked at 2560 in all seropositive pigs by 6 weeks postinoculation (PI) but declined to < 1:160 by 15 weeks PI; this test may be useful in determining recency of T. gondii infection in pigs. Overall, the MAT (test A) gave most consistent results.

Agglutination Tests↗