Biomedical subjects

T Möller

Publications and source records attributed to T Möller.

At least 37 records · Page 2Linked to original sources

PubMed2002

Carcinoma of the parotid and submandibular glands--a study of survival in 2465 patients.

Salivary gland carcinomas demonstrate a wide diversity of histopathological types and biological behavior. The aim of this study was to analyze relative survival of patients with major salivary gland carcinomas with special reference to histopathology, gender and age. All new carcinomas of the major salivary glands reported to the National Swedish Cancer Registry 1960-1995 were searched for and the vital status of the cases was updated by record linkage to the Swedish Population Registry through December 31 1996. The study comprised 2465 patients with carcinoma of the parotid or submandibular glands. Relative survival differed markedly according to histopathological typing (P<0.001). For parotid tumors, acinic cell carcinomas had the best prognosis with a 10-year relative survival of 88%. The corresponding figures for mucoepidermoid carcinomas, adenoidcystic carcinomas and carcinoma ex pleomorphic adenoma were 80, 74 and 73%. Adenocarcinoma NOS and undifferentiated carcinoma had worse prognosis, with 10-year relative survival of 55 and 44%. Patients with submandibular gland cancer had similar relative survival to those with parotid cancers, besides those with mucoepidermoid cancer and adenocarcinoma NOS, who carried worse prognosis. Age and gender had an impact on relative survival for patients with mucoepidermoid carcinoma, adenocarcinoma and undifferentiated cancer of the parotid.

Adolescent↗

PubMed2001

Observation of atomiclike electronic excitations in pure 3He and 4He clusters studied by fluorescence excitation spectroscopy.

The structure of the electronically excited states of 3He and 4He clusters is investigated using fluorescence excitation spectroscopy. Distinct bands are observed energetically close to atomic 1s-ns, nd, np transitions and attributed to perturbed excited He atomiclike states with different principle and orbital quantum numbers. The line shifts and widths of the bands of 3He and 4He clusters of the same size are different and correlate with the average particle density inside the clusters calculated using the density functional method.

Journal Article↗

PubMed2001

Relation between drug treatment and cancer in hypertensives in the Swedish Trial in Old Patients with Hypertension 2: a 5-year, prospective, randomised, controlled trial.

BACKGROUND: Is cancer related to hypertension and blood pressure? Do antihypertensive drugs promote cancer? Do antihypertensive drugs protect against cancer? We previously analysed the frequency of cardiovascular mortality and morbidity in elderly people who participated in the Swedish Trial in Old Patients with Hypertension 2 (STOP-Hypertension-2). We have also looked at the frequency of cancer in these patients. METHODS: We randomly assigned 6614 elderly patients with hypertension (mean age 76 years, median time of follow-up 5.3 years) to one of three treatment strategies: conventional drugs (diuretics or b-blockers), calcium antagonists, or ACE inhibitors. We matched the patients to the Swedish Cancer Registry and compared our findings with expected values based on age, sex, and calendar-year-specific reference frequencies for the general Swedish population. We also compared the number of cancers between the three treatment groups. FINDINGS: At baseline, 607 (9%) patients had previous malignant disease. Diagnoses were closely similar to the distribution of cancer types that might be seen in elderly patients. During follow-up, there were 625 new cases of cancer in 590 patients. The frequency of cancer did not differ significantly between the treatment strategies, including all cancers and those at individual sites. The standardised incidence ratios (SIRs) for all cancers were also close to unity: 0.92 (95% CI 0.80-1.06) for conventional drugs, 0.96 (0.83-1.10) for calcium antagonists, and 0.99 (0.86-1.13) for ACE inhibitors. INTERPRETATIONS: No difference in cancer risk was seen between patients randomly assigned to conventional drugs, calcium antagonists, or ACE inhibitors. Thus, the general message to the practising physician is that more attention should be given to getting the blood pressure down than to the risk of cancer.

Aged↗

PubMed2001

Expression and function of lysophosphatidic acid receptors in cultured rodent microglial cells.

Microglia are the resident tissue macrophages of the central nervous system. They are rapidly activated by a variety of insults; and recently, receptors linked to cytoplasmic Ca(2+) signals have been implicated in such events. One potential class of receptors are those recognizing lysophosphatidic acid (LPA). LPA is a phospholipid signaling molecule that has been shown to cause multiple cellular responses, including increases in cytoplasmic calcium. We examined whether any of the known LPA receptor genes (lp(A1)/Edg2, lp(A2)/Edg4, and lp(A3)/Edg7) are expressed by cultured mouse or rat microglia. Reverse transcriptase-polymerase chain reaction indicated that mouse microglia predominantly expressed the lp(A1) gene, whereas rat microglia predominantly expressed lp(A3). Although LPA induced increases in the cytoplasmic Ca(2+) concentration in both microglial preparations, the responses differed substantially. The Ca(2+) signal in rat microglia occurred primarily through Ca(2+) influx via the plasma membrane, whereas the Ca(2+) signal in mouse microglia was due to release from intracellular stores. Only at high concentrations was an additional influx component recruited. Additionally, LPA induced increased metabolic activity in mouse (but not rat) microglial cells. Our findings provide evidence for functional LPA receptors on microglia. Thus, LPA might play an important role as a mediator of microglial activation in response to central nervous system injury.

Animals↗

PubMed2001

Activation of mitogen-activated protein kinase by muscarinic receptors in astroglial cells: role in DNA synthesis and effect of ethanol.

Mitogen-activated protein kinase (MAPK) can be phosphorylated by mitogens binding to G-protein-coupled receptors and is considered a major pathway involved in cell proliferation. In this study, we report on the activation of MAPK by muscarinic acetylcholine receptors in astroglial cells, namely the 1321N1 human astrocytoma cell line, primary rat cortical astrocytes, and fetal human astrocytes. Carbachol caused a rapid and transient phorphorylation of MAPK (ERK1/2) in all cell types, with an increase in MAPK activity, without changing the levels of MAPK proteins. Human astrocytoma cells were used to characterize the effect of carbachol on MAPK. Experiments with M2- and M3-receptor subtype-selective antagonists, and with pertussis toxin, indicated that the M3 subtype is responsible for activating MAPK in glial cells. Pretreatment of cells with the protein kinase C (PKC) inhibitor bisindolylmaleimide I, or downregulation of PKC by 24-h treatment with the phorbol ester TPA inhibited carbachol-induced MAPK activation. Additional experiments with PKC alpha- or PKC epsilon-specific compounds indicated that the epsilon isozyme of PKC is primarily involved in MAPK activation by carbachol. Chelation of calcium also inhibited MAPK activation by carbachol. Two MEK (MAPK kinase) inhibitors inhibited carbachol-induced DNA synthesis but only at concentrations that exceeded those sufficient to block carbachol-induced MAPK activation. Ethanol (< or =200 mM) had no effect on MAPK when present alone and did not affect carbachol-induced MAPK activation under various experimental conditions, although it inhibits carbachol-induced DNA synthesis at low concentrations (10-100 mM). These results suggest that activation of MAPK by carbachol may be necessary but not sufficient for its mitogenic effect in astroglial cells, and that does not represent a target for ethanol-induced inhibition of DNA synthesis elicited by muscarinic receptors.

Animals↗

PubMed2001

Dietary intake of some important mycotoxins by the Swedish population.

To estimate the intake of some mycotoxins from food in Sweden, approximately 600 samples were collected and analysed for aflatoxins, ochratoxin A, patulin and trichothecenes. Intakes were calculated for average and high consumers among adults and children and compared with the tolerable daily intake (TDI) of the respective toxin. Mycotoxin levels in the food samples were generally below the European/national maximum limits. However, high levels of aflatoxins were found in some samples of Brazil nuts and pistachios. The intake of ochratoxin A, patulin and trichothecenes was found to be below the temporary, TDI values (tTDI) proposed for these toxins by international expert groups, although the intake of trichothecenes (expressed as T-2 toxin equivalents) in children with a high consumption of cereals was close to the tTDI for T-2 toxin. Since there is to date no established numerical tTDI for aflatoxins, such a value was estimated for use within the project. The calculated intake of aflatoxins in high consumers exceeded this tTDI by a factor of two. In conclusion, the exposure to mycotoxins in Sweden did not generally, give rise to any major health concerns in the present study. However, the high levels of aflatoxins in certain commodities emphasize the need for preventive measures and improved control of toxin levels in these food items. Furthermore, the need for regulatory levels for trichothecenes in cereal products should be evaluated.

Adolescent↗

PubMed2001

Gender and time differences in initial location and histological grade of non-Hodgkin's lymphomas in Southern Sweden.

In accordance with international data, non-Hodgkin's lymphomas (NHL) in the Southern Health Care Region of Sweden were more common in men than in women and there was an inreasing incidence for both genders in the 1980s and 1990s. A study of the years 1983 and 1992, i.e. the beginning and the end of a 10-year period, was carried out. Case records for 94% of all adults diagnosed in 1983 and 1992 (220 men and 171 women) were reviewed. The sites of the lymphomas and malignancy grade (Kiel classification) were recorded. Comparisons were made between the genders and between the two years studied. Among 170 men with nodal lymphomas, 49 were localized (stage I-II) in lymphoid tissue regional to the respiratory tract, 18 were localized elsewhere and 103 were generalized (stage III-IV). The corresponding sites in 138 women were 28, 33 and 77, respectively (p = 0.002), implying a predominance of stage I-II lymphomas regional to the respiratory tract in men and a larger number of localized lymphomas elsewhere, mostly abdominal retroperitoneal with or without inguinal engagement in women. High-grade nodal lymphomas were more common in 1992 (54%) than in 1983 (34%, p = 0.01). suggesting an increasing number of mainly high-grade lymphomas. For extranodal lymphomas (50 in men and 33 in women), no clear differences were observed for gender and the years studied. Risk factors, e.g. occupational hazards, are probably different for men and women. The gender differences in initial nodal location suggest that initial lymphoma sites may be related to different risk factors. Epidemiologic studies where both malignancy grade and initial lymphoma locations are taken into account may be helpful in defining risk factors.

Adolescent↗

PubMed2001

Increasing prevalence of adenocarcinoma of the oesophagus and gastro-oesophageal junction: a study of the Swedish population between 1970 and 1997.

OBJECTIVE: To see whether there was an increasing incidence of adenocarcinoma of the oesophagus and gastric cardia in the Swedish population. If there is a rising trend and variations in it can be found, could it be explained as a period or cohort phenomenon? The data were also compared with the incidence of squamous cell carcinoma and gastric cancer with the gastric cardia excluded. DESIGN: Retrospective study. SETTING: Sweden. SUBJECTS: Swedish population. MAIN OUTCOME MEASURES: Age standardised incidence for each sex was calculated using the age distribution of the world population as a reference. Age-period-cohort models were fitted to data using Poisson regression to model log incidence rates. RESULTS: For the combined group of adenocarcinoma in the oesophagus and gastric cardia age standardised incidence gradually increased during the study period. The median increase between adjacent five-year intervals was 20% in women and 14% in men. A period effect was evident in men. CONCLUSION: This study shows that the incidence of adenocarcinoma of the oesophagus and gastroesophageal junction is rising for both men and women in the Swedish population. This is explained as a period effect. As well as previously-described risk factors such as gastro-oesophageal reflux, obesity, and smoking, the increasing incidence can be explained as a shift in classification from squamous cell carcinoma to adenocarcinoma after 1985.

Adenocarcinoma↗

PubMed2000

Second malignant neoplasms after cancer in childhood and adolescence: a population-based case-control study in the 5 Nordic countries. The Nordic Society for Pediatric Hematology and Oncology. The Association of the Nordic Cancer Registries.

Our purpose was to assess the risk of developing a second malignant neoplasm (SMN) after cancer in childhood and adolescence associated with different treatment modalities. Our investigation was performed as a nested case-control study within a Nordic cohort of 25,120 patients younger than 20 years old at first malignant neoplasm (FMN) diagnosed in 1960 through 1987. SMNs were diagnosed in 1960 through 1991. For each case of SMN, 3 controls were sampled, matched by sex, age, calendar year of diagnosis and length of follow-up. For the final analysis, there were 234 cases and 678 controls. Relative risks (RRs) of various exposures were estimated by means of conditional logistic regression, with non-exposed as the reference. The RR of developing SMN in the radiated volume was 4.3 (95% confidence interval 3.0-6.2). The risk was highest in children diagnosed before the age of 5 years; it increased with the dose of radiation and with increasing follow-up time after FMN. Chemotherapy alone was not associated with an increased RR, but it significantly potentiated the effect of radiotherapy. RRs were unchanged between the periods 1960-1973 and 1974-1987, and since the use of chemotherapy increased in the latter period, the number of SMNs may increase. Hereditary factors were important for the occurrence of SMN independently of therapy. We conclude that radiation was the most important treatment-related risk factor for the development of SMN. Chemotherapy appeared to play only an accessory role during the study period, potentiating the carcinogenic effect of radiotherapy.

Adolescent↗

PubMed2000

Increased cancer risk in offspring of women with colorectal carcinoma: a Swedish register-based cohort study.

BACKGROUND: Colorectal carcinoma is one of the most common malignancies in the Western population, and a considerable proportion of colorectal carcinomas are estimated to have a familial background. METHODS: Individuals whose mothers were diagnosed with colon carcinoma or rectal carcinoma from 1958 to 1993, a total of 1. 48 million person-years, constituted the cohort of this Swedish population-based register study. The children were born during the period 1941-1993, and the cancer incidence was observed during the period 1961-1993, with the expected national Swedish incidence used as a reference. RESULTS: A significantly increased risk of colon carcinoma, rectal carcinoma, and non-Hodgkin lymphoma was observed in the cohort. The cancer risk was more pronounced in children whose mothers were age < 50 years at the time of diagnosis or had developed metachronous colorectal carcinoma. Whereas colon carcinoma in the proband implied an increased risk for both colon tumors and rectal tumors, the offspring of women who were diagnosed with rectal carcinoma were at increased risk of developing rectal carcinoma, but no significantly altered risk of colon carcinoma was observed. In the cohort, the cumulative risk for colorectal carcinoma before age 50 years was increased about 3.0 times compared with the general population. CONCLUSIONS: This report shows a significant familial aggregation of colorectal carcinoma, demonstrates possible differences in hereditary pattern between colon carcinoma and rectal carcinoma, and confirms that younger age at the time of diagnosis or the occurrence of metachronous tumors indicate familial carcinoma.

Cohort Studies↗

PubMed2000

Activation of mouse microglial cells affects P2 receptor signaling.

Microglial cells are the immunocompetent cells of the CNS, which are known to exist in several activation states. Here we investigated the impact of microglial activation on the P2 receptor-mediated intracellular calcium ([Ca(2+)](i)) signaling by means of fluo-3 based Ca(2+)-imaging. Cultured mouse microglial cells were treated with either astrocyte-conditioned medium to induce a ramified morphology or LPS to shift the cells toward the fully activated stage. The extracellular application of ATP (100 microM) induced a [Ca(2+)](i) elevation in 85% of both untreated and ramified microglial cells, whereas only 50% of the LPS-activated cells responded to the stimulus. To characterise the pharmacological profile of microglial P2 receptors we investigated the effects of various P2 agonists on [Ca(2+)](i) in cultured microglial cells. Untreated and ramified microglial cells demonstrated a very similar sensitivity to the different P2 agonists. In contrast, in LPS-activated microglia, a sharp decrease of responses to P2 agonist stimulation was seen. This indicates that microglial activation influences the capability of microglial cells to generate [Ca(2+)](i) signals upon P2 receptor activation.

Adenosine Triphosphate↗

PubMed2000

Rapid ischemic cell death in immature oligodendrocytes: a fatal glutamate release feedback loop.

Ischemic injury of immature oligodendrocytes is a major component of the brain injury associated with cerebral palsy, the most common human birth disorder. We now report that cultured immature oligodendrocytes [O4(+)/galactoceramide (GC)(-)] are exquisitely sensitive to ischemic injury (80% of cells were dead after 25.5 min of oxygen and glucose withdrawal). This rapid ischemic cell death was mediated by Ca(2+) influx via non-NMDA glutamate receptors. The receptors were gated by the release of glutamate from the immature oligodendrocytes themselves via reverse glutamate transport and included a significant element of autologous feedback of glutamate from cells onto their own receptors. High (> or = 100 microM) extracellular glutamate was protective against ischemic injury as a result of non-NMDA glutamate receptor desensitization. Other potential pathways of Ca(2+) influx, such as voltage-gated Ca(2+) channels, NMDA receptors, or the Na(+)-Ca(2+) exchanger, did not significantly contribute to ischemic Ca(2+) influx or cell injury. Release of Ca(2+) from intracellular stores was also not an important factor. In agreement with previous studies, more mature oligodendrocytes (O4(-)/GC(+)) were found to be less sensitive to ischemic injury than were the immature cells studied here.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2000

Accrual rate-limiting factors in a Swedish randomised ductal carcinoma in situ (DCIS) trial - a demographic study.

In the last two decades the introduction of mammographic screening in the Western world has increased the number of diagnosed ductal carcinomas in situ (DCIS) considerably. In situ carcinoma of the breast is considered a heterogeneous disease, the natural history of which is not well known. Thus, appropriate treatment needs to be established. For this reason, a randomised trial studying the effect of breast conserving operation with or without postoperative radiotherapy was instituted in Southern Sweden in 1987. The aim of the present study was to assess patient accrual, identify limiting factors, and evaluate possible ways to influence these factors in order to increase patient accrual. Between 1987 and 1992, 331 patients had been registered with DCIS in the Regional Tumour Registry, 96 of which had been randomised. All 331 were subjected to chart review studying clinical data, mammography reports, cytology and pathology reports to identify inclusion and exclusion criteria according to the design of the trial. It was found that 5% (18/331) had an incorrect diagnosis of DCIS. According to the trial protocol 52% were not eligible (162/313). Fifty-eight per cent (n=88) of the 151 eligible patients had been correctly randomised. The most common reason for exclusion was lesion size. In 21% (66/313) the lesion was 'too large'. Several other limiting factors were identified such as in cytological and pathological definitions and reports, lack of information/awareness in certain physicians, patient reluctance to participate, which in turn may be influenced by the previous factor. With increased information to participating hospitals and considering the above given facts it should be possible to increase accrual from the 28% noted in the present consecutive demographic study to at least one-third of the diagnosed cases of DCIS.

Breast Neoplasms↗

PubMed2000

Thrombin-induced activation of cultured rodent microglia.

Microglia are the resident immune cells of the CNS. Upon brain damage, these cells are rapidly activated and function as tissue macrophages. The first steps in this activation still remain unclear, but it is widely believed that substances released from damaged brain tissue trigger this process. In this article, we describe the effects of the blood coagulation factor thrombin on cultured rodent microglial cells. Thrombin induced a transient Ca(2+) increase in microglial cells, which persisted in Ca(2+)-free media. It was blocked by thapsigargin, indicating that thrombin caused a Ca(2+) release from internal stores. Preincubation with pertussis toxin did not alter the thrombin-induced [Ca(2+)](i) signal, whereas it was blocked by hirudin, a blocker of thrombin's proteolytic activity. Incubation with thrombin led to the production of nitric oxide and the release of the cytokines tumor necrosis factor-alpha, interleukin-6, interleukin-12, the chemokine KC, and the soluble tumor necrosis factor-alpha receptor II and had a significant proliferative effect. Our findings indicate that thrombin, a molecule that enters the brain at sites of injury, rapidly triggered microglial activation.

Adenosine Triphosphate↗

PubMed2000

["Non-solvent shock agglomeration technology" as a new alternative method for work on ibuprofen. 4. Production and evaluation of quick release forms].

During compaction of shock-agglomerated S(+)ibuprofen it was of interest if and how far the sometimes strongly differing quality or the origin of the source material has effects on the tabletting properties and on tablet quality. Moreover, conventional and shock agglomerated substances are compared with regard to the parameters mentioned. The technology of "non-solvent shock agglomeration" results in substances suitable for direct tabletting. Additionally, the resulting comprimates have characteristics which can be clearly traced back to the special quality of the ibuprofen-shock agglomerates. By using different agents in the process of substance preparation specific galenic properties can be achieved.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

["Non-solvent shock agglomeration"--technology of a new alternative method for sustained release of ibuprofen. 5. Production and evaluation of retard formulations].

Conventional and prepared racemic and optically pure substances were assessed with regard to their suitability to be processed into retarded formulations by direct tabletting. In this respect conventional ibuprofen and specially granulated substances usually show only insufficient properties. Fluid bed granulated S(+)ibuprofen, however, can be suitably transformed into slow release forms by using traditional agents (above all cellulose ether); the low bulk and tapped volume of these granulates, however, is a limiting factor. Shock agglomerated ibuprofen (in particular racemic substance) offers all preconditions of dissolution in acid environment correspondingly prepared substances can cause significant release retardation in artificial intestinal juice. Moreover acceptable tablet qualities (e.g. hardness) can be guaranteed.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

["Non-solvent shock agglomeration"--the technology of a new alternative method for determination of ibuprofen. 6. Stability of s(+)-ibuprofen].

Due to its low melting range approx. 53 degrees C optically pure ibuprofen can be regarded as problematic in a pharmaceutic-technological sense. With regard to the non-solvent shock agglomeration method this means that the process and product temperatures must strictly be kept in the range of 10 K above the melting point of the substance. Higher temperatures can induce degradation of S(+)ibuprofen. During storage under stress conditions (31 degrees C for a period of 18 months) ibuprofen shows extreme stability independent of its optical activity. Racemic ibuprofen is inert to the influence of light; in individual cases optically pure substance containing an increased level of impurities can show slight degradation tendencies. The thermal and photo stability of ibuprofen is independent of the preparation technology. For comparison, conventional, fluid bed granulated, briquetted and from organic solvents especially recrystallised and optically active substances were investigated besides the shock agglomerated substances.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Lysophosphatidic acid-induced calcium signals in cultured rat oligodendrocytes.

Oligodendrocytes are the myelin forming glial cells of the CNS and are known to express receptors linked to ion channels and intracellular second messenger cascades. In this paper, we describe the intracellular calcium responses of cells from the oligodendrocyte lineage to application of lysophosphatidic acid (LPA), a naturally occurring, growth factor-like phospholipid. Oligodendrocyte precursors did not respond to application of LPA (1 microM). In mature oligodendrocytes, however, LPA (1 microM) induced an increase in the intracellular calcium concentration ([Ca2+]i). In the majority of cells this increase was followed by a persistent plateau phase. The LPA-induced [Ca2+]i signal vanished in Ca2+-free medium, implying that it arose due to a Ca2+ influx across the plasma membrane. Preincubation of the cells with Pertussis-toxin prevented the generation of LPA-induced [Ca2+]i signals. We conclude that cultured rat oligodendrocytes express functional LPA receptors, which mediate a transmembrane Ca2+ influx via a Pertussis-toxin-sensitive G-protein.

Animals↗