Molecular evidence for tuberculosis in an ancient Egyptian mummy.
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DNA, Bacterial↗
Biomedical subjects
A Zink
Publications and source records attributed to A Zink.
An open distributed medical image and signal data server network with World Wide Web front-end.
In modern patient care and medical research diagnostic imaging from multiple modalities plays an essential role. In general these digital image data are acquired at different locations. An efficient access to the data via network is often not provided due to technical, organisational and political reasons. This article presents an approach to solve the problem by means of an open distributed data server network with Web-based front-ends and describes the prototype DACHS that has been developed at the University Hospital of the Technical University of Munich.
Computer Communication Networks↗
Importance of psychological well being and disease activity in termination of an initial DMARD therapy.
OBJECTIVE: To estimate the frequency of and to identify possible risk factors involved with terminating an initial disease modifying antirheumatic drug (DMARD) therapy. We hypothesized that treatment termination depends not only on side effects and inefficacy but also on the therapeutic setting and the health beliefs of the patient. METHODS: We observed an inception cohort of 302 patients with early rheumatoid arthritis (< 2 years) and first prescription of DMARD for 3 years. Survival analysis was used to estimate treatment continuation under rheumatological care. The study group comprised 4 rheumatological outpatient clinics and 7 private practices in Berlin. RESULTS: Of the initial cohort 80% continued the same drug or were in remission after one year, 70% after 2 years. Within the first 2 years, methotrexate therapy was terminated in 15% of the cases and sulfasalazine therapy in 40%, respectively. In both forms of therapy, the discontinuation rate was dependent on initial disease activity. However, the influence of the patient's psychological status at baseline was equally strong. DMARD treatment was terminated earlier and more frequently in patients with poor psychological well being. These findings hold true after controlling for disease activity or severity. CONCLUSION: Patient psychological well being and disease activity at start of initial DMARD therapy are important predictors of early drug discontinuation. By influencing psychological well being (e.g., by patient education programs), continuation of DMARD therapy might be further improved.
Adult↗
Oral type II collagen treatment in early rheumatoid arthritis. A double-blind, placebo-controlled, randomized trial.
OBJECTIVE: To investigate the efficacy of oral type II collagen in the treatment of early rheumatoid arthritis (RA). METHODS: Ninety patients with RA (disease duration < or = 3 years) were treated for 12 weeks with oral bovine type II collagen at 1 mg/day (n = 30) or 10 mg/day (n = 30) or with placebo (n = 30), in a double-blind randomized study. RESULTS: There were no significant difference between the 3 groups in terms of response to treatment. However, we observed a higher prevalence of responders in the type II collagen-treated groups: 7 responders in the 10-mg type II collagen group and 6 in the 1-mg group, versus 4 in the placebo group. Furthermore, 3 patients in the 10-mg type II collagen group and 1 patient in the 1-mg type II group, but no patients in the placebo group, had very good response. A total of 14 patients had to be withdrawn from the study: 2 because of side effects (nausea) and 12 because of lack of efficacy. CONCLUSION: Only a minority of patients responded to treatment with oral type II collagen. These results justify further efforts to identify which patients will have good response to such therapy.
Administration, Oral↗
Clinical studies of multiple endocrine neoplasia type 1 (MEN1)
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid, pancreatic islet and anterior pituitary tumours. To facilitate a screening programme for MEN1, we investigated 709 people (364 males and 345 females, age range 1-84 years) from 62 MEN1 families, and 36 non-familial MEN1 patients. Of those investigated, 220 (95 males and 125 females, age range 8-79 years) suffered from MEN1. Parathyroid, pancreatic and pituitary tumours occurred in 95%, 41% and 30% of the patients, respectively. Parathyroid tumours were the first manifestation of MEN1 in 87% of patients, and amongst the pituitary and pancreatic tumours, somatotrophinomas and gastrinomas were more common in patients above the age of 40 years, whilst insulinomas occurred more frequently in patients below the age of 40 years. Biochemical screening indicated that the penetrance of MEN1 by the ages of 20, 35 and 50 years was 43%, 85% and 94%, respectively, and that the development of MEN1 was confined to first-degree relatives in 91% of patients and to second-degree relatives in 9% of patients. These findings have helped to define a proposed screening programme for MEN1.
Adolescent↗
[Results of early rehabilitation using various knee prosthesis models].
The present contribution deals with the early rehabilitation outcomes achieved using total knee arthroplasties with major differences in design. Hinged and unhinged total knee replacements are compared for a total of 100 patients included in the prospective study (48 hinged prostheses, and 52 unhinged ones). Evaluation of the functional and subjective parameters included shows that major improvements in total scores had been achieved in both groups already after 5 weeks, even more pronounced after 10 weeks. With a number of differences found for the various criteria assessed, it in particular is the fact of early stability of the joint in using the hinged prostheses that entails speedy progress and a good rehabilitation outcome. Due consideration of the different early outcomes for the various parameters, hence, is imperative in pre-operative decision-making.
Activities of Daily Living↗
[Health care status of rheumatic patients in rheumatologic centers 1993].
Since 1992 the Federal Minister of Health has supported 21 arthritis centres in all regions of Germany. Their major aim is to improve collaboration between the various experts involved in the health care of arthritis patients. Results of the uniform patient documentation are presented. Compared to previous reports, the collaboration in outpatient care seems to have improved: the majority of patients seen in specialized care is referred within the first two years. Nevertheless, only less than one fourth of the true prevalence of rheumatoid arthritis has been seen by the specialists. There are still deficits concerning comprehensive care like occupational therapy, patient education, and psychological support in coping with pain. There is also a deficit concerning early rehabilitation. This is associated with a high rate of early retirement: 30% of the patients in the working age with a disease duration of five years or more have been retired for health reasons. As it was described in the USA, we found an association of formal education and functional status in patients suffering from rheumatoid arthritis: after having controlled for age, sex, and duration of disease, it became evident that patients with a low educational level have a significantly lower functional capacity.
Adolescent↗
Adenosine A1-receptors inhibit cAMP and Ca2+ mediated calcitonin secretion in C-cells.
The effect of the adenosine A1 receptor activation on calcitonin secretion was studied in medullary thyroid carcinoma cells of the rat (rMTC 6-23). Calcitonin was determined by radioimmunoassay, intracellular cAMP by protein binding assay, intracellular calcium in fura-2 loaded single cells using microspectrofluorimetry, and calcium channel activity by patch clamp technique. The adenosine A1 receptor analogue N-6 phenylisopropyl-adenosine (PIA) (10(-10)-10(-6) M) inhibits dose-dependently glucagon (10(-7) M) and rGRH (10(-7) M) stimulated cAMP formation and calcitonin secretion. These effects were partly abolished by pretreatment with pertussis toxin (PT) (100 ng/ml). PIA (10(-10)-10(-6) M) also suppressed extracellular calcium-stimulated calcitonin secretion, rises in intracellular calcium, and calcium channel currents. PT (100 ng/ml) pretreatment again partly abolished this inhibitory effect. The addition to the medium of adenosine deaminase (0.4 U/ml) stimulated calcitonin secretion. Our results suggest that in calcitonin-secreting cells A1 receptors couple to adenylate cyclase and calcium channels via PT-sensitive G proteins and thus inhibit calcitonin secretion. Adenosine seems to act as an autocrine/paracrine factor in calcitonin-secreting cells.
Adenosine↗
[The role of somatostatin on the cellular level].
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Adenylyl Cyclases↗
Regulation of calcitonin secretion in vitro.
The concentration of extracellular calcium rightly regulates calcitonin secretion by calcium influx through dihydropyridine-sensitive voltage-dependent calcium channels; the result is an increase in intracellular calcium. There also exists a cAMP-dependent pathway of calcitonin release activated by glucagon or growth hormone releasing hormone. In thyroid C-cells, as in all cells, there is dual regulation of adenylate cyclase, mediated by inhibitory or stimulatory G proteins; glucagon stimulated cAMP production can be inhibited by somatostatin via pertussis toxin sensitive inhibitory G proteins. Somatostatin inhibits not only cAMP dependent but also calcium-dependent calcitonin secretion. Furthermore, somatostatin inhibits voltage dependent calcium channel currents thereby lowering cytosolic calcium. These actions also involve a pertussis toxin-sensitive inhibitory G protein but they occur independently of changes in the cytosolic cAMP concentration. Thus multiple interactions between second messenger systems at different cellular levels modulate calcitonin secretion.
Animals↗
Long-term exposure to SMS 201-995 inhibits proliferation and calcitonin release in neoplastic C-cells.
The effect of the long-acting somatostatin analogue SMS 201-995 on cellular proliferation and calcitonin production was examined in rMTC 6-23 cells. A dose-dependent inhibition of calcitonin release and cellular calcitonin content was obtained in cells exposed to SMS 201-995 for 72 hrs. The dose-dependent antiproliferative effect of SMS 201-995 (10(-8)-10(-6) M) was significant after 72 hrs of exposure. SMS 201-995 has an inhibitory effect on calcitonin secretion and synthesis as well as on the growth of C-cells.
Animals↗
Major role of dihydropyridine-sensitive Ca2+ channels in Ca(2+)-induced calcitonin secretion.
Endocrine cells are known to possess multiple types of Ca2+ channels. In neurons, omega-conotoxin-sensitive N-type Ca2+ channels have been shown to play a dominant role in neurotransmitter release, but uncertainty remains about the types of Ca2+ channels involved in stimulus-secretion coupling in endocrine cells. We investigated the relative contribution of 1,4-dihydropyridine-sensitive and omega-conotoxin-sensitive Ca2+ channels to Ca(2+)-induced calcitonin release in parafollicular cells of the thyroid (C cells). In whole cell voltage-clamp experiments, both 1,4-dihydropyridine-sensitive and omega-conotoxin-sensitive Ca2+ channel currents were identified. The dihydropyridine isradipine (1 microM) but not omega-conotoxin (1 microM) inhibited the steady-state Ca2+ influx at physiological membrane potentials, the spontaneous electrical activity, and calcitonin secretion (at 2-h incubations). Moreover, suppression of the spontaneous electrical activity by the Na+ channel blocker tetrodotoxin did not affect calcitonin release. We conclude that 1,4-dihydropyridine-sensitive Ca2+ channels play a major role in Ca(2+)-dependent calcitonin release and that calcitonin secretion due to Ca2+ influx proceeds even in the absence of action potentials.
Animals↗
Regulation of calcitonin secretion and calcitonin gene expression.
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Aging↗
Evaluation of sensitive PDN-21 (katacalcin) determination as tumor marker in medullary thyroid carcinoma.
PDN-21 (katacalcin), a peptide from the calcitonin (CT) gene, was measured in plasma from healthy persons and patients with medullary thyroid carcinoma (MTC). PDN-21 was detectable (greater than or equal to 10 ng/l) in 73% of normal persons (n = 40). In 17 normal persons with undetectable basal plasma levels, PDN-21 became detectable (greater than or equal to 10 ng/l) by stimulation with iv pentagastrin in 7 cases. Basal levels were more often detectable in men than in women. In 65 patients with MTC, PDN-21 levels were highly correlated with CT levels as determined by an "in house" RIA (r = 0.99); the mean ratio of CT/PDN-21, on a molar base, was 0.96 +/- 0.33 over the entire range. In iv stimulation tests with pentagastrin, PDN-21 and CT showed good parallelism (mean ratio of CT/PDN-21: 1.1 +/- 0.62); in MTC patients with normal basal levels, however, peak to basal ratios during iv pentagastrin testing were higher for PDN-21 than for CT, due to the more sensitive PDN-21 assay. In a selective venous catheter study of a patient with MTC, the mean CT/PDN-21 ratio for all samples was 1.04 +/- 0.12, but the peak to peripheral levels were higher for PDN-21 (4.1-fold) than for CT (2.8-fold). In conclusion, determination of PDN-21 by RIA is equivalent to determination of CT in diagnosing MTC patients. In few patients, it might be even slightly more sensitive. PDN-21 should be determined in all cases with borderline CT results.
Biomarkers, Tumor↗
Inhibitory effect of somatostatin on cAMP accumulation and calcitonin secretion in C-cells: involvement of pertussis toxin-sensitive G-proteins.
The effect of somatostatin on cAMP accumulation and calcitonin secretion in C-cells of the rat medullary thyroid carcinoma cell line rMTC 6-23 was investigated. Intracellular cAMP accumulation as well as calcitonin secretion could be dose-dependently stimulated by rat growth hormone releasing factor (rGRF). The long-acting somatostatin analogue octreotide inhibited rGRF-stimulated cAMP accumulation and calcitonin secretion dose dependently but failed to block 8-bromo-cAMP-stimulated calcitonin secretion. The inhibitory effect of octreotide on rGRF-induced calcitonin secretion was partially abolished by pretreating the cells with pertussis toxin. The octreotide effect was not due to changes in the degradation of cAMP, as it was similarly seen in the presence of isobutylmethylxanthine. Thus we conclude that pertussis toxin-sensitive G-proteins are involved in the cAMP-mediated regulation of calcitonin secretion in C-cells.
Animals↗
Inhibition of Ca(2+)-induced calcitonin secretion by somatostatin: roles of voltage dependent Ca2+ channels and G-proteins.
Somatostatin has recently been applied therapeutically for hypercalcitonemia in patients with calcitonin-producing tumours. Using calcitonin-secreting cells (C-cells) of the medullary thyroid carcinoma cell line rMTC 44-2, we investigated the inhibitory action of somatostatin on calcitonin release, cytosolic Ca2+ and Ca2+ channel currents. The Ca(2+)-induced rises of the cytosolic Ca2+ and calcitonin secretion were greatly inhibited by somatostatin or its stable analogue octreotide. The effects of somatostatin were pertussis toxin-sensitive. Under voltage clamp conditions, C-cells exhibited slowly inactivating Ca2+ channel currents. Bath application of 100 nM somatostatin reversibly reduced the Ca2+ channel current by about 30%. The Ca2+ channel current and its inhibition by somatostatin were not affected by intracellularly applied cyclic AMP. Moreover, pretreating the cells with pertussis toxin had no effect on the control Ca2+ channel currents but greatly abolished its inhibition by somatostatin. The data show that somatostatin suppresses the Ca(2+)-stimulated calcitonin secretion by inhibiting voltage-dependent Ca2+ channel currents and by lowering cytosolic Ca2+. These actions of somatostatin involve pertussis toxin-sensitive G-proteins and occur independently of changes in the cyclic AMP concentration.
Animals↗
Clinical features of multiple endocrine neoplasia type 1 and type 2.
The term 'Multiple Endocrine Neoplasia' (MEN) denotes a genetically determined syndrome characterized by the independent appearance of benign or malignant changes of several endocrine organs as well as occasional changes of neural, muscular and connective tissue. Three different forms have been identified: MEN 1 (Werner's syndrome) includes parathyroid hyperplasia in combination with pancreatic islet cell and pituitary tumours; MEN 2a (Sipple's syndrome) includes medullary thyroid carcinoma in association with phaeochromocytoma and parathyroid hyperplasia; MEN 2b includes medullary thyroid carcinoma, phaeochromocytoma and mucosal neuromas. MEN syndrome is transmitted as an autosomal dominant trait with a high degree of penetrance. The changes in the individual glands appear to be causally and temporally independent of each other. A spectrum of pathological changes exist in the affected glands which range from hyperplasia to adenoma to carcinoma. The pathological process is almost always multicentric, often resulting in bilateral disease of organs. The appearance of an endocrine tumour known to be associated with MEN should alert the physician to the possibility of a MEN syndrome. When the possibility of such a syndrome exists, screening and long-term observation should be initiated to diagnose a carcinoma in its earliest stage, or before the development of clinical manifestations of hormone excess.
Adenoma, Islet Cell↗
Determination of serum calcitonin by immunometric two-site assays in normal subjects and patients with medullary thyroid carcinoma.
We evaluated the clinical usefulness of a commercial two-site immunoassay for calcitonin, which is based on two monoclonal antibodies against distinct epitopes of calcitonin. The potential lower detection limit of the assay was 2 ng/l. Inter-assay and intra-assay variation were both < 11%. No cross reaction with calcitonins from different species (salmon and eel calcitonin) was found. Of the various fragments of human calcitonin, only the 11-32 fragment could be detected. Basal calcitonin concentrations in normals (n = 69) ranged from < 2 ng/l to 50 ng/l. Basal calcitonin concentrations in 30% of the men (< 2-48 ng/l) and 51% of the women (< 2-10 ng/l) were undetectable. Stimulation of calcitonin with pentagastrin (0.5 microgram/kg body weight) in normal subjects was followed by an increase in calcitonin in all men (n = 17) and in 60% of the women (n = 12). The upper reference value for pentagastrin-stimulated calcitonin concentrations for all 29 normals was 78 ng/l (defined as the 95th percentile): 79 ng/l for men, and 50 ng/l for women. Using a different immunoradiometric two-site assay, a similar percentage of "positive" responses to pentagastrin in normals was obtained (20 out of 29). Four previously thyroidectomized patients with medullary thyroid carcinoma had normal basal, but pathological stimulated calcitonin values at follow-up. At reoperation, cervical lymph nodes with tumour tissue were removed. Postoperatively, the patients had basal and stimulated calcitonin concentrations within the limits of the established reference range. In conclusion, reference ranges for basal and pentagastrin-stimulated calcitonin concentrations have been established for an immunometric two-site assay.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗