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Biomedical subjects

Thomas Schreiner

Publications and source records attributed to Thomas Schreiner.

8 recordsLinked to original sources

[Endogenous Cushing's syndrome].

BACKGROUND: Untreated endogenous Cushing's syndrome is a serious condition with high morbidity and mortality. New diagnostic procedures make today's assessment more accurate. We describe which tests should be done when there is suspicion of the syndrome. Treatment options are mentioned. MATERIAL AND METHODS: The paper is based on current international literature and reflects the experience of the authors. RESULTS AND INTERPRETATION: Endogenous Cushing's syndrome is caused by elevated cortisol levels. The reason can be overproduction of ACTH or an adrenocortical pathology. It should be considered when combinations of symptoms like central obesity, proximal muscle weakness, striae and menstrual irregularities are seen. Osteoporosis and impotence are other important symptoms. Diagnosis of Cushing's syndrome is often challenging. Measurement of urinary free cortisol or overnight dexamethasone suppression test has usually been performed initially. Midnight salivary cortisol seems promising as an alternative. The final diagnosis is often made after a combined evaluation of dynamic tests. The first-line treatment of endogenous Cushing's syndrome is surgery.

Adrenocorticotropic Hormone↗

Positive effects of a physiological dose of GH on markers of atherogenesis: a placebo-controlled study in patients with adult-onset GH deficiency.

OBJECTIVE: GH deficiency is associated with an increased cardiovascular mortality. Fifty-five patients with adult-onset GH deficiency (AO-GHD) (24 female, 31 male, mean age 49 years) were enrolled in a placebo-controlled double-blind crossover study to investigate the effects of GH therapy on a variety of cardiovascular risk factors representing different aspects of atherogenesis, including apolipo-proteins (Apo A-1, Apo B), markers of subclinical inflammation (high-sensitivity C-reactive protein (CRP) and interleukin-6) and markers of endothelial function (intercellular adhesion molecule-1, von Willebrand factor and sCD40L (a pro-atherogenic factor and marker for plaque destabilization)). METHODS: GH therapy was individually dosed to obtain an IGF-I concentration within the normal range for age and sex. GH and placebo were administered for 9 months each, separated by a 4 month washout period. RESULTS: The final mean dose of GH was 50% higher for women and IGF-I increased to the same level in both sexes. Compared with placebo, substitution with GH showed a significant effect on Apo B (mean change -0.15 (-0.22 to -0.08) mg/l) and CRP (-1.8 (-3.3 to -0.3) mg/l). The baseline level of and change in IGF-I during treatment with GH contributed significantly to the improvement in both markers. No effects were found on interleukin-6 or Apo A-1, or on markers of endothelial function. No gender differences were observed for any of the markers at baseline or following intervention. CONCLUSIONS: GH substitution to naïve patients with AO-GHD at a low, individually titrated dose aiming at normalizing IGF-I was followed by significant reductions in Apo B and CRP, indicating a positive effect of GH on cardiovascular risk.

Adult↗

Immediate drug release from solid oral dosage forms.

Fast drug release from solid dosage forms requires a very fast contact of the vast majority of the drug particles with the solvent; this, however, is particularly delayed in tablets and granulations. Starch and cellulose substances favor the matrix disintegration during the starting phase and the generation of the effective dissolution surface of the drug substance, thereby. To investigate the very complex interrelation between the functionality of commonly used excipients and the structural effects of the production processes, wettability, porosity, water uptake, and drug release rates of several ketoprofen-excipient preparations (powder blends, granulations, tablets) were measured. Significant linear correlation between these parameters, however, was not achieved; only qualitative tendencies of the effects could be detected. In consequence, a general mathematical model describing the mechanistic steps of drug dissolution from solid dosage forms in a fully correct way was not realized. However, the time-dependent change of the effective dissolution surface follows stochastic models: a new dissolution equation is based on the differential Noyes-Whitney equation combined with a distribution function, e.g. the lognormal distribution, and numerically solved with the software system EASY-FIT by fitting to the observations. This new model coincides with the data to a considerably higher degree of accuracy than the Weibull function alone, particularly during the starting, matrix disintegration, and end phases. In combination with a procedure continuously quantifying the dissolved drug, this mathematical model is suitable for the characterization and optimization of immediate drug release by the choice and modification of excipients and unit operations. The interdependence of some characteristic effects of excipients and production methods is discussed.

Algorithms↗

Low-dose GH improves exercise capacity in adults with GH deficiency: effects of a 22-month placebo-controlled, crossover trial.

Fifty-five patients with adult-onset GH deficiency (mean age, 49 years) were enrolled in a placebo-controlled, crossover study to investigate the effects of GH therapy on exercise capacity, body composition, and quality of life (QOL). GH and placebo were administered for 9 months each, separated by a 4-month washout period. GH therapy was individually dosed to obtain an IGF-I concentration within the normal range for age and sex. The final mean daily dose of GH was 1.2 IU/day for men and 1.8 IU/day for women. Mean IGF-I concentration at baseline was higher in men than in women (95+/-33 vs 68+/-41 microg/l respectively; P < 0.04) and increased to a similar level on GH therapy. Body fat mass was reduced by 1.9+/-2.9 kg and lean body mass was increased by 1.8+/-2.8 kg (P = 0.0001 for each) with GH treatment. Total and low-density cholesterol levels decreased. Absolute maximal oxygen uptake increased by 6% (P = 0.01), relative to body weight by 9% (P = 0.004), and there was a trend toward increased endurance performance by 7% (P = 0.07). There were no significant effects on QOL. In conclusion, treatment with a low, physiologic dose of GH produced positive effects on body composition and lipids and improved exercise capacity, likely to be of clinical relevance. No changes in QOL were seen, possibly because of a good QOL at baseline.

Adult↗

[Hormonally inactive pituitary adenomas].

BACKGROUND: This paper surveys hormonally inactive pituitary tumours on the basis of the current international literature; it also reflects the experience of the authors. INTERPRETATION: Pituitary tumours are frequently diagnosed and usually show a low potential for growth. Although benign they may invade adjacent structures such as the cavernous and sphenoid sinuses. The diagnosis is usually made on the basis of pituitary failure or visual problems, or incidentally. Tumour debulking or removal, usually by transsphenoidal surgery, is indicated if there is a compression of the optic chiasm or if the tumour shows signs of growth on consecutive MRI scans. Surgery is an effective treatment of these tumours, with little risk of complications. Repeated surgery, either transsphenoidally or by craniotomy, is indicated if chiasmal decompression is not achieved initially. Fractionated single beam irradiation or stereotactic radiosurgery is indicated in cases where there is a residual of growing tumours that may not be removed surgically.

Acromegaly↗

[Prevalence of hypothyroidism and hyperthyroidism in Nord-Trondelag].

BACKGROUND: The objective of this survey was to examine the prevalence of thyroid disease including autoimmunity in Norway. MATERIALS AND METHODS: All 94,009 inhabitants aged 20 and above in Nord-Trøndelag county, Norway were invited to participate in a health survey. RESULTS: The prevalence of formerly diagnosed hyperthyroidism was 2.5% in women and 0.6% in men, hypothyroidism 4.8% and 0.9% respectively, increasing with age. In individuals without a history of thyroid disease the median, 2.5 and 97.5 percentiles for TSH (mU/l) were 1.8 and 0.49-5.7 for women and 1.5 and 0.56-4.6 for men. When excluding individuals with positive thyroid peroxidase antibodies (TPOAb), the 97.5 percentiles were 3.6 mU/l for women and 3.4 mU/l for men. The prevalence of pathological TSH values in women and men were TSH > or = 10 mu/l 0.9% and 0.4%; TSH 4.1-9.9 mU/l 5.1% and 3.7%; TSH < or = 0.05 mU/l 0.5% and 0.2%. The prevalence of positive TPOAb was 13.9% in women and 2.8% in men, the lowest percentage was seen with TSH 0.2-2.0 mU/l and increased both with higher and lower TSH values and was higher in women except for those with TSH > or = 10 mU/l (85% TPOAb positive). CONCLUSION: In spite of a high prevalence of recognised thyroid disease in the population a considerable number have undiagnosed thyroid dysfunction and positive TPOAb.

Adult↗

[Hyperprolactinemia and prolactinemia--investigation and treatment].

BACKGROUND: Prolactinoma represents the most commonly occurring hormone-secreting pituitary adenoma. The majority of prolactinomas are small, only rarely do we find larger prolactinomas, so-called macroadenomas. They are almost exclusively benign. The symptoms are mainly caused by elevated prolactin levels and result in changes to the reproductive and sexual function. In cases of macroprolactinomas, symptoms caused by local mass effects can be seen. A variety of other conditions may also cause hyperprolactinaemia; the goal of the examination is to identify the cause. MATERIAL AND METHODS: We have reviewed recent literature and compared findings with current management of hyperprolactinaemia and prolactinoma in Norwegian university hospitals. RESULTS AND INTERPRETATION: The primary treatment is medical, intended to normalize prolactin levels, restore gonadal function, and reduce tumour size. With the new selective dopamine agonists, the treatment is often simple and efficient, but not all patients are in need of treatment.

Adenoma↗

Loss of the F-actin binding and vesicle-associated protein comitin leads to a phagocytosis defect.

Comitin is an F-actin binding and membrane-associated protein from Dictyostelium discoideum, which is present on Golgi and vesicle membranes and changes its localization in response to agents affecting the cytoskeleton. To investigate its in vivo functions we have generated knockout mutants by gene replacement. Based on comitin's in vitro functions we examined properties related to vesicular transport and microfilament function. Whereas cell growth, pinocytosis, secretion, chemotaxis, motility, and development were unaltered, comitin-lacking cells were impaired in the early steps of phagocytosis of Saccharomyces cerevisiae particles and of Escherichia coli, whereas uptake of latex beads was unaffected. Furthermore, the lack of comitin positively affected survival of pathogenic bacteria. Mutant cells also showed an altered response to hyperosmotic shock in comparison to the wild type. The redistribution of comitin during hyperosmotic shock in wild-type cells and its presence on early phagosomes suggest a direct involvement of comitin in these processes.

Actins↗