1,377 research outputs found
Endocrine Factors, Retinal Vessels, and Risk of Dementia
First described 100 years ago by Alois Alzheimer, the clinico-pathological entity that we
now call Alzheimer disease was initially presented as a clinically unusual type of dementia.
1 Nowadays, Alzheimer disease is recognized as the main cause of dementia and one
of the most disabling and burdensome health conditions worldwide.2,3 The number of
people affected by dementia is estimated to double every 20 years to over 80 million by
2040.3 This will not only affect patients and their caregivers, but will also put an enormous
demand on health care and welfare resources
Serum inhibin B as a marker of spermatogenesis
Inhibin B is produced by Sertoli cells, provides negative feedback on FSH
secretion, and may prove to be an important marker for the functioning of
seminiferous tubules. The purpose of the present study was to examine the
relationship between the spermatogenic function of the testis of
subfertile men and the plasma concentrations of inhibin B and FSH. These
parameters were estimated in a group of 218 subfertile men. Serum inhibin
B levels were closely correlated with the serum FSH levels (r = -0.78, P <
0.001), confirming the role of inhibin B as feedback signal for FSH
production. The spermatogenic function of the testis was evaluated by
determining testicular volume and total sperm count. Inhibin B levels were
significantly correlated with the total sperm count and testicular volume
(r = 0.54 and r = 0.63, respectively; P < 0.001). Testicular biopsies were
obtained in 22 of these men. Inhibin B was significantly correlated with
the biopsy score (r = 0.76, P < 0.001). Receiver operating characteristic
analysis revealed a diagnostic accuracy of 95% for differentiating
competent from impaired spermatogenesis for inhibin B, whereas for FSH, a
value of 80% was found. We conclude that inhibin B is the best available
endocrine marker of spermatogenesis in subfertile men
Clinical aspects of glucocorticoid sensitivity
Recent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor gene make 6.6% of the normal population relatively 'hypersensitive' to glucocorticoids, while 2.3% are relatively 'resistant.' These abnormalities might explain why some individuals develop severe adverse effects during low dose glucocorticoid therapy, while others do not develop side effects even during long-term therapy with a much higher dose. Awareness of this heterogeneity in glucocorticoid sensitivity in the normal population might eventually allow the prediction of a 'safe' dose of glucocorticoid in individual patients. 'Resistance' to the beneficial clinical effects of glucocorticoid therapy in part of the patients with severe rheumatoid arthritis and asthma is probably rarely related to generalized primary (hereditary) glucocorticoid resistance. In the majority of patients this 'resistance' seems to be acquired and localized to the sites of inflammation, where it reflects high local cytokine production, which interferes with glucocorticoid action. Recognition of localized, acquired glucocorticoid resistance is of great importance indicating as alternative drug therapy with other immune-modulating drugs like cyclosporin and methotrexate. Chronic high dose glucocorticoid treatment in such patients is ineffective in alleviating symptomatology, while generalized side effects occur, reflecting the patient's normal systemic sensitivity to these drugs
Prediction of survival with alternative modeling techniques using pseudo values
Background: The use of alternative modeling techniques for predicting patient survival is complicated by the fact that some alternative techniques cannot readily deal with censoring, which is essential for analyzing survival data. In the current study, we aimed to demonstrate that pseudo values enable statistically appropriate analyses of survival outcomes when used in seven alternative modeling techniques. Methods: In this case study, we analyzed survival of 1282 Dutch patients with newly diagnosed Head and Neck Squamous Cell Carcinoma (HNSCC) with conventional Kaplan-Meier and Cox regression analysis. We subsequently calculated pseudo values to reflect the individual survival patterns. We used these pseudo values to compare recursive partitioning (RPART), neural nets (NNET), logistic regression (LR) general linear models (GLM) and three variants of support vector machines (SVM) with respect to dichotomous 60-month survival, and continuous pseudo values at 60 months or estimated survival time. We used the area under the ROC curve (AUC) and the root of the mean squared error (RMSE) to compare the performance of these models using bootstrap validation. Results: Of a total of 1282 patients, 986 patients died during a median follow-up of 66 months (60-month survival: 52% [95% CI: 50%-55%]). The L
Long-term treatment with the dopamine agonist quinagolide of patients with clinically non-functioning pituitary adenoma
OBJECTIVE: This study was performed to evaluate the effect of prolonged
treatment with the dopamine agonist quinagolide on serum gonadotropin and
alpha-subunit concentrations and tumor volume in patients with clinically
non-functioning pituitary adenomas (CNPA). DESIGN: Ten patients with CNPA
were treated with quinagolide (0.3 mg daily). The median duration of
treatment was 57 months (range 36-93 months). Blood samples for
measurement of serum gonadotropin and alpha-subunit concentrations were
drawn before treatment, after 5 days, and at each outpatient visit.
Computerized tomography or magnetic resonance imaging of the pituitary
region and Goldmann perimetry were done before and at regular intervals
during treatment. RESULTS: A significant decrease of serum FSH, LH or
alpha-subunit concentrations was found in nine patients. The levels
remained low during the entire treatment period. In two out of three
patients with pre-existing visual field defects a slight improvement was
shown during the first months of treatment, but eventually deterioration
occurred in all three patients. A fourth patient developed unilateral
ophthalmoplegia dur
Fertility and body composition after laparoscopic bilateral adrenalectomy in a 30-year-old female with congenital adrenal hyperplasia
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused
by an inborn defect in the 21-hydroxylase gene (CYP21), leading to
virilization of female patients and causing ambiguous genitals in the
majority of female infants. Adult women may suffer from loss of libido,
irregular or absent cycles, and reduced fertility, despite intensive
medical treatment. These problems have stimulated the search for
alternative treatment modalities. We present an adult female patient, who
was difficult to treat medically and whose clinical situation markedly
improved after laparoscopic bilateral adrenalectomy. The procedure was
well tolerated and without side effects. Postoperatively the elevated
serum progesterone and 17-hydroxyprogesterone levels, as well as the
undetectable LH levels, normalized. The procedure resulted in marked
clinical improvement. Within 12 months after surgery she lost 11 kg in
weight. This weight loss consisted mainly of adipose tissue. Acne
disappeared, and she had a regular 4-week menstrual cycle, with
progesterone levels that are compatible with a luteal phase. The
introduction of laparoscopic techniques may give an impulse to the
application of surgical therapy at a larger scale in patients with
21-hydroxylase deficiency who are difficult to treat with adrenal
suppression therapy
A composite measure of cognitive and functional progression in Alzheimer's disease: Design of the Capturing Changes in Cognition study
markdownabstract__Introduction__ Cognitive testing in Alzheimer's disease (AD) is essential for establishing diagnosis, monitoring progression, and evaluating treatments. Assessments should ideally be brief, reliable, valid, and reflect clinically meaningful changes. There is a lack of instruments that meet all these criteria. In the Capturing Changes in Cognition (Catch-Cog) study, we seek to correct these deficiencies through the development and validation of a composite measure combining cognition and function: the cognitive-functional composite (CFC). We expect that the CFC is able to detect clinically relevant changes over time in early dementia stages of AD.
__Methods/Design__ We will include patients (n = 350) with mild cognitive impairment or mild dementia due to AD from memory clinics in the Netherlands and the United Kingdom. We will include cognitively healthy volunteers (n = 30) as a control group. The CFC is based on the “cognitive composite” and the Amsterdam instrumental activities of daily living questionnaire. We will investigate test–retest reliability with baseline and 2- to 3-week follow-up assessments (n = 50 patients and n = 30 healthy controls). We will involve experts and participants to evaluate the initial feasibility and refine the CFC if needed. Subsequently, we will perform a longitudinal construct validation study in a prospective cohort (n = 300) with baseline, 3-, 6-, and 12-month follow-up assessments. The main outcome is cognitive and functional progression measured by the CFC. Reference measures for progression include traditional cognitive and functional tests, disease burden measures, and brain imaging methods. Using linear mixed modeling, we will investigate longitudinal changes on the CFC and relate these to the reference measures. Using linear regression analyses, we will evaluate the influence of possible confounders such as age, gender, and education on the CFC.
__Discussion__ By performing an independent longitudinal construct validation, the Catch-Cog study of the novel CFC will contribute to the improvement of disease monitoring and treatment evaluation in early dementia stages of AD
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