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Biomedical subjects

S Happe

Publications and source records attributed to S Happe.

30 records · Page 2Linked to original sources

Sleep disorders and depression in patients with Parkinson's disease.

OBJECTIVES: Sleep disorders and depression are frequent in patients with Parkinson's disease (PD). However, the exact prevalence and the causality are still unknown. PATIENTS AND METHODS: We interviewed 56 consecutive PD patients and 59 age-matched healthy controls concerning sleep disorders and depression. Sleep Disorders Questionnaire (SDQ) and Zung Depression Scale (ZDS) were used as standardized valid and reliable psychometric tests. RESULTS: Patients with PD had significantly higher values in the clinical-diagnostic scale narcolepsy (P=0.01), correlating with the L-dopa dose (P=0.007). Concerning sleep apnea (P=0.49), psychiatric sleep disorder (P=1.00) and periodic limb movement disorder (P=0.12), no significant difference could be identified. PD patients showed significantly higher depression scores than healthy control subjects (P=0.01), increasing with the duration of PD (P=0.04). CONCLUSION: The significant higher narcolepsy score in PD patients must be seen due to dopaminergic medication and PD-specific neurodegeneration and immobility rather than due to narcolepsy. This leads to the conclusion that extreme caution is advised when carrying out the SDQ and interpreting the results in various persons and patient groups with motor problems. The strong association of depression, disease severity and sleep disorders in PD patients underlines the importance of identifying and treating both conditions in these patients.

Aged↗

Axonal polyneuropathy in obstructive sleep apnoea.

Chronic hypoxaemia in chronic obstructive pulmonary disease is a well known risk factor for polyneuropathy but the impact of intermittent hypoxaemia on peripheral nerve function has not been established so far. A case-control study was performed to evaluate the prevalence of polyneuropathy in obstructive sleep apnoea (OSA). Out of 24 patients with OSA, 17 (71%) had clinical signs of polyneuropathy versus seven (33%) out of 21 matched controls. The mean amplitude of the sural sensory nerve action potential was smaller in the OSA group than in the control group, indicating axonal nerve damage. The differences were significant and could not be attributed to other known risk factors for polyneuropathy. The severity of axonal damage in patients with OSA correlated with the percentage of the night time with an O(2) saturation below 90%. It is assumed that recurrent intermittent hypoxaemia in OSA is an independent risk factor for axonal damage of peripheral nerves.

Adult↗

[Progressive multifocal leukoencephalopathy in AIDS. Overview and retrospective analysis of 17 patients].

We describe retrospectively the course of 17 AIDS patients with progressive multifocal leukoencephalopathy (PML) and give a review of their clinical symptoms and survival times. The relative frequency of PML in our cohort of AIDS patients was 2.6%. The mean of CD4-positive cells was 80.5 +/- 82.5/microliter. CD4-positive cells were > 200/microliter only in one patient and increased significantly under a combination of three antiretroviral drugs whereas, with the other patients, CD4-positive cells did not increase with a maximum of two antiretroviral drugs. The mean survival time was 6.6 (1.5-20) months and correlated positively with the number of CD4-positive cells. The diagnosis of PML can be regarded as confirmed when JC-virus DNA is detectable in cerebrospinal fluid, typical changes can be seen in MRI and typical clinical symptoms occur. No effective therapy is known to date. Single case reports on therapy with cidofovir, as in one of the cases described here, showed positive results.

AIDS-Related Opportunistic Infections↗

Coatomer vesicles are not required for inhibition of Golgi transport by G-protein activators.

The G-protein activators guanosine 5'-O-(3-thiodiphosphate) (GTP gamma S) and aluminum fluoride (AIF) are thought to inhibit transport between Golgi cisternae by causing the accumulation of nonfunctional coatomer-coated transport vesicles on the Golgi. Although GTP gamma S and AIF inhibit transport in cell-free intra-Golgi transport systems, blocking coatomer vesicle formation does not. We therefore determined whether inhibition of in vitro Golgi transport by these agents requires coatomer vesicle formation. Depletion of coatomer was found to completely block coated vesicle formation on Golgi cisternae without affecting inhibition of in vitro transport by either GTP gamma S or AIF. Depletion of ADP-ribosylation factor (ARF) prevented inhibition of transport by GTP gamma S, but not by AIF, suggesting that the AIF-sensitive component in transport may not be a GTP-binding protein. Surprisingly, depletion of cytosolic ARF did not prevent the GTP gamma S-induced formation of Golgi-coated vesicles, whereas ARF was required for AIF-induced vesicle formation. Although ARF or coatomer depletion caused an increase in the fenestration of cisternae, no other ultrastructural changes were observed that might explain the inhibition of transport by GTP gamma S or AIF. These findings suggest that ARF-GTP gamma S and AIF act by distinct and coatomer-independent mechanisms to inhibit membrane fusion in cell-free intra-Golgi transport.

ADP-Ribosylation Factors↗

Maternal cerebral hemodynamics in pregnancy-related hypertension. A prospective transcranial Doppler study.

AIM: To compare maternal cerebral hemodynamics, as assessed by transcranial Doppler studies, with the clinical and radiological findings in different types of pregnancy-related hypertension and to determine their pathophysiology. METHODS: A prospective study of 66 consecutive pregnant women with hypertensive disorders (eclampsia, n = 3; pre-eclampsia, n = 41; isolated hemolysis, elevated liver enzymes, and low platelet count (HELLP)-syndrome, n = 12; pre-eclampsia superimposed on chronic hypertension, n = 5; chronic hypertension, n = 5) and 21 women with uncomplicated pregnancies. Mean blood flow velocities (Vmean) were assessed serially by means of transcranial Doppler in all basal arteries and correlated with changes in mean arterial blood pressure (MABP) and the clinical course. RESULTS: Patients with the pre-eclampsia/eclampsia syndrome showed significantly elevated Vmean values as compared to controls. In the course of the illness Vmean over the whole length of all insonated basal arteries rose simultaneously. The three eclamptic patients showed the highest Vmean values (156, 182, 192 cm/s, respectively), of the middle cerebral artery (MCA) while MABP was 135, 135, and 150 mmHg, respectively. In pre-eclamptic patients the maximal Vmean MCA ranged from 80 (67, 93) to 145 (114, 151) cm/s [median (25th, 75th percentile)] depending on the severity of clinical presentation. In patients with isolated HELLP-syndrome changes in Vmean were either mild (5/12 cases) or absent (7/12 cases). CONCLUSIONS: Considerable differences in cerebral hemodynamics were observed in the various types of pregnancy-related hypertensive disorders examined in this study. Our findings in patients with pre-eclampsia/eclampsia syndrome suggest a breakdown of autoregulation with hyperperfusion and vasogenic edema being the most probable pathophysiological mechanism.

Cerebrovascular Circulation↗

[Buschke adult scleroderma as a rare differential stiff-man syndrome diagnosis].

Stiff-man syndrome is a rare disorder of the central nervous system characterized by muscular rigidity and superimposed spasms. The etiology is still unknown and an autoimmune cause is discussed. Many differential diagnoses of muscular rigidity and of induration of the skin have to be considered. A 22 year old patient was admitted under suspicion of a stiff-man syndrome. He has had developed a painful rigidity of the trunk, starting in the neck. Massive stiffness of the trunk with pale appearance of the skin and a beginning disorder of swallowing and respiration were observed. Clinical investigation, EMG, cerebrospinal fluid and laboratory findings were all normal, thus excluding a stiff-man syndrome and other neuromuscular diseases. Skin biopsy showed typical changes of Buschke's scleredema adultorum, a rare connective tissue disorder of unknown etiology. Therapy with corticosteroide and ciclosporin led to a mild improvement of symptoms. Although rare, Buschke's scleredema adultorum should be regarded as a differential diagnosis of the stiff man syndrome.

Adult↗

[Cidofovir (vistide) in therapy of progressive multifocal leukoencephalopathy in AIDS. Review of the literature and report of 2 cases].

The progressive multifocal leukoencephalopathy (PML), a complication of the acquired immunodeficiency syndrome (AIDS) in 4%-5% of all cases, is an encephalitis caused by the JC papovavirus. The prognosis is very poor with a mean survival time after diagnosis of 3 to 6 months. No effective therapy is known to date. Therapeutic trials in small groups of patients with alpha-interferon, didanosine, and arabinoside were of minor success. A controlled study with cytarabine did not show any efficacy. Single case reports on a therapy with cidofovir (Vistide), an approved nucleotide-analogone in the therapy of cytomegalovirus-retinitis in AIDS-patients without renal dysfunction, showed positive results. We describe 2 more cases of a therapy of cidofovir in AIDS-associated PML. Out of 22 cases described in the literature, including these 2 cases, with a therapy of cidofovir in AIDS-associated PML, 16 patients improved under therapy, 2 remained stable, and only 4 patients still worsened fulminantly. These results indicate an additive antiviral effect of cidofovir against JC-virus. This may be used in the therapy of PML in AIDS-patients because no alternative antiviral therapy of PML is available at present. The efficacy of cidofovir for the therapy of PML is suggested by case reports. The exact mechanisms leading to an improvement under a therapy with cidofovir in the 16 cases described so far should be evaluated in a randomised, controlled study with an adequate size of cohorts.

AIDS-Related Opportunistic Infections↗

Cell-free transport to distinct Golgi cisternae is compartment specific and ARF independent.

The small GTPase ADP-ribosylation factor (ARF) is absolutely required for coatomer vesicle formation on Golgi membranes but not for anterograde transport to the medial-Golgi in a mammalian in vitro transport system. This might indicate that the in vivo mechanism of intra-Golgi transport is not faithfully reproduced in vitro, or that intra-Golgi transport occurs by a nonvesicular mechanism. As one approach to distinguishing between these possibilities, we have characterized two additional cell-free systems that reconstitute transport to the trans-Golgi (trans assay) and trans-Golgi network (TGN assay). Like in vitro transport to the medial-Golgi (medial assay), transport to the trans-Golgi and TGN requires cytosol, ATP, and N-ethylmaleimide-sensitive fusion protein (NSF). However, each assay has its own distinct characteristics of transport. The kinetics of transport to late compartments are slower, and less cytosol is needed for guanosine-5'-O-(3-thiotriphosphate) (GTPgammaS) to inhibit transport, suggesting that each assay reconstitutes a distinct transport event. Depletion of ARF from cytosol abolishes vesicle formation and inhibition by GTPgammaS, but transport in all assays is otherwise unaffected. Purified recombinant myristoylated ARF1 restores inhibition by GTPgammaS, indicating that the GTP-sensitive component in all assays is ARF. We also show that asymmetry in donor and acceptor membrane properties in the medial assay is a unique feature of this assay that is unrelated to the production of vesicles. These findings demonstrate that characteristics specific to transport between different Golgi compartments are reconstituted in the cell-free system and that vesicle formation is not required for in vitro transport at any level of the stack.

ADP-Ribosylation Factor 1↗

Peripartal temporal course of endothelin 1, angiotensin II, and atrial natriuretic peptide in pre-eclampsia and normotensive pregnancy.

OBJECTIVE: To investigate the temporal peripartal course of plasma endothelin 1 (ET-1), angiotensin II (ANG II), and atrial natriuretic peptide (ANP) in patients with pre-eclampsia as compared to women with normotensive pregnancy. METHODS: Levels of ET-1, ANG II, and ANP were measured by means of radio-immunoassay twice a week in 17 patients with pre-eclampsia and in 17 women with normotensive uncomplicated pregnancy during four different periods: (a) from admission to 1 week before delivery, (b) 1st week before delivery, (c) 1st week after delivery, and (d) 2nd week after delivery. RESULTS: ET-1 levels were not statistically different between the two groups. ANG II concentrations were lower in the pre-eclampsia group than in the control group with statistical significance in period c (2.8 +/- 3.0 vs. 7.1 +/- 5.9 pg/ml, mean +/- SD). ANP levels were higher in pre-eclamptic women than in the control group, the difference being statistically significant in period a (54 +/- 46 vs. 11 +/- 16 pg/ml) and in period c (122 +/- 134 vs. 39 +/- 22 pg/ml). CONCLUSIONS: There are considerable differences in ANP and ANG II concentrations during the peripartal period between patients with pre-eclampsia and normotensive pregnant women. Decreased ANG II and elevated ANP levels in the 1st week postpartum may reflect the clinical observation that some women deteriorate in this period.

Adult↗