Mechanisms of postural instability in hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) is characterized by progressive lower extremity spasticity and weakness, due to retrograde axonal degeneration of the corticospinal tract and posterior spinal columns. HSP patients fall frequently. We hypothesized that delayed postural responses contribute to their balance impairments. To distinguish between a delay in afferent and efferent signals, we combined postural responses with a startling acoustic stimulus (SAS). The SAS triggers a postural response directly, bypassing afferent proprioceptive input. We performed two experiments. First, 18 HSP patients and nine healthy controls stood on a balance platform and were instructed to counteract forward and backward balance perturbations, without taking a step or grabbing a handrail. Second, 12 HSP patients and nine controls received backward perturbations, while a SAS accompanied onset of platform motion in 25 % of trials. HSP patients were less successful than controls in maintaining balance following backward and forward perturbations. Furthermore, latencies of postural responses were significantly delayed in HSP-patients, by 34 ms in gastrocnemius following forward, and by 38 ms in tibialis anterior following backward perturbations. A SAS accelerated postural responses in all participants, but more so in HSP patients whose latencies were normalized. Our results suggest that delayed postural responses in HSP patients contribute to their balance problems. Combining balance perturbations with a SAS restored normal latencies, suggesting that conduction of efferent signals (presumably by the reticulospinal tract) is normal. We therefore suggest that the delayed postural responses in HSP are caused by slowed conduction time via the posterior spinal columns.     

Immunolocalization of Picornavirus RNA in infected cells with antibodies to Tyr-pUp, the covalent linkage unit between VPg and RNA

The genomic RNA of picornaviruses is attached to a small protein (VPg) via a covalent bond between a tyrosine and a 5′-terminal uridine phosphate. The same structure is present in potyvirus and calicivirus families. VPgs play a key role in initiation of viral replication by acting as primers for RNA synthesis. The model compound [N(Ac),CO(NHMe)]Tyr-(5′P → O)Up-O-(CH₂)₆NH₂ (mCLU), mimicking this ‘covalent linkage unit’ (CLU) and containing Tyr-pUp was synthesized in solution following the phosphoramidite scheme and used to raise antibodies for studying picornavirus infection. The antibodies recognized CLU-containing mengovirus RNA and showed minimal cross-reactivity with RNAs lacking CLU. Immunofluorescence staining of cells infected with a human rhinovirus demonstrated co-localization of the signals from anti-mCLU and from anti-VPg antibodies. Efficient synthesis of mCLU and anti-mCLU antibodies might be of great utility for investigating viral replication and identifying yet unknown viral and cellular CLU-containing RNA-protein complexes.     

Hormone replacement therapy and the wellbeing of menopausal women]

BACKGROUND AND AIMS: The authors performed a retrospective analysis of 682 patients attending the Menopause Centre from 1994 to today. These patients were referred for a wide variety of symptoms occurring in premenopause and menopause. METHODS: All patients initially underwent general screening which was followed by appropriate therapy on the basis of objective examination, blood chemical and instrumental tests, and the subjective clinical situation. RESULTS AND CONCLUSIONS: It was found that the most frequently used treatment was sequential or combined oestroprogestin replacement treatment (63%), with tibolone in 9% of cases and veralipride in 5%. The best results from the point of view of the improved wellbeing of the woman were obtained using HRT and tibolone.     

Long-term, cause-specific mortality after myocardial infarction in diabetes.

AIMS: To compare long-term, cause-specific mortality after reperfusion therapy for ST segment elevation myocardial infarction (STEMI) in patients with and without diabetes. METHODS AND RESULTS: Patients with STEMI (n = 395) were randomised to intravenous streptokinase (SK) or primary percutaneous coronary intervention (PCI). Median follow-up was 7.5 years (interquartile range 5.6-8.5). A total of 74 patients (19%) had diabetes. Reduced left ventricular ejection fraction (<40%) after STEMI was more often observed in patients with diabetes (27% vs. 15%, P = 0.02). Patients with diabetes had a higher total mortality compared to patients without diabetes (HR 2.4; P < 0.001). Multivariate analysis confirmed that diabetes was an independent risk factor for long-term mortality (HR 2.3; P < 0.001). The incidence of sudden death was comparable in both patient groups (HR 1.6; P = 0.23). The increased mortality in patients with diabetes was mainly caused by heart failure (HR 3.1; P = 0.004). In patients with diabetes, primary PCI was associated with an improved prognosis. CONCLUSIONS: Despite reperfusion therapy, STEMI patients with diabetes have an increased long-term mortality. This is due to death by heart failure and not by an increase in sudden death. Primary PCI is associated with an improved prognosis, particularly in patients with diabetes.