Semantic activation in Parkinson's disease patients on and off levodopa

Research suggests that dopamine may exert a neuromodulatory influence on automatic spreading activation within semantic networks. In order to investigate the influence of dopamine depletion on semantic activation in Parkinson's disease (PD), nine patients with PD performed a lexical decision task when on and off levodopa medication. Eleven healthy controls matched to the PD patients in terms of sex, age and education also participated in the study. Both directly related word pairs (e.g., tiger - stripe) and indirectly related word pairs (word pairs related via a mediating word, e.g., chalk - black) were used to measure semantic activation across stimulus onset asynchronies (SOAs) of 270 msec, 520 msec and 1020 msec. Analysis of variance statistics revealed that the activation of directly related and indirectly related targets was slower for the PD group relative to the control group. Within group comparisons revealed further changes to semantic activation in PD patients off medication, with no activation of directly or indirectly related target words evident in PD patients off medication. These results further clarify the nature of dopamine's neuromodulatory influence on semantic activation, and suggest that the nature of altered semantic activation in PD may depend on the magnitude of dopamine depletion.     

Effects of cholinergic modulation on responses of neocortical neurons to fluctuating input

Neocortical neurons in vivo are spontaneously active and intracellular recordings have revealed strongly fluctuating membrane potentials arising from the irregular arrival of excitatory and inhibitory synaptic potentials. In addition to these rapid fluctuations, more slowly varying influences from diffuse activation of neuromodulatory systems alter the excitability of cortical neurons by modulating a variety of potassium conductances. In particular, acetylcholine, which effects learning and memory, reduces the slow alterhyperpolarization, which contributes to spike frequency adaptation. We used whole-cell patch-clamp recordings of pyramidal neurons in neocortical slices and computational simulations to show, first, that when fluctuating inputs were added to a constant current pulse, spike frequency adaptation was reduced as the amplitude of the fluctuations was increased. High- frequency, high-amplitude fluctuating inputs that resembled in vivo conditions exhibited only weak spike frequency adaptation. Second, bath application of carbachol, a cholinergic agonist, significantly increased the firing rate in response to a fluctuating input but minimally displaced the spike times by < 3 ms, comparable to the spike jitter observed when a visual stimulus is repeated under in vivo conditions. These results suggest that cholinergic modulation may preserve information encoded in precise spike timing, but not in interspike intervals, and that cholinergic mechanisms other than those involving adaptation may contribute significantly to cholinergic modulation of learning and memory.      

Parental mosaicism and autosomal dominant mutations causing structural abnormalities of collagen I are frequent in families with osteogenesis imperfecta type III/IV

Abstract Protein-chemical and molecular studies were conducted on all osteogenesis imperfecta (OI) type III/IV patients referred to our hospital during the last 15 y. Of a total of 16 OI type III/IV patients studied, 15 patients were heterozygous for a mutation in one of the two genes coding for collagen I, COL1A1 or COL1A2. Cultured fibroblasts from these 15 patients produced both normal and abnormal collagen I molecules, pointing to a dominant-negative effect of the mutation. Nine mutations had not been described previously. Parental mosaicism was demonstrated in three families. In the 16th child the causative mutation was not found. In conclusion, OI type III/IV in most patients of Western European ancestry is caused by dominant mutations in the genes for collagen I, and recurrence of OI is caused in most cases by parental gonadal mosaicism.     

Thrombosed central venous catheters: restoring function with 6-hour urokinase infusion after failure of bolus urokinase.

Nineteen central venous catheters with radiographically proven thrombotic occlusion failed to have function restored with a mean of 1.6 5000-unit boluses of urokinase per catheter. Catheters then underwent a 6-hour infusion of urokinase at 40,000 units per hour followed by repeat contrast injection and evaluation of function. Reduction in thrombus size occurred in all but one patient. Catheter function was restored in 15 patients. In two patients, thrombus dissolved but catheters remained occluded because of tip malposition. In the remaining two patients, catheter function was restored with an additional 6-hour infusion. No adverse reactions to the infusion were seen. After infusion catheters continued to function normally for a mean of 36.2 days. Five catheters rethrombosed, two of which responded to urokinase bolus instillation. Thrombosed catheters failing standard intracatheter bolus urokinase are generally salvaged with a 6-hour infusion of low-dose urokinase.     

Epidural blood patch for atypical headache following obstetric epidural analgesia

A case of atypical headache presenting following otherwise unremarkable epidural analgesia in labour is presented. Although there was no suggestion of accidental dural puncture during insertion of the epidural catheter, and despite the unusual features of the headache and complicated case history, an epidural blood patch was performed 13 weeks post-partum, with improvement of the patient's symptoms. A repeat epidural blood patch 2 weeks later completely resolved her headache.     

Organ dysfunction following stem cell transplantation: relationship to plasma cytokine concentrations.

Patients receiving high-dose preparation for stem cell transplantation are at risk for organ dysfunction (OD). Signs of early OD include hypoxia, mental status changes, and liver dysfunction. These early signs have not been correlated with potential cytokine mediators. We compared plasma concentrations of IL-6, TNF-alpha, and IL-10 in OD patients and controls. Cytokines were measured before preparation, 5 days before OD, day of OD, and 5 days after OD. TNF-alpha and IL-10 were not measurable prior to preparation. IL-10 was more likely to be measurable in OD patients than in controls 5 days prior to onset of OD (P = 0.039), on the day of OD (P = 0.023), and 5 days later (P < 0.0001). TNF-alpha was more likely to be measurable only on the day of OD (P = 0.0035). IL-6 was significantly elevated in OD patients at all time points. Patients who had measurable IL-6 on admission were 5.1 times more likely to develop OD (95% CI = 1.4-17.9; P = 0.011). Five days prior to OD for each 100 pg/ml increase in IL-6, patients were 2.75 times more likely to develop OD (95% CI = 1.3-5.8; P = 0.0087). The early elevation of IL-6 in patients who develop OD may help identify a high risk group where preventive therapies can be evaluated.