Normal pressure hydrocephalus and cerebral blood flow: a PET study of baseline values.

Regional cerebral blood flow (CBF) was studied with O(15)-water positron emission tomography and anatomic region-of-interest analysis on co-registered magnetic resonance in patients with idiopathic (n = 12) and secondary (n = 5) normal pressure hydrocephalus (NPH). Mean CBF was compared with values obtained from healthy volunteers (n = 12) and with clinical parameters. Mean CBF was significantly decreased in the cerebrum and cerebellum of patients with NPH. The regional analysis demonstrated that CBF was reduced in the basal ganglia and the thalamus but not in white matter regions. The results suggest that the role of the basal ganglia and thalamus in NPH may be more prominent than currently appreciated. The implications for theories regarding the pathogenesis of NPH are discussed.     

Inhibition of tumor cell proliferation by type IV collagen requires increased levels of cAMP

Previous studies from our laboratories demonstrated that a peptide from the noncollagenous domain of the alpha3 chain of basement membrane collagen (COL IV), comprising residues 185-203, inhibits polymorphonuclear leukocyte activation and melanoma cell proliferation; this property requires the presence of the triplet -SNS- in residues 189-191 (Monboisse et al., J. Biol. Chem., 269, 25475, 1994; Han et al., J. Biol. Chem., 272, 20395, 1997). In the present study, we demonstrate that whole native COL IV and -SNS- containing synthetic peptides (10 microg/ml) added to culture medium inhibit the proliferation of not only melanoma cells, but also breast-, pancreas- and stomach-tumor cells up to 67%, and prostate tumor cells by 15%. ALC-COL IV at 5 microg/ml was shown to inhibit melanoma cell proliferation maximally at 69% and the alpha3(IV)185-203 peptide inhibited proliferation (62%) maximally at 10 microg/ml. Treatment of the alpha3(IV)185-203 peptide with either a specific mAb or a polyclonal antibody, prepared against the sequence alpha3(IV)179-208, decreased the ability of the peptide to inhibit cell proliferation by 97%, while treatment of ALC-COL IV with the same antibodies inhibited proliferation by 44%. Exposure of the above tumor cells to COL IV or the peptides resulted in an increase of intracellular cAMP that was inhibited by prior treatment of the protein with the above antibodies. To investigate the role of cAMP in the inhibition of cell proliferation, cAMP analogs and inhibitors were used. cAMP analogs mimicked the inhibitory effect of the peptide. Rp-cAMPS, a cAMP competitive inhibitor, suppressed the inhibitory effect of ALC-COL IV and of the cAMP analogs. The protein kinase-A inhibitor H-89 blocked the ability of ALC-COL IV and of the alpha3(IV)185-203 peptide to inhibit tumor cell proliferation. These data suggest that ALC-COL IV, through its alpha3(IV) chain, inhibits tumor cell proliferation utilizing a signal transduction pathway which includes cAMP and cAMP-dependent protein kinase(s).     

Incidence of Sciatic Nerve Palsy After Revision Hip Arthroplasty Through a Posterior Approach

Sciatic nerve palsy after revision hip arthroplasty is rare, but can have substantial impacts. The purpose of this study is to report the safety and reliability of limited sciatic nerve exposure during revision surgery. A retrospective case series of 350 revision hip surgeries performed by a single surgeon underwent sciatic nerve identification. In each case, the sciatic nerve was identified and tagged loosely with a Penrose drain. Three hundred forty-eight of 350 patients (99.4%) underwent successful revision hip arthroplasty. One patient developed a transient sensory palsy; and another patient, a delayed palsy. Both nerve palsies recovered by the 1-year visit. We advocate visual nerve identification and tagging in revision hip surgery as 1 possible method to potentially reduce the risks of sciatic nerve injury.     

A randomized clinical trial of valacyclovir in multiple sclerosis

OBJECTIVE: The human Herpesvirus type-6 (HHV-6) has been implicated in multiple sclerosis (MS). Valacyclovir is an antiviral agent with an excellent safety profile. A two-year placebo-controlled, double-blind study was conducted to (1) ascertain if high-dose, prolonged treatment with valacyclovir would be safe and (2) observe if valacyclovir would delay the progression of MS clinically or by magnetic resonance imaging (MRI). DESIGN/METHODS: Fifty-eight patients were stratified as to severity and randomly assigned to receive valacyclovir (3000 mg/day) or placebo for a period of two years. Patients were followed clinically over the two-year period by means of the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI) and brain MRI scans. Patients underwent routine lab studies every three months. Patients continued on the medication for two years unless they had a sustained progression or repeated exacerbations. RESULTS: No patient discontinued the study due to side effects or toxicity. In Relative Ranking of Progression, time to first attack, attack rate, and time to withdrawal there were trends (but not statistically significant) toward drug effect over placebo in the Severe clinical category. MRI evaluation showed no significant drug effect. CONCLUSIONS: Although not statistically significant, positive trends were detected for acyclovir by clinical measures, but not by MRI.     

Link between vasogenic waves of intracranial pressure and cerebrospinal fluid outflow resistance in normal pressure hydrocephalus

Recent studies on normal pressure hydrocephalus (NPH) have pointed to a possible link between the disturbance in CSF circulation and cerebrovascular factors. We investigated the quantitative relationship between the resistance to CSF outflow (Rcsf) and vasogenic waves of ICP in patients with normal pressure hydrocephalus. Forty-five patients with NPH were investigated by an infusion study. The magnitudes of vasogenic ICP components: pulse, respiratory and slow vasogenic waves were assessed, and compared with Rcsf. Both baseline respiratory and slow waves of ICP were positively correlated with Rcsf. The respiratory wave at baseline was a single independent predictor of Rcsf (r = 0.66, p < 0.0002). All vasogenic components increased significantly during the infusion test. The magnitude of the increase was positively correlated with Rcsf. The vasogenic ICP waves, notably the respiratory wave of ICP, correlate with the resistance to CSF outflow.     

Nonlinear poroplastic model of ventricular dilation in hydrocephalus

OBJECT: The mechanism of ventricular dilation in normal-pressure hydrocephalus remains unclear. Numerical finite-element (FE) models of hydrocephalus have been developed to investigate the biomechanics of ventricular enlargement. However, previous linear poroelastic models have failed to reproduce the relatively larger dilation of the horns of the lateral ventricles. In this paper the authors instead elaborated on a nonlinear poroplastic FE model of the brain parenchyma and studied the influence of the introduction of these potentially more realistic mechanical behaviors on the prediction of the ventricular shape. METHODS: In the proposed model the elasticity modulus varies as a function of the distension of the porous matrix, and the internal mechanical stresses are relaxed after each iteration, thereby simulating the probable plastic behavior of the brain tissue. The initial geometry used to build the model was extracted from CT scans of patients developing hydrocephalus, and the results of the simulations using this model were compared with the real evolution of the ventricular size and shape in the patients. RESULTS: The authors' model predicted correctly the magnitude and shape of the ventricular dilation in real cases of acute and chronic hydrocephalus. In particular, the dilation of the frontal and occipital horns was much more realistic. CONCLUSIONS: This finding suggests that the nonlinear and plastic mechanical behaviors implemented in the present numerical model probably occur in reality. Moreover, the availability of such a valid FE model, whose mechanical parameters approach real mechanical properties of the brain tissue, might be useful in the further modeling of ventricular dilation at a normal pressure.