Predictors of perceived health status in elderly men and women. The Cardiovascular Health Study

Baseline data on the perceived health status of participants (N = 5,201) in the Cardiovascular Health Study of the Elderly (CHS) are reported. The authors examined the predictive utility of health-related factors representing eight different domains, assessed gender differences in the prediction of perceived health, and tested a hypothesis regarding the role of known clinical conditions versus subclinical disease in predicting perceived health. Multivariate analyses showed that the majority of the explained variance in self-assessed health is accounted for by variables that fall into four general categories. Although gender differences were small, the analysis showed that the relative importance of several predictor variables did vary by gender.     

An open-randomized clinical trial of selegiline in amyotrophic lateral sclerosis

Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25–80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS.     

Analysing ion channels with hidden Markov models

Ion channel current amplitudes () and open probabilities (P _o) have been analysed so far by defining a 50% threshold to distinguish between open and closed states of the channels. With this standard method (SM) it is very difficult or even impossible to analyse channels of different size in one membrane patch correctly. A stochastical model, named the hidden Markov model (HMM), separates between observation noise and the stochastic process of opening and closing of ion channels. The HMM allows the independent analysis of , P _o, and mean dwell times () of different channels in one membrane patch, without defining threshold levels. Using this method errors in the analysis are not summarized like in the SM because all different analysing procedures (e. g. filtering, setting of threshold, fitting processes) are done in one step. Two different K⁺ channels in excised basolateral membranes of the cortical collecting duct of rat (CCD) were analysed by the SM and the HMM. The value of the intermediate-conductance K⁺ channel (i-K⁺) was 3.9±0.1 pA (SM) and 3.8±0.2 pA (HMM) for 11 observations. The P _o value of this channel was 10.2±4.2% (SM) and 10.1±4.0% (HMM). The mean values were 5.4±0.6 ms for the open state and 9.6±2.2 ms and 145±21 ms for the closed states (SM) and 7.8±1.1 ms, 7.7±0.9 ms and 148±24 ms (HMM), respectively. For seven small-conductance K⁺ (s-K⁺) channels, which were found in the same membrane patches as the i-K⁺, an accurate analysis of P _o and was not possible with the SM. The value was 1.0±0.1 (SM), 0.9±0.1 (HMM) pA. P _o was 16.6±4.6%, the open value was 11.1±2.8 ms, and the closed value was 34.9±8.5 ms. The HMM allows the analysis of single-channel currents, P _o, and mean values when different or more than one ion channel(s) are colocalized in one membrane patch. Where analysis with the SM was possible results did not significantly differ from those obtained with the HMM. Thus for this kind of analysis the method of setting a 50% threshold appears justified.     

Plasma concentrations and renal clearance of orotic acid in argininosuccinic acid synthetase deficiency

Argininosuccinic acid synthetase deficiency (ASD) is a rare disorder of urea cycle metabolism, with pronounced citrullinemia and orotic aciduria being characteristic biochemical features. To further investigate the role of plasma orotic acid and its possible use for monitoring the metabolic status in ASD, we determined plasma orotic acid, amino acid, and ammonium levels in plasma samples collected over a period of 3 years from a patient who is now 8 years of age. Orotic acid plasma concentrations varied widely from less than 1 μmol/l to more than 60 μmol/l. The renal clearance of orotic acid was eightfold the glomerular filtration rate, thus supporting an active mechanism underlying the excretion of this pyrimidine. Data obtained during a metabolic crisis yielded a statistically significant linear correlation of orotic acid plasma levels with those of glutamine and ammonium, which are generally accepted for assessment of the successful treatment of this disorder. Our data revealed no advantage of plasma orotic acid concentrations over the established amino acids (glutamine and arginine) and ammonium for determining acute treatment responses. Since several effects of high levels of orotic acid have been described in mammals, further research is necessary to assess a possible contribution of orotic acid to the pathogenesis of ASD and the use of plasma orotic acid levels in the long-term monitoring of these patients. Received: 3 November 1998 / Revised: 3 May 1999 / Accepted: 3 May 1999     

Effect of pulse pressure on vascular smooth muscle cell migration: the role of urokinase and matrix metalloproteinase

Plasminogen activator (PA) expression plays an important role in smooth muscle cell (SMC) migration and may therefore contribute to mechanical force-induced arterialization of vein grafts. The aim of this study was to determine whether pulse pressure due to pulsatile flow modulates SMC migration via urokinase (u-PA)-dependent mechanisms. Using a perfused transcapillary culture system, human umbilical vein SMC were exposed to pulse pressures (0-56 mmHg), in the absence or presence of human umbilical vein endothelial cells (EC) by varying pulsatile flow rates (0 ml/min to 25 ml/min). SMC cultured in the absence of EC increased their migration following exposure to increased pulse pressure (248+/-14%). Both u-PA and matrix metallo-proteinase 1 (MMP-1) expression was significantly elevated in SMC exposed to pressure as compared to static controls. The role of proteases in the pulse pressure-induced enhancement of SMC migration was confirmed following pretreatment with aprotinin, an anti u-PA antibody and metalloproteinase inhibitors (181+/-14% for aprotinin vs. 256+/-25% for control, 108+/-4% for anti-u-PA antibody vs. 233+/-17% for non-immune IgG, and 114+/-9% for BB-94, 105+/-7% for BB-3103 vs. 222+/-5% for control). Using SMC derived from u-PA gene knock-out mice, the SMC migratory response to increased pulse pressure was completely inhibited despite a significant increase in MMP expression in these cells. These results suggest that pulse pressure due to pulsatile flow induces SMC migration in vitro via u-PA and MMP-dependent mechanisms. Moreover, u-PA gene deletion results in blunting of pressure-induced SMC migration despite the endogenous upregulation of metalloproteinase. Modulation of u-PA expression by pressure may thus represent an important mechanism whereby hemodynamic forces regulate smooth muscle cell migration.     

Cognitive development in benign focal epilepsies of childhood

Benign focal epilepsy of childhood (BFEC) is the most common form of epilepsy, in children from 3 to 12 years. Its prognosis is always favourable as far as the epilepsy is concerned. Nevertheless, recent clinical data suggest that children affected by BFEC are more likely to show learning difficulties and behavioural disturbances than their peers. We report here the preliminary findings of a prospective study of 22 children affected with BFEC. Electroclinical and neuropsychological changes observed during the first 18 months of the follow-up strengthen the conclusion of recent neuropsychological studies stressing the correlation between epilepsy and cognitive performances. The cognitive deficits affecting mainly non-verbal functions were significantly correlated with the frequency of seizures and spike-wave discharges and to the lateralization of the epileptic focus in the right hemisphere, whereas frontal functions like attention control, response organization and fine motor speed, were impaired in the presence of active BFEC independently of the lateralization of the epileptic focus. Our results indicate that maturing cognitive functions subserved by a cortical area distant from the epileptic focus are susceptible to interference with epilepsy. Copyright Copyright 1999 S. Karger AG, Basel     

Hydroxyapatite cement to repair skull base defects: radiologic appearance.

PURPOSETo describe the radiologic appearance of hydroxyapatite cement (HAC), which, when mixed with liquid, forms a paste that can be contoured to osseous defects and, over time, becomes "osseointegrated" (native bone grows into the pores of the HAC and forms a strong chemical bond with the substance).METHODSBetween March 1992 and June 1993, 24 adults (16 men, eight women) underwent skull base surgery that included reconstruction or closure with HAC. Fourteen patients had HAC placed in the paranasal sinuses or facial bones, and 10 had HAC placed in the mastoid cavity.RESULTSHAC is homogeneously radiopaque on CT scans and plain radiographs. Large amounts (ablating a frontal sinus or mastoid air cells) are readily seen; small amounts are inconspicuous. On MR images, HAC is a signal void. Infected HAC in one patient was surrounded be enhancing soft tissue on MR images, separated from native bone by an irregular radiolucent cleft on CT scans.CONCLUSIONSHAC is a valuable addition to the surgical armamentarium for the repair of skull base defects. More experience will determine the time course for normal osseointegration, as well as the typical appearance of infection.     

Septo-optic dysplasia and growth hormone deficiency: accelerated pubertal maturation during GH therapy

We report four patients (three male, one female) with septo-optic dysplasia and growth hormone deficiency. All had GH therapy for a period of four to eight years until reaching final height. In all four cases bone maturation during puberty was accelerated (1.4 to 1.9 "years"/year), resulting in a final height which was clearly below the predicted height. The progress of pubertal stages was very short in all patients. In three patients TSH and prolactin release after TRH stimulation were increased. These data support a hypothalamic original of the endocrine disorder. Insufficient GH release, even after repeated GHRH stimulation, is in contrast to this assumption. In one case there was a late manifestation of neurohormonal diabetes insipidus, which indicates the possibility of later disease progression. MR imaging of the brain demonstrated variable malformation of the septum pellucidum, chiasma and nervus opticus or the pituitary gland, respectively.     

Epidural "sulmycin implant" coverage for local prevention of infection in surgical management of open craniocerebral injuries]

In various series reported in the literature on the operative management of severe head injuries with compound depressed skull fractures and penetrating wounds of the brain, the rates of infection differ from 1 to 17%. In this paper the operative experience with 22 cases of penetrating head injuries is discussed. In conventional operative therapy, depressed skull fracture and lacerated dura were covered by "Sulmycin Implant" containing Gentamycin as a helpful bacteriological barrier. 18 patients survived, 7 patients had severe neurological defects, 5 patients had mild neurological deficits and 6 patients recovered completely. There were no signs of suppurative complications in superficial wounds or in the brain. 4 patients died due to their severe brain damage with multiple contusional lesions. Postoperative complications were as follows: one patient suffered extradural and one patient subdural rebleeding. Another patient with a frontal base skull fracture suffered a pneumatocele because the fracture was not correctly covered. The revision was done successfully using the "Sulmycin Implant". Presently, however, the intradural use of "Sulmycin Implant" is not recommended without further testing for the level of gentamycin in the cerebrospinal fluid which is released by the "Sulmycin Implant".