Effects of amyotrophic lateral sclerosis serum on cultured chick spinal neurons

We used a quantitative immunoassay to examine the effects of human serum and immunoglobulins on neurofilament protein expression in cultures of chick spinal neurons. Compared with cultures grown in the presence of serum from healthy controls or patients with other neurologic disorders, ALS serum lowered the level of neurofilament proteins. Effects were similar with or without muscle-derived neurotrophic factors; there was no specificity for motor neurons. No neurotoxic activity was found in immunoglobulin fractions, and there was no evidence of circulating antibodies that might neutralize muscle-derived neurotrophic factors or induce cytolysis of spinal neurons.     

Organization of the callosal connections of visual areas V1 and V2 in the macaque monkey

The interhemispheric efferent and afferent connections of the V1/V2 border have been examined in the adult macaque monkey with the tracers horseradish peroxidase and horseradish peroxidase conjugated to wheat germ agglutinin. The V1/V2 border was found to have reciprocal connections with the contralateral visual area V1, as well as with three other cortical sites situated in the posterior bank of the lunate sulcus, the anterior bank of the lunate sulcus, and the posterior bank of the superior temporal sulcus. Within V1, callosal projecting cells were found mainly in layer 4B with a few cells in layer 3. Anterograde labeled terminals were restricted to layers 2, 3, 4B, and 5. In extrastriate cortex, retrograde labeled cells were in layers 2 and 3 and only very rarely in infragranular layers. In the posterior bank of the lunate sulcus, labeled terminals were scattered throughout all cortical layers except layers 1 and 4. In the anterior bank of the lunate sulcus and in the superior temporal sulcus, anterograde labeled terminals were largely focused in layer 4. Callosal connections in all contralateral regions were organized in a columnar fashion. Columnar organization of callosal connections was more apparent for anterograde labeled terminals than for retrograde labeled neurons. In the posterior bank of the lunate sulcus, columns of callosal connections were superimposed on regions of high cytochrome activity. The tangential extent of callosal connections in V1 and V2 was found to be influenced by eccentricity in the visual field. Callosal connections were denser in the region of V1 subserving foveal visual field than in cortex representing the periphery. In V1 subserving the fovea, callosal connections extended up to 2 mm from the V1/V2 border and only up to 1 mm in more peripheral located cortex. In area V2 subserving the fovea, cortical connections extended up to 8 mm from the V1/V2 border and only up to 3 mm in peripheral cortex.     

Cutaneous postural vasoconstriction is modified by exogenous but not endogenous female hormones in young women

Previously reported attenuation of skin postural vasoconstriction in women during the luteal menstrual cycle phase may be due to a progesterone-mediated decrease in myogenic or veno-arteriolar (VAR) mechanisms. Skin perfusion was measured in the shin and foot dorsum by Laser Doppler Fluxometry during leg dependency that increased vascular transmural pressure below (myogenic constriction only) and above (myogenic and VAR) the 25 mmHg threshold for activation of the VAR, and during venous distension to activate the VAR alone (cuff inflation to 50 mmHg). In six young women with normal menstrual cycles, vasoconstrictor responses to all interventions did not differ between days 7–13 (follicular) and 18–23 (luteal) of the normal menstrual cycle when progesterone levels were low and at their peak respectively. In eight women taking combined oral contraceptives (OC) and tested during pill consumption days, reductions in foot skin perfusion were smaller (P = 0.05) than in the luteal phase of the normal cycle for leg dependency below (−36.9 ± 5.2% OC vs. −52.5 ± 7.8% luteal, mean ± S.E.M.) and above (−43.7 ± 3.4% OC vs. −55.1 ± 4.8% luteal) the VAR threshold, and for venous distension (−53.1 ± 2.6% OC vs. 66.4 ± 5.5% luteal). In women with normal menstrual cycles, impaired postural vasoconstriction may be confined to those who experience pre-menstrual symptoms rather than a direct effect of endogenous hormones. Reduced vasoconstriction in the dependent foot during OC use is consistent with the known vasodilator action of exogenous hormones and its long-term effects     

Power law analysis of the signal-averaged electrocardiogram for identification of patients with ventricular tachycardia: effect of bundle branch block.

Signal-averaged ECGs that use time-domain analysis are useful for the identification of patients at risk for ventricular tachycardia (VT). Bundle branch block (BBB) and other conduction defects reduce the value of this approach, but frequency-domain analysis has shown promise in such patients. The purpose of the present study was to examine a new frequency-domain approach to signal-averaged ECGs in patients with and without BBB: power law scaling (PLS). PLS was performed by plotting the power spectrum of the entire signal-averaged ECG on a plot of log power versus log frequency and determining the slope (beta) by least-squares regression. This method was studied in 346 patients. Results of discriminant analysis revealed better sensitivity, specificity, positive predictive value, negative predictive value, and percentage correctly predicted when this method was compared with time-domain indexes. A large proportion of the variance in PLS (19%) was found to be due to findings in patients with VT; whereas the best time-domain index, duration of the filtered QRS signal, explained only 6% of the variance in the group with VT. Mean levels of PLS (+/- standard deviation) were decreased for the group with VT (-3.55 +/- 0.95) as compared with the group without VT (-4.34 +/- 0.59; p < 0.001), suggesting a decrease in the time correlation of the signal. Thus this method of frequency-domain analysis of the signal-averaged ECG was useful in identifying patients with sustained VT despite the presence of significant conduction defects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anterior circulation aneurysms: surgical perspectives

Aneurysms arising from the internal carotid circulation represent 85% of all intracranial aneurysms. The intimate relationship of the internal carotid artery and its branches with the brain and cranial nerves, and the distribution of the internal carotid artery flow, make these aneurysms challenging, and potentially complicated in their surgical management. Great attention to detail, and clear understanding of the operative anatomy of the carotid system, facilitate the safe and successful treatment of these aneurysms. The surgical experience with 475 anterior circulation aneurysms treated from 1980 to 1992 is presented. The aneurysms arose from the internal carotid artery: 230(40%), middle cerebral artery: 152(32%), and anterior cerebral artery: 133(28%). Of aneurysms arising from the internal carotid artery, there were 142(30%) from the posterior communicating artery; internal carotid bifurcation: 29(6%), and anterior choroidal artery: 19(4%). There were 62(13%) giant aneurysms evenly distributed among the middle cerebral, internal carotid bifurcation and anterior cerebral artery. Serious neurological morbidity was observed in 13(3%) patients, who presented a combination of different neurological symptoms including: hemiplegia 3, hemiparesis 6, dysphasia 7, and loss of vision 4. Two patients developed a myocardial infarct and survived. Mortality occurred in 16(3%); these patients died from: a hemispheric infarction 7, severe vasospasm 6, myocardial infarction 2, and pulmonary emboli 1. All aneurysms appeared angiographically obliterated. Vasospasm was observed in 75(16%) patients of which nine were symptomatic, and six of them died. Six major arterial trunks were occluded in the post-operative angiogram, and three patients had occlusion of the internal carotid artery, not identified during surgery. Three of these patients with unexpected occlusions died from a major cerebral infarction, and three had lasting hemipareses and dysphasia. Surgical correction of internal carotid aneurysms can be conducted safely when the anatomical characteristics of the intracranial vessels is preserved, and when these patients are treated with appropriate medical support.     

Influence of pancreas transplantation on cardiorespiratory reflexes, nerve conduction, and mortality in diabetes mellitus

Cardiorespiratory reflexes (CRR) were studied by measuring heart-rate variation during 6 breaths/min respiration and a Valsalva maneuver in 232 insulin-dependent diabetic subjects. Abnormalities were found in 175 patients. During a 7-yr follow-up, 41 (23.4%) patients with abnormal and 2 (3.5%) with normal CRR tests died. The mortality rates of diabetic patients with abnormal autonomic function tests were 17% at 2.5 yr, 33% at 5 yr, and 40% at 7 yr, significantly higher (P less than 0.002) than in patients with normal tests (rates of 4.6, 4.6, and 13.8% at the respective intervals). Nerve conduction studies (NCS) were indicative of somatic neuropathy in 148 of 205 patients. Mortality rates were higher in patients with abnormal NCS than in those with normal results (P less than 0.025). Among patients with abnormal autonomic function, patients with a functioning pancreas transplantation (PTx) had better survival rates than patients with a failed PTx (P less than 0.005) and, on long-term follow-up, better rates than patients without PTx. Similar results were found comparing the same group of patients who had abnormal NCS.     

Lack of effect of cimetidine on cigarette smoking

Summary The efficacy of cimetidine as a treatment that could reduce smoking in heavily dependent smokers has been determined. In a randomised, double-blind, double-crossover experiment, 43 heavy smokers were divided into two groups, one receiving cimetidine 400 mg orally three times a day, and the other receiving placebo for two weeks followed by the alternative treatment (placebo or cimetidine).No significant difference in the mean alveolar carbon monoxide, nicotine or cotinine levels was found between the two treatment groups compared to baseline. Since the alveolar carbon monoxide level reflects the intensity of smoking behaviour, the results suggest that no change in smoking behaviour occurred in the subjects.Contrary to our previous findings that cimetidine decreased the total body clearance of nicotine by 30% in a population of non-smokers, in the heavily dependent smokers, cimetidine did not appear to alter nicotine elimination. One possible explanation for the discrepancy is that tobacco smoking is known to induce nicotine metabolism and the induction might have offset any effect of cimetidine on nicotine elimination.Cimetidine does not appear to be a useful treatment leading to a reduction or cessation of cigarette smoking.