Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies.

Multiple chemical sensitivity (MCS)--differential diagnosis in clinical neurotoxicology: a German perspective.

The multiple chemical sensitivity syndrome (MCS) is a new cluster of environmental symptoms which have been described and commented on for more than 15 years now in the USA. In the meantime it has also been observed in European countries. The main features of this syndrome are: multiple symptoms in multiple organ systems, precipitated by a variety of chemical substances with relapses and exacerbation under certain conditions when exposed to very low levels which do not affect the population at large.

Neurological investigations in 23 cases of pyrethroid intoxication reported to the German Federal Health Office.

In 1993, 64 cases of chronic pyrethroid intoxication were reported to the Federal Health Office in Germany. Shortly afterwards the media spoke of thousands of cases of pyrethroid intoxication in homes. 23 of the persons reported were examined in a neurological department on an inpatient basis using clinical neurological, neuroradiological and laboratory investigations, including the examination of pyrethroid values in blood and urine.

Clinical data on three cases of occupationally induced PCB-intoxication.

Since the ban of PCBs at the end of the 1970s, extensive measures have been undertaken in Germany to dispose of PCB contaminated transformers. We report on three patients with considerable skin exposure to PCBs, in particular to Clophen A 30, while repairing or dismounting transformers. The periods of exposure range from 4 and 5 to 20 years.

[Multiple chemical sensitivity syndrome].

The multiple chemical sensitivity syndrome (MCS) is a novel constellation of symptoms in environmental medicine that has been extensively described and commented on in the USA. The main features of this syndrome are: multiple symptoms in different organ systems triggered by a variety of chemical substances, with relapses and exacerbations under certain precipitating circumstances at very low levels which do not cause any reactions in the population at large. There are no lab markers or specific investigative findings.

PCBs have a predominantly neurotoxic effect on dissociated cultures of the nervous system.

Although their manufacture and use have been restricted or banned in Europe and the United States since the 1970s, polychlorinated biphenyls (PCBs) are still an ubiquitous environmental contaminant whose low-term effects are as yet not completely clear. Clinical case studies of patients with occupational exposure report cognitive impairment and peripheral neuropathy. In our defined nerve cell culture models in which we use pure neurons, pure glia and mixed cultures prepared from dorsal root ganglia of chick embryos we observed a neurotoxic effect after the application of a PCB compound (Clophen).

Specific neurotoxic effects of different organic solvents on dissociated cultures of the nervous system.

Pure neurons were prepared from dorsal root ganglia (DRG) of 8 day old chick embryos (E8). The substances tested in this model were pure n-hexane, 2.5-hexanedione (2.

2,5-Hexanedione is a potent gliatoxin in in-vitro cell cultures of the nervous system.

Of the metabolites of hexane, 2,5-hexanedione (2,5 HD) has the strongest neurotoxic effect. There is a wealth of experimental studies in animals showing an axonotoxic mechanism consisting of an accumulation of 10 nm neurofilaments. Only few studies deal with a possible action of 2,5-HD on Schwann cells, glia cells or both.

Type 2a fibre rhabdomyolysis in myoadenylate deaminase deficiency.

A 31-year-old woman developed an acute, potentially fatal rhabdomyolysis of undetermined origin. Muscle biopsy revealed selective lysis involving exclusively type 2a fibers. Myoadenylate-deaminase (MAD) deficiency was proven by a negative histochemical reaction as well as by an enzymatic biochemical determination.

Effects of lipoic acid in hexacarbon-induced neuropathy.

The effects of lipoic acid on hexacarbon neurotoxicity in rats were investigated. Rats were exposed by inhalation to n-hexane for 24 hours/day, 7 days/week, up to a total period of 9 weeks. Eight animals were exposed to 700 ppm n-hexane only, and eight animals were exposed to 700 ppm n-hexane and additionally received 100 mumol/kg lipoic acid PO daily.

Neurotoxicity of organic solvent mixtures: embryotoxicity and fetotoxicity.

The toxicity of organic solvents at different concentrations was examined to determine their effect on pregnant rats and their offspring. A very serious effect which inhalational exposure to n-hexane, methyl-ethyl-ketone and a mixture of the two organic solvents produced in pregnant rats was a concentration-dependent increase of intrauterine mortality. In cases of only prenatal exposure, the persistence of reduced body growth was an important result obtained at all concentrations we investigated (first solvent experiment, 500 ppm; second solvent experiment, 800 ppm; and third solvent experiment, 1000 to 1500 ppm; 23 hr day).

Variability and reproducibility of arterial and venous circulation parameters in the forearm and calf measured at one-week intervals.

In 12 healthy men aged 22 to 29 years the variability of basal arterial blood flow, maximal arterial blood flow as induced by a 5-min arterial occlusion, vascular resistances, total venous capacity and venous emptying rate and the reproducibility of the measurements were studied in both the upper and lower limbs 3 times at one week's interval under strictly standardised conditions using an automatic venous occlusion plethysmograph. Means, medians, standard errors, and standard deviations were virtually identical or very similar without any statistically significant difference between the 3 study occasions; this implies that valid comparisons can be made when measurements are repeated at several days' interval provided measuring conditions are rigorously standardised. Basal and maximal arterial blood flows and venous emptying rates per 100 ml of tissue were significantly higher (p less than 0.

Effect of prolonged physical exercise on fluid regulating hormones.

Sixteen well-trained young men performed a test marathon to study the behaviour of atrial natriuretic peptide (ANP) and its second messenger cyclic guanosine monophosphate (cGMP) in relation to changes in plasma volume (PV) and plasma proteins, arginine vasopressin (AVP), renin, aldosterone, potassium and sodium. Blood samples were drawn under standardized conditions before and immediately after the run, as well as 3 h and 31 h after the run. Directly after the run, a two-and-a-half fold increase of plasma ANP and a twofold increase of plasma cGMP level were found, whereas PV decreased significantly by 7.

Effect of prolonged physical exercise on the fibrinolytic system.

The effect of a test marathon race on plasma fibrinolytic activity (FA) was studied in 16 endurance athletes before, immediately after, 3 h, and 31 h after the run. Tissue plasminogen activator (t-PA) activity increased about 31-fold immediately after the run. Similar increases were found in t-PA antigen concentration.

Influence of prolonged physical exercise on plasma volume, plasma proteins, electrolytes, and fluid-regulating hormones.

Fluid-regulating hormones [arginine vasopressin (AVP) and aldosterone] as well as electrolytes, plasma volume (PV), and plasma proteins were studied in 16 well-trained male amateur runners (mean age 31.8 years) before t0), immediately after (t1), and 60 min (t2) and 22 h (t3) after a marathon run. Immediately after the run PV was significantly decreased by 12.

Assessment of arterial and venous circulation in upper and lower extremities by venous occlusion strain gauge plethysmography. Normal values and reproducibility.

In 10 healthy men aged 25 to 35 years the variability of basal arterial blood flow (BBF), maximal arterial blood flow (MBF) as induced by a 5-minute arterial occlusion, total venous capacity (TVC) and venous emptying rate (VER) were studied in both the upper and lower limbs by repeated measurements over 5 hours under strictly standardised conditions using an automatic venous occlusion plethysmograph. Mean values obtained at the initial examination in the forearm and calf respectively were: BBF: 3.7 +/- 1.

The neurotoxicological aspects of the toxic oil syndrome (TOS) in Spain.

The pathomechanism of the Spanish mass oil poisoning, which affected more than 20,000 people in the spring of 1981 and has so far caused more than 500 deaths, has not yet been clarified. Subsequent to a toxic-allergic initial phase of the disease with fever as well as lung and skin manifestations, 10 to 20% of the patients, after passing through an interval of reduced symptoms, entered a second disease phase characterized by marked vasculitis and fibrosis in diverse organ systems. The most frequent manifestation type involved in this connection was a severe neuromyopathy with pronounced joint contractures and skin alterations.

[The hemostatic and fibrinolytic system in normal subjects and myocardial infarct patients. Effect of a standardized aerobic and anaerobic ergometric stress test].

After clinical examination, 14 asymptomatic post-infarction male patients and 12 healthy control persons, aged 35-62 years, underwent two bicycle-ergometry tests. After a 20-min aerobic test of moderate intensity both groups had slight activation of the clotting system simultaneously with favorably increased fibrinolytic activity. After stepwise submaximal aerobic exercise, postinfarction patients had marked activation of the thrombocytic system; beta-thromboglobulin rose significantly from 36 to 102 ng/ml.

Inhalant abuse and heroin addiction: a comparative study on 574 opiate addicts with and without a history of sniffing.

In the present study, a comparison relating to various social aspects was made between 74 opiate addicts who had abused or continued to abuse solvents and 500 fixers without sniffing experience (SE). The results show clear differences between the two groups with reference to age, sex, social status, socialization conditions, family structure, education, vocational training, drug sequence and criminality as well as attitude and motivation towards withdrawal therapy. Contrary to hitherto existing assumptions, solvent abuse among children and juveniles can lead to opiate addiction, given a certain set of social circumstances.

Ultrastructural alteration of intrapulmonary nerves after exposure to organic solvents. A contribution to 'sniffers disease'.

The effects of the solvents n-hexane, butanone (methyl-ethyl-ketone, MEK) and a mixture of both in the intrapulmonary nerve system of rats were studied by light and electron microscopy. The alteration in the fine structures of the tissue consisted in a disseminated swelling of axons due to a striking multiplication of neurofilaments. Nonspecific axonal alterations could be demonstrated as well.