The usefulness of the prognostic inflammatory and nutritional index (PINI) in a haemodialysis population.

BACKGROUND AND AIM: Protein-Energy Wasting and inflammation are the principal risk factors of haemodialysis complications. We evaluated the reliability of a simple and non expensive test, the Prognostic Inflammatory and Nutritional Index (PINI), for regular screening of maintenance haemodialysis (MHD) patients in order to detect early onset of inflammation and malnutrition. METHODS AND RESULTS: 121 adult patients on maintenance dialysis were followed up for 32 months and screened every 6 months for PINI, calculated as alpha1-Acid Glycoprotein (alpha1-AG)xC-Reactive Protein (CRP)/AlbuminxTransthyretin. PINI score < or =1 was considered normal. Patients were stratified according to their PINI score: 86 patients (71.66%) had a normal score, whereas 35 (28.33%) had PINI > or = 1. The latter also had higher CRP levels, despite no clinical evidence of inflammation at the time of enrolment. Survival in patients with normal PINI was similar to patients with normal CRP, while in patients with abnormal PINI it was significantly lower than in patients with low serum albumin (p<0.05) or elevated CRP (p<0.05). After follow-up, all surviving MHD patients with PINI > or = 1 had at least one cardiovascular event vs 2.5% of patients with PINI > or = 1. CONCLUSION: The assessment of PINI can reliably identify MHD patients at higher risk of mortality and morbidity even in the absence of overt Malnutrition-Inflammation Complex Syndrome (MICS). This simple test appears to be more sensitive and specific of the single components, and not expensive, so that it could be routinely used to identify patients with sub-clinical inflammation and/or malnutrition.

Drug action on the metabolic changes induced by acute hypoxia on synaptosomes from the cerebral cortex.

The synaptosomal fractions obtained from the motor area of the cerebral cortex of normocapnic, normoxic, or hypoxic, untreated beagle dogs and of pentobarbital (Nembutal)- or cytidine diphosphate (CDP)-choline-treated dogs were incubated and analyzed for ATP, ADP, AMP, creatine phosphate, pyruvate, and lactate. The data were compared with data obtained by the surface freezing technique from the whole contralateral cortical area. The in vivo intracarotid perfusion of the drug differentially affected the content of the metabolites and their ratio. This occurred whether the evaluations were performed in the incubated synaptosomal preparations or in whole cerebral tissue, both during normoxia and after hypoxia (15 min; PaO2 = 17-19 mm Hg). Thus, intracarotid perfusion of nembutal increased the synaptosomal phosphorylation state both in normoxic and in hypoxic animals, whereas the effect on the metabolism of the contralateral cortical motor area as a whole was in all cases less than that observed in the synaptosomal fraction. Perfusion with CDP-choline increased synaptosomal phosphorylation after the hypoxic condition, but had no effect in normoxia or on the whole cortical tissue of the motor area. The possibility of obtaining a cerebral sparing action by utilizing molecules devoid of anesthetic action is suggested.

Influence of aging on cerebral derangement by acute severe hypoxia during hypovolemic hypotension.

In synaptosomes isolated from the motor area of the cerebral cortex of beagle dogs and incubated in Krebs-Henseleit-Hepes buffer (for 10 min at 24 degrees C), the energetic state was defined by the balance of the labile phosphates (ATP, ADP, AMP, and creatine phosphate), the redox state of the intramitochondrial NAD-couple, and the respiratory rate. By the experimental model utilized in the present research, it is possible to evaluate the potential synaptosomal damage induced by the in vivo hypoxic insult. Aging affects the phosphorylation state of the posthypoxic incubated synaptosomes. Although the oxygen consumption rate is the same in the synaptosomal fractions from the motor area of hypoxic beagle dogs of different ages, the cytochrome c and a contents are lower in the preparations from older brains. This points to higher activity of cytochromes in the synaptosomes from "mature" and "senescent" hypoxic animals. In dogs of different ages, hypoxia lowers the respiration of the synaptosomes but aging affects the oxygen consumption rates only in post-hypoxic synaptosomes incubated with succinate. In synaptosomes isolated from older hypoxic brains, the free energy utilized for the synthesis of two moles of ATP (delta GATP) is progressively lower than that released upon the transfer of electrons from the NADH to cytochrome c (delta Gox-red).

Unilateral reduction of head pain and facial vasodilatation after gasserian ganglion lesion.

The features of histamine-induced headache and its associated vascular responses were studied in 52 patients with different surgical lesions of the gasserian ganglion and in 12 control subjects. Certain features of headache (eg, intensity, type, and duration) were similar in patients and control subjects. However, the pain was absent on the side of the trigeminal lesion in 26 (50%) of the patients. This unilateral absence of pain was not related to the hypoesthesia that was caused by the operation, and it was associated with a decrease in vascular responses (histamine-induced facial flushing and increase in temperature) on the side operated on. These abnormalities were more prevalent in patients who had undergone thermocoagulation and presented with more severe damage of the trigeminal ganglion than in those who were subjected to trigeminal compression or glycerolization. The trigemino-vascular system seems to control headache of a vascular type and associated craniofacial vasodilatation in human subjects.

Influence of age upon the cerebral metabolic changes induced by acute hypoxia on the synaptosomes from dog brain.

The synaptosomal fraction obtained from the motor area of the cerebral cortex of normocapnic, normoxic or hypoxic "young adult," "mature" and "senescent" beagle dogs is incubated and analyzed for : ATP, ADP, AMP, creatine phosphate, pyruvate and lactate. The data are compared with those obtained from the whole controlateral cortical motor area, by the surface freezing technique. After hypoxic hypoxia /15 min; PaO2 = 17-19 mm Hg), the metabolite contents and ratios are differently affected by ageing when the evaluations are performed in the incubated synaptosomal preparation or in the controlateral whole cerebral tissue. In fact, ageing does not affect so much the cerebral changes that occur in the overall energetic state during the hypoxic assault in vivo, but rather those that the synaptosomes remember the tend to reverse during the subsequent incubation in vitro. The protective action of several drugs on the synaptosomal phosphorylation state is tested. Phenobarbital shows a quite broad, age-independent spectrum of action. (-)Eburnamonine and dihydroergocristine exhibits a more limited, age-dependent effectiveness, but are devoid of anesthetic action. Papaverine proves unable to affect the tested biochemical parameters.

[Anomalies of the pattern of lumbosacral nerve roots and its clinical significance (author's transl)]. / Anomale Wurzelabgänge im lumbosacralen Bereich und ihre klinische Bedeutung

Twenty personal observations and 18 cases collected from the literature are analysed. The most frequently encountered anomaly were: common dural origin of 2 nerve roots and common exit of 2 nerve roots through the intervertebral foramen. Other anomalies comprised: interradicular connections and Y-shaped or horizontla course of the nerve root. Multiple anomalies were not encountered. In 9 out of 20 patients in the own series and in 6 out of 18 patients reported in the literature, history and clinical findings suggested prolapsed intervertebral disc, operation revealed only nerve root anomalies. Decompression produced improvement or complete relieve of previously existing signs and plain X-rays is not possible. The diagnosis is based on myelographic findings. The pathogenesis of the anomalies is discussed. It is suggested that they should not be considered as a causative factor of low back pain or sciatica.

Striatal cholinergic receptors and dyskinetic motor activity in the rat.

An injection of D-tubocurarine into the rat striatum produces a complex motor syndrome resembling in part that induced by picrotoxin. The destruction of the dopaminergic terminals by 6-hydroxydopamine does not prevent these effects of D-tubocurarine on motor activity. Hence neither dopamine release nor the presynaptic acetylcholine receptors are responsible for the D-tubocurarine-induced movements. On the other hand, lesion of the striatum by kainic acid abolishes the motor abnormalities due to D-tubocurarine but not those due to picrotoxin injection. Therefore, the effects of picrotoxin might be attributable to an action on GABA receptors still present in the kainic acid-treated striatum, whereas the effects of D-tubocurarine might be due to its action on striatal postsynaptic acetylcholine receptors.

One year treatment with lisuride delivery pump in Parkinson's disease.

1. A group of 14 fluctuating Parkinsonian patients underwent the subcutaneous Lisuride treatment, administered by an insulin delivery pump. Clinical response has been studied during a one year period. 2. Some patients (8 out of 14) were in combined therapy, assuming a relative small amount of oral L-Dopa together with subcutaneous Lisuride. 3. Lisuride confirmed, also by the subcutaneous route, its antiparkinsonian properties, without any loss of therapeutical efficacy during the 12 month period considered. 4. 7 patients dropped-out from the study, due to psychiatric or systemic side-effects and to "technical" management of the pump. 5. The only 2 patients assuming a 24 hour regimen of Lisuride infusion were among the withdrawn subjects. They were also the only to complain severe psychiatric disturbances.

CBF and cognitive evaluation of Alzheimer type patients before and after IMAO-B treatment: a pilot study.

Ten patients diagnosed as affected by primary degenerative dementia of the Alzheimer type, with a mild to moderate cognitive and behavioral impairment, were studied in a double blind design when taking for 60 days 5 mg twice a day of L-deprenyl or placebo. Cognitive functions and cerebral blood flow were assessed at the beginning and at the end of treatment by a wide array of memory, attention, and language efficiency measures and by SPECT-99TcHMPAO procedure. Reduced CBF on the parietal lobes was demonstrated in the patients at baseline together with a reduction of memory and cognitive efficiency. At the end of the treatment patients who received L-deprenyl showed an improvement in cognitive efficiency and no changes in CBF, while patients treated with placebo showed a worsening of cognitive efficiency and further reduction of parietal lobe CBF.

Problems in daily motor performances in Parkinson's disease: the continuous dopaminergic stimulation.

Fluctuations in motor performances are the major problem in the longterm management of Parkinson's disease. In this study the clinical effects of L-dopa intravenous infusion were evaluated in 18 parkinsonian patients with fluctuations. 14 out of these were given Lisuride intravenous infusion in a following study. Lisuride is a potent dopamine agonist and it is highly soluble in water. The results obtained with L-dopa were very good and we found a close correlation between oral and intravenous dosage. The dosage of L-dopa infusion ranged between 360-1,250 mg for 12 hours. Lisuride proved to be able to give prolonged mobile state in 8 patients out of 14. The other 6 patients showed a different response to the drug. The dosage used ranged between 0.6 and 2.4 mg per day. No severe side-effects were observed during both studies except for nausea and vomiting occurring during Lisuride infusion.

The role of MAO-b inhibitors in the treatment of Parkinson's disease.

The classical treatment of Parkinson's disease (PD) using L-dopa plus a peripheral decarboxylase inhibitor (DI) often leads after 3-5 years to the onset of the so-called long-term L-dopa syndrome (LTS). LTS could depend on the chronic overload of L-dopa + ID and could be due to a consequent "receptor disease" and derangement of the neuronal functionality mainly in regard to the enzymatic chains, storage mechanisms and hyperactivity of the monoamine oxidase type B (MAO B). Deprenyl is a selective MAO-B inhibitor thought to be able to slow down the catabolism of dopamine and therefore to allow a decrease of the therapeutic regimen of L-dopa while in the meantime to obtain a more stable plasma and tissue levels and a constant therapeutic response. 76 parkinsonian patients were studied. Their L-dopa regimen was halved and 10 days after (-)deprenyl was added. After the decrease of L-dopa therapy a worsening of symptomatology was observed as expected. The association with (-)deprenyl was able to reverse this trend and when the inhibition of MAOB was really effective patients showed an improvement of symptoms even when compared to baseline values. No relevant side effects were observed and no patients dropped out.

Subcutaneous lisuride infusion in Parkinson's disease: clinical results using different modes of administration.

The continuous dopaminergic stimulation provided by infusion of dopamine agonist drugs, is a very effective strategy to control ON-OFF fluctuation in Parkinson's disease. Lisuride is a potent dopamine agonist drug, very soluble in water and can be administered subcutaneously. Many authors have shown that the subcutaneous infusion of lisuride can control fluctuations when applied in combination with oral levodopa as a 24 hour continuous infusion regimen. In this study, lisuride was given without any other antiparkinsonian medicament and using a 12 hour infusion regimen wherever possible. 13 fluctuating Parkinsonian patients were studied. 6 out of these 13 were satisfactory treated with lisuride alone and the remaining 7 with a combination of Lisuride + oral levodopa. Only in 3 out of 13 patients the 24 hour infusion regimen was required.

Enterogenous intraspinal cysts.

The authors have reviewed the literature and recorded the distinguishing features of intraspinal enterogenous cysts. There are no characteristic clinical findings or history associated with this disease. These congenital space-occupying lesions frequently go undiagnosed, and the patient may be treated for many years as a case of multiple sclerosis. The teratogenic "determination period" is decisive for the development of anomalies affecting one, two, or all three of the germinal layers. All of these cysts belong to the same group, and their structure is an expression of the differing determination periods. The various theories about their etiology are discussed. True intraspinal enterogenous cysts are usually found in the cervical region. After careful operative removal, the prognosis is favorable.

Effect of cholinergic and anticholinergic drugs on short-term memory in Alzheimer's dementia: a neuropsychological and computerized electroencephalographic study.

A correlation was found among the degree of memory loss, intellectual impairment, the quantity of senile plaques, and a decrease in choline acetyltransferase and acetylcholinesterase activity in patients affected by senile dementia of the Alzheimer type. In this study, patients were subjected to a series of computerized electroencephalographic (EEG) recordings and neuropsychological evaluations after acute administration of the following drugs: placebo; the cholinergic drugs physostigmine, pyridostigmine bromide, and edrophonium chloride; and the anticholinergic drugs scopolamine and orphenadrine. The results obtained show that the acute administration of some cholinergic drugs improved memory and attention performances, whereas the anticholinergic drugs induced opposite effects. The cholinergic drugs exhibited a tendency to shift the EEG spectrum analysis into more normal patterns compatible with the patient's age. This study supports the view that the cholinergic system plays an important role in memory and attention disturbances found in senile dementia of the Alzheimer type.

Increased reactivity to a met-enkephalin analogue in the control of autonomic responses in migraine patients.

The effects of naloxone and a met-enkephalin analogue on head pain, vascular responses, and autonomic-associated symptoms were studied in 24 migraine patients, 12 patients suffering from tension-type headache, and 24 normal subjects in whom headache was induced by intravenous injections of increasing doses of histamine (histamine test). A hypersensitivity to histamine was found in migraine patients. Naloxone slightly increased the intensity of pain in migraine and tension-type headache sufferers. The met-enkephalin analogue did not affect the intensity of pain in migraine patients, tension-type headache patients, and normal subjects, but it reduced the intensity and duration of facial flushing (p less than 0.001) and the autonomic symptoms (p less than 0.001) in migraine patients when the pretreatment was not given shortly before histamine. In migraine patients, there seems to be an increased reactivity (receptor supersensitivity?) to the met-enkephalin analogue at the level of systems that inhibit facial vasodilatation and autonomic symptoms.

Effects of terguride in patients with Huntington's disease.

trans-Dihydrolisuride, a partial dopamine receptor agonist, was tested for its effects on chorea in a double-blind, crossover clinical study in 10 patients with Huntington's disease. In eight patients, a neurophysiological evaluation was also performed. No reduction in choreic movements or improvement in voluntary movement performance was observed. However, in some patients, there was a slight improvement in patients' alertness and a reduction of the movement reaction time.

Antagonist effect of terguride in Parkinson's disease.

The effects of the partial dopamine agonist terguride (9,10 transdihydrolisuride; THDL) on striatal dopamine receptors were studied by its i.v. administration to 13 patients with Parkinson's disease. Patients were maintained in a steadily mobile state with abnormal involuntary movements by a constant i.v. infusion of levodopa. Terguride showed dopamine antagonist properties in nine patients. In two of these nine patients, a decrease in dyskinesia score was observed without a concomitant worsening of parkinsonian symptoms, whereas in the remaining seven, full parkinsonian akinesia followed THDL administration. The subsequent i.v. injection of the dopamine agonist lisuride reversed THDL-induced akinesia in these seven patients. In the remaining four patients, no clinically significant motor effects were observed. These results show dopamine antagonist activity of terguride in patients with Parkinson's disease treated with Levodopa. Further studies using a wider dose titration are required to evaluate the possible role of dopamine partial agonists in the therapy of levodopa-induced dyskinesias.

The clinical efficacy of oral levodopa methyl ester solution in reversing afternoon "off" periods in Parkinson's disease.

We compared the efficacy of a single dose of an oral solution of levodopa methyl ester (ME) to that of standard levodopa, in the form of a single dose of Madopar, in reversing afternoon "off" periods in 12 patients with Parkinson's disease (PD). The highly soluble ME solution led to a significantly more rapid reversal of "off" periods. This preparation may therefore convey a clinical advantage in patients experiencing motor fluctuations whilst taking multiple daily dosages of levodopa, particularly in those with long or highly variable latency to the next "on" period.

A clinical and neurophysiological evaluation of clotiazepam, a new thienodiazepine derivative.

The effects of 3 different dosages of clotiazepam, a new short-acting thienodiazepine derivative, were evaluated by using psychometric ratings and EEG spectrum analysis. A random double-blind study versus placebo was performed on 8 patients affected by generalized anxiety disorder (DSM III). The effects of acute administration of clotiazepam 5 mg, 10 mg, 20 mg and placebo per os were evaluated by using HRSA and a time-signed semiquantitative scale for anxiety. The results of the trial confirm the effectiveness of clotiazepam in the treatment of anxiety symptoms, mainly in the reduction of peak anxiety levels, with dose-dependent characteristics. The modifications of the EEG parameters which resulted were dose-dependent and short-lasting with slight sedative findings.

Double-blind controlled study on the clinical efficacy and safety of fluoxetine vs clomipramine in the treatment of major depressive disorders.

In the present double-blind controlled study the efficacy and safety of fluoxetine 20 mg/day versus clomipramine 75 mg/day was evaluated during 5 weeks of treatment in 30 hospitalized patients. The sample was selected according to DSM III criteria for major depressive disorders with a score of at least 18 on the first 17 items of the Hamilton Rating Scale for Depression (HRSD). Therapeutic efficacy was evaluated weekly by using HRSD, Zung Self Rating Scale for Depression, Montgomery-Asberg Scale for Depression, Clinical Global Impression for severity and improvement of depressive symptoms. Safety was monitored weekly by recording body weight, blood pressure, pulse rate, temperature, physical conditions, laboratory tests, adverse experiences and concomitant medication. The results confirm the effectiveness and good tolerability of fluoxetine in the treatment of depressive disorders.