Hallucinations, REM sleep, and Parkinson's disease: a medical hypothesis.
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Biomedical subjects
Publications and source records attributed to P Mazzarello.
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The Italian pathologist Giulio Bizzozero began his haematological investigations more than 130 years ago. Among his outstanding achievements was the discovery of the role of platelets in haemostasis and the identification of the bone marrow as the site of production of blood cells. One hundred years after his untimely death, the significance of these, and many more of his findings, is still recognized.
The objective of this study was to compare the efficacy and tolerability of gabapentin and amitriptyline monotherapy in painful diabetic neuropathy. This was a 12-week, open-label, prospective, randomized trial. Twenty-five type-II diabetic patients with pain attributed to diabetic neuropathy and a minimum score of 2 on a pain intensity scale ranging from 0 (no pain) to 4 (excruciating pain) were randomized to receive either gabapentin, titrated from 1,200 mg/day to a maximum of 2,400 mg/day, or amitriptyline, titrated from 30 mg/day to a maximum of 90 mg/day. Both drugs were titrated over a 4-week period and maintained at the maximum tolerated dose for 8 weeks. The main outcome measures were weekly pain intensity and paresthesia intensity, measured on two categorical scales. Thirteen patients received gabapentin and 12 received amitriptyline. All 25 patients completed the trial. Gabapentin produced greater pain reductions than amitriptyline (mean final scores were 1.9 vs. 1.3 points below baseline scores; P = 0.026). Decreases in paresthesia scores also were in favor of gabapentin (1.8 vs. 0.9 points; P = 0. 004). Adverse events were more frequent in the amitriptyline group than in the gabapentin group: they were reported by 11/12 (92%) and 4/13 (31%) of patients, respectively (P = 0.003). Side effects were the main limiting factor preventing dose escalation. Gabapentin produced greater improvements than amitriptyline in pain and paresthesia associated with diabetic neuropathy. Additionally, gabapentin was better tolerated than amitriptyline. Further controlled trials are needed to confirm these preliminary results.
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Radial glial cells are now recognized as a transient population that serves as scaffolding for neuronal migration. The recognition of the existence and role of radial glia has not been smooth, and here we provide a brief historical overview on the pioneering studies on this subject. The histologists and embryologists Albert Kölliker and Wilhelm His performed seminal investigations on cortical morphogenesis in the last decades of the 19th century. However, the introduction of the silver impregnation Golgi technique, and its diffusion in the late 1880s, played a crucial role in the detection of radial glial processes. The radial arrangement of fibers emerging from the neuroepithelium lining the central canal was initially detected in the embryonic spinal cord by Camillo Golgi himself. The first Golgi impregnation of the cerebral cortex of mammalian fetuses was performed by Giuseppe Magini, who detected radial fibers extending from the ventricular neuroepithelium, and observed cells intercalated along these processes. Radial fibers, regarded as epithelial or ependymal processes, were then observed in the developing spinal cord and cerebral cortex by several investigators. Santiago Ramón y Cajal was the first to suggest that radial fibers were modified astrocytic processes functioning as a support during cortical histogenesis. Cajal acknowledged Magini's findings, but he criticized Magini's observations on the existence of neurons along radial fibers. With the advent of electron microscopy, the existence of radially arranged glial processes along which young neurons migrate was finally ascertained in the early 1970s by Pasko Rakic, thus opening a new era in the cellular and molecular biology of radial glia.
After the first observations of life under the microscope, it took two centuries of research before the 'cell theory', the idea that all living things are composed of cells or their products, was formulated. It proved even harder to accept that individual cells also make up nervous tissue.
Born in Corteno, a tiny village in the province of Brescia, Camillo Golgi studied at the University of Pavia where he graduated in medicine in 1865 under the guidance of the psychiatrist Cesare Lombroso who sparked his vocation to study the brain. Golgi then began to learn histological techniques under the direction of the pathologist Giulio Bizzozero. In 1872 he moved to Abbiategrasso as chief of a hospital for chronic diseases. In a rudimentary laboratory he developed the silver-bichromate staining technique, the 'black reaction', which was a breakthrough for nervous tissue structure research. While in Abbiategrasso Golgi demonstrated the branching of the axons, and observed striatal and cortical lesions in a case of chorea. He returned to Pavia as Professor of Histology and General Pathology, and made a series of important discoveries that still bear his name: the Golgi tendon organ, the Golgi-Mazzoni corpuscles, another Golgi method to stain nerve cells based on the use of potassium dichromate and mercuric chloride, the canaliculi of the parietal cells of the gastric glands (Muller-Golgi tubules), the Golgi-Rezzonico myelin's annular apparatus (or Golgi-Rezzonico horny funnels), the cycle of malarian parasites (Golgi cycle), the relationship between recurrent malarian fever bouts and the multiplication of the Plasmodium in the blood (Golgi law), the relationship between the vascular pole of the Malpighian glomerulus and the distal tubule, the Golgi's pericellular nets and finally, and most importantly, the cytoplasmic 'internal reticular apparatus' (Golgi apparatus). In 1906 Golgi was awarded the Nobel prize for Medicine or Physiology. He died in Pavia on 21 January 1921.
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In April 1898 at the Medico-Surgical Society of Pavia, Camillo Golgi communicated his finding of a novel intracellular structure, which he had detected in nerve cells by means of a variant of the "black reaction" he had developed earlier for the staining of the nervous tissue. On the basis of the "netlike" appearance and intracellular location of this structure, Golgi defined it as "internal reticular apparatus". The reality of the organelle was debated for fifty years, since some investigators believed that the structure, which was soon designated as Golgi apparatus, represented an artifact of metallic impregnation. The controversy was finally solved in the mid-1950s by studies based on electron microscopy. Linked to the cell organelle he had discovered, Golgi's contributions to cytology had a great impact on biomedical sciences of the twentieth century.
Camillo Golgi played a key role in the studies of malaria infection. Among his outstanding contributions to the topic are the description of the intraerythrocytic cycle of the malaria parasite Plasmodium, responsible for the quartan and tertian fever, and the discovery of the temporal relationship between the recurrent attacks of fever and parasite's multiplication in human blood. Moreover, Golgi was also actively involved in the campaigns against malaria performed in the first ten years of this century by his pupil Adelchi Negri. Golgi's archive at the Museum for the History of the Pavia University keeps important materials on the role of this scientist in the history of malariology. Here we summarize and report some brief extracts of the documents (mainly letters from the nineteenth century biologists to Golgi) relevant to the history of human malaria.
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Ottorino Rossi was a remarkable Italian neurologist of the first half of this century. He made important contributions to many fields of clinical neurology, neurophysiopathology and neuroanatomy. Among these are: the identification of glucose as the reducing agent of the cerebrospinal fluid, the demonstration that fibres from the spinal ganglia pass into the dorsal branch of the spinal roots, and the description of the cerebellar symptom which he termed "the primary asymmetries of positions". Moreover, he conducted important studies on the immunopathology of the nervous system, on the serodiagnosis of neurosyphilis and on the regeneration of the nervous system. He studied pathological anatomy under Camillo Golgi and clinical neurology under Casimiro Mondino and completed his clinical preparation in Florence with Eugenio Tanzi, and in Munich at the Institute directed by Emil Kraepelin. Ottorino Rossi taught at the Universities of Siena, Sassari and Pavia; in the last town he was made Dean of the University and managed to have the buildings of the new San Matteo Polyclinic completed. Ottorino Rossi was one of Camillo Golgi's most illustrious pupils as well as one of the most eminent descendants of Pavia's medico-biological tradition.