The neuroregulatory properties of L-DOPA. A review of the evidence and potential role in the treatment of Parkinson's disease

Accumulating evidence suggests that L-dihydroxyphenylalanine (L-DOPA) has neurotransmitter-like and/or neuromodulatory properties in the CNS. Such evidence is based on a wide range of findings including the existence of specific L-DOPAergic neurons in several regions of the CNS, neurotransmitter-like characteristics and specific pharmacological effects. This review attempts to outline the main evidence for this conception and to relate such findings to L-DOPA treatment effects in Parkinson's disease. In this context L-DOPA in itself has been shown to potentiate D2 receptor-mediated effects, inhibit acetylcholine release and increase the release of L-glutamate, neuropharmacological effects which can be linked to treatment side-effects in advanced Parkinson's disease. It is suggested that supersensitive L-DOPA-mediated effects contribute to the pathogenesis underlying L-DOPA-induced motor complications in advanced Parkinson's disease. However, since specific L-DOPA receptors have yet to be identified, the assessment of the relative importance of L-DOPA-mediated effects in this clinical context must be regarded as incomplete.     

The soluble alpha-mannosidases of Drosophila melanogaster

The alpha-mannosidases are implicated in both the catabolism of carbohydrates and the N-linked glycosylation pathway in insects, but little is known of the biochemistry of these glycosidases. In order to study the soluble alpha-mannosidases of Drosophila melanogaster we have used artificial fluorogenic substrates for detection of activity in situ following non-denaturing gel electrophoresis. This approach also permitted examination of the mannosidases present in different tissues and the sensitivity of the enzymes to known mannosidase inhibitors. Fluorogenic substrates were also used to determine the pH optima of partly purified mannosidases. We report that D. melanogaster contains several soluble alpha-mannosidase activities. Acidic mannosidases were detected in the gut, fat body and haemolymph of third-instar larvae. The major activity detected in larval guts was a neutral mannosidase presumed to be involved in digestion.     

Studies on the hypodermosis affecting red deer in central and southern Spain

From November 1992 to February 1993, 455 red deer (Cervus elaphus) were surveyed in order to estimate the prevalence of warble fly (Hypoderma actaeon) larvae under the skin of this ungulate species. Material came from Montes de Toledo, Sierra Morena, Sierra de Alcaraz, and Sierras de Cazorla, Segura y Las Villas Natural Park (central and southern Spain). We observed a prevalence of 92%, with a mean +/- SD intensity of 35.7 +/- 41.3 grubs per parasitized host; there was a maximum of 317 larvae per host. No significant differences in prevalence by host sex were found, although significant differences were observed in prevalences among different host age classes. The main location of feeding larvae in deer was in the back tissues.     

Gastrointestinal autonomic nerve tumors. A clinicopathological, immunohistochemical, and ultrastructural study of 12 cases

The gastrointestinal autonomic nerve tumor (GAN tumor) is an uncommon stromal tumor of the intestinal tract and retroperitoneum first described by Herrera and associates in 1984. Distinction of GAN tumors from other gastrointestinal stromal tumors is based on electron microscopic findings. Thus far there have been 12 reported cases. We present an additional 12 GAN tumors, identified by us during 4 years. There were seven male and five female patients and they ranged in age from 10 to 85 years (mean: 58 years). Sites of the tumors were stomach (three), jejunum (two), ileum (four), mesentery (one), and retroperitoneum (two). Eight of the tumors measured > 10 cm in greatest dimension. Usually well circumscribed, the neoplasms were tan to light pink, sometimes hemorrhagic, and soft. There was a variety of histologic patterns including fascicles, palisades, and whorls. Mitotic activity varied from 0 to 23 mitosis per 10 high-power fields (HPF). Using a panel of 10 immunohistochemical stains, only vimentin was consistently positive. There was neuron-specific enolase reactivity in six and S-100 protein reactivity in two cases. All muscle markers were negative. Ultrastructural studies showed neuron-like cells with long axonic cytoplasmic processes ending in bulbous synapse-like structures containing dense-core neurosecretory granules and clear vesicles. Basement membrane was absent. These features are reminiscent of ganglia of the intestinal autonomic nervous system. The patients were followed for 5-125 months (mean of 26 months). Tumor recurred or metastasized to the liver in seven patients (58%) and four patients died with tumor. There were correlations between tumor size (> 10 cm), mitotic count (at least five per 10 HPF), and aggressive behavior.     

Specificity of antiperinuclear factor for rheumatoid arthritis in rheumatoid factor-positive sera

Although antiperinuclear factor (APF) has the same specificity for rheumatoid arthritis (RA) as rheumatoid factor (RF), there is no evidence that this specificity is maintained in patients with positive RF-agglutination tests. Thus, we evaluated the specificity and usefulness of APF for RA diagnosis, regardless of RF titre. APF was tested (1:100 threshold) on 214 sera sent for RF evaluation over a 9-month period. These sera were previously determined to have latex or Rose-Waaler (RW) titres > or = 12 or 4 IU, respectively, but not necessarily above the threshold values of 100 and 32 IU. The APF test was performed blindly, and physicians were not advised of the results. In the patient population (119 RA and 95 non-RA) APF still demonstrated good specificity (0.82) for RA. As expected, APF proved useful for RA diagnosis in 28/33 (85%) RA cases with an RF level below 1:100 for latex and 1:32 for RW, thus reducing the number of 'seronegative' RA from 33/119 to 5/119. However, it also improved the serological positive predictive value for RA, even in cases when RW results were > or = 32 IU. Indeed, the positive predictive value for RA when both tests were positive was 0.94 (68/72), whereas concordant results (either positive or negative) for both APF and RW tests allowed correct classification (RA or non-RA) in 94% of cases.     

Assessment of pseudarthrosis in pedicle screw fusion: a prospective study comparing plain radiographs, flexion/extension radiographs, CT scanning, and bone scintigraphy with operative findings

Tribal warfare is a way of life in the highlands of Papua New Guinea. In earlier times direct confrontation with bushknives and axes, and shooting with bows and arrows were common. In recent years there have not been as many instances of direct confrontation with bushknives and axes, but the use of bows and arrows is on the rise. Since 1993, guns have been increasingly used, with devastating results. In 1993, 18 deaths were reported from tribal warfare in one area of the Southern Highlands Province, especially from gunshots, while in 1994, 24 deaths were reported from another area. A five-year review of tribal fight admissions to Mendi Hospital, from 1990 to 1994, showed an increase in the number and proportion of gunshot wounds; there were none in 1990-1992 but they constituted 18% of tribal fight injuries in 1993 and 33% in 1994.