Calcitriol oral pulse therapy in children with renal osteodystrophy

A 6-month protocol of oral pulse calcitriol was used in nine uraemic children (2–14 years old) on dialysis who presented with renal osteodystrophy. Calcitriol was administered twice a week, 4 g per dose for patients over 30 kg and 3g for patients less than 30 kg. Plasma levels of parathyroid hormone, calcium, phosphorus and alkaline phosphatase were carefully controlled during the study. Parathyroid hormone levels decreased by 68% and 56% by the 2nd and 6th months of treatment in seven patients, while they remained unchanged in two patients with focal segmental glomerulosclerosis and massive proteinuria. Eight hypercalcaemic episodes from 77 determinations were observed, all of them recovered after 1 week of vitamin D withdrawal. We conclude that oral calcitriol pulse therapy is a good alternative for renal osteodystrophy in uraemic children. Careful monitoring of plasma parathyroid hormone and calcium is needed during follow-up when using this approach in paediatric patients.     

Genetic markers in primary open-angle glaucoma

Purpose: To investigate possible associations between genetic markers and Primary Open-Angle Glaucoma (POAG). Methods: A number of genetic markers were typed in 84 unrelated patients with POAG and compared with a random sample of healthy individuals. The markers were Transferrin, Group Specific Component, G1m (1), G1m (2) and G3m (5) Allotypes, Adenylate Kinase, Adenosin Deaminase, Glyoxalase I and Acid Phosphatase and PCR-based markers HLA-DQA1 and D1S80. Results: No significant differences were found except the strong association between the group of POAG patients and Acid Phosphatase ACP^*C allele (² = 32.86; p < 0.0001). Conclusions: Since Acid Phosphatase gene is localized to chromosome 2p23, this result could be a first comprehensive step in the localization of POAG genes.     

Metabolic and neuroanatomical correlates of barrel-rolling and oculoclonic convulsions induced by intraventricular endothelin-1: a novel peptidergic signaling mechanism in visuovestibular and oculomotor regulation?

The neuroactive peptide endothelin-1 has receptors distributed abundantly among subdivisions and nuclei of the visuovestibular and oculomotor systems. In previous work, we and others described the convulsive manifestations resulting from central injection of this neuropeptide, including nystagmus, oculoclonus, exophthalmos, tonic hindlimb extension, and a generalized repetitive motor disturbance called barrel-rolling. We applied the quantitative, autoradiographic [¹⁴C]deoxy-glucose method to examine the hypothesis that visuovestibular and oculomotor structures would become metabolically stimulated when endothelin was introduced into the brain via the ventricular system in conscious rats. Since previous work had demonstrated that hypermetabolic responses to endothelin in other neural systems were inhibited by an antagonist of neuronal calcium L-type channels, nimodipine, we further tested whether the increased function of vestibulooculomotor nuclei whose metabolic activity was sensitive to endothelin could be altered following nimodipine pretreatment via the ventricle. A single unilateral injection of endothelin (9 pmol in 3 l saline) into a lateral ventricle provoked significantly increased rates of glucose metabolism in 22 of 39 individual anatomical structures of the visuovestibular and oculomotor systems. Among those affected were the superficial stratum of the caudal superior colliculus (+25%), the optic tract bilaterally (+ 35 to 43%), the oculomotor cranial nerve nuclei (III, IV, VI; range of +21 to 47%), and the medial terminal nucleus of the accessory optic tract which harbors dense fields of endothelin binding sites (bilateral increase of +70 to 96%). Several other nuclei involved in the proprioceptive and visuovestibular disturbance caused by endothelin displayed increased metabolic activity, including the cuneate, gracile, sensory trigeminal, and prepositus hypoglossal nuclei, the vestibular subnuclear system, and the cerebellar flocculus. Identification of hypermetabolic responsivity to endothelin in these structures provides further information on the anatomical substrates mediating the behavioral phenomenology of endothelin-induced motor convulsions which involve the paroxysmal participation of the extraocular muscles and motor control systems producing barrel-rolling convulsions. Nimodipine pretreatment inhibited both the convulsive activity and the cerebral hypermetabolic responses to intraventricular endothelin. The results indicate that the neural systems sensitive to intraventricular endothelin become functionally active via a calcium-mediated process that may involve the neuropeptide as an intrinsic signaling molecule.     

Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients

Treatment of retinitis by cytomegalovirus (CMV) in AIDS patients requires frequent repetitive injections of intravitreal ganciclovir (GCV). This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped GCV could prolong intraocular therapeutic levels when compared with the intravitreal injection of free GCV, and the clinical effectiveness of this approach in AIDS patients. Intraocular concentration of GCV was determined by means of an ELISA test in rabbit vitreous 2, 3, 7, and 14 days after a single intravitreal injection of either different doses of the free drug (0.2–20 mg) or 1 mg of liposomally-entrapped GCV. After 72 h, only the vitreous of rabbits injected with doses of free GCV greater than or equal to 5 mg showed therapeutic levels of the drug; no GCV was detected after 72 h with any of the doses applied. Moreover, the microscopic study revealed GCV-induced damage in retinal structures in the animals injected with a free GCV dose greater than or equal to 15 mg. Intravitreal injection to rabbits of 1 mg of liposomally-encapsulated GCV showed no retinal toxicity at any of the time points studied, and therapeutic levels were detected up to 14 days after injection (4.67 ± 0.39 g/ml). Five AIDS patients suffering CMV retinitis were injected with 0.5 mg of liposomally-entrapped GCV (2 mg of lecithin). Complete remission of the CMV retinitis was observed already at the third injection of 0.5 mg GCV (one per week) and relapse did not occur during the 2–4 month follow-up of the patients. In view of the results presented, it can be concluded that intravitreal injection of liposomally-encapsulated GCV increases the time period required for reinjections in the treatemnt of CMV retinitis.Abbreviations AIDS acquired immunodeficiency syndrome - AZT zidovudine - CMV cytomegalovirus - GCV ganciclovir     

Anodontites trapesialis: A biological monitor of organochlorine pesticides

The mussel Anodontites trapesialis (Lam, 1819) was used as an indicator of organochlorine pollutants in the Pardo River, located in the municipality of Ribeirão Preto (21° 07S and 47° 45W), State of São Paulo, Brazil.Biological monitoring was performed for one year at the site of a sugar cane grove on the left bank of the river. Forty-three animals were placed in two aluminum enclosures on the river bottom at this site and 4 animals of each enclosure were sacrificed for pesticide analysis at 3-month intervals, each collection corresponding to one season of the year.The animals were found to have been exposed to DDT, lindane, heptachlor, aldrin and dieldrin. Endrin was not detected in any of the analyses.Research supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP).     

Gallium scintigraphy in Hansen's disease

Gallium 67 imaging was used in 12 patients with documented Hansen's disease undergoing treatment or not, in an attempt to determine the pattern of the disease. Diagnosis was confirmed by histopathology in all patients. The Mitsuda reaction was seen in all patients. Specific nuclear studies were performed when needed to evaluate particular organs better. Gallium 67 images show homogeneous, diffuse and moderate accumulation over the entire skin surface (except for the face) of untreated patients with multibacillary disease. The facial skin in these cases presented homogeneous, diffuse but very marked uptake of gallium. Internal organ involvement was variable. There was a very good correlation among clinical, scintigraphic, immunological and histopathological data. The pattern of the body skin (skin outlining) and facial skin (beard distribution) may be distinct for untreated patients with multibacillary leprosy.     

Combination chemotherapy of the epipodophyllotoxin derivatives,Teniposide and Etoposide

Summary Previous studies in vitro on the influence of extracellular protein binding of Teniposide (VM26) and Etoposide (VP16-213) on subsequent cellular uptake by experimental murine tumor cells [Cancer Res 38: 2549 (1978); Drug Metab Rev 8: 119 (1978)] suggested that a timed-sequential combination of VM26 and VP16-213 may increase the bioavailability of VP16-213. This was studied clinically in six cancer patients with ascites (five ovarian, one rectal) whereby VM26 (20 mg/m²) was given i.p. 2 h prior to VP16-213 (100 mg/m²; i.p.). In some patients, this regimen was administered i.v. The i.v. regimen was found to be more toxic (myelosuppression, nausea, vomiting) than i.p. regimen at same doses of drugs. Several patients remained stable to disease during 1–2 courses of therapy (3 weeks per course), one patient had partial remission, and has been stable in her disease for more than 4 months.In two patients, plasma and ascites fluid was analyzed for VP16-213 and VM26 by a new reverse-phase high performance liquid chromatography method. Both VM26 and VP16-213 could be eluted isocratically (28% v/v acetonitrile in water) from a c₁₈ column with retention times of 6.6 and 13.3 min, respectively. Subsequent pharmacokinetic analysis of one patient suggests that protein binding displacement of VP16-213 in plasma and perhaps ascites fluid increased the pharmacokinetic volume of distribution (28 l) and reduced the elimination half-life (12 h). The data suggests that VP16-213 is distributed more widely in the body and is represented by a single compartment pharmacokinetic model. Analysis of VM26 in ascites and plasma suggests that the so-called deep pharmacokinetic compartment represents ascites equivalent space and that the plasma concentration represents VM26 as free and protein-bound drug in kinetic distinguishable compartments.Determinants of drug action are potentially composed of a multiplicity of physiological, biochemical, and other factors. The potential for manipulating the pharmacodynamic properties of drugs to achieve greater therapeutic potential needs further study.     

Effects of sympathectomy on the in vivo α and β-responses of the parotid gland

Summary Salivary secretion in response to noradrenaline and isoprenaline was measured in innervated and chronically sympathectomized parotid glands of the rat. In innervated glands, the responses to isoprenaline lasted longer than those to noradrenaline. Chronic sympathetic denervation enhanced the responses to both noradrenaline and isoprenaline. The magnitude of the supersensitivity to isoprenaline was related to the dose and the time at which the responses were analyzed. Supersensitivity was greater for the initial than for the total secretion elicited by isoprenaline. Propranolol (1 mg/kg) and phenolamine (5 mg/kg) were used in order to determine the relative participation of and -adrenoceptors in the enhanced responses to isoprenaline. The results suggest that postjunctional supersensitivity for the secretory responses of this organ to isoprenaline is mainly mediated through -adrenoceptors of the secretory cells and -adrenoceptors of the myoepithelial cells.     

Double tumor of the larynx: a case report

Ohne Zusammenfassung