Prevalence of serologic markers of HBV, HDV, HCV and HIV in non-injection drug users compared to injection drug users in Gran Canaria, Spain

Von Hippel-Lindau disease (VHL) is an autosomal dominant tumour syndrome caused by germline mutations of the VHL tumour suppressor gene located on chromosome 3p25-26. In VHL tumours may occur in 14 different target organs, including the eye. Retinal angiomas are considered the first manifestation of VHL disease in 43% of cases, and the cumulative probability of developing a retinal angioma in one or both eyes rises during each decade of life, reaching 80% for patients over 80 years old. Since 1976 patients with VHL at the University Hospital of Utrecht and their at-risk relatives have been screened periodically by a multidisciplinary team. Long-term follow-up ophthalmological data were analysed with special attention to natural course and results of treatment. In addition, we looked for a genotype-phenotype correlation. Retinal angiomas were found in all families. In one large family with a missense mutation (V170D) of the VHL gene, in which the complete spectrum of visceral- and central nervous system (CNS) features of VHL is present, macular, parapapillary, optic disc and ora serrata angiomas were also found. In general, however, a clear-cut genotype-phenotype correlation could not be found. Only early detection and treatment of peripheral retinal angiomas can be expected to decrease the percentage of patients with decreased visual acuity. Therefore, early detection and treatment of these tumours is of paramount importance. Ophthalmological screening of patients and persons at risk should start as early as possible. In patients with apparently sporadic retinal angiomas it is advisable to perform germline DNA analysis, since the risk of developing VHL is high, especially if the angiomas are bilateral, or unilateral and multifocal, if the patient is young, or if there is a family history suggestive of VHL.     

Parenteral nutrition in oncologic patients]

A B16 melanoma-specific CD8+ T cell line (AB1) was established from the spleen cells of C57BL/6 mice cured of B16 melanoma with interleukin (IL)-12 treatment. The AB1 line exclusively used T cell receptor Vbeta11. The AB1 cells exhibited a cytolytic activity against both syngeneic B16 melanoma and allogeneic P815 mastocytoma, whereas a cold inhibition assay revealed specificity of the AB1 cells against B16 melanoma. Their lostability to kill a class I loss variant of B16 melanoma was restored by the transfection of H-2Kb gene. In addition, their interferon (IFN)-gamma production was significantly suppressed by the addition of anti-H-2Kb monoclonal antibody, and RT-PCR analysis showed that the AB1 line expressed the mRNA encoding IFN-gamma, but not IL-4 or IL-10. The experiment using synthetic peptides of tyrosinase-related protein-2 (TRP-2) revealed that the AB1 cells could recognize TRP-2(181-188) peptide. Moreover, the AB1 cells showed an in vivo antitumor effect against established pulmonary metastases of B16 melanoma. Overall, these results indicate that the Tc1-type Vbeta11+ AB1 cells exert an antitumor activity against syngeneic B16 melanoma through recognition of TRP-2(181-188) peptide in an H-2Kb-restricted manner.     

Three cases of tuberculosis after heart transplantation in Spain

The fibrinolytic capacity of patients with acute myocardial infarction (AMI) is known to be impaired. The primary regulatory element of the fibrinolytic system is plasminogen activator inhibitor (PAI). It has been previously observed that there are 2 peaks in the plasma PAI level of AMI patients at 4h and 16h after thrombolytic therapy with recombinant tissue plasminogen activator (rtPA). Lanoteplase/SUN9216 is a mutant tPA with a biological half-life longer than that of rtPA. Thrombolytic therapy with mutant tPA or rtPA was carried out consecutively in 21 patients with AMI (8 patients as the mutant tPA group, and 13 patients as the rtPA group). The recanalization time of the mutant tPA group was significantly faster than that of the rtPA group (16.1 +/- 3.9 min vs 39.6 +/- 4.8 min, p<0.01). The PAI activity at 4h after the initiation of thrombolysis was significantly lower in the mutant tPA group than in the rtPA group (8.74 +/- 5.46IU/L vs 26.74 +/- 3.35 IU/L, p<0.01). There was a one mild peak in serial plasma PAI activity levels 24h after the initiation of thrombolysis. The results suggest that thrombolytic therapy with mutant tPA reduced the impairment of fibrinolytic capacity. The mutant tPA gives faster recanalization and lower PAI activity after successful thrombolysis, compared with rtPA.     

Liquid chromatographic determination of five benzoylurea insecticides in fruit and vegetables

A liquid chromatographic (LC) method was developed to determine 5 benzoylureas--diflubenzuron, hexaflumuron, teflubenzuron, flufenozuron, and lufenuron--in peppers, tomatoes, eggplants, cucumbers, and oranges. Preparation of samples involve extraction with acetone and partitioning into dichloromethane-petroleum ether. A portion of this extract is cleaned up with a solid-phase extraction aminopropyl disposable column. With LC analysis using an RP-8-DB microbore column, acetonitrile-water (70 + 30, v/v) as mobile phase, and photodiode array detection at 254 nm, recovery and repeatability data were collected for the 5 benzoylureas on 4 vegetables and citrus in the range 0.04-2.0 mg/kg. Validated limits of detection and quantitation were 0.01 and 0.04 mg/kg, respectively. The method is reliable for routine analysis of vegetables and fruits.     

Differential chromosome sensitivity to 5-azacytidine in Alzheimer''s disease

The chemiluminescence (CL) technique with scavengers for superoxide anion (superoxide dismutase) and hydrogen peroxide (catalase) was used to characterize the generation of reactive oxygen species (ROS) inside and outside the human neutrophil after stimulation with both soluble (formyl-methionyl-leucyl-phenylalanine, FMLP) and particulate (urate crystals, zymosan, oxidized LDL) stimuli. Depending on the stimulus used, ROS generation differed in composition and absolute amounts. The ratio between extracellularly and intracellularly produced ROS ranged from 0.3 (zymosan) to 4.2 (FMLP). While enhancing substantially FMLP-stimulated CL, horseradish peroxidase inhibited CL induced by particulate stimuli by 40-80%. Furthermore, an azide-insensitive and therefore peroxidase-independent part of CL was found in FMLP-, LDL- and zymosan-stimulated cells. The results indicate that different agonists may lead through distinct chemical pathways to neutrophil luminol-amplified light generation.     

Antigenic stimuli do not influence thymic B lymphocytes: a morphological and functional study in germ-free and conventionally reared piglets

We have recently reported that thymic B lymphocytes (TBL) are the first B-cell subpopulation undergoing isotype switching to IgG and IgA during embryonic life. The aim of this study is to analyze the influence of antigenic stimulation on TBL location and activity using a germ-free (GF) newborn pig model, in which maternal antibodies and antigens do not affect B-cell development. Immunohistological analysis showed that TBL were disseminated mainly in the thymic medulla. There were no differences in the distribution of TBL, both in GF newborn piglets before and after colonization with Escherichia coli and in older conventionally reared (CONV) piglets. The number of immunoglobulin (Ig)-secreting cells measured by the ELISPOT method was not influenced by microflora and food antigens. IgM-positive cells secreting IgM and CD45RC-positive cells spontaneously producing IgM, IgG, and IgA were detected in newborn thymus. Our findings suggest that TBL differentiation and Ig switching to IgG and IgA-secreting cells is not influenced by external antigens and that the thymic microenvironment plays an important role in this process.     

Mumps orchitis; review of 8 cases]

The occurrence of secondary hypogonadism is a common finding in males who seek help with erectile dysfunction, although the relationship to diminished testosterone is unclear. Two possibilities exist regarding both the genesis and maintenance of the hypogonadotropic hypogonadal state. First, a defect in hypothalamic function, resulting in downregulation as well as in alterations of anterior pituitary function; second, estradiol inhibition of gonadotropin release, both of which result in decreased testosterone production. As testosterone levels decrease and estradiol levels increase, the ratio of free testosterone to estradiol reaches a critical point and the estrogenic gonadotropin suppressive effects predominate. This ratio may signal the biological point of no return and could become one of the criteria for defining the separation of the transitional hypogonadal state from the final 'end stage' hypogonadotropic hypogonadal state. As the aging process continues, there is a relative accumulation of fatty tissue, and aromatization accelerates the conversion of testosterone to estradiol. This additional secondary estradiol inhibition results in the maintenance of the testosterone deficient state, and the aging process continues uncontested.     

Physiopathology of neurological signs of hypoxanthine-guanine phosphoribosyltransferase deficiency

OBJECTIVE: Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is characterized by an increase in renal uric acid excretion, usually with hyperuricemia and may be associated with more or less important neurological symptoms. Based on a series of 20 patients from 16 Spanish families we propose that HPRT deficiency could be clinically classified in four different groups. In the more severe form (classic Lesch-Nyhan syndrome) HPRT deficiency is characterized by choreoathetosis, spasticity, mental retardation and compulsive self-mutilation behavior. The pathophysiology of the neurological symptoms remains unclear and there is no effective therapy. This review is intended to provide a research strategy for a better knowledge of the neurological pathophysiology of HPRT deficiency. DEVELOPMENT: We have analyzed the knowledge on the neurological symptoms of HPRT deficiency. This knowledge comes from histopathological studies of the brains from Lesch-Nyhan patients, chemical studies of the cerebrospinal fluid, experimental animal models (pharmacologic and lesioning and genetic approaches), and human in vivo studies with positron-emission tomography. CONCLUSIONS: The observed findings suggest that the neurological symptoms of Lesch-Nyhan syndrome could be related with the neonatal neuronal and/or dopaminergic terminations damage. This damage could be due to lost or reorganization of dopaminergic system, and is associated with a reduced dopamine levels and with hypersensitivity of the D1 subclass dopamine receptors.     

Olfactory epithelium of the rat. Lectin-mediated histochemical studies

BACKGROUND: Twenty-nine patients with large bulbous and giant aneurysms of the paraclinoid segment of the internal carotid artery (ICA) were operated on, using Dolenc's combined epi- and subdural approach, between 1985 and 1994. Ages ranged from 25 to 79 (83% female; 17% male). METHODS: Proximal control was established in all patients through either an extracranial or petrous carotid exposure. The aneurysm was approached through a wide exposure by removing the anterior clinoid extradural. All but one aneurysm was clipped directly. A saphenous vein graft from the petrous-to-supraclinoid bypass was performed in this remaining case. RESULTS: Surgical morbidity was assessed at 20%. One patient developed a postoperative subdural hematoma and remained severely disabled. Two patients developed permanent third nerve palsy. One patient experienced severe disabling cognitive deficit. One patient died from complications related to a stroke. One patient developed transient diabetes insipidus. Visual outcome, which was assessed separately, was unimproved in 50% of the cases during a follow-up period that averaged 7 years. CONCLUSIONS: With the development of cranial base procedures such as Dolenc's combined epi- and subdural approach, large and giant aneurysms of the paraclinoid segment can be directly clipped with acceptable morbidity, allowing the ICA to remain patent.