Cardiovascular risk factors in recipients of successful kidney-pancreas transplantation.
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Publications and source records attributed to M Aragona.
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The imidazopyridine zolpidem is a short-acting hypnotic chemically distinct from benzodiazepines (BZs). According to its peculiar neuropharmacologic activity (selectivity for the omega 1-BZ receptors), zolpidem is expected to be a pure hypnotic, without the other effects of BZs. In particular, it has been stressed that zolpidem is well tolerated in adults and in the elderly, and that tolerance, abuse, dependence, rebound insomnia, and other withdrawal effects do not develop in relation to zolpidem administration. However, despite these assumptions, zolpidem abuse, dependence, and withdrawal effects have been recently discussed and reviewed herein. In addition, the case of a 43-year-old woman who had an epileptic attack after abrupt interruption of an abused, high dose of zolpidem (600 mg/d), is reported and discussed. At the clinical level, it is stressed that the subjective effects ofzolpidem are comparable to those of other BZs, and that abuse, dependence, and withdrawal seizures cannot be avoided simply shifting the regimen of a BZ abuser to zolpidem. At the pharmacologic level, it is important to note that zolpidem's clinical effects cannot be explained on the basis of the old distinction between omega I and 2 receptors because this distinction is no longer valid; the new classification ofGABAA receptor subtypes is reported and zolpidem activity at this level is discussed herein.
BACKGROUND: Occasional case reports describe urinary incontinence in patients taking the selective serotonin and norepinephrine reuptake inhibitor antidepressant venlafaxine. OBJECTIVE: In this study the authors investigated the possible effect of venlafaxine on urinary function in a series of 9 patients with urinary retention resulting from spinal cord lesions. They primarily sought to understand whether the reported venlafaxine-induced urinary incontinence was a specific drug-induced effect and, if so, whether venlafaxine might be an effective treatment of urinary retention. METHODS: During a 1-week baseline period, patients measured postvoiding residual volume through a catheter and recorded the number of micturitions within 24 hours. At the end of the baseline period, venlafaxine 75 mg extended-release on a once-daily evening administration schedule was added to their therapy for 1 week. RESULTS: None of the patients reported severe/uncontrollable side effects while taking venlafaxine. Extended-release venlafaxine (75 mg/day) significantly reduced the postvoiding residual volume and increased the micturition rate; the volume diminished on the first day of treatment and remained stable over the ensuing days. CONCLUSION: These findings suggest that venlafaxine could be useful to improve voiding in patients with spinal cord disease.
Comorbidity is widely used in psychiatry, although few studies have considered the conceptual and methodological problems deriving from the transposition of this term from medicine to psychiatry. Comorbidity should be defined as two or more diseases, with distinct aetiopathogenesis (or, if the aetiology is unknown, with distinct pathophysiology of organ or system), that are present in the same individual in a defined period of time. In psychiatry, comorbidity is often an artefact for several reasons: (a) different assessment methods; (b) improper utilisation of the term comorbidity to indicate the association of symptoms instead of diseases; (c) number and characteristics of hierarchical exclusion rules used in classification systems; (d) nosologic classification in disorders (a generic term) instead of syndromes (a more precise concept, that allows clinicians to consider the hierarchy and the qualitative specificity of symptoms); (e) excessive splitting of classical syndromes into small disorders with inappropriate and overlapping boundaries; (f) too frequent revision of the diagnostic criteria, that changes diagnostic threshold; (g) number of clinical entities considered. Biological and psychological hypotheses that investigate the complexity of comorbidity findings are here presented; it is underlined that comorbidity should be the epidemiological descriptive starting point to build hypotheses that must be clear and rigorously defined, with specified usefulness and limits. Finally, the hypotheses should be tested with specific methodologies.
AIMS AND BACKGROUND: The treatment of inoperable malignant pleural mesothelioma is a challenge for the oncologist. Available chemotherapy regimens achieve poor results, therefore new agents or combinations are needed. In a phase I study, the combination of oxaliplatin and raltitrexed was shown to be active against malignant pleural mesothelioma. We herein report the results of a pilot study about the treatment of this disease. METHODS: From April 1999 to June 2000, we enrolled 11 chemotherapy-naïve patients with inoperable malignant pleural mesothelioma suitable to receive the following combination chemotherapy: raltitrexed, 3 mg/m2 iv, and oxaliplatin, 130 mg/m2, as a 2-hr infusion every 3 weeks. RESULTS: Four partial responses, 1 regression of disease (objective response rate, 45%; 95% CI, 15.6-74.4%), 4 stable diseases and 2 progressions of disease were observed. An improvement in disease-related symptoms was recorded in all responders and in 2 patients with stable disease. Toxicity was mild, with no toxic-related death and only 1 episode of grade 4 neurotoxicity. CONCLUSIONS: We consider the combination promising and worthy of further studies.
The maintenance of telomere length has been hypothesized to be involved in the early steps of cancerogenesis. A physiologic modulation of telomere maintenance is exerted by TRF1 (telomeric-repeat binding factor-1), which deletion permits telomere elongation. Gastrointestinal neoplastic (n=19) and non-neoplastic tissues (six inflammatory disease and six normal mucosa distant from tumor at least 5 cm) were studied, by immunohistochemistry, for TRF1 expression, by using a polyclonal antibody anti-TRF1. Differentiated and not proliferating epithelial secretory cells (Ki67 and p53 negative cells) were stained by anti-TRF1, which did not stain tumor cells in all cases but one (p<0.0001). p53 was expressed by 26% of tumor cases. Inflammatory gastrointestinal non-tumor tissues showed lower expression of TRF1 in epithelial secreting cells compared to normal tissues (p=0.008). These preliminary data suggest that down-regulation of the TRF1 expression in tumor cells may be involved in cell immortalization as an initial step in gastrointestinal carcinogenesis (before p53 alteration), and may open new perspectives, when confirmed, in gastrointestinal tumor prognosis.
The therapeutic approach to cancer is generally limited to the advanced phases of disease. The preventive strategies aim at eliminating or reducing the exposition to known carcinogenes. We act with pharmacological and/or with an accurate dietary education to induce cellular differentiation phenomena, cytostasis and apoptosis. Chemoprevention acts both on the inductive phase (metabolic activation, DNA adducts), as well as on the promotion/proliferation of the long pre-clinical period of latency (antioxidants, anti-inflammatory, retinoids, carotenoids, vitamins and micronutrients, hormones and hormonal inhibitors, polyamine inhibitors, ditholetions, isothiocyanates, telomerase inhibitors, etc). Unanimous agreement has been reached on the preventive role of retinoids in head and neck tumors and of the cervical uterus, of hormonal inhibitors in breast and prostate cancer, and of anti-inflammatory in colorectal cancer. New and more accurate parameters for the evaluation of results and individual applications of chemopreventive strategies are linked to the biological research of high-risk subjects (genetic damage) or increased individual susceptibility. Caution, instead, should be applied in the clinical trial planning. An increased risk in developing and dying of lung tumor in smokers has been shown for the use vitamin A. Many clinical studies have been started in order to establish an efficient chemoprevention in oncology, and with the early diagnostic programs, and the evaluation of genotypic and phenotypic alterations, encouraging results will be reached for the next millennium.
Normal somatic cells have a defined number of divisions, a limited capacity to proliferative. The telomeres, sequences of TTAGGG repeats at the ends of chromosomes, are considered the direct responsible of the control of the cellular cycle. In fact, the progressive shortening of telomere length at each cellular division, causes the entrance of the cells in a phase of senescence and than apoptosis. The maintenance of the length of telomeres is carried out through: the telomerase, a DNA polymerase reverse transcriptase that extends sequence TTAGGG repeats, or the alternative lengthening of telomeres (ALT), between which the adaptive mechanisms, inactivation of TRF1, a protein bound to the telomeres with the functions of inhibiting the telomerase activity and Tankirase-PARP, an enzymatic complex that ADP-ribosylate TRF1 and reduce its binding to DNA. The alteration of the mechanism of maintenance of the telomeres length (Telomerase, TRF1, Tankirase-PARP) may represent a first step toward the cell immortalization and cancerogenesis. Together with the alteration of the control mechanisms of the telomere length, also the cell genic contest should be considered. In fact, the oncogene activation and/or oncosuppressor gene inactivation (p53, Rb, ras) may allow or reduce the cancerogenesis. From this point of view, the telomerase, the TRF1, Tanchirase-PARP and other proteins involved in telomere length could be, in a near future, used as new indicators of prognosis and as markers for new anti-cancer therapies.
BACKGROUND: The telomeric-repeat binding factor (TRF1) participates in a physiological homeostatic mechanism controlling telomere shortening by inhibiting telomerase activity: down-regulation of TRF1 expression results in telomere elongation and may be involved in cell immortalization. PATIENTS AND METHODS: To determine the TRF1 expression by immunohistochemistry (IHC) in human brain tumors, a cohort of 20 consecutive flash-frozen surgical specimens (14 meningiomas and 6 anaplastic astrocytomas (AA)) were collected. RESULTS: Variable levels of TRF1 expression in 12 out of the 14 (87.5%) meningioma samples were observed. By contrast, no expression of TRF1 in tissue samples from AA (p = 0.008) was detected. Positive TRF1 cells were usually more differentiated (less atypical features) and Ki67 negative (inverse statistical association, chi2 = p < 0.001). CONCLUSION: We demonstrated, for the first time, that routine IHC techniques are capable of identifying TRF1 expression in intracranial tumors, which is heterogeneously expressed in meningiomas, but absent in AA. Although these preliminary observations need confirmation from larger studies, the TRF1 status in intracranial tumors might become of prognostic value.
We describe a 40 years old patient deceased of pheochromocytoma-caused heart failure, with no previous specific symptomatology. At autopsy the heart was characterised by thin cardiac walls and cavity dilatation. Histologic pattern showed extensive myocardial fibrosis and some acute myocytolytic areas. This pattern is equal to that of prolonged and decompensated stress cardiomyopathy. These pathologic pictures are both caused by catecholamines cardiotoxicity.
P. graminea is the casual agent of barley leaf stripe. An early selection method of resistant types of barley leaf stripe was realized and validated in this research. This new method, based on Microrganism Genetically Modified (MOGM) GUS2 construction, obtains results comparable with those of classical method, reduces the work time, the use of chemicals (pesticides) and productive plants as greenhouses. Moreover, the use of MOGM GUS2 is restricted in laboratory ambient, therefore the risk of environmental spread is reduced. The early selection method has allowed to estimate the reaction to P. graminea agent in 12 several barley types usually farmed in Italy. The results were compared both, with the classical method data based on artificial clone Dg2 inoculum, and with natural inoculum data obtained in field. At all times we observed a ranking likeness.
The effects of stress are usually studied in animal models. The organs of 103 subjects who died instantly or very rapidly from gunshot wound were histologically studied. Everyone, within organized criminality, lives under chronic stress. In the hypothalamus a marked depletion of neurosecretive granules of neurons in the supraopticus nucleus, paraventricular nucleus and median eminence was observed, with frequent spreading of these granules along the axons, towards the neurohypophysis. Glial proliferation and frequent chronic perivascular edema were observed in the white substance, as were typical stress lesions in the adrenal gland, a marked depletion of lymphocytes in the splenic follicles, a focal coagulative myocytolysis and the consequent fibrosis in the heart, etc. These findings are the expression of the chronic stress response and of the related psychological state that may also be an aspect of depressive disorders.
Venlafaxine blocks the specific monoamine transporters and is devoid of significant action on muscarinic cholinergic receptors. To our knowledge, no cases of glaucoma have been reported so far. Because pain perception involves both serotonergic and noradrenergic mechanisms, venlafaxine also may be useful in neuropathic pain therapy. We report on two patients with narrow angle glaucoma affected by chronic pain. When venlafaxine treatment was begun, their ocular pressure was steadily around 17-18 mmHg. Venlafaxine was chosen (daily dose 75 mg) because this drug is claimed not to bind on muscarinic cholinergic receptors. However, 4 days later the ocular pressure of the first patient increased to 22 mmHg, which led to suspension of the drug. The ocular pressure of the second patient was 18.5 mmHg after a week, 21 mmHg after 2 weeks, and 23 mmHg after 16 days. One week after suspension, ocular pressure of the patients was 17 and 18 mmHg, respectively. Possible explanations of this ocular effect are offered: pharmacokinetic interference on the drugs used in glaucoma treatment, in vivo action on the muscarinic receptor, indirect effect via dopaminergic receptors, or direct effect on the ocular sympathetic postganglionic neurones. In any case, from a clinical viewpoint, caution should be used when giving venlafaxine to patients with narrow-angle glaucoma, and ocular pressure must be monitored.